1. Introduction to the Poisoned Patient Department of Emergency Medicine The Ottawa Hospital

2. Outline Directed toxicology history Toxidromes Cases/Treatment

3. Toxicology - Objectives -Determine whether poisoning has occurred, the substance involved, how severe the exposure was, how toxic it is likely to become, and the causticity of substance. -Perform supportive care, decontamination or prevention of further absorption, give antidote where indicated, and enhance elimination of the poison. - Discuss special considerations in the management of poisoning with aspirin, acetaminophen, tricyclic antidepressants, and methanol.

4. Clinical Timeline HistoryToxidromeTreatment Confirm or refute Reassess Laboratory

5. Directed Tox History When (most NB) What How –How much? –Method? Whose? –Compliance Coingestants? –Access –Specifics Self treatment? –Ipecac –Induced emesis –Ethanol Intent? Symptoms Work hard to get it, then be suspect!

6. Toxidrome What it is: –a clustering of symptoms and/or signs –consistent with a class of drugs/medications What it isn’t: –a way to identify a specific substance –a way to discriminate well among “contradictory agents” until repeated over time

7. Common Toxidromes Narcotic (coma resp depression, miosis) Anticholinergic (mad as a hatter …) Cholinergic (DUMBELS) Sedative/Hypnotic (pupillary rxn spared) Stimulant or Sympathomimetic Hallucinogens Extrapyrimidal Serotonergic

8. Anticholinergics TCA’s, atropine, scopolamine, antihistamines –Mad as a hatter (delerium) –Hot as a hare (fever) –Blind as a bat (mydriasis) –Dry as bone (dry mucous membrane, urinary retention, decreased BS) –Red as beet (flushing) –Bowel and bladder lose tone and heart goes on alone) Difference with adrenergics = –Bowel sounds present –Diaphoresis

9. Cholinergics Pheostigmine, organophosphtes (insecticides), and nerve gas (DUMBELS) –Diaphoresis, diarrhea, decreased BP –Urination frequent –Miosis –Bronchospasm, bronchorrhea, bradycardia –Emesis, excitation of skeletal muscle –Lacrimation –Salivation / seizures

10. Sympathomimetics Amphetamine, cocaine –Resemble paranoid schizophrenic –CNS stimulation –Seizures –Psychosis –Increased BP, pulse, Temp

11. Hallucinogens: Hallucinations May be oriented to time / place / person Tachy HTN mydriasis

12. Opioids Coma Resp depression Miosis (not with demerol)

13. Sedatives Barbituarates, ethanol, benzo’s, ethanol, GHM (gamma hydroxybutyric acid) –CNS depression –Resp depression –Coma –Pupil rxn usually spared

14. Extrapyramidal chlorpromazine, stemetil, halodol, metocloperamide –Dystonia (occulogyric crisis, laryngospasm, torticollis) –Akithesia –Parkinson like sx (tremor, ridgidity, akinesia, postural instability) –Dyskinesia (tic, spasm, chorea, myoclonus)

15. Seratonergic Mimics NMS (neuroleptic malignant syndrome) of increased BP, increased pulse, increased temp, increased resp rate (onset within 24 hours, hyperactive, clonus, hyperreflexic, clonus) NMS (due to massive dopamine blockade) (FARMERS) –Fever –Autonomic changes (increased bp, pulse, sweating) / acidosis (rare) –Rigidity of muscles / rhabdomyolyis –Mental status changes (eg. Confusion) –Elevated BP, HR, pulse, RR –Rhabdomysolysis –Seizures –Onset days to weeks

16. Case A 78 yo F presents with agitation and confusion. BP 180/105, P 110 RR 16 T 38.2 C. Physical exam reveals an acutely agitated pt, pupils 6 mm, CVS/resp normal except tachycardia. Is a toxidrome present? What are the treatment priorities? What tests do you want to order?

17. Investigations Serum levels –acetaminophen (4 hour level) –ASA –Ethanol –ingestion specific (eg phenytoin, digoxin level) Electrolytes, BUN/Cr EKG Serum osmolarity

18. What about a “Tox Screen”? Urine immunoassays –lab determines which tests to include on the “screen” Often clinically irrelevant –confuse the clinical picture positive cocaine in a patient with an opioid toxidrome “toxic” TCA level in a cyclobenzaprine (Flexeril) overdose Treat the patient, not the test!

19. Case A 78 yo F presents with agitation and confusion. BP 180/105, P 110 RR 16 T 38.2 C. Physical exam reveals an acutely agitated pt, pupils 6 mm, CVS/resp normal except tachycardia. Is a toxidrome present? What are the treatment priorities? What tests do you want to order?

