TABLE 10. Diagnosis and management of APAP hepatotoxicity.

Recommendation	Intentional overdose	Unintentional overdose
Diagnostic approach
Time of ingestion	Single time point	Several days of repeated use
Dose	Supratherapeutic (typically > 4 g over 24 h)	Repeated therapeutic (up to 4 g per day) or supratherapeutic dosing
Presence of coingestants	Diphenhydramine and other sedatives can lead to central nervous system depression	Opioids often used in combination
Liver injury parameters	From time of ingestion: 24–72 h: rapid rise in ALT to > 1000 IU/L associated with variable rise in INR; total bilirubin is typically < 10 mg/dl. 72–96 h: Biochemical elevations peak, and can progress to acute liver failure or rapid and full recovery	Presentation is often delayed, but still see rapid rise in ALT to > 1000 IU/L, associated with rise in INR. Comorbid conditions, such as alcohol use, can affect total bilirubin levels. Eventually, liver injury can progress to acute liver failure or recovery
Serum APAP level	Use modified Rumack‐Matthew nomogram to estimate risk of hepatotoxicity	Often undetectable at initial presentation. APAP‐protein adducts useful but assay not commercially available
Excluding other causes of acute liver injury	Review clinical history to exclude risk factors for hepatic ischemia and perform tests for acute viral hepatitis
Management
GI decontamination	Activated charcoal (1 g/kg, max dose 50 g) if within 4 h of ingestion. Gastric lavage also used in some cases175	Usually not helpful nor recommended
N‐acetylcysteine	Oral dosing: 140 mg/kg load followed by 70 mg/kg every 4 h; antiemetics as needed. Intravenous dosing176: preferred if intolerant of oral intake/ileus or pregnant; telemetry monitoring recommended 150 mg/kg load over 15–60 min, followed by 50 mg/kg (12.5 mg/kg/h) over the next 4 h then 100 mg/kg (6.25 mg/kg/h) over 16 h thereafter (total 300 mg/kg over 24 h). For those with evidence of liver injury, treatment is extended at 6.25 mg/kg/h until ALT is decreasing and INR is < 2
Evidence of acute liver failure (coagulopathy and encephalopathy)	Close monitoring in intensive care unit and consider prompt referral to a liver transplant center

Abbreviation: GI, gastrointestinal.