Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado.
Department of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee.
Pharmacotherapy. 2019 Mar;39(3):232-241. doi: 10.1002/phar.2212. Epub 2019 Jan 21.
Venous 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.
A 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.
The 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).
In 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.
危重症患者常发生静脉血栓栓塞症（VTE），而肝素预防对此无效。肝素虽可预防 VTE，但预防效果仍不理想。增加肝素剂量可能更有助于预防 VTE。
本回顾性研究利用 Premier 公司的 Perspectives 数据库，评估了危重症患者中不同肝素预防剂量策略的效果。纳入标准为机械通气至少 1 天且 ICU 住院时间至少 2 天的成年危重症患者。患者接受每日 2 次或 3 次 5000 单位肝素治疗。主要终点为新发 VTE。次要重点结局包括临床重要出血、血小板减少和死亡率。采用倾向性匹配控制混杂因素。对 VTE 的危险因素进行多变量分析。
该研究纳入了来自 374 家医院的 30800 例患者，根据肝素剂量进行了倾向性匹配。每日 3 次肝素组的新发 VTE 发生率为 6.16%，每日 2 次肝素组为 6.23%（p=0.8）。两组肺栓塞（0.91% vs 0.8%，p=0.29）和深静脉血栓（5.56% vs 5.70%，p=0.59）发生率无显著差异。两种肝素剂量方案在院内死亡率（15.8% vs 15.15%）、出血（0.23% vs 0.33%）或血小板减少（5.19% vs 5.34%，p>0.08）方面无差异。VTE 的相关危险因素包括腹腔和尿路感染、袢利尿剂、营养不良、肥胖、血小板减少、肌松剂、血管加压素、女性、外周血管疾病、脓毒症、中性粒细胞减少和终末期肾病。抗血小板治疗、心力衰竭、糖尿病和物质滥用与 VTE 减少相关（p<0.05）。
在危重症患者中，每日 3 次与每日 2 次预防性给予肝素并未导致新发 VTE 或安全性结局的差异。确定了一些可改变的 VTE 危险因素。
