Toxicology: A Practical Approach Lou Hampers, MD Pediatric Emergency Medicine The Children’s Hospital Denver, CO Thanks to: Carl Baum MD Toxikon Cook County Hosp. Chicago, IL

Toxicology: the ABCs Airway Breathing Circulation Diagnosis Decontamination Enhanced removal

Diagnosis What? How much? When? Containers PoisIndex and Pill ID Avoid PDR How much? Assume largest amount When?

Diagnosis Pupils Constricted sympatholytics cholinergics barbiturates opiates PCP ethanol / sedative-hypnotics other: heatstroke; pontine or subarachnoid hemorrhage

Diagnosis Pupils Dilated sympathomimetics anticholinergics

Toxidromes: anticholinergic Diagnosis Toxidromes: anticholinergic Mad as a hatter Red as a beet Hot as a hare Blind as a bat Dry as a bone

Toxidromes: cholinergic Diagnosis Toxidromes: cholinergic muscarinic Salivation Lacrimation Urination Defecation GI motility nicotinic tachycardia, hypertension fasciculations, paralysis

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

Diagnosis Elevated anion gap Are organic acids present? gap = Na - Cl - CO2 (normal = 8 - 12 meq/L)

Diagnosis Elevated anion gap Alcohol (but not isopropyl!) Tolulene Methanol Uremia Diabetes mellitus Paraldehyde Iron, Isoniazid Lactic acidosis Ethylene glycol Salicylates, Strychnine

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

Diagnosis “Tox screen” Plasma/Serum Urine 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

Diagnosis Abdominal xrays “Bet-a-chip” Barium Enteric coated tablets Tricyclics Antihistamines Chloral hydrate, Cocaine, Condoms Heavy metals Iodides Potassium, Phenothiazines

Decontamination Universal Antidote Burned toast Milk of magnesia Strong tea

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

Decontamination Gastric lavage Indications Contra-indications removal of ingested material administration of charcoal/cathartics Contra-indications obtunded/comatose/convulsing corrosives (?)

Decontamination Activated charcoal Indications Contra-indications numerous poisons, except some which are not well adsorbed: alcohols, alkalis, acids CN, Fe, K, Li, Pb Contra-indications ileus/obstruction corrosives (endoscopy)

Decontamination Repeat-dose charcoal Cathartics Whole Bowel Irrigation some anti-convulsants salicylates theophylline Cathartics magnesium citrate (4 ml/kg) use with caution in children < 2 years Whole Bowel Irrigation

Enhanced Elimination Methods Urinary Hemodialysis Hemoperfusion Peritoneal dialysis Multi-dose charcoal Whole bowel irrigation

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

Acetaminophen History When? Acute or chronic? How much? Physical dosage? 80, 160, 325, 500, 650? toxic: >150 mg/kg Physical Nausea, emesis

Acetaminophen Acetaminophen NAPQI is hepatotoxic Sulfate, Glucuronide (major) NAPQI (minor) NAPQI is hepatotoxic Glutathione detoxifies NAPQI

Acetaminophen Laboratory Acetaminophen (draw after 4 h) AST, ALT, PT may increase, but after 24 h Bili, Ammonia may also increase

Rumack-Matthew Nomogram Acetaminophen Rumack-Matthew Nomogram 200 150 mcg/ml 4 h

Acetaminophen Treatment Glutathione substitute Precursor for sulfate Antioxidant

N-acetylcysteine (NAC, Mucomyst®) 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

Methanol, Ethylene Glycol Alcohols and Glycols Methanol, Ethylene Glycol alcohol dehydrogenase Organic Acids

Alcohols and Glycols History Lethargy, ataxia Physical Hypothermia Respiratory depression CNS depression (“intoxication”)

Alcohols and Glycols Laboratory Check d-stick Check anion and osm gap Send out methanol or ethylene glycol level

Alcohols and Glycols Treatment Provide supportive care Block formation of toxic metabolites Dialysis

