Evaluation of Poisoning and Drug

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Evaluation of Poisoning and Drug 
Overdose 
Kara Lynch, PhD, DABCC 
University of California San Francisco 
San Francisco, CA 
 
Learning Objectives 
• Understand the laboratories role in the diagnosis and 
treatment of toxicology cases 
• Review the pathophysiology of toxic exposures 
• Identify the common toxidromes 
• Calculate the osmolar gap and anion gap 
• Be able to recognize drug overdoses 
 
 
Paraclesus – “father of toxicology” 
• “All things are poison, and 
nothing is without poison; only 
the dose permits something 
not to be poisonous.” 
• “The dose makes the poison.” 
• substances considered toxic 
are harmless in small doses, 
and an ordinarily harmless 
substance can be deadly if 
over-consumed 
 Paraclesus, 1490 - 1541 
• A poisoning occurs when a person’s exposure 
to a natural or manmade substance has an 
undesirable effect - CDC 
• Poisonings can be classified as: 
– Self-harm or suicide 
– Assault or homicide 
– Unintentional or accidental, when no harm was 
intended – includes overdoses resulting from drug 
misuse, drug abuse or taking too much of a drug 
for medical reasons 
Definition of “Poisoning” 
• AAPCC – American Association of Poison 
Control Centers – 
– National poison data system (NPDS) annual report 
• DAWN – Drug Abuse Warning Network 
• SAMHSA World Drug Report – Substance 
Abuse and Mental Health Services 
Administration 
• CDC – Center for Disease Control – National 
Vital Statistics System (NVSS) 
Monitoring Poisonings 
Poisoning / Overdose Trends 
Poisoning / Overdose Trends 
AAPCC: Top 25 human exposures 
AAPCC: Top 25 pediatric exposures 
Increase in Exposure – Top 4 
• ABCs (airway, breathing, circulation) 
• Supportive Care 
• Antidote if available and indicated 
• Decontamination (surface and gastrointestional) 
– Wash skin and irrigate eyes, emesis or gastric lavage, 
activated charcoal or cathartic, whole-bowel irrigation 
• Enhanced Elimination 
– Hemodialysis 
– Hemoperfusion 
– Repeat-dose charcoal 
Poisoning: Treatment Approach 
• Airway → Endotracheal intubation 
– Check gag/cough reflex 
– Position patient 
– Clear/suction airway 
• Breathing → ventilatory failure, hypoxia, bronchospasm 
– Obtain arterial blood gases 
– Assist with bag/mask device 
– Give supplemental oxygen 
• Circulation → bradycardia, tachycardia, prolonged QRS 
interval, arrhythmias, hypotension, hypertension 
– Measure blood pressure/pulse 
– Monitor electrocardiogram 
– Start 1-2 IV lines 
– Obtain routine bloodwork 
Treatment: ABC’s or CAB 
Antidote or Specific Treatment 
Toxin Antidote/Treatment 
Acetaminophen N-Acetylcysteine (NAC, Mucomyst) 
Aluminum or Iron Deferoxamine 
Anticholinergic agents Physostigmine 
Arsenic and Mercury Unithiol, Dimercaprol (BAL), oral succimer (DMSA) 
Benzodiazepines Flumazenil 
Beta-blockers Glucagon 
Calcium channel blockers Calcium 
Carbon monoxide Oxygen (normobaric or hyperbaric) 
Cyanide Amyl nitrite, sodium nitrite, sodium tiosulfate 
Digoxin Digibind (Fab fragments) 
Ethylene glycol, methanol Ethanol, fomepizole (5-methylpyrazol), hemodialysis 
Isoniazid Pyridoxine (Vitamin B6) 
Lead Calcium EDTA, Dimercaprol (BAL), oral succimer (DMSA) 
Nitrites, nitrates Methylene blue 
Opioids Naloxone 
Salicylates Bicarbonate, hemodialysis, alkaline diuresis 
Poisoning Evaluation: toxidromes 
• Toxidrome = A collection of symptoms and 
signs that consistently occur after ingestion of 
