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Morgan and Mikha il’s Clin ica l 
Anesthesiology Flashcards
New York / Chicago / San Francisco / Lisbon / London / Madrid / Mexico City
Milan / New Delhi / San Juan / Seoul / Singapore / Sydney / Toronto
Richa rd D. Urman, MD, MBA, CPE
Assistant Professor of Anesthesia
Harvard Medical School
Medical Director, Procedural Sedation Safety
Co-Director, Center for Perioperative Management 
& Medical Informatics
Brigham and Women’s Hospital
Boston, Massachusetts
Jesse M. Ehrenfe ld, MD, MPH
Associate Professor of Anesthesiology, 
Surgery, and Biomedical Informatics
Vanderbilt University School of Medicine
Director, Center for Evidence Based Anesthesia
Director, Perioperative Data Systems Research
Department of Anesthesiology
Vanderbilt University Medical Center
Nashville, Tennessee
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 1 The Practice of Anesthesiology
 2 The Opera ting Room Environment
 3 Brea th ing Systems
 4 The Anesthesia Machine
 5 Cardiovascula r Monitoring
 6 Nonca rdiovascula r Monitoring
 7 Pha rmacologica l Princip les
 8 Inha la tion Anesthe tics
 9 Intravenous Anesthe tics
 10 Ana lgesic Agents
 11 Neuromuscula r Blocking Agents
 12 Cholineste rase Inhib itors and Othe r Pha rmacologic 
Antagonists to Neuromuscula r Blocking Agents
 13 Anticholine rgic Drugs
 14 Adrenergic Agonists and Antagonists
 15 Hypotensive Agents
 16 Loca l Anesthe tics
 17 Adjuncts to Anesthesia
v
Contents
 18 Preope ra tive Assessment, Premedica tion , 
and Periope ra tive Documenta tion
 19 Airway Management
 20 Cardiovascula r Physio logy and Anesthesia
 21 Anesthesia for Pa tients with Cardiovascula r Disease
 22 Anesthesia for Ca rdiovascula r Surge ry
 23 Respira tory Physiology and Anesthesia
 24 Anesthesia for Pa tients with Respira tory Disease
 25 Anesthesia for Thoracic Surgery
 26 Neurophysio logy and Anesthesia
 27 Anesthesia for Neurosurge ry
 28 Anesthesia for Pa tients with Neurologic 
and Psychia tric Diseases
 29 Rena l Physio logy and Anesthesia
 30 Anesthesia for Pa tients with Kidney Disease
 31 Anesthesia for Genitourinary Surge ry
 32 Hepa tic Physiology and Anesthesia
 33 Anesthesia for Pa tients with Live r Disease
 34 Anesthesia for Pa tients with Endocrine Disease
 35 Anesthesia for Pa tients with Neuromuscula r Disease
 36 Anesthesia for Ophtha lmic Surgery
 37 Anesthesia for Otorhinolaryngologic Surgery
 38 Anesthesia for Orthopedic Surge ry
 39 Anesthesia for Trauma and Emergency Surge ry
 40 Ma te rna l and Fe ta l Physio logy and Anesthesia
 41 Obste tric Anesthesia
 42 Pedia tric Anesthesia
 43 Geria tric Anesthesia
 44 Ambula tory, Non–Opera ting Room, 
and Office -Based Anesthesia
 45 Spina l, Epidura l, and Cauda l Blocks
 46 Pe riphe ra l Nerve Blocks
 47 Chronic Pa in Management
 48 Pe riope ra tive Pa in Management 
and Enhanced Outcomes
 49 Management of Pa tients with Flu id 
and Electro lyte Disturbances
 50 Acid–Base Management
 51 Fluid Management and Blood Component The rapy
 52 Thermoregula tion , Hypothe rmia , 
and Malignant Hyperthermia
 53 Nutrition in Pe riopera tive and Critica l Care
 54 Anesthe tic Complica tions
 55 Cardiopulmonary Resuscita tion
 56 Postanesthesia Ca re
 57 Critica l Care
vi
Aaron J. Broman, MD
Resident, Departmentof Anesthesiology
Vanderbilt University Medical Center
Nashville, Tennessee
Chapters 23, 44, 53
W. Cross Dudney IV, MD
Resident, Department of Anesthesiology 
Vanderbilt University Medical Center 
Nashville, Tennessee
Chapters 2, 3, 4, 14
Nikan H. Kha tib i, MD, MBA
Resident, Department of Anesthesiology
Loma Linda University Medical Center
Loma Linda, California
Chapters 8, 26, 27, 28, 35
Lori Kie fe r, MD
Resident, Department of Anesthesiology
Vanderbilt University
Nashville, Tennessee
Chapters 50, 54, 55
Jennife r Maziad, MD
Resident, Department of Anesthesiology
Vanderbilt University
Nashville, Tennessee
Chapters 17, 39, 40, 41, 52
Ange la Nichols, MD
Resident, Department of Anesthesiology
Harvard Medical School
Brigham and Women’s Hospital
Boston, Massachusetts
Chapters 19, 31, 34
Ioana Pasca , MD
Resident, Department of Anesthesiology 
Loma Linda University
Loma Linda, California
Chapters 9, 10, 16, 20, 21, 22
Jonah H. Pa te l, MD
Resident, Department of Anesthesiology
Harvard Medical School
Brigham and Women’s Hospital
Boston, Massachusetts
Chapters 13, 15, 45
vii
Contributors
viii
Timothy D. Quinn, MD
Clinical Fellow in Anaesthesia
Harvard Medical School
Brigham and Women’s Hospital
Boston, Massachusetts
Chapters 38, 46, 48
Allan F. Simpao, MD
Assistant Professor of Anesthesiology 
and Critical Care 
University of Pennsylvania 
Perelman School of Medicine and 
The Children’s Hospital of Philadelphia
Philadelphia, Pennsylvania
Chapters 5, 6, 42
Heidi A.B. Smith, MD, MSCI
Pediatric Anesthesiology Clinical Fellow
Pediatric Intensivist
Department of Anesthesiology
Vanderbilt University
Nashville, Tennessee
Chapters 18, 43, 57
Yi Ca i Isaac Tong, MD
Resident, Department of Anesthesiology
Brigham and Women’s Hospital
Harvard Medical School
Boston, Massachusetts
Chapters 7, 47, 49, 56
Jona than P. Wandere r, MD, M.Phil
Instructor, Department of Anesthesiology
Associate Director, Perioperative Data Systems 
Research
Vanderbilt University School of Medicine
Nashville, Tennessee
Chapters 11, 12, 25, 36, 37
Justin J. Wright, MD 
Cardiothoracic Fellow
Department of Anesthesiology
Emory University School of Medicine
Atlanta, Georgia
Chapters 24, 29, 30, 32, 33, 51
THE PRACTICE OF ANESTHESIOLOGY 1-1
Key Dates and People in the History of Anesthesiology
• 1842: Ether first used as an anesthetic agent when Crawford W. Long and William E. Clark independently 
used it on patients for surgery and dental extraction.
• 1844: Gardner Colton and Horace Wells credited with first use of nitrous oxide as an anesthetic.
• 1884: Carl Koller is the first to use cocaine for topical anesthesia.
• 1898: August Bier is credited with administering the first spinal anesthetic.
• 1908: Bier is the first to describe intravenous regional anesthesia (Bier Block).
• 1962: Ketamine first synthesized by Stevens and first used clinically in 1965 by Corssen and Domino.
• 1986: The release of propofol (1989 in the United States) is a major advance in outpatient anesthesia 
because of its short duration of action.
John Snow: Often considered the father of anesthesia, was the first to scientifically investigate ether and the 
physiology of general anesthesia.
William T.G. Morton: First demonstration of general anesthesia for surgery using ether, on October 16, 1846.
Thomas D. Buchanan: First physician to be appointed professor of anesthesia, 1905 at New York Medical 
College.
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THE OPERATING ROOM ENVIRONMENT 2-1
Oxygen
• A reliable source of oxygen is critical to the practice of anesthesia. Medical grade oxygen is at least 99% 
pure and is made by fractional distillation of liquefied air. Oxygen may be stored in pressurized gas cylinders 
or in refrigerated liquid form; to be stored as a liquid, temperature must be kept below the critical tempera-
ture of oxygen, −119°C.
• A pressure of 1000 psig inside an oxygen E-cylinder indicates that it is approximately half full and repre-
sents 330 L of oxygen at atmospheric pressure and a temperature of 20°C. If the oxygen is exhausted at a 
rate of 3 L/min, a cylinder that is half full will be empty in 110 min.
Nitrous Oxide
• Because the critical temperature of nitrous oxide (36.5°C) is above room temperature, it can be kept lique-
fied without an elaborate refrigeration system. N2O E-cylinders contain nitrous oxide in both its liquid and 
gaseous state. Because of this, the volume remaining in a cylinder is not proportional to cylinder pressure. 
By the time the liquid nitrous oxide is expended and the tank pressure begins to fall, only about 400 L of 
nitrous oxide remains. The only way to determine the volume of residual N2O inside the cylinder is to weight 
the cylinder.
THE OPERATING ROOM ENVIRONMENT 2-2
Medical Gas Delivery
• Medical gases are delivered from a central supply to the operating room via piping systems. Pipes are sized 
such that the pressure drop across the whole system never exceeds 5 psig. Gas pipes are usually constructed 
of seamless copper tubing using a special welding technique.
• A pin safety system has been widely adopted that discourages incorrect cylinder attachments; each type of 
gas has a unique configuration of holes that correspond to a set of specific pins in the yoke of the anesthesia 
machine.
• Modern anesthesia machines are required to monitor the fraction of inspired oxygen (FIO2). Analyzers have 
a variable threshold setting for the minimal FIO2 but should be configured to prevent disabling this alarm. 
Because of gas exchange, flow rates, and shunting, a marked difference can exist between the monitored 
FIO2 and O2 levels at the tissue level.
THE OPERATING ROOM ENVIRONMENT 2-3
Electrosurgery
• Electrosurgical units (ESUs, e.g., Bovie) generate an ultrahigh-frequency electrical current that passes from 
an electrode at the tip of the device and through the patient’s tissue and exits by way of a large surface 
area dispersal electrode. Ventricular fibrillation is prevented by the use of ultrahigh electrical frequencies 
(0.1–3 MHz).
• Malfunction of the dispersal pad electrode may result from disconnection from the ESU, inadequate patient 
contact, or insufficient conductive gel within the pad. In this case, current will exit through another point of 
egress, e.g., electrocardiographic (ECG) leads or the metal operating room table, which can cause electrical 
burns. This current can cause malfunction of implanted cardiac devices.
• Bipolar electrosurgical cautery devices confine current propagation to a distance of only millimeters, thus 
obviating the need for a return electrode. Because of this, they often do not interfere with implanted cardiac 
devices and as such do not require the same precautions that are necessary when monopolar ESUs are used.
THE OPERATING ROOM ENVIRONMENT 2-4
Precautions in Electrosurgery
• Precautions to prevent electrosurgical burns include proper return electrode contact and placement, avoiding 
bony protuberances and prosthesis, and elimination of patient-to-ground contacts.
• Current flow through an implanted cardiac rhythm management device can be minimized by placing the 
dispersal electrode as close to the surgical field and as far from the implanted device as possible. If such 
placement is not possible, discuss with the surgery team whether the use of a monopolar electrosurgical 
device is mandatory for the case.
• Because pacemaker and ECG interference is possible, pulse and heart sounds should be closely monitored 
whenever a monopolar ESU is used. Implanted cardioversion and defibrillating devices should be suspended 
if monopolar ESU is used, and any implanted cardiac rhythm management device should be interrogated after 
use of a monopolar ESU.
BREATHING SYSTEMS 3-1
Anesthetic Breathing Systems
• Insufflation: The blowing of gases across a patient’s face (e.g., via a facemask). There is no permanent 
connection between the breathing circuit and the patient’s airway. If fresh gas flow rates are highenough 
(>10 L/min), very little rebreathing of gases occurs.
• Draw-over anesthesia: Draw-over devices have nonrebreathing circuits that use ambient air or supplemen-
tal oxygen as the carrier gas. Air is drawn through a low-resistance vaporizer as the patient inspires. The 
fraction of inspired oxygen (FIO2) can be supplemented using an open-ended reservoir tube attached to a 
t-piece at the upstream side of the vaporizer. The devices can be fitted with connections and equipment that 
allow intermittent positive-pressure ventilation, continuous positive airway pressure, and positive end-
expiratory pressure. The greatest advantage of the draw-over systems is their simplicity and portability; they 
are useful in places where compressed gases or ventilators are not available.
• Mapleson circuits: Incorporate breathing tubes, fresh gas inlets, adjustable pressure-limiting (APL) valves, 
and reservoir bags into the breathing circuit for greater control of gas delivery. The relative location of these 
components determines circuit performance and is the basis of the Mapleson classification system.
BREATHING SYSTEMS 3-2
Anesthetic Breathing Systems
• Disadvantages of insufflation and draw-over systems: Poor control of inspired gas concentration and 
depth of anesthesia, difficult airway management during head and neck surgery, and pollution of the operat-
ing room with large volumes of waste gas with inability to scavenge waste gas.
• Mapleson classification:
Mapleson A: Expiratory valve is close to a facemask separated by a corrugated tube from a reservoir bag 
and supply of fresh gases.
Mapleson B: Expiratory valve and supply of fresh gases are close to the facemask separated by a corrugated 
tube from a reservoir bag.
Mapleson C: Expiratory valve, supply of fresh gases, and a reservoir bag are all close to the facemask; there 
is no corrugated tube.
Mapleson D: Supply of fresh gases is close to the facemask separated by corrugated tube from the reservoir 
bag and expiratory valve.
Mapleson E: Supply of fresh gases is close to the face mask. There is an open length of corrugated tube 
(i.e., no connections). There is no reservoir bag or expiratory valve.
Mapleson F: Supply of fresh gases is close to face mask, which is separated by a corrugated tube from a 
reservoir bag with an expiratory port, but no expiratory valve.
BREATHING SYSTEMS 3-3
Components of Mapleson Circuits
• Breathing tubes: Made of rubber or plastic; connect the patient to the Mapleson circuit. Large-diameter 
tubing is often used to ensure low resistance. 
• Fresh gas inlet: The point of entry of anesthetic gases and oxygen into the Mapleson circuit. The relative 
positioning of the fresh gas inlet is a key differentiating factor in determining the Mapleson classification 
and system performance. 
• Reservoir bag: Function as a reservoir of anesthetic gas and a method of generating positive-pressure ven-
tilation. They are designed to have high compliance.
• Adjustable pressure-limiting (APL) valve: An expiratory valve that allows for exit of gases from the cir-
cuit. It allows for a variable pressure threshold for venting gases from the circuit. Partial closure of the APL 
valve limits gas exit, thus permitting positive pressures during reservoir bag compressions.
BREATHING SYSTEMS 3-4
Components of the Circle System
• Fresh gas inlet: the point of entry of anesthetic gases and oxygen into the circle system.
• CO2 absorber: allows for removal of CO2 from alveolar gas so that rebreathing can safely occur, thus con-
serving heat and humidity.
• Inspiratory unidirectional valve with inspiratory breathing tube (inspiratory limb): opens to allow entry of 
fresh gas to the patient during inspiration without backflow to the machine side of the circuit.
• Expiratory unidirectional valve with expiratory breathing tube (expiratory limb): opens to allow egress of 
expired gases without backflow to the patient side of the circuit.
• Y-connector: located near the patient, the point where the inspiratory and expiratory tubing limbs converge.
• Adjustable pressure limiting (APL) valve: a variable pressure threshold valve that is placed between the CO2 
absorber and the unidirectional expiratory valve, and closely to the reservoir bag.
• Reservoir bag: function as a reservoir of anesthetic gas and a method of generating positive-pressure venti-
lation. They are designed to have high compliance.
BREATHING SYSTEMS 3-5
CO2 Absorber Systems
• CO2 combines with water to form carbonic acid. CO2 absorbents such as soda lime, calcium hydroxide lime, 
and Amsorb contain hydroxide salts that neutralize carbonic acid. The end products of this reaction include 
heat (the heat of neutralization), water, and calcium carbonate.
• The most commonly used CO2 absorber is soda lime. It is capable of absorbing up to 23 L of CO2 per 100 g 
of absorbent. It consists primarily of calcium hydroxide (80%) along with sodium hydroxide, water, and a 
small amount of potassium hydroxide.
• Barium hydroxide lime is no longer used as a CO2 absorbent because of a risk of fire in the breathing system.
• Amsorb is a CO2 absorbent consisting of calcium hydroxide and calcium chloride with calcium sulfate and 
polyvinylpyrrolidone added to increase hardness. It possesses greater inertness than soda lime, resulting in 
less degradation of the volatile anesthetics.
BREATHING SYSTEMS 3-6
CO2 Absorber Systems
• Color conversion of a pH indicator dye (e.g., ethyl violet from white to purple) by increasing hydrogen ion 
concentration signals absorbent exhaustion. Absorbent should be replaced when 50% to 70% has changed 
color.
• Hydroxide salts are irritating to the skin and mucous membranes. Increasing the hardness of soda lime by 
adding silica minimizes the risk of inhalation of sodium hydroxide dust and decreases resistance of gas flow.
• Absorbent granules can absorb and later release significant amounts of volatile anesthetic. This can contrib-
ute to delayed induction or emergence. The drier the soda lime, the more likely it will absorb and degrade 
volatile anesthetics.
• Volatile anesthetics can be broken down to carbon monoxide by dry absorbent (e.g., sodium or potassium 
hydroxide). The formation of carbon monoxide is highest with desflurane.
• Compound A is a byproduct of degradation of sevoflurane by absorbent. Higher concentrations of sevoflu-
rane, prolonged exposure, and low-flow anesthetic technique appear to increase the formation of compound 
A. Compound A has been shown to be nephrotoxic in animal models.
THE ANESTHESIA MACHINE 4-1
Machine Basics
• Basic components of most anesthesia machines include pressure regulators that decrease gas pressure from 
a central supply to levels safe for the patient, vaporizers that add volatile anesthetics to the gas mixture, a 
breathing circuit that connects to the patient’s airway, a mechanical ventilator, a manual (bag) ventilator, an 
auxiliary oxygen supply, and a suction apparatus.
• Gas is supplied from both a central supply through a piping network and by smaller gas cylinders (called 
E-cylinders) located on the machine itself. The E-cylinders are used as a secondary gas supply in case the 
central gas supply fails. Both gas supplies use redundant safety mechanisms, including color coding of gases 
and non-interchangeable inlet connection systems. One-way check valves prevent retrograde flow and filter 
eliminate debris.
• Oxygen is delivered directly into the machine via its flow control valve; however, other gases such as air, 
N2O, and heliox must first pass through safety mechanisms before reaching their flow control valves. In this 
manner, delivery of hypoxic gas mixtures is prevented. Most anesthesia machines use pressure from the 
oxygen supply to drive their mechanical components, such as the ventilator bellows, gas flush valves, and 
so on.
• The approximate pipeline pressure of gases delivered from the central gas supply to the anesthesia machine 
is 50 psi.Pressure regulator valves are used to reduce the pressure from the secondary E-cylinder supply to 
45 to 47 psi before the gases enter the machine. This pressure, slightly lower than the pipeline supply, allows 
preferential use of the pipeline supply if an E-cylinder is accidentally left open. All machines also have an 
oxygen supply low-pressure sensor that activates an alarm when inlet O2 pressure drops below a threshold 
value, usually 20 to 30 psi.
THE ANESTHESIA MACHINE 4-2
Machine Basics
• At 70°F (20°C), a full O2 E-cylinder contains 600 L of oxygen at a pressure of 1900 psi. A full N2O 
E-cylinder contains 1590 L of nitrous oxide at 745 psig. In the United States, E-cylinders are color coded 
as follows: oxygen = green; nitrous oxide = blue; carbon dioxide = gray; medical air = yellow; helium = 
brown; and nitrogen = black. The international coding system is slightly different with oxygen = white and 
air = black and white.
• Anesthetic gas delivery systems are divided into a high-pressure system and a low-pressure system. Gas 
lines located between the gas inlet and the flow control valve-flowmeter apparatus are subject to higher 
pressures and are therefore considered the high-pressure system. Gas lines located between the flow control 
valve–flowmeter apparatus and the common gas outlet are considered the low-pressure system.
• As a safety feature, the knob of the oxygen flowmeter is usually fluted and larger and protrudes farther than 
the knobs of the other flowmeters. The oxygen flowmeter is positioned farthest to the right, downstream to 
the other gases; this arrangement helps to prevent hypoxia if leakage were to occur from a flowmeter 
 positioned upstream.
THE ANESTHESIA MACHINE 4-3
Flow-Control Valves and Flowmeters
• The oxygen flow valves are usually designed to deliver a minimum flow of 150 mL/min when the anesthe-
sia machine is turned on. This safety feature helps ensure that some oxygen enters the breathing circuit even 
if the operator forgets to turn on the oxygen flow.
• Flow-control knobs control gas entry into the flowmeters by adjustment via a needle valve. When the knob 
of the flow-control valve is turned, a needle valve is disengaged from its seat, allowing gas to flow through 
the valve. Touch- and color-coded control knobs make it more difficult to turn the wrong gas off or on.
• Flowmeters may be either analog or electronic. Analog flowmeters, also known as constant-pressure 
 variable-orifice flowmeters, use an indicator ball, bobbin, or float that is supported by the flow of gas 
through a tube with a tapered bore that is calibrated to each particular gas. Electronic flowmeters take 
similar measurements and perform calculations to report flow rates in a digital display.
• Which law of physics allows for the calibration of flowmeter tubes and the determination of flow rates for 
the different gases? (Turn over card for answer.)
THE ANESTHESIA MACHINE 4-4
Flow-Control Valves and Flowmeters
• Poiseuille’s law allows for the measurement of flow rates via flowmeters. Flow rate across a constriction 
(i.e., the tapered tube) depends on the gas’s viscosity at low laminar flows and its density at high turbulent 
flows. To minimize the effect of friction between the float and the tube’s wall, floats are designed to rotate 
constantly, which keeps them centered in the tube. Coating the tube’s interior with a conductive substance 
grounds the system and reduces the effect of static electricity.
• Causes of flowmeter malfunction include debris in the flow tube, vertical tube misalignment, and sticking 
or concealment of a float at the top of a tube. If a leak develops within or downstream from the oxygen 
flowmeter, a hypoxic gas mixture could be delivered to the patient. To reduce this risk, oxygen flowmeters 
are always positioned downstream to all other flowmeters (i.e., nearest the vaporizers).
• As a safety feature, the flow-control knob of the oxygen flowmeter is usually fluted, larger, and protrudes 
farther than the knobs of the other flowmeters. The oxygen flowmeter is positioned farthest to the right, 
downstream to the other gases; this arrangement helps to prevent hypoxia if leakage were to occur from a 
flowmeter positioned upstream.
• Newer machines equipped with electronic flowmeters have an auxiliary constant-pressure variable-orifice 
(analog) flowmeter for the oxygen flow-control valve in the event that the electronic flowmeters fail.
THE ANESTHESIA MACHINE 4-5
Vaporizers
• Each volatile anesthetic agent has a specific vapor pressure for a given temperature. Vapor pressure is the 
pressure exerted on the walls of a container by the gaseous phase when a solution is at equilibrium between 
gas and liquid at a given temperature. This physical property describes the tendency of a substance to leave 
the liquid phase to enter the gaseous phase. The word volatile is a relative term that refers to substances that 
have high vapor pressures at normal working temperatures.
• Volatile anesthetic agents are converted into gases and delivered to the patient via vaporizers. Vaporizers 
have concentration-calibrated dials that precisely add volatile anesthetic agents to the combined gas flow. 
All modern vaporizers are volatile agent specific and temperature corrected, capable of delivering a constant 
concentration of agent regardless of temperature changes or flow through the vaporizer.
• Vaporization requires energy, called the latent heat of vaporization, which results in a loss of heat from the 
liquid. As vaporization proceeds, the temperature of the remaining liquid anesthetic drops and vapor pres-
sure decreases unless heat is readily available to enter the system.
• Most modern vaporizers use a variable-bypass mechanism. In this system, a portion of the total gas flow 
from the machine enters the vaporizer and is diverted into two streams. One gas stream flows over a cham-
ber containing volatile anesthetic, which is carried to the outlet of the vaporizer. The other stream bypasses 
the chamber. These two streams are mixed before exiting the vaporizer to enter the common gas pipeline. 
By controlling the ratio of these streams, the concentration of volatile anesthetic delivered into the system 
can be controlled.
THE ANESTHESIA MACHINE 4-6
Vaporizers
• Temperature affects vapor pressure; as such, the amount of volatile anesthetic delivered by a vaporizer can 
fluctuate because of temperature changes. Temperature compensation within the vaporizer is achieved by a 
strip composed of two different metals welded together. The metals within this strip expand and contract 
differently in response to temperature changes. With changes in temperature, differential contraction of 
these metals causes the strip to bend in a calibrated fashion, allowing more or less gas to pass through the 
vaporizer. Such bimetallic strips are also used in home thermostats. In this manner, the concentration of 
volatile anesthetic delivered by the vaporizer remains stable over a wide range of temperatures.
• Some vaporizers are electronically controlled. Desflurane requires an electronic vaporizer; it is the most 
commonly encountered electronic vaporizer. The vapor pressure of desflurane is so high that at sea level, its 
boiling point approaches room temperature. This high vapor pressure and desflurane’s low potency present 
unique problems:
 � The vaporization required for general anesthesia produces a cooling effect that would overwhelm the abil-
ity of conventional vaporizers to maintain a constant temperature.
 � Because desflurane vaporizes so extensively, a tremendously high fresh gas flow would be necessary to 
dilute the carrier gas to clinically relevant concentrations.
• A reservoir (sump) containing desflurane is electrically heated to 39°C (significantly higher than its boiling 
point), creating a vapor pressure of 2 atm. This vaporizer does not use a variable bypass mechanism. Unlike 
a variable-bypass vaporizer, no freshgas flows through the desflurane sump. Rather, pure desflurane vapor 
joins the fresh gas mixture before exiting the vaporizer. The amount of desflurane vapor released from the 
sump depends on the concentration selected by turning the control dial and the fresh gas flow rate.
THE ANESTHESIA MACHINE 4-7
O2 Analyzers and Spirometers
• The presence of an O2 analyzer in the breathing circuit is vital to the safe delivery of general anesthesia. Three types of 
oxygen analyzers are available: polarographic (Clark electrode), galvanic (fuel cell), and paramagnetic. The first two types 
use electrochemical sensors that contain cathode and anode electrodes embedded in an electrolyte gel separated from the 
sample gas by an oxygen-permeable membrane. As oxygen reacts with the electrodes, a current is generated that is pro-
portional to the oxygen partial pressure in the sample gas. Paramagnetic analyzers use a magnetic field that attracts O2 
much more than other gases. In this manner, O2 levels can be analyzed quickly enough to distinguish between inspired and 
expired O2 concentrations. Paramagnetic devices are more expensive but are self-calibrating and have no consumable parts.
• All oxygen analyzers should have a low-level alarm that is automatically activated by turning on the anesthesia machine. 
The sensor should be placed into the inspiratory or expiratory limb of the breathing circuit but not into the fresh gas line. 
As a result of the patient’s oxygen consumption, the expiratory limb has a slightly lower oxygen partial pressure than the 
inspiratory limb, particularly at low fresh gas flows.
• Spirometers located in the expiratory limb of the breathing circuit are used to measure tidal volumes. Some machines 
contain an additional spirometer that measures inspiratory tidal volumes. A common spirometry method involves a rotat-
ing vane of low mass as a sensor. The flow of gas across vanes within the spirometer causes their rotation, which is 
measured electronically, photoelectrically, or mechanically, and is converted to a tidal volume. A hot-wire spirometer uses 
a fine platinum wire that is electrically heated at a constant temperature inside the gas flow. The cooling effect of increas-
ing gas flow on the wire electrode causes a change in electrical resistance, which can be converted to a tidal volume.
• Most modern vaporizers utilize a variable-bypass mechanism. In this system, a portion of the total gas flow from the machine 
enters the vaporizer and is diverted into two streams. One gas stream flows over a chamber containing volatile anesthetic, 
which is carried to the outlet of the vaporizer. The other stream bypasses the chamber. These two streams are mixed prior to 
exiting the vaporizer to enter the common gas pipeline. By controlling the ratio of these streams, the concentration of volatile 
anesthetic delivered into the system can be controlled.
THE ANESTHESIA MACHINE 4-8
Waste Gas Scavenging Systems
• Waste gas scavengers dispose of gases that have been vented from the breathing circuit by the APL valve 
and ventilator spill valve. Pollution of the operating room environment with anesthetic gases may pose a 
health hazard to operating room personnel. Although it is difficult to define safe levels of exposure, the 
National Institute for Occupational Safety and Health (NIOSH) recommends limiting the room concentra-
tion of nitrous oxide to 25 ppm and halogenated agents to 2 ppm in time-integrated samples.
• Excess gas volume is vented from the adjustable pressure-limiting (APL) and ventilator spill valves into 
tubing that leads to the scavenging interface, which may inside or outside the machine. There are two types 
of scavenging systems: a closed interface and an open interface. An open interface is open to the outside 
atmosphere and usually requires no pressure relief valves. A closed interface is closed to the outside atmo-
sphere and requires negative and positive pressure relief valves that protect the patient from the negative 
pressure of the vacuum system and positive pressure from an obstruction in the disposal tubing.
• The scavenging system outlet may be a direct line to the outside via a ventilation duct beyond any point of 
recirculation (known as passive scavenging) or a connection to the hospital’s vacuum system (called active 
scavenging). In active scavenging, a reservoir chamber accepts waste gas overflow when the capacity of the 
vacuum is exceeded. The vacuum control valve on an active system should be adjusted to allow the evacu-
ation of 10 to 15 L of waste gas per minute. This rate is adequate for periods of high fresh gas flow (i.e., 
induction and emergence) yet minimizes the risk of transmitting negative pressure to the breathing circuit 
during lower flow conditions (i.e., maintenance of general anesthesia).
CARDIOVASCULAR MONITORING 5-1
Arterial Blood Pressure (BP)
• During systole, left ventricle of the heart ejects blood into the 
vasculature, resulting in arterial BP.
• As a pulse moves through the arterial tree, wave reflection distorts 
the pressure waveform.
• Thus, BP measurement can be greatly affected by the location of 
the measurement.
 � Systolic arterial blood pressure (SBP): Peak pressure gener-
ated during systolic contraction.
 � Diastolic arterial blood pressure (DBP): Trough pressure 
during diastolic relaxation.
 � Pulse pressure (PP): The difference between systolic and dia-
stolic pressures.
 � Mean arterial pressure (MAP): Time-weighted average of 
arterial pressures during a pulse cycle.
Noninvasive Arterial Blood Pressure Monitoring
Indications: Any anesthetic delivery is an absolute indication for 
arterial BP measurement. The patient’s condition and the surgical 
procedure determine the technique and frequency of BP determina-
tion. In most cases, an oscillometric BP measurement every 3 to 5 minutes is adequate.
Contraindications: BP cuff techniques should be avoided in extremities with vascular abnormalities (e.g., dialysis shunts) 
or with intravenous lines.
Clinical considerations: Adequate oxygen delivery to vital organs must be maintained during anesthesia. Arterial blood 
pressure is used as a measure of organ blood flow because instruments that monitor specific organ perfusion and oxygenation 
are complex, expensive, and often unreliable.
Aortic root
Circula tion
Centra l
Pe riphera l
Subclavian arte ry
Axilla ry arte ry
Brachia l a rte ry
Radia l a rte ry
Femora l a rte ry
Dorsa lis pedis a rte ry
(Reproduced with permission from Shah N, Bedford 
RF: Invasive and noninvasive blood pressuring moni-
toring. In: Clinical Monitoring: Practical Applications 
in Anesthesia and Critical Care Medicine. Lake CL, 
Hines RL, Blitt CD [editors]. WB Saunders, Philadelphia, 
2001, p 182.)
CARDIOVASCULAR MONITORING 5-2
Noninvasive Arterial Blood Pressure Monitoring: Techniques
BP cuffs: Proper cuff size is crucial for an accurate BP measurement. The cuff bladder should extend at least 
halfway around the extremity, and the cuff width should be 20% to 50% greater than the diameter of the 
extremity. Incorrect use of automated BP cuffs has resulted in nerve palsies and extravasation of intravenous 
fluids.
Palpation: SBP (not DBP or MAP) can be determined by occluding flow at a palpable peripheral pulse with 
a BP cuff. The cuff pressure is released 2 to 3 mm Hg per heartbeat until the pulse is again palpable. SBP is 
underestimated because of the insensitivity of touch and the delay between pulses and flow under the cuff.
Auscultation: A BP cuff can be inflated to a pressure between SBP and DBP to partially collapse an underly-
ing artery and produce turbulent flow and the characteristic Korotkoff sounds, which are audible to a stetho-
scope placed under the distal third of the BP cuff. Pressure is measured with a manometer. Korotkoff sounds 
may be difficult to hear during episodes of hypotension or peripheral vasoconstriction.
Doppler probe: The Doppler Effect is the shift in soundwave frequency when a source moves relative to an 
observer. A Doppler probe transmits an ultrasonic beam that is reflected by underlying tissue. The probe should 
be positioned directly above an artery so that the beam passes through the vessel wall. A Doppler probe can 
be used to detect flow under the BP cuff. Only systolic pressures can be reliably determined with the Doppler 
technique.
CARDIOVASCULAR MONITORING 5-3
Noninvasive Arterial Blood Pressure 
Monitoring: Techniques
Oscillometry: Arterial pulsations cause 
small oscillations in cuff pressure when 
the cuff is inflated above SBP. As cuff 
pressure decreases closer to SBP, the 
oscillations increase because of pulse 
transmission to the entire cuff. Maximal 
oscillation occurs at MAP, after which 
oscillations decrease. Automated BP 
monitors derive SBP, MAP, and DBP 
after electronically measuring the pressures at which oscillation amplitudes change. Measurements may be 
unreliable during arrhythmias and when on cardiopulmonary bypass.
Arterial tonometry: Several independent pressure transducers are applied to the skin overlying an artery; 
beat-to-beat BP is sensed by the pressure required to partially flatten the artery. The contact stress between the 
transducer directly over the artery and the skin reflects intraluminal pressure. Limitations include movement 
artifact and the need for frequent calibrations.
170
162
Oscilla tion
amplitude
S
y
s
t
o
l
e
M
A
P
D
i
a
s
t
o
l
e
154
146
138
130
122
114
106
98
90
82
74
66
58
Time
Cuff
pre ssure
CARDIOVASCULAR MONITORING 5-4
Invasive Arterial Blood Pressure Monitoring
Indications: Induced hypotension, anticipated wide blood pressure swings, end-organ disease necessitating 
precise beat-to-beat blood pressure regulation, and the need for multiple arterial blood samples.
Contraindications: Catheterization should be avoided in arteries of extremities with inadequate collateral 
blood flow or suspicion of vascular insufficiency (e.g., Raynaud phenomenon).
Selection of Artery for Cannulation
Radial artery: Commonly cannulated because of its superficial location and collateral blood flow. Inadequate 
collateral flow occurs in 5% of patients because of incomplete palmar arches. Ulnar collateral circulation 
adequacy can be assessed via the Allen test, palpation, Doppler probe, plethysmography, or pulse oximetry.
Ulnar artery: Deeper and more tortuous than the radial artery. Normally not considered because of a risk of 
hand blood flow compromise, especially if the ipsilateral radial artery has been punctured.
Brachial artery: Large and easily identifiable in the antecubital fossa and has less waveform distortion because 
of its proximity to the aorta. Its location predisposes to kinking of the catheter during flexion at the elbow.
Femoral artery: Provides excellent access but is prone to pseudoaneurysm and atheroma formation. The 
femoral site has been associated with an increased incidence of infections complications and arterial thrombo-
sis, as well as aseptic necrosis of the femoral head in children.
Dorsalis pedis and posterior tibial arteries: The most distorted waveforms because of its distance from the aorta.
Axillary artery: Surrounded by the axillary region of the brachial plexus, and thus nerve damage can result 
from a hematoma or traumatic cannulation. Flushing of the left axillary artery can easily result in transmission 
of air or thrombi to the cerebral circulation.
CARDIOVASCULAR MONITORING 5-5
Invasive Arterial Pressure Monitoring: Radial Artery Cannulation Technique
• Supination and wrist extension provide optimal exposure of the radial artery.
• Pressure-tubing-transducer system should be nearby and flushed for easy connection.
• Radial artery course is determined by lightly palpating over the maximal impulse of the radial pulse with 
the fingertips.
• The skin is prepped with a bactericidal agent, and 0.5 mL of lidocaine is infiltrated directly above the radial 
artery.
• A 20- or 22-gauge catheter over a needle is passed through the skin at a 45° angle directed toward the point 
of palpation.
• Upon blood flashback, a guidewire may be advanced through the catheter into the artery and the catheter 
advanced over the guidewire. Alternatively, the needle is lowered to a 30° angle and advanced 1-2 mm to 
ensure the catheter tip is in the vessel 
lumen.
• The needle is withdrawn while firm 
pressure is applied over the artery 
proximal to the catheter tip to mini-
mize blood loss as the tubing is being 
connected.
• Tubing is firmly connected and 
secured with waterproof tape or suture.
To transducer
High-pressure
tubing
ED
45° 30°
CBA
CARDIOVASCULAR MONITORING 5-6
Invasive Arterial Blood Pressure Monitoring: Complications
Complications: Hematoma, bleeding, vasospasm, arterial thrombosis, air embolization, skin necrosis overlying the catheter, 
nerve damage, infection, necrosis of digits, and unintentional intraarterial drug administration.
Factors associated with increased rate of complications: Prolonged cannulation, hyperlipidemia, repeated insertion 
attempts, female gender, extracorporeal circulation, and the use of vasopressors.
Complication risk is minimized by the following: When the ratio of catheter to artery size is small, heparinized saline is 
continuously infused through the catheter at a rate of 2 to 3 mL/h, flushing of the catheter is limited, and meticulous attention 
is paid to aseptic technique.
Invasive Arterial Blood Pressure Monitoring: Clinical Considerations
Continuous, beat-to-beat measurement via arterial cannulation is the gold standard of BP monitoring.
The transduced waveform depends on the dynamic characteristics of the catheter–tubing–transducer system. Tubing, stop-
cocks, and air all can lead to overdamping, which will underestimate the systolic pressure.
Underdamping can also occur, which can lead to overshoot and a falsely high, overestimated SBP.
Improve system dynamics: Low-compliance tubing, minimize tubing and stopcocks, remove air bubbles.
Transducers convert the mechanical energy of the arterial pressure wave to an electrical signal, and their accuracy depends 
on correct calibration and zeroing procedures.
Motion or electrocautery artifacts can result in misleading arterial waveform readings.
The arterial waveform shape provides clues to hemodynamic variables. The rate of upstroke indicates contractility, and the 
rate of downstroke indicates peripheral vascular resistance. Exaggerated variations in size during the respiratory cycle sug-
gest hypovolemia. MAP is calculated by integrating the area under the pressure curve.
CARDIOVASCULAR MONITORING 5-7
Electrocardiography
Electrodes are placed on the patient’s body to monitor the electrocardiogram (ECG).
The ECG is a recording of myocardial cells’ electrical potentials that allows the detection of arrhythmias, myocardial isch-
emia, conduction abnormalities, pacemaker malfunction, and electrolyte disturbances.
ECG leads are positioned throughout the body to provide different perspectives of the electrical potentials.
Indications: All patients should have intraoperative ECG monitoring. There are no contraindications.
Electrocardiography: Techniques and Complications
Lead selection determines the diagnostic sensitivity of the ECG.
Lead II—arrhythmias and inferior wall ischemia: Lead II’s electrical axis is �60° from the right arm to the left leg, 
parallel to the atria’s electrical axis, resulting in the largest P wave voltages of any surface lead.
Lead V5—anterior and lateral wall ischemia: Lies at the fifth intercostal space at the anterior axillary line.
A true V5 requires at least five lead wires; a modified V5 can be monitored by three leads.
Electrocardiography: Clinical Considerations
Artifacts are a major problem because of the small voltage potentials being measured. Patient or lead-wire movement, use 
of electrocautery, 60-cycle interference, and faulty electrodes can simulate arrhythmias.
Depending on equipmentavailability, a preinduction rhythm strip can be printed or frozen on the monitor’s screen to com-
pare with intraoperative tracings. To interpret ST-segment changes properly, the ECG must be standardized so that a 1-mV 
signal results in a deflection of 10 mm on a standard strip monitor. Newer units continuously analyze ST segments for early 
detection of myocardial ischemia.
CARDIOVASCULAR MONITORING 5-8
Central Venous Catheterization
Indications: Central venous pressure (CVP) monitoring, fluid administration to treat hypovolemia and shock, infusion of 
caustic drugs and total parenteral nutrition, aspiration of air emboli, insertion of transcutaneous pacing leads, and gaining 
venous access in patients with difficult or poor peripheral veins.
Contraindications: Tumors, clots or tricuspid valve vegetations that could be dislodged during cannulation. Internal jugular 
vein cannulation is relatively contraindicated in patients who have had an ipsilateral carotid endarterectomy.
Central Venous Catheterization: Techniques and Complications
Placement: A catheter is placed in a vein so that its tip lies at the junction of the superior vena cava and the right atrium. 
Most central lines are placed using Seldinger technique (catheter over guidewire). The patient is placed in the Trendelenburg 
position to reduce the air embolism risk and to distend the internal jugular vein. Full aseptic technique must be observed, 
and ultrasound guidance should be used. It is crucial that the vein is cannulated because carotid artery cannulation can lead 
to hematoma, stroke, and airway compromise. The risk of vein dilator or catheter placement in the carotid artery can be 
reduced by transducing the vessel’s pressure waveform or comparing the blood’s PaO2 with an arterial sample. 
Transesophageal echocardiography can also be used to confirm that the wire is in the right atrium.
Complications: The risks of central venous cannulation include infection, air or thrombus embolism, arrhythmias (indicat-
ing that the catheter tip is in the right atrium or ventricle), hematoma, pneumothorax, hemothorax, hydrothorax, chylothorax, 
cardiac perforation, cardiac tamponade, trauma to nearby nerves and arteries, and thrombosis. Subclavian vein catheteriza-
tion is associated with significant risk of pneumothorax. Left-sided catheterization carries an increased risk of vascular 
erosion, pleural effusion, and chylothorax.
CARDIOVASCULAR MONITORING 5-9
Central Venous Catheterization: Clinical Considerations
Whereas CVP approximates right atrial pressure, ventricular volumes are related to pressures through compli-
ance. A CVP measurement may only reveal limited information about ventricular volumes and filling because 
highly compliant ventricles accommodate volume with minimal changes in pressure but noncompliant ven-
tricles have larger pressure swings with smaller volume changes. Changes associated with volume loading may 
be a better indicator of the patient’s volume 
responsiveness when coupled with other hemo-
dynamic measures (e.g., blood pressure, heart 
rate, urine output).
The morphology of the central venous wave-
form corresponds to the cardiac cycle: a waves 
from atrial contraction are absent in atrial fibril-
lation and are exaggerated in junctional rhythms 
(cannon a waves); c waves are caused by tricus-
pid valve elevation during early ventricular 
contraction; v waves reflect venous return 
against a closed tricuspid valve; and the x and y 
descents are probably caused by the downward 
displacement of the tricuspid valve during sys-
tole and tricuspid valve opening during diastole.
a
P
m
m
 
H
g
c
T
Q
S
R
ECG
tracing
Jugular
tracing
x
v
y
CARDIOVASCULAR MONITORING 5-10
Central Venous Catheterization: Seldinger Technique
Inte rna l
jugula r ve in
Mastoid
process
Exte rna l
jugula r ve in
Ste rnum
Clavicle
Trende lenburg pos ition
Media l head
s ternocle idomas toid muscle
La tera l head
s te rnocle idomas toid
muscle
A
C
B
30°
18-gauge needle
18-gauge
thinwall needle
J -wire is inserted
through needle
D
Cathete r s lides over J -wire,
which is subsequently removed
J-wire
CARDIOVASCULAR MONITORING 5-11
Pulmonary Artery Catheterization
The pulmonary artery (PA) catheter or Swan-Ganz catheter provides measurements of cardiac output and pulmo-
nary artery occlusion pressures. PA catheters can be used to guide hemodynamic therapy, especially in unstable 
patients. Determination of the PA occlusion or wedge pressure permits (in the absence of mitral stenosis) estima-
tion of left ventricular end-diastolic pressure (LVEDP) and ventricular volume. The ability to measure cardiac 
output (CO) also enables determination of stroke volume (SV) and systemic vascular resistance (SVR):
Cardiac output = Stroke volume × Heart rate
Blood pressure = Cardiac output × Systemic vascular resistance
PA catheters have been used to discern whether hypotension is caused by hypovolemia or low SVR and to 
subsequently guide the determination of the appropriate course of therapy (e.g., fluid bolus, inotrope).
However, numerous large observational studies indicated that patients managed with PA catheters did worse 
than similar patients without PA catheters. Less invasive alternatives include transpulmonary thermodilution 
cardiac output measurements and pulse contour analyses.
Contraindications: Relative contraindications include complete left bundle branch block (because of the risk 
of complete heart block), Wolff–Parkinson–White syndrome and Ebstein malformation (because of possible 
tachyarrhythmias). A catheter with pacing capability is better suited to these situations.
Complications: Bacteremia, endocarditis, thrombogenesis, pulmonary infarction, pulmonary valvular dam-
age, arrhythmias, ventricular puncture, catheter knotting, potentially lethal pulmonary artery rupture, and the 
routine complications of central venous catheterization.
CARDIOVASCULAR MONITORING 5-12
Pulmonary Artery Catheterization: Techniques
The most popular PA catheter design integrates five lumens into a 7.5-Fr catheter, 110 cm long, with a poly-
vinylchloride body. The lumens house the following: wiring to connect the thermistor near the catheter tip to 
a thermodilution cardiac output computer; an air channel for inflation of the balloon; a proximal port 30 cm 
from the tip for infusions, cardiac output injections, and measurements of right atrial pressures; a ventricular 
port at 20 cm for infusions; and a distal port for aspiration of mixed venous blood samples and measurements 
of pulmonary artery pressure.
Before insertion, the PA catheter is checked by inflating and deflating its balloon and irrigating all three intra-
vascular lumens with heparinized saline. The distal port is connected to a transducer that is zeroed to the 
patient’s midaxillary line.
