SIGNS AND SYMPTOMS 
Acute overdose:
- 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 Rumack-Matthew nomogram).
- 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
[Outline]
PRE-HOSPITAL
- Transport all pill bottles/pills involved in overdose for identification in ED.
- OTC cold remedies often contain APAP.
INITIAL STABILIZATION/THERAPY
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 manufacturer's 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.
Pregnancy Considerations
- No teratogenicity with NAC
- NAC may be effective in protecting fetal liver:
- Fetal liver metabolizes APAP to toxic NAPQI after 14 wk gestation.
ALERT
A shortened oral NAC protocol may be considered with poison center or toxicology consultation.
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
Pregnancy Considerations
Treating the mother maximizes treatment for the fetus. NAC crosses the placenta and is considered safe PO or IV.
[Outline]
DISPOSITION
Admission Criteria
- Hepatotoxic level of APAP requiring full course of NAC therapy (see "Treatment")
- 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
Issues for Referral
Evidence of significant hepatotoxicity at time of ED arrival warrants early evaluation by hepatology and/or transplant service.
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.
[Outline]
ICD9
965.4 Poisoning by aromatic analgesics, not elsewhere classified
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
[Outline]