Dela
We sit down with one of our toxicologists to discuss acetaminophen toxicity.
Hosts:
Marlis Gnirke, MD
Brian Gilberti, MD
Tags: Toxicology
Show NotesTable 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 Acetaminophen ToxicityUse this tool to assess the need for liver transplant evaluation in cases of acetaminophen-induced hepatic failure. Includes criteria for pH, INR, creatinine, and more.Poison Control Center (available 24/7 for consultation): 1-800-222-1222
ReferencesGoldfrank’s Toxicologic Emergencies, 9th Edition was consulted for information on the pharmacokinetics and clinical presentation of acetaminophen toxicity.For more details, see: Nelson, L. S., Howland, M. A., Lewin, N. A., Smith, S. W., Goldfrank, L. R., & Hoffman, R. S. (Eds.). (2011). Goldfrank’s toxicologic emergencies (9th ed.). McGraw-Hill Education.
Podden och tillhörande omslagsbild på den här sidan tillhör Core EM. Innehållet i podden är skapat av Core EM och inte av, eller tillsammans med, Poddtoppen.