anestesia total intravenosa

Prévia do material em texto

Total Intravenous Anesthesia in
Horses
Phillip Lerche, BVSc, PhD
KEYWORDS
� Alpha-2 adrenoceptor agonist � Ketamine � Guaifenesin � Midazolam � Horse
� Total intravenous anesthesia (TIVA)
KEY POINTS
� Total intravenous anesthesia (TIVA) is useful for procedures less than 60 minutes in dura-
tion to avoid accumulation of drugs leading to poorer recoveries.
� TIVA protocols use multiple drugs infused at the same time to provide unconsciousness,
muscle relaxation, and analgesia.
� Cardiorespiratory depression tends to be minimal during TIVA using clinically useful
doses.
� Recovery from TIVA is generally smooth and predictable.
INTRODUCTION
The sole use of intravenous (IV) drugs to induce and maintain anesthesia in the horse
(total intravenous anesthesia [TIVA]) is the most common means used to anesthetize
equids.1
TIVA has several benefits compared with inhalational anesthesia:
� Ease of use
� Reduced cost, because expensive anesthetic equipment is not required
� Useful to provide anesthesia distant from an oxygen source (field anesthesia)
� No requirement for scavenging, or risk of operator exposure to, anesthetic
inhalant gases
� Better cardiovascular function (higher cardiac index and arterial blood pressure)
� Lesser stress response
� Recovery is generally smoother and more predictable
TIVA also has disadvantages:
� Cumulative effects of IV drugs leading to weaker or poor-quality recoveries for
anesthetic episodes lasting longer than 1 hour
Department of Veterinary Clinical Sciences, The Ohio State University, 601 Vernon Tharp Street,
Columbus, OH 43210, USA
E-mail address: lerche.1@osu.edu
Vet Clin Equine 29 (2013) 123–129
http://dx.doi.org/10.1016/j.cveq.2012.11.008 vetequine.theclinics.com
0749-0739/13/$ – see front matter � 2013 Published by Elsevier Inc.
mailto:lerche.1@osu.edu
http://dx.doi.org/10.1016/j.cveq.2012.11.008
http://vetequine.theclinics.com
Lerche124
� Control of anesthetic depth is easier with inhalant anesthesia
� Oxygen supplementation is harder to provide under field anesthesia conditions
� Relies on liver metabolism for clearance
� Availability of IV drugs may be limited
THE IDEAL INJECTABLE ANESTHETIC DRUG
An ideal drug for TIVA in the horse would:
� Provide muscle relaxation, analgesia, and unconsciousness
� Be water soluble
� Not accumulate, being rapidly metabolized to inactive metabolites
� Be nontoxic to tissues
� Be free of side effects
� Allow a smooth recovery
� Be readily available
� Be economical to use.
However, the ideal injectable anesthetic drug does not exist. The equine anesthetist
therefore makes use of combinations of drugs, with an understanding of their pharma-
cology, to achieve these goals.
TECHNIQUES FOR TIVA IN HORSES
Pharmacokinetic and pharmacodynamic information on many of the drugs discussed
in this article are discussed in the article on balanced anesthesia and constant rate
infusions. At the time of writing, several of the drugs discussed in this article are
unavailable in some parts of the United States because of manufacturing and distribu-
tion issues.
INDUCTION OF ANESTHESIA
Regardless of the technique selected for maintenance of anesthesia, induction typi-
cally follows the same pattern. It is essential that all personnel involved understand
how to use any equipment that may be used (swing doors, ropes, tables, hoists) as
well as how to handle the horse as it transitions from the standing position to recum-
bency. The person controlling the horse’s head during this time has an essential job,
and should be familiar with the anesthetic induction process.
