JAMA Internal Medicine: Drug Dosing Topic Collection

Enoxaparin Outcomes in Patients With Moderate Renal Impairment Enoxaparin Outcomes in Moderate Renal Impairment

DeCarolis DD, Thorson JG, Clairmont MA, et al. — Mon, 10 Dec 2012 00:00:00 GMT

Background

Enoxaparin sodium has predictable pharmacokinetics that allow for simplified dosing without laboratory monitoring. Reliance on renal function for excretion may lead to accumulation of enoxaparin in patients with moderate renal impairment. However, there is no dose adjustment recommended for these patients. We conducted a review to compare bleeding events in patients with moderate renal impairment compared with those with normal renal function.

Methods

Patients received enoxaparin sodium, 1 mg/kg, every 12 hours or 1.5 mg/kg once daily between June 1 and November 30, 2009. Moderate renal impairment was defined as creatinine clearance (CrCl) of 30 to 50 mL/min. Normal renal function was defined as CrCl greater than 80 mL/min. The primary outcome was major bleeding, defined as any bleeding resulting in death, hospital admission, lengthened hospital stay, or an emergency department visit. The secondary outcome was thromboembolism.

Results

A total of 164 patients met the inclusion criteria: 105 with normal renal function and 59 with moderate renal impairment. The primary outcome occurred in 6 of 105 patients (5.7%) with normal renal function vs 13 of 59 patients (22.0%) with moderate renal impairment, representing an unadjusted odds ratio of 4.7 (95% CI, 1.7-13.0; P = .002). The odds ratio using multivariable logistic regression adjusting for differences in risk was 3.9 (95% CI, 0.97-15.6; P = .055). There was no recurrent thromboembolism in either group.

Conclusions

Our results suggest an increased risk of major bleeding in patients with moderate renal impairment who receive enoxaparin. Because enoxaparin is frequently used and outcomes can be life saving or life threatening, we encourage further study of the appropriate dose in patients with moderate renal impairment.

Moderate Renal Impairment and Risk of Bleeding With Anticoagulation Comment on “Enoxaparin Outcomes in Patients With Moderate Renal Impairment” Renal Impairment, Risk of Bleeding, and Enoxaparin

Minichiello T. — Mon, 10 Dec 2012 00:00:00 GMT

Bleeding is the most feared complication of anticoagulant therapy and, unfortunately, it is not uncommon. The 2011-2012 National Patient Safety Goals mandate efforts to “reduce the likelihood of patient harm associated with the use of anticoagulant therapy.” This is a call for coordinated efforts to decrease adverse events related to anticoagulant therapy, with recommendations for improved oversight and evidence-based management of these agents in the inpatient and outpatient settings.

Supratherapeutic Dosing of Acetaminophen Among Hospitalized Patients Supratherapeutic Dosing of Acetaminophen

Zhou L, Maviglia SM, Mahoney LM, et al. — Mon, 10 Dec 2012 00:00:00 GMT

Background

We investigated acetaminophen use and identify factors contributing to supratherapeutic dosing of acetaminophen in hospitalized patients.

Methods

We retrospectively reviewed the electronic health records of adult patients who were admitted to 2 academic tertiary care hospitals (hospital A amd hospital B) from June 1, 2010, to August 31, 2010, and who received acetaminophen during their hospitalization. Patients' acetaminophen administration records (including drug name, dose, administration time, hospital units, etc), demographic data, diagnoses, and results from liver function tests were obtained. The main outcome measures included acetaminophen exposure rate and supratherapeutic dosing rate among hospitalized patients, hazard ratios (HRs) and 95% confidence intervals (CIs) for risk factors for supratherapeutic dosing, and changes in liver function test before and after supratherapeutic dosing.

Results

A total of 14 411 patients (60.7%) were exposed to acetaminophen, of whom 955 (6.6%) exceeded the 4 g per day maximum recommended dose. In addition, 22.3% of patients who were 65 years or older and 17.6% of patients with chronic liver diseases exceeded the recommended limit of 3 g per day. Patients receiving excessive doses of acetaminophen tended to have significant alkaline phosphatase elevations, although causal relationship cannot be concluded. A significantly higher risk of supratherapeutic dosing was observed in hospital A (HR, 1.6 [95% CI, 1.4-1.8]), white patients (HR, 1.5 [95% CI, 1.3-1.7]), patients diagnosed as having 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 product 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]). A lower risk was found for pro re nata (as needed) administrations (HR, 0.7 [95% CI, 0.6-0.9]) and in nonsurgical and non–intensive care units (HR, 0.6 [95% CI, 0.5-0.7]).

Conclusions

Supratherapeutic dosing of acetaminophen was significantly associated with multiple factors. Interventions to reduce the incidence of some risk factors may prevent supratherapeutic acetaminophen dosing in hospitalized patients.

Using Health Information Technology to Improve Health Care: Emphasizing Speed to Value Comment on “Supratherapeutic Dosing of Acetaminophen Among Hospitalized Patients” Using Health IT to Improve Health Care

Ettinger WH. — Mon, 10 Dec 2012 00:00:00 GMT

The US health care system has been slow to change. Thirteen years have passed since the seminal report, “To Err is Human,” was published by the Institute of Medicine, yet meaningful improvements in quality have been agonizingly slow to come, and injury and error remain commonplace. The cost of health care continues to increase at a rate that exceeds the US gross domestic product, as it has for over 40 years, squeezing out investments in infrastructure, education, research and development, and real gains in wages. Moreover, the health care industry has lagged behind other industries in improving operational performance and adopting technology-enabled process improvements to quality, safety, and efficiency.