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Toxicology:A Practical Approach
Lou Hampers, MDPediatric Emergency Medicine
The Children’s Hospital
Denver, CO
Thanks to:
Carl Baum MDToxikonCook County Hosp.Chicago, IL
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Toxicology: the ABCs
• Airway
• Breathing
• Circulation
• Diagnosis
• Decontamination
• Enhanced removal
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Diagnosis
• What?– Containers– PoisIndex and Pill ID– Avoid PDR
• How much?– Assume largest amount
• When?
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Diagnosis
Pupils
• Constricted• sympatholytics• cholinergics• barbiturates• opiates• PCP• ethanol / sedative-hypnotics• other: heatstroke; pontine or subarachnoid
hemorrhage
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Diagnosis
Pupils
• Dilated• sympathomimetics• anticholinergics
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Diagnosis
Toxidromes: anticholinergic• Mad as a hatter
• Red as a beet
• Hot as a hare
• Blind as a bat
• Dry as a bone
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Diagnosis
Toxidromes: cholinergic• muscarinic
• Salivation• Lacrimation• Urination• Defecation• GI motility
• nicotinic• tachycardia, hypertension• fasciculations, paralysis
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Diagnosis
Odors
• arsenic, organophosphates, thallium: garlic• chloral hydrate, paraldehyde: pear• chloroform, isopropyl alcohol: acetone• cyanide (only 50% can detect): almond• methylsalicylate: oil of wintergreen• naphthalene, paradichlorbenzene: mothball• water hemlock: carrot
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Diagnosis
Elevated anion gap
• Are organic acids present?
gap = Na - Cl - CO2
(normal = 8 - 12 meq/L)
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Diagnosis
Elevated anion gap• Alcohol (but not isopropyl!)• Tolulene• Methanol• Uremia• Diabetes mellitus• Paraldehyde• Iron, Isoniazid• Lactic acidosis• Ethylene glycol• Salicylates, Strychnine
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Diagnosis
Elevated osmolal gap
• What is the difference between what is measured and
what is calculated?
2 (Na) + glucose/18 + BUN/2.8 [calculated osm]
+ Methanol/2.8
+ Ethanol/4.3
+ Ethylene Glycol/5.0
+ Isopropanol/5.9
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Diagnosis
“Tox screen”
• Plasma/Serum • good for levels of selected substances
– Acetaminophen, ASA, CO, CBZ, Dig, DPH, EtOH, Fe, Li, Phenobarb, Theo
• avoid comprehensive (send-out)
• Urine• good for drugs of abuse screen (in-house)
– amphetamines, barbs, benzodiazepines, cocaine, cannabinoids, opiates, pcp
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Diagnosis
Abdominal xrays
“Bet-a-chip”Barium
Enteric coated tablets
Tricyclics
Antihistamines
Chloral hydrate, Cocaine, Condoms
Heavy metals
Iodides
Potassium, Phenothiazines
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Decontamination
Universal Antidote
• Burned toast
• Milk of magnesia
• Strong tea
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Decontamination
Emesis (ipecac)
• Indications (not many!)• home-management of Fe, Li, K
• Contra-indications• obtunded/comatose/convulsing• likelihood of rapid progression
– TCA, camphor, cocaine, INH• corrosives• petroleum distillates
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Decontamination
Gastric lavage
• Indications• removal of ingested material• administration of charcoal/cathartics
• Contra-indications• obtunded/comatose/convulsing• corrosives (?)
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Decontamination
Activated charcoal
• Indications• numerous poisons, except some which are not well
adsorbed:• alcohols, alkalis, acids• CN, Fe, K, Li, Pb
• Contra-indications• ileus/obstruction• corrosives (endoscopy)
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Decontamination
• Repeat-dose charcoal• some anti-convulsants• salicylates• theophylline
• Cathartics• magnesium citrate (4 ml/kg)• use with caution in children < 2 years
• Whole Bowel Irrigation
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Enhanced Elimination
Methods
• Urinary
• Hemodialysis
• Hemoperfusion
• Peritoneal dialysis
• Multi-dose charcoal
• Whole bowel irrigation
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Enhanced Elimination
Specific “Antidotes”• Acetaminophen N-acetylcysteine• COHb oxygen, HBO• Digoxin Fab• Ethylene Glycol EtOH, dialysis• Iron deferoxamine• Lithium fluids, dialysis• Methanol EtOH, dialysis• Salicylate alkalinization, dialysis• Theophylline repeat AC, hemoperfusion
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Acetaminophen
History• When? Acute or chronic? • How much?
– dosage? 80, 160, 325, 500, 650?– toxic: >150 mg/kg
Physical• Nausea, emesis
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Acetaminophen
• AcetaminophenSulfate, Glucuronide (major)
NAPQI (minor)
• NAPQI is hepatotoxic
• Glutathione detoxifies NAPQI
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Acetaminophen
Laboratory
• Acetaminophen (draw after 4 h)
• AST, ALT, PT may increase, but after 24 h
• Bili, Ammonia may also increase
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Acetaminophen
Rumack-Matthew Nomogram
200
150
mcg/ml
4 h
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Acetaminophen
Treatment
• Glutathione substitute
• Precursor for sulfate
• Antioxidant
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Acetaminophen
N-acetylcysteine (NAC, Mucomyst®)
• Dilute to 5%, cover, on the rocks!• Load: 140 mg/kg po• Maint: 70 mg/kg po q 4 h x 17 doses• Premedicate with antiemetics prn• Follow LFTs, PT
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Alcohols and Glycols
Methanol, Ethylene Glycol
alcohol dehydrogenase
Organic Acids
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Alcohols and Glycols
History
• Lethargy, ataxia
Physical
• Hypothermia
• Respiratory depression
• CNS depression (“intoxication”)
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Alcohols and Glycols
Laboratory
• Check d-stick
• Check anion and osm gap
• Send out methanol or ethylene glycol level
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Alcohols and Glycols
Treatment
• Provide supportive care
• Block formation of toxic metabolites
• Dialysis
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Alcohols and Glycols
Treatment
• Ethanol block– level (osm gap) > 20 mg/dl
• Dialysis– level (osm gap) > 50 mg/dl
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Alcohols and Glycols
4-methylpyrazole (fomepizole, Antizol™)
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Hydrocarbons
• Aromatics: systemic toxicity– benzene, toluene, xylene
• Aliphatics: aspiration hazard– gasoline, kerosene, lamp oil– Hx or PE significant for cough, dyspnea,
fever, cyanosis, rales
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Hydrocarbons
• Aromatics– remove via NG if > 1 ml/kg
• Aliphatics– do not remove unless > 5 ml/kg– clinical/radiographic signs of pneumonitis
may be delayed– antibiotics, steroids not helpful
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Iron
How much?