Insertion of a PA catheter requires central venous access, which can be accomplished using the Seldinger 
technique. Instead of a central venous catheter, a dilator and sheath are threaded over the guidewire. The 
sheath’s lumen accommodates the PA catheter after removal of the dilator and guidewire.
CARDIOVASCULAR MONITORING 5-13
Pulmonary Artery Catheterization: 
Placement and Waveforms
The PA catheter is advanced through the 
introducer and into the internal jugular 
vein. During the catheter’s advancement, 
the ECG should be monitored for arrhyth-
mias. Transient ectopy from irritation of 
the right ventricle (RV) by the catheter is 
common but rarely requires treatment.
Waveforms: At approximately 15 cm, the 
distal tip should enter the right atrium. The 
balloon is then inflated with air to protect the endocardium from the catheter tip and to allow the RV’s cardiac 
output to direct the catheter forward. Conversely, the balloon is always deflated during withdrawal. A sudden 
increase in the systolic pressure on the distal tracing indicates the catheter tip in the RV. Entry into the PA 
normally occurs by 35 to 45 cm and isheralded by a sudden increase in diastolic pressure.
Wedging: After attaining a PA position, minimal advancement results in a PA occlusion pressure (PAOP) 
waveform. The PA tracing should reappear when the balloon is deflated. Wedging before maximal balloon 
inflation signals an overwedged position, and the catheter should be slightly withdrawn with the balloon down. 
The frequency of wedge readings should be minimized because of the risk of PA rupture.
Confirmation: A chest radiograph can confirm the catheter position.
RA
0–8
(mean)
PAOP
5–15
(mean)
RV
15–30/0
PA
15–30/0
10
20
30
40
m
m
 
H
g
CARDIOVASCULAR MONITORING 5-14
Pulmonary Artery Catheterization: Clinical Considerations
PA catheters allow both sampling of mixed venous blood and more precise estimation of left ventricular pre-
load than CVP or physical examination. Some catheters have self-contained thermistors that enable cardiac 
output measurements or electrodes that allow ECG recording and pacing. Optional fiberoptic bundles allow 
continuous measurement of mixed venous blood oxygen saturation.
Wedge pressure and pulmonary artery occlusion pressure (PAOP): The distal lumen of a correctly wedged 
PA catheter is isolated from right-sided pressures by the balloon; thus, its distal opening is exposed only to 
pulmonary capillary pressure, which equals left atrial pressure in the absence of high airway pressures or 
pulmonary vascular disease.
PAOP and left ventricular end-diastolic pressure (LVEDP): The relationship between the two can become 
unreliable during conditions with changing left atrial or ventricular compliance, mitral valve function, or 
pulmonary vein resistance:
PAOP > LVEDP: Mitral stenosis, left atrial myxoma, pulmonary venous obstruction, elevated alveolar 
pressure.
PAOP < LVEDP: Decreased left ventricular compliance (stiff ventricle or LVEDP >25 mm Hg), aortic insuf-
ficiency.
CARDIOVASCULAR MONITORING 5-15
Cardiac Output: Thermodilution
A known quantity of fluid that is below body temperature is injected into the right atrium. This changes the temperature of 
the blood in contact with the PA catheter thermistor. The degree of change is inversely proportional to cardiac output (CO). 
Plotting the temperature change as a function of time produces a thermodilution curve; a computer integrates the area under 
that curve to determine CO. A special catheter and monitor system can enable continuous CO measurement.
Factors determining accurate measurements: Rapid and smooth injection, precisely known injectant temperature and 
volume, correct computer calibration factors for the type of PA catheter, avoidance of measurements during electrocautery, 
and absence of tricuspid regurgitation and cardiac shunts.
Transpulmonary thermodilution: Uses thermodilution without PA catheterization; requires a central line and a thermistor-
equipped (usually femoral, not radial) arterial catheter. This method can determine not only CO but also global end-diastolic 
volume and extravascular lung water, which may help in determining the patient’s volume status.
Cardiac Output: Dye Dilution
An indicator dye is injected through a central venous catheter. Its appearance in the systemic arterial circulation can be 
analyzed with a detector, generating a dye indicator curve that is related to CO.
Lithium chloride: A combined analysis of blood pressure and CO can calculate beat-to-beat stroke volume in systems that 
use lithium (LiDCO). A small lithium chloride bolus is injected, and a lithium-sensitive electrode in an arterial catheter 
measures the lithium concentration decay over time. This method can be used in patients who have only peripheral venous 
access, and measurements can be affected by nondepolarizing muscle relaxants. Lithium should not be administered to 
patients in the first trimester of pregnancy. Problems include indicator recirculation, arterial blood sampling, and background 
tracer buildup.
CARDIOVASCULAR MONITORING 5-16
Cardiac Output: Pulse Contour Devices
The arterial pressure trace is used to estimate CO and parameters such as pulse pressure and stroke volume variation with 
mechanical ventilation, which may suggest whether or not hypotension is likely to respond to fluid therapy. Pulse contour 
devices rely on algorithms that measure the area of the systolic portion of the arterial pressure trace from end-diastole to the 
end of ventricular ejection.
The devices must compensate for dynamic vascular compliance. This is accomplished by incorporating a calibration factor 
that some devices generate using transpulmonary or lithium thermodilution data; other devices use statistical analysis of their 
algorithms to account for changes in vascular compliance.
Cardiac Output: Esophageal Doppler
Doppler principle: Esophageal Doppler relies on the Doppler principle to measure the velocity of blood flow in the 
descending thoracic aorta. Blood in the aorta is in relative motion compared with the Doppler probe in the esophagus. When 
blood flows toward the transducer, its reflected frequency is higher than that which was transmitted by the probe. When 
blood cells move away, the frequency is lower than that which was initially sent by the probe.
Determination of aortic area and blood flow: The Doppler equation is used to determine the velocity of blood flow in the 
aorta. Mathematically integrating the velocity over time graph represents the distance that the blood travels. The monitor 
approximates the area of the descending aorta using normograms.
The stroke volume of blood in the descending aorta is calculated. Knowing the heart rate allows calculation of that portion 
of the cardiac output flowing through the descending thoracic aorta, which is approximately 70% of total cardiac output. 
Correcting for this 30% allows the monitor to estimate the patient’s total cardiac output.
Limitation: Esophageal Doppler depends on many mathematical assumptions and normograms, which may hinder its abil-
ity to accurately reflect cardiac output in a variety of clinical situations.
CARDIOVASCULAR MONITORING 5-17
Cardiac Output: Thoracic Bioimpedance
Changes in thoracic volume cause changes in thoracic resistance (bioimpedance) to low-amplitude, high-frequency currents. 
Six chest electrodes inject microcurrents and sense bioimpedance. Cardiac output is calculated using mathematical assump-
tions and correlations. Accuracy is questionable.
Disadvantages: Susceptibility to electrical interference; reliance on correct electrode positions.
Cardiac Output: Fick Principle
The amount of oxygen consumed by an individual (V̇O2) equals the difference between arterial and venous (a–v) oxygen 
content (C) (CaO2 and Cv O2) multiplied by cardiac output (CO). Therefore:
CO = 
Oxygen consumption
a–v O2 content difference
 = 
V̇O2
CaO2 − Cv O2
If a PA catheter and arterial line are in place, one may easily obtain the mixed venous and arterial oxygen content data; 
oxygen consumption can be calculated from the difference between the oxygen content in inspired and expired gas.
Cardiac Output: Echocardiography
Echocardiography uses ultrasound to generate images of heart structures. Perioperative transthoracic (TTE) and trans-
esophageal (TEE) echocardiography are powerful tools. TTE is noninvasive, yet it may be difficult to acquire “windows” to 
view the heart. Limited access in the operating room makes TEE an ideal option to visualize the heart. Disposable TEE 
probes are now available for use.
Basic or hemodynamic TEE: Used perioperatively to discern the source of hemodynamic instability, including whether the 
heart is adequately volume loaded, contracting appropriately, not externally compressed, and devoid of an grossly obvious 
structural defects. This information is correlated to the patient’s general condition.
Advanced TEE: Forms the basis of therapeutic and surgical recommendations depending on the TEE interpretations of the 
anesthesiologist, who should be certified in perioperative echocardiography.CARDIOVASCULAR MONITORING 5-18
Cardiac Output: Echocardiography
Uses:
• Guiding surgical interventions (e.g., mitral valve repair)
• Determination of the source of hemodynamic instability, including myocardial ischemia, heart failure, valvular abnor-
malities, hypovolemia, and pericardial tamponade.
• Measuring hemodynamic parameters such as stroke volume, cardiac output, and intracavitary pressures.
• Assessment of structural disease of the heart such as valvular and aortic disease and cardiac shunts.
Doppler effect and Bernoulli equation: Echocardiography often uses the Doppler effect to evaluate the direction and 
velocity of blood flow and tissue movement. The Bernoulli equation (Pressure change = 4V2, where V is the area of maximal 
velocity) allows one to determine the pressure gradient between areas of different velocity. Using Doppler, it is possible to 
ascertain the maximal velocity as blood accelerates through a pathologic heart structure, such as a stenotic aortic valve.
Color-flow Doppler: Creates a visual picture of the heart’s blood flow by assigning a color code to the velocities in the 
heart. Blood flow directed away from the echocardiographic transducer is colored blue; blood moving toward the probe is 
red. Flow pattern changes are used to identify areas of pathology.
Cardiac output: Can be estimated using TTE and TEE. Assuming the left ventricular outflow tract (LVOT) is a cylinder, its 
diameter can be measured and then the area through which blood flows is calculated using the equation: Area = 0.785 × Diameter2. 
A Doppler beam is aligned in parallel to the LVOT, and the velocities passing through it are used by the computer to integrate 
the velocity/time curve to determine the distance that the blood traveled.
Myocardial tissue movement: Directionality and velocity of the heart’s movement can be examined by Doppler. Tissue 
velocity is normally 8 to 15 cm/s. Reduced myocardial velocities are associated with impaired diastolic function and higher 
left ventricular end diastolic pressures.
CARDIOVASCULAR MONITORING 5-19
A 68-year-old man with a medical history of hypertension and recently diagnosed diet-controlled diabetes is scheduled for 
a mitral valve replacement. A preoperative echocardiogram reveals a left ventricular ejection fraction of 55%, severe mitral 
regurgitation (MR) and a dilated RV with mild dysfunction. No occlusion of the coronary arteries is seen during the preop-
erative cardiac catheterization.
Allergy: Penicillin (hives).
Medications: Metoprolol, hydrochlorothiazide.
Physical examination and other studies
Wt 223 lb Ht 70 in BP 138/89 HR 64 RR 14 Physical examination reveals an elderly male in no distress.
ECG: normal sinus rhythm, left ventricular hypertrophy CXR: cardiomegaly
 1. Which of the following monitors should be used in addition to the standard monitors?
A. Arterial blood pressure monitor
B. Pulmonary artery catheter
C. Transesophageal echocardiogram (TEE)
D. All of the above
 2. After additional monitor placement but before surgical incision, the patient’s peak airway pressures increase from 20 cm 
H2O to 40 cm H2O without any changes to the ventilator settings or patient position. The end-tidal CO2 has decreased 
by half, although the slope of the expiratory phase of the capnograph waveform remains unchanged. What is the likely 
cause of the airway pressure increase?
A. A stuck inspiratory valve
B. Bronchospasm
C. Mainstem intubation
D. Pneumothorax
CARDIOVASCULAR MONITORING 5-20
Answers
 1. Valve replacement surgery necessitates arterial blood pressure monitoring because of anticipated blood 
pressure swings and the need for precise beat-to-beat blood pressure regulation to guide the administration 
of vasoactive medications. Multiple blood samples will likely also be drawn. Although the patient has 
diabetes, he does not have a history of vascular insufficiency (e.g., Raynaud phenomenon); a radial artery 
catheter should not be contraindicated. Although there is a lack of scientific data proving a reduction in 
morbidity and mortality with the use of a pulmonary artery catheter, one may prove useful for intraop-
erative and postoperative cardiac output measurements while providing access for central delivery of vaso-
active medications. TEE is extremely helpful for cardiac cases, especially in the assessment of the valve 
replacement in this case scenario. The TEE can also be used to determine total body fluid status and to 
identify myocardial ischemia. Thus, all of the options should be used for this patient.
 2. Although a stuck expiratory valve may result in increased airway pressures, a stuck inspiratory valve would 
instead be evident by rebreathing of end-tidal CO2. Bronchospasm can cause increased airway pressures. 
Although the patient is on beta-blocker therapy, which may exacerbate or potentiate bronchospasm, he has no 
history of reactive airway disease. Furthermore, airway obstruction would likely cause an increased slope in the 
capnograph expiratory phase; in the case scenario, the capnograph waveform remains unchanged. Mainstem 
intubation would likely have presented as increased airway pressures right after intubation; in contrast, in this 
case scenario, airway pressures were initially normal. Although endotracheal tubes can and do migrate into the 
right mainstem bronchus (especially in infants and neonates, in whom the airway distances are relatively 
smaller), the scenario states that the patient has not been moved. The scenario fits the picture of a pneumothorax, 
which can occur during the placement of central venous access such as a pulmonary artery catheter.
NONCARDIOVASCULAR MONITORING 6-1
Pulse Oximetry
Mandatory monitor for any anesthetic, including moderate seda-
tion. There are no contraindications.
A sensor with a light source and detector is placed across a per-
fused tissue (e.g., finger, earlobe) that can be transilluminated. 
Whereas oxygenated hemoglobin absorbs more infrared light 
(940 nm), deoxyhemoglobin absorbs more red light (660 nm). The 
change in light absorption is the basis of oximetric determinations. 
A microprocessor analyzes the ratio of red and infrared absorptions 
to provide the oxygen saturation (SpO2) of arterial blood based on 
established norms. Arterial pulsations, identified by plethysmogra-
phy, allow corrections for absorption by nonpulsatile venous blood 
and tissue.
Deoxyhemoglobin
Oxyhemoglobin
20,000
10,000
5000
1000
500
550 650
(Red) (Infra red)
750 850 950
100
50
10
NONCARDIOVASCULAR MONITORING 6-2
Pulse Oximetry: Clinical Considerations
In addition to SpO2, pulse oximeters provide an indication of tissue perfusion (pulse amplitude) and measure heart rate. Because 
SpO2 is normally close to 100%, only gross abnormalities are detectable in most anesthetized patients. Depending on a particu-
lar patient’s oxygen–hemoglobin dissociation curve, an SpO2 of 90% may indicate a PaO2 of less than 65 mm Hg. This compares 
with clinically detectable cyanosis, which requires 5 g of desaturated hemoglobin and usually corresponds to an SpO2 of less 
than 80%. Bronchial intubation usually goes undetected by pulse oximetry in the absence of lung disease or low fraction of 
inspired oxygen concentrations (F IO2).
Methemoglobinemia: Methemoglobin has the same absorption coefficient at both red and infrared wavelengths. The 
 resulting 1:1 absorption ratio corresponds to a saturation reading of 85%.
Causes of pulse oximetry artifact: Excessive ambient light, motion, methylene blue dye, venous pulsations in a dependent 
limb, low perfusion, malpositioned sensor and leakage of light from the light-emitting diode to the sensor (bypassing the 
arterial bed).
Extensions of Pulse Oximetry Technology
Mixed venous blood oxygen saturation: Requires the placement of a pulmonary artery (PA) catheter containing fiberoptic 
sensors that continuously determine S VO2. A variation involves placing the sensor in the internal jugular vein, which providesmeasurements of jugular bulb oxygen saturation to assess cerebral oxygen delivery.
Noninvasive brain oximetry: Monitors regional oxygen saturation (rSO2) of hemoglobin in the brain. A forehead sensor emits 
light of specific wavelengths and measures the light reflected back to the sensor. In contrast to pulse oximetry, brain oximetry 
measures venous, capillary, and arterial saturation, thereby providing an average oxygen saturation of all regional hemoglobin 
(�70%). Cardiac arrest, cerebral embolization, deep hypothermia, or severe hypoxia can cause a dramatic decrease in rSO2.
NONCARDIOVASCULAR MONITORING 6-3
Capnography
Capnographs rely on the absorption of infrared light by CO2. 
Determination of end-tidal CO2 (E TCO2) concentration to confirm ade-
quate ventilation is mandatory during all anesthetic procedures.
Capnography: Nondiverting (Flowthrough)
Nondiverting (mainstream) capnographs measure CO2 passing through 
an adaptor placed in the breathing circuit. Infrared light transmission 
through the gas is measured and CO2 concentration is determined by 
the monitor.
Capnography: Diverting (Aspiration)
Diverting capnographs continuously suction gas from the circuit into a sample cell in the monitor. CO2 con-
centration is determined by comparing infrared absorption in the cell with a chamber devoid of CO2.
Aspiration rates: High aspiration rates (up to 250 mL/min) and low-deadspace sampling tubing usually 
increase sensitivity and decrease lag time. If tidal volumes (VT) are small (e.g., pediatric patients), however, a 
high rate of aspiration may entrain fresh gas from the circuit and dilute ETCO2 measurement. Low aspiration 
rates (less than 50 mL/min) can underestimate ETCO2 during rapid ventilation.
Water precipitation: Diverting units are prone to water precipitation in the aspiration tube and sampling cell 
that can cause obstruction of the sampling line and erroneous readings.
Expiratory valve malfunction is detected by the presence of CO2 in inspired gas.
End-tida l
CO2 monitor
Infra red
transduce r
NONCARDIOVASCULAR MONITORING 6-4
Capnography: Clinical Considerations
Capnographs reliably indicate esophageal intubation but do not reliably detect bronchial intubation. Sudden 
cessation of CO2 during the expiratory phase may indicate a circuit disconnection. A marked rise in E TCO2 may 
be caused by the increased metabolic rate associated with malignant hyperthermia.
The PaCO2-E TCO2 gradient (usually 2–5 mm Hg) reflects alveolar dead space (alveoli that are ventilated but not 
perfused). Capnographs display a CO2 waveform that allows recognition of a variety of conditions:
A. Normal capnograph with the three phases of expiration: phase I—dead space; phase II—dead space and 
alveolar gas; phase III—alveolar gas plateau.
B. Capnograph of severe chronic obstructive pulmo-
nary disease. No plateau is reached before the next 
inspiration. The ETCO2 and arterial CO2 gradient is 
increased.
C. Depression during phase III indicates spontaneous 
respiratory effort.
D. Failure of the inspired CO2 to return to zero may be 
attributable to an incompetent expiratory valve or 
exhausted CO2 absorbent.
E. Persistence of exhaled gas during the inspiratory 
cycle signals the presence of an incompetent inspira-
tory valve.
I II III I II III
40 40
00
Inspir-
a tion
Expira tion Inspira tionExpira tion
D E
40 40
Inspir-
a tion
Inspir-
a tion
Expira tion Inspir-
a tion
Expira tionExpira tion
II IIII II IIIII II
40
0 0 0
A B C
NONCARDIOVASCULAR MONITORING 6-5
Anesthetic Gas Analysis
Anesthetic gas analysis is essential during any inhalational anesthetic use. There are no contraindications.
Infrared absorption: Relies on a variety of techniques similar those used in capnography. Based on the Beer-Lambert law; 
the absorption of infrared light passing through a solvent (inspired or expired gas) is proportional to the amount of the unknown 
gas. O2 and N2 do not absorb infrared light and must be measured by other means.
Piezoelectric analysis: Uses oscillating quartz crystals, one of which is covered in lipid. Volatile anesthetics dissolve in the 
lipid layer, and their concentration is determined by the change in oscillation frequency. This method cannot distinguish 
different anesthetic agents.
Oxygen Analysis
Galvanic cell: Galvanic cell hydroxyl ions are formed at the gold cathode and react with the lead anode. An electrical current 
is produced that is proportional to the amount of oxygen being measured.
Paramagnetic analysis: Oxygen is a nonpolar gas that is paramagnetic and expands when placed in a magnetic field. 
By switching the field on and off, the volume change can be used to measure O2 content.
Polarographic electrode: A semipermeable membrane separates a gold cathode and silver anode. A voltage is applied, and 
hydroxide ions are formed from O2; the resultant current is proportional to the amount of O2.
Spirometry
Anesthesia machines can measure and manage airway pressures, volume, and flow; calculate resistance and compliance; 
and then display the relationships of these variables as flow–volume or pressure–volume loops.
Low and high peak inspiratory pressure: Indicate circuit disconnect or airway obstruction, respectively.
Minute ventilation: Obtained by measuring VT and breathing frequency.
Spirometric loops and waveforms are altered by certain disease processes and events (e.g., obstruction, bronchial intubation).
NONCARDIOVASCULAR MONITORING 6-6
Neurologic System Monitors: Electroencephalography
The electroencephalogram (EEG) is a recording of electrical potentials generated by cells in the cerebral cortex that can be 
used during cerebrovascular surgery to confirm adequate cerebral oxygenation.
EEG waves: Alpha waves (8–13 Hz) are found in a resting adult with eyes 
closed. Beta waves (8–13 Hz) are found in concentrating individuals and at 
times under anesthesia. Delta waves (0.5–4 Hz) are found in brain injury, deep 
sleep, and anesthesia. Theta waves (4–7 Hz) are also found in deep sleep and 
anesthesia. EEG waves are characterized by their amplitude and are examined 
for left–right symmetry. Inhalational agents cause initial beta activation, then 
slowing, burst suppression, and isoelectricity.
EEG functions: EEG is sometimes used during surgery to detect areas of cere-
bral ischemia as well as during epilepsy surgery; EEG is also used to detect 
EEG isoelectricity during hypothermic arrest.
Bispectral index (BIS): Processed two-channel EEG to indicate wakefulness via a 
dimensionless variable. Four EEG components are examined: low frequency (deep 
anesthesia), high frequency (“light” anesthesia), suppressed EEG waves, and burst 
suppression. Some devices include measures of spontaneous muscle activity as 
indicators of subcortical activity to aid in anesthetic depth assessment. Controversy 
persists regarding the exact role of processed EEG devices in assessing anesthetic 
depth. Individual EEG responsiveness to anesthetic agents may be variable, and 
many monitors have a delay that may only indicate a risk for patient wakefulness 
after the patient had already become conscious. BIS values of 65 to 85 suggest 
sedation; values of 40 to 65 have been recommended for general anesthesia.
(Reproduced with perm ission from 
Johansen JW et al: Development and 
clinical application of electroencephalo-
graphic bispectrum monitoring. Anesthe-
siology 2000;93:1337.)
NONCARDIOVASCULAR MONITORING 6-7
Evoked Potentials (EPs)
EP monitoring assesses neural function by measuring electrophysiologic responses to sensory or motor pathway stimulation. 
Commonly monitored EPs are brainstem auditory evoked responses (BAERs), somatosensory-evoked potentials (SEPs), and 
motor-evoked potentials (MEPs). For SEPs, an electrical current is applied to a sensory or mixed peripheral nerve by elec-
trodes. If the intervening pathway is intact, the action potential will be transmitted to the contralateral sensory cortex to 
produce an EP thatis detected by scalp electrodes. EPs are plotted as voltage versus time, and the waveforms are analyzed 
for their poststimulus latency and peak amplitude. These are compared with baseline tracings to detect neural damage.
Indications: Surgical procedures associated with possible neurologic injury, including spinal fusion with instrumentation, 
spine and spinal cord tumor resection, brachial plexus repair, thoracoabdominal aortic aneurysm repair, epilepsy surgery, and 
cerebral tumor resection. EPs can detect spinal cord or cerebral cortex ischemia and can be used for probe localization dur-
ing stereotactic neurosurgery.
Contraindications: Although no specific contraindications exist for SSEPs, they are limited by the availability of monitor-
ing sites, equipment, and trained personnel. MEPs are contraindicated in patients after seizures and any major cerebral insult 
or with retained intracranial metal, a skull defect, or implantable devices. Brain injury secondary to repetitive stimulation of 
the cortex and inducement of seizures is a concern with MEPs.
Clinical considerations: Variables other than neural damage can alter EPs. In general, N2O and opioids cause minimal 
changes, and volatile agents are best avoided or used at a low dose. Changes in BAERs may reflect depth of anesthesia. 
Physiologic and pharmacologic factors should be kept constant.
Persistent obliteration of EPs is predictive of postoperative neurologic deficit. SEPs identify dorsal spinal cord sensory pathway 
damage but not necessarily motor pathway damage. MEPs monitor the ventral spinal cord and are more sensitive to spinal cord 
ischemia than SSEPs. However, monitoring of MEPs requires monitoring the level of neuromuscular blockade, and MEPs are 
sensitive to volatile agents, high-dose benzodiazepines, and moderate hypothermia (i.e. temperature less than 32°C).
NONCARDIOVASCULAR MONITORING 6-8
Cerebral Oximetry and Jugular Venous Bulb Saturation
Cerebral oximetry: Uses near-infrared spectroscopy (NIRS). Near-infrared light is emitted by a scalp probe, with receptors 
positioned to detect the reflected light from intracranial structures. Saturations less than 40 on NIRS measures or changes 
of greater than 25% of baseline may reflect decreased cerebral O2.
Jugular venous bulb saturation: A probe is placed in the internal jugular vein and directed toward the brain to determine 
the brain oxygen tension, which should be kept at 20 mm Hg or greater. Interventions to improve brain tissue oxygen content 
include increasing FIO2 and hemoglobin, adjusting cardiac output, and decreasing oxygen demand.
Temperature Monitors
Temperature is usually measured using a thermistor or thermocouple probe. Disposable probes are used to monitor tem-
perature of the tympanic membrane, nasopharynx, esophagus, bladder, rectum, or skin. Complications usually are caused by 
probe placement trauma (e.g., tympanic membrane perforation).
Clinical considerations: Hypothermia is usually defined as a body temperature less than 36°C and may occur during anes-
thesia. Risk factors for unintentional perioperative hypothermia include extremes of age, abdominal surgery, procedures of 
long duration, and cold ambient operating room temperature. Although hypothermia has been shown to be protective during 
times of cerebral or cardiac ischemia, hypothermia also has deleterious physiological effects. Postoperative shivering 
increases O2 consumption as much as fivefold and is correlated with an increased risk of myocardial ischemia and angina.
Anesthesia-induced vasodilation can cause a redistribution of heat from warm central compartments to cooler peripheral 
tissues. Furthermore, general anesthesia inhibits hypothalamic function, reducing the body’s compensatory response to 
hypothermia. Solutions include prewarming with forced-air warming blankets, administering warm intravenous fluids, and 
raising operating room temperature.
NONCARDIOVASCULAR MONITORING 6-9
Urinary Output
Bladder catheterization is usually performed by surgical or nursing personnel or by a urologist in the case of 
abnormal urethral anatomy. A Foley catheter is inserted into the bladder transurethrally and connected to a 
collection chamber, which should remain at a level below the bladder to minimize urine reflux and the risk of 
infection. Complications include urethral trauma and urinary tract infections. Catheterization is the only reli-
able urinary output monitor and is indicated in patients with congestive heart failure, renal failure, hepatic 
disease, or shock. Catheterization is routine in cardiac, aortic, renal vascular, or major abdominal surgery; 
craniotomy; and procedures during which large fluid shifts or diuretic administration may occur.
Contraindications: Utmost care should be observed in patients at high risk for infection.
Clinical considerations: An additional benefit of a Foley catheter is the ability to include a thermistor in the 
tip to measure bladder temperature (which reflects core temperature if urinary output is high). Urinary output 
reflects kidney perfusion and function and indicates renal, cardiovascular, and fluid volume status. Inadequate 
urinary output (oliguria) is often arbitrarily defined as urinary output less than 0.5 mL/kg/h but is actually a 
function of the patient’s concentrating ability and osmotic load. Urine electrolyte composition, osmolality, and 
specific gravity aid in the differential diagnosis of oliguria.
NONCARDIOVASCULAR MONITORING 6-10
Peripheral Nerve Stimulation: Indications and Contraindications
The neuromuscular function of patients receiving neuromuscular blocking agents (NMBAs) should be monitored. Peripheral 
nerve stimulation can not only assess paralysis during rapid-sequence inductions or continuous infusions of NMBA but also 
help locate nerves to be blocked by regional anesthesia.
Contraindications: Atrophied muscles caused by hemiplegia or nerve damage may appear refractory to NMBA because of 
receptor proliferation, which could lead to potential overdosing of NMBA.
Peripheral Nerve Stimulation: Techniques and Clinical Considerations
A peripheral nerve stimulator delivers current (60–80 mA) to a pair of ECG pads or needles placed over a motor nerve. 
Visual or tactile observation of muscle contraction is usually relied on in clinical practice.
Nerve sites: Simulation of the ulnar nerve (i.e., adductor pollicis muscle) and facial nerve (i.e., orbicularis oculi) is usually 
monitored. Avoid direct muscle stimulation (i.e. placing electrodes directly over the muscle) to ensure that the neuromuscu-
lar junction is being monitored properly. Muscle groups differ in their sensitivity to NMBA; the nerve stimulator should not 
replace observation of the muscles (e.g., the diaphragm) that must be relaxed for a procedure. The diaphragm, rectus 
abdominis, laryngeal adductors, and orbicularis oculi muscles recover from neuromuscular blockade sooner than the adduc-
tor pollicis. Indicators of recovery include sustained (≥5 s) head lift, the ability to generate inspiratory pressure of at least 
–25 cm H2O, and a forceful hand grip.
Clinical considerations: Patterns of electrical stimulation are applied; stimuli are 200 µs in duration, square-wave pattern, 
and equal current intensity. A twitch is a pulse delivered every 1 to 10 s.
Train-of-four: Four successive 200-µs stimuli in 2 s (2 Hz); twitches fade progressively as relaxation increases. The ratio of 
the first and fourth twitches is a sensitive indicator of NMBA relaxation. Loss of the fourth twitch represents a 75% block, the 
third an 80% block, and the second a 90% block. Clinical relaxation usually requires 75% to 95% neuromuscular blockade.
Tetany: Tetany at 50 or 100 Hz is a sensitive test of neuromuscular function. Sustained contraction for 5 s indicates 
 adequate—but not necessarily complete—reversal from neuromuscular blockade.
PHARMACOLOGICAL PRINCIPLES 7-1
Pharmacokinetics
Absorption: Process by which a drug moves from site of administrationto the bloodstream
• Influenced by the physical characteristics of the drug (solubility, pKa; diluents, binders, and formulation), 
dose, and site of absorption (e.g., gut, lung, skin, muscle).
• Bioavailability is the fraction of the administered dose reaching the systemic circulation.
• Nonionized forms of drugs are preferentially absorbed. Therefore, an acidic environment favors the absorp-
tion of acidic drugs, and an alkaline environment favors basic drugs.
• Routes of systemic drug absorption are oral, sublingual, rectal, inhalational, transdermal, transmucosal, 
subcutaneous, intramuscular, and intravenous.
• Oral absorption may be limited by first-pass metabolism in the liver.
• Sublingual or buccal drug absorption bypasses the liver and first-pass metabolism.
• Transdermal drug administration can provide prolonged continuous administration; however, the stratum 
corneum is an effective barrier to all but small, highly potent, lipid-soluble drugs.
• Subcutaneous and intramuscular absorption depends on diffusion from the site of injection to the circulation, 
which depends on the blood flow to the area and the carrier vehicle (solutions are absorbed faster than sus-
pensions). Irritating preparations can cause pain and tissue necrosis.
• Intravenous injection completely bypasses the process of absorption because the drug is placed directly into 
the bloodstream.
PHARMACOLOGICAL PRINCIPLES 7-2
Pharmacokinetics
Distribution: The circulation of a drug in the blood throughout the body
• Highly perfused organs (brain, heart, liver, kidney, endocrine glands) receive a disproportionate fraction of the 
cardiac output and thus receive a disproportionate amount of drug in the first minutes after drug administration.
• The less well-perfused organs (primarily fat and skin) equilibrate more slowly because of the relatively 
smaller blood flow.
• Drug molecules obey the law of mass action. When plasma concentration exceeds the concentration in tis-
sue, drug moves from plasma to tissue. When the plasma concentration is less that the concentration in 
tissue, drug moves from tissue back to the plasma.
• Whereas albumin binds many acidic drugs (e.g., barbiturates), α 1-acid glycoprotein (AAG) binds basic drugs 
(local anesthetics).
• Albumin levels are decreased in renal disease, liver disease, chronic congestive heart failure, and malignancies.
• AAG levels are increased in trauma (including surgery), infection, myocardial infarction, and chronic pain.
• AAG levels are reduced in pregnancy.
Volume of Distribution (Vd):
• The apparent volume into which a drug has been distributed is called its volume of distribution (Vd) and is 
determined by dividing the dose of drug administered by the plasma concentration.
Vd = Dose
Concentration
• Most anesthetic drugs are lipophilic, resulting in a Vd that exceeds total body water (�40 L). For example 
the Vd of fentanyl is about 350 L in adults, and the Vd for propofol may exceed 5000 L.
PHARMACOLOGICAL PRINCIPLES 7-3
Pharmacokinetics
Biotransformation: The chemical alteration of the drug molecule. Also referred to as metabolism.
• The liver is the primary organ of metabolism. The end products are usually—but not necessarily—inactive 
and water soluble. The latter property allows excretion by the kidney.
• Can be divided into phase I and phase II reactions.
 � Phase I reactions convert drug into more polar metabolites through oxidation, reduction, or hydrolysis.
 � Phase II reactions couple (conjugate) a parent drug or a phase I metabolite with an endogenous substrate 
(e.g., glucuronic acid) to form water-soluble metabolites that are eliminated in the urine or stool.
• Phase I metabolites may be excreted without undergoing phase II biotransformation, and a phase II reaction 
can precede or occur without a phase I reaction.
Hepatic clearance: Volume of plasma or blood cleared of drug per unit of time
• The hepatic clearance is liver blood flow times the hepatic extraction ratio (which is the fraction of drug 
entering the liver that is metabolized.)
• Example: If the extraction ratio is 50%, then hepatic clearance is half of liver blood flow.
Excretion
• The kidneys are the principal organ of excretion. The nonionized fraction of drug is reabsorbed in the renal 
tubules, and the ionized portion is excreted in urine.
• Renal clearance is the rate of elimination of a drug from kidney excretion and can be calculated by renal 
blood flow times the renal extraction ratio.
• Enterohepatic recirculation: drug excreted into the bile and then reabsorbed in the intestine.
PHARMACOLOGICAL PRINCIPLES 7-4
Pharmacokinetics
Compartment Models
• Multicompartment models provide a mathematical 
framework to relate drug dose to drug concentration 
over time.
Two-Compartment Model
• Distribution phase or alpha phase: After an initial 
bolus of drug, there is a very rapid drop in concentra-
tion over the first few minutes as drug quickly diffuses 
into peripheral compartments.
• Elimination phase or beta phase: Continued—but 
less steep—decline in plasma concentration.
PHARMACOLOGICAL PRINCIPLES 7-5
Pharmacodynamics: How a drug affects the 
body, and involves the concepts potency, effi-
cacy, and therapeutic window.
Dose–Response Relationships
• Dose–response curves express the relationship 
between drug dose and pharmacologic effect.
• The shape of the relationship is typically sig-
moidal in a log scale.
• The sigmoidal shape arises from the observa-
tion that often a certain amount of drug must 
be present before there is any measurable 
physiologic response.
• The left side of the curve is flat until the drug 
concentration reaches a minimum threshold. 
On the right side, the curve is also flat, reflecting 
the maximum physiologic response of the body.
• The therapeutic window for a drug is the dis-
tance between the concentration associated with a desired therapeutic effect and the concentration associ-
ated with a toxic drug response.
• The therapeutic index is the toxic concentration divided by the therapeutic concentration.
PHARMACOLOGICAL PRINCIPLES 7-6
Drug Receptors
• Drug receptors are macromolecules, typically proteins that bind a drug (agonist) and mediate the drug 
response. Pharmacologic antagonists reverse the effects of the agonist.
• Competitive antagonism occurs when the antagonist competes with the agonist for the binding site, each 
displacing the other.
• Noncompetitive antagonism occurs when the antagonist, through covalent binding or another process, 
permanently impairs the drug’s access to the receptor.
• The drug effect is governed by the fraction of receptors occupied. That fraction is based on the concentration 
of drug, concentration of receptor, and strength of the binding between the drug and the receptor.
• Receptor occupancy is only the first step in mediating drug effect. Binding of the drug to the receptor can 
trigger a myriad of subsequent steps, including opening or closing an ion channel, activating a g protein, 
activating an intracellular kinase, interacting directly with a cellular structure, or binding directly to DNA.
• Prolonged binding and activation of a receptor may lead to hypo-reactivity (“desensitization”) and tolerance. 
If the binding of an endogenous ligand is chronically blocked, then receptors may proliferate, resulting in 
hyperreactivity and increased sensitivity.
INHALATION ANESTHETICS 8-1
Pharmacokinetics of Inhalational Anesthetics
Pharmacokinetics: Describes the relationship between a drug’s dose, tissue concentration, and elapsed time. 
For anesthesia to occur, a therapeutic concentration must be reached in the central nervous system, which is 
influenced by four factors: inspiratory concentration (FI), alveolar concentration (FA), arterial concentration 
(Fa), and elimination factors.
FI: Depends on fresh gas flow rate, volume of breathing system, and absorption by the machine or breathing 
circuit. The higher rates, smaller system volumes, and lowerabsorption he faster the induction.
FA: Ideally, the FA/FI ratio should equal 1, but the pulmonary circulation takes up gases to perfuse the body 
during induction, so FA/FI < 1. Three factors affect anesthetic uptake:
 1. Blood solubility: Table 8-1 lists the various gas solubilities. (See card 8-6.)
 2. Alveolar blood flow: Essentially is cardiac output. As cardiac output increases, so does anesthetic uptake, 
and the rise in FA decreases, thus delaying induction.
 3. Partial pressure differences between alveolar gas and venous blood: Depend on tissue uptake; as uptake 
increases, more anesthetic agent will be needed, which will slow the rise in FA and thus slow induction.
Fa: Ventilation–perfusion mismatches are the primary cause for changes in Fa because they restrict normal flow 
and increase the alveolar–arterial difference (i.e., venous admixture, alveolar dead space).
Elimination: The most important route for elimination for inhalational anesthetics is the alveolus. Many of 
the factors that speed induction also speed recovery.
INHALATION ANESTHETICS 8-2
Pharmacokinetics of Inhalational Anesthetics
Minimum alveolar concentration (MAC): Defined as the alveolar concentration of an inhalational anesthetic 
at which 50% of patients do not move in response to surgical stimulation. Important because it allows anes-
thesiologists to compare potencies among various agents and mirrors brain partial pressure. MAC values are 
additive between anesthetics and can be altered by various factors.
• MAC decreased (anesthetic potency increases): Hypoxia with a PaO2 below 40, anemia, benzodiazepines, 
barbiturates, hypercarbia with a PaCO2 above 95, cholinesterase inhibitors, chronic amphetamines, cloni-
dine, narcotics, ketamine, pregnancy (normal by 72 hours postpartum), lithium, local anesthetics, opioids, 
elderly age (6% decrease in MAC per decade of age).
• MAC unchanged: Duration of anesthesia, gender, hyper- or hypothyroidism.
• MAC increased (anesthetic potency decreases): Chronic alcoholism, hyperthermia, hypernatremia, drugs 
that increase catecholamines (e.g., ephedrine, acute cocaine or amphetamines, monoamine oxidase 
 inhibitors).
INHALATION ANESTHETICS 8-3
Inhalational Pharmacology
Shared properties: Almost all inhalational anesthetics (IAs) result in an increase in cerebral blood flow (CBF) 
and intracranial pressure, depression of myocardial activity, rapid shallow breathing pattern, pulmonary bron-
chodilation, decrease in renal blood flow and glomerular filtration rate and, to a certain degree, cause a relax-
ation of skeletal muscle.
Nitrous oxide (NO): Colorless, odorless gas that antagonizes the N-methyl-D-aspartic acid (NMDA) receptor. 
Unlike volatile agents, nitrous oxide is a gas at room temperature and ambient pressure. It can be kept as a 
liquid under pressure because its critical temperature lies above room temperature. It also does not provide 
significant muscle relaxation and has been shown to cause postoperative nausea and vomiting. Even though 
nitrous oxide directly depresses myocardial contractility, arterial blood pressure, cardiac output, and heart rate 
are essentially unchanged or slightly elevated because of its stimulation of catecholamines. Importantly, NO is 
contraindicated in patients with pneumothorax, pulmonary embolus, pneumocephalus, and bowel obstruction 
because NO is 35 times more soluble then nitrogen in blood.
Halothane is no longer used in the United States. Its use results in a dose-dependent reduction of arterial blood 
pressure from a direct myocardial depression (most pronounced of the IA). Although halothane is a coronary 
artery vasodilator, coronary blood flow decreases because of the drop in systemic arterial pressure. By dilating 
cerebral vessels, halothane lowers cerebral vascular resistance and increases CBF. Autoregulation, the mainte-
nance of constant CBF during changes in arterial blood pressure, is blunted. Halothane is oxidized in the liver 
by a particular isozyme of cytochrome P-450 (2EI) to its principal metabolite, trifluoroacetic acid.
INHALATION ANESTHETICS 8-4
Inhalational Pharmacology
Isoflurane is a nonflammable volatile anesthetic with a pungent ethereal odor. It causes minimal cardiac 
depression and thus maintains CO thru a rise in heart rate because of partial preservation of carotid barore-
flexes. But there is a drop in blood pressure from a decrease in systemic vascular resistance (SVR). Rapid 
increases in isoflurane concentration lead to transient increases in heart rate, arterial blood pressure, and 
plasma levels of norepinephrine. Although isoflurane is a dilator of coronary arteries, it may cause coronary 
steal syndrome because dilation of normal coronary arteries causes redirection of blood from stenotic vessels. 
Similar to halothane, its oxidation can produce trifluoroacetic acid. At concentrations greater than 1 MAC, 
isoflurane increases CBF and intracranial pressure; at 2 MAC, it produces an electrically silent electroen-
cephalogram.
Desflurane is structurally similar to isoflurane. Its low solubility in blood and body tissues causes a very rapid 
washing and washout of anesthetic—in fact, the fastest of the current anesthetics. It has the highest vapor pres-
sure of all of the IAs, requiring constant heating of the vaporizer to maintain an accurate meter. Rapid increas-
es in desflurane concentration lead to transient but sometimes worrisome elevations in heart rate, blood pres-
sure, and catecholamine levels that are more pronounced than occur with isoflurane, particularly in patients 
with cardiovascular disease. Pungency and airway irritation during desflurane induction can be manifested by 
salivation, breath-holding, coughing, and laryngospasm. Airway resistance may increase in children with reac-
tive airway susceptibility. These problems make desflurane less than ideally suited for inhalation inductions.
INHALATION ANESTHETICS 8-5
Inhalational Pharmacology
Sevoflurane: Similar to desflurane, sevoflurane is halogenated with fluorine. Nonpungency and rapid 
increases in alveolar anesthetic concentration make sevoflurane an excellent choice for smooth and rapid 
inhalation inductions in pediatric and adult patients. Sevoflurane mildly depresses myocardial contractility. 
SVR and arterial blood pressure decline slightly less than with isoflurane or desflurane. Because sevoflurane 
causes little, if any, rise in heart rate, cardiac output is not maintained as well as with isoflurane or desflurane. 
Sevoflurane may prolong the QT interval, the clinical significance of which is unknown. The liver microsomal 
enzyme P-450 metabolizes sevoflurane at a rate one-fourth that of halothane but 10 to 25 times that of isoflu-
rane or desflurane and may be induced with ethanol or phenobarbital pretreatment. Theoretically, it can cause 
an accumulation of compound A with increased respiratory gas temperature, low-flow anesthesia, dry barium 
hydroxide absorbent (Baralyme), high sevoflurane concentrations, and anesthetics of long duration.
Xenon is an odorless, nonexplosive noble gas. With a MAC of 0.71 and a BG coefficient of 0.115, it is very 
fast in onset and emergence. Xenon’s anesthetic effects appear mediated by NMDA inhibition by competing 
with glycine at the glycine binding site. It appears to have little effect on the cardiovascular, hepatic, or renal 
systems and has been found to be protective against neuronal ischemia. Cost and limited ability have pre-
vented its use.
INHALATION ANESTHETICS 8-6
Inhalational Pharmacology
Insoluble agents, such as nitrous oxide, are taken up by the blood less avidly than soluble agents, such as 
halothane. As a consequence, the alveolar concentration of nitrous oxide rises faster than that of halothane, and 
induction is faster; Solubilities of an anesthetic in air, blood, and tissues are expressed as partition coefficients; 
The higher the blood/gas coefficient, the greater the IA’s solubility and the greater its uptake by thepulmonary 
circulation; As a consequence, alveolar partial pressure rises more slowly, and induction is prolonged.
Table 8-1. Partition Coefficients of Volatile Anesthetics at 37°C1
Agent Blood/ Gas Bra in / Blood Muscle / Blood Fa t/ Blood
Nitrous oxide 0.47 1.1 1.2 2.3
Halothane 2.4 2.9 3.5 60
Isoflurane 1.4 2.6 4.0 45
Desflurane 0.42 1.3 2.0 27
Sevoflurane 0.65 1.7 3.1 48
1These values are averages derived from multiple studies and should be used for comparison purposes, not as exact numbers.
INTRAVENOUS ANESTHETICS 9-1
Barbiturates (Thiopental, Methohexital, Thiamylal, Phenobarbital)
Mechanism of action: Depress the reticular activating system by potentiating the action of γ-aminobutyric 
acid (GABA) in increasing the duration of openings of chloride-specific ion channels.
Distribution: The duration of highly lipid-soluble barbiturates is determined by redistribution, not metabolism 
or elimination. If serum albumin is low or if nonionized fraction is increased (acidosis), higher brain and heart 
concentrations will be achieved for a given dose. Repetitive dosing saturates peripheral compartments so that 
duration depends on elimination not redistribution (termed context sensitivity).
Clearance: Biotransformation via hepatic oxidation (CYP-450), which is eliminated by renal excretion.
Cerebral effects: Vasoconstrict, decrease cerebral blood flow (CBF), decrease intracranial pressure (ICP), 
increase cerebral perfusion pressure, and decrease cerebral metabolic rate. They are protective in transient 
episodes of focal ischemia but not global ischemia. Small doses can cause a state of excitement.
