Toxicology

UNC Emergency MedicineMedical Student Lecture Series

Objectives

• General approach to the poisoned patient

• Toxidromes

• Specific antidotes

• Decontamination and enhanced elimination

General Approach

• ABC’s

• History

• Physical examination

• Labs, imaging

• Diagnosis, antidotes

• Disposition

ABC’s

Airway• Airway obstruction can cause death after poisoning

– Flaccid tongue– Aspiration– Respiratory arrest

• Evaluate mental status and gag/cough reflex

• Airway interventions – Sniffing position– Jaw thrust– Head-down, left-sided position– Examine the oropharynx – Clear secretions– Airway devices: nasal trumpet, oral airway

• Intubation?– Consider naloxone first

Breathing• Determine if respirations are adequate• Give supplemental oxygen• Assist with bag-valve-mask• Check oxygen saturation, ABG• Auscultate lung fields

– Bronchospasm: Albuterol nebulizer– Bronchorrhea/rales: Atropine– Stridor: Determine need for immediate intubation

Circulation• IV access • Obtain blood work• Measure blood pressure, pulse• Hypotension treatment:

– Normal saline fluid challenge, 20 mL/kg– Vasopressors if still hypotensive– PRBC’s if bleeding or anemic

• Hypertension treatment:– Nitroprusside, beta blocker, or nitroglycerin

• Continuous ECG monitoring– Assess for arrhythmias, treat accordingly

Supportive Care

• Foley catheter

• Rectal temperature

• Accucheck, treat hypoglyemia

• Coma cocktail– Thiamine: 100 mg IV, before dextrose– Dextrose: 50 grams IV push– Naloxone: 0.01 mg/kg IV

Supportive Care

• Treat Seizures – Lorazepam 2 mg IV, may repeat as needed

– Dilantin 10 mg/kg IV

• Control agitation– Haldol 5-10 mg IM

– Ativan 2-4 mg IM or IV

– Geodon 20 mg IM

• Think about trauma

REASSESS

. . . frequently

History

• What, when, how much, why?• Rx, OTC, herbals, supplements, vitamins• Talk to family, friends, EMS • Pill bottles, needles, beer cans, suicide note • Call pharmacy • Allergies, medical problems

Physical examination

• Vital signs: BP, HR, RR, T, O2 sat• Mouth: odors, mucous membranes • Pupils• Breath sounds• Bowel sounds• Skin• Urination/defecation• Neurologic exam

Essential Laboratory Tests

• Electrolytes• Glucose• BUN and creatinine• LFT’s, CK• Urinalysis, urine drug screen• Etoh, alcohol screen• Serum osmolality• Acetaminophen, salicylates• Specific drug levels• Pregnancy test

Anion Gap

• Na – (HCO3 + Cl)• Normal: 8-12 mEq/L• Causes:

– Methanol– Uremia– DKA– Paraldehyde, phenformin– Iron, isoniazid, ibuprofen– Lithium, lactic acidosis– Ethylene glycol– Strychnine, starvation, salicylates

Osmolar Gap

• Calculated osmolality – measured osmolality• 2(Na) + glucose/18 + BUN/2.8• Normal = 285-290 mOsm/L• Gap > 10 mOsm/L suggests the presence of extra

solutes:– Ethanol, methanol– Ethylene glycol, isopropyl alcohol– Mannitol, glycerol

• Clinical Pearl: Anion gap acidosis with an osmolar gap should suggest methanol or ethylene glycol poisoning

Electrocardiogram• Prolonged QRS

– TCAs– Phenothiazines– Calcium channel blockers

• Sinus bradycardia/AV block– Beta-blockers, calcium channel

blockers– TCAs– Digoxin– organophosphates

• Ventricular tachycardia– Cocaine, amphetamines– Chloral hydrate– Theophylline– Digoxin– TCAs

Diagnosis

• May not identify ingested substance(s)

• Provide ABCs and supportive care

• Give antidote when appropriate

• Call regional poison control center– Carolinas Poison Center, Charlotte– 800-848-6946

Disposition

• Case-based • ICU admission• Period of observation• Psychiatric evaluation

Toxidromes

Cholinergic ToxidromeDiarrhea SalivationUrination LacrimationMiosis UrinationBradycardia DefecationBronchospasm GI upsetEmesis EmesisLacrimationLimp Salivation, sweating

Cholinergics• Organophosphates

– Irreversibly bind cholinesterases• Carbamate

– Reversibly bind cholinesterases, poor CNS penetration• Muscarinic and nicotinic effects• Pesticides, nerve agents

– Military personnel– Field workers, crop dusters– Truckers – Pest control, custodial workers

• Antidote– Atropine for muscarinic effects– Pralidoxime reverses phosphorylation of cholinesterase

Anticholinergics • Atropine• Scopolamine• Glycopyrrolate• Benztropine• Antispasmotics

