The Poisoned Patient: A Medical Student Review

1. The Poisoned Patient:A Medical Student Review William Beaumont Hospital Department of Emergency Medicine

2. Introduction • All chemicals, especially medicines, have the potential to be toxic • 2006 TESS data • 2.7 million exposures • 19.8% were treated in a healthcare facility • 21.6% of those had more than minor outcomes including death • Over half of poisonings occur in children less than 5 years of age

3. The Initial Approach • Always consider poisoning in differential dx • IV, O2, monitor • Accucheck – in all pts with altered mental status • D50 +/-Thiamine or Naloxone as indicated • Decontamination, protect yourself • Enhanced elimination • Antidotal therapy • Supportive care

4. History • Name, quantity, dose and route of ingestant(s) • Time of ingestion • Any co-ingestions • Reason for ingestion – accidental, suicidal • Other medical history and medications • EMS – inquire what they saw at the scene, notes left, smells, unusual materials, pill bottles, etc.

5. Pupils • Dilated – anticholinergic or sympathomimetic • Constricted – Cholinergic • Pinpoint – Opiods • Nystagmus – horizontal – ethanol, phenytoin, ketamine • Nystagmus – rotatory or vertical - PCP

6. Skin Hyperpyrexia – anticholinergic, sympathomimetic, salicylates Hypothermic – Opiods, sedative-hypnotics Dry skin – anticholinergics Moist skin – cholinergics, sympathomimetics Color – cyanosis, pallor, erythema

7. Overall exam • Stimulants – everything is UP •  temp, HR, BP, RR, agitated • Sympathomimetics, anticholinergics, hallucinogens • Depressants – everything is DOWN •  temp, HR, BP, RR, lethargy/coma • Cholinergics, opioids, sedative-hypnotics • Mixed effects: Polysubstance overdose, metabolic poisons (hypoglycemic agents, salicylates, toxic alcohols)

8. Laboratory studies • Accucheck • Chemistries (BUN, Cr, CO2) • Urinalysis – Calcium oxalate crystals in ehtylene glycol poisoning • Drugs of abuse and comprehensive drug screen • Acetaminophen, aspirin and ethanol levels • Urine HCG if warranted • EKG • ABG, serum osmolality, Toxic Alcohol screen, LFTS if warranted

9. General Decontamination • Remove all clothing, wash away any external toxic substances • If suspect transmittable contaminant, perform in special decontamination area • If ocular exposure – flush eyes copiously with at least 2 L NS using lid retractors, until pH 7 – 7.5

10. GI Decontamination • Three methods • Gastric emptying • Bind the toxin in the gut • Enhance elimination • Always consider the patient’s mental status, risk of aspiration, airway security and GI motility before attempting any method

11. Orogastric Lavage • Indications – life threatening ingestions who present one hour within ingestion • With the patient in the left lateral decub position, a 36 fr tube is passed oral - gastric to evacuate gastric contents and lavage with room temperature water until effluent is clear • Studies show little benefit (may remove as little as 35% of the substance), the need of a secure airway and relatively high complication rate

12. Activated Charcoal • Adsorbs toxin within the gut making it unavailable for absorption • 1 g/kg PO or via NGT • Contraindications: bowel obstruction or perforation, unprotected airway, caustics and most hydrocarbons, anticipated endoscopy • Not effective for alcohols, metals (iron, lead), elements (magnesium, sodium, lithium)

13. Multi-dose Activated Charcoal • MDAC • Large doses of toxin • Slow release toxins • Enterohepatic or enterenteric circulation • Toxins that form bezoars • “gastrointestinal dialysis” • Phenobarbital, theophylline, carbamazepine, dapsone, quinine

14. Cathartics • 70% Sorbitol 1g/kg, administered with charcoal • Decreased transit time of both toxin and charcoal through the GI tract • Typically only used with the first dose if MDAC • Do not use in children under 5, caustic ingestions, or possible bowel obstruction

15. Whole Bowel Irrigation (WBI) • Go-Lytely via PO or NGT at a rate of 2L/hr (500 ml/hr in peds) • Typically used for those substances not bound by Activated Charcoal • Do not use in patients with potential bowel obstruction