Respiratory effects: Barbiturates cause depression of the medullary ventilatory center, decreasing the ventila-
tory response to hypercapnia and hypoxia, leading to apnea. They do not completely depress noxious airway 
reflexes, so beware of laryngospasm and bronchospasm.
Cardiovascular effects: Barbiturates decrease mean arterial pressure (MAP) and increase heart rate, but car-
diac output (CO) is maintained by compensatory baroreceptor reflexes. Sympathetically induced vasoconstric-
tion of resistance vessels may increase peripheral vascular resistance. However, in hypovolemia, congestive 
heart failure (CHF), or β-adrenergic blockade, CO and systolic blood pressure may fall dramatically because 
of unmasked direct myocardial depression.
INTRAVENOUS ANESTHETICS 9-2
Propofol
Mechanism of Action: Facilitates inhibitory neurotransmission of GABA; increases binding affinity of GABA 
to the GABAA receptor.
Onset: As quick as thiopental; one arm to brain circulation time.
Elimination: Conjugation in the liver results in inactive metabolites eliminated by renal clearance, but elimi-
nation is not affected by hepatic or renal failure.
Cerebral, respiratory, and cardiovascular effects: Causes decreased CBF and decreased ICP. In patients 
with elevated ICP, propofol may cause critical decreased cerebral perfusion pressure. Antiemetic effects. 
Causes apnea after induction by inhibiting hypoxic ventilatory drive and depresses normal response to hyper-
carbia. Propofol can release histamine but causes fewer symptoms in individuals with asthma than other 
agents and is not contraindicated in those with asthma. Decreased PVR, decreased contractility, and decreased 
preload.
Preparation: Propofol formulations can support the growth of bacteria, so sterile technique must be observed 
in preparation and handling. Propofol should be administered within 6 hours of opening the ampule.
Dosage: Induction: 2 to 2.5mg/kg (2.5–3.5 mg/kg child); maintenance load, 100 to 150 mcg/kg/min until 
sedated; then 25 to 75 mcg/kg/min.
INTRAVENOUS ANESTHETICS 9-3
Benzodiazepines
Mechanism of Action: Binds the GABAA receptor, which increases the frequency of opening of the associated 
chloride ion channel.
Biotransformation and elimination: Action is limited by redistribution. Benzodiazepines are biotransformed 
by phase I reactions and excreted in urine.
Cerebral Effects: Decrease the cerebral metabolic rate of oxygen (CMRO2), decrease CBF, decrease ICP, 
prevent and control grand mal seizures.
Respiratory and cardiovascular effects: Depress ventilatory response to CO2. Apnea is relatively uncommon 
after benzodiazepine induction, but respiratory arrest can occur. Minimal cardiovascular depressant effects. 
When administered with opioids, benzodiazepines rapidly reduce arterial blood pressure and PVR.
Effects on MAC: Reduce MAC by as much as 30%.
Effects of midazolam with heparin: Displaces from protein binding sites and increases drug availability up 
to 200% after 1000 units of heparin.
INTRAVENOUS ANESTHETICS 9-4
Benzodiazepines
Agent Use Route Dose (mg/ kg)
Diazepam Premedication
Sedation
Induction
Oral
IV
IV
0.2–0.51
0.04–0.2
0.3–0.6
Midazolam Premedication
Sedation
Induction
IM
IV
IV
0.07–0.15
0.01–0.1
0.1–0.4
Lorazepam Premedication
Sedation
Oral
IM
IV
0.053
0.03–0.052
0.03–0.042
IM, intramuscular; IV, intravenous.
1Maximum dose 15 mg.
2Not recommended for children.
INTRAVENOUS ANESTHETICS 9-5
Ketamine
Mechanism of action: Blocks postsynaptic reflexes in the spinal cord and inhibit excitatory neurotransmitters 
in selected areas of the brain. Dissociates thalamus from limbic system involved in awareness. NMDA recep-
tor antagonist.
Structure: Structural analogue of PCP.
Cerebral, respiratory, and cardiovascular Effects: Increased CMRO2, increased CBF, and increased ICP. 
Ventilatory drive is minimally affected. Potent bronchodilator, so good induction agent in patients with asthma. 
Increased MAP, increased heart, increased CO because of central stimulation of the sympathetic nervous 
 system and inhibits reuptake of norepinephrine. Increase PAP and myocardial work.
Metabolism: Duration limited by redistribution (half-life, 10–15 min). Biotransformed in the liver and 
excreted by the kidneys.
Side effects: Can cause direct myocardial depression and may lead to decreased CO in sympathetic blockade, 
spinal cord transection, or exhaustion of catecholamine stores (severe end-stage shock). Relatively contraindi-
cated in coronary artery disease, CHF, uncontrolled hypertension, and aneurysms.
Dosage: Induction: 1 mg/kg (5–10 mg/kg intramuscularly or per rectum); sedation load: 200 to 1000 mcg/kg; 
then 30 to 80 mcg/kg/min for maintenance.
INTRAVENOUS ANESTHETICS 9-6
Etomidate
Mechanism of action: Depresses the reticular activating system and mimics the inhibitory effects of GABA, 
so it is a sedative and hypnotic with no analgesic properties.
Biotransformation and excretion: Redistribution is responsible for its short half-life. Hepatic microsomal 
enzymes and plasma esterases rapidly hydrolyze etomidate to inactive metabolites. These metabolites are 
excreted in urine.
Cerebral, respiratory, and cardiovascular effects: Decreased CMRO2, decreased CBF, and decreased ICP. 
Ventilation is minimally affected. Minimal effects on the cardiovascular system. CO and contractility are usu-
ally unchanged. However, because etomidate induces light anesthesia, hypertension and tachycardia may be 
seen with intubation.
Dosage: Induction: 0.2 to 0.6 mg/kg (for age >10 years).
Side effects: Induction doses of etomidate transiently inhibit enzymes involved in cortisol and aldosterone 
synthesis. Long-term infusions can lead to adrenocortical suppression. Etomidate induction is associated with 
a 30-60% incidence of myoclonus potentially from disinhibitory effects on the parts of the nervous system that 
control extrapyramidal motor activity.
INTRAVENOUS ANESTHETICS 9-7
Case Card
A 58-year-old woman is brought into the trauma bay in a cervical collar 15 minutes after a motor vehicle 
accident. Her Glasgow Coma Scale (GCS) score is 7, and an initial examination shows multiple facial lacera-
tions, chest and abdominal bruising, and a right proximal femur fracture. Vital signs are heart rate, 127 beats/
min; blood pressure, 89/43 mm Hg; respiratoryrate, 14 breaths/min; and pulse ox, 91%.
What are your next steps?
INTRAVENOUS ANESTHETICS 9-8
Case Card
Answer
The airway must be secured in this obtunded woman (GSC score <8) with unknown medical history and lim-
ited knowledge of current injury. Vital signs are likely related to hemorrhagic shock, and further decreases in 
SVR can lead to circulatory collapse, limiting the usefulness of barbiturates or propofol induction. Although 
ketamine might improve blood pressure and CO, intracranial injury is unknown, and ketamine may induce 
increased ICP, potentially worsening cerebral injury. Etomidate or a high-dose benzodiazepine would be the 
optimal intravenous anesthetic for this trauma patient.
ANALGESIC AGENTS 10-1
Opioids: General Concepts
Mechanism of action: Opiate receptor activation inhibits the presynaptic release and postsynaptic response to 
excitatory neurotransmitters, acetylcholine, and substance P from the nociceptive neurons. The properties of 
specific opioids depend on which receptor is bound and the binding affinity of the drug. In the case of spinal 
and epidural administration of opioids, transmission of pain impulses are modified in the dorsal horn of the 
spinal cord. Opioid effects vary based on the duration of exposure, and long opioid administration leads to 
opioid tolerance and changes in opioid responses.
Absorption: Affected by lipid solubility. Low lipid soluble morphine slows blood–brain barrier (BBB) pas-
sage into the systemic circulation so that onset is slow and duration prolonged. Highly lipid-soluble fentanyl 
has a rapid onset and short duration. The low molecular weight and high lipid solubility of fentanyl also favor 
transdermal absorption.
Distribution: After intravenous administration, the distribution half-lives of all of the opioids are fairly rapid 
(5–20 min). The low fat solubility of morphine slows passage across the BBB, however, so its onset of action 
is slow and its duration of action is prolonged. This contrasts with the increased lipid solubility of fentanyl and 
sufentanil, which are associated with faster onsets and shorter durations of action when administered in small 
doses. When fentanyl or sufentanil is administered in large doses, biotransformation, not redistribution, deter-
mines “half-time.” “Context-sensitive half-time” is the time required for the plasma drug concentration to 
decline by 50% after termination of an infusion.
ANALGESIC AGENTS 10-2
Opioids: General Concepts
Biotransformation: Except for remifentanil, all opioids depend on the liver for biotransformation and their 
clearance depends on liver blood flow. Morphine and hydromorphone undergo conjugation with glucuronic 
acid to form, in the former case, morphine 3-glucuronide and morphine 6-glucuronide, and in the latter case, 
hydromorphone 3-glucuronide. Meperidine is N-demethylated to normeperidine, an active metabolite associ-
ated with seizure activity, particularly after very large meperidine doses. The small volume of distribution (Vd) 
of alfentanil results in a short elimination half-life of 1.5 hours. Remifentanil has an ester group that is hydro-
lyzed by esterase hydrolysis, so its elimination half-life is less than 10 minutes with no cumulative effects even 
in prolonged infusions.
Excretion: The end products of morphine and meperidine biotransformation are eliminated by the kidneys, 
with less than 10% undergoing biliary excretion. Morphine administration in patients with renal failure has 
been associated with prolonged narcosis and ventilatory depression. Renal dysfunction increases the chance of 
toxic effects from normeperidine accumulation. Metabolites of sufentanil are excreted in urine and bile. 
Remifentanil is not affected by renal or hepatic failure.
Drug interactions: Meperidine administered with monamine oxidase can result in hypertension, hypoten-
sion, hyperpyrexia, coma, or respiratory arrest. Barbiturates, benzodiazepines, and other central nervous 
system depressants can have synergistic cardiovascular, respiratory, and sedative effects with opioids. The 
biotransformation of alfentanil after treatment with erythromycin may lead to prolonged sedation and respira-
tory depression.
ANALGESIC AGENTS 10-3
Opioids: Effects on Organ Systems
Cerebral effects: Decrease the cerebral metabolic rate of oxygen (CMRO2), decrease intracranial pressure 
(ICP), decrease cerebral blood flow (CBF), no amnesia. All opioids stimulate the medullary chemoreceptor 
trigger zone to cause nausea and vomiting. Meperidine may induce seizures, especially in end-stage renal 
disease due to metabolite normeperidine.
Respiratory effects: Depress ventilation, particularly respiratory rate. The apneic threshold, the highest 
PaCO2 at which point a patient becomes apneic, is elevated, and hypoxic drive is decreased. Opioids (particu-
larly fentanyl, sufentanil, and alfentanil) can induce chest wall rigidity severe enough to prevent adequate 
ventilation; this is more likely after large boluses and responds to neuromuscular blocking drugs (NMBDs).
Cardiovascular effects: Meperidine increases heart rate; all others cause vagal-mediated bradycardia. 
Meperidine and morphine release histamine, which can cause profound hypotension; this is minimized by 
infusing opioids slowly or by pretreatment with histamine antagonists. Arterial blood pressure often falls as a 
result of bradycardia, venodilation, and decreased sympathetic reflexes. Intraoperative hypertension during 
opioid anesthesia may signal inadequate anesthetic depth. When administered with benzodiazepines, opioids 
may reduce cardiac output.
Gastrointestinal: Opioids slow gastrointestinal motility by binding to opioid receptors in the gut and reducing 
peristalsis, which can lead to severe constipation. Opioids may cause biliary colic by inducing contraction of 
the sphincter of Oddi.
Endocrine: Opioids block the secretion of catecholamines, antidiuretic hormone, and cortisol to surgical 
stimulation.
ANALGESIC AGENTS 10-4
 Uses and Doses of Common Opioids
Agent Use Route Dose 1
Morphine Postoperative analgesia IM 0.05–0.2 mg/ kg
IV 0.03–0.15 mg/ kg
Fentanyl Intraoperative anesthesia IV 2–150 µg/ kg
Postoperative analgesia IV 0.5–1.5 µg/ kg
Sufentanil Intraoperative anesthesia IV 0.25–30 µg/ kg
Alfentanil Intraoperative anesthesia
Loading dose IV 8–100 µg/ kg
Maintenance infusion IV 0.5–3 µg/ kg/ min
Remifentanil Intraoperative anesthesia
Loading dose IV 1.0 µg/ kg
Maintenance infusion IV 0.5–20 µg/ kg/ min
Postoperative analgesia/ sedation IV 0.05–0.3 µg/ kg/ min
IM, intramuscular; IV, intravenous.
1Note: The wide range of opioid doses reflects a large therapeutic index and depends upon which other anesthetics are simultaneously administered.
ANALGESIC AGENTS 10-5
 Classification of Opioid Receptors1
Receptor Clin ica l Effect Agonists
µ Supraspinal analgesia (µ-1) Morphine
Respiratory depression (µ-2) Met-enkephalin2
Physical dependence β-Endorphin2
Muscle rigidity Fentanyl
κ Sedation Morphine
Spinal analgesia Nalbuphine
Butorphanol
Dynorphin2
Oxycodone
δ Analgesia Leu-enkephalin2
Behavioral β-endorphin2
Epileptogenic
σ Dysphoria Pentazocine
Hallucinations Nalorphine
Respiratory stimulation Ketamine
1Note: The relationships among receptor, clinical effect, and agonist are more complex than indicated in this 
table . For example, pentazocine is an antagonist at µ receptors, a partial agonist at κ receptors, and an agonist 
at σ receptors.
2Endogenous opioid.
ANALGESIC AGENTS 10-6
 Physical Characteristics of Opioids that Determine Distribution
Agent Nonionized Fraction Prote in Binding Lipid Solubility
Morphine ++ ++ +
Meperidine + +++ ++
Fentanyl + +++ ++++
Sufentanil ++ ++++ ++++
Alfentanil ++++ ++++ +++
Remifentanil +++ +++ ++
+, very low; ++, low; +++, high; ++++, very high.
ANALGESIC AGENTS 10-7
COX Inhibitors: General Concepts
Mechanism of Action: Inhibition of cyclooxygenase (COX), thekey step in prostaglandin synthesis. COX-1 
receptors are widely distributed throughout the body, including gut and in platelets. COX-2 is produced in 
response to inflammation.
Clinical uses: Agents that inhibit COX nonselectively (e.g., aspirin) inhibit fever, inflammation, pain, and 
thrombosis. COX-2 selective agents (e.g., acetaminophen [paracetamol], celecoxib, etoricoxib) can used peri-
operatively without concerns regarding platelet inhibition or gastrointestinal (GI) upset.
Side effects: Although COX-1 inhibition inhibits thrombosis, selective COX-2 inhibition increases the risk of 
heart attack, thrombosis, and stroke. Aspirin is unique in that it irreversibly inhibits COX-1 by acetylating a 
serine residue in the enzyme. The irreversible nature of its inhibition underlies the nearly 1-week duration of 
its clinical effects (e.g., return of platelet aggregation to normal) after drug discontinuation.
ANALGESIC AGENTS 10-8
COX Inhibitors: Effects on Organ Systems
Cerebral effects: No consistent data on the effects of COX inhibitors on CBF or cerebral physiology in 
humans.
Respiratory effects: Aspirin overdose has complex effects on acid–base balance and respiration.
Cardiovascular effects: No direct cardiovascular effects.
Gastrointestinal effects: COX 1 inhibition can be complicated by GI upset and even upper GI bleeding. 
Acetaminophen abuse or overdosage is one of the most common causes of fulminant hepatic failure resulting 
in hepatic transplantation in Western societies.
NEUROMUSCULAR BLOCKING AGENTS 11-1
The Basics
The neuromuscular junction: Motor neurons and muscle cells are separated by the synaptic cleft. 
Depolarization of the motor neuron results in acetylcholine (ACh) release, which diffuses across the synaptic 
cleft and binds to nicotinic cholinergic receptors on the muscle cell. Each neuromuscular junction contains 
approximately 5 million of these receptors, but activation of only about 500,000 receptors is required for nor-
mal muscle contraction. ACh is metabolized by acetylcholinesterase.
Neuromuscular blocking agents are divided into two classes: depolarizing and nondepolarizing.
• Nondepolarizing muscle relaxants act as competitive antagonists. ACh receptors are bound but are inca-
pable of inducing the conformational change necessary for ion channel opening. Because ACh is prevented 
from binding to its receptors, no end-plate potential develops.
• Depolarizing muscle relaxants bind to ACh receptors, generating a muscle action potential. Unlike ACh, 
however, these drugs are not metabolized by acetylcholinesterase, and their concentration in the synaptic 
cleft does not fall as rapidly, resulting in a prolonged depolarization of the muscle end-plate.
 � Phase I block: The end-plate cannot repolarize as long as the depolarizing muscle relaxant continues to 
bind to ACh receptors. This is phase I block.
 � Phase II block: After a period of time, prolonged end-plate depolarization can cause ionic and conforma-
tional changes in the ACh receptor that clinically resembles that of nondepolarizing muscle relaxants. This 
is phase II block.
NEUROMUSCULAR BLOCKING AGENTS 11-2
Disease States and Monitoring
Disease states can affect the neuromuscular junction.
• Muscle denervation: Stimulates a compensatory increase in the number of ACh receptors and promotes 
expression of extrajunctional ACh receptors, leading to exaggerated response to depolarizing muscle relax-
ants (with more receptors being depolarized) but a resistance to nondepolarizing relaxants (more receptors 
that must be blocked).
• Myasthenia gravis: Few ACh receptors lead to resistance to depolarizing relaxants and an increased sensi-
tivity to nondepolarizing relaxants.
• Eaton-Lambert myasthenic syndrome: Decreased release of ACh.
Peripheral nerve stimulators are used to monitor neuromuscular function. Most commonly they are used for 
tetany (a sustained stimulus of 50–100 Hz) and train-of-four (a series of four twitches in 2 s).
• Fade, a gradual diminution of evoked response during prolonged or repeated nerve stimulation, is indicative 
of a nondepolarizing block. Adequate clinical recovery correlates well with the absence of fade.
• Phase I depolarization block does not exhibit fade during tetanus or train-of-four, and it does not demon-
strate posttetanic potentiation. If enough depolarizer is administered, however, the quality of the block 
changes to resemble a nondepolarizing block (phase II block).
NEUROMUSCULAR BLOCKING AGENTS 11-3
Succinylcholine
Mechanism of action: Depolarizing muscle relaxant, the only one in clinical use today.
Dosage: 1 to 1.5 mg/kg for intubation; can maintain with infusion or small repeated doses.
Onset: 30 to 60 seconds; typically lasts less than 10 minutes.
Mechanism of termination of action: Diffuses from neuromuscular junction, metabolized by pseudocholin-
esterase.
Prolonged by: Hypothermia (slightly prolonged); reduced pseudocholinesterase levels as found in pregnancy, 
liver disease, renal failure (2–20 minutes); abnormal pseudocholinesterase enzyme (heterozygous for atypical 
pseudocholinesterase results in 20 to 30-minute block, homozygous for atypical pseudocholinesterase results 
in 4- to 5-hour block).
Clinical note: Dibucaine inhibits normal pseudocholinesterase enzyme by 80% (the dibucaine number) and 
atypical pseudocholinesterase by 20%. Heterozygous individuals have a dibucaine number of 40% to 60%.
Structure: Two joined ACh molecules.
NEUROMUSCULAR BLOCKING AGENTS 11-4
Succinylcholine
Succinylcholine has two important drug interactions:
• Cholinesterase inhibitors prolong the action of succinylcholine.
• Nondepolarizing neuromuscular blocking agents can antagonize a phase I block.
Contraindications: Routine use of succinylcholine is relatively contraindicated in children because of the 
risk of hyperkalemia, rhabdomyolysis, and cardiac arrest from undiagnosed myopathies.
Side Effects
• Cardiovascular: Succinylcholine stimulates all ACh receptors, which can lead to bradycardia or tachycar-
dia. Bradycardia occurs most frequently in children but can occur in adults after a second dose.
• Fasciculations denote the onset of paralysis.
• Hyperkalemia: Normal muscle releases potassium with succinylcholine elevating the plasma potassium by 
0.5 mEq/L. This can be life threatening with preexisting hyperkalemia or in patients who have suffered burn 
injury, massive trauma, or other conditions.
• Muscle pains are sometimes noted postoperatively after succinylcholine administration.
• Elevation of intracranial, intragastric, and intraocular pressures have been reported.
• Masseter muscle rigidity occurs transiently.
• Prolonged action (discussed on front side of card)
• Malignant hyperthermia can be triggered in susceptible patients by succinylcholine.
NEUROMUSCULAR BLOCKING AGENTS 11-5
The Nondepolarizers
Nondepolarizing neuromuscular block agents can be classified into three categories: benzylisoquinolinium, 
steroidal, and chlorofumarates.
• Benzylisoquinolines: Tend to release histamine.
• Steroidal: Tend to be vagolytic.
Maintaining neuromuscular blockade can be done by administering intermittent boluses or by continuous 
infusion but should be guided by a nerve stimulator and clinical signs.
Potentiation can occur by volatile anesthetics (10%–15% dose reduction) and by adding other nondepolariz-
ing neuromuscular blockers (more than additive). Additionally, hypothermia, respiratory acidosis, hypoka-
lemia, hypocalcemia, and hypermagnesemia can prolong a nondepolarizing block.
Muscle groups vary in response to blockade. In general, the diaphragm, jaw, larynx, and facial muscles 
(orbicularis oculi) respond to and recover from muscle relaxation sooner than the thumb.
Side effects include histamine release and autonomic effects, depending on the drug.
Hepatic clearance can impact pancuronium and vecuronium significantly.
Renal excretion is significant in clearing doxacurium, pancuronium, vecuronium, andpipecuronium.
NEUROMUSCULAR BLOCKING AGENTS 11-6
Nondepolarizing Muscle Relaxants
Atracurium (benzylisoquinoline)
Metabolism and excretion: Undergoes ester hydrolysis from nonspecific esterases and Hofmann elimination 
(spontaneous breakdown dependent on physiologic pH and temperature).
Dosage: 0.5 mg/kg for intubation; intermediate duration.
Side effects: Histamine release (hypotension, tachycardia, bronchospasm), laudanosine toxicity (breakdown 
product of Hofmann elimination that can cause central nervous system excitation and is metabolized by liver), 
prolonged action (at abnormal pH and temperature).
Cisatracurium (benzylisoquinoline; stereoisomer of atracurium)
Metabolism and excretion: Same as atracurium.
Dosage: 0.1 to 0.15 mg/kg for intubation; intermediate duration.
Side effects: Laudanosine toxicity (significantly lower levels than with atracurium), prolonged action 
(at abnormal pH and temperature).
NEUROMUSCULAR BLOCKING AGENTS 11-7
Nondepolarizing Muscle Relaxants
Pancuronium (steroidal)
Metabolism and excretion: Excretion is primarily renal (40%); limited liver metabolism and bile clearance.
Dosage: 0.08 to 0.12 mg/kg for intubation; long duration
Side effects: Hypertension and tachycardia (caused by vagal blockade, sympathetic stimulation), arrhythmias.
Vecuronium (steroidal)
Metabolism and excretion: Excretion is primarily biliary and secondarily renal (25%); limited liver 
 metabolism.
Dosage: 0.08 to 0.12 mg/kg for intubation; intermediate duration
Side effects: Can precipitate if administered with thiopental; possible prolonged duration in liver failure; active 
metabolites can lead to prolonged duration after long infusion.
NEUROMUSCULAR BLOCKING AGENTS 11-8
Nondepolarizing Muscle Relaxants
Rocuronium (steroidal)
Metabolism and excretion: No metabolism; excreted primarily by the liver and slightly by the kidneys.
Dosage: 0.45 to 0.9 mg/kg intravenously for routine intubation; 0.9 to 1.2 mg/kg intravenously for rapid intu-
bation; can be given 1 to 2 mg/kg intramuscularly (onset, 3–6 min); intermediate duration at lower dose range.
Side effects: Prolonged action at higher dosage range.
Gantacurium (chlorofumarate)
Metabolism and excretion: Cysteine adduction and ester hydrolysis.
Dosage: 0.2 mg/kg for intubation with onset in 1 to 2 minutes; duration of action is 5 to 10 minutes (can be 
accelerated by edrophonium or exogenous cysteine).
Side effects: Histamine release at higher dosages.
Note: Not yet commercially available in the United States.
CHOLINESTERASE INHIBITORS AND OTHER PHARMACOLOGIC 
ANTAGONISTS TO NEUROMUSCULAR BLOCKING AGENTS 12-1
Cholinergic Pharmacology: The Basics
Acetylcholine (ACh) synthesis: ACh is 
synthesized in nerve terminals by the 
enzyme choline acetyltransferase from 
choline and acetylcoenzyme A.
ACh degradation: ACh is hydrolyzed by 
the enzyme acetycholinesterase into ace-
tate and choline.
CHOLINESTERASE INHIBITORS AND OTHER PHARMACOLOGIC 
ANTAGONISTS TO NEUROMUSCULAR BLOCKING AGENTS 12-2
Cholinergic Pharmacology: The Basics
The two receptors types are nicotinic and muscarinic.
Nicotinic receptors stimulate autonomic ganglia and skeletal mus-
cle. These receptors are also activated by the nicotine alkaloid.
Muscarinic receptors stimulate end-organ receptors. These recep-
tors are also activated by the alkaloid muscarine.
CHOLINESTERASE INHIBITORS AND OTHER PHARMACOLOGIC 
ANTAGONISTS TO NEUROMUSCULAR BLOCKING AGENTS 12-3
Cholinergic Pharmacology: Clinical Aspects
Normal muscle action: Neuromuscular transmission depends on the release of ACh from presynaptic neurons 
and activation of postsynaptic nicotinic cholinergic receptors on the motor end plate.
Nondepolarizing muscle relaxants: Neuromuscular transmission is blocked by nondepolarizing muscle 
relaxants that bind to postsynaptic nicotinic cholinergic receptors.
Reversal of Nondepolarizing Muscle Relaxants
• Spontaneous reversal: Occurs with gradual diffusion, redistribution, metabolism, and excretion of nonde-
polarizing muscle relaxants.
• Pharmacologic reversal: Occurs with the administration of specific reversal agents. Reversal with acetyl-
cholinesterase inhibitors should be monitored with a peripheral nerve stimulator. At least one twitch with 
train-of-four (TOF) stimulation should be present before reversal. Suggested endpoints for recovery are 
sustained tetanus for 5 s in response to a 100-Hz stimulus in anesthetized patients, an adequate TOF ratio 
greater than 0.9 as assessed by acceleromyography, or sustained head or leg lift in awake patients.
Organophosphates are used in ophthalmology and pesticides. They irreversibly bind to cholinesterase 
 inhibitors.
CHOLINESTERASE INHIBITORS AND OTHER PHARMACOLOGIC 
ANTAGONISTS TO NEUROMUSCULAR BLOCKING AGENTS 12-4
Cholinergic Pharmacology: Clinical Aspects
Side effects of acetylcholinesterase inhibitors: In addition to increasing the availability of acetylcholine at 
the neuromuscular junction, inhibition of acetylcholinesterase can increase cholinergic receptor activity else-
where, leading to side effects.
• Cardiovascular system: The predominant muscarinic effect on the heart is a vagal-like bradycardia that can 
progress to sinus arrest.
• Pulmonary receptors: Muscarinic stimulation can result in bronchospasm and increased respiratory secre-
tions.
• Cerebral receptors: Physostigmine is a cholinesterase inhibitor that can cross the blood–brain barrier 
(BBB). It can cause diffuse activation of the electroencephalogram by stimulating muscarinic and nicotinic 
receptors within the central nervous system (CNS).
• Gastrointestinal receptors: Muscarinic stimulation increases peristaltic activity (esophageal, gastric, and 
intestinal) and glandular secretions (e.g., salivary, parietal). Perioperative bowel anastomotic leakage, nau-
sea and vomiting, and fecal incontinence have been attributed to the use of cholinesterase inhibitors.
CHOLINESTERASE INHIBITORS AND OTHER PHARMACOLOGIC 
ANTAGONISTS TO NEUROMUSCULAR BLOCKING AGENTS 12-5
Cholinergic Pharmacology: Drugs
Neostigmine
Mechanism of action: Acetylcholinesterase inhibitor.
Dosage: Up to 0.08 mg/kg in children; 5 mg in adults.
Onset: Effects apparent in 5 to 10 minutes; peak at 10 minutes and last more than 1 hour.
Clinical note: Typically administered with glycopyrrolate to prevent bradycardia.
Structure: Carbamate moiety (binds to acetylcholinesterase) and quaternary ammonium group (prevents pas-
sage across the BBB).
CHOLINESTERASE INHIBITORS AND OTHER PHARMACOLOGIC 
ANTAGONISTS TO NEUROMUSCULAR BLOCKING AGENTS 12-6
Cholinergic Pharmacology: Drugs
Pyridostigmine
Mechanism of action: Acetylcholinesterase inhibitor.
Dosage: Up to 0.4 mg/kg in children; 20 mg in adults.
Onset: Effects apparent in 10 to 15 minutes and lasts more than 2 hours.
Clinical note: Typically administered with glycopyrrolate to prevent bradycardia.
Structure: Carbamate moiety (binds to acetylcholinesterase) and quaternary ammonium incorporated into 
phenol ring (prevents passage across the BBB).
CHOLINESTERASE INHIBITORS AND OTHER PHARMACOLOGIC 
ANTAGONISTS TO NEUROMUSCULAR BLOCKING AGENTS 12-7
Cholinergic Pharmacology: Drugs
Edrophonium
Mechanism of action: Acetylcholinesterase inhibitor.
Dosage: 0.5 to 1 mg/kg.
Onset: Most rapid onset and shortest duration for class. Effects apparent in 1 to 2 minutes. Higher dosages last 
up to 1 hour.
Clinical note: Typically administered with atropine to prevent bradycardia. If used with glycopyrrolate, should 
be given several minutes after glycopyrrolate so that onset time matches.
Structure: Noncovalent binding to acetylcholinesterase. Quaternary ammonium group (prevents passage 
across the BBB).
CHOLINESTERASE INHIBITORS AND OTHER PHARMACOLOGIC 
ANTAGONISTS TO NEUROMUSCULAR BLOCKING AGENTS 12-8
Cholinergic Pharmacology: Drugs
Physostigmine
Mechanism of action: Acetylcholinesterase inhibitor.
Dosage: 0.01 to 0.03 mg/kg.
Clinical note: Can be used to treat central anticholinergictoxicity from scopolamine or atropine overdose. 
Also reverses some of the CNS depression from benzodiazepines and volatile anesthetics.
Structure: Carbamate moiety. Lack of quaternary ammonium allows passage across the BBB.
CHOLINESTERASE INHIBITORS AND OTHER PHARMACOLOGIC 
ANTAGONISTS TO NEUROMUSCULAR BLOCKING AGENTS 12-9
Cholinergic Pharmacology: Drugs
Sugammadex
Mechanism of action: Hydrophobic structural interactions trap aminosteroid neuromuscular blocking agents 
(rocuronium, vecuronium) within cyclodextrin cavity, terminating neuromuscular block.
Dosage: 4 to 8 mg/kg.
Onset: Can reverse shallow and deep neuromuscular blockade within 2 minutes.
Clinical note: Because of concerns about hypersensitivity and allergic reactions, not yet approved by the U.S. 
Food and Drug Administration. Currently is available and used in Europe.
Structure: Modified cyclodextrin.
CHOLINESTERASE INHIBITORS AND OTHER PHARMACOLOGIC 
ANTAGONISTS TO NEUROMUSCULAR BLOCKING AGENTS 12-10
Cholinergic Pharmacology: Drugs
L-Cysteine
Mechanism of action: Combines with gantacurium to form less active degradation products.
Dosage: 10 to 50 mg/kg.
Clinical note: Still in investigative stages.
Structure: An endogenous amino acid.
ANTICHOLINERGIC DRUGS 13-1
Mechanism of Action
• Ester linkage essential for effective binding to acetylcholine (ACh) receptors
• Competitive antagonism of ACh, thereby preventing activation of second messenger pathways, specifically 
cGMP.
• Muscarinic ACh receptor subtypes: neuronal (M1), cardiac (M2), glandular (M3).
Clinical pharmacology: Extent of anticholinergic effect depends on the degree of baseline vagal tone.
Cardiovascular
• Blockade of muscarinic ACh receptors in sinoatrial node = tachycardia
 � Useful in reversing bradycardia from vagal reflexes: baroreflex, peritoneal stimulation, oculocardiac reflex
 � Transient bradycardia (paradoxical) has been reported in response to low doses of anticholinergics, sug-
gesting a weak peripheral agonist effect
• Facilitation of conduction through the atrioventricular node
 � Decreases P-R interval
 � Decreases vagally mediated heart block
• Atrial arrhythmias and nodal (junctional) rhythms occasionally occur.
• Presynaptic muscarinic receptors on adrenergic nerve terminals are known to inhibit norepinephrine 
release, so antagonism may modestly enhance sympathetic activity.
• Large doses may result in dilation of cutaneous blood vessels (i.e., atropine flush).
ANTICHOLINERGIC DRUGS 13-2
Clinical Pharmacology
Respiratory: Effects particularly pronounced in patients with asthma and chronic obstructive pulmonary 
disease (COPD).
• Inhibit the secretions of the respiratory tract mucosa
• Relaxation of the bronchial smooth muscle
 � Reduces airway resistance
 � Increases anatomic dead space
Cerebral: Spectrum of effects depending on drug and dosage.
• Stimulation: Excitation, restlessness, hallucinations
• Depression: Sedation, amnesia
• Physostigmine, a cholinesterase inhibitor that crosses the blood–brain barrier, promptly reverses
Gastrointestinal
• Salivary secretions are markedly reduced
• Gastric secretions are also reduced (requires larger doses)
• Decreased intestinal motility and peristalsis = prolonged gastric emptying
• Lower esophageal sphincter pressure reduced
Ophthalmic
• Mydriasis and cycloplegia: papillary dilation and an inability to accommodate to near vision
• Acute, angle-closure glaucoma unlikely after administration of anticholinergics
ANTICHOLINERGIC DRUGS 13-3
Clinical Pharmacology
Genitourinary
• May decrease ureter and bladder tone as a result of smooth muscle relaxation = urinary retention, particu-
larly in older men with prostatic hypertrophy
Thermoregulation
• Inhibition of sweat glands = rise in body temperature (i.e., atropine fever)
 Specific Anticholinergic Drugs
Atropine Scopolamine Glycopyrrola te
Tachycardia +++ + ++
Bronchodilatation ++ + ++
Sedation + +++ 0
Antisialagogue effect ++ +++ +++
0, no effect; +, m inimal effect; ++, moderate effect; +++, marked effect.
ANTICHOLINERGIC DRUGS 13-4
Atropine
Dosage
• Premedication (antisialagogue effect): intravenous (IV) or intramuscular (IM) 0.01 to 0.02 mg/kg up to the 
usual adult dose of 0.4 to 0.6 mg
• Severe bradycardia: Larger IV doses up to 2 mg may be required
Clinical Considerations
• Most efficacious anticholinergic for bradyarrhythmias
• Patients with coronary artery disease may not tolerate the increased myocardial oxygen demand or decreased 
oxygen supply associated with atropine-induced tachycardia
• Ipratropium bromide solution (0.5 mg in 2.5 mL) is a derivative of atropine; metered-dose inhibitor treat-
ment of bronchospasm; particularly effective in acute COPD when combined with a β-agonist (i.e., alb-
uterol)
• Rapidly crosses the BBB; central nervous system (CNS) effects are minimal at usual doses, although toxic 
doses are typically associated with excitatory reactions
• Associated with mild postoperative memory deficits
• Cautious use in narrow-angle glaucoma, prostatic hypertrophy, and bladder-neck obstruction
ANTICHOLINERGIC DRUGS 13-5
Scopolamine
Dosage
• Premedication (antisialagogue effect): usually given IM 0.01 to 0.02 mg/kg up to the usual adult dose of 
0.4 to 0.6 mg
• Scopolamine hydrobromide solutions available as 0.3, 0.4, and 1 mg/mL
Clinical Considerations
• More potent antisialagogue than atropine
• Greater CNS effects: drowsiness, amnesia, (restlessness and delirium possible); sedative effects may be 
useful as premedication; may interfere with awakening after short procedures
• Prevention of motion sickness: lipid solubility allows transdermal absorption
• Avoid in patients with closed-angle glaucoma
ANTICHOLINERGIC DRUGS 13-6
Glycopyrrolate
Dosage
• Usual dose is one-half that of atropine (i.e., premedication: 0.005–0.01 mg/kg up to 0.2–0.3 mg in adults)
• Glycopyrrolate injection packaged as 0.02-mg/mL solution
Clinical Considerations
• Because of its unique structure (quaternary amine in contrast with atropine and scopolamine, which are both 
tertiary amines), does not cross the BBB; no CNS or ophthalmic activity
• Most potent inhibition of salivary and respiratory secretions
• Heart rate increases after IV (but not IM) administration
• Longer duration of action than atropine (2–4 h vs. 30 min) after IV administration
ANTICHOLINERGIC DRUGS 13-7
Case Discussion: Central Anticholinergic Syndrome
Scenario
An elderly patient is scheduled for enucleation of a blind, painful eye. Scopolamine 0.4 mg is administered 
intramuscularly as premedication. In the preoperative holding area, the patient becomes agitated and disori-
ented. The only other medication the patient has received is 1% atropine eye drops.
Initial Questions
 1. How many milligrams of atropine are in one drop of a 1% solution?
 2. How are ophthalmic drops systemically absorbed?
 3. What are the signs and symptoms of anticholinergic poisoning?
Answers to Initial Questions:
 1. A 1% solution contains 10 mg/mL. Eyedroppers average 20 drops/mL (although this may vary). Therefore, 
1 drop contains 0.5 mg of atropine.
 2. Absorption by vessels in the conjunctival sac is similar to subcutaneous injection. More rapid absorption is 
possible by the mucosa of the nasolacrimal duct.
 3. Anticholinergic overdose involves several organ systems. Central anticholinergic syndrome refers to CNS 
changes ranging from unconsciousness to hallucinations. Agitation and delirium are more common in 
elderly patients. Systemic manifestations include dry mouth, tachycardia, atropine flush, atropine fever, and 
impaired vision (although not in this case).
ANTICHOLINERGIC DRUGS 13-8
Case Discussion: Central Anticholinergic Syndrome
Follow-up Questions:
 1. What other drugs possess anticholinergic activity that could predispose to the central anticholinergic syn-
drome?
 2. What drug is an effective antidote to anticholinergic overdose?
 3. Should this case be cancelled?
Answers to Follow-up Questions:1. Tricyclic antidepressants, antihistamines, and antipsychotics have antimuscarinic properties that may 
potentiate the side effects of anticholinergic drugs.
 2. Cholinesterase inhibitors indirectly increase the amount of acetylcholine available to compete with anticho-
linergic drugs at the muscarinic receptor. Neostigmine, pyridostigmine, and edrophonium possess a quater-
nary ammonium group that prevents CNS penetration. In contrast, physostigmine, a tertiary amine, is lipid 
soluble and effectively reverses central anticholinergic toxicity (an initial dose of 0.01–0.03 mg/kg may 
have to be repeated after 15–30 minutes).
 3. This procedure is clearly elective. If the anticholinergic overdose were accompanied by tachycardia, fever, 
and so on, it would be prudent to postpone the surgery in this elderly patient. However, if the patient’s 
mental status responds to physostigmine and there are no other apparent anticholinergic side effects, it 
would be reasonable to proceed.
ADRENERGIC AGONISTS AND ANTAGONISTS 14-1
Adrenergic Receptors
• Alpha-1 adrenergic receptors: G protein–coupled receptors that increase intracellular calcium ion concentration, 
thus leading to smooth muscle contraction. These receptors are widely distributed throughout the body, and their 
effect depends on end-organ distribution. Alpha-1 agonists cause vasoconstriction, bronchoconstriction, uterine con-
traction, contraction of sphincter muscles of the gastrointestinal (GI) tract, and mydriasis.
• Alpha-2 adrenergic receptors: Principle function is as presynaptic autoreceptors, which decrease adenylate cyclase 
activity, thus decreasing calcium entry into neuronal terminal, limiting subsequent exocytosis of storage vesicles 
containing norepinephrine. This negative feedback mechanism reduces endogenous norepinephrine release from 
central nervous system neurons, causing sedation, decreased sympathetic outflow, and subsequent peripheral vasodi-
lation with decreased systemic vascular resistance.
• Beta-1 adrenergic receptors: Located chiefly in postsynaptic membranes of heart. They function to increase adenyl-
ate cyclase activity, converting adenosine triphosphate to cyclic adenosine monophosphate, thus initiating a kinase 
phosphorylation cascade. Beta-1 agonists cause increased chronotropy, dromotropy (increased conduction velocity), 
and inotropy.
• Beta-2 adrenergic receptors: Mostly postsynaptic receptors located in smooth muscle and gland cells. They are 
G protein–coupled receptors that also activate adenylate cyclase; however, they produce smooth muscle relaxation, 
manifested in various end organs as bronchodilation, vasodilation, uterine relaxation (tocolysis), and relaxation of 
bladder and GI smooth muscle. Beta-2 agonists also cause glycogenolysis, lipolysis, gluconeogenesis, and insulin 
release. Beta-2 receptors activate the Na-K pump, driving potassium intracellularly, which can lead to hypokalemia and 
arrhythmias. 
ADRENERGIC AGONISTS AND ANTAGONISTS 14-2
Receptor Selectivity of Adrenergic Agonists
 Alpha-1 Affinities Alpha-2 Affinities
Phenylephrine +++ +
Norepinephrine ++ ++
Epinephrine ++ ++
Ephedrine ++ ?
Dopamine ++ ++
Dobutamine 0/+ 0
Clonidine + ++
 Beta-1 Affinities Beta-2 Affinities
Phenylephrine 0 0
Norepinephrine ++ 0
Epinephrine +++ ++
Ephedrine ++ +
Dopamine ++ +
Dobutamine +++ +
Clonidine 0 0
HYPOTENSIVE AGENTS 15-1
Nitrovasodilators
Sodium Nitroprusside: Mechanism of Action
• Relaxes both arteriolar and venous smooth muscle. As the drug is metabolized, nitric oxide (NO) is 
released, which activates the cGMP pathway, thereby inhibiting the release of intracellular calcium, which 
results in smooth muscle relaxation.
• NO has an ultra-short half-life (<5 s), which provides sensitive endogenous control of regional blood flow.
Clinical Uses: Potent and reliable antihypertensive
• Diluted to a concentration of 100 µg/mL.
• Administered as a continuous intravenous (IV) infusion: 0.5 to 10 µg/kg/min.
• Extremely rapid onset (1–2 min) and fleeting duration of action allow precise titration of arterial blood pres-
sure (BP).
• 1- to 2-µg/kg bolus may minimize �BP during laryngoscopy (may result in transient hypotension).
• Requires intraarterial BP monitoring and use of infusion pump.
• Must be protected from light because of photodegradation.
HYPOTENSIVE AGENTS 15-2
Nitrovasodilators
Sodium Nitroprusside: Metabolism
Key Points
• Thiocyanate is slowly cleared by the kidneys. In 
patients with renal failure, accumulation of large 
amounts of thiocyanate may result in thyroid dys-
function, muscle weakness, nausea, hypoxia, and 
acute toxic psychosis.
• The last of the three cyanide reactions is respon-
sible for the development of acute cyanide toxic-
ity, which is characterized by metabolic acidosis, 
cardiac arrhythmias, and increased venous oxygen 
content (inability to utilize oxygen).
• Another early sign of cyanide toxicity is the acute resistance to the hypotensive effects of escalating doses of 
sodium nitroprusside (tachyphylaxis).
• Cyanide toxicity can usually be avoided if cumulative dose of sodium nitroprusside is less than 0.5 mg/kg/h.
• Pharmacologic treatment of cyanide toxicity: Aim to shunt cyanide away from cytochrome oxidase.
 � Sodium thiosulfate (150 mg/kg over 15 min)
 � 3% sodium nitrate (5 mg/kg over 5 min): Oxidizes hemoglobin to methemoglobin
 � Hydroxocobalamin: Combines with cyanide to form cyanocobalamin (vitamin B12)
• Methemoglobinemia from excessive doses of sodium nitroprusside or sodium nitrate can be treated with methy-
lene blue (1–2 mg/kg of a 1% solution over 5 min); reduces methemoglobin to hemoglobin.
HYPOTENSIVE AGENTS 15-3
Nitrovasodilators
Sodium Nitroprusside: Effect on Organ Systems
• Combined dilation of venous and arteriolar vascular beds = ���preload and �afterload = �BP.
Cardiac: Cardiac output is generally unchanged in normal patients.
• Cardiac output is increased in patients with congestive heart failure (CHF), mitral regurgitation, and aortic 
regurgitation secondary to �afterload.
• ���Preload, �myocardial work, and therefore �likelihood of ischemia.
• Reflex-mediated tachycardia and contractility (offset the favorable changes in myocardial oxygen requirements).
• Dilation of coronary arterioles by sodium nitroprusside may result in an intracoronary steal of blood away from 
ischemic areas that are already maximally dilated.
Cerebral: Dilates cerebral blood vessels and abolishes cerebral autoregulation.
• Cerebral blood flow (CBF) is maintained (or increased) unless BP is markedly reduced.
• Increased cerebral blood volume leads to increased intracranial pressure (ICP), particularly in patients with 
reduced intracranial compliance (e.g., brain tumor).
• Intracranial hypertension may be minimized by slow administration and hyperventilation or hypocapnia.
Pulmonary: Vasculature dilates.
• Reductions in pulmonary artery pressure decrease perfusion to normally ventilated alveoli, thereby �physiologic 
dead space = �V/Q mismatch and �arterial oxygenation.
• Inhibits hypoxic pulmonary vasoconstriction: �V/Q mismatch and �arterial oxygenation.