a particular toxin or drug class 
• Often identified with a basic history and 
physical examination 
• Rapid identification of the toxidrome saves 
time in evaluating and managing a poisoned 
patient 
Poisoning Evaluation: toxidromes 
Kinetic Anatomy with Web Resource, 3rd Edition 
Toxidrome Clinical Manifestation Agents commonly involved 
Anticholinergic • Hypertermia, tachycadia, 
hypertension 
• Agitation, delirium, seizures 
• Mydriasis 
• Decreased bowel sounds 
• Nonselective antihistamines 
• Tricyclic antidepressants 
• Antipsychotic drugs 
• Benztropine 
• Scopolamine, atropine 
• Jimsonweed, deadly nightshade, 
amanita muscaria 
Cholinergic – 
Nicotinic / Muscarinic 
• Bradycardia(M), Tachycardia(N) 
• Hypertension (N) 
• Miosis 
• Bronchorrhea 
• Salivation, Lacrimation, 
Urination, Diarrhea, GI upset, 
Emesis – “SLUDGE” 
• Organophosphates, carbamates 
• Physostigmine 
• Pilocarpine 
• Betel nut 
• Mushrooms: clitocybe dealbata, 
C. illudens, Inocybe lacera 
• Black widow spider venom (N) 
Sympathomimetic • Hyperthermia, tachycardia, 
hypertension 
• Agitation, delirium, seizures 
• Mydriasis 
• Increased bowel sounds 
• Dry, flushed skin 
• Cocaine, amphetamines 
• Theophylline, caffeine 
• Salicylates 
• Monoamine oxidase (MAO) 
inhibitors 
• Sedative/hypnotic withdrawal 
Opioid • Hypopnea/bradypnea 
• Lethargy, obtundation 
• Miosis 
• All opiates and phenothiazines 
• Hypoglycemic agents 
• Clonidine 
Sedative-hypnotic • Hypothermia, bradypnea/ 
hypopenia 
• Lethargy, stupor, obtundation 
• Ethanol 
• Benzodiazepines, barbiturates 
• Meprobamate, methaqualone, 
chloral hydrate 
Blood 
Pressure 
Heart 
Rate 
Resp. 
Rate 
Temp. Pupil 
size 
Bowel 
sounds 
Diaph-
oresis 
Anticholinergic ↑ ↑ ↑ ↓ ↓ 
Cholinergic ↓ ↑ ↑ 
Opioid ↓ ↓ ↓ ↓ ↓ ↓ ↓ 
Sympathomimetic ↑ ↑ ↑ ↑ ↑ ↑ ↑ 
Sedative-hypnotic ↓ ↓ ↓ ↓ ↓ ↓ 
Poisoning Evaluation: toxidromes 
psychiatryonline.org 
Illicit Drugs: Mechanism of Action 
• Serum osmolality and calculation of the osmolar gap 
• Electrolytes for determination of sodium, potassium and 
anion gap 
• Serum glucose 
• BUN and creatinine for evaluation of renal function 
• Liver function tests 
• Complete blood count 
• Urinalysis to check for crystalluria, hemoglobinuria or 
myoglobinuria 
• Stat serum acetaminophen and serum ethanol level 
• Pregnancy test (females of childbearing age) 
• Electrocardiogram 
Essential Laboratory Tests 
Toxic Alcohols 
• Ethanol 
• Methanol 
• Isopropanol 
• Acetone 
• Ethylene glycol 
• First-order kinetics – rate of elimination is proportional to the 
amount of drug present 
• Zero-order kinetics – rate of elimination is constant regardless 
of the amount of drug present in the system 
• Capacity-limited kinetics – occurs when the rate of elimination 
shifts from first-order to zero-order based on the saturation of 
the elimination processes (overdoses) 
• Serum half-life – time required for serum concentrations to 
decrease by one half 
• First-pass effect – applies to drugs cleared by the liver before 
reaching systemic circulation 
• Steady-state – applies to repeated dosing; reached in about 4 
half-lives 
Pharmacokinetics: Review 
Toxic Alcohols: Ethanol 
• Ethanol or ethanol combined with other drugs 
accounts for the highest number of toxic 
exposures 
• Potent central nervous system depressant 
• Effects vary with concentration 
• Common cause of hyperosmolality in the ED 
• Metabolism follows zero-order kinetics 
 
