Acetaminophen Poisoning

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Contents 1 Introduction 2 Etiology 3 Epidemiology 4 Pathology 5 Clinical-manifestations 6 Laboratory 7 Management 8 More General Terms 9 Additional Terms 10 References

Introduction

• In acute acetaminophen overdose, the main site of injury is the liver. 1-10% of patients treated only with supportive care with suffer acute renal failure in conjunction with severe hepatic failure.

Etiology

• toxicity occurs when the amount of acetaminophen ingested exceeds the liver's capacity of glucuronidation & sulfation
• metabolism of acetaminophen by hepatic microsomal enzymes results in a reactive intermediate which overwelms the detoxification capacity of glutathione S-transferase
• risk factors

• 2.6 g/day may be toxic in a poorly nourished alcoholic
• fasting reduces glutathione stores

Epidemiology

• 1/2 of overdoses are unintentional [2]
• individuals taking multiple acetaminophen-containing medications & elderly at risk [2]

Pathology

• hepatitis begins in phase 2
• hepatic necrosis occurs in phase 3
• complete resolution of hepatic dysfunction in phase 4 unless irreversible injury has occurred

Clinical-manifestations

• phase 1

• may begin shortly after ingestion
• duration 12-24 hours
• nausea, vomiting, anorexia, diaphoresis
• some patients may be asymptomatic

• phase 2

• 24-72 hours after ingestion
• right upper quadrant pain

• phase 3

• 72-96 hours
• resembles severe viral hepatitis
• hepatic encephalopathy

• phase 4

• 4 days to 2 weeks
• resolution

Laboratory

• abnormal liver function tests (phase 2)

• serum ALT may be > 6000 U/L

• serum acetaminophen levels

• serum levels > 200 ug/mL obtained at least 4 hours after ingestion mandate N-acetylcysteine administration
• average levels 840 ug/mL with intentional overdose [2] 160 ug/mL with unintentional overdose [2]

Management

• gastric decontamination

• ipecac: beneficial only within 2 hours of ingestion
• gastric lavage

• performed prior to administration of charcoal
• 34-40 French orogastric tube (adults)
• 150-200 mL aliquots of warm water or normal saline
• 5-10 liters total
• beneficial only within 2 hours of ingestion

• activated charcoal

• with & without sorbitol
• beneficial within 4 hours of ingestion

• antidote: N-acetylcysteine

• maximum benefit with 8 hours, but useful up to 24 hours after ingestion
• oral

• load 140 mg/kg PO or NG, then
• 70 mg/kg q 4h X 17
• may be mixed in water or soda

• intravenous:

• 140 mg/kg infused into a peripheral IV over 1 hour using an in-line 0.2-m millipore filter
• maintainance doses q4h of 70 mg/kg infused into a peripheral IV over 1 hour using an in-line 0.2-m millipore filter
• IV solution made by diluting a 20% solution of acetyl- cysteine to 3% with D5W.

• average length of treatment is 48 h
• treatment may be stopped after 5 inital doses of acetyl- cysteine (20 hours) when: [3]

• acetaminophen level is undetectable
• ALT, AST & PT ( INR) are normal

• once severe hepatic toxicity has occurred, treatment is supportive

More General Terms

• toxicity; poisoning; overdose

Additional Terms

• acetaminophen (Tylenol, Paracematol, Panadol, Tempra, Datril, APAP)
• acetylcysteine (Mucomyst, Mucosol, Acetadote)

References

1. Medical Knowledge Self Assessment Program (MKSAP) 11, American College of Physicians, Philadelphia 1998
2. Larson AM et al, Acetaminophen-induced acute liver failure: Results of a United States multicenter, prospective study. Hepatology 2005 Dec; 42:1364 PMID: [1]
3. Betten DP, Cantrell FL, Thomas SC, Williams SR, Clark RF. A prospective evaluation of shortened course oral N-acetylcysteine for the treatment of acute acetaminophen poisoning. Ann Emerg Med. 2007 Sep;50(3):272-9. Epub 2007 Jan 8. PMID: [2]
   - Dart RC, Rumack BH. Patient-tailored acetylcysteine administration. Ann Emerg Med. 2007 Sep;50(3):280-1. Epub 2007 Apr 5. PMID: [3]
4. National Guideline Clearinghouse
   - Clinical policy: critical issues in the management of patients presenting to the emergency department with acetaminophen overdose. (American College of Emergency Physicians) ngc-guideline: [4]

acetaminophen poisoning