HYPOTENSIVE AGENTS 15-4
Nitrovasodilators
Sodium Nitroprusside: Effect on Organ Systems
Renal: Renin and catecholamines are released in response to �BP
Notable Drug Interactions
• Neuromuscular blockade: May indirectly delay the onset and prolong the duration of blockade by decreas-
ing muscle blood flow secondary to arterial hypotension
Nitrovasodilators
Nitroglycerin: Mechanism of Action
• Same as sodium nitroprusside; relaxes vascular smooth muscle through NO pathway, with venous dilation 
predominating over arterial dilation
Clinical uses: Relieves myocardial ischemia, hypertension, and ventricular failure
• Commonly diluted to a concentration of 100 µg/mL
• Administered as a continuous IV infusion: 0.5 to 10 µg/kg/min
• Glass containers and special IV tubing are recommended because of adsorption of nitroglycerin to poly-
vinylchloride
• Mayalso be administered by a sublingual (peak effect, 4 min) or transdermal (sustained release for 24 h) route
• Chronic use may result in tolerance: may be due to depletion of reactants necessary for NO formation, 
compensatory increase in vasoconstrictive substances, or volume expansion
HYPOTENSIVE AGENTS 15-5
Nitrovasodilators
Nitroglycerin: Metabolism
• Rapid, reductive hydrolysis in the liver and blood: glutathione-organic nitrate reductase.
• One metabolite produced, nitrite, can convert hemoglobin to methemoglobin.
Nitroglycerin: Effect on Organ Systems
Cardiac: ���Preload (venous dilation) and �afterload (arteriolar dilation); reduces myocardial oxygen 
demand, increases myocardial supply.
• �Pooling of blood in large-capacitance vessels, �venous return, �preload, �ventricular end-diastolic pres-
sure = �myocardial oxygen demand and �endocardial perfusion.
• �Afterload, �end-systolic pressure, �oxygen demand.
• Reminder: A significant decrease in diastolic pressure may lower coronary perfusion and actually decrease 
myocardial oxygen supply.
• Nitroglycerin redistributes coronary blood flow to ischemic areas of subendocardium.
• May relieve coronary artery spasm.
• Decreases platelet aggregation and may improve patency of coronary vessels.
• Profound preload reduction is very useful in relieving cardiogenic pulmonary edema.
• Heart rate is largely unchanged; rebound hypertension less likely after discontinuation (in contrast with 
sodium nitroprusside).
Cerebral: Dilates cerebral blood vessels and abolishes cerebral autoregulation.
• �CBF, �cerebral blood volume = Headache is a common side effect.
HYPOTENSIVE AGENTS 15-6
Nitrovasodilators
Nitroglycerin: Effect on Organ Systems
Pulmonary: Vasculature dilates
• Reductions in pulmonary artery pressure decrease perfusion to normally ventilated alveoli, thereby 
 �physiologic dead space = �V/Q mismatch and �arterial oxygenation
• Inhibits hypoxic pulmonary vasoconstriction: �V/Q mismatch and �arterial oxygenation
• Relaxes bronchial smooth muscle
Uterine: 50- to 100-µg boluses have been shown to be effective, although transient, in helping with uterine 
relaxation during certain obstetric procedures with:
• Retained placenta
• Uterine inversion
• Uterine tetany
• Breech extraction
• External version of the second twin
HYPOTENSIVE AGENTS 15-7
Nitrovasodilators
Hydralazine: Mechanism of Action
• Relaxes arteriolar smooth muscle, causing dilation of precapillary resistance vessels via increased cGMP
Clinical Uses
• Intraoperative hypertension is usually controlled with an IV dose of 5 to 20 mg
• Onset of action is 15 min, with effect lasting 2 to 4 h
• Continuous infusions are less frequently used (0.25–1.5 µg/kg/min); slow onset and long duration of action
• Pregnancy-induced hypertension 
Metabolism
• Acetylation and hydroxylation in the liver
Effects on Organ Systems
Cardiac: �Peripheral vascular resistance, �arterial blood pressure
• Reflex � in HR, myocardial contractility, and cardiac output; may be detrimental in a patient with coronary 
artery disease; minimize with concurrent administration of β-adrenergic antagonist
• �Afterload often beneficial in patients with CHF
Cerebral: Potent cerebral vasodilator and inhibitor of autoregulation
• Unless BP markedly reduced, �CBF and ICP
HYPOTENSIVE AGENTS 15-8
Nitrovasodilators
Hydralazine: Effects on Organ Systems
Renal: Blood flow usually maintained or even increased
• Good for patients with renal disease
Non-nitrovasodilator Hypotensive Agents
Fenoldopam: Mechanism of Action
• Causes rapid vasodilation by selectively activating D1-dopamine receptors
• Moderate affinity for α 2-adrenoceptors
Clinical Uses
• 0.01 to 1.6 µg/kg/min used in clinical trials
• Reduces systolic and diastolic blood pressure in hypertensive patients; effect is comparable to that of sodium 
nitroprusside
• Side effects: Headache, flushing, nausea, tachycardia, hypokalemia, and hypotension
• Onset within 15 minutes; discontinuation of an infusion quickly reverses the effect without rebound hyper-
tension; tolerance may develop after 48-h infusion
• Conflicting data regarding renal protective effect
HYPOTENSIVE AGENTS 15-9
Non-nitrovasodilator Hypotensive Agents
Fenoldopam: Metabolism
• Conjugation in the liver; no CYP450 involvement
• Clearance unaltered in the presence of renal or hepatic failure; no dosage adjustments necessary
Effects on Organ Systems
Cardiac
• �Systolic blood pressure, �diastolic blood pressure
• Reflex � in heart rate; tachycardia decreases over time but remains substantial at higher doses
• Low initial doses (0.03–0.1 µg/kg/min) titrated slowly have been associated with less reflex tachycardia than 
higher doses (>0.3 µg/kg/min)
Ocular
• �Intraocular pressure; use caution or avoid in patients with glaucoma
Renal
• ���Renal blood flow
• Despite a decrease in arterial blood pressure, glomerular filtration rate is maintained
• �Urinary flow rate, �sodium extraction, �creatinine clearance compared with sodium nitroprusside
HYPOTENSIVE AGENTS 15-10
Non-nitrovasodilator Hypotensive Agents
Calcium Antagonists
• Dihydropyridine calcium channel blockers (nicardipine, clevidipine)
 � Arterial selective vasodilators used for perioperative blood pressure control in cardiothoracic surgical 
patients; bind L-type calcium channels and impair calcium entry into the vascular smooth muscle
 � Nicardipine: 5 to 15 mg/hr titrated to effect
 � Clevidipine: Short half-life allows for rapid titration
 � Minimal effects on cardiac conduction and ventricular contractility (unlike the nondihydropyridine agents 
diltiazem and verapamil)
 � L-type calcium channels are more prevalent on arterial vessels than on venous capacitance vessels; cardiac 
filling and preload less affected when these agents are used (in contrast to nitrates)
 � With preload maintained, cardiac output often increases in the setting of reduced vascular tone
LOCAL ANESTHETICS 16-1
General Concepts
Structure
Local anesthetics consist of a lipophilic aromatic benzene ring separated from a hydrophilic group—usually a 
tertiary amine—by an ester or amide linkage. They are weak bases, usually with a positive charge at the tertiary 
amine group at physiological pH. Physicochemical properties are determined by linkage, substitutions in the 
aromatic ring, and alkyl groups attached to the amine nitrogen.
Mechanism of Action
Neurons have voltage-gated Na channels that can produce and transmit membrane depolarization along the 
nerve membrane after chemical, mechanical, or electrical stimuli. All local anesthetics bind the α subunit of 
the transmembrane Na channel on nerve fibers and inhibit the voltage-gated Na channels from activation and 
Na influx associated with membrane depolarization. The resting membrane potential is not altered. At high 
enough local anesthetic concentrations and with a sufficient fraction of local anesthetic-bound Na channels, an 
action potential can no longer be generated because Na cannot cross the membrane, and impulse propagation 
is abolished.
Available Preparations
Generally prepared commercially as water-soluble hydrochloride salts (pH of 6–7). Because epinephrine is 
unstable in alkaline environments, epinephrine-containing local anesthetics are more acidic (pH of 4–5) with 
a lower concentration of free base and a slower onset. Adding 1 mL of 8.4% sodium bicarbonate per 10 mL of 
local anesthetic speeds the onset and improves the quality of the block.
LOCAL ANESTHETICS 16-2
General Concepts
Nerve Fiber Sensitivity
Sensitivity of nerve fibers to local anesthetics is determined by axonal diameter, myelination, and other ana-
tomic and physiological factors. Small diameter and myelination increases sensitivity to local anesthetics so 
that smaller, unmyelinated Aδ fibers are more sensitive than larger unmyelinated Aα fibers. In spinal local 
anesthetic anesthesia, blockade usually follows autonomic > sensory > motor.
Potency
Potency correlates with octanol solubility,which reflects the local anesthetic’s ability to permeate the nerve’s 
hydrophobic membrane. Potency is increased by adding large alkyl groups to parent molecules. The minimum 
concentration that will block nerve impulse conduction is affected by fiber size, type, myelination, pH (acidic 
pH antagonizes block), frequency of nerve stimulation, and electrolyte concentrations (hypokalemia and 
hypercalcemia antagonize block).
Onset of Action
Onset of action depends on lipid solubility and pKa, the pH at which the fraction of the nonionized lipid- soluble 
form (B) to the ionized water-soluble form (BH+) are equal. Generally, the closer to physiologic pH the faster 
the onset except chloroprocaine. Less potent, less lipid-soluble agents generally have faster onsets than more 
potent, more lipid-soluble agents.
Duration of Action
Highly lipid-soluble local anesthetics have longer durations of action, possibly because they have slower 
 diffusion away from the lipid-rich environment to the aqueous bloodstream.
LOCAL ANESTHETICS 16-3
Local Anesthetic Toxicity
Early Signs of Toxicity
Early symptoms may include circumoral numbness, tongue paresthesia, and dizziness. Sensory complaints 
include tinnitus and blurry vision. Excitatory signs such as restlessness, agitation, nervousness, and paranoia 
often precede central nervous system depression (e.g., unconsciousness). Muscle twitching signals the onset 
of tonic-clonic seizures.
Cardiovascular Toxicity
Cardiovascular toxicity is caused by three times the local anesthetic dose that produces seizures. Under general 
anesthesia, the presenting sign of local anesthetic overdose is usually cardiac arrhythmias or circulatory collapse.
Treatment of Local Anesthetic Toxicity
 1. Maintain a clear airway with adequate ventilation and oxygenation.
 2. Propofol (0.54–2 mg/kg), benzodiazepines, or barbiturates quickly terminate seizure activity.
 3. Vasopressors may include epinephrine, norepinephrine, and vasopressin.
 4. The antiarrhythmic amiodarone should be considered.
 5. Give intralipid 1.5 mL/kg in patients who do not respond to standard therapy.
 6. Provide cardiopulmonary bypass until local anesthetic is metabolized.
LOCAL ANESTHETICS 16-4
Ester Versus Amide Local Anesthetics
General
Whereas ester anesthetics have one I in the name, amides have two I’s (e.g., procaine vs. lidocaine).
Metabolism
Ester local anesthetics are predominantly metabolized by pseudocholinesterase. Amide local anesthetics are 
metabolized by the microsomal P-450 enzymes in the liver (N-dealkylation and hydroxylation).
Hypersensitivity Reactions
True hypersensitivity reactions are uncommon and should be carefully separated from signs of toxicity. Esters 
appear more likely to produce a true allergic reaction because of their association with the metabolite para-
aminobenzoic acid (PABA), a known allergen. The reaction is mediated by IgG or IgE antibodies.
LOCAL ANESTHETICS 16-5
 Nerve Fiber Classification
Fibe r Type Moda lity Se rved Diamete r (mm) Conduction (m/ s) Mye lina ted?
Aα Motor efferent 12–20 70–120 Yes
Aα Proprioception 12–20 70–120 Yes
Aβ Touch, pressure 5–12 30–70 Yes
Aγ Motor afferent (muscle spindle) 3–6 15–30 Yes
Aδ Pain
Temperature
Touch
2–5 12–30 Yes
B Preganglionic autonomic fibers <3 3–14 Some
C
Dorsal root
Pain
Temperature
0.4–1.2 0.5–2 No
C
Sympathetic
Postganglionic sympathetic fibers 0.3–1.3 0.7–2.3 No
LOCAL ANESTHETICS 16-6
Systemic Absorption of Injected Local Anesthetics
 1. Depends on vascularity of site of injection: intravenous > tracheal > intercostal > paracervical > 
 epidural > brachial plexus > sciatic > subcutaneous.
 2. The presence of vasoconstrictors causes vasoconstriction at the site of administration. The decreased 
absorption decreases the peak local anesthetic concentration in the blood and facilitates neuronal uptake, 
enhances the quality of analgesia and prolongs the duration of the block, and limits toxic side effects. The 
effect is greater on short-acting agents (extends duration of lidocaine by at least 50%) than long-acting 
agents (little or no effect on bupivacaine).
 3. Lipid-soluble agents are more slowly absorbed.
Distribution of Local Anesthetics
 1. Highly perfused organs are responsible for the initial uptake (α phase), which is followed by a slower 
redistribution (β phase) to moderately perfused tissues (muscle and gut).
 2. Increased lipid solubility is associated with greater plasma protein binding and greater tissue uptake from 
an aqueous compartment.
 3. Muscle provides the greatest reservoir for distribution of local anesthetic agents in the bloodstream 
because of large mass.
LOCAL ANESTHETICS 16-7
Systemic Effects
Neurologic Effects
Intravenous (IV) lidocaine decreases cerebral blood flow and attenuates the rise in intracranial pressure that 
accompanies intubation in patients with decreased intracranial compliance. The central nervous system (CNS) 
is vulnerable to local anesthetic toxicity and is the site of premonitory signs of rising blood concentrations in 
awake patients such as circumoral numbness, tongue paresthesia, and excitatory signs. Muscle twitching her-
alds the onset of tonic-clonic seizures. Higher concentrations lead to respiratory depression and coma. Highly 
lipid-soluble local anesthetics produce seizures at lower blood concentrations than less potent agents. 
Benzodiazepines and hyperventilation raise the threshold of local anesthetic-induced seizures. Both respiratory 
and metabolic acidosis reduce the seizure threshold.
Pulmonary Effects
Lidocaine depresses the hypoxic drive. Apnea can result from phrenic or intercostal nerve paralysis or depres-
sion of the medullary respiratory center after direct exposure to local anesthetic agents. Apnea after a “high” 
spinal or epidural is nearly always the result of hypotension rather than phrenic block. Local anesthetics relax 
bronchial smooth muscle and may be effective in blocking the reflex bronchoconstriction sometimes associ-
ated with intubation.
LOCAL ANESTHETICS 16-8
Systemic Effects
Cardiovascular Effects
• All local anesthetics depress myocardial automaticity (spontaneous phase IV depolarization) by inhibition 
of the autonomic nervous system and cardiac Na channels. IV lidocaine provides effective treatment for 
some forms of ventricular arrhythmias. Myocardial contractility and arterial blood pressure are generally 
unaffected by the usual IV doses. All local anesthetics except for cocaine produce smooth muscle relaxation 
at higher concentrations, which may cause some degree of arteriolar vasodilatation. At low concentrations, 
all local anesthetics inhibit nitric oxide, causing vasoconstriction.
• At increased blood concentrations, the combination of arrhythmias, heart block, depression of ventricular 
contractility, and hypotension may result in cardiac arrest. During anesthesia, cardiac arrhythmias and cir-
culatory collapse are the usual presenting signs of local anesthetic overdose during general anesthesia. In 
awake patients with local anesthetic toxicity and CNS excitation, transient tachycardia and hypertension 
may precede cardiac arrest.
• Unintentional administration of bupivacaine during regional anesthesia may produce severe refractory car-
diovascular toxicity with left ventricular depression, atrioventricular heart block, and life-threatening 
arrhythmias such as ventricular tachycardia and fibrillation. Pregnancy, hypoxemia, and respiratory acido-
sis are predisposing risk factors. The R(+) optical isomer of bupivacaine, levobupivacaine, more avidly 
blocks and dissociates more slowly from cardiac Na channels than the S(−) optical isomer. Ropivacaine is 
an anesthetic similar to bupivacaine but only has the less toxic S(−) optical isomer. Onset, duration, and toxic 
dosage are similar to bupivacaine.
LOCAL ANESTHETICS 16-9
Este rs
Techniques
Concentra tions 
Ava ilable (%)
Maximum 
Dose (mg/ kg)
Typica l Dura tion 
of NerveBlocks 
Chloroprocaine Epidural, infiltration, peripheral 
nerve block, spinal (large volumes 
of chloroprocaine unintentionally 
injected into spinal space can 
cause prolonged neurologic 
 deficits)
1, 2, 3 12 Short
Cocaine Topical 4, 10 3 NA
Procaine Spinal, local infiltration 1, 2, 10 12 Short
Tetracaine 
(amethocaine)
Spinal, topical (eye) 0.2, 0.3, 0.5, 1, 2 3 Long
NA, not applicable.
LOCAL ANESTHETICS 16-10
Amides
Techniques
Concentra tions 
Ava ilable (%)
Maximum Dose 
(mg/ kg)
Typica l 
Dura tion of 
Nerve Blocks 
Bupivacaine Epidural, spinal, infiltration, peripheral 
nerve block
0.25, 0.5, 0.75 3 Long
Lidocaine 
(lignocaine)
Epidural, spinal infiltration, peripheral 
nerve block, intravenous regional, topical
5% lidocaine has been associated with 
cauda equina syndrome after infusion 
through small-bore spinal catheters
0.5, 1, 1.5, 2, 4, 5 4.5
7 (with epinephrine)
Medium
Mepivacaine Epidural, infiltration, peripheral nerve 
block, spinal
1, 1.5, 2, 3 4.5
7 (with epinephrine)
Medium
Prilocaine EMLA (topical), epidural, IV regional 
 (outside North America)
0.5, 2, 3, 4 8 Medium
Ropivacaine Epidural, spinal, infiltration, peripheral 
nerve block
0.2, 0.5, 0.75, 1 3 Long
EMLA, eutectic mixture of local anesthetics; IV, intravenous.
LOCAL ANESTHETICS 16-11
Case Card
A 25-year-old G5P3SA1 at 41 weeks, 2 days of gestation is scheduled for induction and epidural placement. 
The patient’s preprocedure vital signs are weight, 81 kg; height, 62 inches; heart rate, 95 beats/min; blood 
pressure, 120/80 mm Hg; respiratory rate, 18 breaths/min; and pulse oximetry, 97%. She is otherwise healthy, 
has had an uneventful pregnancy, and has had epidurals with all deliveries without complications. The epidural 
space is located with loss of resistance to a saline-filled syringe, and negative pressure reveals no cerebrospinal 
fluid (CSF) or blood. An epidural catheter is inserted with 5 cm left in the epidural space and again aspirated 
with no CSF or blood. The epidural is started with 10 mL/hr 0.1% bupivacaine with 0.005% fentanyl. Ten 
minutes later, the blood pressure is 55/30 mm Hg and heart rate is 30 beats/min, and within seconds, the patient 
is no longer responsive.
What are your first steps?
What caused the symptoms?
How could you minimize the occurrence of this event?
LOCAL ANESTHETICS 16-12
Case Card Answers
The patient has had a total spinal from inadvertent injection of a large dose of local anesthetic into the spinal 
space and subsequent depression of the cervical spinal cord and brainstem. Bradycardia, hypotension, and 
sometimes cardiopulmonary arrest occur from unopposed vagal tone and blockade of the cardioaccelerator 
fibers (T1–T4). Other symptoms include apnea, upper extremity weakness, loss of consciousness, and pupil-
lary dilatation.
Treatment: Secure the airway and ventilate the patient. Bolus the patient with colloids and crystalloids. If the 
vital signs do not improve, start using Advanced Cardiovascular Life Support doses of sympathomimetics, 
especially epinephrine 1mg. Determine with the obstetrician whether an emergency cesarean section is needed 
to protect the fetus from hypoperfusion. A total spinal lasts less than the duration of a spinal, and symptom 
management is essential until reabsorption of local anesthetic from the CSF reverses the effects.
Causes: The toxic dose of bupivacaine is 3 mg/kg and 243 mg for this patient. Although local anesthetic car-
diotoxicity is a well-known complication of bupivacaine, the patient received about 1.6 mg of bupivacaine.
Minimizing total spinals: Although no CSF or blood were aspirated, there have been rare occurrences of total 
spinals after epidural injections. A test dose should always be given with verification of epidural levels before 
an epidural is started.
ADJUNCTS TO ANESTHESIA 17-1
Aspiration
• Application of cricoid pressure (Sellick maneuver) and rapid-sequence induction can be used to prevent 
aspiration but offer only limited protection. Cricoid pressure can be misdirected and fail to occlude the 
esophagus.
• Anesthetic agents can reduce the lower esophageal sphincter tone and decrease or obliterate the gag reflex. 
Patients inadequately anesthetized can vomit without the ability to protect the airway.
• A full stomach, abdominal pathology, hiatal hernia, obesity, pregnancy, reflux disease, and insufficient 
anesthesia all can increase the risk of aspiration.
Medications That Lower the Risk of Aspiration Pneumonia
H2 Receptor Antagonists (cimetidine, famotidine, nizatidine, and ranitidine):
• Competitively inhibit histamine binding to H2 receptors, thereby reducing gastric acid output and raising 
gastric pH.
• Only affect the pH of the gastric secretions that occur after their administration. When given to reduce the 
risk of aspiration pneumonia, they should be given at bedtime and at least 2 hours before surgery.
• Elimination occurs primarily by the kidneys, and doses should be reduced in patients with renal dysfunction.
• Side effects: Rapid intravenous (IV) injection may lead to hypotension, bradycardia, arrhythmias, and car-
diac arrest (more common after the administration of cimetidine to critically ill patients). Famotidine, on the 
other hand, can be safely injected over 2 minutes. Long-term cimetidine use can lead to hepatotoxicity, 
interstitial nephritis, granulocytopenia, and thrombocytopenia.
ADJUNCTS TO ANESTHESIA 17-2
Aspiration
Antacids: Neutralize the acidity of gastric fluid by providing a base that reacts with hydrogen ions to form 
water. They raise the pH of gastric contents to protect against the effects of aspiration pneumonia. They work 
immediately and lose their effectiveness after 30 to 60 minutes. They increase the intragastric volume. Whereas 
aspiration of particulate antacids (aluminum or magnesium hydroxide) causes abnormalities in lung function, 
nonparticulate antacids (sodium citrate or sodium bicarbonate) are less damaging to the lungs if aspirated.
Metoclopramide: Enhances the stimulatory effects of acetylcholine on the intestinal smooth muscle to increase 
lower esophageal sphincter tone, speed gastric emptying, and lower gastric volume. It also blocks dopamine recep-
tors in the chemoreceptor trigger zone of the central nervous system, but at doses used clinically, its ability to 
reduce postoperative nausea and vomiting is limited. It is excreted in the urine (reduce dose in renal dysfunction).
Side effects: Rapid IV injection can cause abdominal cramping; induce a hypertensive crisis in patients with 
pheochromocytoma; and may cause sedation, nervousness, and extrapyramidal signs from dopamine antago-
nism (avoid in patients with Parkinson disease). Rarely, it can cause hypotension and arrhythmias.
Proton pump inhibitors: These drugs include omeprazole, lansoprazole, rabeprazole, esomeprazole, and 
pantoprazole. They bind to the proton pump of parietal cells in the gastric mucosa and inhibit the secretion of 
hydrogen ions. They are eliminated primarily in the liver; therefore, repeat doses should be decreased in 
patients with liver dysfunction.
Side effects: Nausea, abdominal pain, constipation, and diarrhea. Rarely, they can cause myalgias, anaphy-
laxis, angioedema, and severe dermatologic reactions.
ADJUNCTS TO ANESTHESIA 17-3
Agents for Prophylaxis and Treatment of Postoperative Nausea and Vomiting (PONV)
5-HT3 Receptor Antagonists (ondansetron, granisetron, dolasetron, palonsetron)
• Selectively block serotonin 5-HT3 receptors, which are located peripherally (abdominal vagal afferents) and cen-
trally (chemoreceptor trigger zone of the area postrema and nucleus tractus solitaries) with little or no effect on 
dopamine receptors.
• They are effective antiemetics and are generally given at the end of surgery.
• Metabolized extensively in the liver (reduce dose in liver dysfunction).
• Side effects: Minimal; the most common side effect is headache. All can slightlyprolong the QT interval on the 
electrocardiogram (may be more frequent with dolasetron).
Butyrophenones
• Droperidol given at the end of the procedure blocks dopamine receptors, which contribute to the development 
of PONV.
• A black box warning exists because these drugs may cause QT prolongation and the development of torsades de 
pointes. However, the dose typically used for PONV is fairly low; thus, the risk of sudden cardiac death periop-
eratively is debatable. Caution use in patients with Parkinson disease and those with extrapyramidal signs because 
they antagonize dopamine.
Phenothiazines
• Prochlorperazine has effects at histamine, dopamine, and muscarinic receptors. It can also lead to extrapyramidal 
signs and anticholinergic side effects.
• Promethazine (Phenergan) works primarily as an anticholinergic and an antihistamine agent. It may be associated 
with sedation, delirium, confusion, and vision changes.
ADJUNCTS TO ANESTHESIA 17-4
Agents for Prophylaxis and Treatment of Postoperative Nausea and Vomiting (PONV)
Dexamethasone: In small doses (4 mg), it is equally effective as ondansetron in reducing the incidence of 
PONV. It should be given at induction; its mechanism of action is unclear. There are no major side effects.
Neurokinin-1 receptor antagonist (NK1): Aprepitant is an NK1 receptor antagonist that inhibits substance 
P at central and peripheral receptors to reduce PONV. It has been found to be effective in reducing PONV, 
especially when combined with ondansetron.
Anticholinergics: Transdermal scopolamine may be used to reduce the incidence of PONV. It may cause side 
effects related to central anticholinergics such as confusion, blurred vision, and dry mouth.
Alternative therapies: Acupuncture, acupressure, and transcutaneous electrical stimulation of the P6 acu-
puncture point can reduce the incidence of PONV.
ADJUNCTS TO ANESTHESIA 17-5
Postoperative Nausea and Vomiting
Incidence of PONV: If untreated, PONV occurs in approximately 20% to 30% of the general surgical popula-
tion and up to 70 to 80% in patients who are considered high risk.
Risks factors for PONV: As anesthetic duration increases, the risk of PONV also increases. Other risk factors 
are listed in the table below. Obesity, anxiety, and reversal of neuromuscular blockade are not independent risk 
factors for PONV.
Risk Factors for Postopera tive Nausea and Vomiting
Patient Factors
• Nonsmoking status
• Female gender
• History of postoperative emesis
• History of motion sickness
Surgica l Risk Factors
Duration of surgery (the longer the 
surgery, the higher the POV risk)
Anesthe tic Risk Factors
• General anesthesia
• Drugs
 � Opioids
 � Volatile agents
 � Nitrous oxide
Type of Surge ry
ADJUNCTS TO ANESTHESIA 17-6
Postoperative Nausea and Vomiting
Recommendations from the Society of Ambulatory Anesthesia (SAMBA):
 1. Identify patients at risk for PONV.
 2. Use management strategies to reduce PONV risk.
 3. Use one to two prophylactic measures in adults at moderate PONV risk.
 4. Use multiple interventions in patients at high PONV risk.
 5. Administer prophylactic antiemetic therapy to children at high risk using combination therapy.
 6. Provide antiemetic therapy to patients with PONV who did not receive prophylactic therapy or in whom 
prophylaxis failed. Therapy should be with a drug from a different class than that which failed to provide 
prophylaxis.
ADJUNCTS TO ANESTHESIA 17-7
Other Adjuvants
Ketorolac: A parenterally administered nonsteroidal antiinflammatory drug that provides analgesia by inhibit-
ing prostaglandin synthesis. It is used for short-term management of pain (<5 days). It does not cause respira-
tory depression, sedation, or nausea and vomiting.
Side effects: Inhibits platelet aggregation and prolongs bleeding time. Long-term use may cause renal toxicity 
or GI tract ulceration with bleeding and perforation. It should be avoided in patients with renal failure. It is 
contraindicated in patients allergic to aspirin or NSAIDs. 
Clonidine: An imidazoline derivative with predominantly α2 adrenergic agonist activity. It is an antihyperten-
sive agent but also possesses analgesic properties and has local anesthetic effects. It may be used as an adjunct 
for epidural, caudal, and peripheral nerve block anesthesia and analgesia.
Side effects: Sedation, dizziness, bradycardia, and dry mouth are common side effects. Less commonly, bra-
dycardia, orthostatic hypotension, nausea, and diarrhea may occur. Abrupt discontinuation following long-term 
administration (>1 month) can lead to withdrawal symptoms characterized by rebound hypertension, agitation, 
and sympathetic overactivity.
Dexmedetomidine: A parenteral selective α2 agonist with sedative properties. It appears to be more selective 
for the α2 receptor than clonidine. It causes dose-dependent sedation, anxiolysis, and some analgesia, and 
blunts the sympathetic response to surgery and other stress. It does not significantly depress respiratory drive. 
Side effects: Bradycardia, heart block, and hypotension. It may also cause nausea.
ADJUNCTS TO ANESTHESIA 17-8
Doxapram: A peripheral and central nervous system stimulant. Selective activation of carotid chemoreceptors by low doses 
of doxapram stimulates hypoxic drive, producing an increase in tidal volume and a slight increase in respiratory rate. It 
mimics a low PaO2 and may therefore be useful in patients with chronic obstructive pulmonary disease who are dependent 
on hypoxic drive yet require supplemental oxygen. Drug-induced respiratory and central nervous system depression can be 
temporarily overcome. 
Side effects: Changes in mental status, cardiac abnormalities, and pulmonary dysfunction. It should not be used in patients with 
a history of epilepsy, cerebrovascular disease, acute head injury, coronary artery disease, hypertension, or bronchial asthma.
Naloxone: Competitive opioid receptor antagonist that reverses the agonist activity associated with endogenous or exoge-
nous opioid compounds. Some degree of opioid analgesia may be spared if the dose of naloxone is limited to the minimum 
amount to maintain adequate ventilation.
Side effects: Sympathetic stimulation (tachycardia, ventricular irritability, hypertension, pulmonary edema) caused by 
severe, acute pain and an acute withdrawal syndrome in patients who are opioid dependent.
Naltrexone: A pure opioid antagonist with a high affinity for the µ receptor but with a significantly higher half-life than 
naloxone. It is used orally for maintenance treatment of opioid addicts and for ethanol abuse.
Flumazenil: An imidazobenzodiazepine that is useful in the reversal of benzodiazepine sedation and the treatment of ben-
zodiazepine overdose. It promptly reverses the hypnotic effects of benzodiazepines, but amnesia has proved to be less reli-
ably prevented.
Side effects: Rapid administration may cause anxiety in previously sedated patients and symptoms of withdrawal in those 
on long-term benzodiazepine therapy. It has been associated with increases in intracranial pressure in patients with head 
injuries and abnormal intracranial compliance. It may induce seizures if benzodiazepines have been given as anticonvulsants 
or in conjunction with an overdose of tricyclic antidepressants. Nausea and vomiting are not uncommon.
PREOPERATIVE ASSESSMENT, PREMEDICATION, AND PERIOPERATIVE DOCUMENTATION 18-1
The preoperative assessment is extremely important and consists of a physical examination and medical history, which 
includes a thorough review of all recent and current medications, past anesthetics and surgeries, any drug allergies, blood 
diatheses, and family history pertinent to anesthesia.
The main purposes of the preoperative assessment include the following:
 1. Identify patients who require medical therapy for a disease or condition before elective surgery (e.g., a 65-year-old 
patient who has unstable left main coronary artery disease scheduled to undergo a total hip arthroscopy).2. Identify patients whose medical conditions are so poor that the proposed surgery will hasten their death instead of 
improving the quality of their lives (e.g., a patient with end-stage kidney failure and myocardial failure who is sched-
uled for an 8-hour multilevel spinal fusion).
 3. Identify patients with specific characteristics that will alter the anesthetic plan (e.g., difficult airway, history of malig-
nant hyperthermia, severe postoperative nausea and vomiting, or postoperative delirium).
 4. Provide the patient with an estimate of anesthetic risk.
 5. Provide the patient with a description of the anesthetic plan, provide psychological support, answer questions or con-
cerns, and obtain informed consent.
All patients undergoing an anesthetic in the United States are assigned a classification of relative risk before conscious seda-
tion or surgical anesthesia referred to as the American Society of Anesthesiologists (ASA) classification. “E” is added to the 
ASA classification if the reason for surgery is an emergency.
 I. A normal healthy patient.
 II. A patient with mild systemic disease.
 III. A patient with severe systemic disease.
 IV. A patient with severe systemic disease that is a constant threat to life.
 V. A moribund patient who is not expected to survive without the operation.
 VI. A declared brain-dead patient whose organs are being removed for donor purposes.
PREOPERATIVE ASSESSMENT, PREMEDICATION, AND PERIOPERATIVE DOCUMENTATION 18-2
ASA Classification Examples
 I. Patient who is healthy with no major organic, physiologic, or psychiatric disturbances. This patient would 
have good exercise tolerance. This patient would not be at either end of the age continuum (very young 
or old).
 II. This patient has no functional limitations and therefore has good exercise tolerance. A well-controlled 
disease of one organ system may be present such as hypertension, diabetes without complications, ciga-
rette smoking without chronic obstructive pulmonary disease (COPD) or emphysema, mild obesity, or 
pregnancy.
 III. This patient demonstrates some functional limitation. The patient has a controlled disease state of more 
than one organ system but without imminent concern for death. Patients may have controlled congestive 
heart failure (CHF), stable angina, a history of myocardial ischemia, poorly controlled hypertension, 
morbid obesity, chronic renal failure, cigarette smoking with COPD or emphysema, or bronchospastic 
disease with intermittent symptoms.
 IV. This patient has at least one severe disease that is poorly controlled or at the end stage of medical manage-
ment. This patient has the risk of death with or without surgery. This patient may have unstable angina, 
symptomatic COPD, symptomatic CHF, or hepatorenal failure.
PREOPERATIVE ASSESSMENT, PREMEDICATION, AND PERIOPERATIVE DOCUMENTATION 18-3
System-Based Approach to the Preoperative Assessment
Cardiovascular issues: Determine whether the patient’s condition can or must be improved before the sur-
gery. The type of surgery also affects decision tree (elective arthroscopy vs. resection pancreatic cancer). The 
indication for cardiac testing does not change based on having surgery. Symptoms should always drive whether 
any test is completed to evaluate organ function.
Pulmonary issues: Perioperative pulmonary complications (reintubation or prolonged ventilation) are increas-
ing issues because of severe obesity and obstructive sleep apnea. Pulmonary complications are closely associ-
ated with the following: (1) ASA class III and IV carry a markedly increase risk of pulmonary complications 
after surgery, (2) cigarette smoking, (3) longer surgeries (>4 hours), (4) surgery type (abdominal, thoracic, 
aortic aneurysm, head and neck, and emergency surgery), and (5) general anesthesia. Prevention of complica-
tions may occur with (1) cessation of cigarette smoking before surgery, (2) lung expansion techniques (incen-
tive spirometry), (3) consideration of airway disease (asthma) with appropriate treatment perioperatively, and 
(4) appropriate use of opioids and sedatives to decrease postoperative respiratory depression.
Endocrine and metabolic disease issues: (1) Diabetes mellitus and a plan for blood glucose control must be 
discussed preoperatively. In addition, hemoglobin A1C may provide insight into the health of the patient and 
disease control. This may lead to consultation before surgery for improvement of glycemic control. 
(2) Electrolyte abnormalities (hyperkalemia) in the setting of certain disease states (renal disease) may require 
intervention before surgery (dialysis).
PREOPERATIVE ASSESSMENT, PREMEDICATION, AND PERIOPERATIVE DOCUMENTATION 18-4
System-Based Approach to the Preoperative Assessment (continued)
Coagulation issues: Most that affect the anesthetic and surgical plan can be dealt with preoperatively.
 1. How are patients on chronic warfarin therapy managed?
Most surgeries require discontinuation of warfarin at least 5 days before surgery to avoid excessive hemorrhaging. 
However, a therapeutic plan must be made for patients with certain disease states.
• Mechanical heart valves, atrial fibrillation, prior cerebrovascular accident or pulmonary embolus, or significant history 
of deep venous thrombosis require bridging therapy, usually with heparinoids (intramuscular or continuous intravenous).
• High risk of thrombosis without disease does not necessarily require bridging therapy.
 2. How are patients on clopidogrel and related agents managed?
Clopidogrel and related agents are usually given with aspirin as “dual antiplatelet therapy” for patients with coronary 
artery disease and a history of intracoronary stenting. Without antiplatelet therapy, these patients are at extremely high 
risk for thrombosis formation and death.
• All but “dire emergencies” should be postponed at least 1 month after coronary interventions.
• Patients with drug-eluting stents should receive antiplatelet therapy up to 12 months before interruption for elective 
surgery.
• Consultation with a cardiologist, hematologist, or both is highly recommended.
 3. How is regional anesthesia provided to chronically anticoagulated patients or those requiring postoperative anticoagula-
tion safely?
This is a highly debated topic for anesthesiologists and hematologists. The American Society of Regional Anesthesia 
publishes an updated consensus guideline to take into consideration the type of anticoagulation, placement of a peripheral 
nerve catheter versus a single-shot peripheral nerve block, and use of neuraxial anesthesia.
PREOPERATIVE ASSESSMENT, PREMEDICATION, AND PERIOPERATIVE DOCUMENTATION 18-5
System-Based Approach to the Preoperative Assessment
A healthy 45-year-old woman presents for bilateral tubal ligation. She has not had surgery in the past. She has 
been nil per os (NPO) since midnight.
Medications: None
Allergies: One
Weight: 120 kg
Height: 63 inches
During the preoperative interview, you inquire about gastroesophageal reflux disease (GERD), and the patient 
answers that she takes TUMS after every meal and at bedtime because she gets severe heartburn but does not 
have “reflux.” The anesthetic plan had included use of a laryngeal mask airway (LMA).
 1. Which of the following is the most appropriate option for airway management in patients with severe GERD?
A. Rapid-sequence intubation
B. LMA
C. Mask-bag ventilation with oral airway
D. Cancel the surgery
 2. Which of the following medications could be given to decrease the severity of aspiration?
A. Famotidine
B. Ondansetron
C. Particulate antacids
D. Midazolam
PREOPERATIVE ASSESSMENT, PREMEDICATION, AND PERIOPERATIVE DOCUMENTATION 18-6
System-Based Approach to the Preoperative Assessment
Gastrointestinal issues: The main issue is the risk of aspirating gastric contents, leading to pneumonitis, prolonged ventila-
tory support, and the possibility of death in a previously healthy patient or one in whom death was not an expected outcome.Patient groups at greatest risk for reflux of gastric contents:
 1. Parturients: After 20 weeks of gestation, all patients are considered as having full stomachs.
 2. Severe GERD
 3. Gastrointestinal obstruction (e.g., pyloric stenosis, bowel obstruction.)
 4. Patients who have not had time for gastric emptying after a meal
NPO guidelines vary among hospitals, and there remains no consensus within the ASA. General guidelines include NPO 
status of 8 hours for solids. No good outcome data are available on the benefit of restricting fluid intake. Pediatric patients 
are allowed to have fluids up to 2 hours before anesthesia, and many other patient populations (e.g., patients with diabetes) 
may benefit from that practice without worsening outcomes.
Patients with GERD provide a dilemma in care in that patients vary from having “occasional” symptoms to patients having 
symptoms multiple times per day or requiring medication to avoid reflux. Patients who require daily medical therapy or are 
symptomatic multiple times per day should have a plan to decrease the acidity of gastric contents with use of nonparticulate 
antacids or H2 blockers (e.g., famotidine) or decrease the quantity of contents with a gastroprokinetic agent (e.g., metoclo-
pramide) (question 2’s answer is A). The airway should be managed during general anesthesia, such as a rapid-sequence 
intubation with placement of an endotracheal tube (question 1’s answer is A), which will decrease the risk of aspiration. Use 
of an LMA may cause gastric distention and lead to a greater risk of emesis and aspiration.
AIRWAY MANAGEMENT 19-1
Anatomy
 1. Upper airway: Pharynx, nose, mouth, larynx, trachea, 
mainstem bronchi.
 2. Pharynx: U-shaped fibromuscular structure extending 
from base of the skull to cricoid cartilage
• Nasopharynx: Opens into nasal cavity
• Oropharynx: Opens into mouth
• Laryngopharynx: Opens into larynx
 3. Epiglottis: Separates oropharynx from laryngopharynx
• Prevents aspiration by covering glottis during swall-
owing
 4. Larynx: Composed on nine cartilages—thyroid, cricoid, 
epiglottic, and (in pairs) arytenoid, corniculate, and cunei-
form.
AIRWAY MANAGEMENT 19-2
Anatomy
 1. Sensory innervation: The trigeminal 
nerve divisions innervate the nose. 
The lingual nerve (branch of trigemi-
nal nerve V3) and glossopharyngeal 
nerve provide sensation to the anterior 
two-thirds and posterior third of the 
tongue, respectively. Branches of the 
vagus nerve provide sensation below 
the epiglottis. The internal superior 
laryngeal nerve (SLN) branch pro-
vides sensation to the larynx between 
the epiglottis and vocal cords. The 
recurrent laryngeal nerve (RLN) 
branch innervates the larynx below 
the vocal cords and trachea.
 2. Motor innervation: The RLN inner-
vates all larynx muscles except the 
cricothyroid muscle, which is innervated by the external branch of the SLN. The posterior cricoarytenoid muscles abduct 
the vocal cords while the lateral cricoarytenoid muscles adduct.
 3. Paralysis: Unilateral SLN denervation has little clinical effect. Bilateral SLN palsy results in hoarseness. Unilateral RLN 
paralysis results in deterioration in voice quality. However, acute bilateral RLN palsy can lead to stridor and respiratory 
distress. Chronic RLN denervation can lead to aphonia without airway compromise caused by compensatory mechanisms.
AIRWAY MANAGEMENT 19-3
Airway Assessment
 1. Mouth opening: Incisor distance of 3 cm or greater in adults.
 2. Upper lip bite test: Lower teeth brought in front of upper teeth to test range of motion of temporoman-
dibular joints.
 3. Mallampati classification: The greater the tongue obstructs the view of the pharyngeal structures, the 
more difficult the intubation may be
 I. Entire palatal arch is visible
 II. Upper part of faucial pillar and most of uvula are visible
 III. Only soft and hard palate are visible
 IV. Only hard palate is visible
 4. Thyromental distance: Greater than 3 fingerbreadths is desirable.
 5. Neck circumference: Greater than 27 inches suggests difficulty in visualizing glottic opening.
AIRWAY MANAGEMENT 19-4
Mallampati Classification
(Reproduced, with permission, from Mallampati SR: Clinical signs to predict difficult tracheal 
intubation [hypothesis]. Can Anaesth Soc J 1983;30:316.)
AIRWAY MANAGEMENT 19-5
Equipment
Oral and nasal airways: Anesthetized patients lose upper airway muscle tone, causing the tongue and epiglottis to fall back 
against the posterior pharynx. An artificial airway can maintain air passage. Awake or lightly anesthetized patients can 
develop laryngospasm during insertion. Avoid nasal airways in anticoagulated patients, as well as patients with basilar skull 
fractures.
Bag and mask ventilation (BMV): Effective mask ventilation requires a gas-tight mask fit and a patent airway. Limit 
positive-pressure ventilation to 20 cm H2O to avoid stomach inflation. The mask is in the operator’s left hand with the face 
lifted into the mask by the third, fourth, and fifth digits. If ventilation is ineffective, place an oral or nasal airway. Difficult 
mask ventilation is seen in patients with beards, morbid obesity, and craniofacial deformities. Prolonged mask ventilation 
may lead to damage of trigeminal and facial nerves.
Supraglottic airway devices (SADs): SADs consist of a hypopharyngeal cuff, which seals and directs airflow to the glottis, 
trachea, and lungs, as well as a tube that connects to the respiratory circuit or breathing bag. Laryngeal mask airways (LMA), 
a type of SAD, provide a low-pressure seal around the larynx. There are a variety of designs, but none offers the same pro-
tection from aspiration pneumonitis as a cuffed endotracheal tube. Contraindications to LMAs include pharyngeal pathol-
ogy, pharyngeal obstruction, full stomachs, and low pulmonary compliance requiring peak inspiratory pressures greater than 
30 cm H2O. LMAs are an important aspect of the difficult airway algorithm because of their ease of insertion and ability to 
act as a conduit for endotracheal intubation.
Tracheal tubes (TTs): Most adult TTs have a cuff, creating a tracheal seal to permit positive-pressure ventilation and reduce 
aspiration. High-pressure (low-volume) or low-pressure (high-volume) cuffs may be used. High-pressure cuffs are associ-
ated with more tracheal ischemia; low-pressure cuffs cause more sore throats, aspiration, and difficult insertions. Cuff pres-
sure may rise with nitrous oxide general anesthesia because of diffusion of gas into the cuff.
AIRWAY MANAGEMENT 19-6
Equipment
Rigid laryngoscopes: Laryngoscopes are used to examine the 
larynx and facilitate tracheal intubation. These require proper 
alignment of oral, pharyngeal, and laryngeal structures to allow a 
direct view of the glottis. Macintosh and Miller blades are the 
most commonly used blades.
Video laryngoscopes: These use a video chip or lens and mir-
ror at the tip of the intubation blade to transmit a view of the 
glottis to the operator, allowing for indirect laryngoscopy. 
Visualization of the glottis does not equate to successful intu-
bation. A styleted TT bent into a curve similar to the blade is 
recommended. Different varieties of these laryngoscopes 
include Storz SCI Video laryngoscope (allows direct and indi-
rect laryngoscopy), McGrath laryngoscope, GlideScope 
(60 degree angle view), Airtraq (includes a channel to guide the 
TT to the glottis), and Video Intubating Stylet.
Flexible fiberoptic bronchoscopes: Allow indirect visualiza-
tion of the larynx for awake intubation as well as for patients 
with unstable cervical spines and airway anomalies. These also 
include aspiration channels for secretion suctioning, insuffla-
tion of oxygen, or local anesthetic instillation.
AIRWAY MANAGEMENT 19-7
Techniques for Direct and Indirect Laryngoscopy and Intubation
Rigid laryngoscopy: Prepare for intubation by checking equipment and 
properly positioning the patient. A suction unit should be available for pos-
sible secretions,blood, or emesis. 