– Dicyclomine– Hyoscyamine– Oxybutynin– clidinium

• TCAs• Mydriatics

• Antihistamines– Chlorpheniramine– Cyproheptadine– Hydroxyzine– Diphenhydramine– Meclizine– promethazine

• Antipsychotics – Clozapine– Olanzapine– Thioridazine

• Jimson weed

Anticholinergic Toxidrome• Dry mucus membranes (Dry as a bone)• Mental status changes (Mad as a hatter)• Flushed skin (Red as a beet)• Mydriasis (Blind as a bat)• Fever (Hot as a hare)• Tachycardia• Hypertension• Decreased bowel sounds• Urinary retention• Seizures • Ataxia

Toxidromes• Opioids

– Respiratory depression– Miosis– Hypoactive bowel sounds

• Sympathomimetics– Hypertension– Tachycardia– Hyperpyrexia– Mydriasis– Anxiety, delirium

Clinical Pearl: Sweating differentiates sympathomimetic and anticholinergic toxidromes

Antidotes

• Acetaminophen N-acetylcysteine• Organophosphates Atropine, pralidoxime • Anticholinergic physostigmine• Arsenic, mercury, gold dimercaprol• Benzodiazepines flumazenil• Beta blockers glucagon• Calcium channel block calcium• Carboxyhemoglobin 100% O2• Cyanide nitrite, Na thiosulfate• Digoxin digoxin antibodies

Antidotes

• Ethylene glycol fomepizole, HD• Heparin protamine• Iron deferoxamine• Isoniazid pyridoxime• Methanol fomepizole, HD• Methemoglobin methylene blue• Opioids naloxone• Salicylate alkalinization, HD• TCA’s sodium bicarbonate• Warfarin FFP, vitamin K

Decontamination

Principles of Decontamination

• External– Protect yourself and others– Remove exposure– Irrigate copiously with water or normal

saline– Don’t forget your ABC’s

• Internal– Patient must be fully awake or

intubated– Most common complication is

aspiration– Very little evidence for their use

Decontamination

• Skin– Protect yourself and other HC

workers– Remove clothing– Flush with water or normal saline– Use soap and water if oily

substance– Chemical neutralization can

potentiate injury– Corrosive agents injure skin and

can have systemic effects

Decontamination

• Eyes– remove contact lens– Flush copiously with water or normal saline– Use local anesthetic drops– Continue irrigation until pH is normal– Slit lamp and fluorescein exam

Decontamination

• Inhalation– Give supplemental humidified oxygen– Observe for airway obstruction– Intubate as necessary

GI Decontamination • Syrup of ipecac

– Within minutes of ingestion– Aspiration, gastritis, Mallory-Weiss tear, drowsiness– Rarely, if ever, given in ED

• Gastric lavage– Does not reliably remove pills and pill fragments– Used 30-60 minutes after ingestion– Useful after caustic liquid ingestion prior to endoscopy– Not used for sustained release/enteric coated ingestions– Perforation, nosebleed, vomiting, aspiration

• Recent studies suggest that activated charcoal alone is just as effective as gut emptying followed by charcoal.

GI Decontamination

• Activated charcoal– Limits drug absorption in the GI tract– Within 60 minutes of ingestion– Patient must be awake or intubated– Vomiting, aspiration, bezoar formation– Contraindication: bowel obstruction or ileus

with distention– 1 gram/kg PO or GT

Activated Charcoal

• Not good for:– Lithium

– Iron

– Alcohols

– Lead

– Hydrocarbons

– Caustics

GI Decontamination

• Cathartics– Hasten passage of ingestions or AC– Contraindications: obstruction or ileus– Severe fluid loss, hypernatremia, hyperosmolarity– 10% magnesium citrate 3ml/kg or 70% sorbitol 1-2

…./kg

• Whole bowel irrigation– Large ingestions, SR or EC tablets, packers (ex.

cocaine)– Contraindications: obstruction or ileus– Aspiration, nausea, may decrease effectiveness of

charcoal

Enhanced Elimination

• Urinary manipulation– Forced diuresis– Alkalinization

• Repeat-dose activated charcoal– Very large ingestions of toxic substance– Sustained release and enteric coated preparations

• Carbamazepine, phenobarbital, phenytoin• Salicylate, theophylline, digitoxin

• Hemodialysis, Hemoperfusion• Peritoneal dialysis, Hemofiltration

Enhanced Elimination

• Does the patient need it?– Severe intoxication with a deteriorating

condition despite maximal supportive care– Usual route of elimination is impaired– A known lethal dose or lethal blood level– Underlying medical conditions that can

increase complications

Specific Toxins

• Acetominophen

• Salicylates

• Tricyclic Antidepressants (TCA)

Acetominophen (apap)

• Max dose: – 4g/day adults – 90 mg/kg day kids

• Peak serum levels: 4 hours after overdose

• What are the three methods of APAP metabolism?– Glucuronidation (90% normal thru pathway)– Sulfonation – P450 mixed oxidase enzymes (5% nl thru pathway)

