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Toxicology

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Toxicology

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  1. Toxicology UNC Emergency Medicine Medical Student Lecture Series

  2. Objectives • General approach to the poisoned patient • Toxidromes • Specific antidotes • Decontamination and enhanced elimination

  3. General Approach • ABC’s • History • Physical examination • Labs, imaging • Diagnosis, antidotes • Disposition

  4. ABC’s

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. REASSESS. . . frequently

  11. 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

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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. Disposition • Case-based • ICU admission • Period of observation • Psychiatric evaluation

  19. Toxidromes

  20. Cholinergic Toxidrome Diarrhea Salivation Urination Lacrimation Miosis Urination Bradycardia Defecation Bronchospasm GI upset Emesis Emesis Lacrimation Limp Salivation, sweating

  21. 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

  22. Atropine Scopolamine Glycopyrrolate Benztropine Antispasmotics Dicyclomine Hyoscyamine Oxybutynin clidinium TCAs Mydriatics Antihistamines Chlorpheniramine Cyproheptadine Hydroxyzine Diphenhydramine Meclizine promethazine Antipsychotics Clozapine Olanzapine Thioridazine Jimson weed Anticholinergics

  23. 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

  24. Toxidromes • Opioids • Respiratory depression • Miosis • Hypoactive bowel sounds • Sympathomimetics • Hypertension • Tachycardia • Hyperpyrexia • Mydriasis • Anxiety, delirium Clinical Pearl: Sweating differentiates sympathomimetic and anticholinergic toxidromes

  25. 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

  26. 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

  27. Decontamination

  28. 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

  29. 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

  30. 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

  31. Decontamination • Inhalation • Give supplemental humidified oxygen • Observe for airway obstruction • Intubate as necessary

  32. 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.

  33. 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

  34. Not good for: Lithium Iron Alcohols Lead Hydrocarbons Caustics Activated Charcoal

  35. 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

  36. 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

  37. 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

  38. Specific Toxins • Acetominophen • Salicylates • Tricyclic Antidepressants (TCA)

  39. Acetominophen (apap) Magic number to remember is 140 • 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)

  40. Acetominophen (apap) • Toxicity • 140mg/kg acute ingestion • Direct hepatocellular toxicity with centrolobular distribution (hepatic vein) • Can also have renal damage and pancreatitis

  41. 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

  42. 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) Need 4 hour level andN-acetylcysteine (NAC)

  43. Acetominophen (apap) • If time of ingestion unknown, draw level immediately and again at 2-4 hours. • Labs: LFTs, coags, lytes, aspirin, ETOH, tox screen

  44. NAC indications • Ingestions with potential toxicity • Late presentations with potential or ongoing toxicity • Chronic overdose with evidence of hepatic damage

  45. 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.

  46. 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

  47. 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 Salicylates Symptoms

  48. 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

  49. 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