16. Hemodialysis • Useful for Salicylates, Methanol, Ethylene Glycol, Lithium, Amanita mushrooms, Isopropyl alcohol, Chloral hydrate • Patients must be hemodynamically stable and without bleeding disturbances • Charcoal hemoperfusion – essentially HD with a charcoal filter in the circuit • Barbituates, Carbamazepine, Phenytoin, Methotrexate, Theophylline and Amanita poisonings

17. Acetaminophen Anticholinergic agent Benzodiazepines Beta blockers or calcium channel blockers Carbon monoxide Cardiac glycosides Cyanide N-Acetylcysteine Physostigmine Flumazenil Glucagon, calcium Oxygen Digoxin-specific Fab fragments Amyl nitrate, sodium nitrate, sodium thiosulfate, hydroxycobalamin Toxin Antidotes

18. Ethylene glycol Heparin Hydrofluoric acid Iron Isoniazid Lead Mercury, arsenic, gold Methanol Nitrites (Methemoglobin) 4-Methylpyrazole, ethanol Protamine sulfate Calcium gluconate Desferoxamine Pyridoxime (Vit B6) BAL or DMSA, Calcium disodium EDTA BAL 4-Methylpyrazole, ethanol Methylene blue Toxin Antidote

19. Opiates, propoxyphene, lomotil Organophosphates Sulfonylureas Tricyclic antidepressants Naloxone (Narcan) Atropine, pralidoxime Glucose, octreotide Sodium bicarbonate, benzodiazepines Toxins Antidote

20. Case One 56 y/o male found unconscious in a basement. He has snoring respirations, frothing at the mouth, and rales on pulmonary exam. His pupils are pinpoint. He wakes up swearing and swinging at staff after a little narcan. What could it be?

21. The Toxidromes - Opioid • Heroin, Morphine, fentanyl • CNS depression, lethargy, confusion, coma, respiratory depression, miosis • Vital signs:  temp, HR, RR, +/- BP • Pulmonary edema, aspiration, resp arrest • Check for track marks, rhabdomyolysis, compartment syndrome • Tx: Naloxone 0.4 - 2 mg iv/im/sc slowly • May result in severe agitation • Monitor closely and re-dose if necessary

22. The Toxidromes - Sympathomimetic • Cocaine, amphetamines (speed, dex, ritalin), Phencyclidine (PCP), methamphetamines (crank, meth, ice), MDMA (Ecstasy, X, E) • Stimulant: Meth > amphetamines > MDMA • Hallucinogen: MDMA > Meth > amphetamines • Agitation,  temp, HR, BP, mydriasis • Seizures, paranoia, rhabdomyolysis, MI, arrythmias

23. Toxidromes - Sympathomimetics • Management - primarily supportive - Benzo’s, IV hydration, cooling if hyperthermic • Treat HTN with benzodiazepines, nitrates, phentolamine • MI – avoid beta blockers • Bodystuffers (small amount, poorly contained) • Asymptomatic - AC, monitor for toxicity • Symptomatic - AC, WBI, treat symptoms • Bodypackers (lg amount, well contained) • Asymptomatic - WBI followed by imaging • Symptomatic - Immediate surgical consultation

24. The Toxidromes - Cholinergic • Organophosphates • Insecticides, nerve gas (Sarin, Tabun, VX) • Irreversible binding to ACHe – “aging” • Carbamates • Insecticides (Sevin) • Reversible binding to ACHe – short duration • Physostigmine, Edrophonium, Nicotine • All increase Ach at CNS, autonomic nervous system and neuromuscular jx

25. The Toxidromes - Cholinergic • Common Clinical Findings • SLUDGE Syndrome • Parasympathetic hyperstimulation • Salivation, Lacrimation, Urinary Incontinence, Defecation, GI pain, Emesis • Killer B’s • Bradycardia, Bronchorrhea, Bronchospasm • Bronchorrhea and respiratory failure is often the cause of death • Miosis, garlic odor, CNS ( MS, seizures, muscle fasciculations and weakness, resp depression, coma

26. The Toxidromes - Cholinergic • Diagnose – RBC or plasma cholinesterase level • Management • Decontamination – protect yourself • Supportive therapy • Atropine - competitive inhibition of ACH • Large doses required - 2-5 mg q 5 minutes • End point is the drying of secretions • Pralidoxime (2-PAM) - breaks OP-ACHe bond • Start with 1-2 g IV over 30 minutes, give before “aging” • Adjust dose based on response, ACHe level

27. Case 2 22 y/o F presents with decreased urine output. She is febrile, confused, flushed and has dilated pupils on exam. You also notice a linear, vesicular rash on her lower legs. What do you want to know?