Adequate sedation of the horse before induction is paramount, and is usually
achieved with an alpha-2 adrenoceptor agonist, several of which are available
(Table 1).2–4 Signs of appropriate sedation are related to the muscle-relaxing and
sedative effects of this drug class. Muscle relaxation, which may be less noticeable
with romifidine, leads to ataxia, a wide-based stance, knuckling at the carpal joints,
lowering of the head, and drooping of the lip, whereas sedation leads to a decreased
Table 1
Alpha-2 agonists used for preanesthetic medication in horses
Drug Dose
Xylazine 0.4–1.1 mg/kg, IV
Detomidine 0.005–0.03 mg/kg, IV
Romifidine 0.06–0.1 mg/kg, IV
Total Intravenous Anesthesia in Horses 125
level of responsiveness to external stimuli. Alpha-2 agonist drugs also provide
analgesia.5
Sedation can be enhanced by combining an alpha-2 agonist with the opioid anal-
gesic butorphanol (0.04 mg/kg IV). Butorphanol and the alpha-2 agonists are water
soluble and can be combined in 1 syringe for ease of administration.
Anesthesia in horses is typically induced with ketamine, a dissociative anesthetic
agent with analgesic properties attributed to its action as an N-methyl-D-aspartate
(NMDA) receptor antagonist. A benzodiazepine (midazolam, diazepam) can be added
to ketamine to provide additional muscle relaxation, because muscle rigidity may be
seen following induction of anesthesia with ketamine. As an alternative, the muscle
relaxant guaifenesin can be delivered to good effect before ketamine is administered
(Table 2).
The length of surgical time following anesthesia with a single dose of ketamine is up
to 15 minutes, allowing short procedures to be completed without need for additional
drug administration in most horses. Recovery from an alpha-2 adrenoceptor agonist
plus ketamine induction is typically smooth, and occurs within 20 to 25 minutes.
Tiletamine and zolazepam (Telazol, Fort Dodge) are longer-lasting dissociative and
benzodiazepine drugs that produce similar effects to ketamine combinedwith a benzo-
diazepine. Recovery is usually similar to that seen after ketamine, although sometimes
less coordinated.6
SHORT-TERM TIVA (20 TO 30 MINUTES)
Following a single-dose injectable protocol, it is possible that a procedure may last
longer than anticipated, or that the useful anesthetic duration is shorter than expected
(the horse returns to consciousness more rapidly than expected). Anesthesia can be
extended by administering one-third to one-half of the original doses of alpha-2 and
ketamine. This dose can be repeated as needed, but multiple redosing usually leads
to longer recovery times.7
LONG-TERM TIVA (UP TO 60 MINUTES)
For procedures lasting up to an hour in which TIVA is used, the equine anesthetist
usually administers an infusion of combined drugs (coinfusion) to maintain anesthesia.
This technique is advantageous because it decreases the peaks and troughs of high
and low plasma concentrations of the drugs being infused. By providing a constant
plasma concentration once steady state has been reached, toxicity (peaks) and inad-
equate anesthetic depth (troughs) are avoided.
KETAMINE-BASED PROTOCOLS
Combinations of an alpha-2 agonist, ketamine, and guaifenesin have been in general
use for TIVA in horses for more than 25 years. The first combination reported,
Table 2
Drugs that provide muscle relaxation used with ketamine (2.2 mg/kg IV) for anesthetic
induction
Drug IV Dose (mg/kg) Note
Diazepam 0.04–0.1 mg/kg, IV Combined in the same syringe as ketamine
Midazolam 0.04–0.1 mg/kg, IV
Guaifenesin 35–50 mg/kg, IV Ketamine is given as soon as the horse shows signs of
marked ataxia (frequent knuckling at the carpus joints)
Lerche126
guaifenesin, ketamine, and xylazine (GKX) is frequently referred to as triple drip.8 It is
essential that guaifenesin is infused intravenously, and it is recommended that an
indwelling intravenous catheter be used because guaifenesin can cause tissue irrita-
tion and sloughing if inadvertent extravascular administration occurs. It is important
to recognize that the infusion rates that are required to maintain anesthesia may
vary with individual horses and with different procedures. Frequent monitoring of
patient status (discussed later) and adjustment of infusion rate accordingly is
essential.
