Module 9: Summary

This module summarizes the key concepts covered in the acetaminophen toxicity course.

Key Chapter Summaries

• Introduction: Acetaminophen poisoning is common worldwide and is the leading cause of acute liver failure in many countries. Risk assessment and antidotal therapy with NAC have greatly improved outcomes. However, controversies remain regarding alternative risk stratification tools, optimized NAC regimens, and advanced management strategies.
• Clinical Manifestations: The clinical course progresses through four stages, from asymptomatic to hepatic injury onset, maximal hepatotoxicity, and finally recovery in survivors. AST elevation precedes hepatic dysfunction. Fulminant failure brings complications like coagulopathy, renal failure, metabolic acidosis and cerebral edema.
• Diagnostic Evaluation: A serum acetaminophen level plotted on the Rumack-Matthew nomogram at 4 hours post-ingestion determines the need for NAC in acute overdoses. Unknown times or repeated doses require checking AST/ALT, with NAC indicated for values above normal.
• Management Principles: NAC is highly effective when initiated within 8 hours of ingestion. Oral dosing is 140 mg/kg loading dose then 70 mg/kg every 4 hours for up to 72 hours. IV dosing is a 150 mg/kg infusion over 1 hour then maintenance doses over 20 hours.
• Special Considerations: Higher NAC doses may help in massive ingestions with prolonged elevated acetaminophen levels. Elimination techniques include hemodialysis and MARS dialysis. Special care is needed in pediatrics, pregnancy, renal disease, and chronic alcohol use.
• In summary, acetaminophen remains a highly utilized and largely safe analgesic when used appropriately. However, toxicity carries a significant morbidity and mortality if not properly recognized and treated. Expertise is this domain is crucial for emergency clinicians and poison control specialists tasked with risk stratification, antidote administration, and nuanced management.

High Yield Learning Points

• Acetaminophen is safe when used appropriately but is the leading cause of acute liver failure from overdose. Toxicity occurs from the reactive metabolite NAPQI depleting glutathione and binding proteins.
• Risk assessment involves plotting the 4-hour acetaminophen level on the Rumack-Matthew nomogram. Levels above the treatment line warrant NAC therapy. Special considerations are needed for unknown times, repeated doses, and IV acetaminophen.
• N-acetylcysteine (NAC) replenishes glutathione and is highly effective at preventing hepatotoxicity if given within 8 hours of ingestion. Oral and IV routes are equally efficacious. The IV route is preferred for toxicity during pregnancy and with vomiting/coma.
• Oral NAC dosing is 140 mg/kg loading dose then 70 mg/kg every 4 hours for 17 doses. IV NAC dosing is 150 mg/kg over 1 hour, then 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours.
• Hepatotoxicity markers like elevated AST and coagulopathy guide the duration of NAC therapy. Fulminant hepatic failure warrants NAC infusion until resolution of altered mental status and INR < 2.
• Massive acute ingestions may benefit from higher NAC doses. Elimination techniques include hemodialysis for prolonged high acetaminophen levels and MARS for liver failure.

References

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