Ethanol 
Acetate 
Acetaldehyde 
UGT 1A1 
UGT 2B7 SULTs 
Ethylsulfate (EtS) Ethylglucuronide (EtG) 
ADH1B 
ADH1C 
ALDH2 
CYP2E1 
Urine ~ 80 hours Urine ~ 80 hours 
Serum ~ 3.5 hours 
Ethanol Metabolism 
Ethanol Measurement 
• Enzymatic methods – alcohol dehydrogenase 
• CH3CH2OH CH3CHO 
 
 
• ADH is selective but not specific for ethanol, 
although current assays have minimal reactivity 
with non-ethanol alcohols 
• Other enzymes that involve NADH can potentially 
interfere (ie: lactate, LD) 
• Other methods - Headspace GC-MS 
 
NAD+ 
ADH 
NADH 340 nm 
• Toxicity if primarily related to metabolites:– Ethanol → Acetaldehyde → Acetate 
– Isopropanol → Acetone 
– Methanol → Formaldehyde → Formic Acid 
– Ethylene Glycol → Oxalate and Hippuric Acid 
• Effects: 
– Isopropanol (Acetone)- 2X more potent CNS 
depressant than ethanol, can cause upper GI bleeding 
– Methanol – can cause metabolic acidosis, blindness 
and death after a latent period of 6-30 hours 
– Ethylene glycol – same CNS depressant effects as 
ethanol but with toxic metabolites – myocardial 
depression and renal necrosis 
 
Other toxic alcohols 
Other toxic alcohols 
• measured Osmol – calc. Osmol = osmolal gap 
• Osmolality = 2(Na in mmol/L) + (Glucose in mg/dL / 18) + 
(BUN in mg/dL / 2.8) 
• Other contributors: 
– [ethanol] / 4.6 
– [methanol] / 3.2 
– [isopropanol] / 6.0 
– [ethylene glycol] / 6.2 
– [acetone] / 5.8 
• Causes: 
– Methanol 
– Ethylene Glycol 
– Diuretics 
– Isopropanol 
– Ethanol 
Osmolal Gap 
Anion Gap 
MUDPILES: 
 
• Methanol → formate 
• Uremia → chronic renal failure (impaired excretion of acids) 
• Diabetic Ketoacidosis – DKA (also AKA) → acetaldehyde → 
acetylCoA → B-hydroxybutyrate, acetoacetate 
• Paraldehyde, Phenformin, Propylene glycol 
• Isoniazide → lactic acidosis 2° to seizure activity OR Iron → 
lactic acidosis → uncoupling of oxidative phosphorylation 
• Lactate 
• Ethylene glycol → glyoxylate, glycolate, oxalate 
• Salicylates → ketones, lactate 
 
(Na+ + K+) – (Cl- + HCO3-) = 16 (range 10-20) 
Ingestion of Alcohols: Lab Findings 
Alcohol Osmolal 
Gap 
Metabolic Acidosis 
with anion gap 
Serum 
Acetone 
Urine Oxalate 
Ethanol + - - - 
Methanol + + - - 
Isopropanol + - + - 
Ethylene glycol + + - + 
• Healthy 50 year-old man was found unconscious in this 
home, believed to be down for ~24 hours 
• Emergency response – GCS 3, vitals normal, oxygen 
saturation 80%, patient intubated and brought to UCSF 
ED 
• Remarkable lab findings: HCO-3 5, osmolol gap and 
anion gap >35, pH 6.7, lactate above the ULOQ, 
creatinine 2.4 
• LFTs, tox screen, APAP and salicylate normal 
• Normal head and abdominal CT, all cultures negative 
no vasopressors required 
• Patient received IVFs and died before they could start 
dialysis 
Case Study 
Case Study 
• Ethanol, methanol or ethylene glycol? 
 
 
 
 
 