28. Case 2 • Meds • She has been using oral benadryl and topical caladryl lotion for the poison ivy What is her toxidrome?

29. The Toxidromes - Anticholinergic • Agents • Antihistamines: diphenhydramine, loratadine, meclizine, prochlorperazine • Antipsychotics: chlorpromazine (Thorazine), Thiroidazine (Mellaril), • Belladonna Alkaloids: Jimsonweed, deadly nightshade, mandrake, atropine, scopolamine • Cyclic Antidepressants: amitriptyline (Elevil), nortriptyline (Pamelor), fluoxetine (Prozac) • OTC’s: Excedrin PM, Actifed, Dristan, Sominex • Muscle Relaxants: Orphenadrine (Norflex), cyclobenzaprine (Flexeril) • Amanita mushrooms The Toxidromes - Anticholinergic

30. The Toxidromes - Anticholinergic • Common Clinical Findings • Dry as a bone - lack of sweating, dry skin and mucous membranes • Red as a beet - flushed, vasodilated • Hot as Hades - hyperthermia, may be agitation induced • Blind as a bat - mydriasis • Mad as a hatter - anticholinergic delirium, hallucinations • Stuffed as a pipe - hypoactive bowel sounds, ileus, decreased GI motility, urinary retention • VS:  temp, HR, BP

31. The Toxidromes - Anticholinergic • R/O psychiatric disorders, DTs, sympathomimetic toxicity • Dry skin and absent bowel sounds indicate likely anticholinergic toxicity • Management • Sedation with high dose benzodiazepines • AC (esp if  BS), temp control • Treat widened QRS and dysrhythmias with bicarb • Physostigmine • far more effective but use only in clear cut cases • 0.5 to 2.0 mg IVP, every 30-60 minutes • Monitor for excess cholinergic response - SLUDGE

32. The Toxidromes - Salicylate • Aspirin, oil of wintergreen, OTC remedies • Altered mentation, tinnitus, diaphoresis, nausea and vomiting, tachycardia • Metabolic acidosis and respiratory alkalosis • Dx: + anion gap, salicylate level > 30mg/dl • Treatment • Multidose AC • Alkalinize urine • HD if levels > 100 mg/dl, altered MS, renal failure, pulmonary edema, severe acidosis or hypotension

33. The Toxidromes - Serotonin Syndrome (SS) • SSRI’s: fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), citalopram (Celexa), escitalopram (Lexapro) • MAOI’s, meperidine, tricyclics, trazadone, mertazapine, dextromethorphan, LSD, lithium, buproprion, tramadol • SS may be caused by any of the above, but usually occurs with a combination of agents, even if in therapeutic doses

34. The Toxidromes - Serotonin Syndrome (SS) • altered MS, mydriasis, myoclonus, hyperreflexia, tremor, rigidity (especially lower extremities), seizures, hyperthermia, tachycardia, hypo or hypertension • Citalopram and escitalopram - prolonged QT and QRS • No confirmatory tests – diagnosis is based on clinical suspicion

35. The Toxidromes - Serotonin Syndrome Treatment • Supportive care • Single dose AC (ensure airway control) • Benzodiazepines to treat discomfort, muscle contractions or seizures) and cooling measures • Treat prolonged QT with magnesium • Treat widened QRS with Bicarb • Cyproheptadine (antiserotonin agent) - 4 to 8 mg PO. Dose may be repeated in 2 hrs. If positive response, give 4 mg PO q 6 hrs for 48 hrs.

