Supratherapeutic amounts of acetaminophen were given to at least 4% of adult inpatients studied, according to a retrospective review of the electronic medical records of 14,000 patients treated in two hospitals during a three-month period.

Li Zhou, MD, PhD, a senior medical informatician in the Clinical Informatics Research & Development department at Partners HealthCare and an instructor in medicine at Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, and colleagues published their results online November 12 in the Archives of Internal Medicine.

Acetaminophen is one of the most widely used medications for relieving pain and reducing fever, but it is also the most common cause of acute liver failure, the authors note.

The study population comprised 14,411 patients (60.7%) who received acetaminophen. A total of 955 of 23,750 (6.6%) of all hospitalized adults were given in excess of 4 g/d (9.6% at hospital A and 4.2% at hospital B). The recommended limit of 3 g/d was exceeded by 22.3% of patients 65 years or older and 17.6% of patients with chronic liver disease.

Averaged over the entire hospital stay, those who were given supratherapeutic dosing received more administrations per day (3.5 vs 1.5; P < .001) and a higher dose per administration (791 mg vs 651 mg; P < .001).

Almost half (45.9%) of the occurrences of supratherapeutic dosing were at least 5 g/d. About 40% of patients were given supratherapeutic dosing for at least 3 days and 4.0% for at least 10 days.

Preexisting chronic liver disease 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 likelihood of supratherapeutic dosing (OR, 4.2 [95% CI, 3.6 - 5.0]).

No difference in supratherapeutic dosing rate was found between those who were given multi-ingredient products and those who were not; however, a higher risk was found in patients who used single-ingredient products (OR, 3.4 [95% CI, 2.5 - 4.6]).

Patients who were given more than 1 type of acetaminophen-containing medication had higher supratherapeutic dosing rates (OR, 1.8 [95% CI, 1.5 - 2.1]). Almost one fifth (20.7%) of the 164 patients who received at least 3 different acetaminophen-containing products had supratherapeutic dosing.

In multivariate analysis, the strongest risk factors for supratherapeutic dosing were recurring scheduled administrations (hazard ratio [HR], 16.6 [95% CI, 13.5 - 20.6]), the number of different products given to a patient (HR, 2.4 for each additional product [95% CI, 2.0 - 2.9]), and the use of products that contain 500-mg acetaminophen (HR, 1.9 [95% CI, 1.5 - 2.3]). Investigators adjusted the multivariate analysis for age, sex, race, hospital, hospital unit, diagnosis, dosing instructions, and several other factors found to be statistically significant in the univariate analysis.

White patients (HR, 1.5 [95% CI, 1.3 - 1.7]), those with osteoarthritis (HR, 1.4 [95% CI, 1.3 - 1.6]), and patients admitted to the hospital (HR, 1.6 [95% CI, 1.4 - 1.8]) were more likely to receive excessive dosing. The risk was lower among patients admitted to medicine or other units (HR, 0.6 [95% CI, 0.5 - 0.7]) and patients who had as-needed administrations (HR, 0.7 [95% CI, 0.6 - 0.9]).

"While no causal relationship can be inferred, patients who received supratherapeutic dosing were more likely to have statistically significant elevations in ALP [alkaline phosphatase] level, statistically insignificant elevations in ALT [alanine aminotransferase] level, but neither clinically nor statistically significant changes in other liver injury markers," the authors write.

Commitment to Change Needed

In an invited commentary, Walter H. Ettinger, MD, MBA, Department of Medicine, University of Massachusetts Medical School, Worcester, and Accretive Health Inc, Chicago, Illinois, writes, "[E]xcessive dosing of acetaminophen should be a 'never event.' The best way to prevent excessive dosing is to engineer a process and imbed it in the [electronic health record] such that it creates a hard stop that prevents ordering and administering more than 4 g/d of acetaminophen."

Hospitals need to be committed to reducing the time it takes to bring improvements to patients, and technology, such as electronic medical records, needs to be flexible enough to change to meet patient and provider needs.

"[T]o drive change and innovation we need a large investment in performance improvement and process engineering, business intelligence systems, and analytical capabilities to take full advantage of HIT [health information technology] and to move us toward the goal of becoming a rapid-learning health system," Dr. Ettinger explains.

The study was funded by the Partners-Siemens Research Council. The study authors have disclosed no relevant financial relationships. Dr. Ettinger is an employee of, and has stock options from, Accretive Health Inc.

Arch Intern Med. Published online November 12, 2012. Abstract

Troy Brown • Medscape Medical News © 2012 WebMD, LLC