Positioning: Align the oral and pharyngeal axes by having the patient in a “sniff-
ing” position. Keep the neck in neutral position if cervical pathology is suspected. 
Morbidly obese patients should be positioned on 30-degree upward ramp.
Preoxygenation with 100% oxygen: Important for denitrogenation of the 
functional residual capacity (FRC), thus allowing for increased duration of 
apnea without desaturation.
Orotracheal intubation: Laryngoscope in the left hand, scissor mouth open with 
right hand, sweep tongue to the left. Curved blades are inserted into the vallecula 
and straight blades cover the epiglottis. Raise the handle up and away from the 
patient to expose the vocal cords. With the right hand, pass the TT through vocal 
cords. Inflate the cuff up to 30 mm Hg to minimize the risk of tracheal ischemia. 
Monitor capnography (gold standard) and auscultate to ensure the TT is in the 
trachea. If the TT is endobronchial, peak inspiratory pressures will be high. 
Palpate the cuff at sternal notch while compressing the pilot balloon to confirm 
positioning. If failed intubation, make changes: change tube size, reposition the 
patient, use a different blade or indirect laryngoscope, or use the help of another 
anesthesiologist. If unable to ventilate, refer to difficult airway algorithm.
Nasotracheal intubation: Spray phenylephrine nose drops to vasoconstrict vessels in the nostril the patient breathes most 
easily through. Lubricate TT and advance tube into nares until tip is in oropharynx. Then perform laryngoscopy and advance 
the tube into the trachea. Use Magill forceps if needed to direct TT but avoid damaging the cuff. Avoid this technique in 
patients with severe midfacial trauma because of the risk of intracranial placement.
(Modified and reproduced, with permission, 
from Dorsch JA, Dorsch SE: Understanding 
Anesthesia Equipm ent: Construction, Care, 
and Com plications. Williams & Wilkins, 1991.)
AIRWAY MANAGEMENT 19-8
Techniques for Direct and Indirect Laryngoscopy and Intubation
Fiberoptic intubation (FOI): FOI can be performed awake or asleep via oral or nasal routes. If awake intuba-
tion, topicalize the airway with anesthetic spray and provide sedation. Keep the shaft of the bronchoscope 
straight for better control. Pulling the tongue forward or thrusting the jaw forward may help facilitate intuba-
tion. When in the trachea, the TT is advances off the fiberoptic bronchoscope (FOB); confirm placement before 
withdrawing FOB.
Surgical Airway Techniques
 1. Surgical cricothyroidotomy: Surgical incision of cricothyroid membrane (CTM) and placement of breath-
ing tube. This can also be done with a Seldinger catheter/wire/dilator technique.
 2. Catheter cricothyroidotomy: Place a 16- or 14-gauge intravenous cannula with syringe through the CTM. 
Ventilate with either jet ventilation or via a breathing circuit attachment. Allow adequate exhalation to avoid 
barotrauma. This can result in subcutaneous or mediastinal emphysema.
 3. Retrograde intubation: Pass a wire through a catheter placed in the CTM and advance to the mouth or 
nose. Thread wire into a FOB loaded with TT or into a small TT to secure the airway.
A
I
R
W
A
Y
 
M
A
N
A
G
E
M
E
N
T
1
9
-
9
Difficult Airway Alg orithm
1. Assess the like lihood and clinica l impact of bas ic management problems.
A. Difficult ventila tion
B. Difficult intuba tion
C. Difficulty with pa tient coopera tion or consent
D. Difficult tracheos tomy
2. Active ly pursue opportunitie s to de live r supplementa l oxygen throughout the process of difficult
 a irway management.
3. Cons ide r the re la tive merits and fea s ibility of bas ic management choices :
4. Deve lop primary and a lte rna tive s tra tegies .
Noninvas ive technique for initia l 
approach to intuba tion
Invas ive technique for initia l 
approach to intuba tionvs.
B.
P re se rva tion of spontaneous 
ventila tion
Abla tion of spontaneous 
ventila tionvs.
C.
Awake intuba tion Intuba tion a ttempts a fte r 
induction of gene ra l anes thes iavs.
A.
Airway approached by 
noninvas ive intuba tion
Airway secured by 
invas ive access*
Cance l 
ca se
Cons ide r fea s ibility 
of other options a
Invas ive a irway 
access a*
FAIL
Awake IntubationA.
Succeed*
Initia l intuba tion 
a ttempts 
success ful*
Initia l intuba tion a ttempts 
UNSUCCESSFUL
FROM THIS POINT ONWARD 
CONSIDER:
1. Ca lling for he lp
2. Re turning to spontaneous
 ventila tion
3. Awakening the pa tient
Intubation Attempts after Induction
o f General Anes thes ia
B.
Face mask ventila tion adequa te Face mask ventila tion not adequa te
Cons ider/a ttempt LMA
LMA adequa te* LMA not adequa te or not fea s ible
Emerg ency Pathway
Ventila tion inadequa te , intuba tion 
unsuccess ful
Nonemerg ency Pathway
Ventila tion adequa te , intuba tion unsuccessful
Alte rna tive approaches to intuba tionc Ca ll for he lp
Emergency noninvas ive a irway ventila tione
Invas ive a irway
ventila tionb*
Awaken pa tientdCons ide r fea s ibility of
other options a
Success ful
intuba tion*
Success ful
ventila tion*
Emergency 
invas ive 
a irway 
access b*
FAIL a fte r multiple
a ttempts
FAIL
(Reproduced, with permission, from the American Society of Anesthesiolo-
gists Task Force on Management of the Difficult Airway. Practice guidelines 
for management of the difficult airway: an updated report by the American 
Society of Anesthesiologists Task Force on Management of the Difficult 
Airway. Anesthesiology 2003;98:1269.)
AIRWAY MANAGEMENT 19-10
Complications of Laryngoscopy and Intubation
 1. Airway trauma: Dental injury, sore throat, tracheal stenosis caused by high cuff pressures compromising 
tracheal blood flow. Postintubation croup is seen in children. Vocal cord paralysis from cuff compression 
or RLN trauma can result in hoarseness and increase aspiration risk. Choosing a smaller TT can lead to less 
postoperative sore throat.
 2. Errors in TT positioning: Esophageal intubation—avoid with monitoring capnography (gold standard), 
auscultation, chest radiography, or FOB. Mainstem intubation—typically right-sided because of the less 
acute angle between the right main bronchus and trachea. Signs include unilateral breath sounds, hypoxia, 
high peak inspiratory pressures, and inability to palpate TT cuff in sternal notch. Minimal testing for TT 
position includes chest auscultation, routine capnography, and occasional cuff palpation. If the patient is 
repositioned, reconfirm TT placement. Neck extension or lateral rotation moves TT away from carina, and 
neck flexion moves the TT toward the carina.
 3. Physiological responses to airway instrumentation: Hypertension and tachycardia (less with LMA than TT). 
Decrease these responses with lidocaine, opioids, β-blockers, or deeper planes of inhalational anesthesia prior 
to laryngoscopy. Laryngospasm caused by sensory stimulation of SLN is involuntary spasm of laryngeal 
musculature. Prevent with extubation of either a deeply asleep or fully awake patient. Treatment includes 
positive-pressure ventilation with 100% oxygen or IV lidocaine administration. Succinylcholine (0.25-0.5 mg/kg) 
with or without propofol may be needed if laryngospasm persists. Laryngospasm can lead to negative-pressure 
pulmonary edema in healthy young adults caused by large negative intrathoracic pressure.
 4. Tracheal tube malfunction: Polyvinyl chloride tubes can ignite with cautery or laser in an oxygen/nitrous 
oxide-enriched environment. TT obstruction from kinking and thick secretions can also occur.
AIRWAY MANAGEMENT 19-11
Problems After Intubation
 1. Decreased oxygen saturation: Auscultate the chest to confirm breath sounds and listen for wheezes, 
rhonchi, and rales. Check breathing circuit. Fiberoptic bronchoscopy can clear mucous plugs. Use 
bronchodilators to treat bronchospasm. Add positive end-expiratory pressure to obese patients to improve 
oxygenation.
 2.Decreased CO2: Sudden decrease can indicate pulmonary or air embolism. Also consider decline in 
cardiac output or circuit leak.
 3. Increased CO2: Hypoventilation, malignant hyperthermia, sepsis, or breathing circuit malfunction.
 4. Increased airway pressure: Obstructed TT or reduced pulmonary compliance.
 5. Decreased airway pressure: Leaks in breathing circuit or inadvertent extubation.
AIRWAY MANAGEMENT 19-12
Techniques of Extubation
Extubate awake or deeply anesthetized patients. Ensure adequate recovery of neuromuscular blockade. Avoid 
extubation in light anesthetic plane because of the risk of laryngospasm. Awake extubation is associated with 
coughing on the TT, leading to increases in heart rate, blood pressure, intracranial pressure, and intraocular 
pressure. Avoid awake extubation if the patient cannot tolerate these effects. However, do not extubate deeply 
anesthetized patients if there is a risk for aspiration or difficult airway. Before extubation, suction the pharynx 
and place the patient on 100% oxygen. After extubation, deliver oxygen by facemask during transportation to 
the postanesthesia care area.
CARDIOVASCULAR PHYSIOLOGY AND ANESTHESIA 20-1
Cardiac Action Potentials
• The myocardial cell membrane is normally permeable to K+ but is relatively impermeable to Na+. A mem-
brane-bound Na+–K+-adenosine triphosphatase (ATPase) concentrates K+ intracellularly in exchange for 
extrusion of Na+ out of the cells. Intracellular Na+ concentration is kept low, but intracellular K+ concentra-
tion is kept high relative to the extracellular space. Movement of K+ out of the cell and down its concentra-
tion gradient results in a net loss of positive charges from inside the cell. An electrical potential is established 
across the cell membrane, with the inside of the cell negative with respect to the extracellular environment 
because anions do not accompany K+. Thus, the resting membrane potential represents the balance between 
two opposing forces: the movement of K+ down its concentration gradient and the electrical attraction of the 
negatively charged intracellular space for the positively charged potassium ions.
CARDIOVASCULAR PHYSIOLOGY AND ANESTHESIA 20-2
• Normal ventricular cell resting membrane potential is −80 to −90 mV. As with other excitable tissues (nerve 
and skeletal muscle), when the cell membrane potential becomes less negative and reaches a threshold value, 
a characteristic action potential (depolarization) develops. The action potential transiently raises the mem-
brane potential of the myocardial cell to +20 mV. In contrast to action potentials in neurons, the spike in 
cardiac action potentials is followed by a plateau phase that lasts 0.2 to 0.3 s. Whereas the action potential 
for skeletal muscle and nerves is caused by the abrupt opening of fast sodium channels in the cell membrane, 
in cardiac muscle, it is due to the opening of both fast sodium channels (the spike) and slower calcium chan-
nels (the plateau). Depolarization is also accompanied by a transient decrease in potassium permeability. 
Subsequent restoration of normal potassium permeability and closure of sodium and calcium channels 
eventually restore the membrane potential to normal.
CARDIOVASCULAR PHYSIOLOGY AND ANESTHESIA 20-3
Initiation and Conduction of the Cardiac Impulse
• The cardiac impulse normally originates in the sinoatrial (SA) node, a group of specialized pacemaker cells 
that leak sodium. The slow influx of sodium, which results in a less negative, resting membrane potential 
(−50 to −60 mV), has three important consequences: constant inactivation of fast sodium channels, an action 
potential with a threshold of −40 mV that is primarily caused by ion movement across the slow calcium 
channels, and regular spontaneous depolarizations. During each cycle, intracellular leakage of sodium 
causes the cell membrane to become progressively less negative; when the threshold potential is reached, 
calcium channels open, potassium permeability decreases, and an action potential develops. Restoration of 
normal potassium permeability returns the cells in the SA node to their normal resting membrane potential.
• The impulse generated at the SA node is normally rapidly conducted across the atria and to the atrioven-
tricular (AV) node. The AV node in the right atrial septal wall has two junctional regions and a middle nodal 
region. Both junctional areas possess intrinsic automaticity at a rate 40 to 60 times/min, allowing a junc-
tional heart rhythm if the rate of SA nodal depolarization decreases.
• The lower fibers of the AV node combine to form the common bundle of His, which passes into the inter-
ventricular septum before dividing into left and right branches to form the complex network of Purkinje 
fibers that depolarize both ventricles.
CARDIOVASCULAR PHYSIOLOGY AND ANESTHESIA 20-4
Anesthetic Effects on the Heart
Volatile anesthetics: Depress the SA node automaticity but have only modest effects on the AV node, so 
junctional tachycardia may be seen under GA with anticholinergics.
Intravenous anesthetics: Limited electrophysiologic effects in clinical doses.
Local anesthetics: At high concentrations, local anesthetics depress conduction by binding to fast sodium 
channels; at extremely high concentrations, they also depress the SA node. Bupivacaine, the most cardiotoxic 
local anesthetic, binds inactivated fast sodium channels and dissociates from them slowly. It can cause pro-
found sinus bradycardia and sinus node arrest as well as malignant ventricular arrhythmias.
Opioids: Fentanyl and sufentanil can depress cardiac conduction, increasing AV node conduction and refrac-
tory period and prolonging the duration of the Purkinje fiber action potential.
CARDIOVASCULAR PHYSIOLOGY AND ANESTHESIA 20-5
Mechanism of Contraction of Myocardial Cells
• Myocardial cells contract as a result of the interaction of two overlapping, rigid contractile proteins, actin 
and myosin. These proteins are fixed in position within each cell during both contraction and relaxation.
• Dystrophin, a large intracellular protein, connects actin to the cell membrane (sarcolemma). Cell shortening 
occurs when actin and myosin are allowed to fully interact and slide over one another.
• Troponin and tropomyosin normally prevent the interaction of actin and myosin.
• Troponin has 3 subunits: troponin I, troponin C, and troponin T.
• Whereas troponin is attached to actin at regular intervals, tropomyosin lies within the center of the actin 
structure. An increase in intracellular calcium concentration (from about 10−7 to 10−5 mol/L) promotes con-
traction as calcium ions bind troponin C. The resulting conformational change in these regulatory proteins 
exposes the active sites on actin that allow interaction with myosin bridges (points of overlapping). The 
active site on myosin functions as a magnesium-dependent ATPase whose activity is enhanced by the 
increase in intracellular calcium concentration.
• Relaxation occurs as calcium is actively pumped back into the sarcoplasmic reticulum by a Ca2+–Mg2+-
ATPase; the resulting drop in intracellular calcium concentration allows the troponin–tropomyosin complex 
to again prevent the interaction between actin and myosin. The force of contraction is directly dependent on 
the magnitude of the initial calcium influx.
CARDIOVASCULAR PHYSIOLOGY AND ANESTHESIA 20-6
Innervation of the Heart
• Parasympathetic fibers primarily innervate the atria and conducting tissues. Acetylcholine acts on specific 
cardiac muscarinic receptors (M2) to produce negative chronotropic, dromotropic, and inotropic effects.
• Sympathetic fibers are more widely distributed throughout the heart. Cardiac sympathetic fibers originate in 
the thoracic spinal cord (T1–T4) and travel to the heart initially through the cervical ganglia (stellate) and 
then as the cardiac nerves. Norepinephrine release causes positive chronotropic, dromotropic, and inotropic 
effectsprimarily through activation of β1-adrenergic receptors. β2-Adrenergic receptors found primarily in 
the atria increase heart rate. α 1-Adrenergic receptors have a positive inotropic effect.
CARDIOVASCULAR PHYSIOLOGY AND ANESTHESIA 20-7
Cardiac Cycle
• Most diastolic ventricular filling occurs passively before atrial contraction. Contraction of the atria normally 
contributes 20% to 30% of ventricular filling. Patients with reduced ventricular compliance are most 
affected by loss of a normally timed atrial systole.
• Atrial pressure tracings: The a wave is caused by atrial systole. The c wave coincides with ventricular 
contraction and is said to be caused by bulging of the AV valve into the atrium. The v wave is the result of 
pressure buildup from venous return before the AV valve opens again. The x descent is the decline in pres-
sure between the c and v waves and is thought to be caused by a pulling down of the atrium by ventricular 
contraction. The notch in the aortic pressure tracing is referred to as the incisura and represents transient 
backflow of blood into the left ventricle just before aortic valve closure.
CARDIOVASCULAR PHYSIOLOGY AND ANESTHESIA 20-8
Hemodynamic Parameters
• Stroke volume (SV) is normally determined by three major factors: preload, afterload, and contractility.
• Ventricular preload is end-diastolic volume, which is dependent on ventricular filling. In the absence of 
pulmonary or right ventricular dysfunction, venous return is also the major determinant of left ventricular 
preload. Venous return is affected by PPV, posture, tachycardia above 120 beats/min, ineffective atrial con-
traction as in supraventricular arrhythmias, and pericardial pressures.
• Afterload depends on ventricular wall tension during systole and arterial impedance to ejection. The larger 
the ventricular radius, the greater the wall tension required to develop the same ventricular pressure, but an 
increase in wall thickness reduces ventricular wall tension. Left ventricular afterload usually equals systemic 
vascular resistance (SVR), which is primary dependent on arteriolar tone.
• SVR = 80 × 
MAP − CVP
CO
 (normal values are 900 – 1500 dyn � s cm−5)
• CI = HR × SV/BSA (normal values are 2.5 – 4.2 L/min/m2)
where MAP is mean arterial pressure, CVP is central venous pressure, CI is cardiac index, HR is heart rate, 
SV is stroke volume, and BSA is body surface area.
• Contractility is related to the rate of myocardial muscle shortening, which in turn depends on the intracel-
lular calcium concentration during systole. Norepinephrine, sympathomimetic drugs, and secretion of epi-
nephrine from the adrenal glands increase contractility via β1-receptor activation.
• Myocardial contractility is depressed by anoxia, acidosis, depletion of catecholamine stores within the heart, 
and loss of functioning muscle mass as a result of ischemia or infarction. Most anesthetics and antiarrhythmic 
agents are negative inotropes (i.e., they decrease contractility).
CARDIOVASCULAR PHYSIOLOGY AND ANESTHESIA 20-9
Abnormal Cardiac Function
• Ventricular wall abnormalities: Hypokinesis (decreased contraction), akinesis (failure to contract), and 
dyskinesis (paradoxic bulging) during systole reflect increasing degrees of contraction abnormalities. 
Although contractility may be normal or even enhanced in some areas, abnormalities in other areas of the 
ventricle can impair emptying and reduce SV.
• Valvular dysfunction: Whereas stenosis of an AV valve reduces SV by decreasing ventricular preload, 
stenosis of a semilunar valve reduces SV by increasing ventricular afterload. Regurgitation can reduce SV 
by regurgitant volume with each contraction.
CARDIOVASCULAR PHYSIOLOGY AND ANESTHESIA 20-10
Regulation of Vascular Tone
• Most tissue beds regulate their own blood flow (autoregulation). These phenomena are likely caused by both 
an intrinsic response of vascular smooth muscle to stretch and the accumulation of vasodilatory metabolic 
byproducts. The latter may include K+, H+, CO2, adenosine, and lactate.
• The vascular endothelium secretes or modifies substances that control blood pressure or flow such as vaso-
dilators (e.g., nitric oxide, prostacyclin [PGI2]), vasoconstrictors (endothelins, thromboxane A2), anticoagu-
lants (e.g., thrombomodulin, protein C), fibrinolytics (tissue plasminogen activator), and factors that inhibit 
platelet aggregation (nitric oxide and PGI2).
• Autonomic control of the entire vasculature except the capillaries is primarily sympathetic via the thoracic 
and the first two lumbar segments. Sympathetic-induced vasoconstriction (via α 1-adrenergic receptors) can 
be potent in skeletal muscle, kidneys, the gut, and the skin; it is least active in the brain and heart. The most 
important vasodilatory fibers are those to skeletal muscle, mediating an increase in blood flow (via 
β2-adrenergic receptors) in response to exercise. Vasodepressor (vasovagal) syncope, which can occur after 
intense emotional strain associated with high sympathetic tone, results from reflex activation of both vagal 
and sympathetic vasodilator fibers.
• Vascular tone and autonomic influences on the heart are controlled by vasomotor centers in the reticular 
formation of the medulla and lower pons. They are also responsible for the adrenal secretion of catechol-
amines as well as the enhancement of cardiac automaticity and contractility.
CARDIOVASCULAR PHYSIOLOGY AND ANESTHESIA 20-11
Control of Arterial Blood Pressure
• Immediate control: Minute-by-minute control of blood pressure (BP) is primarily the function of auto-
nomic nervous system reflexes. Changes in BP are sensed centrally (hypothalamic and brainstem areas) and 
peripherally by specialized sensors (baroreceptors). Decreases in arterial blood pressure enhance sympa-
thetic tone, increase adrenal secretion of epinephrine, and suppress vagal activity. The resulting systemic 
vasoconstriction, elevation in heart rate, and enhanced cardiac contractility increase blood pressure. 
Conversely, hypertension decreases sympathetic outflow and enhances vagal tone. Peripheral baroreceptors 
are located at the bifurcation of the common carotid arteries and the aortic arch. Elevations in blood pressure 
increase baroreceptor discharge, inhibiting systemic vasoconstriction and enhancing vagal tone (barorecep-
tor reflex).
• Intermediate control: Over a few minutes, sustained decreases in arterial pressure together with enhanced 
sympathetic outflow activate the renin–angiotension–aldosterone system, increase secretion of arginine 
vasopressin (AVP), and alter normal capillary fluid exchange. Both angiotensin II and AVP are potent arte-
riolar vasoconstrictors.
• Long-term control: The effects of renal mechanisms occur hours after sustained changes in arterial pres-
sure. The kidneys alter total body sodium and water balance to restore BP to normal.
CARDIOVASCULAR PHYSIOLOGY AND ANESTHESIA 20-12
Anatomy and Physiology of the Coronary Circulation
• The blood supply is derived entirely from the right and left coronary arteries. After perfusing the myocar-
dium, blood returns to the right atrium via the coronary sinus and anterior cardiac veins.
• The right coronary artery (RCA) normally supplies the right atrium, most of the right ventricle, and a vari-
able portion of the left ventricle (inferior wall). In 85% of persons, the RCA gives rise to the posterior 
descending artery (PDA), which supplies the superior–posterior interventricular septum and inferior wall.
• The left coronary artery (LCA) normally supplies the left atrium, most of the interventricular septum, and 
most of the left ventricle. The LCA bifurcates into the left anterior descending coronary artery (LAD) and 
left circumflex (CX) coronary artery. The LAD supplies the septum and anterior wall and the CX supplies 
the lateral wall.
• Thus, coronary perfusion pressure is usually determined by the difference between aortic pressure and ventricu-
lar pressure,and the left ventricle is perfused almost entirely during diastole. Increases in heart rate also decrease 
coronary perfusion because of disproportionately greater reduction in diastolic time as heart rate increases.
• Sympathetic stimulation of the coronaries increases myocardial blood flow because of increased metabolic 
demand and a predominance of β2-receptor activation.
• Coronary vessel tone can be autoregulated between perfusion pressures of 50 and 120 mm Hg. The endo-
cardium is most vulnerable to ischemia during decreases in coronary perfusion pressure.
• Most volatile anesthetic agents are coronary vasodilators. Whereas vasodilation caused by desflurane is 
primarily autonomically mediated, sevoflurane appears to lack coronary vasodilating properties. Dose-
dependent abolition of autoregulation may be greatest with isoflurane.
• Volatile agents reduce myocardial oxygen requirements and are protective against reperfusion injury.
CARDIOVASCULAR PHYSIOLOGY AND ANESTHESIA 20-13
Heart Failure
• In most forms of heart failure, cardiac output is reduced, and inadequate oxygen delivery to tissues is 
reflected by a low mixed venous oxygen tension and an increase in the arteriovenous oxygen content differ-
ence. High cardiac output heart failure can be seen in sepsis or other hypermetabolic states, which are typi-
cally associated with low SVR.
• Systolic heart failure occurs when the heart is unable to pump a sufficient amount of blood to meet the 
body’s metabolic requirements.
• Clinical manifestations usually reflect the effects of the low cardiac output on tissues (e.g., fatigue, oxygen 
debt, acidosis), the damming up of blood behind the failing ventricle (systemic or pulmonary venous con-
gestion), or both.
• Left ventricular failure most commonly results from primary myocardial dysfunction (usually from coro-
nary artery disease) but may also result from valvular dysfunction, arrhythmias, or pericardial disease.
• In patients with diastolic heart failure, the impaired heart relaxes poorly and produces increased left ven-
tricular end-diastolic pressures. These pressures are transmitted to the left atrium and pulmonary vascula-
ture, resulting in symptoms of congestion. Diastolic dysfunction can also cause symptoms of heart failure 
as a result of atrial hypertension. Common causes include hypertension, coronary artery disease, hypertro-
phic cardiomyopathy, and pericardial disease.
• To compensate for heart failure, the body responds by increasing preload, increasing sympathetic tone (and 
afterload), and ventricular hypertrophy, which all worsen cardiac function. The failing heart becomes 
increasingly dependent on catecholamines and sympathetic stimulation, which both decrease with anesthetic 
induction.
CARDIOVASCULAR PHYSIOLOGY AND ANESTHESIA 20-14
Basic Concepts of Heart Failure
• In ventricular failure, the body attempts to compensate for left ventricular systolic function through the 
sympathetic and renin–angiotensin–aldosterone systems. Consequently, patients experience salt retention, 
volume expansion, sympathetic stimulation, and vasoconstriction. The heart dilates to maintain the SV 
despite decreased contractility. Anesthetic induction often reduces sympathetic tone and decreases venous 
return, reducing cardiac output and resulting in hypotension and decreased tissue oxygen delivery.
• Patients with systolic heart failure are likely to present to surgery having been previously treated with diuret-
ics, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers and possibly aldosterone 
antagonists.
• Electrolytes need to be followed because heart failure therapies frequently lead to changes in serum potas-
sium concentration.
ANESTHESIA FOR PATIENTS WITH CARDIOVASCULAR DISEASE 21-1
Endocarditis Prophylaxis
• The American College of Cardiology (ACC) and American Heart Association (AHA) currently suggest 
(class IIa recommendations) endocarditis prophylaxis for patients at the highest risk undergoing dental pro-
cedures involving gingival manipulation or perforation of the oral mucosa: (1) prosthetic cardiac valves or 
patients with prosthetic heart materials, (2) patients with a history of endocarditis, (3) patients with con-
genital heart disease that is either partially repaired or unrepaired, (4) patients with congenital heart disease 
with residual defects after repair, (5) patients with congenital heart disease completely repaired within 
6 months of either catheter- or surgical-based repair, and (6) cardiac transplant patients with structurally 
abnormal valves.
• The ACC/AHA guidelines note that many patients and physicians expect and may give endocarditis prophy-
laxis in patients with valvular heart disease, aortic coarctation, and hypertrophic cardiomyopathy.
• The AHA notes that antibiotics should continue to be given where needed for prevention of wound infection.
• Endocarditis prophylaxis is not recommended for routine gastrointestinal or genitourinary procedures.
ANESTHESIA FOR PATIENTS WITH CARDIOVASCULAR DISEASE 21-2
Risk Factors for Perioperative Myocardial Infarction
• Ischemic heart disease (known history of myocardial infarction, electrocardiographic [ECG] evidence, 
chest pain)
• Congestive heart failure (dyspnea, pulmonary edema on chest radiography, echocardiography findings)
• Cerebrovascular disease (stroke)
• High-risk surgery (vascular, thoracic, abdominal, orthopedic surgery)
• Preoperative insulin therapy
• Preoperative creatinine greater than 2 mg/dL
ANESTHESIA FOR PATIENTS WITH CARDIOVASCULAR DISEASE 21-3
Noninvasive Stress Testing: AHA/ACC Guidelines
• Stress testing is only indicated if it would change patient management.
• Guidelines include noninvasive stress testing in patients scheduled for noncardiac surgery with active cardiac 
conditions (class I).
• Guidelines (class IIa) also suggest that there may be benefit of such testing in patients with three or more 
clinical risk factors and poor functional capacity.
• Noninvasive testing (class IIb) can be of some possible benefit in patients with one or two clinical risk fac-
tors undergoing intermediate-risk or vascular surgery.
• The AHA guidelines do not recommend the indiscriminate use of noninvasive cardiac testing for patients 
with no risk factors undergoing intermediate-risk surgery or patients undergoing low-risk surgery.
ANESTHESIA FOR PATIENTS WITH CARDIOVASCULAR DISEASE 21-4
Testing for Cardiac Disease
• Holter monitor: Continuous ambulatory electrocardiographic (Holter) monitoring is useful in evaluating 
arrhythmias, antiarrhythmic drug therapy, and the severity and frequency of ischemic episodes.
• Exercise electrocardiography: Limited usefulness in patients with baseline ST-segment abnormalities and 
those who are unable to increase their heart rate (>85% of maximal predicted) because of fatigue, dyspnea, 
or drug therapy. For most ambulatory patients, exercise ECG testing is ideal because it estimates functional 
capacity and detects for myocardial ischemia.
• Myocardial perfusion scans: Myocardial perfusion imaging using thallium-201 or technetium-99m is used 
in evaluating patients who cannot exercise (e.g., peripheral vascular disease) or who have underlying ECG 
abnormalities that preclude interpretation during exercise (e.g., left bundle-branch block). If the patient can-
not exercise, images are obtained before and after injection of an intravenous coronary dilator (e.g., dipyri-
damole or adenosine) to produce a hyperemic response similar to exercise.
• Echocardiography: This technique provides information about both regional and global ventricular func-
tion and may be carried out at rest, after exercise, or with administration of dobutamine.
• Coronary angiography: Gold standard in detecting coronary artery disease (CAD). In evaluating fixed 
stenotic lesions, occlusions greater than 50% to 75% are generally considered significant. Significant steno-
sis of the left main coronary artery is ominousbecause it affects almost the entire left ventricle.
ANESTHESIA FOR PATIENTS WITH CARDIOVASCULAR DISEASE 21-5
Indications for Preoperative Coronary Revascularization
• The ACC/AHA guidelines note that only the subset of patients with CAD who would benefit from revascu-
larization irrespective of their need for a nonemergent surgical procedure are likely to benefit from preop-
erative coronary interventions.
• The indications for testing of those patients as candidates for a coronary intervention is predicted by their 
general requirement for such evaluation as a part of the management of CAD irrespective of the planned 
surgery.
• General contraindications to surgery are an myocardial infarction (MI) less than 1 month before surgery with 
persistent ischemic risk by symptoms or noninvasive testing, uncompensated heart failure, and severe aortic 
or mitral stenosis.
• Patients with stable angina and significant left main, stable angina and three-vessel disease, stable angina 
and two-vessel disease with an ejection fraction below 50%, unstable angina, non–ST-segment elevation MI, 
and acute ST segment elevation MI benefit from revascularization before noncardiac surgery (class I).
• Conversely, revascularization is not indicated in patients with stable angina (class III).
• Moreover, elective noncardiac surgery is not recommended within 4 to 6 weeks after bare metal stent place-
ment or within 12 months of placement of a drug-eluting stent if antiplatelet therapy needs to be discontinued.
• Anesthesia staff should never of their own volition discontinue antiplatelet or antithrombotic agents periop-
eratively but should work in collaboration with the patient’s surgeons and cardiologists.
ANESTHESIA FOR PATIENTS WITH CARDIOVASCULAR DISEASE 21-6
Guidelines for Perioperative Blood Pressure
• Intraoperative blood pressure (BP) should generally be kept within 10% to 20% of preoperative levels.
• In treating hypertension, an angiotensin-converting enzyme (ACE) inhibitor is considered an optimal first-
line choice for patients with left ventricular dysfunction or heart failure, but an ACE inhibitor or angiotensin 
receptor blocker is not considered an optimal initial single agent in the setting of hyperlipidemia, chronic 
kidney disease, or diabetes (particularly with nephropathy). A β-adrenergic blocker or, less commonly, a 
calcium channel blocker is used as a first-line agent for patients with CAD.
• Treatment guidelines recommend a diuretic with or without β-adrenergic blockade or a calcium channel 
blocker alone for elderly patients.
• Elective surgical procedures on patients with sustained preoperative diastolic BP higher than 110 mm Hg—
particularly those with evidence of end-organ damage despite attempts to correct the BP with intravenous 
agents—should be delayed until BP is better controlled over the course of several days.
• Patients who present with elevated BP the morning of surgery are at high likelihood for hypotension with 
induction and then exaggerated hypertension with intubation.
• Direct intraarterial pressure monitoring is needed for patients with wide swings in BP and for major surger-
ies associated with large changes in cardiac preload or afterload.
• Malignant hypertension is a true medical emergency characterized by severe hypertension (>210/120 mm Hg) 
associated with papilledema and, frequently, encephalopathy and requires vasodilator infusions and inpatient 
admission.
ANESTHESIA FOR PATIENTS WITH CARDIOVASCULAR DISEASE 21-7
Perioperative Myocardial Ischemia
• Common causes include severe hypertension or tachycardia (particularly in the presence of ventricular 
hypertrophy); coronary artery vasospasm or anatomic obstruction; severe hypotension, hypoxemia, or 
 anemia; and severe aortic stenosis or regurgitation. Sudden withdrawal of antianginal medication 
 perioperatively—particularly β-blockers—can precipitate a sudden increase in ischemic episodes (rebound 
hypertension, tachycardia, or both).
• Symptom history, such as chest pain, dyspnea, poor exercise tolerance, syncope, or near syncope, includes 
important indicators of ischemia.
• Unstable angina is defined as (1) an abrupt increase in the severity, frequency (more than three episodes 
per day), or duration of anginal attacks (crescendo angina); (2) angina at rest; or (3) new onset of angina 
(within the past 2 months) with severe or frequent episodes (more than three per day). It usually reflects 
severe underlying coronary disease and frequently precedes MI. Critical stenosis is present in more than 80% 
of patients, and they should be evaluated for coronary angiography and revascularization. Laboratory evalu-
ation for patients who have a history compatible with recent unstable angina and are undergoing emergency 
procedures should also include serum cardiac enzymes.
• Chronic stable angina symptoms are generally absent until the atherosclerotic lesions cause 50% to 75% 
occlusions in the coronary circulation. When a stenotic segment reaches 70% occlusion, maximum compen-
satory dilatation is usually present distally; blood flow is generally adequate at rest but becomes inadequate 
with increased metabolic demand. Chronic stable (mild to moderate) angina does not appear to increase 
perioperative risk substantially.
ANESTHESIA FOR PATIENTS WITH CARDIOVASCULAR DISEASE 21-8
Treatment of Ischemic Heart Disease
• Correction of risk factors in the hope of slowing disease progression
• Modification of the patient’s lifestyle to reduce stress and improve exercise tolerance
• Correction of complicating medical conditions that can exacerbate ischemia, such as hypertension, anemia, 
hypoxemia, hyperthyroidism, fever, infection, or adverse drug effects
• Pharmacologic manipulation of the myocardial oxygen supply–demand relationship
• Correction of coronary lesions by percutaneous coronary intervention (angioplasty with or without stenting, 
or atherectomy) or coronary artery bypass surgery
ANESTHESIA FOR PATIENTS WITH CARDIOVASCULAR DISEASE 21-9
Guidelines for β-Blocker Therapy
• Preoperative β-receptor blockers have been shown to reduce perioperative mortality and the incidence of 
postoperative cardiovascular complications; however, other studies have shown an increase in stroke and 
death after widespread use of β-blockers.
• β-Blockers and statins should be continued perioperatively in patients prescribed these drug therapies pre-
operatively.
• β-Blockers are useful in patients undergoing vascular surgery with evidence of ischemia on their evaluative 
workup (class I). β-Blockers should be started at least 1 week before surgery to ensure adequate β-blockade 
and to help identify side effects such as heart block.
ANESTHESIA FOR PATIENTS WITH CARDIOVASCULAR DISEASE 21-10
QT Prolongation
• Patients with a long QT interval are at risk for developing ventricular arrhythmias, particularly polymorphic 
ventricular tachycardia (torsade de pointes), which can lead to ventricular fibrillation.
• A long rate-corrected QT interval (QTc >0.44 s) may reflect underlying ischemia, drug toxicity (usually class 
Ia antiarrhythmic agents, antidepressants, or phenothiazines), electrolyte abnormalities (hypokalemia or 
hypomagnesemia), autonomic dysfunction, mitral valve prolapse, or (less commonly) a congenital abnor-
mality.
• In contrast to polymorphic ventricular arrhythmias with a normal QT interval, which respond to conven-
tional antiarrhythmics, polymorphic tachyarrhythmias with a long QT interval generally respond best to 
pacing or magnesium.
• Elective surgery should be postponed until drug toxicity and electrolyte imbalances are excluded.
• Patients with congenital prolongation generally respond to β-adrenergic blocking agents.
ANESTHESIA FOR PATIENTS WITH CARDIOVASCULAR DISEASE 21-11
Guidelines for Perioperative Management of Atrial Fibrillation
• Perioperatively atrial fibrillation (AF) can be rate controlled with β-blockers unless the patient has a preex-
citationsyndrome such as Wolff-Parkinson-White syndrome. Chemical cardioversion can be attempted with 
amiodarone or procainamide. If the duration of AF is greater than 48 hours or unknown, the ACC/AHA 
recommends anticoagulation for 3 weeks before and 4 weeks after either electrical or chemical cardiover-
sion. Alternatively, transesophageal echocardiography (TEE) can be used to rule out a left atrial or left atrial 
appendage thrombus before cardioversion.
• Postoperatively, unless contraindicated, ventricular rate response can be controlled with atrioventricular 
(AV) nodal blocking agents (digitalis, verapamil, or cardizem).
• If AF results in hemodynamic instability, synchronized cardioversion can be attempted.
• Patients at high risk for AF after cardiac surgery can be treated with prophylactic amiodarone.
• The ACC/AHA also recommends antithrombotic therapy (warfarin or aspirin) for patients with long-stand-
ing AF. The CHADS score can be used to help determine need for warfarin therapy.
ANESTHESIA FOR PATIENTS WITH CARDIOVASCULAR DISEASE 21-12
Guidelines for Perioperative Management of Ventricular Arrhythmias
• Ventricular tachycardia: Nonsustained ventricular tachycardia (VT) is short runs of ventricular ectopy that 
spontaneously terminate, lasting less than 30 seconds. Sustained VT persists for longer than 30 seconds. VT 
is either monomorphic or polymorphic depending on the QRS complex. If the QRS complex morphology 
changes, it is designated as polymorphic VT. Torsades de pointes is a form of VT associated with a prolonged 
QT interval producing a sine wave–like VT pattern on the ECG.
• Ventricular fibrillation: Ventricular fibrillation requires immediate resuscitative efforts and defibrillation. 
Amiodarone can be used to stabilize the rhythm after successful defibrillation.
• Exercise testing, echocardiography, and nuclear perfusion studies are all recommended for patients with 
ventricular arrhythmias as part of their workup and management by the ACC/AHA. Electrophysiologic stud-
ies are undertaken to determine the possibility for catheter-mediated ablation of ventricular tachycardias.
• If VT presents perioperatively, cardioversion is recommended at any point when hemodynamic compromise 
occurs.
• Torsades de pointes is associated with conditions that lengthen the QT interval. If the arrhythmia develops 
in association with pauses, then pacing or isoproterenol infusions can be effective. Magnesium sulfate may 
be useful in long QT and episodes of torsades de pointes.
ANESTHESIA FOR PATIENTS WITH CARDIOVASCULAR DISEASE 21-13
Guidelines for Perioperative Implantable Cardioverter Defibrillator (ICD) Management
• Preoperative: Establish the type of device and if it is used for antibradycardia functions. Consult with the 
patient’s cardiologist preoperatively as to the device’s function and use history. The manufacturer should be 
contacted to determine the best method for managing the device (e.g., reprogramming or applying a magnet) 
before surgery.
• Intraoperative: Determine what electromagnetic interference is likely to present intraoperatively and advise 
the use of bipolar electrocautery when possible. Ensure the availability of temporary pacing and defibrilla-
tion equipment and apply pads as necessary. Patients who are pacer dependent can be programmed to an 
asynchronous mode to mitigate electrical interference. Magnet application to ICDs may disable the antit-
achycardia function but not convert to an asynchronous pacemaker. Consultation with cardiology and inter-
rogation of the device is advised. Use of bipolar cautery, placement of the grounding pad far from the ICD 
device, and limiting use of the cautery to only short bursts help reduce the likelihood of problems but do not 
eliminate them.
• Postoperative: The device must be interrogated to make sure that therapeutic functions have been restored. 
Patients should be continuously monitored until the antitachycardia functions of the device are restored and 
its function confirmed.
ANESTHESIA FOR PATIENTS WITH CARDIOVASCULAR DISEASE 21-14
Anticoagulation
• Patients with AF and prosthetic valves routinely present for noncardiac surgery and often require disruption 
of anticoagulation (usually warfarin and aspirin).
• In patients with AF without mechanical prosthetic heart valves, the ACC/AHA suggest it is acceptable to 
discontinue anticoagulation for up to 1 week before surgical procedures without instituting heparin antico-
agulation.
• ACC/AHA guidelines indicate that patients at low risk for thrombosis such as those with bileaflet mechani-
cal valves in the aortic position with no additional problems (e.g., atrial fibrillation, hypercoagulable states) 
can have their warfarin discontinued 48 to 72 hours preoperatively so that the international normalized ratio 
(INR) falls to below 1.5.
• In consulting with the patient’s surgeon and primary physicians, patients at higher risk for thrombosis should 
have warfarin discontinued and heparin started when the INR falls below 2.0, Heparin can be discontinued 
4 to 6 hours in advance of surgery and then restarted as soon as surgical bleeding permits until the patient 
can be restarted on warfarin therapy. Fresh-frozen plasma may be given if needed in an emergency situation 
to interrupt warfarin therapy. Vitamin K should not be administered because it might lead to a hypercoagu-
lable state.
ANESTHESIA FOR PATIENTS WITH CARDIOVASCULAR DISEASE 21-15
Guidelines for Perioperative Management of Valvular Disease
• Preoperative evaluation should be primarily concerned with determining the severity of the lesion and its 
hemodynamic significance; residual ventricular function; the presence of secondary effects on pulmonary, 
renal, and hepatic function; and the presence of concomitant CAD.
• The ventricular rate should be less than 80 to 90 beats/min at rest and should not exceed 120 beats/min with 
stress or exercise.
• Preoperative evaluation includes electrolytes, blood urea nitrogen (BUN), and creatinine to evaluate renal 
impairment. Liver function tests are useful in assessing hepatic dysfunction caused by passive hepatic con-
gestion in patients with severe or chronic right-sided failure. Arterial blood gases should be measured in 
patients with significant pulmonary symptoms. Reversal of anticoagulants should be documented with a 
prothrombin time and partial thromboplastin time before surgery. Chest radiography assesses cardiac size 
and pulmonary vascular congestion.
• Although most significant murmurs and valvular lesions are detected preoperatively, anesthetists are con-
cerned that undiagnosed, critical aortic stenosis might be present, leading to hemodynamic collapse with 
either regional or general anesthesia.
• When new murmurs are detected in a preoperative evaluation, consultation with the patient’s primary physi-
cian is necessary to determine the need for echocardiographic evaluation.
ANESTHESIA FOR PATIENTS WITH CARDIOVASCULAR DISEASE 21-16
Tricuspid Regurgitation
• Clinically significant tricuspid regurgitation is most commonly caused by dilatation of the right ventricle 
from pulmonary hypertension associated with chronic left ventricular failure. Tricuspid regurgitation can 
also follow infective endocarditis (usually in injecting drug abusers), rheumatic fever, carcinoid syndrome, 
or chest trauma or may be caused by Ebstein anomaly (downward displacement of the valve because of 
abnormal attachment of the valve leaflets).
• Tricuspid regurgitation is generally well tolerated by most patients. In the absence of pulmonary hyperten-
sion, many even tolerate complete surgical excision of the tricuspid valve.
• Intraoperative hemodynamic goals should be directed primarily toward the underlying disorder. Hypovolemia 
and factors that increase right ventricular afterload, such as hypoxia and acidosis, should be avoided to 
maintain effective right ventricular stroke and left ventricular preload. Positive end-expiratory pressureand 
high mean airway pressures may also be deleterious during mechanical ventilation because they reduce 
venous return and increase right ventricular afterload.
• Thermodilution cardiac output measurements are falsely elevated in patients with tricuspid regurgitation.
• Patients tolerate spinal and epidural anesthesia well. Coagulopathy secondary to hepatic dysfunction should 
be excluded before any regional technique.
ANESTHESIA FOR PATIENTS WITH CARDIOVASCULAR DISEASE 21-17
Mitral Stenosis
• Most commonly occurs after rheumatic heart disease and results from progressive fusion and calcification 
of the valve leaflets. Symptoms usually occur 20 to 30 years after rheumatic heart disease with reduction of 
the valve area to less than 2 cm2. Fewer than 50% of patients have isolated mitral stenosis; usually mitral 
stenosis is associated with mitral regurgitation or aortic valve pathology.
• Increases in either cardiac output or heart rate (decreased diastolic time) necessitate higher flows across the 
valve and result in higher transvalvular pressure gradients.
• The left atrium is often dilated and can lead to supraventricular tachycardias, particularly atrial fibrillation, 
which can lead to systemic emboli.
• Acute elevations in left atrial pressure are rapidly transmitted back to the pulmonary capillaries and eventu-
ally can lead to irreversible increases in pulmonary vascular resistance and pulmonary hypertension. If right 
ventricular failure follows, tricuspid or pulmonary valve regurgitation can occur.
• The time from onset of symptoms to incapacitation averages 5 to 10 years. At that stage, most patients die 
within 2 to 5 years. Surgical correction (open valvuloplasty) is therefore usually undertaken when significant 
symptoms develop.
• Anesthetic hemodynamic goals are to maintain a sinus rhythm (if present preoperatively) and to avoid tachy-
cardia, large increases in cardiac output, and both hypovolemia and fluid overload by judicious fluid therapy. 
Vasopressors (phenylephrine preferred) are often needed to maintain vascular tone after anesthetic induction. 
Intraoperative tachycardia may be controlled by a β-blocker or by deepening anesthesia with an opioid.
ANESTHESIA FOR PATIENTS WITH CARDIOVASCULAR DISEASE 21-18
Mitral Regurgitation
• The principal derangement is a reduction in forward stroke volume caused by backward flow of blood into 
the left atrium during systole with compensation via left ventricular dilatation and increasing end-diastolic 
volume. The patients develop progressive left ventricular hypertrophy and impairment in contractility, as 
reflected by a decrease in ejection fraction (<50%). Eventually, wall stress increases, resulting in an 
increased demand for myocardial oxygen supply.
