Episode 203: Acetaminophen Toxicity

We sit down with one of our toxicologists to discuss acetaminophen toxicity. Hosts: Marlis Gnirke, MD Brian Gilberti, MD https://media.blubrry.com/coreem/content.blubrry.com/coreem/Acetaminophen_Toxicity.mp3 Download One Comment Tags: Toxicology Show Notes Table of Contents 0:35 – Hidden acetaminophen toxicity in OTC products 3:24 – Pharmacokinetics and toxicokinetics 6:06 – Clinical Course 9:22 – The antidote – NAC 11:02 – The Rumack-Matthew Nomogram 17:36 – Treatment protocols 22:34 – Monitoring and Lab Work 23:23 – Considerations when treating pediatric patients 23:57 – IV APAP overdose, fomepizole 25:42 – Take Home Points Acetaminophen vs. Tylenol: The importance of recognizing that acetaminophen is found in many products beyond Tylenol. Common medications containing acetaminophen, such as Excedrin, Fioricet, Percocet, Dayquil/Nyquil, and others. The risk of unintentional overdose due to combination products. Prevalence of Acetaminophen Toxicity: Widespread availability and under-recognition contribute to its prevalence. The potential for unintentional overdose when taking multiple medications containing acetaminophen. Pharmacokinetics and Metabolism: Normal metabolism pathways of acetaminophen and the role of glutathione. Formation of the toxic metabolite NAPQI during overdose situations. Saturation of safe metabolic pathways leading to hepatotoxicity. Pathophysiology of Liver Injury: How excessive NAPQI leads to hepatocyte death, especially in zone III of the liver. The difference between therapeutic dosing and overdose metabolism. Clinical Stages of Acetaminophen Toxicity: Stage 1: Asymptomatic or nonspecific symptoms (first 24 hours). Stage 2: Onset of hepatic injury (24-72 hours), elevated AST/ALT. Stage 3: Maximum hepatotoxicity (72-96 hours), signs of liver failure. Stage 4: Recovery phase, complete hepatic regeneration if survived. Antidote – N-Acetylcysteine (NAC): Mechanisms of NAC in replenishing glutathione and detoxifying NAPQI. The importance of early administration, ideally within 8 hours post-ingestion. NAC’s role even in late presenters and in fulminant hepatic failure. The Rumack-Matthew Nomogram: How to use the nomogram for acute overdoses to determine the need for NAC. Limitations in chronic overdoses and late presentations. Emphasis on obtaining accurate time of ingestion and acetaminophen levels. Treatment Protocols: Standard 21-hour IV NAC protocol and dosing specifics. Managing anaphylactoid reactions associated with IV NAC. Criteria for extending NAC therapy beyond 21 hours. Monitoring and Laboratory Work: Importance of trending AST/ALT, INR, creatinine, lactate, and phosphate. Use of the King’s College Criteria for potential liver transplant evaluation. Special Considerations: Adjustments in pediatric patients regarding NAC dosing volumes. Awareness of IV acetaminophen overdoses and their management. Emerging discussions on the use of fomepizole in massive overdoses. Take-Home Points: Comprehensive Medication History: Always inquire about all medications taken to assess for potential acetaminophen exposure. Early Recognition and Treatment: Due to often silent initial stages, maintain a high index of suspicion and measure acetaminophen levels promptly. Understanding Metabolism and Toxicity: Recognize how overdose alters metabolism, leading to toxic NAPQI accumulation. N-Acetylcysteine Efficacy: NAC is most effective when administered early but remains beneficial even in advanced stages. Proper Use of the Nomogram: Utilize the Rumack-Matthew Nomogram appropriately for acute ingestions and consult toxicology when in doubt. Monitoring and Continuing Care: Be vigilant in monitoring laboratory values and prepared to extend NAC therapy as needed. Consultation and Resources: Engage with poison control centers and utilize available resources for complex cases.   Resources Mentioned Rumack-Matthew Nomogram Rumack-Matthew Nomogram, credit: MDCalc King’s College Criteria King’s College Criteria for Aceta

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