Availability of other alpha-2 agonists for use in horses has led to other protocols
being used, and the term triple drip issometimes applied to all of these protocols.
Triple drip using detomidine may be abbreviated as GKD (guaifenesin, ketamine,
and detomidine)9 and, likewise, when romifidine is part of the protocol, the abbrevia-
tion is GKR (Table 3).10
Guaifenesin formulated at concentrations greater than 10% in water or 5%
dextrose solutions may cause hemolysis (leading to hemoglobinuria) and the
delayed complication of venous thrombosis. Stabilized 15% guaifenesin solutions
are available in some countries and are less likely to cause these problems, although
thrombosis may still occur.11 The availability of commercially prepared guaifenesin
in the United States has been limited. Practitioners must therefore either prepare
solutions themselves or contract with a pharmacy willing to compound it. A TIVA
infusion using midazolam in place of guaifenesin has been evaluated (MKX).12
Moderate to marked ataxia after standing was a common finding in this study,
most likely attributable to midazolam concentrations. The authors recommend using
a reduced concentration of midazolam (see Table 3). Protocols using xylazine and
ketamine alone at various doses to maintain anesthesia in horses for up to one
hour has been described (Mama 2005).13 However these horses may need oxygen
Table 3
Protocols for TIVA infusions
TIVA Preparation Final Concentrations
Infusion Rate
(mL/kg/h)
GKX Add 250mg xylazine and 500–1000 mg ketamine
to 500 mL of 5% guaifenesina
G: 50 mg/mL
K: 1–2 mg/mL
X: 0.5 mg/mL
1.5
GKD Add 10 mg detomidine and 500–1000 mg of
ketamine to 500 mL of 5% guaifenesina
G: 50 mg/mL
K: 1–2 mg/mL
D: 20 mg/mL
1.2–1.6
GKR Add 40 mg romifidine and 3.3 g ketamine to
500 mL of 5% guaifenesina,b
G: 50 mg/mL
K: 6.6 mg/mL
R: 80 mg/mL
1
MKX Add 25 mg midazolam,c 650 mg ketamine and
325 mg xylazine to 500 mL of 0.5% salined
M: 0.05 mg/mL
K: 1.3 mg/mL
X: 0.65 mg/mL
1.6
Abbreviation: MKX, midazolam, ketamine, and xylazine.
a When using 500mL of 10% guaifenesin as the basis, drugs added should be doubled, leading
to final concentrations that are doubled, and infusion rate will be halved.
b The concentration of romifidine is slightly lower than the original report (80 mg/mL versus
82.5 mg/mL). A higher concentration of guaifenesin was administered for the first 30 minutes in
the original report.
c Diazepam can NOT be substituted for midazolam because diazepam is not water soluble and
may result in the formation of a precipitate.
d The final concentrations have been modified from the original report; see text for details.
Total Intravenous Anesthesia in Horses 127
supplementation. The use of ketamine alone does not provide satisfactory anes-
thesia and is not recommended.
PROPOFOL
Propofol is a rapidly acting, non-barbiturate, anesthetic agent that is rapidly redistrib-
uted and cleared from the plasma by hepatic metabolism. Propofol has also demon-
strated extrahepatic clearance that likely occurs in pulmonary and renal tissues. This
pharmacokinetic profile makes it a potentially useful drug for maintaining anesthesia
as it is rapidly redistributed and cleared so that rapid changes in depth of anesthesia
via titration are easily achieved, particularly in species other than horses. Additionally,
these same properties allow for a rapid recovery following a single dose or continuous
infusion of propofol, and recoveries are typically very smooth.14 However, in clinical
use with horse, TIVA with propofol has variable kinetics and its quality of anesthesia
may not be as reliable.15 Loss of response to noxious stimuli (surgery) may not occur
and increasing the dose may result in involuntary muscle movements (myclonus or
dystonia).
Propofol is unlikely to replace ketamine for adult or large horses for field anesthesia
as large volumes (up to 200ml) are required and induction, even with the use of alpha-2
agonists, often results in dangerous excitement of horses.16 Additionally hypoventila-
tion can be seen following propofol induction, which, while usually transient, can be
problematic if it persists and an oxygen source is not present. It is recommended
that oxygen supplementation be available when using propofol in horses.