36. Acetaminophen Poisoning • Common Clinical Findings • Stage I 0-24 hrs, nausea, vomiting, anorexia • Stage II 24-72 hrs, RUQ pain, elevation of AST and ALT, also elevation of bilirubin and PT if severe poisoning • Stage III 72-96 hrs, peak of AST, ALT, bilirubin and PT, possible renal failure and pancreatitis • Stage IV > 5 days, resolution of hepatotoxicity or progression to multisystem organ failure

37. Acetaminophen Poisoning Rummack-Mathew nomogram acetaminophen levels vs time Plot 4 hr level Useful for single acute ingestion only

38. Acetaminophen Poisoning • Management • AC assume polypharmacy OD • NAC - N-acetylcysteine (NAC) indicated if • patient ingested over 140 mg/kg OR toxic level on nomogram • IV dose: 150mg/kg IV load, 50 mg/kg over 4 hrs, then 100mg/kg over 16 hrs • PO dose: 140 mg/kg load, then 70 mg/kg q 4 hrs x 17 • Draw baseline LFTs and PT

39. CASE: UNKNOWN LIQUID 17 y/o M brought in by family for acting “drunk.” He is lethargic, confused, disoriented. Vitals: 130, 90/60, 16, 37 C. Labs: Etoh 0, CO2 12 What else do you want to know?

40. CASE UNKNOWN LIQUID Accucheck: 102 Serum Osmolality 330 Na 140, K 4.0, Cl 100, CO2 12, glucose 90 BUN 28, Cr 2.0 UDS, APAP, ASA are all negative U/A has calcium oxalate crystals What are we hinting at?

41. Toxic Alcohols • Typical Agents • Ethanol • Isopropanol • Methanol • Ethylene glycol (EG) • All toxic alcohols cause an osmolar gap • Methanol and EG cause an anion gap acidosis

42. Useful Equations • Anion Gap (mEq/L) Na - (Cl + HCO3) • Calculated Osmolarity (mosm/L) 2Na + BUN/2.8 + Glu/18 + ETOH/4.6

43. Toxic Alcohols - Isopropanol • Rubbing alcohol > solvents, antifreeze, disinfectants • It is the second most commonly ingested alcohol • Isopropyl alcohol has twice the CNS depressing potency and up to 4 times the duration as ethanol • Toxic dose of 70% isopropanol is 1ml/kg • Lethal dose is as little as 2ml/kg

44. Toxic Alcohols - Isopropanol • Metabolized by alcohol dehydrogenase to acetone • Fruity breath, ketonuria, + osmolar gap, no acidosis • Clinically may appear similar to ethanol intoxication with greater CNS depression • Hypotension, respiratory depression, coma • Nausea, vomiting, abdominal pain and upper GI bleeding secondary to hemorrhagic gastritis

45. Toxic Alcohols - Methanol • Typical agent is wood alcohol, used in solvents, paint removers, antifreeze and windshield washer fluid. Also may be found in bootleg liquor. • Is rapidly metabolized to toxic formaldehyde and formic acid • Can cause permanent retinal injury and blindness as well as parkinsonian syndrome if not treated promptly • May have a long latent period (12 to 18 hours), especially if co-ingested with ethanol

46. Methanol diagnosis • Common Clinical Findings • Lethargy, nausea, vomiting, abd pain • Visual symptoms seen in 50% - blurring, tunnel vision, color blindness •  HR, RR, BP (poor prognosis if present) • CNS - head ache, seizures or coma • Wide anion-gap metabolic acidosis with osmolar gap • Toxic alcohol screen to confirm

47. Toxic Alcohols - Ethylene Glycol • Typical agent is antifreeze • Often seen in alcoholics, suicide attempts and children • Colorless, odorless and sweet • Metabolism and treatment similar to methanol • Is rapidly absorbed and converted to toxic acids responsible for clinical signs and symptoms • Lethal dose is as low as 2 ml/kg

48. Toxic Alcohols - Ethylene Glycol • Common Clinical Findings • Three phases • 1-12 hours - CNS Depression: inebriation, vomiting, seizures, coma, tetany (hypocalcemia) • 12-24 hours - Cardiopulmonary Phase: hypotension, tachydysrhythmias, tachypnea and ARDS • 24-72 hours - Nephrotoxic Phase: Oliguric renal failure, ATN, flank pain, calcium oxylate crystalluria

49. Toxic Alcohols - Ethylene Glycol • Additional findings • Hypocalcemia secondary to precipitation with oxylate, excreted as urinary calcium oxylate crystals • Urine may also fluoresce secondary to fluorescence dye in antifreeze • EKG: QT prolongation (hypocalcemia) and peaked T’s (hyperkalemia) • Myalgias, secondary to acidosis and elevated CPK

50. Diagnose Ethylene Glycol (EG) Always consider EG in aninebriated patient without alcohol breath, an anion-gap metabolic acidosis, osmolar gap and calcium oxylate crystalluria