General Approach to the Poisoned Patient (An introduction to Toxicology)

1. General Approach to the Poisoned Patient(An introduction to Toxicology) Khalid Gabralla, MD Assistant Professor Emergency Medicine King Saud University

2. Outline • Initial approach • Toxic Syndromes • Decontamination • Diagnostic Tests • Observation

3. Case. . . • 18 years old man • found “down” • EMS transports • Reports from scene: “he took something” • No pill bottles on scene • No family with him • Friends that found him are long gone • He is now in your ED

4. You are never going to know exactly what he took. . . • What do I do with him? • What do I order? • How do I treat him? • How do I decontaminate him? • Do I give him an antidote? • When can he go to psych (MEDICALLY CLEARED?

5. You can. . . • Start with the basics • Airway, breathing, circulation • Get a better history form many sources! • Get EMS to get pill bottles, tell you what they do know (found outside, inside, garage…) • Call friends, family, neighbors • Check Medical charts to see what he is on regularly • Establish a pattern to his symptoms • Toxic syndrome (TOXIDROM)

6. TOXIDROME constellation of physical findings that can be attributed to a specific class of toxins and can provide important clues to narrow the differential diagnosis

7. Toxidromes • Not every drug fits into a broad based category • Lots of meds have unique effects not easily grouped • Polydrug overdoses may result in overlapping and confusing mixed syndromes. • 5 Basic Toxidromes • Sympathomimetic • Opiate • Anticholinergic • Cholinergic • Seditive Hypnotic

8. Toxidromes: Sympathomimetic • Cocaine • Methamphetamine/Amphetamines • Ecstasy (MDMA) • ADHD meds like ritalin, adderal • Ephedrine • Caffeine

9. Why do they do what they do? Excessive SYMPATHETIC stimulation involving epinephrine, norepinephrine and dopamine Excessive stimulation of alpha and beta adrenergic system

10. Features: • Tachycardia +/- arrythmias • Mydriasis • Diaphorisis • Hypertension +/- ICH • Confusion with agitation • Seizures • Rhabdomyolysis • Renal failure can result

11. What do you do about it? • Supportive care • Monitor airway, diagnose ICH, rhabdo • IVF for insensible loses and volume repletion • Benzos, benzos, benzos, benzos • BP mgmt if severe • NEVER GIVE BETA BLOCKERS

12. Toxidrome: Opiate • Morphine and codeine • Heroin • Methadone • Meperidine • Hydrocodone • Oxycodone

13. Features: • Coma • Miosis • Respiratory depression • Peripheral vasodilation • Orthostatic hypotension • Flushing (histamine) • Bronchospasm • Pulmonary edema • Seizures (meperidine, propoxyphene)

14. What do you do about it? • Competitive opioid antagonist: Naloxone • Goal of return of spontanous respirations sufficient to ventilate the patient appropriately • May have to re-dose as opiates may act longer than antagonist

15. Toxidrome: Anticholinergic • Antihistamines, • Antiparkinsonians, • Atropine, • Scopolamine, • Amantadine, • Antipsychotics, • Antidepressants, • Antispasmodics, • Mydriatics, • Muscle relaxants, • Many plants (e.g., jimson weed, Amanita muscaria)

16. Why do they do what they do? • By definition these agents ANTAGONIZE the effects of endogenous Acetylcholine by blocking the receptors.

17. What goes wrong? • CNS muscarinic blockade: • Confusion • Agitation • Myoclonus • Tremor • Abnormal speech • Hallucinations • Coma • Peripheral muscarinic effects: • Mydriasis • Anhidrosis • Tachycardia • Urinary retention • Ileus

18. What do you do about it? • Supportive care • IVF to replace insensible losses from agitation, hyperthermia • Benzos to stop agitation • Physostigmine • Induces cholinergic effects • Short acting • May help with uncontrollable delirium • Do not use if ingestion not known • Danger with TCAs

19. Toxidrome: Cholinergic Organophosphate and carbamate insecticides. Physostigmine, edrophonium, some mushrooms.

20. Pathophysiology Normal • Block acetylcholinesterase from working • End up with excess of acetylcholine in synapses • Leads to excess stimulation of the muscarinic and nicotinic systems E= Acetylcholinesterase NA= nerve agent Ach= acetylcholine With blockade

21. Toxidrome: Cholinergic Features: • S - Salivation • L - Lacrimation • U - Urination • D - Diaphoresis • G - Gasterointestinal upset • vomiting, diarrhea • E - Eye • miosis

22. What do you do about it? • Antagonize muscarinic symptoms • Atropine • Stop aging of enzyme blockade • 2-PAM • Prevent and terminate seizures • Diazepam • Supportive care

