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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.

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Aspirin & Paracetamol (Acetaminophen) Poisoning

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  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

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