1 / 25

Aspirin & Paracetamol (Acetaminophen) Poisoning

Aspirin & Paracetamol (Acetaminophen) Poisoning. Kent R. Olson, M.D. California Poison Control System University of California, San Francisco. Case Study:. A 76 year old woman was brought by her family because of increasing confusion and agitation, and difficulty breathing.

Audrey
Download Presentation

Aspirin & Paracetamol (Acetaminophen) 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.

E N D

Presentation Transcript


  1. Aspirin & Paracetamol (Acetaminophen) Poisoning Kent R. Olson, M.D. California Poison Control System University of California, San Francisco

  2. Case Study: • A 76 year old woman was brought by her family because of increasing confusion and agitation, and difficulty breathing. • Exam: restless, irritable elderly woman.Temp: 38.2 C Resp: 26HR: 102 BP: 110/76

  3. Case, continued: Anion gap: 18 mmol/L • Laboratory:Na: 144 K: 3.2Cl: 110 HCO3: 16BUN: 10 mmol glucose: 5 mmol/L • Arterial blood gases:pH: 7.48 pCO2: 14 pO2: 98 • Salicylate:68 mg/dL (5 mmol/L)

  4. Acute Overdose: younger age child: accidental adult: suicidal no underlying illness ASA levels high mortality rate lower Chronic Intoxication: older age accidental overmedication underlying disease serum ASA variable mortality >25% Acute vs. Chronic Salicylism:

  5. Mechanisms of Salicylate Toxicity: • Respiratory center stimulation: • tachypnea, respiratory alkalosis • compensatory loss of bicarbonate in urine • Uncoupling of oxidative phosphorylation: • generation of excess heat • lactic acidosis • Cellular metabolic dysfunction • metabolic acidosis

  6. MILD to MODERATE tinnitus, nausea, vomiting tachypnea with respiratory alkalosis metabolic acidosis irritability, lethargy low-grade fever dehydration SEVERE POISONING hyperpnea - resp. distress hyperpyrexia severe acidosis coagulopathy (PT elev.) coma, convulsions pulmonary edema/ARDS cardiovascular collapse Clinical Findings in Salicylism:

  7. Estimation of Severity of Salicylism: • History: • acute ingestion of > 200 mg/kg • chronic use of > 4 gm/day • Clinical indicators: • mental status • metabolic acidosis & respiratory alkalosis • Serum salicylate level

  8. Salicylate Levels: • May help predict severity after single acute OD • 6 hr serum level > 100 mg/dL (7 mmoL) serious • Pitfalls in use of “Done” Nomogram: • massive ingestion: tablet mass & delayed peak • chronic intoxication • altered serum pH may contribute to toxicity

  9. Salicylate is a Weak Acid (pKa 3.5): TISSUES (pH 6.8) BLOOD (pH 7.4) URINE (pH variable) HA HA HA H++A- H+ + A- H+ +A- Acidosis Alkalosis

  10. Treatment of Salicylate Poisoning: • Gastrointestinal decontamination • for acute OD • activated charcoal (goal is 10:1 AC:ASA ratio) • lavage for massive recent ingestion • Supportive measures: • ABCs plus dextrose if low blood glucose • volume replacement with IV fluids • external cooling

  11. Enhanced Elimination of Salicylate: • Urine alkalinization: • 1 liter dextrose in 0.25 NS + 100 mEq NaHCO3 • add KCl 20 mEq/L once urine flow established • run at 150-200 mL/hr (2-3 cc/kg) • monitor urine pH (goal 7-8) • Repeated dose activated charcoal • assures adequate gut decontamination • may enhance elimination by “gut dialysis”

  12. Indications for Hemodialysis: • Serum salicylate levels: • acute OD: >100-120 mg/dL (7-8 mmoL) • chronic: 60-80 mg/dL if elderly, altered CNS • Severe acidosis • Renal failure • Coma, convulsions • Progressive deterioration

  13. Case Study: • A 17 year old young man took a bottle of aspirin and several glasses of whiskey after failing his exams. He is drunk and depressed. • BP 120/80 HR 105Resp 14 Temp 37 C • Glucose 5 mmoL (90 mg/dL)EtOH 30 mmoL (140 mg/dL)Anion gap 12 mmoL

  14. Case, continued: • Serum salicylate: not detectable • He is treated with intravenous fluids, given a psychiatric referral, and sent home with his parents. • 3 days later he returns with jaundice and lethargy. WHAT IS YOUR DIAGNOSIS?

  15. Paracetamol Poisoning • Common analgesic • frequently considered “aspirin” by lay persons • often found in combination products • Diagnosis easily missed • often overlooked in history • no characteristic early symptoms or signs • only reliable Dx: STAT SERUM LEVEL

  16. Mechanism of Paracetamol Toxicity: • Normal metabolism - 3 routes: • glucuronidation • sulfation • mixed function oxidase (p-450 system) • creates a highly reactive intermediate metabolite • normally rapidly scavenged by intracellular glutathione Nontoxic metabolites

  17. Paracetamol Toxicity: • Overdose: • sulfation and glucuronidation saturated • increased production of p-450 metabolite • glutathione eventually depleted • reactive intermediate injures cells • Higher-risk groups: enhanced p-450 activity • chronic alcoholics • chronic use of anticonvulsants, INH

  18. Clinical Manifestations of Toxicity: • Early: non-specific • anorexia, vomiting • 24-48 hrs: • onset of liver injury • AST, ALT may exceed 10,000 IU • prothrombin time (PT) often elevated early • uncertain prognostic value • renal injury may also occur

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

  20. Prediction of Paracetamol Toxicity: • History: • acute ingestion of 150-200 mg/kg or 7-8 gm • chronic use of 4-6 gm/day in high-risk group • Clinical evaluation: • serum paracetamol level is only reliable predictor • levels associated with “probable toxicity”: • 200 mg/L at 4 hrs after acute ingestion • 100 at 8 hrs • 50 at 12 hrs

  21. Tylenol “Extended Relief” Case: Serum APAP 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

  22. Pitfalls with Nomogram: • Chronic intoxication • Delayed or erratic absorption • massive or mixed ingestion • Extended-Relief Tylenol (new USA product) • High-risk groups • reduce nomogram line by 50%?

  23. Treatment of APAP Poisoning: • Gut decontamination • activated charcoal +/- lavage • avoid ipecac-induced emesis • Antidote: N-acetylcysteine (NAC) • provides SH group to bind to toxic intermediate • most effective if started within 8-10 hrs after ingestion • may have nonspecific antioxidant benefit • prolonged administration for liver failure

  24. ORAL (USA) Dose: 140 mg/kg PO...followed by 70 mg/kg q 4 hrs Duration - controversial: standard: 72 hrs some centers: 24-36 hrs INTRAVENOUS Dose: 150 mg/kg IV over 15 min...followed by 50 mg/kg over 4 hrs...followed by 100 mg/kg over 16 hrs Total duration 20 hrs N-acetylcysteine Prophylaxis: • Initiate NAC within 8-10 hours, if possible • Extended treatment may be needed for liver failure

More Related