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If some is good, more is better: An enoxaparin dosing strategy to improve pharmacologic venous thromboembolism prophylaxis

Berndtson, Allison E. MD; Costantini, Todd W. MD; Lane, James PharmD; Box, Kevin PharmD; Coimbra, Raul MD, PhD

Journal of Trauma and Acute Care Surgery: December 2016 - Volume 81 - Issue 6 - p 1095–1100
doi: 10.1097/TA.0000000000001142
WTA 2016 Plenary Papers
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CME

BACKGROUND Empiric enoxaparin dosing is inadequate for most trauma patients, leading to below target initial anti-Xa levels and requiring dose adjustment for optimal venous thromboembolism prophylaxis. We hypothesize that patient factors affecting initial anti-Xa levels can be identified based on drug pharmacokinetics, allowing creation of a new dosing protocol that will provide a higher percentage of in-target (0.2–0.4 IU/mL) patients at initial anti-Xa level assessment.

METHODS Records of 318 trauma patients were evaluated, and NONMEM and PSN software were used to analyze 11 variables for their effects on anti-Xa levels. Computer modeling was used to select a new dosing protocol, which was implemented on the trauma service as a quality improvement project. The first 145 patients appropriately enrolled were assessed for response and complications.

RESULTS Only 29.5% of the pre-intervention group had initial anti-Xa levels in the appropriate prophylactic range (Fig. 1). Levels were most strongly influenced by patient weight, outweighing contributions from all other variables. A new regimen for initial dosing was therefore designed with three weight-defined categories for ease of administration. The post-intervention group showed an increase in in-target initial anti-Xa levels to 74.5% (p < 0.001), with a corresponding decrease in subprophylactic patients from 68.0% to 20.7%. There was an increase in supraprophylactic levels to 4.8%, but no supraprophylactic patients had hemorrhagic complications.

Figure 1

Figure 1

CONCLUSIONS Implementation of a new, categorized, weight-based enoxaparin dosing protocol was safe and significantly improved the percentage of trauma patients with in-target anti-Xa levels on initial assessment. Further studies are needed to determine whether such dosing decreases venous thromboembolism rates.

LEVEL OF EVIDENCE Therapeutic/care management study, level II.

From the Division of Trauma, Surgical Critical Care, Burns and Acute Care Surgery (A.E.B., T.W.C., R.C.), Skaggs School of Pharmacy and Pharmaceutical Sciences (J.L.), and Department of Pharmacy (K.B.), University of California, San Diego, San Diego, California.

Submitted: February 14, 2016, Revised: April 16, 2016, Accepted: April 18, 2016, Published online: May 27, 2016.

This study was presented at the 46th annual meeting of the Western Trauma Association, February 28–March 4, 2016, in Lake Tahoe, California.

Address for reprints: Raul Coimbra, MD, PhD, FACS, 200 W Arbor Drive, Mail Code 8896 San Diego, CA 92103; email: rcoimbra@ucsd.edu.

© 2016 Lippincott Williams & Wilkins, Inc.