OTHER DRUGS
Several other anesthetic drugs have been investigated as components of TIVA in
horses, including medetomidine, tiletamine, and climazolam. For further reading and
review of all the methods that have been used to provide TIVA in horses, the reader
is directed elsewhere.1
MONITORING DURING TIVA
Given that most TIVA procedures occur in the field, it is usually not possible to monitor
patients as invasively as in the clinic setting. At a minimum, depth of anesthesia, heart
rate, and respiratory rate should be monitored closely.
Signs of central nervous system activity (eye position and palpebral reflexes) are
often difficult to interpret. Horses’ eye signs can remain active during TIVA, particularly
with protocols using ketamine, and it is common to see tear production and sponta-
neous blinking.
Signs that the anesthetic plane is getting lighter usually include an increase in respi-
ratory rate and depth, and increasing activity of the eyeball (eg, slow nystagmus pro-
gressing to rapid nystagmus) and palpebral reflex (eg, slight response progressing to
spontaneous blinking). Physical movement of limbs and stretching or tensing of the
neck also indicate a plane of anesthesia that is too light to allow the procedure to
continue without potential injury to the horse or personnel. The plane of anesthesia
is typically deepened by either increasing the infusion rate or giving additional boluses
of ketamine. In addition, TIVA can be augmented with local anesthetic techniques,
such as intratesticular lidocaine for castrations.
Anesthesia that is too deep can have any of the following signs: rapid shallow
breathing that progresses to apnea or a pattern of Cheyne-Stokes breathing (deeper
and sometimes faster breathing followed by a gradual decrease until a temporary
Lerche128
apnea occurs, and then cycles again), pulses that are difficult to palpate, and dull eye
signs (absent palpebral reflex, centrally positioned globe, absent corneal reflex). Anes-
thetic plane can be decreased by slowing or stopping the infusion until the appropriate
depth has been achieved.
Portable physiologic parameter monitors are available and can be used to supple-
ment physical signs when monitoring horses anesthetized with TIVA. Pulse oximetry
can be used to determine pulse rate and the need for oxygen supplementation.
Portable electrocardiogram and indirect blood pressure monitors can also be used,
particularly in field situations involving critically ill horses.
RECOVERY
Recovery from TIVA relies on redistribution of the drugs away from the central nervous
system and metabolism. As plasma concentrations decrease, the level of conscious-
ness of the patient increases until the horse makes a successful attempt to stand.
Recovery from TIVA lasting less than 60 minutes is generally smooth and predict-
able. Longer durations of infusions lead to accumulation of drugs, longer times to
recovery, and a less predictable course of achieving the standing position (additional
information can be found in the article on recovery elsewhere in this issue).
PARTIAL INTRAVENOUS ANESTHESIA
Any of the intravenous infusion combinations can also be given during inhalant anes-
thesia. This technique, which is designed to allow reduction in dose of both injectables
and inhalant, thus minimizes the side effects of both, and is referred to as balanced
anesthesia, or partial intravenous anesthesia (PIVA).
Anesthetic infusions can be administered at up to one-tenth to one-quarter of the
standard TIVA doses, which decreases the likelihood of decreased metabolism and
drug accumulation during an inhalant anesthetic lasting several hours. It is essential
that patients, as well as the rate of intravenous drug administration, be monitored
closely to ensure that the depth of anesthesia does not become excessive. It is also
possible thatsome drug effects are additive, as opposed to being minimized (eg,
respiratory depression from ketamine and inhalant anesthetic).
The concentration of inhalant required to maintain an adequate depth of anesthesia
can also be decreased by concurrent infusion of other drugs, such as lidocaine,
opioids, alpha-2 agonists, and subanesthetic doses of ketamine (see the article on
balanced anesthesia and constant rate infusions).
