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Acetaminophen Poisoning, Emergency Medicine

Therapeutic plasma concentration is 5-20 ╬╝g/mL. ## Diagnosis

- Phase 1: 0.5-24 hr postingestion: - Nausea, vomiting, malaise - Occurs with large overdoses - May not be present with smaller toxic doses

- Phase 2: 24-72 hr postingestion: - Decreased GI symptoms - Hepatic damage is occurring. - Right upper quadrant pain and tenderness - Elevation of liver enzymes, PT/INR, bilirubin - Oliguria - Prolonged (>4 hr) APAP half-life implies hepatic toxicity.

- Phase 3: 72-96 hr postingestion: - Critical time period in the prognosis - Peak liver function abnormalities - Hepatic encephalopathy develops. - If the PT/INR continues to rise and/or renal insufficiency develops beyond the 3rd day postingestion, there is high likelihood that the patient will require hepatic transplantation.

- Suspect APAP as coingestant with other drugs in overdose. - Causes of acute onset hepatotoxicity: - Infectious hepatitis - Reye syndrome - Amanita sp. mushrooms toxicity - Herbal and dietary supplements - Other drug ingestions

- >24 hr postingestion or chronic repeated APAP ingestion - Initiate NAC if: - Ingestion >150 mg/kg APAP - Symptomatic - Abnormal hepatic screening panel - Discontinue NAC if APAP falls to nondetectable level and no AST elevation occurs by 36 hr postingestion. - Call poison center ([800] 222-1222) or toxicologist for help.

- IV NAC (2 options): - Acetadote « infusion given per manufacturers instructions - Oral NAC given by IV route if: - Oral form not tolerated because of vomiting - Acetadote « not available - Contact local poison center or toxicologist for help.

para>(Adapted from Rumack áBH, Matthew áH. Acetaminophen poisoning and toxicity. Pediatrics. 1975;55:871-876.)View OriginalRumack-Matthew nomogram.

(Adapted from Rumack áBH, Matthew áH. Acetaminophen poisoning and toxicity. Pediatrics. 1975;55:871-876.)

View Original

Diagnosis

Signs and Symptoms

Acute overdose: á

  • Phase 1: 0.5-24 hr postingestion:Nausea, vomiting, malaiseOccurs with large overdosesMay not be present with smaller toxic doses
  • Phase 2: 24-72 hr postingestion:Decreased GI symptomsHepatic damage is occurring.Right upper quadrant pain and tendernessElevation of liver enzymes, PT/INR, bilirubinOliguriaProlonged (>4 hr) APAP half-life implies hepatic toxicity.
  • Phase 3: 72-96 hr postingestion:Critical time period in the prognosisPeak liver function abnormalitiesHepatic encephalopathy develops.If the PT/INR continues to rise and/or renal insufficiency develops beyond the 3rd day postingestion, there is high likelihood that the patient will require hepatic transplantation.
  • Phase 4: 96 hr to 10 days postingestion:Resolution of hepatic injury or progression to complete hepatic failure

Essential Workup

  • Ingestion history of all APAP-containing products
  • Time of ingestion
  • APAP level:Obtain 4 hr postingestion level or immediately on presentation if >4 hr postingestion.Use Rumack-Matthew nomogram as therapeutic guide for single acute overdose (see Fig. 1).In chronic or very late ingestions (>24 hr), obtain level, but do not use nomogram for therapeutic guidance.
  • Call poison center ([800] 222-1222) or toxicologist.

Diagnosis Tests & Interpretation

Lab

  • APAP level
  • Electrolytes, BUN, creatinine, and glucose
  • Liver enzymes:Elevated AST is the first abnormality detected.AST/ALT levels may rise >10,000 in stage III of toxicity.Bilirubin
  • PT/INR
  • Pregnancy test
  • Toxicology screen

Differential Diagnosis

  • Suspect APAP as coingestant with other drugs in overdose.
  • Causes of acute onset hepatotoxicity:Infectious hepatitisReye syndromeAmanita sp. mushrooms toxicityHerbal and dietary supplementsOther drug ingestions

Treatment

Pre-Hospital

  • Transport all pill bottles/pills involved in overdose for identification in ED.
  • OTC cold remedies often contain APAP.

Initial Stabilization/Therapy

  • Airway, breathing, circulation (ABCs)
  • Administer supplemental oxygen.
  • Administer naloxone, thiamine, D50 (or Accu-Chek) for altered mental status.

Ed Treatment/Procedures

  • Supportive care:
  • Gastric decontamination:Administer a single dose of activated charcoal if recent ingestion.

