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
Therapeutic plasma concentration is 5-20 ╬╝g/mL.
Diagnosis
Signs and Symptoms
Acute overdose: á
- 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.
- 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 hepatitis
- Reye syndrome
- Amanita sp. mushrooms toxicity
- Herbal and dietary supplements
- Other 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 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.
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 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.
- 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)