Excessive Acetaminophen Dosing Prevalent in Hospitals

Acetaminophen is one of the most commonly used medications for relieving pain and reducing fever, but it is also the leading cause of acute liver failure. The results of a retrospective study found that at least 4% of all hospitalized patients received a supratherapeutic dose of acetaminophen over a 3-month period [Arch Intern Med. 2012;172(22):1721-1728].

To investigate acetaminophen use in the inpatient setting, researchers conducted a retrospective review of electronic health records for >14,000 patients ≥12 years of age admitted to 2 tertiary care hospitals in Boston, Massachusetts, between June 1, 2010, and August 1, 2010. The main outcome measures included acetaminophen exposure rate and supratherapeutic dosing rate among patients, risk factors for excessive dosing, and changes in liver function test before and after supratherapeutic dosing. An occurrence of supratherapeutic dosing was defined as any cumulative administration of acetaminophen >4 g a day.

Of the 23,750 patients hospitalized during this period, 14,411 patients (60.7%) received acetaminophen and were included in the study. The patients’ average age was 55.4 years, 35.1% were ≥65 years of age, and 6.9% had chronic liver disease (CLD). A total of 955 of 23,750 (6.6%) of all hospitalized patients exceeded the 4 g-a-day limit (9.6% at hospital A and 4.2% at hospital B). The recommended limit of 3 g a day was exceeded by 22.3% of patients ≥65 years of age and 17.6% of patients with CLD. Averaged over the entire hospital stay, patients who were given excessive dosing had more administrations per day and a higher dose per administration compared with the control group (3.5 vs 1.5 and 791 mg vs 651 mg, respectively; P<.001 for both comparisons).

Pre-existing CLD was associated with a decreased risk for supratherapeutic dosing (odds ratio [OR], 0.5; 95% confidence interval [CI], 0.4-0.7), and osteoarthritis was associated with an increased risk (OR, 4.2%; 95% CI, 3.6-5.0). No difference in supratherapeutic dosing rate was observed between those given multi-ingredient products and those who were not; however, a greater risk was seen in patients who received single-ingredient products (OR, 3.4; 95% CI, 2.5-4.6).

In the multivariate analysis, a significantly greater risk of supratherapeutic dosing was found in hospital A (hazard ratio [HR], 1.6; 95% CI, 1.4-1.8), white patients (HR, 1.5; 95% CI, 1.3-1.7), patients diagnosed with osteoarthritis (HR, 1.4; 95% CI, 1.3-1.6), and those who received scheduled administrations (HR, 16.6; 95% CI, 13.5-20.6), multiple drug formulations (HR, 2.4; 95% CI, 2.0-2.9), or the 500-mg strength formulation (HR, 1.9; 95% CI, 1.5-2.3). The risk was lower among patients who had as-needed administrations (HR, 0.7; 95% CI, 0.6-0.9) and were admitted to medicine or other units (HR, 0.6; 95% CI, 0.5-0.7). While patients receiving excessive doses of acetaminophen were likely to have statistically significant alkaline phosphate elevations, no causal relationship can be concluded.

“Our findings showed that despite policies and procedures to monitor and control patients’ acetaminophen exposure, the incidence of supratherapeutic acetaminophen dosing in hospitalized patients remains high,” the researchers said.

They noted that a number of risk factors for excessive dosing are within the hospitals’ control including recurring scheduling of doses, use of products with >325 mg of acetaminophen per dose, and use of multiple products containing acetaminophen.