N-acetylcysteine (NAC) Administration

  • Administer if toxic level detected as defined by Rumack-Matthew nomogram.
  • NAC virtually 100% hepatoprotective if initiated within 8 hr of an acute overdose
  • NAC available in oral form or IV form
  • <8 hr postingestion:Check APAP level.Initiate NAC if APAP level will not be available within 8 hr of ingestion and toxic ingestion suspected.Discontinue NAC if APAP level nontoxic.
  • ≥8 hr postingestion:Initiate NAC immediately if suspected toxic ingestion.Check APAP level.Discontinue NAC if APAP level is nontoxic.
  • >24 hr postingestion or chronic repeated APAP ingestionInitiate NAC if:Ingestion >150 mg/kg APAPSymptomaticAbnormal hepatic screening panelDiscontinue NAC if APAP falls to nondetectable level and no AST elevation occurs by 36 hr postingestion.Call poison center ([800] 222-1222) or toxicologist for help.

NAC Preparations

  • Oral NAC:Poor taste and odor:Dilute to 5% with fruit juice or soft drink to increase palatability.Use antiemetics (metoclopramide or ondansetron) liberally to facilitate PO administration.If the patient vomits NAC within 1 hr of administration, repeat the dose.Administer NAC as a drip through nasogastric (NG) tube if vomiting continues.Given q4h
  • IV NAC (2 options):Acetadote « infusion given per manufacturers instructionsOral NAC given by IV route if:Oral form not tolerated because of vomitingAcetadote « not availableContact local poison center or toxicologist for help.
  • No teratogenicity with NAC
  • NAC may be effective in protecting fetal liver:Fetal liver metabolizes APAP to toxic NAPQI after 14 wk gestation.

A shortened oral NAC protocol may be considered with poison center or toxicology consultation. á

Medication

  • NAC: 140 mg/kg PO loading (adult and pediatric) followed by 70 mg/kg q4h for 17 additional doses
  • Acetadote: 21 hr IV infusion: 150 mg/kg over 60 min, then 50 mg/kg over 4 hr, then 100 mg/kg over 16 hr for total dose 300 mg/kg (see package insert for additional guidance, especially for pediatric infusion dosing)
  • Activated charcoal: 1-2 g/kg PO
  • Dextrose: D50W 1 amp (50 mL or 25 g; peds: D25W 2-4 mL/kg) IV
  • Metoclopramide: Start with 10 mg (peds: 1 mg/kg) IV (1 mg/kg max.)
  • Naloxone (Narcan): 0.4-2 mg (peds: 0.1 mg/kg) IV or IM initial dose
  • Ondansetron: >80 kg, 12 mg; 45-80 kg, 8 mg (peds: 0.15 mg/kg) IV
  • Thiamine (vitamin B1): 100 mg (peds: 50 mg) IV or IM

Treating the mother maximizes treatment for the fetus. NAC crosses the placenta and is considered safe PO or IV. á

Follow-Up

Disposition

Admission Criteria

  • Hepatotoxic level of APAP requiring full course of NAC therapy (see "Treatment"Ł)
  • LFT abnormalities in the setting of chronic ingestion or late presentation
  • Nontoxic suicide attempt requiring psychiatric treatment

Discharge Criteria

Asymptomatic patients with nontoxic ingestions not requiring full course of NAC therapy á

Issues for Referral

Evidence of significant hepatotoxicity at time of ED arrival warrants early evaluation by hepatology and/or transplant service. á

Follow-Up Recommendations

  • Substance abuse referral for patients with oral opiate abuse
  • Patients with unintentional (accidental) poisoning require poison prevention counseling.
  • Patients with intentional (e.g., suicide) poisoning require psychiatric evaluation.

Pearls and Pitfalls

  • Consider occult APAP poisoning in patients evaluated for oral opiate abuse.
  • Do not use the nomogram for patients with chronic ingestion or late presentation.
  • Do not stop NAC therapy until nondetectable APAP level and improvement (or resolution) of laboratory and clinical evidence of hepatotoxicity.

Additional Reading

  • Brok áJ, Buckley áN, Gluud áC. Interventions for paracetamol (acetaminophen) overdose. Cochrane Database Syst Rev. 2006;19(2):CD003328.
  • Heard áK. Acetylcysteine for acetaminophen poisoning. N Engl J Med. 2008;359(3):285-292.
  • Larson áAM, Polson áJ, Fontana áR, et al. Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology. 2005;42(6):1364-1372.
  • Rumack áBH. Acetaminophen misconceptions. Hepatology. 2004;40(1):10-15.
  • Williamson áK, Wahl áMS, Mycyk áMB. Direct Comparison of 20-Hour IV, 36-Hour Oral, and 72-Hour Oral Acetylcysteine for Treatment of Acute Acetaminophen Poisoning. Am J Ther. 2013;20(1):37-40.

Codes

ICD9

965.4 Poisoning by aromatic analgesics, not elsewhere classified á

ICD10

  • T39.1X1A Poisoning by 4-Aminophenol derivatives, accidental, init
  • T39.1X2A Poisoning by 4-Aminophenol derivatives, self-harm, init
  • T39.1X4A Poisoning by 4-Aminophenol derivatives, undetermined, init

SNOMED

  • 70273001 Poisoning by acetaminophen
  • 290134002 Accidental acetaminophen poisoning (disorder)
  • 290136000 Acetaminophen poisoning of undetermined intent (disorder)