• Ethanol, methanol results negative 
• Ethylene glycol positive 162 mg/dL, range of 
toxic doses – 50 -775 mg/dL 
Case Study 
Alcohol Osmol 
Gap 
Metabolic Acidosis 
with anion gap 
Serum 
Acetone 
Urine Oxalate 
Ethanol + - - - 
Methanol + + - - 
Isopropanol + - + - 
Ethylene glycol + + - + 
• Analgesic and antipyretic 
• Peak concentrations – 4 hours post-ingestion 
• Normal half-life 2-3 hours; >4 hours hepatic 
toxicity; >12 hours hepatic coma likely 
• Acute liver damage threshold; adults 150-250 
mg/kg 
• Children under the age of 10 more resistant to 
toxicity 
• Measured by enzymatic / colorimetric methods 
• Antidote is N-acetylcysteine 
Acetaminophen (Tylenol) 
Acetaminophen: metabolism 
Acetaminophen: hepatic toxicity 
Salicylate (Aspirin) 
• Analgesic, antipyretic and anti-inflammatory 
• Therapeutic dose – single dose – 10 mg/kg; daily dose 
– 40-60 mg/kg 
• Mild intoxication – 150-200 mg/kg; severe intoxication 
– 300-500 mg/kg; chronic toxicity - >100 mg/kg/day 
• Lab results reveal mixed metabolic acidosis / 
respiratory alkalosis 
• Tinnitus, hyperthermia, hyperventilation, CNS 
• Measured by enzymatic / colorimetric methods 
• Treatment of salicylate overdose 
– Hydration, glucose, K+ supplements, bicarbonate, 
hemodialysis 
• Most common cause of fatal poisonings – smoke 
inhalation 
• Colorless, odorless, tasteless gas 
• Has 240x the affinity for hemoglobin than oxygen 
→ carboxyhemoglobin (COHb) 
• Symptoms begin at COHb levels of 10-20% and 
50% can be fatal 
• Nonsmokers – 1-2% COHb, smokers 5-6% COHb 
• Treatment: fresh air, 100% O2 or hyperbaric 
oxygen may be indicated 
Carbon Monoxide 
Wavelength (nm) 
A
bs
or
ba
nc
e 
→
 methemoglobin 
oxyhemoglobin 
reduced hemoglobin 
carboxyhemoglobin 
UV Absorption of Hb forms 
Comparison of absorbencies at different wavelengths allows estimation of the 
relative concentrations of different forms of hemoglobin 
beer-lambert law – A = ɛbc or A = ɛ1bc1 + ɛ2bc2 + ɛ3bc3 …. 
Lead Poisoning 
• Demyelinates nerve fibers 
• Inhibits Fe incorporation into 
heme 
• Chronic lead poisoning 
causes hypochromic anemia, 
with basophilic stippling 
• Treatment – chelation – EDTA 
• Laboratory Test – whole 
blood – ICP-MS, atomic 
absortion, anodic stripping 
voltammetry 
• Erythrocyte protoporphyrin is 
not sensitive to low level Pb 
exposure, but is a definitive 
marker of acute exposure source: www.aafp.org 
Iron Poisoning 
• Approximately 5,000 case per year – mostly children 
• Toxicity of related to the dose of elemental iron 
 
 
 
 
 
• Treatment: 
– Serial monitoring of serum iron 
– Obtain creatinine, electrolytes, hemoglobin, PT, LFTs and arterial 
blood gases 
– Calculate elemental iron dose ingestion; 20-60 mg Fe/kg 
moderate risk; >60 mg/kg high risk 
– <350 μg/dL and no symptoms – supportive care 
– >300 μg/dL and symptoms – deferoxamine infusion 
Compound Elemental Iron 
Ferrous sulfate (hydrate) 20% 
Ferrous fumarate 33% 
Ferrous gluconate 12% 
Ferrous chloride (hydrate) 28% 
Ferric chloride (hydrate) 20% 
1. Which toxidrome is characterized by Salivation, Lacrimation, 
Urination, Diarrhea, GI upset, Emesis – “SLUDGE”? 
a) Anticholinergic 
b) Cholinergic 
c) Sympatomemetic 
d) Sedative-hypnotic 
2. A blood ethanol concentration of 130 mg/dL will contribute how 
much to a serum osmolality? 
a) 2.8 mOsm/kg 
b) 3.5 mOsm/kg 
c) 28 mOsm/kg 
d) 35 mOsm/kg 
e) 280 mOsm/kg 
3. By what mechanism does N-acetylcystine help prevent hepatic 
damage in acetaminophen overdose? 
a) Blocks absorption of acetaminophen 
b) Provides a source of glutathione 
c) Prevents hepatic conjugation of acetaminophen 
d) Blocks acetaminophen receptors on hepatocytes 
e) Forms an in active complex with acetaminophen 
Self-Assessment Questions 
	Evaluation of Poisoning and Drug Overdose
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