Nomogram line crossing after acetaminophen combination product overdose.

BACKGROUND: The Rumack-Matthew nomogram predicts the risk of hepatotoxicity following acute acetaminophen overdose based on a serum concentration obtained ≥ 4-hour post-ingestion. Some patients with low-risk concentrations at 4 hours may have subsequent values indicating increased risk (above the nomogram treatment line), especially if coingestants that slow gastrointestinal motility are involved. The treatment line currently used to identify low risk patients in the United States, Canada, and Australia begins at 150 mcg/mL (993 µmol/L) and intersects at 18.75 mcg/mL (124.1 µmol/L) 16 hours post-ingestion. OBJECTIVE: To determine the incidence of nomogram line crossing after acute overdose of acetaminophen combination products containing an opioid or antihistamine. METHODS: This was a prospective cohort study of hospitalized patients reported to a regional poison center (RPC) after acute overdose of a combination product containing an opioid or antihistamine. If a 4-hour acetaminophen concentration was detectable but below the nomogram treatment line, the RPC recommended repeat concentrations. Patients were entered into the study if at least one subsequent concentration was available. During follow-up calls hospital providers were queried regarding clinical features, treatment, and indicators of liver injury. RESULTS: Over a 4-year period 76 patients met entry criteria. 5/76 (6.6%) had measureable acetaminophen concentrations below the treatment line at or close to 4-hour post-ingestion followed by values above the line obtained at 6.5-12.5 hours. Four of the five were treated with acetylcysteine and none developed hepatotoxicity. Four of the five had clinical features reported to the RPC suggesting toxicity from the opioid or antihistamine component. CONCLUSION: After acute overdose of acetaminophen combination products, patients with detectable but non-toxic 4-hour acetaminophen concentrations should have repeat concentrations obtained in a time frame that would allow providers to initiate acetylcysteine treatment, if needed, without undue delay.

Acetaminophen concentrations prior to 4 hours of ingestion: impact on diagnostic decision-making and treatment.

BACKGROUND: Consensus recommendations for acute acetaminophen exposure include plotting an acetaminophen concentration at ≥ 4 h post ingestion on the Rumack-Matthew nomogram to determine the need for acetylcysteine treatment. We studied the frequency of acetaminophen concentrations drawn within 4 h post ingestion and whether the Rumack-Matthew nomogram was properly used in making acetylcysteine treatment decisions. METHODS: This was a retrospective, observational case series at three regional poison centers of acute acetaminophen exposures between 1/1/13 and 12/31/13. Cases were analyzed for demographics, timing of acetaminophen concentrations, and application of the Rumack-Matthew nomogram in acetylcysteine initiation or termination. RESULTS: 1,123 cases of acute acetaminophen exposure were reviewed. Of 520 acute acetaminophen exposure cases presenting < 4 h post ingestion, 323 (62%) had a pre-4-hour acetaminophen concentration measured and 197 (38%) did not. Those with a known pre-4-hour acetaminophen concentration were less likely to have a 4-hour acetaminophen concentration (59% vs. 93%) or an acetaminophen concentration within 8 h (87% vs. 99%) and were more likely to be treated with acetylcysteine (29% vs. 17%) and less likely to be treated based on the Rumack-Matthew nomogram (72% vs. 97%). CONCLUSIONS: Patients with a known exposure time and presenting within 4 h of acetaminophen ingestion had a pre-4-hour acetaminophen concentration obtained 62% of the time. Pre-4-hour acetaminophen concentrations cannot be used to determine the need for acetylcysteine therapy and are associated with an increased likelihood of not obtaining optimally timed acetaminophen concentrations and acetylcysteine management not based on the proper application of the Rumack-Matthew nomogram. Current practice results in additional cost, unnecessary treatment, potential adverse medication effects, and the possibility of non-treatment of patients at risk of hepatotoxicity.