Excessive Acetaminophen Dosing Common in Hospitals

Despite monitoring and recording of inpatient acetaminophen dosing, the results of a study find that 1 in 25 patients admitted to a pair of hospitals received a supratherapeutic dose, putting them at risk of severe adverse effects.

One in 25 patients admitted to a pair of hospitals over a 3-month period received a supratherapeutic dose of acetaminophen at least once during their hospital stay, putting them at risk of liver damage, acute liver failure, and death, according to the results of a study published in the December 10/24, 2012, edition of Archives of Internal Medicine.

The potential for acetaminophen overdose has received more attention in the outpatient setting than the inpatient setting, where clinicians are more aware of the risks of overdose and where the patient’s consumption of acetaminophen is monitored and recorded. Nonetheless, there is a risk that tracking of daily dosages will fail to catch instances of inadvertent supratherapeutic dosing. To discover how common this is, the researchers conducted a retrospective review of electronic health records of patients aged 12 years and older admitted to 2 academic tertiary care hospitals in Boston between June and August 2010.

Of 23,750 patients admitted during this period, 14,411 (60.7%) received acetaminophen and were included in the study. The patients’ average age was 55.4 years, 35.1% were aged 65 years or older, and 6.9% had chronic liver disease. Of the patients who received acetaminophen, 955 (6.6%) received more than the 4 g per day maximum recommended dose, and almost half (45.9%) of the supratherapeutic doses exceeded 5 g per day. (Counting all hospitalized patients, 4.0% received a supratherapeutic dose of acetaminophen.) In addition, 22.3% of patients aged 65 years and older and 17.6% of patients with chronic liver disease received more than the recommended daily limit for these populations of 3 g of acetaminophen.

Patients who received a supratherapeutic dose of acetaminophen received more administrations of the medication per day (3.5 vs. 1.5) and a higher dose per administration (791 mg vs. 651 mg) compared with patients who did not receive a supratherapeutic dose. Each patient who received a supratherapeutic dose had an average of 4.9 incidences, comprising an average of 2.9 days

A significantly higher risk of supratherapeutic dosing was found in white patients (hazard ratio of 1.5), in patients diagnosed with osteoarthritis (HR of 1.4), and in those who received scheduled administrations of acetaminophen (HR of 16.6), multiple product formulations containing acetaminophen (HR of 2.4 for each additional product), or the 500-mg formulation of acetaminophen (HR of 1.9). A lower risk of supratherapeutic dosing was found in those who received acetaminophen as needed (HR of 0.7) and those in nonsurgical and non—intensive care units (HR of 0.6). In addition, patients who received supratherapeutic dosing were more likely to have statistically significant elevations in ALP level and statistically insignificant elevations in ALT level, but had neither clinically nor statistically significant changes in other liver injury markers.

Despite measures taken to control and monitor acetaminophen exposure, this study’s findings indicate that the incidence of supratherapeutic dosing in hospitalized patients remains high. The researchers note that a number of the risk factors for supratherapeutic dosing are within hospitals’ control: recurring scheduling of doses, use of products with more than 325 mg of acetaminophen per dose, and the use of multiple products with acetaminophen. The use of recurring doses was a particularly big risk factor, and the typical regimen for extra-strength acetaminophen of 1 g every 6 hours leaves no room for error in the timing of acetaminophen administration. The researchers note that it may be time to reassess this regimen. In addition, they recommend that computerized tracking of acetaminophen dosing could help ensure that supratherapeutic dosing occurs less frequently.