Acetaminophen Overdose and NAC Dosing

Why Use

The Rumack-Matthew nomogram is the most sensitive risk prediction tool in medical toxicology. It identifies patients at very low risk of developing hepatotoxicity after acetaminophen overdose and who do not require NAC. All patients above the nomogram line should be treated with NAC to decrease the risk of developing hepatotoxicity (See Evidence ).

When to Use

When to use the Rumack-Matthew nomogram: Acute, single ingestions (where entire ingestion occurs within an 8-hour period). A known time of ingestion. Immediate release formulation. Absence of formulations or coingestants that alter absorption and bowel motility (e.g. anticholinergics, opioids).

Formula

Pearls / Pitfalls

An acetaminophen concentration obtained prior to 4 hours post-ingestion cannot be plotted on the Rumack-Matthew nomogram, and only confirms acetaminophen exposure, not toxicity. Get an accurate time of ingestion: the Rumack-Matthew nomogram is entirely dependent on knowing time of ingestion. Start NAC treatment within 8 hours post-ingestion to decrease the risk of hepatotoxicity (AST or ALT >1000 IU/L). In patients presenting 8-24 hours post-ingestion, start NAC while awaiting the acetaminophen concentration; once this is resulted, NAC can be continued or discontinued depending on the level.

Management

If known time of ingestion Obtain acetaminophen concentration at 4 hours post-ingestion or as soon as possible thereafter. Plot acetaminophen concentration on Rumack-Matthew nomogram (see above). If above “treatment line” (line connecting 150 µg/mL (993 µmol/L) at 4 hours and 4.7 µg/mL (31 µmol/L) at 24 hours), NAC is indicated. Unknown time of ingestion Determine earliest possible time of ingestion: If <24 hours post-ingestion, plot on Rumack-Matthew nomogram and initiate NAC if above “treatment line.” If earliest time of ingestion cannot be estimated, treatment with NAC is indicated if: Detectable acetaminophen concentration. Abnormal aminotransferases (AST or ALT). Extended release formulations/coingestions of opioids, anticholinergics, or other medications that will slow gut motility Obtain initial 4 hour post-ingestion acetaminophen concentration. If above treatment line, NAC is indicated.* If below treatment line, repeat acetaminophen concentration at 6 to 7 hours post-ingestion. If above treatment line, NAC should be initiated within 8 hours post-ingestion. Chronic acetaminophen ingestion Patients taking repeated, supratherapeutic (>4 g/day) acetaminophen ingestions. Treatment with NAC indicated if: Detectable acetaminophen concentration. Abnormal aminotransferases (AST or ALT).

Critical Actions

Serum acetaminophen concentration should be sent in all patients presenting with intentional overdose or those using excessive amounts of acetaminophen containing products. NAC treatment should be initiated within 8 hours post-ingestion to decrease risk of hepatotoxicity.

Advice

Early administration of NAC (<8 hours post-ingestion) is vital to decreasing the risk of hepatotoxicity; acetaminophen is a leading cause of drug-induced liver injury. Acetaminophen is widely available in prescription and over-the-counter medications, either as single agent or combination products (e.g. dextromethorphan, opioids, diphenhydrAMINE). Maintain a strong index of suspicion for acetaminophen toxicity in all patients with intentional drug overdose and those with therapeutic misadventures (e.g. taking excessive amounts of a single product, or using recommended doses of several different acetaminophen containing products).

More Information

Best if NAC started within 8-10 hours of ingestion, but may still be effective up to 24 hours after ingestion. May be given PO or IV. Oral formulation (Mucomyst, generic) 140 mg/kg orally loading dose then 70 mg/kg orally every 4 hours for 68 hours (17 doses). IV formulation (Acetadote, or using oral solution) 150 mg/kg over 60 minutes, then 50 mg/kg over 4 hours (12.5 mg/kg/hr), then 100 mg/kg over 16 hours (6.25 mg/kg/hr).