• Paul M Reynolds, Edward T Van Matre, Garth C Wright, Robert Brett McQueen, Ellen L Burnham, Pei Jai Michael Ho, Marc Moss, Robert William Vandivier, Tyree H Kiser, and Colorado Pulmonary Outcomes Research Group (CPOR).
• Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado.
• Pharmacotherapy. 2019 Mar 1; 39 (3): 232-241.

BackgroundVenous thromboembolism (VTE) occurs frequently in critically ill patients without heparin prophylaxis. Although heparin prevents VTE, VTEs occur frequently despite prophylaxis. A higher heparin dosage may be more effective for preventing VTE.MethodsA retrospective study was conducted using the Premier Incorporated Perspective Database to evaluate comparatively the effects of different heparin prophylaxis dosing strategies in the critically ill patient. Critically ill adult patients who were mechanically ventilated for at least 1 day and had an intensive care unit (ICU) length of stay of at least 2 days were included. Patients received 5000 units of heparin either twice/day or 3 times/day. The primary outcome was development of a new VTE. Key secondary outcomes included clinically important bleeding, thrombocytopenia, and mortality. Patients were propensity matched to control for confounding. Multivariable analysis was conducted for VTE risk factors.ResultsThe study included 30,800 patients from 374 hospitals who were propensity matched by heparin dosage. New VTE occurred in 6.16% of patients treated with 3 times/day heparin versus 6.23% with twice/day heparin (p=0.8). No significant differences in the incidence of pulmonary embolism (0.91% vs 0.8%, p=0.29) or deep vein thrombosis (5.56% vs 5.70% p=0.59) were observed between the two types of heparin dosing. No differences were observed between the two types of heparin dosing in in-hospital mortality (15.8% vs 15.15%), bleeding (0.23% vs 0.33%), or thrombocytopenia (5.19% vs 5.34%, p>0.08 for all), respectively. Risk factors associated with VTE included intraabdominal and urinary tract infections, loop diuretics, malnutrition, obesity, thrombocytopenia, paralytics, vasopressors, female sex, peripheral vascular disease, sepsis, neutropenia, and end-stage renal disease. Antiplatelet therapy, heart failure, diabetes, and substance abuse were associated with reduced VTE (p<0.05 for all).ConclusionsIn critically ill patients, prophylactic dosing of heparin 3 times/day versus twice/day was not associated with differences in new VTE or safety outcomes. Several modifiable VTE risk factors were identified.© 2019 Pharmacotherapy Publications, Inc.

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