• Acute mitral regurgitation is usually caused by myocardial ischemia or infarction (papillary muscle dysfunc-
tion or rupture of a chorda tendinea), infective endocarditis, or chest trauma.
• Chronic mitral regurgitation is usually the result of rheumatic fever (often with concomitant mitral stenosis); 
congenital or developmental abnormalities of the valve apparatus; or dilatation, destruction, or calcification 
of the mitral annulus.
• Afterload reduction is beneficial in most patients and may even be lifesaving in patients with acute mitral 
regurgitation. Reduction of SVR increases forward SV and decreases the regurgitant volume. Surgical treat-
ment is usually reserved for patients with moderate to severe symptoms.
• Anesthesia management includes avoiding bradycardia (maintain heart rate at 80 to 100 beats/min) and 
avoiding acute increases in afterload. Patients with moderate to severe ventricular impairment are very sen-
sitive to the depressant effects of volatile agents, so a primary opioid based anesthetic may be more suitable.
ANESTHESIA FOR PATIENTS WITH CARDIOVASCULAR DISEASE 21-19
Mitral Valve Prolapse
• Mitral valve prolapse (MVP) is classically characterized by a midsystolic click with or without a late apical 
systolic murmur on auscultation and is confirmed by echocardiography. MVP may progress to mitral regur-
gitation or may cause systemic emboli or infective endocarditis.
• Anticoagulation or antiplatelet agents may be used for patients with a history of emboli; β-adrenergic block-
ing drugs are commonly used for those with arrhythmias.
• Ventricular arrhythmias may occur intraoperatively, particularly after sympathetic stimulation, and generally 
respond to lidocaine or β-adrenergic blocking agents.
• Mitral regurgitation caused by prolapse is generally exacerbated by decreases in ventricular size. 
Hypovolemia and factors that increase ventricular emptying—such as increased sympathetic tone or 
decreased afterload—should therefore be avoided. Vasopressors with pure α -adrenergic agonist activity 
(e.g., phenylephrine) may be preferable to those that are primarily β-adrenergic agonists (ephedrine).
ANESTHESIA FOR PATIENTS WITH CARDIOVASCULAR DISEASE 21-20
Aortic Stenosis
• In contrast to acute obstruction of left ventricular outflow, which rapidly dilates the ventricle and reduces 
SV, obstruction caused by valvular aortic stenosis is almost always gradual, allowing the ventricle, at least 
initially, to compensate and maintain SV. Concentric ventricular hypertrophy enables the left ventricle to 
maintain SV by generating a significant transvalvular gradient and reducing ventricular wall stress. Valvular 
aortic stenosis is nearly always congenital, rheumatic, or degenerative.
• Critical aortic stenosis is said to exist when the aortic valve orifice is reduced to 0.5 to 0.7 cm2 (normal is 
2.5–3.5 cm2), which generally corresponds to a transvalvular gradient of approximately 50 mm Hg at rest. 
Cardiac output may be normal in symptomatic patients at rest, but characteristically, it does not appropriately 
increase with exertion.
• Patients with advanced aortic stenosis have the triad of dyspnea on exertion, angina, and orthostatic or exer-
tional syncope. Arrhythmias leading to severe hypoperfusion may cause syncope and sudden death in some 
patients.
• Anesthesia management includes maintenance of normal sinus rhythm, heart rate, and intravascular volume 
in patients with aortic stenosis. Loss of a normally timed atrial systole often leads to rapid deterioration, 
particularly when associated with tachycardia. The combination of the two (atrial fibrillation) seriously 
impairs ventricular filling and necessitates immediate cardioversion. Patients are very sensitive to abrupt 
changes in intravascular volume. Many patients have a fixed SV despite adequate hydration; cardiac output 
becomes rate dependent, and bradycardia (<50 beats/min) is poorly tolerated. Spinal and epidural anesthesia 
are contraindicated in patients with severe aortic stenosis, and volatile anesthetics should be carefully 
titrated.
ANESTHESIA FOR PATIENTS WITH CARDIOVASCULAR DISEASE 21-21
Aortic Regurgitation
• Aortic regurgitation is usually congenital (bicuspid valve) or caused by rheumatic fever. Diseases (mostly 
connective tissue disorders) affecting the ascending aorta cause regurgitation by dilating the aortic annulus.
• Aortic regurgitation produces volume overload of the left ventricle. The effective forward SV is reduced 
because of backward (regurgitant) flow of blood into the left ventricle during diastole. Systemic arterial 
diastolic pressure and SVR are typically low. The decrease in cardiac afterload helps facilitate ventricular 
ejection. Total SV is the sum of the effective SV and the regurgitant volume.
• Slow heart rates increase regurgitation because of the associated disproportionate increase in diastolic time, 
but increases in diastolic arterial pressure favor regurgitant volume by increasing the pressure gradient for 
backward flow.
ANESTHESIA FOR PATIENTS WITH CARDIOVASCULAR DISEASE 21-22
Aortic Regurgitation (continued)
• Diuretics and afterload reduction, particularly with ACE inhibitors, generally benefitpatients with advanced 
chronic aortic regurgitation. The decrease in arterial blood pressure reduces the diastolic gradient for regur-
gitation. Patients with acute aortic regurgitation typically require intravenous inotropic and vasodilator 
therapy. Early surgery is also recommended.
• The heart rate should be maintained toward the upper limits of normal (80–100 beats/min). Whereas brady-
cardia and increases in SVR increase the regurgitant volume in patients with aortic regurgitation, tachycardia 
can contribute to myocardial ischemia. Spinal or epidural anesthesia is ideal; isoflurane or desflurane should 
be used if general anesthesia is required. Large amounts of phenylephrine can increase SVR and worsen 
regurgitation.
ANESTHESIA FOR PATIENTS WITH CARDIOVASCULAR DISEASE 21-23
Case Card
A 71-year-old man is scheduled for large excision of basal cell carcinoma on the neck that extended beyond 
the borders of a previous resection. His medical history includes moderate AS, stage 3 CKD, DM type II, 3V 
CABG 6 years ago, and chronic back pain that limits activity to less than 4 MET. The patient admits to many 
years of chronic dyspnea, orthopnea, and angina. ECG shows NSR 67 beats/min with Q waves in leads II, III, 
and aVF, with LVH and RBBB. The preoperative clinic requests documentation from the patient’s cardiologist 
with the last echocardiogram and cardiac optimization note. On the 6-month-old echocardiogram, the patient’s 
EF is 55% with normal left ventricular function, and the aortic valve area is 0.9 mm. The cardiologist’s opti-
mization note discusses no need for aortic valve replacement because the patient is stable on a medical regimen 
of an ACE inhibitor, β-blocker, nitroglycerin, low-dose aspirin, insulin, and methadone. The cardiologist notes 
that the patient is at moderate risk for general anesthesia and recommends excision of the skin lesion with 
MAC/local. However, the patient requests general anesthesia because of significant pain during the first exci-
sion under MAC/local.
What are your anesthetic options?
ANESTHESIA FOR PATIENTS WITH CARDIOVASCULAR DISEASE 21-24
As the patient’s anesthesiologist, it would be prudent to repeat the echocardiogram and review the case with a 
cardiologist at your institute. The patient clearly has significant symptoms with moderate AS that could have 
progressed in severity in the past 6 months. The patient may benefit from aortic valve replacement before 
attempting a nonemergent surgery on a patient who has poor anesthetic options. If the case is done with MAC/
local, benzodiazepines, fentanyl, or propofol could cause hypotension, respiratory distress, pulmonary hyper-
tension, and cardiopulmonary arrest. Likewise, a regional anesthetic or general anesthetic in this patient could 
lead to cardiopulmonary arrest. Guidance by a cardiothoracic anesthesiologist may be beneficial to determine 
intraoperative hemodynamic management such as avoiding fluctuations in heart rate and blood pressure. 
Pressors and vasodilators should be available and carefully titrated if proceeding with general anesthesia in this 
patient. The anesthesiologist should also have a very thorough discussion with the patient and family regarding 
his anesthetic risks.
ANESTHESIA FOR CARDIOVASCULAR SURGERY 22-1
Preoperative Evaluation
• Adult preoperative evaluation: Establishing the adequacy of the patient’s preoperative cardiac function 
should be based on exercise (activity) tolerance, measurements of myocardial contractility such as ejection 
fraction, the severity and location of coronary stenoses, ventricular wall motion abnormalities, cardiac end-
diastolic pressures, cardiac output, and valvular areas and gradients.
• Pediatric preoperative evaluation: In the preoperative evaluation in children, the hemodynamic signifi-
cance of the lesion and the planned surgical correction must be clearly understood. The patient’s condition 
must be optimized. Congestive heart failure and pulmonary infections should be treated. Prostaglandin E1 
infusion (0.05–0.1 µg/kg/min) is used preoperatively to prevent closure of the ductus arteriosus in patients 
dependent on ductal flow for survival. The results of echocardiography, heart catheterization, electrocardi-
ography, and chest radiography should be reviewed. Laboratory evaluation should include a platelet count, 
coagulation studies, electrolytes, blood urea nitrogen, and serum creatinine.
ANESTHESIA FOR CARDIOVASCULAR SURGERY 22-2
Cardiopulmonary Bypass
• Mechanism: Cardiopulmonary bypass (CPB) is a technique that diverts venous blood away from the heart 
(most often from one or more cannula in the right atrium), adds oxygen, removes CO2, and returns the blood 
through a cannula in a large artery (usually the aorta). As a result, nearly all blood flow through the heart 
and lungs ceases.
• Physiology: Blood flow is nonpulsatile and leads to systemic inflammation, and end-organ damage may 
result.
• Hypothermia is induced to decrease O2 metabolic requirements using either cardioplegia (a chemical solu-
tion for arresting myocardial electrical activity) or a topical ice-slush solution.
• Anticoagulation: Anticoagulation must be established before CPB to prevent acute disseminated intravas-
cular coagulation and formation of clots in the CPB pump.
• Priming: Before use, the CPB circuit must be primed with fluid, generally lactated Ringer solution often 
with other components such as colloid, mannitol, heparin, and bicarbonate. This causes hemodilution typi-
cally to 22% to 27% hematocrit in most patients. Blood is used in priming solutions for small children and 
severely anemic adults to prevent severe hemodilution.
ANESTHESIA FOR CARDIOVASCULAR SURGERY 22-3
Cardiopulmonary Bypass Circuit Components
• Tubing between the CPB machine and patient: Tubing to the CBP machine includes one or two venous can-
nulas in the right atrium, the superior and inferior vena cava, or possibly a femoral vein. Tubing to the patient 
includes a cannula in the ascending aorta or femoral artery.
• Reservoir: With most circuits, blood flows to the reservoir by gravity drainage so that the driving force for flow 
is the difference in height between the patient and the reservoir but inversely proportional to the resistance of the 
cannulas and tubing. With some circuits, especially small venous cannulas, assisted venous drainage may be 
required; a regulated vacuum together with a hard shell venous reservoir or centrifugal pump may be needed.
• Oxygenator: Contains blood gas interface that allows blood to equilibrate with the gas mixture (usually oxygen 
and a volatile anesthetic). Oxygen tension depends on inspired oxygen concentration, and CO2 tension depends on 
total gas flow past the oxygenator.
• Heat exchanger: Blood from the oxygenator enters the heat exchanger and can be warmed or cooled by conduc-
tion to water flowing through the exchanger.
• Main pump: The main pump propels blood through the CPB circuit either using an electrically driven double-arm 
roller or centrifugal pump. The roller produces nonpulsatile flow by compressing large-bore tubing in the main 
pumping chamber with flow directly proportional to the number of revolutions per minute. A roller pump can be 
used but may allow air to enter the arterial cannula if the reservoir empties and can cause organ damage or death. 
A centrifugal pump does not allow the reservoir to empty and is less traumatic to blood. Centrifugal pumps consist 
of spinning cones that use centrifugal forces to propel the blood from the centrally located inlet to the periphery.
• Arterial filter: An arterial filter is usually connected to the cannula entering the ascending aorta or femoral artery 
to prevent air, clots, and debris from entering the patient.
ANESTHESIA FOR CARDIOVASCULAR SURGERY 22-4
Setup for On-Pump Cardiovascular Surgery
• Check the anesthesia machine, monitors, infusion pumps, and blood warmer.
• At least one vasodilator and one inotropicinfusion solution should be ready.
• Two large-bore (16-gauge or larger) intravenous (IV) catheters are used with one in a large central vein such 
as the right internal jugular vein or right subclavian vein (avoid left-sided central venous catheters because 
they may kink with surgical retraction).
• Central catheter should have multiple ports: (1) drug infusion pumps, (2) drug and fluid boluses, and 
(3) pulmonary catheter (use is based on patient, procedure, and surgical team).
• Arterial cannulation is usually in the radial artery in the nondominant hand and is performed before induc-
tion of anesthesia for close hemodynamic monitoring during induction.
• Record paper tracing of baseline electrocardiogram (ECG).
• Pulmonary artery catheters should be routinely pulled back (2–3 cm) during CPB and the balloon subse-
quently inflated slowly to avoid a potentially lethal pulmonary artery rupture. If the catheter wedges with 
less than 1.5 mL of air in the balloon, it should be pulled back farther.
• A Foley catheter is used to monitor urinary output and bladder temperature.
• Temperature probes in bladder or rectum, esophageal, and pulmonary artery for simultaneous temperature 
measurements.
• Blood gases, hematocrit, serum potassium, ionized calcium, activated clotting time (ACT), glucose, and in 
some centers thromboelastography measurements should be immediately available.
• Transesophageal echocardiography.
• Heparin (300–400 U/kg) to be administered before CPB and protamine for reversal.
ANESTHESIA FOR CARDIOVASCULAR SURGERY 22-5
Anesthetic Agents for On-Pump Cardiac Surgery
• High-dose opioid anesthesia: Fentanyl 50 to 100 µg/kg or sufentanil 15 to 25 µg/kg. Side effects include 
postoperative respiratory depression (12–24 hr), a high incidence of recall, or failure to control the hyper-
tensive response to stimulation.
• Total intravenous anesthesia (TIVA): Propofol 0.5 to 1.5 mg/kg followed by 25 to 100 µg/kg/min and 
modest doses of fentanyl (total doses of 5-7 mcg/kg) or remifentanil, 0 to 1 µg/kg bolus followed by 0.25 to 
1 µg/kg/min (beneficial in “fast-track” cardiac surgery). If using remifentanil, give IV morphine or hydro-
morphone for postoperative analgesia.
• Mixed intravenous and inhalation anesthesia: Induction with propofol (0.5–1.5 mg/kg) or etomidate 
(0.1–0.3 mg/kg). Opioids (fentanyl, maximum of 5 µg/kg or sufentanil 15 µg/kg) and volatile agent (0.5–1.5 
minimum alveolar concentration [MAC] sevoflurane, isoflurane, or desflurane) for maintenance anesthesia 
and to blunt the sympathetic response to stimulation.
• Muscle relaxants: Rocuronium, vecuronium, and cisatracurium have almost no hemodynamic effects on 
their own. Vecuronium may cause bradycardia with large doses of opioids. Pancuronium may be used in 
β-blocked patients with marked bradycardia because of its vagolytic effects. Judicious dosing and nerve 
stimulator monitoring should be used to avoid prolonged muscle paralysis. Succinylcholine may be used 
especially if difficult airway is anticipated.
ANESTHESIA FOR CARDIOVASCULAR SURGERY 22-6
Guidelines for Cardiopulmonary Bypass Maintenance
• Serial ACT measurements before CPB and every 20 to 30 minutes afterward to keep ACT greater than 
400 ms.
• Serial hematocrit with goal hematocrit between 20% and 25% and red blood cell transfusion into pump 
reservoir when necessary.
• Maintain venous oxygen saturations greater than 70%; in the absence of hypoxemia, a low SVO2 with pro-
gressive metabolic acidosis or reduced urinary output may indicate inadequate CPB flow rates.
• Keep blood flow rate at 2 to 2.5 L/min/m2 (50–60 mL/kg/min) and mean arterial pressure (MAP) between 
50 and 80 mm Hg. Systemic vascular resistance (SVR) can be increased with phenylephrine. Persistent and 
excessive decreases (<30 mm Hg) should prompt a search for unrecognized aortic dissection.
• Blood glucose should be checked at least once in patients without diabetes and hourly in patients with dia-
betes.
ANESTHESIA FOR CARDIOVASCULAR SURGERY 22-7
Cardioplegia
• Composition: Potassium solution with potassium concentration below 40 mEq/L because higher levels can 
be associated with an excessive potassium load and excessive potassium concentrations at the end of termi-
nation of bypass. Sodium concentration in cardioplegic solutions is usually less than in plasma (<140 mEq/L) 
because ischemia tends to increase intracellular sodium content. A small amount of calcium (0.7–1.2 mmol/L) 
is needed to maintain cellular integrity; magnesium (1.5–15 mmol/L) is usually added to control excessive 
intracellular influxes of calcium. A buffer—most commonly bicarbonate—is necessary to prevent excessive 
buildup of acid metabolites; alkalotic perfusates are reported to produce better myocardial preservation.
• Recovery from cardioplegia: Inadequate “washout” and recovery from cardioplegia can result in an 
absence of electrical activity, atrioventricular conduction block, or a poorly contracting heart at the end of 
bypass. Persisting systemic hyperkalemia may also result. Calcium administration improves hyperkalemia; 
excessive calcium can promote and enhance myocardial damage. Myocardial performance generally 
improves with time as the contents of the cardioplegia are cleared from the heart.
ANESTHESIA FOR CARDIOVASCULAR SURGERY 22-8
Hypothermia
• General concepts: Hypothermia (<34°C) potentiates general anesthetic potency, but failure to give anes-
thetic agents, particularly during rewarming on CPB, may result in awareness and recall. Intentional hypo-
thermia usually decreases body temperature to 20° to 32°C. Hypothermia is accomplished via ice slush, 
cardioplegia, and the heat exchanger in the CPB circuit. Metabolic oxygen requirements are approximately 
halved with each 10°C change in body temperature. During rewarming, the heat exchanger usually restores 
normal body temperature.
• Profound hypothermia: Temperatures of 15° to 18°C allow total circulatory arrest for complex repairs for 
durations of as long as 60 minutes. During this time, both the heart and the CPB machine are stopped.
• Side effects: The adverse effects of hypothermia include platelet dysfunction, reversible coagulopathy, and 
depression of myocardial contractility.
ANESTHESIA FOR CARDIOVASCULAR SURGERY 22-9
Myocardial Preservation
• Myocardial risk factors: Most patients sustain some reversible myocardial injury during CPB, most commonly 
from incomplete myocardial preservation during CBP but also from hemodynamic instability or surgical tech-
nique. Patients at greatest risk are those with poor preoperative ventricular function, ventricular hypertrophy, or 
severe coronary artery disease. Myocardial ischemia can result from low arterial pressures, coronary embolism, 
reperfusion injury, coronary artery or bypass graft vasospasm, and contortion of the heart causing compression or 
distortion of the coronary vessels. Ventricular fibrillation and distention are important causes of increased myocar-
dial oxygen demand and decreased oxygen supply. Coronary air emboli can cause ventricular dysfunction at the 
end of CPB and preferentially enters the right coronary ostium because of its superior location in the aortic root in 
the supine patient.
• Signs of myocardial damage: Inadequate myocardial preservation is usually manifested at the end of bypass as a 
persistently reduced cardiac output, worsened ventricular function by transesophageal echocardiography (TEE), or 
cardiac arrhythmias. ECG signs of myocardial ischemia are often difficult to detect because of frequent use of 
electrical pacing. Myocardial stunning is reversible systolic and even diastolic dysfunction seen on TEE from 
ischemia and reperfusion injuries.
• Methods for preservation: Decrease cellular energy requirements to minimal levels, initially by potassium car-
dioplegia either hypothermic or progressively cooler. Then maintain myocardial temperature 10° to 15°C by topi-
cal cardiac hypothermia (ice slush).Myocardial hypothermia reduces basal metabolic oxygen consumption, and 
the potassium cardioplegia minimizes energy expenditure by arresting both electrical and mechanical activity. The 
aortic cross-clamping required during CPB reduces coronary blood flow to 0, with a limit of CPB times to less 
than 120 minutes. To prevent cardiac distention, vents placed in the right superior pulmonary vein and left atrium 
drain the left ventricle. To prevent coronary air emboli, cardiac chambers and coronary artery grafts are carefully 
deaired at the end of repair.
ANESTHESIA FOR CARDIOVASCULAR SURGERY 22-10
Anesthetic Management of Cardiac Surgery
• Redo sternotomy: Blood should be immediately available for transfusion if the patient has already had a 
midline sternotomy (a “redo”); in these cases, the right ventricle or coronary grafts may be adherent to the 
sternum and may be accidentally entered during the repeat sternotomy.
• Pulmonary artery catheterization: In general, pulmonary artery catheterization has been most often used 
in patients with compromised ventricular function (ejection fraction <40%–50%) or pulmonary hypertension 
and in those undergoing complicated procedures. The use of pulmonary artery catheterization is largely 
dependent on institutional practices.
• TEE provides valuable information about cardiac anatomy and function during surgery. Two-dimensional, 
multiplane TEE can detect regional and global ventricular abnormalities, chamber dimensions, valvular 
anatomy, and the presence of intracardiac air. Three-dimensional TEE provides a more complete description 
of valvular anatomy and pathology.
• Anesthetic doses: Severely compromised patients should be given anesthetic agents in incremental, small 
doses.
ANESTHESIA FOR CARDIOVASCULAR SURGERY 22-11
Coming Off Cardiopulmonary Bypass
• Wash out the cardioplegia solution.
• Rewarm the patient to 37°C.
• Reduce systemic perfusion pressure just before clamp release; then increase initially to 40 mm Hg before 
being gradually increased and maintained at about 70 mm Hg.
• Correct acidosis (target pH >7.20), electrolytes (target K <5.5 mEq/L), glucose (target >72 mg/dL), and 
anemia (target hematocrit >22%).
• Remove intracardiac air.
• Administer lidocaine 100 to 200 mg and magnesium sulfate 1 to 2 g before aortic cross-clamp removal to 
decrease the likelihood of fibrillation.
• The heart should start contracting in an empty state for 5 to 10 minutes before weaning from CPB to ensure 
adequate cardiac rate and rhythm via ECG and adequate cardiac valve and wall function with TEE. 
Atrioventricular pacing is often necessary to get the heart rate 80 to 100 beats/min, and supraventricular 
tachycardias generally require cardioversion.
• Restart ventilation with 100% oxygen and low-dose volatile anesthetic.
• Recalibrate monitors.
• In patients with low SVR, a positive inotrope (epinephrine, dopamine, dobutamine) with milrinone can be 
started. In patients with pump failure, CPB may need to be reinstituted while inotropic therapy is initiated. 
In patients with poor preoperative ventricular function, milrinone may be administered as the first-line agent 
before separation from CPB.
• If drug therapies fail to provide adequate cardiac output, use an intraaortic balloon pump.
ANESTHESIA FOR CARDIOVASCULAR SURGERY 22-12
Post–Cardiopulmonary Bypass Hemodynamic Subgroups
Group I: 
Vigorous
Group II: 
Hypovolemic
Group IIIA: LV 
Pump Fa ilure
Group IIIB: 
RV Fa ilure
Group IV: Vasodila ted 
(Hyperdynamic)
Blood pressure Normal Low Low Low Low
Central venous 
pressure
Normal Low Normal or high High Normal or low
Pulmonary 
wedge pressure
Normal Low High Normal or high Normal or low
TEE findings Normal Underfilled RV 
or LV
Reduced LV 
performance
Dilated RV Normal or underfilled 
RV or LV
Cardiac output Normal Low Low Low High
Systemic vascular 
resistance
Normal Low, normal, 
or high
Low, normal, 
or high
Normal or high Low
Therapy None Volume Inotrope; IABP, 
LVAD
Inotrope, 
pulmonary 
vasodilator; RVAD
Vasoconstrictor
CPB, cardiopulmonary bypass; IABP, intraaortic balloon pump; LV, left ventricular; LVAD, left ventricular assist device; RV, right ventricular; RVAD, 
right ventricular assist device; TEE, transesophageal echocardiography.
ANESTHESIA FOR CARDIOVASCULAR SURGERY 22-13
Persistent Bleeding After Cardiopulmonary Bypass
• Reversing heparin effects: Protamine should be used to return ACT to baseline (usually 1 mg per 100 U of 
heparin is needed with additional doses of 25–50 mg if inadequate). Administering protamine too rapidly 
may result in severe hypotension or pulmonary hypertension.
• Persistent bleeding after bypass: Often occurs after prolonged durations of bypass (>2 hr) and usually is 
caused by inadequate surgical control of bleeding sites, incomplete reversal of heparin, thrombocytopenia, 
platelet dysfunction, hypothermia-induced coagulation defects, undiagnosed preoperative hemostatic 
defects, newly acquired factor deficiency, or hypofibrinogenemia. Platelet, fresh-frozen plasma, or cryopre-
cipitate transfusion should be considered. Accelerated fibrinolysis confirmed by elevated fibrin degradation 
products (>-32 mg/mL) or evidence of clot lysis should be treated with ε-aminocaproic acid or tranexamic 
acid.
• Antifibrinolytic therapy: Should be considered for patients who are undergoing a repeat operation; who 
refuse blood products, such as Jehovah’s Witnesses; who are at high risk for postoperative bleeding because 
of recent administration of glycoprotein IIb/IIIa inhibitors (abciximab, eptifibatide, or tirofiban); who have 
preexisting coagulopathy; and who are undergoing long and complicated procedures involving the heart or 
aorta.
• Chest tube drainage: In the first 2 hours after surgery of more than 250 to 300 mL/hr (10 mL/kg/hr)—in 
the absence of a hemostatic defect—is excessive and may require surgical reexploration. Intrathoracic bleed-
ing at a site not adequately drained may cause cardiac tamponade, requiring immediate reopening of the 
chest, and is associated with severe hypotension on anesthetic induction.
ANESTHESIA FOR CARDIOVASCULAR SURGERY 22-14
Anesthetic Management of Carotid Surgery
• Indications for carotid endarterectomy (CEA): CEA is recommended for transient ischemic attacks associated 
with ipsilateral severe carotid stenosis (>70% occlusion), severe ipsilateral stenosis in a patient with minor (incom-
plete) stroke, and 30% to 70% occlusion in a patient with ipsilateral symptoms (usually an ulcerated plaque). For 
asymptomatic lesions with greater than 60% stenosis, stenting is generally recommended.
• Anesthetic management: Maintain adequate perfusion to the brain and heart. Neurologic deficits should be 
defined, and other disease states should be optimized. Most patients are elderly, have hypertension, have general-
ized arteriosclerosis, and often have diabetes. Intraoperatively, avoid tachycardia and wide swings in arterial 
pressure. Regional anesthesia with superficial cervical plexus blocks allow the patient to be awake and neuro-
logically examined during surgery. Propofol or etomidate can be used for induction of GA as they reduce CMRO2 
more than CBF. Isoflurane appears to provide the greatest protection against cerebral ischemia. Keep MAP at or 
slightly above preoperative levels. Intraoperative hypertension is common and should be treated with a vasodilator 
like nitroglycerin, nicardipine, or nitroprusside; phenylephrine is used for hypotension. Bradycardia or complete 
heart block can be caused by manipulation of the carotid baroreceptor and is treated with atropine. Maintain 
normocapnia.
• Neurologic monitoring: EEG and SSEP monitoring may be used.
• Complications The perioperative mortality rate is 1% to 4% and is primarily attributable to cardiac complications. 
The perioperative morbidity rate is 4% to 10% and is principally neurologic. Wound hematoma can compromise 
the airway.Damage to the recurrent laryngeal nerve can cause hoarseness, and damage to the hypoglossal nerve 
can cause ipsilateral deviation of the tongue. Denervation of the ipsilateral carotid baroreceptor can cause postop-
erative hypertension, and denervation of the carotid body can blunt the ventilatory response to hypoxemia.
ANESTHESIA FOR CARDIOVASCULAR SURGERY 22-15
Cardiac Tamponade
• Causes: Cardiac tamponade exists when increased pericardial pressure impairs diastolic filling of the heart 
and can be caused by pericardial effusions from viral, bacterial, or fungal infections; malignancies; bleeding 
after cardiac surgery; trauma; uremia; myocardial infarction (MI); aortic dissection; hypersensitivity or 
autoimmune disorders; drugs; or myxedema.
• Signs and symptoms: Decreased cardiac output (CO) from a reduced stroke volume (SV) with increase in 
central venous pressure (CVP). Equalization of diastolic pressure occurs in all chambers of the heart. 
Increase in sympathetics causes increased heart rate and contractility to help maintain CO. Acute cardiac 
tamponade usually presents as sudden hypotension, tachycardia, and tachypnea. Physical examination may 
show jugular venous distention, narrowed arterial pulse pressure, muffled heart sounds, friction rub, or pul-
sus paradoxus. ECG may show decreased voltage in all leads and nonspecific ST- and T-wave abnormalities. 
Electrical alternans may be seen with a large pericardial effusion.
• Anesthetic considerations: Symptomatic cardiac tamponade requires evacuation either by pericardiocente-
sis or surgically (usually for postoperative cardiac tamponade or for large recurrent pericardial effusions). 
Pericardiocentesis may be done with local anesthetic and small doses of ketamine (10 mg IV boluses) if 
supplemental analgesia is needed. Induction can precipitate severe hypotension and cardiac arrest. Have an 
epinephrine infusion immediately available. Pericardiocentesis before induction may improve CO and allow 
safe induction and intubation. Large-bore IV access is mandatory because the patients require large fluid 
boluses to supplement CO. Avoid cardiac depression, vasodilation, slowing of the heart, high airway pres-
sures, and deep anesthesia.
ANESTHESIA FOR CARDIOVASCULAR SURGERY 22-16
Anesthetic Management of Aortic Surgery
• Indications: Indications for aortic surgery include aortic dissections, aneurysms, occlusive disease, trauma, 
and coarctation.
• Anesthetic considerations: Multiple large-bore IVs, arterial waveform transducer, and pulmonary artery 
catheterization are usually required. Ascending aortic surgeries are done with CPB. Nicardipine or nitro-
prusside is used to decrease blood pressure. β-Adrenergic blockade should also be used in the presence of 
an aortic dissection. A left radial arterial line should be placed because clamping of the innominate may be 
required. Avoid bradycardia, which worsens aortic regurgitation. Aortic arch surgeries are done with CPB 
and deep hypothermic circulatory arrest. Anticipate large postoperative blood loss. Descending thoracic 
aorta surgeries may be performed through a left thoracotomy without CPB. A right radial arterial line is 
needed as the left subclavian may be clamped. One-lung ventilation with a right-sided double-lumen tube 
improves surgical exposure. A heparin-impregnated left ventricular apex to femoral artery shunt or partial 
right atrium to femoral artery bypass may be used. The aorta is cross-clamped above and below the lesion 
with acute hypertension above the clamp and hypotension below when not using shunt or partial bypass. The 
sudden increase in left ventricular afterload after application of the aortic cross-clamp during aortic surgery 
may precipitate acute left ventricular failure and MI, particularly in patients with underlying ventricular 
dysfunction or coronary disease. After the release of the aortic cross-clamp, severe systemic hypotension 
may occur.
• Complications: Anticipate large blood losses. Use cell saver and antifibrinolytics if possible. Interruption 
of blood flow to the spinal cord, kidneys, and intestines can produce paraplegia, renal failure, or intestinal 
infarction.
ANESTHESIA FOR CARDIOVASCULAR SURGERY 22-17
Pediatric Cardiovascular Anesthesia
• Premedication: Atropine 0.02 mg/kg intramuscularly (IM) to enhance vagal tone. Midazolam 0.5 to 0.6 mg/kg 
orally (PO) (0.08 mg/kg IM) for sedation, particularly for those with cyanotic lesions (tetralogy of Fallot) 
because agitation and crying worsen right-to-left shunting.
• Monitoring: At least two IV catheters are needed, usually including a right internal jugular vein central 
venous catheter and a 22- or 24-gauge catheter in the radial artery. Pulmonary artery catheterization is almost 
never used in pediatric patients. TEE for assessing surgical repair after CPB is most useful in patients weigh-
ing more than 12 kg with intraoperative epicardial echocardiography commonly used in smaller patients.
• Induction: With obstructive lesions, avoid hypovolemia, bradycardia (decreases cardiac output), tachycar-
dia (impairs ventricular filling), and myocardial depression. In left-to-right shunting, increase PVR and 
decrease SVR. In right-to-left shunting, decrease PVR (hyperventilate to avoid hypercapnia and acidosis) 
and increase SVR (can use phenylephrine). Enhanced sympathetic tone, hypoxia, and high mean airway 
pressures increase PVR. Propofol (2–3 mg/kg), ketamine (1–2 mg/kg), fentanyl (25–50 µg/kg), or sufentanil 
(5–15 µg/kg) can be used for IV induction. High-dose opioids may be suitable for very small and critically 
ill patients when postoperative ventilation is planned. Ketamine 4 to 10 mg/kg can be used for patients with 
decreased cardiac reserve. Slow sevoflurane induction may be used with good heart function.
ANESTHESIA FOR CARDIOVASCULAR SURGERY 22-18
Pediatric Cardiovascular Anesthesia
Maintenance: Opioids (fentanyl or sufentanil) or inhalation anesthetics (sevoflurane or isoflurane) are used 
for maintenance.
Cardiopulmonary bypass: Blood used to prime the circuit for neonates and infants to prevent excessive 
hemodilution. MA tends to be lower (20–50 mm Hg) and can impair systemic perfusion. High flow rates (up 
to 200 mL/kg/min) may be necessary to ensure adequate perfusion in very young patients. If surgical repair is 
adequate, weaning from CPB is usually not a problem in children. Dopamine and epinephrine are the most 
commonly used inotropes in pediatric patients. A phosphodiesterase inhibitor can be used when PVR or SVR 
is increased. Inhalation nitric oxide may be helpful in refractory pulmonary hypertension. Corticosteroids are 
used to decrease the inflammatory response induced by CPB. Complex congenital lesions may require com-
plete circulatory arrest under deep hypothermia (15°C may be safe for up to 60 min). Methylprednisolone and 
mannitol may provide brain protection.
Postbypass period: Heparin reversal, fresh-frozen plasma, and platelets are usually necessary. Patients typi-
cally remain intubated after surgery.
ANESTHESIA FOR CARDIOVASCULAR SURGERY 22-19
Off-Pump Coronary Artery Bypass
• General principles: Advanced epicardial stabilization devices use suction to stabilize and lift the anasto-
motic site rather than compress it down, which allows for greater hemodynamic stability. Can be used rou-
tinely even in patients with multigraft surgery, in redo operations, and in patients with compromised left 
ventricular function.
• Anesthesia management: Full CPB dose heparinization is used and the CPB machine is primed and imme-
diately available if needed. IV fluid loading or low-dose infusion of a vasopressor may be necessary while 
the distal anastomosis is sewn. During proximal anastomosis, the aorta is partially clamped, and a vasodila-
tor is usually needed to reduce the systolic pressure to 90 to 100 mm Hg (nitroglycerin is preferred because 
it reduces myocardial ischemia). Anesthesia maintenance with a volatile agent providesmyocardial protec-
tion. An intraluminal flow-through shunt may be used to maintain coronary blood flow during sewing of 
distal anastomosis.
• Contraindications: Patients with extensive coronary disease may not be good candidates, especially if they 
have poor target vessels.
ANESTHESIA FOR CARDIOVASCULAR SURGERY 22-20
Cardiac Transplant
• General requirements: Candidates are otherwise healthy patients with end-stage heart disease (ejection fraction 
<20%, New York Heart Association class IV, and class D heart failure) who are unlikely to survive 6 to 12 months. 
Patients must not have other major systemic illnesses, and PVR must be normal or at least responsive to oxygen 
or vasodilators. Donor–recipient compatibility is based on size, ABO blood group typing, and cytomegalovirus 
serology.
• Preoperative: Oral cyclosporine must be given preoperatively. Patients are considered to have a full stomach and 
should receive a clear antacid, a histamine H2-receptor blocker, and metoclopramide.
• Induction: Opioids (fentanyl 5–10 µg/kg) with or without etomidate (0.2–0.3 mg/kg) or low-dose ketamine-
midazolam. Rapid-sequence induction can be accomplished with sufentanil 5 mcg/kg followed by succinylcholine 
1.5 mg/kg. Azathioprine infusion is started after induction.
• CPB: Setup and monitoring are similar to other on-pump cardiac surgeries. A pulmonary artery catheter is usually 
necessary for postbypass management but can be placed after transplantation. If the pulmonary artery catheter is 
in place during CPB, it must be completely withdrawn from the heart with its tip in the superior vena cava.
• Transplantation: The recipient’s heart is excised, allowing the posterior wall of both atria with the caval and 
pulmonary vein openings and the atria of the donor heart to be anastomosed to the recipient’s atrial remnants (left 
side first). The aorta and then the pulmonary artery are anastomosed end to end. Methylprednisolone is given 
before aortic cross-clamp release.
• Coming off pump: Isoproterenol infusion is started before stopping CPB because of sympathetic denervation. The 
transplanted heart may still respond to circulating catecholamines. The preload-dependent function of the graft 
makes maintenance of a normal or high cardiac preload desirable. Isoproterenol or epinephrine infusions should 
be readily available to increase the heart rate if necessary.
ANESTHESIA FOR CARDIOVASCULAR SURGERY 22-21
Case Card
A 67-year-old man is undergoing elective coronary revascularization after testing for unstable angina showed 
three-vessel disease. Echocardiogram showed ejection fraction of 35% with posterior and anterior left ven-
tricular hypokinesis. After CPB and coronary revascularization, cardioplegia is reversed, the patient is 
rewarmed, laboratory study results are normalized, and the patient is taken off pump. The heart is directly 
cardioverted for atrial fibrillation but develops subsequent bradycardia in the 30s and systolic pressures of 
50 mm Hg.
What are your next steps?
ANESTHESIA FOR CARDIOVASCULAR SURGERY 22-22
Start milrinone and discuss the adequacy of the surgical procedure with the surgeon. Use monitors to determine 
hemodynamic parameters such as cardiac index, pulmonary artery occlusion pressure, and SVR. If pressures 
continue to be low, often from vasoplegia, start vasopressors such as norepinephrine or epinephrine. Atrial 
pacing at a rate of 80 to 100 beats/min or an intraaortic balloon pump may be needed in refractory bradycardia 
and hypotension. Often postbypass atrial pacing and intraaortic balloon pumps can be discontinued when 
hypothermia and cardioplegia are completely reversed.
RESPIRATORY PHYSIOLOGY AND ANESTHESIA 23-1
• During normal breathing, the diaphragm and the external intercostal muscles 
are responsible for inspiration; expiration is generally passive but may be 
facilitated by the abdominal muscles.
• Humidification and filtering of inspired air are functions of the upper airway 
(nose, mouth, and pharynx). The function of the tracheobronchial tree is to 
conduct gas flow to and from the alveoli.
• The lungs are supplied by two circulations, pulmonary and bronchial. The 
bronchial circulation arises from the left heart and sustains the metabolic 
needs of the tracheobronchial tree.
• Dichotomous division (each branch dividing into two smaller branches), 
starting with the trachea and ending in alveolar sacs, is estimated to involve 
23 divisions, or generations.
Lung Mechanics
• Both the lungs and the chest have elastic properties. Whereas the chest has a 
tendency to expand outward, the lungs have a tendency to collapse. Alveolar 
collapse is directly proportional to surface tension, as demonstrated by the 
law of Laplace: Pressure = 2 × Surface tension/Radius.
• Lung compliance (CL) is defined as: C L = Change in lung volume
Change in transpulmonary pressure
• Lung compliance is influenced by a variety of factors, including lung vol-
ume, pulmonary blood volume, extravascular lung water, and pathological 
processes such as inflammation and fibrosis.
(Reproduced, with permission, from 
Guyton AC: Textbook of Medical 
Physiology, 7th ed. W.B. Saunders, 1986.)
RESPIRATORY PHYSIOLOGY AND ANESTHESIA 23-2
Measurement Definition Average Adult Va lues (mL)
Tidal volume (VT) Each normal breath 500
Inspiratory reserve volume (IRV) Maximal additional volume that can be 
inspired above VT
3000
Expiratory reserve volume (ERV) Maximal volume that can be expired below VT 1100
Residual volume (RV) Volume remaining after maximal exhalation 1200
Total lung capacity (TLC) RV + ERV + VT + IRV 5800
Functional residual capacity (FRC) RV + ERV 2300
(Reproduced, with perm ission, from 
Nunn’s Applied Respiratory Physiology, 
5th ed. Lumb A [editor]. Butterworth-
Heinemann, 2000.)
RESPIRATORY PHYSIOLOGY AND ANESTHESIA 23-3
Ventilation/Perfusion Relationships
• Ventilation is the sum of all exhaled gas volumes in 1 min; Minute ventilation = Respiratory rate × Tidal volume.
• The fraction of inspired gas not participating in alveolar gas exchange is known as dead space. Dead space is composed 
of gases in nonrespiratory airways (anatomic dead space) as well as in alveoli that are not perfused (alveolar dead 
space).
• Dependent areas of both lungs tend to be better ventilated than do the upper areas because of a gravitationally induced 
gradient in intrapleural pressure (and transpulmonary pressure).
• Pulmonary blood flow is also not uniform because dependent portions of the lung receive greater blood flow than upper 
(nondependent) areas regardless of body position. Pulmonary vascular tone is heavily influenced by local factors with 
hypoxia being a powerful stimulus for vasoconstriction.
• The normal ventilation/perfusion (V/Q) ratio is 0.8 (alveolar ventilation is ~4 L/min, and pulmonary capillary ~5 L/min).
• Shunting is the process whereby desaturated, mixed venous blood returns to the left heart without being resaturated with 
O2 in the lungs. Physiologic shunt (e.g., communication between deep bronchial veins and pulmonary veins, the thebesian 
circulation, atelectasis) is typically less than 5%.
Effects of Anesthesia on Respiratory System
• The supine position reduces the FRC by 0.8 to 1.0 L, and induction of general anesthesia further reduces the FRC by 
0.4 to 0.5 L. The decrease in FRC is not related to anesthetic depth and may persist for several hours or days after 
anesthesia.
• Prolonged administration of high inspired O2 concentrations may lead to resorption atelectasis and increases in absolute 
shunt.
• Anesthetic effects on gas exchange include increased dead space, hypoventilation, and increased intrapulmonary shunt-
ing. Inhalation agents, including nitrous oxide, also can inhibit hypoxic pulmonary vasoconstriction in high doses.
RESPIRATORY PHYSIOLOGY AND ANESTHESIA 23-4
Control of Breathing
• The basic breathing rhythm originates in the medulla and consists of dorsal respiratorygroup (primarily 
active during inspiration) and a ventral respiratory group (active during expiration). Two pontine areas influ-
ence the medullary center. Whereas the lower pontine (apneustic) center is excitatory, the upper pontine 
(pneumotaxic) center is inhibitory.
• Central chemoreceptors are thought to lie on the anterolateral surface of the medulla and respond primarily 
to changes in cerebrospinal fluid (CSF) [H+]. Increases in PaCO2 elevate CSF hydrogen ion concentration 
and activate the chemoreceptors. Secondary stimulation of the adjacent respiratory medullary centers 
increases alveolar ventilation. In contrast to peripheral chemoreceptors, central chemoreceptor activity is 
depressed by hypoxia.
• Peripheral chemoreceptors include the carotid bodies and the aortic bodies. The carotid bodies are the prin-
cipal peripheral chemoreceptors in humans, and they interact with central respiratory centers via the glos-
sopharyngeal nerves, producing reflex increases in alveolar ventilation in response to reductions in PaO2, 
arterial perfusion or elevations in [H+] and PaCO2.
• Stretch receptors are distributed in smooth muscle of airways and are responsible for inhibition of inspira-
tion when the lung is inflated to excessive volumes (Hering–Breuer inflation reflex).
• Most general anesthetics promote hypoventilation through central depression of the chemoreceptor and 
depression of external intercostal muscle activity. The magnitude of the hypoventilation is generally propor-
tional to anesthetic depth.
• The peripheral response to hypoxemia is even more sensitive to anesthetics than the central CO2 response 
and is nearly abolished by even subanesthetic doses of most inhalation agents (including nitrous oxide) and 
many intravenous agents.
RESPIRATORY PHYSIOLOGY AND ANESTHESIA 23-5
Mechanisms of Hypoxemia
Low alveolar oxygen tension
Low inspired oxygen tension
Low fractional inspired concentration
High altitude
Alveolar hypoventilation
Third gas effect (diffusion hypoxia)
Increased oxygen consumption
Increased alveolar–arterial gradient
Right-to-left shunting
Increased areas of low V/ Q ratios
Low mixed venous oxygen tension
Decreased cardiac output
Increased oxygen consumption
Decreased hemoglobin concentration
Oxygen Tension
• The alveolar–arterial O2 partial pressure gradient (A–a gradient) is normally less than 15 mm Hg but pro-
gressively increases with age up to 20 to 30 mm Hg. Arterial O2 tension can be approximated by the follow-
ing (in mm Hg): PaO2 = 102 − (Age/3).
• The A–a gradient for O2 depends on the amount of right-to-left shunting, the amount of V/Q mismatch, and 
the mixed venous oxygen tension. Mixed venous oxygen tension depends on cardiac output, O2 consump-
tion, and hemoglobin concentration.
• The greater the shunt, the less likely the possibility that an increase in the fraction of inspired oxygen (FIO2) 
will prevent hypoxemia.
• High O2 consumption rates and low hemoglobin concentrations can increase the A–a gradient and 
depress PaO2, through their secondary effects on mixed venous O2 tension.
RESPIRATORY PHYSIOLOGY AND ANESTHESIA 23-6
Factors Influencing the Hemoglobin Dissociation Curve
• A rightward shift in the oxygen–hemoglobin 
dissociation curve lowers O2 affinity, dis-
places O2 from hemoglobin, and makes more 
O2 available to tissues; a leftward shift 
increases hemoglobin’s affinity for O2, reduc-
ing its availability to tissues. 
• An increase in blood hydrogen ion concentra-
tion reduces O2 binding to hemoglobin (Bohr 
effect).
