1 / 23

Paracetamol Poisoning

Paracetamol Poisoning. Kent R. Olson, M.D. Clinical Professor of Medicine University of California, San Francisco Medical Director, San Francisco Division California Poison Control System. Case Study:.

Télécharger la présentation

Paracetamol Poisoning

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.


Presentation Transcript

  1. Paracetamol Poisoning Kent R. Olson, M.D. Clinical Professor of Medicine University of California, San Francisco Medical Director, San Francisco Division California Poison Control System

  2. Case Study: • A 17 year old young man took “pills” and some alcohol after failing his exams. He is drunk and depressed. • BP 120/80 HR 105 • Resp 14/min Temp 37 C • His airway is patent, he is breathing normally

  3. Case, continued: • He is treated with intravenous fluids, watched until sober, given a psychiatric referral, and sent home with his family. • 3 days later he returns with jaundice. WHAT IS YOUR DIAGNOSIS?

  4. Paracetamol poisoning • Diagnosis easily missed • often overlooked in history • no characteristic early symptoms or signs

  5. Paracetamol Poisoning • Common analgesic • often found in combination products • eg, with antihistamines, codeine

  6. AcetaminophenMetabolism ~ 50% ~ 45% P450 Sulfation (non toxic) Glucuronidation (non toxic) ~ 5% NAPQI N-acetylcysteine (NAC) Glutathione + NAPQI = nontoxic product Liver cell damage

  7. Paracetamol Toxicity: • Overdose: • sulfation and glucuronidation saturated • increased production of p-450 metabolite • glutathione eventually depleted • reactive intermediate NAPQI injures cells

  8. PCM toxicity, cont. • High-risk groups: enhanced p-450 activity • chronic alcoholics • chronic use of isoniazid (INH)

  9. Pharmacokinetics • Tablets dissolve rapidly • Peak level 3-4 hours after ingestion • May be delayed in the presence of other drugs (eg, antihistamines, anticholinergics, opiates)

  10. Pharmacokinetics, cont. • Volume of Distribution approx. 1L/kg • Ingestion of 200 mg/kg ~ 200 mg/L est. blood level • Elimination half-life normally 1-3 hours • Increased to 4-6 hours or more after overdose

  11. Clinical Manifestations of Toxicity: • Early: non-specific • anorexia, vomiting

  12. Clinical toxicicity, cont. • 24-48 hrs: • onset of liver injury • AST, ALT may exceed 10,000 IU • renal injury may also occur

  13. Paracetamol Toxicity, continued: • 2-5 days: • liver & kidney injury resolve in most patients • some patients may develop fulminant liver failure • progressive rise in PT/INR, bilirubin • metabolic acidosis, hypoglycemia • encephalopathy • DEATH

  14. Rarely - massive ingestions only: • > 600 mg/kg: early onset metabolic acidosis • Not due to liver failure • Probably mitochondrial poisoning • One case of massive ingestion >1500 mg/kg • Coma • Hypotension • Acidosis

  15. Prediction of Paracetamol Toxicity: • History: • acute ingestion of >200 mg/kg or >10 gm • 20 tablets in average-sized person • chronic use of >4-6 gm/day in a high-risk group • Chronic alcohol abuse, isoniazid use

  16. Prediction of PCM toxicity, cont. • Clinical evaluation: • serum PCM level is best predictor, if available • levels associated with “probable toxicity”: • 200 mg/L at 4 hrs after acute ingestion • 100 at 8 hrs • 50 at 12 hrs

  17. Tylenol “Extended Relief” Case: Serum PCM level APAP (mg/L) Prob. Toxic Poss. Toxic hrs Note: co-ingestion of Nyquil plus up to 44 g Tylenol ER Ref: Bizovi K et al: J Toxicol Clin Toxicol 1995; 33:510

  18. Potential Pitfalls with Nomogram: • Chronic intoxication • Delayed or erratic absorption • massive ingestion • mixed ingestion with opioids, anticholinergics

  19. Very early and transient increase in the PT/INR may predict later LFT rise • Normal PT/INR at 24 hrs may have good negative predictive value

  20. Gut decontamination for PCM • NO forced emesis • Activated charcoal preferred • Gastric lavage? • only for massive ingestions (eg, > 600 mg/kg)

  21. Treatment, continued • Antidote: N-acetylcysteine (NAC) • provides SH group - binds to NAPQI • most effective if started within 8-10 hrs after ingestion • can be given PO or IV • if vomiting, use IV route or give antiemetic • Alternate medication: oral methionine

  22. Summary • Ingestion < 200 mg/kg probably not toxic • If no serum level available treat based on dose • IV acetylcysteine or oral methionine • Start antidote within 8 hours • Liver or kidney damage delayed 24-48 hrs

More Related