Magic number to remember is 140

Acetominophen (apap)

• Toxicity

• 140mg/kg acute ingestion

• Direct hepatocellular toxicity with centrolobular distribution (hepatic vein)

• Can also have renal damage and pancreatitis

Stages of Tylenol Toxicity

• I (0-24hrs): n/v, but most asymptomatic• II latent stage (24-48hrs): subclinical increase

in ast/alt/bili• III hepatic stage (3-4dys): liver failure, ruq

pain, vomiting, jaundice, coagulopathy, hypoglycemia, renal failure, metabolic acidosis

• IV recovery stage (4dys-2wks): resolution of hepatic dysfunction

Need 4 hour level andN-acetylcysteine (NAC)

• Dx: 4 hour level compared to the Rumack and Matthews nomogram

• 150ug/ml at 4 hours• Rx: NAC 140mg/kg then

70mg/kg every 4 hours for 17 doses

• We Have PO and IV dosing• Only useful for one time

ingestion (not chronic ingestions)

Acetominophen (apap)

• If time of ingestion unknown, draw level immediately and again at 2-4 hours.

• Labs: LFTs, coags, lytes, aspirin, ETOH, tox screen

NAC indications

• Ingestions with potential toxicity

• Late presentations with potential or ongoing toxicity

• Chronic overdose with evidence of hepatic damage

Tylenol Overdose Disposition

• Admit if…..– Known toxicity / potential toxic levels– Lab evidence of hepatic damage– Unknown time of ingestion and sx

consistent with toxicity– Unknown ingestion time with

measurable acetaminophen levels.

Salicylates (asa)

• Weak acid, rapidly absorbed• Enteric coated has delayed absorption• Toxic dose: 160 mg/kg• Lethal dose 480 mg/kg• Mixed respiratory alkalosis-metabolic acidosis• Stimulates respiratory drive causing hyperventilation,

but limits ATP production metabolic acidosis

• Oil of wintergreen, 1ml = 1400mg

Salicylates Symptoms

• Tachypnea, tachycardia, hyperthermia

• Resp alkalosis-metabolic acidosis

• Altered serum glucose

• AG metabolic acidosis (MUDPILES)

• Dehydration (vomiting, tachypnea, sweating)

• Abd pain/n/v

• Tinnitus, hearing loss

• lethargy, seizures, altered mental status

• Noncardiogenic pulmonary edema

Evaluation of ASA Overdose

• Lytes, ABG, LFTs, CBC, preg.test, urine PH

• Serum salicylate levels (toxicity at 25mg/dl)

• Toxicity correlates POORLY with levels

• Evaluation with DONE nomegram based on single ingestion of regular ASA at levels drawn 6 hrs after ingestion

• Underestimates toxicity in cases of severe acidemia or chronic ingestion

Therapy for ASA Overdose

• ABC’s• Activated charcoal• Urinary alkalinization (start if serum level is

greater than 35mg/dl)– 3 amps bicarbinate in 1 L D5W at 150 ml/hr

• By increasing urinary pH to greater than 8, ASA gets trapped in tubes and cannot be reabsorbed

• Dialysis for severe acidemia, volume overload, pulmonary edema, cardiac or renal failure, seizures, coma, levels > 100mg/dl in acute ingestion, or > 60-80 mg/dl in chronic ingestion

Disposion for ASA Overdose

• Pt gets charcoal and remain asymptomatic after 6-8 hours = Possible D/C

• Sustained release requires longer observation period

• Pts with toxic levels, symptomatic, or develop symptoms = Admission

TCA (Tricyclic Antidepressants)

• Leading cause of death by intentional overdose• Blocks sodium channels• Death by cardiovascular dysrhythymias and

cardiovascular collapse• Most TCA’s have anticholinergic effects

– Dry skin, blurry vision, hot

• Severe OD: hypotension, seizures, respiratory depression

• In severe cases: ARDS, rhabdomyolisis, DIC

GET AN EKG

What do you see?Prolonged QRS, sinus tachycardia, “tall R in R” – tall R wave in lead aVR

Treatment of TCA Overdose

• Sodium Bicarbinate – Initial bolus of 2 amps– Drip 3 amps in 1 L D5W at 150 ml/hr

• Titrate for serum pH of 7.45-7.5

• IV fluids

• Lidocaine for perisistent arrhythymias

• AVOID Class Ia drugs (procainimide quinidine)

Thank You!

Any Questions?

References

• Poisoning & Drug Overdose, California Poison Control System. KR Olson, 3rd edition, Appleton & Lange, 1999.

• Emergency Medicine Board Review Series. L Stead, Lippincott Williams & Wilkins, 2000.

• Emergency Medicine, A comprehensive study guide. Tintinalli, 6th edition, McGraw Hill, 2004.