• The high CO2 content of venous capillary 
blood, by decreasing hemoglobin’s affinity 
for O2, facilitates the release of O2 to tissues.
• Carbon monoxide, cyanide, nitric acid, and 
ammonia can combine with hemoglobin at 
O2-binding sites and shift the saturation curve 
to the left. Fetal hemoglobin also shifts the 
curve left.
ANESTHESIA FOR PATIENTS WITH RESPIRATORY DISEASE 24-1
Obstructive Pulmonary Disease
Asthma
• Pathophysiology: Local release of chemical mediators and overactivity of the parasympathetic nervous 
system marked by bronchoconstriction, mucosal edema, and increased secretions at all levels of the lower 
airways. Total lung capacity (TLC), residual volume (RV), and functional residual capacity (FRC) are all 
increased. Hypoxemia is the result of a low ventilation/perfusion (V/Q) ratio. Typically, tachypnea results in 
hypocapnia, and hypercapnia may be a sign of impending respiratory failure.
• Treatment: β-Adrenergic agonists, methylxanthines, glucocorticoids, anticholinergics, leukotriene blockers, 
and mast cell–stabilizing agents.
• Preoperative management: The recent course of the disease should be evaluated along with history of 
hospitalizations and physical examination. Patients with active wheezing and signs of bronchospasm can be 
managed with oxygen, aerosolized β2-agonists, and intravenous (IV) glucocorticoids. Bronchodilators 
should be continued up to the time of surgery. Patients receiving long-term glucocorticoid therapy should be 
given supplemental doses to compensate for adrenal suppression.
ANESTHESIA FOR PATIENTS WITH RESPIRATORY DISEASE 24-2
Obstructive Pulmonary Disease
Asthma (continued)
• Intraoperative management: The manipulation of the airway, pain, drugs causing histamine release, or 
stimulation during light general anesthesia pose an increased risk of bronchospasm. A smooth induction and 
resulting deep anesthesia before intubation is more important than choice of induction agent per se. 
Ketamine offers advantages of bronchodilation. All volatile agents provide bronchodilation, but desflurane 
can provide a mild airway irritant effect. Airflow obstruction during expiration is apparent on capnography 
as a delayed rise of the end-tidal CO2 value. Severe bronchospasm is manifested by rising peak inspiratory 
pressures, wheezing, decreasing exhaled tidal volumes, and hypoxia. Bronchospasm should be treated by 
increasing the concentration of the volatile agent and administering an aerosolized bronchodilator. At the 
conclusion of surgery, deep extubation or IV lidocaine can help prevent bronchospasm on emergence.
ANESTHESIA FOR PATIENTS WITH RESPIRATORY DISEASE 24-3
Obstructive Pulmonary Disease
Chronic Obstructive Pulmonary Disease (COPD)
• Chronic bronchitis: Productive cough on most days of 3 consecutive months for at least 2 consecutive 
years. Airflow obstruction is caused by secretions producing hypertrophied bronchial mucous glands and 
mucosal edema. Smoking, air pollutants, and recurrent pulmonary infections are typically responsible. RV 
is increased, but TLC is normal. Chronic hypoxemia may lead to erythrocytosis, chronic CO2 retention, and 
pulmonary hypertension with eventual right ventricular failure.
• Emphysema: Irreversible enlargement of the airways distal to terminal bronchioles and destruction of 
alveolar septa. Destruction of pulmonary capillaries in the alveolar septa decreases carbon monoxide diffu-
sion capacity and may lead to pulmonary hypertension. Large bullae can also develop. Arterial oxygen ten-
sion and CO2 tensions are typically normal. Causes are almost always smoking related and less commonly 
α 1-antitrypsin deficiency. Expect increases in RV, FRC, TLC, and the RV/TLC ratio.
ANESTHESIA FOR PATIENTS WITH RESPIRATORY DISEASE 24-4
Obstructive Pulmonary Disease
Chronic Obstructive Pulmonary Disease (COPD) (continued)
• Treatment: Inhaled β-agonists, glucocorticoids, and ipratropium. Exacerbations are often related to bron-
chitis, which usually will require broad-spectrum antibiotic coverage. Patients with chronic hypoxemia (PaO2 
<55 mm Hg) require low-flow oxygen therapy.
• Preoperative management: Recent course of the disease with attention paid to changes in dyspnea, sputum, 
and wheezing. COPD symptoms are less amenable to acute interventions compared with the case in people 
with asthma. Recent pulmonary infections or active bronchospasm need to be assessed before elective sur-gery. Smoking cessation leads to a decrease in pulmonary complications. Perioperative glucocorticoids 
should be considered with patients with moderate to severe disease.
• Intraoperative management: Regional anesthesia can be considered, but high spinal or epidural spread can 
lead to decreased lung volumes, dyspnea, and retention of copious secretions. Arterial blood gas (ABG) 
analysis can help guide therapy, particularly ventilator management, because normalization of PaCO2 can 
result in alkalosis. Nitrous oxide should be avoided in patients with bullae, and attention should be paid to 
the risk of developing pneumothoraces.
ANESTHESIA FOR PATIENTS WITH RESPIRATORY DISEASE 24-5
Restrictive Pulmonary Disease
Intrinsic Pulmonary Disorders
• Pathophysiology: Secondary to various causes but results in decreased lung compliance, possible diffusion 
deficits, and reduced lung volumes. Etiologies include intrinsic pulmonary disorders, including interstitial 
lung disease, acute respiratory distress syndrome, and infectious pneumonia. Extrinsic disorders involving 
the pleura, chest wall, or diaphragm or decreased neuromuscular function can also cause decreased lung 
compliance.
• Preoperative management: Patients typically present with dyspnea or nonproductive cough or sometimes 
require mechanical ventilation. Symptoms of cor pulmonale are only seen with chronic disease. A chest 
radiograph will often elucidate the disease severity. Pulmonary function tests and ABG analysis are often 
required preoperatively.
• Intraoperative management: Patients often have reduced FRC, predisposing them to rapid hypoxemia 
after induction. High peak pressures should be avoided during mechanical ventilation, and FiO2 should be 
kept to an acceptable minimum to avoid oxygen-induced toxicity.
ANESTHESIA FOR PATIENTS WITH RESPIRATORY DISEASE 24-6
Restrictive Pulmonary Disease
Pulmonary Embolism
• Pathophysiology: Emboli into the pulmonary circulation can result from blood clots, fat, tumor cells, air, 
amniotic fluid, or foreign material.
Factors Associa ted with Deep Venous Thrombosis
Prolonged bed rest
Postpartum state
Fracture of the lower extremities
Surgery on the lower extremities
Carcinoma
Heart failure
Obesity
Surgery lasting >30 min
Hypercoagulability
Antithrombin III deficiency
Protein C deficiency
Protein S deficiency
Plasminogen-activator deficiency
ANESTHESIA FOR PATIENTS WITH RESPIRATORY DISEASE 24-7
Restrictive Pulmonary Disease
Pulmonary Embolism (continued)
• Pathophysiology: The embolic occlusions will decrease total blood flow into the pulmonary circulation, 
worsening V/Q ratios and increasing pulmonary shunt and hypoxemia. Pulmonary infarction can occur if 
bronchial circulation is insufficient. Pulmonary hypertension will then develop, which increases right ven-
tricular afterload and potentially cardiovascular collapse if the right heart fails.
• Diagnosis: Clinical manifestations may include tachypnea, tachycardia, dyspnea, chest pain, wheezing or 
hemoptysis. ABG analysis typically shows mild hypoxemia with respiratory alkalosis. Chest radiography 
may show a wedge-shaped area of radiolucency, indicating an infarct. Pulmonary angiography is the most 
accurate means of diagnosing a pulmonary embolism (PE), but pulmonary V/Q or helical computed tomog-
raphy scans are widely used. An abnormal V/Q scan result will demonstrate normal ventilation with perfu-
sion defects.
• Treatment: Systemic anticoagulation prevents the formation of new blood clots or the extension of existing 
clots. Pulmonary embolectomy may be indicated for patients with massive embolism and impending cardio-
vascular collapse.
ANESTHESIA FOR PATIENTS WITH RESPIRATORY DISEASE 24-8
Restrictive Pulmonary Disease
Pulmonary Embolism (continued)
• Preoperative management: In most instances, patients will have a history of PE presenting for an unrelated 
surgery. Prevention is key, and the use of perioperative heparin, pneumatic compression stockings, early 
ambulation, and so on is imperative. Anticoagulation goals need to be evaluated before surgery.
• Intraoperative management: Patients may present for placement of a vena cava filter. This percutaneous 
technique is typically very well tolerated. For patients with a history of PE, regional anesthesia for high-risk 
procedures (e.g., hip surgery) decreases the incidence of postoperative deep venous thrombosis and therefore 
PE. However, many of these patients will require systemic anticoagulation, therefore limiting neuraxial 
interventions. Patients presenting for pulmonary embolectomy are critically ill and require the expertise of 
cardiac anesthesiologists.
• Intraoperative pulmonary embolism: Intraoperative diagnosis requires a high index of suspicion. Air 
emboli are common but typically not clinically significant. Fat emboli can occur during orthopedic proce-
dures. Amniotic fluid embolism can be a fatal complication of obstetric delivery. Patients with intraoperative 
embolism usually present with unexplained sudden hypotension, hypoxemia, and decreased end-tidal CO2 
concentration. Invasive cardiac monitoring reveals elevated pulmonary artery pressures and central venous 
pressure. Transesophageal echocardiography can often visualize the clot and help evaluate right heart func-
tion. If air is identified, aspiration can be attempted through a central venous cannula. A saddle embolus 
requires emergent surgical intervention.
ANESTHESIA FOR THORACIC SURGERY 25-1
Lateral Decubitus Position
• This position provides optimal access for most operations on the lungs, pleura, esophagus, the great vessels, 
other mediastinal structures, and vertebrae. Unfortunately, this position may significantly alter the normal 
pulmonary ventilation/perfusion (V/Q) relationships.
Awake Lateral Decubitus V/Q Matching
• Perfusion: The dependent lung receives more perfusion than the upper lung because of gravity.
• Ventilation: The dependent lung receives more ventilation than the upper lung because of more efficient 
hemidiaphragm contraction and favorable position on the compliance curve.
• Ventilation/perfusion: Matched
Postinduction Lateral Decubitus V/Q Matching
• Perfusion: The dependent lung has more perfusion than the upper lung because of gravity.
• Ventilation: The dependent lung now receives less ventilation than the upper lung because of a less favor-
able position on the compliance curve.
• Ventilation/perfusion: Mismatch
Postinduction, Positive-Pressure Lateral Decubitus V/Q Matching
• Perfusion: The dependent lung has more perfusion than the upper lung because of gravity.
• Ventilation: The dependent lung now receives less ventilation than the upper lung because of a less favor-
able position on the compliance curve, which is worsened by abdominal contents pressure from neuromus-
cular blockade. “Bean bag” positioning decreases dependent hemithorax compliance.
• Ventilation/perfusion: Increased mismatch
ANESTHESIA FOR THORACIC SURGERY 25-2
One-Lung Ventilation (OLV)
• OLV occurs when the operative lung is deliberately collapsed for surgery, which facilitates surgery but 
complicates anesthesia.
• Shunt: The collapsed lung is perfused but not ventilated, leading to a large right-to-left shunt.
• Hypoxic pulmonary vasoconstriction (HPV) decreases collapsed lung perfusion and shunt. HPV is inhib-
ited (shunt worsened) by high/low pulmonary artery pressures, hypocapnia, high/low venous PO2, vasodi-
lators, pulmonary infection, and volatile anesthetics. Dependent lung perfusion is decreased (shunt 
worsened) by high airway pressures, low FiO2, vasoconstrictors, and auto-PEEP.
• OLV can be accomplished by placement of a double-lumen bronchial tube (DLT), a single-lumen tube with 
a bronchial blocker, or a single-lumen bronchial tube.
DLTs are used most often for OLV, come in left and right 
versions (sized 35, 37, 39, and 41 Fr), and have both bron-
chial and tracheal cuffs. Lungs can be suctioned indepen-
dently.
Clamping off onelumen allows the ipsilateral lung to col-
lapse while the other lung is ventilated.
Right-sided DLTs have an opening to ventilate the right 
upper lobe (see rightmost image).
ANESTHESIA FOR THORACIC SURGERY 25-3
Establishing One-Lung Ventilation
• A left-sided DLT can be used for most procedures, with the exception of left main bronchus distortion by 
intra- or extrabronchial mass, compression of left main bronchus by aortic aneurysm, left-sided pneumonec-
tomy, and left sleeve resection.
• DLT placement is facilitated by a Mac laryngoscope with the tip of the DLT anterior until after the vocal 
cords are passed, at which point a 90-degree rotation is performed and the DLT is inserted until resistance 
is met (average, 29 cm at teeth). Placement should be confirmed by a fiberoptic bronchoscope.
• DLT complications include hypoxia from malposition, traumatic laryngitis, tracheobronchial rupture from 
placement trauma or overinflation of bronchial cuff, and inadvertent suturing of DLT to a bronchus.
• Single-lumen tubes can be used with bronchial blockers to achieve OLV. Bronchial blockers are placed 
with a fiberoptic bronchoscope. The main advantages compared with DLTs are lack of need for reintubation 
for postoperative ventilation and ability to place in already intubated patients without need for reintubation. 
The main disadvantage is that the blocked lung deflates slowly.
• Single-lumen bronchial tubes are now rarely used.
• In an emergency, a regular single-lumen endotracheal tube (ETT) can be used as a bronchial blocker by blind 
advancement into the right mainstem bronchus. Reliable placement into the left mainstem bronchus requires 
bronchoscopic guidance.
ANESTHESIA FOR THORACIC SURGERY 25-4
Intraoperative Management of One-Lung Ventilation
• FiO2 should be titrated down from 100% with a goal of maintaining SpO2 above 90%.
• Pressure-control ventilation may reduce risk of barotraumas by limiting peak airway pressure.
Hypoxemia During OLV:
 1. Verify appropriate placement of DLT using fiberoptic bronchoscopy and clear secretions.
 2. Increase FiO2 to 100%.
 3. Recruitment of dependent lung may decrease atelectasis and improve shunt.
 4. Optimize positive end-expiratory pressure (PEEP) of dependent lung.
 5. Verify adequate cardiac output and oxygen carrying capacity.
 6. Apply continuous positive airway pressure (CPAP) or blow-by O2 to operative lung while in communica-
tion with surgical team.
 7. Reestablish two-lung ventilation. During pneumonectomy, consider pulmonary artery clamp placement.
 8. Evaluate for the possibility of pneumothorax on the dependent side.
Alternatives to OLV:
 1. Intermittent apnea after establishing 100% oxygen insufflation.
 2. High-frequency jet ventilation.
ANESTHESIA FOR THORACIC SURGERY 25-5
Pulmonary Tumors
• These tumors present with cough, hemoptysis, dyspnea, wheezing, weight loss, fever, pleuritic chest pain 
(pleural extension), postobstructive pneumonias, hoarseness (mediastinal involvement), pericardial effusion 
(cardiac involvement), Horner syndrome (sympathetic chain involvement), dysphagia (esophagus compres-
sion), or superior vena cava (SVC) syndrome (SVC compression).
• Paraneoplastic syndromes from lung carcinoma have variable presentation, including Lambert-Eaton syn-
drome, Cushing syndrome, and hypertrophic osteoarthropathy, among others.
• Benign tumors are most commonly hamartomas but also include bronchial adenomas and pulmonary car-
cinoids (carcinoid syndrome is uncommon). Malignant tumors are divided to small cell and non–small cell 
carcinomas (squamous cell, adenocarcinomas, large cell carcinomas). All of these types occur in smokers; 
adenocarcinomas also occur in nonsmokers.
• Treatment includes surgery, radiation, and chemotherapy.
• Resectability is determined by the anatomic stage of the tumor, but operability depends on the extent of the 
procedure and the physiological status of the patient.
• Staging is performed by bronchoscopy, computed tomography (CT), and mediastinoscopy. Surgical 
options include wedge resection, lobectomy, sleeve resection, and pneumonectomy. The goal of surgery is 
for cure while maintaining sufficient residual pulmonary function.
ANESTHESIA FOR THORACIC SURGERY 25-6
Workup and Indications for Lung Resection
• Operative criteria for lung resection are based on respiratory mechanics, gas exchange, and cardiopulmo-
nary interaction.
• V/Q scanning can determine the relative contribution of each lobe to lung function. This information is used 
with pulmonary function tests (PFTs) and the following calculations:
Postoperative FEV1 (forced expiratory volume in 1 second) = preoperative FEV1 × (1 − % Functional lung 
tissue removed/100)
Postoperative FEV1 <40% = Significant morbidity or mortality
Postoperative FEV1 <30% = May need postoperative mechanical ventilation
Postoperative DLCO (diffusing capacity of the lung for carbon monoxide) <40% = Increased postopera-
tive respiratory and cardiac complications
• High-risk patients receive cardiopulmonary evaluation. Patients unable to climb more than two flights of 
stairs have increased perioperative risk. VO2 below 10 mL/kg is also associated with an increased risk.
• Infections refractory to antibiotic treatment (cavitary lesions, empyemas) can be treated by lung resection.
• Bronchiectasis resulting in massive hemoptysis can also be treated by lung resection when the disease is 
localized.
ANESTHESIA FOR THORACIC SURGERY 25-7
Preoperative Evaluation and Planning
Normal Airway Anatomy:
• Adult trachea length: 11 to 13 cm from cricoid (C6) to bifurcation at carina (T5).
• Right bronchus: Relatively vertical angle from trachea; divides into upper, middle, and lower lobe 
branches.
• Left bronchus: Relatively horizontal angle; divides into upper and lower lobe branches.
Abnormal airway anatomy can result from thoracic tumors. Tracheal or bronchial deviation can compli-
cate intubation and DLT placement; airway compression can cause difficulty with ventilation after induction. 
Review of CT and magnetic resonance imaging (MRI) anatomy can highlight potential problems.
Preoperative preparation includes a plan for airway difficulties and includes DLTs of multiple sizes, a work-
ing fiberoptic bronchoscope, an ETT exchanger, and a CPAP circuit.
A large-bore (14- or 16-gauge) intravenous (IV) line is mandatory for thoracic surgery, and an arterial line 
is indicated for OLV, resection of large tumors, and patients with significant comorbidities. Central venous 
pressure (CVP) monitoring is desirable for pneumonectomies. Placement of an epidural catheter may be 
indicated for postoperative analgesia.
Induction of anesthesia is frequently followed by placement of a single-lumen ETT to facilitate bronchos-
copy by the surgical team, after which a DLT may be placed for OLV. After the DLT is placed, proper 
positioning must be confirmed before positioning for surgery.
ANESTHESIA FOR THORACIC SURGERY 25-8
Intraoperative Management
Positioning for Thoracic Surgery:
• Lateral decubitus for video-assisted thoracic surgery (VATS) or thoracotomy.
• Lower arm flexed and padded
• Upper arm extended
• Pillow between the legs
• Axillary roll w/brachial plexus free
• Eyes and dependent ear free of pressure
Maintenance of Anesthesia:
• Volatile anesthetics provide bronchodilation, depress airway reflexes, allow high FiO2 as needed, and 
impact HPV minimally when <1 MAC.
• Opioids depress airway reflexes, provide analgesia, and have minimal hemodynamic effects.
• Neuromuscular blockade facilitates surgical exposure.
• IV fluids should be kept to a minimum to reduce postoperative acute lung injury (ALI).
• Low tidal volumes (6–8 mL/kg) reduce ALI.
• PEEP (5–10 cm H2O) reduces ALI but needs adjusting on a per-patient basis.
• Low airway pressures (<25 cm H2O plateau, <35 cm H2O peak) reduce ALI.
• Low FiO2 (while maintaining SpO2 >90%) reduces ALI.
• Bronchial anastomoses should be briefly tested for leak under water up to30 cm H2O.
• At the end of surgery, the operative lung should be inflated slowly (peak pressure <30 cm H2O).
ANESTHESIA FOR THORACIC SURGERY 25-9
Postoperative Care
• Patients should be extubated early whenever possible to decrease barotraumas and infection.
• Upright position, incentive spirometry, and close monitoring are indicated.
• Reexpansion edema of the collapsed lung is possible, and patients require close monitoring.
• Postoperative hemorrhage (>200 mL/hr chest tube output) may require operative intervention.
Postoperative Analgesia
• Inadequate pain control leads to poor respiratory mechanics (splinting) and decreased cough, which 
leads to airway closure, atelectasis, and shunting.
• Epidural analgesia is the gold standard for postthoracic surgery pain control.
• Paravertebral nerve blocks and intercostal nerve blocks should be considered when epidural analgesia is not 
possible.
Postoperative Complications
• Significant atelectasis (mediastinal shift) may require therapeutic bronchoscopy.
• Air leaks are common and stop after a few days.
• Bronchopleural fistula (sudden large air leak, lung collapse) can occur from inadequate bronchial stump 
closure (24–72 hours after surgery) or necrosis (delayed, from infection or inadequate blood flow).
• Lobar torsion, phrenic palsy, and cardiac herniation into either hemithorax are rare but serious complica-
tions.
ANESTHESIA FOR THORACIC SURGERY 25-10
Indications for Lung Isolation
Massive pulmonary hemorrhage is defined as more than 500 mL of blood loss from tracheobronchial 
within 24 hours.
• Treatments include bronchial artery embolization, laser coagulation, tamponade, and lung resection.
• Operative mortality exceeds 20% and is most commonly caused by asphyxia from blood in the airway.
• Preoperative considerations: Large-bore IV access; lateral position with affected lung down.
• Induction: Rapid-sequence induction (RSI) because of a full stomach from swallowed blood with semiu-
pright position and cricoid.
• Airway: DLT or bronchial blocker for lung isolation; keep blocker in place until after resection.
Pulmonary cysts and bullae can impair ventilation by compressing the surrounding lung. Positive-pressure 
ventilation (PPV) can cause a tension pneumothorax because these air cavities can have ball-valve physiology. 
Maintain spontaneous ventilation until lung isolation is established. N2O should be avoided. Chest tubes 
should be placed for sudden hypotension, bronchospasm, or an increase in peak airway pressure.
Lung abscesses require lung isolation to prevent contamination of the healthy lung. A DLT should be placed 
after RSI in a semiupright position with tracheal and bronchial cuffs inflated before moving to the lateral posi-
tion. Frequent suctioning of the diseased lung decreases risk of contaminating the healthy lung.
Bronchopleural fistulas can complicate PPV because of a high leak and risk of pneumothorax. DLT place-
ment simplifies airway management.
ANESTHESIA FOR THORACIC SURGERY 25-11
Tracheal Resection
This procedure is performed for tracheal stenosis, tumors, and congenital abnormalities.
• Preoperative evaluation should focus on airway assessment. Dyspnea can occur from tracheal compres-
sion, may be positional, and can include wheezing or stridor with exertion. CT imaging and flow-volume 
loops can help evaluate the severity of the lesion.
• Limited premedication should be given because of the presence of airway obstruction.
• Left radial arterial access is preferred because of the potential for innominate artery compression.
• Induction with sevoflurane in 100% oxygen to maintain spontaneous breathing decreases potential for 
complete airway obstruction.
• Rigid bronchoscopy may be performed to dilate the lesion. An ETT should be placed distal to the 
 obstruction.
• High tracheal lesions can be accessed via a collar incision, but low tracheal lesions require a median 
 sternotomy or posterior thoracotomy.
• Intraoperative ventilation can be performed via a surgically placed ETT or jet ventilation.
• Postoperative neck flexion must be maintained to minimize tension on the anastomosis.
ANESTHESIA FOR THORACIC SURGERY 25-12
Other Thoracic Procedures
• Thoracoscopic surgery is performed using small incisions in the chest in the lateral decubitus position. 
OLV is mandatory. Procedures performed in this manner include lung biopsy, segmental and lobar resec-
tion, pleurodesis, esophagectomy, pneumonectomy, and pericardectomy.
• Rigid bronchoscopy is performed to remove foreign bodies and tracheal dilatation. General anesthesia is 
induced and maintained using a total IV anesthetic technique along with short-acting neuromuscular 
blockers. Ventilation can be achieved by intermittent apnea, ventilation via the rigid bronchoscope or jet 
ventilation.
• Mediastinoscopy is performed to biopsy mediastinal lymph nodes to determine diagnosis or resectability of 
malignancies. Large-bore IV access is mandatory because of the risk of large blood loss. Blood pressure 
should be measured in the left arm because the innominate artery can be compressed; placement of a 
pulse ox or arterial line on the right arm can detect this compression, which can lead to cerebral ischemia. 
Pneumothorax, venous air embolism, phrenic nerve injury, and recurrent laryngeal nerve injuries are known 
complications.
• Bronchoalveolar lavage is performed for patients with pulmonary alveolar proteinosis (excess surfactant). 
Usually this is done in the supine position with DLT placement to ensure adequate ventilation of one lung 
while the other is lavaged. Warm saline is infused and drained until the fluid is clear (10–20 L).
ANESTHESIA FOR THORACIC SURGERY 25-13
Lung Transplantation
• This procedure is performed for end-stage pulmonary parenchymal disease or pulmonary hypertension. 
Patients often have dyspnea, hypoxemia at rest (PaO2 <50 mm Hg), increasing O2 requirement, and CO2 
retention. Eisenmenger syndrome requires combined heart–lung transplantation; in cor pulmonale, right 
ventricular (RV) function may recover when pulmonary artery (PA) pressures normalize.
• Preoperative coordination between transplant and organ-retrieval teams minimizes graft ischemic time.
• Induction is approached with a RSI in the semiupright position because patients typically have full stom-
achs. Aseptic care must be observed during line placement. Hypoxia and hypercarbia should be avoided 
to not worsen existing pulmonary hypertension.
• Maintenance of anesthesia is usually accomplished with a total IV anesthetic. Hypercarbia and acidosis can 
lead to acute right heart failure. Vasopressors should be used to treat hypotension rather than large fluid 
boluses.
• Single-lung transplant can be performed for idiopathic pulmonary fibrosis and is often done without CPB 
via posterior thoracotomy. CPB is indicated if hypoxia or elevated PA pressure occurs after clamping the PA 
of the lung to be removed. Prostaglandin E1, milrinone, nitroglycerin, and dobutamine may be used to con-
trol pulmonary hypertension and prevent RV failure. The donor PA, left atrial cuff (with the pulmonary 
veins), and bronchus are anastomosed.
ANESTHESIA FOR THORACIC SURGERY 25-14
Lung Transplantation
• Double-lung transplant is performed for cystic fibrosis, bullous emphysema, or vascular disease. A “clam-
shell” transverse sternotomy or sequential thoracotomies can be performed.
• Posttransplant goals include minimizing peak inspiratory pressure and reducing FiO2 as tolerated 
while maintaining PaO2 above 60 mm Hg. Methylprednisolone and mannitol are usually administered. 
Hyperkalemia may occur from donor organ preservative fluid. Inhaled nitric oxide and inotropes may be 
necessary. Transesophageal echocardiography can differentiate left ventricular (LV) and RV failure.
• Transplanted lungs have:
 � Disrupted innervation (no cough reflex below carina).
 � Disrupted lymphatics (predisposing to pulmonary edema).
 � Disrupted bronchial circulation(predisposes to ischemic anastomosis breakdown).
 � Normal hypoxic pulmonary vasoconstriction.
• Early extubation is an important goal. Analgesia can be facilitated with a thoracic epidural catheter.
• Organ rejection and infection as well as renal and hepatic dysfunction can complicate the postoperative 
course. Bronchoscopy with lavage and biopsies can differentiate rejection from infection. The phrenic, 
vagus, and left recurrent laryngeal nerves can be damaged.
ANESTHESIA FOR THORACIC SURGERY 25-15
Esophageal Surgery
• This procedure is performed for esophageal tumors, motility disorders, and gastroesophageal reflux disease 
(GERD). Most tumors are in the distal esophagus. Squamous cell carcinomas are most common. After resec-
tion, the stomach is pulled into the neck or part of the colon is interposed. GERD that is refractory to medi-
cal management can be treated by wrapping part of the stomach around the esophagus. Achalasia and 
scleroderma account for most surgical procedures.
• Preoperative evaluation focuses on coexisting disease, particularly coronary artery disease and chronic 
obstructive pulmonary disease. Dyspnea can occur from chronic aspiration, leading to pulmonary fibrosis.
ANESTHESIA FOR THORACIC SURGERY 25-16
Esophageal Surgery
• Induction is focused on the reducing risk of pulmonary aspiration. A preoperative proton pump inhibitor or 
H2 blocker should be considered. RSI with a semiupright position and cricoid pressure is a common 
approach. An awake fiberoptic intubation should be considered in cases of anticipated difficult intubation.
• Thoracotomy or thoracoscopic approach requires DLT placement. A bougie may be placed into the esopha-
gus to facilitate surgery; this should be done with great caution.
• Transhiatal approaches may involve substantial blood loss. Dissection can produce hypotension by tran-
siently reducing venous filling and marked vagal stimulation. Colonic interposition can be lengthy and may 
involve substantial fluid shifts. Complications include phrenic, vagus, and left recurrent laryngeal nerve 
injuries, which may require postoperative ventilation.
ANESTHESIA FOR THORACIC SURGERY 25-17
Case Card: Mediastinal Adenopathy
A 9-year-old boy with mediastinal lymphadenopathy seen on a chest radiograph presents for biopsy of a cervi-
cal lymph node.
 1. What is the most important preoperative consideration?
 2. Does the absence of any preoperative dyspnea make severe intraoperative respiratory compromise less 
likely?
 3. What is the superior vena cava syndrome?
ANESTHESIA FOR THORACIC SURGERY 25-18
 1. Is there any evidence of airway compromise? Tracheal compression may produce dyspnea (proximal 
obstruction) or a nonproductive cough (distal obstruction). Asymptomatic compression is also common 
and may be evident only as tracheal deviation on physical or radiographic examinations. A CT scan of the 
chest provides invaluable information about the presence, location, and severity of airway compression. 
Flow-volume loops also detect subtle airway obstruction and provide important information regarding the 
location and functional importance of the obstruction.
 2. No. Severe airway obstruction can occur after induction of anesthesia in these patients even in the absence 
of any preoperative symptoms. This mandates that the chest radiograph and CT scan be reviewed for 
evidence of asymptomatic airway obstruction. The point of obstruction is typically distal to the tip of the 
tracheal tube. Moreover, loss of spontaneous ventilation can precipitate complete airway obstruction.
 3. SVC syndrome is the result of progressive enlargement of a mediastinal mass and compression of medi-
astinal structures, particularly the vena cava. Lymphomas are most commonly responsible, but primary 
pulmonary or mediastinal neoplasms can also produce the syndrome. SVC syndrome is often associated 
with severe airway obstruction and cardiovascular collapse on induction of general anesthesia. The caval 
compression produces venous engorgement and edema of the head, neck, and arms. Direct mechanical 
compression as well as mucosal edema severely compromise airflow in the trachea. Most patients favor 
an upright posture because recumbency worsens the airway obstruction.
NEUROPHYSIOLOGY AND ANESTHESIA 26-1
Cerebral Physiology
Cerebral Metabolism
• Brain oxygen consumption represents roughly 20% of total body oxygen.
• Cerebral metabolism is expressed as the cerebral metabolic rate of oxygen consumption (CMRO2), which is 3 to 4 mL/100 g/min, 
with greater activity shown in the gray matter of the cerebral cortex.
• Glucose is the primary neuronal energy source (consumed at a rate of 5 mg/100 g/min).
Cerebral Blood Flow (CBF)
• Total CBF: �50 mL/100 g/min or 15% to 20% of cardiac output (gray matter, 80 mL/100 g/min compared with 20 mL/100 g/min 
in the white matter)
• Flow rates below 20 to 25 mL/100 g/min are usually with cerebral impairment; 15 and 20 mL/100 g/min produce a flat 
(isoelectric) electroencephalogram (EEG); values below 10 mL/100 g/min allude to irreversible brain damage.
Regulating CBF: Three mechanisms are responsible for regulating CBF: cerebral perfusion pressure, autoregulation, and 
certain extrinsic factors.
• CPP = MAP − ICP (or CVP). Cerebral perfusion pressure (CPP) is normally 80 to 100 mm Hg, and because intracranial 
pressure (ICP) is normally less than 10 mm Hg, CPP is primarily dependent on mean arterial pressure (MAP). With higher 
ICPs, CPP and CBF can be compromised.
• Autoregulation is the body’s ability to maintain a constant amount of blood flow to the brain despite transient changes in 
blood pressure. In normal individuals, CBF remains constant between a MAP of 60 and 160 mm Hg; beyond these limits, 
CBF becomes pressure dependent.
• Extrinsic mechanisms include respiratory gas tension, temperature, viscosity, and autonomic influences. The most impor-
tant extrinsic influence on CBF is the respiratory gas tension, particularly PaCO2. Blood flow changes approximately 1 to 
2 mL/100 g/min per mm Hg change in PaCO2; this occurs almost immediately.
NEUROPHYSIOLOGY AND ANESTHESIA 26-2
Cerebral Physiology
CBF changes 5% to 7% per 1°C change in tem-
perature with hypothermia directly decreasing both 
CMRO2 and CBF; pyrexia has the opposite effect. 
Normally, changes in blood viscosity do not appre-
ciably alter CBF. But a decrease in hematocrit 
decreases viscosity and can improve CBF; unfortu-
nately, a reduction in hematocrit also decreases the 
oxygen-carrying capacity and thus can potentially 
impair oxygen delivery and vice versa. Intracranial 
vessels are innervated by sympathetic (vasocon-
strictive) and parasympathetic (vasodilatory) 
mechanisms. Intense sympathetic stimulation 
induces marked vasoconstriction in these vessels, 
which can limit CBF. Autonomic innervation may 
also play an important role in cerebral vasospasm 
after brain injury and stroke.
NEUROPHYSIOLOGY AND ANESTHESIA 26-3
Anesthetic Agents and Cerebral Physiology
Overall, most general anesthetics have a favorable effect on the central nervous system (CNS) by reducing electrical activity. 
The effects however depend on the type of agent administered and can be complicated by coadministration of other drugs.
Inhalational anesthetics (IAs): All IAs dilate cerebral 
vessels and impair autoregulation with sevoflurane pro-
ducing the least cerebral vasodilation. They also produce 
a dose-dependent decrease in CMRO2, with isoflurane 
producing the greatest depression.
Importantly, though, the response of the cerebral vascu-
lature to CO2 is generally retained so that hyperventila-
tion (hypocapnia) can actually abolish or blunt the 
initial effects of these agents on CBF. Regarding cere-
brospinal fluid (CSF) dynamics, most IAs impede 
absorption of CSF with minimal effects on formation. 
Isoflurane is the exception because it actually facilitates 
absorption. The net effect of IAs on ICP is the result of 
immediate changes incerebral blood volume, delayed 
alterations on CSF dynamics, and arterial CO2 tension. 
Based on these factors, isoflurane and sevoflurane 
appear to be the volatile agents of choice in patients 
with decreased intracranial compliance.
NEUROPHYSIOLOGY AND ANESTHESIA 26-4
Anesthetic Agents and Cerebral Physiology
Effects of intravenous (IV) agents: With the exception of ketamine, all IV agents and opioids either have 
little effect on or reduce cerebral metabolic rate (CMR) and CBF while also preserving cerebral autoregulation 
and CO2 responsiveness.
Noteworthy
• Etomidate: Associated with a relatively high incidence of myoclonic activity. Should be avoided in patients 
with a history of epilepsy.
• Propofol: Significant anticonvulsant properties and relatively short elimination half-life. Excessive hypo-
tension and cardiac depression in elderly or unstable patients can compromise CPP
• Ketamine: Only IV anesthetic that dilates the cerebral vasculature and increases CBF (50%–60%), resulting 
in a net increase in ICP. Selective activation of certain areas (limbic and reticular) is partially offset by 
depression of other areas (somatosensory and auditory) such that total CMR does not change.
• Anesthetic adjuncts: Intravenous lidocaine decreases CBF by increasing cerebral vascular resistance with-
out causing other significant hemodynamic effects. Droperidol has now been avoided because of its prolon-
gation of QT interval and risk of fatal arrhythmias. Neuromuscular blocking agents (NMBAs) lack direct 
action on the brain but can have important secondary effects. Hypertension and histamine-mediated cerebral 
vasodilation increase ICP, and systemic hypotension (from histamine release) lowers CPP. In particular, 
succinylcholine can increase ICP, but the increase is generally minimal if an adequate dose of propofol 
is given.
NEUROPHYSIOLOGY AND ANESTHESIA 26-5
Neuroprotection
The brain is very vulnerable to ischemic injury because of its relatively high oxygen consumption and near-
total dependence on aerobic glucose metabolism. Interruption of cerebral perfusion, metabolic substrate 
(glucose), or severe hypoxemia rapidly results in functional impairment; reduced perfusion also impairs 
clearance of potentially toxic metabolites. If normal oxygen tension, blood flow, and glucose supply are not 
reestablished within 3 to 8 minutes under most conditions, adenosine triphosphate stores are depleted, and 
irreversible neuronal injury begins.
Strategies for neuroprotection: As anesthesiologists, clinically our goals are to optimize CPP, decrease 
metabolic requirements (basal and electrical), and possibly block mediators of cellular injury.
• Hypothermia is an effective method for protecting the brain during focal and global ischemia. It does so 
through reducing both the basal and electrical metabolic requirements throughout the brain and by reducing 
free radicals as well as mediators of ischemic injury.
• Anesthetics such as barbiturates, etomidate, propofol, and isoflurane can produce complete electrical 
silence of the brain and eliminate the metabolic cost of electrical activity. Even ketamine can provide protec-
tion by its ability to block the actions of glutamate at the NMDA receptor.
• Adjuncts such as nimodipine have cerebral vasodilating properties and have a significant role in manage-
ment of patients with subarachnoid hemorrhage in the treatment of vasospasm.
NEUROPHYSIOLOGY AND ANESTHESIA 26-6
Evoked Potentials
Electrophysiological monitoring (EPM) attempts to assess the functional integrity of the CNS. The two most 
commonly used monitors for neurosurgical procedures are the EEG and evoked potentials.
Four types of evoked potentials currently exist: somatosensory, motor, auditory, and visual evoked potentials. 
Somatosensory evoked potentials (SSEPs) test the integrity of the dorsal spinal columns and the sensory 
cortex and may be useful during resection of spinal tumors, instrumentation of the spine, carotid endarterec-
tomy (CEA), and aortic surgery. Motor function (ventral spinal column) is not directly monitored, and it is 
possible to sustain significant motor deficit without disruption of the SSEP tracing. This is where motor 
evoked potentials (MEPs) become important. Brainstem auditory evoked potentials test the integrity of the 
eighth cranial nerve and the auditory pathways above the pons and are used for surgery in the posterior fossa. 
Visual evoked potentials may be used to monitor the optic nerve and upper brainstem during resections of 
large pituitary tumors.
Interpretation of evoked potentials is more complicated than that of the EEG. Evoked potentials have post-
stimulus latencies that are described as short, intermediate, and long. Short-latency evoked potentials arise 
from the nerve stimulated or from the brainstem. Intermediate- and long-latency evoked potentials are primar-
ily of cortical origin. In general, short-latency potentials are least affected by anesthetic agents, and long-
latency potentials are affected by even subanesthetic levels of most agents. Visual evoked potentials are most 
affected by anesthetics, and brainstem auditory evoked potentials are least affected. In general, IV agents 
in clinical doses have fewer effects on evoked potentials compared with volatile agents but in high doses can 
also decrease amplitude and increase latencies.
NEUROPHYSIOLOGY AND ANESTHESIA 26-7
Monitoring
EEG monitoring is most useful for assessing the adequacy of cerebral perfusion during CEA and controlled 
hypotension, as well as for assessing anesthetic depth.
• EEG activation (a shift to predominantly high-frequency and low-voltage activity) is seen with light anes-
thesia and surgical stimulation.
• EEG depression (a shift to predominantly low-frequency and high-voltage activity) occurs with deep anes-
thesia or cerebral compromise.
• Most anesthetics produce a biphasic pattern on the EEG consisting of an initial activation followed by dose-
dependent depression.
Inhalational anesthetics such as isoflurane can produce an isoelectric EEG at high clinical doses (1–2 MAC); 
desflurane and sevoflurane produce a burst suppression pattern at high doses (>1.2 and >1.5 MAC) but not 
electrical silence. Nitrous oxide is also unusual in that it increases both frequency and amplitude (high-amplitude 
activation).
IV agents such as benzodiazepines produce a typical biphasic pattern on the EEG. Barbiturates, etomidate, 
and propofol produce a typical biphasic pattern as well but also are capable of producing burst suppression and 
electrical silence at high doses. In contrast, whereas opioids produce only a monophasic, dose-dependent 
depression of the EEG, ketamine produces an unusual activation consisting of rhythmic high-amplitude theta 
activity followed by very high-amplitude gamma and low-amplitude beta activities.
NEUROPHYSIOLOGY AND ANESTHESIA 26-8
Monitoring
Electroencepha lographic Changes During Anesthesia
Activa tion Depression
Inhalational agents (subanesthetic) Inhalation agents (1–2 MAC)
Barbiturates (small doses) Barbiturates
Benzodiazepines (small doses) Opioids
Etomidate (small doses) Propofol
Nitrous oxide Etomidate
Ketamine Hypocapnia
Mild hypercapnia Marked hypercapnia
Sensory stimulation Hypothermia
Hypoxia (early) Hypoxia (late) 
Ischemia
ANESTHESIA FOR NEUROSURGERY 27-1
Intracranial Hypertension
• Intracranial hypertension is defined as a sustained increase in intracranial pressure (ICP) above 15 mm Hg. 
Intracranial hypertension may result from an expanding tissue or fluid mass, depressed skull fracture, inter-
ference with normal absorption of cerebrospinal fluid (CSF), excessive cerebral blood flow (CBF), or sys-
temic disturbances promoting brain edema.
• Clinical manifestations: Headache, nausea, vomiting, papilledema, focal neurologic deficits, and altered 
consciousness; Periodic increases in arterial blood pressure with reflex slowing of the heart rate (Cushing 
response)are often observed and can be correlated with abrupt increases in ICP lasting 1 to 15 minutes. 
When ICP exceeds 30 mm Hg, CBF progressively decreases, and a vicious circle is established: ischemia 
causes brain edema, which in turn increases ICP, resulting in more ischemia. If left unchecked, this cycle 
continues until the patient dies of progressive neurologic damage or catastrophic herniation.
• Cerebral edema: An increase in brain water content can be produced by several mechanisms. Disruption 
of the blood–brain barrier (vasogenic edema) is most common and allows the entry of plasma-like fluid into 
the brain. Common causes of vasogenic edema include mechanical trauma, inflammatory lesions, brain 
tumors, hypertension, and infarction. Cerebral edema after metabolic insults (cytotoxic edema), such as 
hypoxemia or ischemia, results from failure of brain cells to actively extrude sodium and progressive cel-
lular swelling. Cerebral edema can also be the result of intracellular movement of water secondary to acute 
decreases in serum osmolality (water intoxication). Interstitial cerebral edema is the result of obstructive 
hydrocephalus and entry of CSF into brain interstitium.
ANESTHESIA FOR NEUROSURGERY 27-2
Intracranial Hypertension
• Treatment: Treatment of intracranial hypertension and cerebral edema is ideally directed at the underlying 
cause. Metabolic disturbances are corrected and operative intervention undertaken whenever possible. 
Vasogenic edema often responds to corticosteroids. Tight blood glucose control should be maintained when 
steroids are used to reduce cerebral edema. Regardless of the cause, fluid restriction, osmotic agents, and 
loop diuretics are usually effective in temporarily decreasing brain edema and lowering ICP until more 
definitive measures can be undertaken. Diuresis lowers ICP chiefly by removing intracellular water from 
normal brain tissue. Moderate hyperventilation (PaCO2 30–33 mm Hg) is often very helpful in reducing CBF.
• Mannitol, in doses of 0.25 to 0.5 g/kg, is particularly effective in rapidly decreasing ICP. Its efficacy is 
primarily related to its effect on serum osmolality. Treatment can transiently decrease blood pressure by 
virtue of its weak vasodilating properties, but its principal disadvantage is a transient increase in intravascu-
lar volume initially, which can precipitate pulmonary edema in patients with borderline cardiac or renal 
function. It is important to remember that mannitol should not be used in patients with intracranial aneu-
rysms, arteriovenous malformations (AVMs), or intracranial hemorrhage until the cranium is opened. 
Osmotic diuresis in such instances can expand a hematoma as the volume of the normal brain tissue around 
it decreases. The combined use of mannitol and furosemide may be synergistic but requires close monitoring 
of the serum potassium concentration.
ANESTHESIA FOR NEUROSURGERY 27-3
Craniotomy Surgery
Craniotomy is commonly undertaken for primary and metastatic neoplasms of the brain.
• Glial cells: astrocytoma, oligodendroglioma, or glioblastoma
• Ependymal cells, ependymoma
• Supporting tissues: Meningioma, schwannoma, or choroidal papilloma
• Childhood tumors: Medulloblastoma, neuroblastoma, and chordoma
Clinical manifestations: Headache, seizures, cognitive decline, neurologic deficits; supratentorial masses: seizures, hemi-
plegia, aphasia; infratentorial masses: cerebellar dysfunction (ataxia, nystagmus, and dysarthria); brainstem compression: 
cranial nerve palsies, altered mental status, and respirations
Preoperative Management
• Review CT and MRI scans for evidence of brain edema, midline shifts, and ventricular size.
• Neurologic examination, including mental status and existing sensory or motor deficits
• Medications reviewed for corticosteroid use, diuretic, and anticonvulsant therapy
• Premedication is best avoided when intracranial hypertension is suspected. Corticosteroids and anticonvulsant therapy 
should be continued until the time of surgery.
Intraoperative Management:
• Direct intraarterial pressure monitoring (A-Line) to obtain arterial blood gases (ABGs) closely regulate PaCO2.
• Bladder catheterization is necessary because of the frequent use of diuretics, the long duration of most procedures, and 
its utility in guiding fluid therapy.
Monitoring
• ICP monitored perioperatively with a ventriculostomy or subdural bolt can be beneficial and is most commonly used and 
is usually placed by the neurosurgeon preoperatively.
ANESTHESIA FOR NEUROSURGERY 27-4
Craniotomy Surgery
Induction: Induction of anesthesia and tracheal intubation are critical periods; prevention of ICP increases is of critical 
importance.