23. Toxidrome: Sed-Hypnotic

24. Why do they do what they do? • Different agents have different mechanisms • Many interfere in the GABA system

25. What goes wrong?

26. What goes wrong? • CNS depression, lethargy • Can induce respiratory depression • Can produce bradycardia or hypotension

27. What do you do about it? • Supportive care • Be wary of the benzo “antidote” Flumazinil • Is an antagonist at the benzo receptor • RARELY INDICATED • If seizures develop either because of benzo withdrawal, a co-ingestant or metabolic derangements, have to use 2nd line agents, barbiturates, for seizure control

28. So back to our patient. . . • Agitated, pupils 8 mm, sweaty, HR 140’s, BP 230/130 • Sympathomimetic • Unarousable, RR 4, pupils pinpoint • Opiate • Confused, pupils 8mm, flushed, dry skin, no bowel sounds, 1000 cc output with Foley • Anticholinergic • Vomiting, urinating uncontrollably, HR 40, Pox 80% from bronchorrhea, pupils 2 mm • Cholinergic • Lethargic, HR 67, BP 105/70, RR 12, pupils midpoint • Sedative Hypnotic

29. So ED approach: • Airway, breathing, circulation • Establish IV, O2 and cardiac monitor • Consider coma cocktail • Thiamine, D50, Narcan • Evaluate history and a thorough physical exam • Look at vitals, pupils, neuro, skin, bowel sounds. . . • Gives you hints regarding the general class of toxins • Guides your supportive care • Draw blood / urine for testing • Time to consider decontamination options

30. Gastric Decontamination Overview • Induce vomiting – Ipecac • Take out pills from the stomach – Lavage • Adsorb the toxins in the gut – Charcoal • Flush out the system – Whole Bowel

31. Gastric Decontamination Overview • The vast majority of patients are unlikely to benefit from gastric decontamination • They have ingested nontoxic substances • They have ingested nontoxic amount of toxic substances • They present long after decontamination would be expected to be of any benefit!

32. Gastric Decontamination Overview • Patients who theoretically may benefit from decontamination: - Present early after ingestion (1 hour) - Have taken a delayed release products - Have taken potentially life-threatening overdose • No prospective studies have demonstrated outcome benefit with gastric decontamination.

33. Ipecac • Emetine and Cephaeline • Induces emesis • DOES NOT HAVE A ROLE IN ED CARE

34. Gastric Lavage • Rarely, if ever, indicated • Life threatening ingestions that occurred within < 1 hour American Academy of Clinical Toxicology • Airway protection is key • Lots of complications

35. Activated Charcoal • No proven outcome benefit, and its use should be carefully weighed against potential complications. • Works to adsorb substances to its matrix • Not for metals, caustics, alcohol,alkali,acid,hydrocarbons • contraindications • Aspiration, ARDS,bowel obstruction • Dosing 1 g/kg po dose, +/- single dose of cathartic

36. If GI decontamination is considered, no matter the method, potential benefit must be weighed against the potential complications.

37. Now you are ready to order diagnostic studies. . . • Want to evaluate • Acid base status • Renal function • Liver function • Cardiac conduction • ECG • Drug levels • Based on history or clinical findings • Any toxin specific findings • CK for cocaine, …etc

38. Other common ingestants may have common dx test abnormalities. . . • Paracetamol • Paracetamol level, LFT, coags • Salicylates • ASA level, metabolic acidosis, respiratory alkalosis, renal insufficiency, anion gap • SSRI • Prolonged QTc • Toxic Alcohols • Osmolal. gap with ethylene glycol, methanol and isopropyl alcohol • Anion gap acidosis with EG and methanol

39. ECG • Evaluate QRS and QTC, presence of blocks, rhythm • QTc > 450 and a QRS > 100 can be concerning for toxin induced (eg TCAs) cardiac abnormalities

40. Radiographs • Limited usefulness • CHIPES • Chloral hydrate, Ca • Heavy metals • Iron, iodides • Phenothiazines • Enteric coated • Slow release • Packers/ stuffers • Aspiration

41. Observation Period • Normal labs, normal ECG, normal exam, no history of extended release drug • Approximately 6 hours • Extended release medications, oral hypoglycemics involved • Depending on agent, 12-24 hours

42. So back to your patient. . . • How do I treat him • Good supportive care, good physical examination • How do I decontaminate him( if I need to do!) • A. Charcoal as long as he is not in aspiration risk • What do I order • Chem, ASA, Paracetamol, ECG at a minimum • Do I give him an antidote • Coma cocktail, others as indicated by clinical condition & or labs. • When can he go to psych? • Observe for 6 hours and re-evaluate

43. Thank You.