20. Supportive treatment of the poisoned patient is the cornerstone of management

21. A 20 yo F comes to the ED saying she just took a whole bottle (1.5 grams) of Elavil (amitriptylline). Her vital signs are normal. She is alert and exam is normal. Treatment considerations?

22. Treatment Elimination: -Activated Charcoal -Whole Bowel Irrigation Removal: -Gastric Lavage Antidotes

23. Treatment Elimination: -Activated Charcoal -Whole Bowel Irrigation Removal: -Gastric Lavage Antidotes

24. Activated Charcoal Ingestion < 1 hr –upto 2 hrs if delayed emptying, bad toxin 1 g/kg or 10 g for each gram of OD drug Ineffective –Pesticides –Hydrocarbons –Alcohols –Iron –Lithium –Alkali’s / acids (contraindicated)

25. Activated Charcoal CX –Aspiration Gastric content aspiration worse than charcoal aspiration But a lot worse if dump charcoal into lungs –Perforation if bowels not moving

26. Cathartics Sorbitol –available premixed with charcoal can use for first dose –contraindicated if < 2 years electrolyte problems –Used with charcoal to counteract its constipating effect

27. To Give or Not to Give... An alert 36 year old M 2 hours post accidental ingestion of antifreeze

28. To Give or Not to Give... A: Not indicated; 2hrs is too late (esp for liquid) and alcohols bind poorly An alert 36 year old M 2 hours post accidental ingestion of antifreeze

29. To Give or Not to Give... A somnolent 45 yo F with ingestion of olanzapine (Zyprexa) and venlafaxine (Effexor) at an undetermined time.

30. To Give or Not to Give... A somnolent 45 yo F with ingestion of olanzapine (Zyprexa) and venlafaxine (Effexor) at an undetermined time. A: Not indicated; undetermined time (likely greater than 1 hr for toxicity to develop from these agents) and risk of aspiration given altered mental status.

31. To Give or Not to Give... An intubated 37 yo F 30 min after collapsed after metoprolol OD.

32. To Give or Not to Give... An intubated 37 yo F 30 min after collapsed after metoprolol OD. A: Indicated; recent ingestion, (very) bad drug and airway is protected.

33. Treatment Elimination: -Activated Charcoal -Whole Bowel Irrigation Removal: -Gastric Lavage Antidotes

34. Decontamination Gastric Lavage –recent (< 1hr) –Life threatening ingestion –no antidote –not adsorbed by AC –sustained release –concretions –no emesis EasyLav

35. Gastric Lavage Large hose with blunt end (need this for tablets to pass) LL decubitus position with pylorus pointing upwards Has to have airway protected either intubated of fully conscious Have bucket of warm water and bucket on floor

36. Gastric Lavage Give warm water through funnel / tube above pt … Percuss stomach … move tube below level of head to drain into bucket … repeat Prevents drug from getting into small intestine as drain directly from stomach

37. Treatment Elimination: -Activated Charcoal -Whole Bowel Irrigation Removal: -Gastric Lavage -Dialysis Antidotes

38. Whole Bowel Irrigation Polyethylene glycol (eg. Golytely) –1-2 L/hr via NGT until clear effluent –Do for 4 to 6 hours until clear effluent via rectal tube SR preps, Lithium, iron, sustained release drugs Body packers/stuffers

39. A 20 yo F comes to the ED saying she just took a whole bottle (1.5 grams) of Elavil (amitriptylline). Her vital signs are normal. She is alert and exam is normal. Treatment considerations?

40. Tricyclic Antidepressants - Sx Block sodium channels Neuro: –mental status changes –anticholinergic toxicity –seizures Cardiac: –(lethal) arrhythmias –AV blocks –hypotension QRS > 120 ms and ‘R” in aVR > 3mm predicts seizures/ arrhythmias

41. Tricyclic Antidepressants - Mgmt Activated Charcoal (no role for dialysis) Alkalinization of blood (7.45 – 7.50) with sodium bicarbonate –Abolishes dysrhythmias and improves hypotension –Use if QRS > 100 msec –Administer as 1 – 2 mEq/kg IV push then 20 mEq / hr drip

42. Enhanced Elimination Diuresis –Alkaline 3 amps NaHCO3 in 1 L D5W with 40 mmol KCl at 250 mL/hr goal: urine pH 7.5-8 E.g Salicylates, Phenobarbital –Neutral Lithium

43. Tricyclic Antidepressants - Mgmt -Seizure mgmt: -avoid dilantin (increases dysrhythmias) -Diazepam/lorazepam/ phenobarbitol -Hypotension -Crystalloid and alkalinization -Vasopressors if no response -Dysrhythmias unresponsive to bicarb -Lidocaine -Consider pacemaker insertion for blocks

44. A 34 yo M presents 4 hours after ingesting 100 regular ASA pills. He complains of tinnitus, is vomiting and has an ASA level of 6 mmol/L. His vital signs are BP 132/78 P 85 RR 28 T 37.5° C Decontamination? Other treatment considerations?