• The most common induction technique uses thiopental or propofol together with hyperventilation to lower ICP and blunt 
the noxious effects of laryngoscopy.
• All patients are hyperventilated with controlled ventilation, and a neuromuscular blocking agent (NMBA) is given to 
facilitate ventilation and prevent straining or coughing. Succinylcholine may increase ICP but may be the agent of choice 
in patients at increased risk for aspiration or with a difficult airway because hypoxemia and hypercarbia are even more 
detrimental.
• Hypertension during induction can be blunted by one of three ways: β-blockade, deepening anesthesia with additional 
propofol, or hyperventilation with low-dose IAs.
• ICPs can be improved by osmotic diuresis, steroids, or removal of CSF via a ventriculostomy drain immediately before 
induction.
Intraoperative
• Anesthesia can be maintained with IAs or by total intravenous agents (TIVA): propofol or dexmedetomidine and remi-
fentanil.
• Hyperventilation should be continued intraoperatively to maintain PaCO2 between 30 and 35 mm Hg.
• Intravenous (IV) fluid replacement should be limited to glucose-free isotonic crystalloid or colloid.
Emergence
• Extubation in the operating room requires special handling during emergence. Straining or bucking on the tracheal tube 
may precipitate intracranial hemorrhage or worsen cerebral edema.
ANESTHESIA FOR NEUROSURGERY 27-5
Posterior Fossa Surgery
• Craniotomy for a mass in the posterior fossa presents similar anesthetic challenges as with a normal craniotomy. The 
exceptions, however, are the unique set of potential problems, including: obstructive hydrocephalus, possible injury to 
vital brainstem centers, unusual positioning, pneumocephalus, postural hypotension, and venous air embolism.
• Obstructive hydrocephalus: Infratentorially located masses can obstruct flow of CSF at the level of the fourth ventricle 
or the cerebral aqueduct. In such cases, a ventriculostomy is often performed under to decrease ICP before induction of 
general anesthesia.
• Brainstem injury: Operations in the posterior fossa can injure vital circulatory and respiratory brainstem centers as well 
as cranial nerves or their nuclei. Such injuries can cause abrupt changes in blood pressure or heart rate or changes in 
cardiac rhythm, which should alert the anesthesiologist to the possibility of such an injury.
• Positioning: The patient is in a semirecumbent, standard sitting position with the head elevated above the heart. Excessive 
neck flexion has been associated with swelling of the upper airway. The sitting position increases the likelihood of sig-
nificant pneumocephalus because air readily enters the subarachnoid space as CSF is lost during surgery. Expansion of 
a pneumocephalus after dural closure can compress the brain. This can cause delayed awakening and continued impair-
ment of neurologic function. Avoid nitrous oxide at all costs.
• Venous air embolism (VAE): Venous air embolism can occur when the pressure within an open vein is subatmospheric 
(i.e., whenever the wound is above the level of the heart). With sitting craniotomies, the incidence is as high as 20% to 
40%. Clinically, signs of VAE are often not apparent until large amounts of air have been entrained. A decrease in end-
tidalCO2 or arterial oxygen saturation might be noticed before any hemodynamic changes. ABG values may show only 
slight increases in PaCO2 as a result of increased pulmonary dead space.
ANESTHESIA FOR NEUROSURGERY 27-6
Posterior Fossa Surgery
• Major hemodynamic manifestations such as sudden hypotension can occur well before hypoxemia is noted. 
Moreover, rapid entrainment of large amounts of air can produce sudden circulatory arrest by obstructing 
right ventricular outflow. That is why many clinicians consider right atrial catheterization mandatory for 
sitting craniotomies. Central venous access frequently allows aspiration of entrained air.
• Paradoxic air embolism can result in a stroke or coronary occlusion, which may be apparent only postop-
eratively. Paradoxic air emboli are more likely to occur in patients with probe-patent foramen ovale, 
particularly when the normal transatrial (left > right) pressure gradient is reversed.
• Monitoring of VAE: Currently, the most sensitive intraoperative monitors are transesophageal echocardiog-
raphy (TEE) and precordial Doppler sonography. TEE has the added benefit of detecting the amount of the 
bubbles and any transatrial passage, as well as evaluating cardiac function.
• Treatment: Notify the surgeon in order to fluid the field with saline. If nitrous oxide is on, turn it off. The 
central venous catheter should be aspirated in an attempt to retrieve the entrained air. Intravascular volume 
infusion should be given to increase central venous pressure (CVP). Vasopressors should be given to treat 
hypotension. Bilateral jugular vein compression, by increasing cranial venous pressure, may slow air 
entrainment and cause back bleeding, which might help the surgeon identify the source of the embolus. 
If the above measures fail, the patient should be placed in a head-down position and the wound closed 
quickly.
ANESTHESIA FOR NEUROSURGERY 27-7
Anesthesia for Stereotactic Surgery & Head Trauma
• Stereotaxis can be used in treating involuntary movement disorders, intractable pain, and epilepsy and can 
also be used when diagnosing and treating tumors that are located deep within the brain. These procedures 
are often performed under local anesthesia to allow periodic evaluation of the patient. Functional neurosur-
gery is increasingly performed for removal of lesions adjacent to speech and other vital brain centers. Often 
patients are managed with an asleep–awake–asleep technique with or without instrumentation of the airway. 
Such operations require the patient to be awake to participate in cortical mapping to identify key speech 
centers such as the Broca area.
• Head trauma: The significance of a head injury depends not only on the extent of the irreversible neuronal 
damage at the time of injury but also on the occurrence of any secondary insults. These additional insults 
include (1) systemic factors such as hypoxemia, hypercapnia, or hypotension; (2) formation and expansion 
of an epidural, subdural, or intracerebral hematoma; and (3) sustained intracranial hypertension. Surgical 
and anesthetic management of these patients is directed at preventing these secondary insults. The Glasgow 
Coma Scale (GCS) score generally correlates well with the severity of injury and outcome. A GCS score 
of 8 or less is associated with approximately 35% mortality rate.
• Preoperative management: Anesthetic care of patients with severe head trauma ideally begins in the emer-
gency department with measures taken to ensure patency of the airway, the adequacy of ventilation and oxy-
genation, and correction of hypotension. All patients must be assumed to have a cervical spine injury until the 
contrary is proven radiographically. Patients with obvious hypoventilation, an absent gag reflex, or a persistent 
GCS below 8 require tracheal intubation and hyperventilation. Regarding intubation, all patients should be 
regarded as having a full stomach and should have cricoid pressure applied during ventilation and intubation.
ANESTHESIA FOR NEUROSURGERY 27-8
Anesthesia for Stereotactic Surgery & Head Trauma
• After adequate preoxygenation and hyperventilation by mask, the adverse effects of intubation on ICP are 
blunted by prior administration of propofol and a rapid-onset NMBA. The use of succinylcholine in closed 
head injury has the potential of increasing ICP; rocuronium may be an alternative
• Hypotension in the setting of head trauma is nearly always related to other associated injuries, including 
spinal cord injuries, because of the sympathectomy associated with spinal shock. In a patient with head 
trauma, correction of hypotension and control of any bleeding take precedence over radiographic studies and 
definitive neurosurgical treatment because systolic arterial blood pressures of less than 80 mm Hg correlate 
with a poor outcome. Invasive monitoring of intraarterial pressure, CVP, and ICP is extremely valuable but 
should not delay diagnosis and treatment. Arrhythmias and electrocardiographic (ECG) abnormalities in the 
T wave, U wave, ST segment, and QT interval are common after head injuries but are not necessarily asso-
ciated with cardiac injury; they likely represent altered autonomic function.
• Intraoperative management: Anesthetic management is generally similar to that for other mass lesions 
associated with intracranial hypertension. In essence, anesthetic technique and agents are designed to pre-
serve cerebral perfusion and mitigate increases in ICP.
• Extubation: The decision whether to extubate the trachea at the conclusion of the surgical procedure 
depends on the severity of the injury, the presence of concomitant abdominal or thoracic injuries, preexisting 
illnesses, and the preoperative level of consciousness.
ANESTHESIA FOR NEUROSURGERY 27-9
Anesthesia for Cerebral Aneurysms and Arteriovenous Malformations
• Most patients who experience an aneurysm are in their 40s to 60s and are in otherwise good health. Typically, aneurysms 
occur at the bifurcation of the large arteries at the base of the brain, the vast majorities which are located in the anterior 
circle of Willis.
• Unruptured aneurysms: The most common symptom is headache, and the most common sign is a third-nerve palsy. 
Other manifestations might include brainstem dysfunction, visual field defects, trigeminal neuralgia, cavernous sinus 
syndrome, seizures, and hypothalamic–pituitary dysfunction. The most commonly used techniques to diagnose an aneu-
rysm are angiography, MRI angiography, and helical CT angiography. After diagnosis, patients are brought to the operat-
ing room or more likely the radiology suite for elective clipping or obliteration of the aneurysm.
• Ruptured aneurysms: Patients typically complain of a sudden severe headache without focal neurologic deficits but 
often associated with nausea and vomiting. Transient loss of consciousness may occur and may result from a sudden rise 
in ICP and a precipitous drop in CPP. The severity of subarachnoid hemorrhage (SAH) is graded according to the Hunt 
Hess scale; the Fisher scale gives the best indication of the likelihood of the development of cerebral vasospasm and 
patient outcome. Delayed complications: Delayed complications include cerebral vasospasm, rerupture, and hydro-
cephalus. Cerebral vasospasm occurs in 30% of patients (usually after 4–14 days) and is the major cause of morbidity and 
mortality.
• Therapy: The calcium channel antagonist nimodipine may mitigate the effects of vasospasm by reducing calcium entry 
into the cells reducing ischemic injury. Both transcranial Doppler and brain tissue oxygen monitoring can be used to guide 
vasospasm therapy. In patients with symptomatic vasospasm, intravascular volume expansion, and induced hypertension 
(triple H therapy: hypervolemia, hemodilution, and hypertension) are added as part of the therapeutic regimen.
ANESTHESIA FOR NEUROSURGERY 27-10
Anesthesia for Cerebral Aneurysms and Arteriovenous Malformations
• Preoperative management:In addition to neurologic findings, evaluation should include a search for coex-
isting diseases. Preexisting hypertension and renal, cardiac, or ischemic cerebrovascular disease should be 
noted.
• Intraoperative management: Aneurysm surgery can result in exsanguinating hemorrhage as a conse-
quence of rupture or rebleeding. Blood should be available before the start of these operations. Anesthetic 
management should focus on preventing rupture (or rebleeding) and avoiding factors that promote cerebral 
ischemia or vasospasm. Sudden increases in blood pressure with tracheal intubation or surgical stimulation 
should be avoided. Controlled hypotension by decreasing the mean arterial blood pressure reduces the trans-
mural tension across the aneurysm, making rupture (or rebleeding) less likely and facilitating surgical clip-
ping. Controlled hypotension can also decrease blood loss and improve surgical visualization in the event 
of bleeding. The combination of a slightly head-up position with a volatile anesthetic enhances the effects 
of any of the commonly used hypotensive agents.
• AVMs: AVMs cause intracerebral hemorrhage more often than subarachnoid hemorrhage. They can present 
at any age, but bleeding is most common between 10 and 30 years of age with complaints of headaches or 
seizures. Acutely, neuroradiologists try to embolize AVMs. When neurordiologic interventions are not suc-
cessful or available, surgical excision may be undertaken. Anesthetic management of surgical patients with 
AVMs is often complicated by extensive blood loss. Venous access with multiple large-bore cannulas and 
direct arterial pressure monitoring is necessary.
ANESTHESIA FOR NEUROSURGERY 27-11
Anesthesia for Surgery of the Spine
• Spinal surgery is most often performed for symptomatic nerve root or cord compression secondary to degen-
erative disorders. Compression may occur from protrusion of an intervertebral disk or osteophytic bone 
(spondylosis) into the spinal canal (or an intervertebral foramen).
• Operations on the spinal column can help correct deformities such as scoliosis, decompress the cord, and 
fuse the spine if disrupted by blunt trauma. Spinal surgery may also be performed to resect a tumor or vas-
cular malformation or to drain an abscess or hematoma.
• Preoperative management: Evaluation should focus on any existing ventilatory impairment and the air-
way. Anatomic abnormalities and limited neck movements caused by disease, traction, or braces complicate 
airway management and necessitate special techniques. All neurologic deficits should be documented. 
Mobility of the neck should be examined in all patients presenting for spine surgery at any level. When 
cervical surgery is planned, discussion with the surgeon regarding the stability of the spine in regards to 
intubation should take place. Patients with unstable cervical spines can be managed with either awake fiber-
optic intubation or asleep intubation with inline stabilization.
• Intraoperative management: Anesthetic management is complicated primarily by the prone position. 
Spinal operations involving multiple levels, fusion, and instrumentation are also complicated by the poten-
tial for large intraoperative blood losses; a red cell salvage device is often used. Whereas a transthoracic 
approach to the spine requires one-lung ventilation, an anterior or posterior approach requires the patient 
flipped in the middle of surgery.
ANESTHESIA FOR NEUROSURGERY 27-12
Anesthesia for Surgery of the Spine
• Positioning: In the prone position, extreme caution is necessary to avoid corneal abrasions or retinal isch-
emia from pressure on either globe or pressure necrosis of the nose, ears, forehead, chin, breasts (females), 
or genitalia (males). The chest should rest on parallel rolls or special supports—if a frame is used—to 
facilitate ventilation. The arms may be at the sides in a comfortable position or extended with the elbows 
flexed (avoiding excessive abduction at the shoulder).
• Deliberate hypotension has been advocated in the past to reduce bleeding associated with spine surgery. 
However, this should only be undertaken after the risks of perioperative vision loss (POVL) are considered; 
they usually occur secondary to ischemic optic neuropathy, perioperative glaucoma, or cortical hypotension. 
Airway and facial edema can likewise develop after prolonged head-down positioning. If reintubation is 
required, it may be more difficult than that encountered at the start of surgery.
• Monitoring: When significant blood loss is anticipated or the patient has preexisting cardiac disease, intra-
arterial and possibly CVP monitoring should be undertaken before prone positioning. Instrumentation of the 
spine requires the ability to intraoperatively detect spinal cord injury from excessive distraction. Monitoring 
somatosensory evoked potentials and motor evoked potentials is an alternative to intraoperative waking to 
assess potential injury.
ANESTHESIA FOR PATIENTS WITH NEUROLOGIC AND PSYCHIATRIC DISEASES 28-1
Cerebrovascular Disease
Cerebrovascular disease (CVD) typically means having a history of transient ischemic attacks (TIAs) or stroke. 
Patients with known CVD brought to surgery for other indications have an increased risk of perioperative stroke.
Risks
• Postoperative stroke risks: Increasing age, type of surgery (highest with cardiovascular surgeries such as 
valve replacement and aorta repair)
• General risk is 0.08 to 0.4%; for patients with known CVD, the risk is only 0.4% to 3.3%.
• Asymptomatic carotid bruits do not increase stroke risks, but allude to coexisting coronary artery disease 
(CAD).
TIAs
Patients with TIAs have a history of transient (<24 h) impairment and, by definition, have no residual neuro-
logic impairment.
• Presentation: Whereas unilateral visual impairment, numbness or weakness of an extremity, or aphasia is 
suggestive of carotid disease, bilateral visual impairment, ataxia, dysarthria, bilateral weakness is suggestive 
of vertebral-basilar disease.
• Perioperative stroke risks: Patients with TIAs have a 30% to 40% chance of developing a thrombotic 
stroke within 5 years; most (50%) occur within the first year. Patients with TIAs should not undergo any 
elective surgical procedure without an adequate medical evaluation that generally includes at least noninva-
sive (Doppler) flow and imaging studies. The presence of an ulcerative plaque of greater than 60% occlusion 
is generally an indication for carotid endarterectomy.
ANESTHESIA FOR PATIENTS WITH NEUROLOGIC AND PSYCHIATRIC DISEASES 28-2
Cerebrovascular Disease
Surgery after a stroke: The period of time after which a patient may be safely anesthetized after a stroke has 
not been determined.
• After 2 weeks, abnormalities in regional blood flow and metabolic rate usually resolve.
• After 4 weeks, CO2 responsiveness and blood–brain barrier alterations improve.
• As a general rule, postpone elective procedures a minimum of 6 to 26 weeks after a completed stroke.
Preoperative Management
• Preoperative evaluation: Stroke type, + neurologic deficits, residual impairments, cardiovascular status
• Coagulation management: Review plan with primary care and surgical teams to determine the risk versus 
benefit of the discontinuation or maintenance of such therapy perioperatively.
Intraoperative Management
Management of the patient after acute embolic stroke is directed toward the embolic source whether it is 
removal of the atrial myxoma, ventricular thrombi, or degenerative heart valves. Patients with acute strokes 
secondary to carotid occlusive disease present for carotid endarterectomy. Monitors may include electroen-
cephalography (EEG), evoked potentials, carotid stump pressure, cerebral infrared spectroscopy, or transcra-
nial Doppler to estimate the adequacy of cerebral oxygen delivery during cross-clamp. Even with adequate 
cerebral blood flow (CBF), perioperative stroke can occur during carotid surgery secondary toemboli.
ANESTHESIA FOR PATIENTS WITH NEUROLOGIC AND PSYCHIATRIC DISEASES 28-3
Seizure Disorder
• Seizures represent abnormal synchronized electrical activity in the brain. They may be a manifestation of an 
underlying central nervous system disease, a systemic disorder, or idiopathic. Mechanisms are thought to 
include (1) loss of inhibitory γ-aminobutyric acid (GABA) activity, (2) enhanced release of excitatory amino 
acids (glutamate), and (3) enhanced neuronal firing caused by abnormal voltage-mediated calcium currents. 
Epilepsy is a disorder characterized by recurrent paroxysmal seizure activity.
• Preoperative management: Preoperative evaluation of patients with a seizure disorder should focus on 
determining the cause and type of seizure activity and on the drugs with which the patient is being treated. 
Seizures in adults are most commonly caused by structural brain lesions (head trauma, tumor, or stroke) or 
metabolic abnormalities (uremia, hepatic failure, hypoglycemia, hypocalcemia, or drug toxicity or with-
drawal). Idiopathic seizures occur most often in children but may persist into adulthood.
• Seizures, particularly grand mal seizures, are serious complicating factors in surgical patients and should be 
treated aggressively to prevent musculoskeletal injury, hypoventilation, hypoxemia, and aspiration of gas-
trointestinal contents. If a seizure occurs, maintaining an open airway and adequate oxygenation are the first 
priorities. Intravenous (IV) propofol (50–100 mg), phenytoin (500–1000 mg slowly), or a benzodiazepine 
such as diazepam (5–10 mg) or midazolam (1–5 mg) can be used to terminate the seizure.
• Most patients with seizure disorders receive antiepileptic drugs preoperatively. Adverse side effects and 
signs of toxicity should be excluded clinically and by laboratory investigations. At toxic levels, most agents 
cause ataxia, dizziness, confusion, and sedation. Antiseizure medications should ideally be continued 
throughout the perioperative period to maintain therapeutic levels, which should also be determined 
preoperatively.
ANESTHESIA FOR PATIENTS WITH NEUROLOGIC AND PSYCHIATRIC DISEASES 28-4
Seizure Disorder
• Intraoperative management: In selecting anesthetic agents, drugs with possible epileptogenic potential 
should be avoided. Ketamine and methohexital (in small doses) theoretically can precipitate seizure activity, 
and hypothetically, large doses of atracurium/cisatracurium or meperidine may be contraindicated because 
of the reported epileptogenic potential of their metabolites, laudanosine and normeperidine. Hepatic micro-
somal enzyme induction should be expected from chronic antiseizure therapy. Enzyme induction may 
increase dose requirement and frequency for intravenous anesthetics and nondepolarizing neuromuscular 
blocking agents (NMBAs) and may increase the potential for hepatotoxicity from halothane.
Classifica tion of Se izures
Partia l (Foca l)
Simple
Complex
Secondarily generalized tonic–clonic
Genera lized
Absence (petit mal)
Myoclonic
Clonic
Tonic
Tonic-clonic (grand mal)
Atonic
Unclassified
ANESTHESIA FOR PATIENTS WITH NEUROLOGIC AND PSYCHIATRIC DISEASES 28-5
Parkinson Disease
• Parkinson disease (PD) is a common movement disorder that typically affects individuals age 50 to 70 years. 
Clinical signs and symptoms: This neurodegenerative disease is characterized by bradykinesia, rigidity, 
postural instability, and resting (pill-rolling) tremor. Additional frequently occurring findings include facial 
masking, hypophonia, dysphagia, and gait disturbances. Early in the course of the disease, intellectual func-
tion is usually preserved, but declines in intellectual function can occur and may be severe over the course 
of the disease. Cause: Progressive loss of dopamine in the nigrostriatum. As the loss of dopamine occurs, 
the activity of the GABA nuclei in the basal ganglia increases, leading to an inhibition of thalamic and 
brainstem nuclei. Thalamic inhibition, in turn, suppresses the motor system in the cortex, resulting in the 
dyskinesia, rigidity, postural instability, and tremor that are characteristic of the disease.
• Treatment: Directed at controlling the symptoms. A variety of drugs may be used for mild disease, including 
the anticholinergic agents trihexyphenidyl, benztropine, and ethopropazine; the irreversible monoamine oxi-
dase (MAO) inhibitors selegiline and rasagiline; and the antiviral drug amantadine. Patients with moderate to 
severe disease are typically treated pharmacologically with dopaminergic agents, either levodopa (a precursor 
of dopamine) or a dopamine-receptor agonist. Levodopa is given with a decarboxylase inhibitor to retard the 
peripheral breakdown of the drug, thereby increasing its central delivery and decreasing the dose of levodopa 
that is required to control symptoms. This includes catechol methyltransferase (COMT) inhibitors such as 
Stalevo and Tolcapone. Dopamine-receptor agonists include both ergot (bromocriptine, cabergoline, lisuride, 
and apomorphine) and nonergot derivatives (pramipexole and ropinirole). The surgical treatment of PD 
includes both ablative procedures (thalamotomy and pallidotomy) and electrical stimulation of the ventral 
intermediate nucleus of the thalamus, the globus pallidus internus, or the subthalamic nucleus.
ANESTHESIA FOR PATIENTS WITH NEUROLOGIC AND PSYCHIATRIC DISEASES 28-6
Parkinson Disease
• Anesthetic management: Medication for PD should be continued perioperatively, including the morning 
of surgery, because the half-life of levodopa is short. Abrupt withdrawal of levodopa can cause worsening 
of muscle rigidity and may interfere with ventilation. Phenothiazines, butyrophenones (droperidol), and 
metoclopramide can exacerbate symptoms as a consequence of their antidopaminergic activity and should 
be avoided. Anticholinergics (atropine) or antihistamines (diphenhydramine) may be used for acute exacer-
bation of symptoms. Diphenhydramine is particularly valuable for premedication and intraoperative seda-
tion in patients with tremor.
• Induction of anesthesia in patients receiving long-term levodopa therapy may result in either marked hypotension 
or hypertension. Cardiac irritability readily produces arrhythmias, so halothane, ketamine, and local anesthetic 
solutions containing epinephrine should be used cautiously. Although the response to NMBAs is generally nor-
mal, a rare occurrence of hyperkalemia after succinylcholine use has been reported. Adequacy of ventilation and 
airway reflexes should be carefully assessed before extubation of patients with moderate to severe disease.
• For patients undergoing surgical intervention (i.e., brain stimulator) for treatment of PD, general anesthesia 
can alter the threshold for stimulation, and correct placement of the electrodes can be affected. An awake 
craniotomy has been the norm for epilepsy surgery for some time, and, increasingly, it is being used for deep 
brain stimulation procedures as well. Two techniques are advocated—a true awake craniotomy with heavy 
sedation and an approach in which the patient receives a general anesthetic, usually total IV anesthesia 
(TIVA) with propofol and remifentanil, and a laryngeal mask airway for control of the airway. After appro-
priate surgical exposure, the IV infusions are discontinued, and the laryngeal mask airway is removed. The 
patient can be reanesthetized after the implantation of leads is complete.
ANESTHESIA FOR PATIENTS WITH NEUROLOGIC AND PSYCHIATRIC DISEASES 28-7
Alzheimer Disease
Alzheimer disease (AD) is the most common neurodegenerative disease, representing 40% to 80% of all cases 
of dementia. It has a 20% prevalence in patients older than age 80 years.
• Characteristics: Slow decline in intellectual function (dementia); progressive memory impairment; decision-
making impairments; emotional lability; extrapyramidal signs, including apraxia and aphasia
• Pathology: Neurofibrillary tangles that contain tau and neuriticprotein plaques composed of the peptide 
β-amyloid
• Imaging: Marked cortical atrophy with ventricular enlargement
Anesthetic Management
• Often complicated by disorientation and uncooperativeness
• Postoperative cognitive impairment is a frequent observation, persisting for 1 to 3 days after surgery.
• Consent must be obtained from the next of kin or a legal guardian if the patient is legally incompetent.
• Because the use of centrally acting drugs must be minimized, premedication is usually not given.
• Centrally acting anticholinergics, such as atropine and scopolamine, could theoretically contribute to post-
operative confusion. Glycopyrrolate, which does not cross the blood–brain barrier, may be the preferred 
agent when an anticholinergic is required.
Anesthetic agents are increasingly associated in laboratory studies with neuron injury and death. The implica-
tions of general anesthesia delivery both in the elderly as well as small children is currently subject of much 
investigation and debate. Consequently, anesthetic use may worsen dementia in the patients with AD; how-
ever, investigations are ongoing.
ANESTHESIA FOR PATIENTS WITH NEUROLOGIC AND PSYCHIATRIC DISEASES 28-8
Multiple Sclerosis
Multiple sclerosis (MS) is characterized by reversible demyelination at random and multiple sites in the brain 
and spinal cord.
• Autoimmune disorder initiated by a viral infection. It primarily affects patients between 20 and 40 years of 
age with a 2:1 female predominance. With time, remissions become less complete, and the disease is pro-
gressive and incapacitating.
• Clinical manifestations frequently include sensory disturbances (paresthesias), visual problems (optic 
neuritis and diplopia), and motor weakness. Early diagnosis confirmed by analysis of cerebrospinal fluid 
(CSF) and magnetic resonance imaging. Treatment primarily symptomatic or slowing the disease process. 
Systemic effects of these therapies on coagulation, immunologic, and cardiac function should be reviewed 
preoperatively.
Anesthetic Management
• Avoid elective surgery during relapse. Preoperative consent should discuss counseling of the patient to the 
effect that the stress of surgery and anesthesia might worsen the symptoms. Avoid spinal anesthesia as reports 
allude to exacerbations of the disease. Peripheral nerve blocks are less of a concern because MS is a disease 
of the central nervous system. Epidural and other regional techniques appear to have no adverse effect.
• In the setting of paresis or paralysis, succinylcholine should be avoided because of hyperkalemia. Regardless 
of the anesthetic technique used, increases in body temperatures should be avoided. Demyelinated fibers are 
extremely sensitive to increases in temperature; an increase of as little as 0.5°C may completely block 
conduction.
ANESTHESIA FOR PATIENTS WITH NEUROLOGIC AND PSYCHIATRIC DISEASES 28-9
Amyotrophic Lateral Sclerosis and Guillain-Barré Syndrome
Amyotrophic lateral sclerosis (ALS) is a rapidly progressive disorder of upper and lower motor neurons.
• Presentation: Muscular weakness in the 40s to 50s, muscle atrophy, fasciculations, or spasticity; at first is 
asymmetric, progressing to generalized weakness within 2 to 3 years. Respiratory muscle weakness leading 
to ventilator dependency. The heart is usually unaffected, but autonomic dysfunction can be seen.
• Anesthetic management: Foremost is judicious respiratory care. Succinylcholine is contraindicated because of 
the risk of hyperkalemia. Nondepolarizing NMBAs should be used sparingly, if at all, because patients often 
display enhanced sensitivity. Adequacy of ventilation should be carefully assessed. Difficulty in weaning patients 
off mechanical ventilation postoperatively is not uncommon in patients with moderate to advanced disease.
Guillain-Barré syndrome (GBS) a common disorder affecting one to four individuals per 100,000 popula-
tion. It is characterized by an immunologic reaction against the myelin sheath of peripheral nerves, particu-
larly lower motor neurons.
• Presentation: Sudden onset of ascending motor paralysis, areflexia, and variable paresthesias; usually fol-
lows a viral respiratory or gastrointestinal infections
• Anesthetic management is complicated by lability of the autonomic nervous system. Exaggerated hypo-
tensive and hypertensive responses during anesthesia may be seen. As with other lower motor neuron disor-
ders, succinylcholine should not be used because of the risk of hyperkalemia. The use of regional anesthesia 
in these patients remains controversial because it might worsen symptoms. When neuraxial techniques are 
chosen in patients with preoperative neurological deficits, dilute local anesthetic agents should be used to 
mitigate against the development of local anesthetic toxicity.
ANESTHESIA FOR PATIENTS WITH NEUROLOGIC AND PSYCHIATRIC DISEASES 28-10
Autonomic Dysfunction and Syringomyelia
Autonomic dysfunction, or dysautonomia, may be caused by generalized or segmental disorders of the central 
or peripheral nervous system. These disorders may be congenital, familial, or acquired.
• Presentation: Impotence; bladder and gastrointestinal dysfunction; abnormal regulation of body fluids; 
decreased sweating, lacrimation, and salivation; and orthostatic hypotension
• Anesthetic management: Watch for severe hypotension, compromising cerebral and coronary blood flow. 
The vasodilatory effects of spinal and epidural anesthesia are poorly tolerated. Continuous intraarterial 
blood pressure monitoring is desirable. Hypotension should be treated with fluids and direct-acting vaso-
pressors. The latter are preferable to indirect-acting agents.
Syringomyelia results in progressive cavitation of the spinal cord. In many cases, obstruction of CSF outflow 
from the fourth ventricle appears to be contributory.
• Presentation: Sensory and motor deficits in the upper extremities usually seen. Extension upward into the 
medulla (syringobulbia) leads to cranial nerve deficits.
• Anesthetic management should focus on defining existing neurologic deficits as well as any pulmonary 
impairment caused by scoliosis. Autonomic instability should be expected in patients with extensive lesions. 
Succinylcholine should be avoided when muscle wasting is present because of the risk of hyperkalemia. 
Adequacy of ventilation and reversal of nondepolarizing NMBAs should be achieved before extubation. 
Neuraxial techniques in the setting of elevated intracranial pressure are contraindicated.
ANESTHESIA FOR PATIENTS WITH NEUROLOGIC AND PSYCHIATRIC DISEASES 28-11
Spinal Cord Injury
• Most spinal cord injuries are traumatic and often result in partial or complete transection. The majority of 
injuries are caused by fracture and dislocation of the vertebral column. The mechanism is usually either 
compression and flexion at the thoracic spine or extension at the cervical spine. Clinical manifestations 
depend on the level of the transection. Injuries above C3–C5 (diaphragmatic innervation) require patients to 
receive ventilatory support to stay alive. Whereas transections above T1 result in quadriplegia, those above 
L4 result in paraplegia. The most common sites of transection are C5–C6 and T12–L1.
• Clinical manifestations: Acute spinal cord transection produces loss of sensation, flaccid paralysis, and 
loss of spinal reflexes below the level of injury. These findings characterize a period of spinal shock that 
typically lasts 1 to 3 weeks. Over the course of the next few weeks, spinal reflexes gradually return, together 
with muscle spasms and signs of sympathetic overactivity. Overactivity of the sympathetic nervous system 
is common with transections at T5 or above but is unusual with injuries below T10. Interruption of normal 
descending inhibitory impulses in the cord results in autonomic hyperreflexia. Cutaneous or visceral 
stimulation below the level of injury can induce intense autonomic reflexes: sympathetic discharge produceshypertension and vasoconstriction below the transection and a baroreceptor-mediated reflex bradycardia and 
vasodilation above the transection. Cardiac arrhythmias are common as well.
• Treatment: Emergent surgical management is undertaken whenever there is potentially reversible compres-
sion of the spinal cord because of dislocation of a vertebral body or bony fragment. Operative treatment is 
also indicated for spinal instability to prevent further injury.
ANESTHESIA FOR PATIENTS WITH NEUROLOGIC AND PSYCHIATRIC DISEASES 28-12
Spinal Cord Injury
Anesthetic Management
• Acute transection: Anesthetic management depends on the age of the injury. In the early care of acute 
injuries, the emphasis should be on preventing further spinal cord damage during patient movement, airway 
manipulation, and positioning. High-dose corticosteroid therapy (methylprednisolone) used for the first 
24 hours after injury to improve neurologic outcome. Patients with high transections often have impaired 
airway reflexes and are further predisposed to hypoxemia by a decrease in functional residual capacity and 
atelectasis. Spinal shock can lead to hypotension and bradycardia before any anesthetic administration. 
Direct arterial pressure monitoring is thus indicated. An IV fluid bolus and the use of ketamine for anesthe-
sia may help prevent further decreases in blood pressure; vasopressors may also be required. Succinylcholine 
can be used safely in the first 24 hours but should not be used thereafter because of the risk of hyperkalemia.
• Chronic transection: Anesthetic management of patients with nonacute transections is complicated by the 
possibility of autonomic hyperreflexia in addition to the risk of hyperkalemia. Autonomic hyperreflexia 
should be expected in patients with lesions above T6 and can be precipitated by surgical manipulations. 
Regional anesthesia and deep general anesthesia are effective in preventing hyperreflexia. Severe hyperten-
sion can result in pulmonary edema, myocardial ischemia, or cerebral hemorrhage and should be treated 
aggressively. Direct arterial vasodilator agents should be readily available. Body temperature should be 
monitored carefully, particularly in patients with transections above T1, because chronic vasodilation and 
loss of normal reflex cutaneous vasoconstriction predispose to hypothermia.
ANESTHESIA FOR PATIENTS WITH NEUROLOGIC AND PSYCHIATRIC DISEASES 28-13
Depression
• Depression is a mood disorder characterized by sadness and pessimism. Its cause is multifactorial, but phar-
macologic treatment is based on the presumption that its manifestations are caused by a brain deficiency of 
dopamine, norepinephrine, and serotonin or altered receptor activities. Current pharmacologic therapy uses 
drugs that increase brain levels of these neurotransmitters: tricyclic antidepressants (TCAs), serotonin reup-
take inhibitors, MAO inhibitors, and atypical antidepressants. The mechanisms of action of these drugs 
result in some potentially serious anesthetic interactions. Despite this, most antidepressant drugs are gener-
ally continued perioperatively. Electroconvulsive therapy (ECT) is increasingly used for refractory and 
severe cases and prophylactically when the patient returns to baseline. The use of general anesthesia for ECT 
is largely responsible for its safety and widespread acceptance.
• TCAs: Increased anesthetic requirements, presumably from enhanced brain catecholamine activity, have 
been reported with these agents. Potentiation of centrally acting anticholinergic agents (atropine and scopol-
amine) may increase the likelihood of postoperative confusion and delirium. The most important interaction 
between anesthetic agents and TCAs is an exaggerated response to both indirect-acting vasopressors and 
sympathetic stimulation. Pancuronium-, ketamine-, meperidine-, and epinephrine-containing local anes-
thetic solutions should be avoided. Chronic therapy with TCAs is reported to deplete cardiac catechol-
amines, theoretically potentiating the cardiac depressant effects of anesthetics. If hypotension occurs, small 
doses of a direct-acting vasopressor should be used instead of an indirect-acting agent.
• MAO inhibitors block the oxidative deamination of naturally occurring amines. Side effects include 
orthostatic hypotension, agitation, tremor, seizures, muscle spasms, urinary retention, paresthesias, and 
jaundice.
ANESTHESIA FOR PATIENTS WITH NEUROLOGIC AND PSYCHIATRIC DISEASES 28-14
Depression
• The most serious sequela of MAO inhibitors is a hypertensive crisis that occurs after ingestion of tyramine-
containing foods (cheeses and red wines) because tyramine is used to generate norepinephrine. The practice 
of discontinuing MAO inhibitors at least 2 weeks before elective surgery is no longer recommended. 
Opioids should generally be used with caution in patients receiving MAO inhibitors because rare but serious 
reactions to opioids have been reported. Most serious reactions are associated with meperidine, resulting in 
hyperthermia, seizures, and coma. Drugs that enhance sympathetic activity such as ketamine, pancuronium, 
and epinephrine (in local anesthetic solutions) should be avoided.
• Atypical antidepressants and selective serotonin reuptake inhibitors (SSRIs) include fluoxetine (Prozac), 
sertraline (Zoloft), and paroxetine (Paxil), which some clinicians consider first-line agents of choice for 
depression. These agents have little or no anticholinergic activity and do not generally affect cardiac conduc-
tion. Their principal side effects are headache, agitation, and insomnia. Patients taking St John’s wort are at 
increased risk of serotonin syndrome as are those taking drugs with similar effects (e.g., MAO inhibitors, 
meperidine). Serotonin syndrome manifestations include agitation, hypertension, hyperthermia, tremor, acido-
sis, and autonomic instability. Treatment is supportive along with the administration of a 5-HT antagonist 
(e.g., cyproheptadine).
• Other agents include bupropion (Wellbutrin, a norepinephrine dopamine reuptake inhibitor) and venlafaxine 
(Effexor, a serotonin norepinephrine reuptake inhibitor).
ANESTHESIA FOR PATIENTS WITH NEUROLOGIC AND PSYCHIATRIC DISEASES 28-15
Bipolar Disease and Schizophrenia
• Mania is a mood disorder characterized by elation, hyperactivity, and flight of ideas. Manic episodes may 
alternate with depression in patients with a bipolar disorder. Mania is thought to be related to excessive 
norepinephrine activity in the brain. Treatment: Both lithium (interferes with sodium ion transport with 
effects on many signaling pathways in the brain, affecting neurotransmitter release) and lamotrigine 
(inhibits sodium channels, modulates release of excitatory amino acids) are the drugs of choice for treating 
acute manic episodes and preventing their recurrence, as well as suppressing episodes of depression. Toxic 
blood concentrations of lithium can produce confusion, sedation, muscle weakness, tremor, and slurred 
speech. Still higher concentrations result in widening of the QRS complex, atrioventricular block, hypoten-
sion, and seizures. Anesthetic management: Although lithium is reported to decrease minimum alveolar 
concentration and prolong the duration of some NMBAs, clinically, these effects appear to be minor. 
Nonetheless, neuromuscular function should be closely monitored when NMBAs are used. The greatest 
concern is the possibility of perioperative toxicity. Blood levels should be checked perioperatively. Sodium 
depletion (secondary to loop or thiazide diuretics) decreases renal excretion of lithium and can lead to 
lithium toxicity. Fluid restriction and overdiuresis should be avoided.
• Schizophrenia: Patients with schizophrenia display disordered thinking, withdrawal, paranoid delusions, and 
auditory hallucinations. This disorder is thought to be related to an excess of dopaminergic activity in the brain. 
The most commonly used antipsychotics include phenothiazines,thioxanthenes, phenylbutylpiperadines, dihy-
droindolones, dibenzapines, benzisoxazoles, and a quinolone derivative; the effect of these agents appears to be 
attributable to dopamine antagonist activity. Continuing antipsychotic medication perioperatively is desirable. 
Reduced anesthetic requirements may be observed in some patients, along with perioperative hypotension.
ANESTHESIA FOR PATIENTS WITH NEUROLOGIC AND PSYCHIATRIC DISEASES 28-16
Neuroleptic Malignant Syndrome and Substance Abuse
• Neuroleptic malignant syndrome is a rare complication of antipsychotic therapy that may occur hours or 
weeks after drug administration. Meperidine and metoclopramide can also precipitate the disorder. The 
mechanism is related to dopamine blockade in the basal ganglia and hypothalamus and impairment of ther-
moregulation. In its most severe form, the presentation is similar to that of malignant hyperthermia. Muscle 
rigidity, hyperthermia, rhabdomyolysis, autonomic instability, and altered consciousness are seen. The mortal-
ity rate approaches 20% to 30%, with deaths occurring primarily as a result of renal failure or arrhythmias. 
Treatment with dantrolene appears to be effective; bromocriptine, a dopamine agonist, may also be effective. 
Differential diagnoses include malignant hyperthermia and serotonin syndrome.
• Substance abuse: Behavioral disorders from abuse of psychotropic (mind-altering) substances may involve 
a socially acceptable drug (alcohol), a medically prescribed drug (e.g., diazepam), or an illegal substance 
(e.g., cocaine). Physical dependence is most often seen with opioids, barbiturates, alcohol, and benzodiaz-
epines. Life-threatening complications primarily caused by sympathetic overactivity can develop during 
abstention. Knowledge of a patient’s substance abuse preoperatively may prevent adverse drug interactions, 
predict tolerance to anesthetic agents, and facilitate the recognition of drug withdrawal. Anesthetic require-
ments for substance abusers vary depending on whether the drug exposure is acute or chronic. For general 
anesthesia, a technique primarily relying on a volatile inhalation agent may be preferable so that anesthetic 
depth can be readily adjusted according to individual need. Awareness monitoring should be likewise con-
sidered. Opioids with mixed agonist–antagonist activity should be avoided in opioid-dependent patients 
because such agents can precipitate acute withdrawal. Clonidine is a useful adjuvant in the treatment of 
postoperative withdrawal syndromes.
RENAL PHYSIOLOGY AND ANESTHESIA 29-1
The Nephron
• The glomerular capillaries: Capillaries that extend into Bowman capsule, providing a large surface area 
for the filtration of blood. Endothelial and epithelial cells with their basement membrane provide an 
effective filtration barrier to cells and large-molecular-weight substances. Glomerular filtration pressure 
(�60 mm Hg) is approximately 60% of mean arterial pressure. Both afferent and efferent arteriolar tone is 
important in determining the glomerular filtration rate (GFR). Pressure is directly proportional to efferent 
arteriolar tone but inversely proportional to afferent arteriolar tone.
• The proximal tubule: About 65% to 75% of ultrafiltrate is reabsorbed in the proximal renal tubes. The 
major function is Na+ reabsorption. Sodium is actively transported out of proximal tubular cells at their 
capillary side by Na+-K+ ATPase. The resulting low intracellular concentration of Na+ allows passive move-
ment of Na+ down its gradient into epithelial cells. Sodium reabsorption is coupled with the reabsorption of 
other solutes and the secretion of H+. Water moves passively out the proximal tubule along osmotic gradients 
through aquaporins that facilitate water movement.
• The loop of Henle: Consists of descending and ascending portions. Mostly responsible for maintaining a 
hypertonic medullary interstitium and indirectly provide the collecting tubules with the ability to concentrate 
urine. About 25% to 35% of the ultrafiltrate formed in Bowman capsule reaches the loop of Henle. About 
15% to 20% of sodium load is reabsorbed. In the ascending thick segment, Na+ and Cl− are reabsorbed in 
excess of water. Therefore, tubular fluid flowing out of the loop of Henle is hypotonic, and the interstitium 
surrounding the loop of Henle is hypertonic.
RENAL PHYSIOLOGY AND ANESTHESIA 29-2
The Nephron
• The distal tubule: Receives hypotonic fluid from the loop of Henle. Normally responsible for only minor 
modifications of tubular fluid. Major site of parathyroid hormone and vitamin D–mediated calcium 
reabsorption.
• The collecting tubule: Cortical collecting tubule secretes potassium and participates in aldosterone-mediated 
Na+ reabsorption. The medullary collecting tubule courses down from the cortex through the hypertonic 
medulla before joining collecting tubules from other nephrons to form a single ureter. Medullary section is 
principal site of action of antidiuretic hormone. Dehydration increases antidiuretic hormone (ADH) secretion, 
which renders the luminal membrane permeable to water via aquaporins. This part of the nephron is also 
responsible for acidifying urine.
• The juxtaglomerular apparatus: A specialized segment of the afferent arteriole and the macula densa. 
Juxtaglomerular cells contain renin and are innervated by the sympathetic nervous system. Release of renin 
depends on β1-adrenergic stimulation, changes in afferent arteriolar wall pressure, and changes in chloride 
flow past the macula densa. Renin acts on angiotensinogen to form angiotensin I, which is converted by 
angiotensin-converting enzyme to angiotensin II. Angiotensin II plays a major role in blood pressure regula-
tion and aldosterone secretion.
RENAL PHYSIOLOGY AND ANESTHESIA 29-3
Renal Circulation
• General characteristics: Only organ that oxygen consumption is determined by blood flow. About 20% to 
25% of total cardiac output. Each kidney is supplied by single renal artery arising from the aorta. The artery 
divides into interlobar arteries, then arcuate arteries, interlobar branches, and eventually a single afferent 
arteriole.
• Clearance: The volume of blood that is completely cleared of that substance per unit of time
• Renal blood flow: 1200 mL/min
• Glomerular filtration rate: The volume of fluid filtered from the glomerular capillaries into Bowman 
capsule per unit of time. Inulin, which is completely filtered but not secreted or reabsorbed, is a good mea-
sure of GFR. Creatinine, however is more practical to measure but less accurate.
• Intrinsic regulation: Autoregulation occurs between mean arterial pressure of 80 and 180 mm Hg. Outside 
of the autoregulation limits, renal blood flow (RBF) becomes pressure dependent. Glomerular filtration 
generally ceases when mean systemic arterial pressure is less than 40 to 50 mm Hg.
• Tubuloglomerular balance and feedback: Whereas increased tubular flow tends to result in reduced GFR, 
decreases in tubular flow tend to result in increased GFR.
• Hormonal regulation: Increases in glomerular arteriolar pressure stimulate renin release, which cause arte-
rial vasoconstriction and reductions in RBF via angiotensin II. GFR is preserved through greater efferent 
arteriole constriction. Catecholamines increase afferent arteriolar tone, but GFR is preserved through renin 
release, angiotensin II formation, and prostaglandin synthesis (which is blocked by nonsteroidal antiinflam-
matory drugs [NSAIDs]).
RENAL PHYSIOLOGY AND ANESTHESIA 29-4
Renal Circulation
Severity of Kidney In jury According to Glomerula r Function
Crea tin ine Clea rance (mL/ min)
Normal 100–120
Decreased renal reserve 60–100
Mild renal impairment 40–60
Moderate renal insufficiency 25–40
Renal failure <25
End-stage renal disease1 <10
1This term applies to patients with chronic renal failure.
RENAL PHYSIOLOGY AND ANESTHESIA 29-5
Effects of Anesthesia and Surgery
• General: Reversible decreases