Toxicology:A Practical Approach

Lou Hampers, MDPediatric Emergency Medicine

The Children’s Hospital

Denver, CO

Thanks to:

Carl Baum MDToxikonCook County Hosp.Chicago, IL

Toxicology: the ABCs

• Airway

• Breathing

• Circulation

• Diagnosis

• Decontamination

• Enhanced removal

Diagnosis

• What?– 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

Diagnosis

Toxidromes: anticholinergic• Mad as a hatter

• Red as a beet

• Hot as a hare

• Blind as a bat

• Dry as a bone

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 • 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• removal of ingested material• administration of charcoal/cathartics

• Contra-indications• obtunded/comatose/convulsing• corrosives (?)

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)

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

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?

– dosage? 80, 160, 325, 500, 650?– toxic: >150 mg/kg

Physical• Nausea, emesis

Acetaminophen

• AcetaminophenSulfate, 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

Acetaminophen

Rumack-Matthew Nomogram

200

150

mcg/ml

4 h

Acetaminophen

Treatment

• Glutathione substitute

• Precursor for sulfate

• Antioxidant

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

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– 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– 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

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 – 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• Various forms of salicylates

Physical• 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 MnemonicsSeizures

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