Negative Predictive Value of Acetaminophen Concentrations Within Four Hours of Ingestion

Abstract

Objectives: The objective was to ascertain whether acetaminophen (APAP) concentrations less than 100 lg/mL obtained between 1 and 4 hours after acute ingestion accurately predict a nontoxic 4-hour concentration. Methods:The authors performed a multicenter, prospective cohort study involving five emergency departments (EDs) participating in the ToxIC Research Network. Data were collected from May 2009 to December 2011. Patients with APAP concentrations <100 lg/mL drawn between 1 and 4 hours after acute ingestions, and concentrations drawn 4 or more hours after ingestions, were included in the study. Exclusion criteria included initial concentration >100 lg/mL, initial APAP concentration drawn prior to 1 hour, two undetectable APAP concentrations, the second concentration drawn prior to 4 hours, and unknown time of ingestion. Toxic concentrations 4 or more hours after ingestion were defined as concentrations that plotted above the 150 lg/mL line on the Rumack-Matthew nomogram.Results: Data were collected on 83 patients who met inclusion criteria. Of the 83 patients with APAP concentrations <100 lg/mL between 1 and 4 hours, one patient (1.2%) had a ≥ 4-hour toxic concentration. Negative predictive value (NPV) for an APAP concentration <100 lg/mL obtained between 1 and 4 hours after an acute ingestion was 98.8% (95% confidence interval [CI] = 93.5% to 99.8%).Conclusions: An APAP concentration of <100 lg/mL obtained between 1 and 4 hours after ingestion has a high NPV for excluding toxic ingestion. We do not recommend reliance on concentrations obtained between 1 and 4 hours to exclude toxicity, because of a potential false-negative rate of 6.5%.ACADEMIC EMERGENCY MEDICINE 2013; 20:1072-1075 © 2013 by the Society for Academic Emergency Medicine T here are approximately 50,000 patients who present to emergency departments (EDs) each year due to acetaminophen (APAP) exposure. 1 Those patients with acute ingestions are risk stratified by plotting their APAP concentrations on the RumackMatthew nomogram. 2 The nomogram is only validated for concentrations drawn 4 hours or later after acute APAP ingestions. The 4-hour starting point was chosen because of the initial available data at the time the nomogram was developed and to include the possibility of delayed absorption. 2 However, based on therapeutic dose pharmacokinetics, APAP concentrations should peak much earlier (within 1 hour), 3 suggesting that earlier concentrations may be predictive of toxicity.From the

Bayesian Forecasting Tool to Predict the Need for Antidote in Acute Acetaminophen Overdose

“…Therefore, it may not be necessary to wait until 4 hours to initiate PAC sampling in a patient to be able to use the Rumack–Matthew nomogram. This contrasts with previous work that explored the ability of one PAC < 100 mg/L between 1 and 4 hours as a predictor of subsequent low concentrations after 4 hours since ingestion (i.e., below the Rumack–Matthew nomogram) . While it was recognized that the reported study was limited by sample size, it was concluded that this method resulted in a proportion of false negatives too high for clinical implementation.…”

“…This contrasts with previous work that explored the ability of one PAC < 100 mg/L between 1 and 4 hours as a predictor of subsequent low concentrations after 4 hours since ingestion (i.e., below the Rumack-Matthew nomogram). 20 While it was recognized that the reported study was limited by sample size, it was concluded that this method resulted in a proportion of false negatives too high for clinical implementation. However, prior information provided by the present population PK model and the Bayesian statistical framework has provided a quantitative method for predicting the most likely concentration-time profile that would have arisen in the patient when given one early PAC observation and their prognostic factors.…”

Early Serum Acetaminophen Levels: How Soon Is Too Soon?

“…1 In one single case, serum APAP increased from 58 lg/mL at 90 minutes postingestion to 240 lg/mL at 5 hours. The calculated negative predictive value (NPV) was 98.8% (95% confidence interval [CI] = 93.5% to 99.8%), using a 100 lg/mL cutoff.…”

“…1 As the authors note, APAP poisoning remains a very common condition; over 130,000 APAP exposures were reported to poison control centers in 2011 alone. 2 Fortunately, the Rumack-Matthew nomogram (plotting serum concentration vs. time after acute ingestion) has long provided clinicians with a useful tool for determining which patients require N-acetylcysteine treatment, based on a single serum APAP concentration.…”

A Basis for the Decision to Rule in or out Acetaminophen Toxicity: Assessment of the Serum Level Within 4 Hours Post Overdose

“…To use this nomogram reliably, the serum levels from 4-24 h post-ingestion should be used. This starting point was chosen because of the initial data available at the time of nomogram production and the possibility of delayed drug absorption [5,6]. On the other hand, acetaminophen is absorbed rapidly and reaches the serum peak level within one hour of the ingestion, suggesting that early serum levels can be predictive of the toxicity [5].…”