45. Commonly Dialysable Drugs Isopropanol Salicylates Theophylline Uremia Methanol Barbiturates Lithium Ethylene Glycol

46. Salicylates - Symptoms Causes metabolic acidosis.. Initially resp alkalosis as stimulates resp centre Mild = ototoxicity (tinnitis, vertigo) Severe = CNS stimulation followed by depression (confusion, delerium, seizures_ –Cardiac dysrhythmias, noncardiogenic pulmonary edema, renal failure, hemorrhage

47. Salicylates – Treatment Treatment is not dependant on specific serum level; it is a CLINICAL diagnosis Done nomogram USELESS Draw levels to ensure declining

48. Salicylates – Evaluation Decontamination with Activated charcoal Consider gastric lavage if < 60 min Alkaline diuresis with bicarb increases elimination of ASA (goal of urine pH 5 – 8) –See TCA OD for bicarb dosing Hemodialysis is most effective means –Indications include renal failure, severe cardiac tox, rising ASA levels despite alkalinization, pulm edema, severe acidbase imbalance

49. Case A 42 yo M presents after ingesting 30 grams of acetaminophen. He is asymptomatic. A serum level 4 hours after ingestion is 1625  mol/L.

50. Antidotes AcetaminophenN-acetylcysteine AtropinePhysostigmine Carbon monoxideoxygen CyanideAmyl nitrite + sodium nitrite + sodium thiosulfate Ethylene glycol / Methanol Ethanol / fomepizole IronDeferoxamine LeadEDTA (calcium disodium edetate)

51. Antidotes NitritesMethylene Blue OrganophosphateAtropine OpiodsNaloxone IsoniazidPyridoxine DigoximDigibind BenzodiazepinesFlumazenil

52. Acetaminophen Delayed hepatoxicity Consider activated charcoal Rumack-Matthew nomogram –predicts toxicity 4 hrs after acute ingestion –No use less than 4 hours before N-acetylcysteine antidote –Minimum 300 mg/kg IV over 20 hrs Goal of therapy is administration of NAC within 8 hrs of ingestion

54. Methanol Found in windshield washing fluid, paint thinners, solvents Converted by alcohol dehydrogenase to formaldehyde (liver) to formic acid –Formic acid – toxic product –Causes high anion gap and osmole gap –Affects optic nerve fxn causing papillitis and retinal edema – “blind drunk”

55. High Anion Gap C (carbon monoxide, cyanide) A (Arsenic) T (toluene) M (methanol, metformin) U (uremia) D (DKA) P (paraldehyde, phenformin) I (INH, iron) L (Lactic acidosis) E (ethylene glycol (antifreeze), everything S (salicylates, strychtnine)

56. Anion and osmole gap –AG = Na – Cl – HCO 3 –Osmole Gap = 2Na + BUN + glucose + ETOH( 1.25) Osmole gap causes: –Ethanol, Isopopanol, Methanol, Ethylene glycol, Acetone, Glycerol, Mannitol, Uremia, Ketocacidosis Isopropanol causes high osmole but not anion gap Peraldehyde and isoniazide cause high AG but not high osmole gap

57. Methanol 8 hour – 30 hour latent period followed by onset of abdo pain, nausea, vomiting, blurred vision, metabolic acidosis –Often dilated pupil with photophobia High anion gap acidosis –Na – Cl – HCO 3 Osmole gap may be high but can be normal –2Na + BUN + glucose + EtOH (1.25) –Normal is 280 – 295 mosm

58. Methanol Supportive measures Consider bicarbonate with severe acidosis ADH inhibitor –Fomepizole – inhibits alcohol dehydrogenase –Ethanol (BEER!) – ethanol infusion as alcohol dehydrogenase preferentially metabolizes ethanol (keep at 22 – 33) Hemodialysis –If symptomatic or methanol level > 8 mmol / L –Severe acidosis

59. TOXICOLOGY AXIOMS The most important aspect of the history is the time of ingestion and coingestants The most critical therapy varies with the time course of the patient’s presentation No evaluation is complete until repeated over time Toxidromes can help identify classes of drugs It is often not important to determine the exact drug taken within a class Supportive tx is the cornerstone of tx