SUMMARY
TIVA is the mainstay of field anesthesia in horses, because cardiorespiratory depres-
sion is mild at clinically useful doses, and recovery is smooth in most horses. Drug
components are selected to provide unconsciousness, muscle relaxation, and anal-
gesia, and TIVA may induce a lesser stress response than inhalant anesthesia. With
an attentive, careful anesthetist, TIVA provides predictable and safe anesthesia for
procedures lasting up to 60 minutes.
REFERENCES
1. Muir WW, Hubbell JA. Equine anesthesia. 2nd edition. St Louis (MO): Saunders
Elsevier; 2009. p. 260–76.
2. Muir WW, Skarda RT, Milne DW. Evaluation of xylazine and ketamine hydrochlo-
ride for anesthesia in horses. Am J Vet Res 1977;38:195–201.
Total Intravenous Anesthesia in Horses 129
3. Clarke KW, Taylor PM, Watkins SB. Detomidine/ketamine anaesthesia in the
horse. Acta Vet Scand Suppl 1986;82:167–79.
4. Kerr CL, McDonnell WN, Young SS. A comparison of romifidine and xylazine
when used with diazepam/ketamine for short-duration anesthesia in the horse.
Can Vet J 1996;37:601–9.
5. Valverde A. Alpha-2 agonists as pain therapy in horses. Vet Clin North Am Equine
Pract 2010;26(3):515–32.
6. Hubbell JA, Bednarski RM, Muir WW. Xylazine and tiletamine-zolazepam anes-
thesia in horses. Am J Vet Res 1989;50:737–42.
7. McCarty JE, Trim CM, Ferguson D. Prolongation of anesthesia with xylazine, ket-
amine and guaifenesin in horses: 64 cases (1986-1989). J Am Vet Med Assoc
1990;197:1646–50.
8. MuirWW, SkardaRT, SheehanW. Evaluation of xylazine, guaifenesin, and ketamine
hydrochloride for restraint in horses. Am J Vet Res 1978;39:1274–8.
9. Taylor PM, et al. Total intravenous anaesthesia in ponies using detomidine,
ketamine and guaifenesin: pharmacokinetics, cardiopulmonary and endocrine
effects. Res Vet Sci 1995;59:17–23.
10. McMurphy RM, et al. Comparison of the cardiopulmonary effects of anesthesia
maintained by continuous infusion of romifidine, guaifenesin and ketamine, with
anesthesia maintained by inhalation of halothane in horses. Am J Vet Res
2002;63:1655–61.
11. Hall LW, Clarke KW, Trim CM. Veterinary anaesthesia. 10th edition. London: Saun-
ders; 2001. p. 174–5.
12. Hubbell JA, et al. Evaluation of a midazolam-ketamine-xylazine infusion for total
intravenous anesthesia in horses. Am J Vet Res 2012;73:470–5.
13. Mama KR, Wagner AE, Steffey EP, et al. Evaluation of xylazine and ketamine for
total intravenous anesthesia in horses. Am J Vet Res 2005;66(6):1002–7.
14. Nolan AM, Hall LW. Total intravenous anesthesia in the horse with propofol.
Equine Vet J 1985;17:394–8.
15. Boscan P, Rezende ML, Grimsrud K, et al. Pharmacokinetic profile in relation to
anaesthesia characteristics after a 5% micellar microemulsion of propofol in the
horse. Br J Anaesth 2010;104(3):330–7.
16. Mama KR, Steffey EP, Pascoe PJ. Evaluation of propofol for general anesthesia in
premedicated horses. Am J Vet Res 1996;57(4):512–6.
	Total Intravenous Anesthesia in Horses
	Key Points
	Introduction
	The ideal injectable anesthetic drug
	Techniques for TIVA in horses
	Induction of anesthesia
	Short-term TIVA (20 to 30 minutes)
	Long-term TIVA (up to 60 minutes)
	Ketamine-based protocols
	Propofol
	Other drugs
	Monitoring during TIVA
	Recovery
	Partial intravenous anesthesia
	Summary
	References