• Vitamins + Fe rarely a problem
• Prenatal iron can be lethal
• Ipecac: home-management of
> 20 mg/kg
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Iron
History
• Within 2 h: GI symptoms
• 6-24 h: fever, metabolic acidosis, hepatic impairment, seizures, shock and coma
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Iron
Laboratory
• Serum Fe level at 2 h – 6 h to r/o delayed absorption
• CBC, electrolytes if symptomatic
• Consider KUB to r/o radio-opaque tablets or bezoar
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Iron
Treatment
• Consider whole bowel irrigation– 25 ml/kg/h
• Deferoxamine if serum Fe > 500 mg/dl– 15 mg/kg/h
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Salicylates
History• Various forms of salicylates
Physical• Hyperthermia• Deep, rapid respirations• Emesis, dehydration• Coma, seizures
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Salicylates
Laboratory
• Initial respiratory alkalosis
• Later metabolic acidosis
• Platelet, coag dysfunction
• Hyper- or hypoglycemia
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Salicylates
Laboratory
• Peak serum levels @ 2 to 6 hours
• Symptomatic > 50 mg/dl
• Potentially fatal > 100 mg/dl
• Nomogram not helpful
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Salicylates
Treatment
• Lower temperature (sponging)• Correct fluid losses, hypoglycemia• Correct prolonged PT with Vitamin K• Urine alkalinization (> pH 7.5)
– shortens half-life via ion trapping– may need potassium
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Salicylates
Laboratory
• Consider multi-dose charcoal
• Consider dialysis for levels > 100 mg/dl
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Tricyclic Antidepressants
Mechanisms
Therapeutic
• anticholinergic effects
• inhibition of neurotransmitter reuptake
• stabilization of membranes
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Tricyclic Antidepressants
Mechanisms
Overdose
• therapeutic mechanisms are seen
• inhibition of fast Na channels– membrane-depressant effects– cardiac toxicity
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Tricyclic Antidepressants
Physical
• Abrupt decompensation
• Tachycardia, dysrhythmias
• Sedation, seizures
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Tricyclic Antidepressants
Laboratory
• ECG may reveal QRS > 100 msec– predicts toxicity– other ECG abnormalities seen
• TCA levels not clinically useful
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Tricyclic Antidepressants
Treatment
• Anticipate dysrhythmias, respiratory failure and ARDS
• Ipecac: NO!
• Give charcoal (via NG prn)
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Tricyclic Antidepressants
Treatment
If QRS prolongation or refractory hypotension:
• serum alkalinization
(pH 7.45-7.55)
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Tricyclic Antidepressants
Serum Alkalinization
bolus Na bicarb 1-2 mEq/kg
• increase extracellular Na may reverse membrane depression
• alkaline pH may stabilize ion channels
• hyperventilation not as effective
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Fun with Mnemonics
Hyperthermia
NASA• NMS, Nicotine• Antihistamines• Salicylates,
Sympathomimet.• Anticholinergics,
Antidepressants
Hypothermia
COOLS• CO• Opiates• Oral hypogly.
(insulin)• Liquor• Sed-hypnotics
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Fun with Mnemonics
Tachycardia
FAST• Free base• Anticholinergics,
Amphetamines• Sympathomim.,
Solvent• Theophylline
Bradycardia
PACED• Propranolol• Anticholin’ase• Clonidine, CCBs• Ethanol• Digoxin
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Fun with Mnemonics
Rapid Respirations
PANT• PCP, Paraquat,
Pneumonitis• ASA• Noncardio. PE• Toxin-induced
metabolic acid.
Slow Respirations
SLOW• Sed-hypnotics• Liquor• Opiates• Weed (marijuana)
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Fun with Mnemonics
Hypertension
CT SCAN• Cocaine• Thyroid, Theoph.• Sympathomim.• Caffeine• Anticholinergics• Nicotine
Hypotension
CRASH• Clonidine, CCBs• Reserpine• Antidepressants• Sed-hypnotics• Heroin
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Fun with MnemonicsSeizures
OTIS CAMPBELL
• Organophosphates• Tricyclics• INH, Insulin• Sympathomim.• Camphor, Cocaine• Amphetamines
• Methylxanthines• PCP• Benzo withdrawl• Ethanol withdrawl• Lithium, Lidocaine• Lead, Lindane
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Non-toxic Ingestions
• Antibiotics• Baby oil• Bleach• Cigarettes• Cologne• Contraceptive pills• Cosmetics• Detergent
• Glue• Hydrogen peroxide• Laxatives• Paint• Rat poison• Shampoo• Thermometers• Vitamins