Alcohols and Glycols Treatment Ethanol block Dialysis level (osm gap) > 20 mg/dl Dialysis level (osm gap) > 50 mg/dl

Alcohols and Glycols 4-methylpyrazole (fomepizole, Antizol™)

Hydrocarbons Aromatics: systemic toxicity benzene, toluene, xylene Aliphatics: aspiration hazard gasoline, kerosene, lamp oil Hx or PE significant for cough, dyspnea, fever, cyanosis, rales

Hydrocarbons Aromatics Aliphatics remove via NG if > 1 ml/kg do not remove unless > 5 ml/kg clinical/radiographic signs of pneumonitis may be delayed antibiotics, steroids not helpful

Iron How much? Vitamins + Fe rarely a problem Prenatal iron can be lethal Ipecac: home-management of > 20 mg/kg

Iron History Within 2 h: GI symptoms 6-24 h: fever, metabolic acidosis, hepatic impairment, seizures, shock and coma

Iron Laboratory Serum Fe level at 2 h CBC, electrolytes if symptomatic 6 h to r/o delayed absorption CBC, electrolytes if symptomatic Consider KUB to r/o radio-opaque tablets or bezoar

Iron Treatment Consider whole bowel irrigation 25 ml/kg/h Deferoxamine if serum Fe > 500 mg/dl 15 mg/kg/h

Salicylates History Physical Various forms of salicylates Hyperthermia Deep, rapid respirations Emesis, dehydration Coma, seizures

Salicylates Laboratory Initial respiratory alkalosis Later metabolic acidosis Platelet, coag dysfunction Hyper- or hypoglycemia

Salicylates Laboratory Peak serum levels @ 2 to 6 hours Symptomatic > 50 mg/dl Potentially fatal > 100 mg/dl Nomogram not helpful

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

Salicylates Laboratory Consider multi-dose charcoal Consider dialysis for levels > 100 mg/dl

Tricyclic Antidepressants Mechanisms Therapeutic anticholinergic effects inhibition of neurotransmitter reuptake stabilization of membranes

Tricyclic Antidepressants Mechanisms Overdose therapeutic mechanisms are seen inhibition of fast Na channels membrane-depressant effects cardiac toxicity

Tricyclic Antidepressants Physical Abrupt decompensation Tachycardia, dysrhythmias Sedation, seizures

Tricyclic Antidepressants Laboratory ECG may reveal QRS > 100 msec predicts toxicity other ECG abnormalities seen TCA levels not clinically useful

Tricyclic Antidepressants Treatment Anticipate dysrhythmias, respiratory failure and ARDS Ipecac: NO! Give charcoal (via NG prn)

Tricyclic Antidepressants Treatment If QRS prolongation or refractory hypotension: serum alkalinization (pH 7.45-7.55)

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

Fun with Mnemonics Hyperthermia NASA NMS, Nicotine Antihistamines Salicylates, Sympathomimet. Anticholinergics, Antidepressants Hypothermia COOLS CO Opiates Oral hypogly. (insulin) Liquor Sed-hypnotics

Fun with Mnemonics Tachycardia FAST Free base Anticholinergics, Amphetamines Sympathomim., Solvent Theophylline Bradycardia PACED Propranolol Anticholin’ase Clonidine, CCBs Ethanol Digoxin

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)

Fun with Mnemonics Hypertension CT SCAN Cocaine Thyroid, Theoph. Sympathomim. Caffeine Anticholinergics Nicotine Hypotension CRASH Clonidine, CCBs Reserpine Antidepressants Sed-hypnotics Heroin

Fun with Mnemonics Seizures OTIS CAMPBELL Organophosphates Tricyclics INH, Insulin Sympathomim. Camphor, Cocaine Amphetamines Methylxanthines PCP Benzo withdrawl Ethanol withdrawl Lithium, Lidocaine Lead, Lindane

Non-toxic Ingestions Antibiotics Baby oil Bleach Cigarettes Cologne Contraceptive pills Cosmetics Detergent Glue Hydrogen peroxide Laxatives Paint Rat poison Shampoo Thermometers Vitamins