Zarychanski Ryan, Doucette Steven, Fergusson Dean, Roberts Daniel, Houston Donald S, Sharma Satendra, Gulati Harlena, Kumar Anand
Section of Critical Care Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
Crit Care Med. 2008 Nov;36(11):2973-9. doi: 10.1097/CCM.0b013e31818b8c6b.
Sepsis and septic shock represent a systemic inflammatory state with substantial pro-coagulant elements. Unfractionated heparin is a known anticoagulant, which also possesses anti-inflammatory properties. Unfractionated heparin has been shown to increase survival in experimental models of septic shock.
To evaluate the impact of intravenous therapeutic dose unfractionated heparin in a cohort of patients diagnosed with septic shock.
Retrospective, propensity matched, multicenter, cohort study.
Regional intensive care units in Winnipeg, Canada between 1989 and 2005.
Two thousand three hundred fifty-six patients diagnosed with septic shock, of which 722 received intravenous therapeutic dose heparin.
The primary outcome of study was 28-day mortality, and mortality stratified by severity of illness (Acute Physiologic and Chronic Health Evaluation II quartile). Safety was assessed by comparing rates of gastrointestinal hemorrhage, intracranial hemorrhage, and the need for transfusion. By using a Cox proportional hazards model, systemic heparin therapy was associated with decreased 28-day mortality (307 of 695 [44.2%] vs. 279 of 695 [40.1%]; hazard ratio 0.85 [confidence interval (CI) 95% 0.73-1.00]; p = 0.05). In the highest quartile of severity of illness (Acute Physiologic and Chronic Health Evaluation II score 29-53), heparin administration was associated with a clinically and statistically significant reduction in 28-day mortality [127 of 184 (69.0%) vs. 94 of 168 (56.0%); hazard ratio 0.70 (CI 95% 0.54-0.92); p = 0.01]. The use of intravenous unfractionated heparin was associated with successful liberation from mechanical ventilation [odds ratio of 1.42 (CI 95% 1.13-1.80); p = 0.003], and successful discontinuation of vasopressor/inotropic support [odds ratio of 1.34 (CI 95% 1.06-1.71); p = 0.01]. No significant differences in the rates of major hemorrhage or need for transfusion were identified.
Early administration of intravenous therapeutic dose unfractionated heparin may be associated with decreased mortality when administered to patients diagnosed with septic shock, especially in patients with higher severity of illness. Prospective randomized trials are needed to further define the role of this agent in sepsis and septic shock.
脓毒症和脓毒性休克是一种具有大量促凝成分的全身炎症状态。普通肝素是一种已知的抗凝剂，也具有抗炎特性。在脓毒性休克的实验模型中，普通肝素已被证明可提高生存率。
评估静脉注射治疗剂量的普通肝素对一组诊断为脓毒性休克患者的影响。
回顾性、倾向匹配、多中心队列研究。
1989年至2005年加拿大温尼伯的地区重症监护病房。
2356例诊断为脓毒性休克的患者，其中722例接受了静脉注射治疗剂量的肝素。
研究的主要结局是28天死亡率，以及按疾病严重程度（急性生理与慢性健康状况评分II四分位数）分层的死亡率。通过比较胃肠道出血、颅内出血发生率及输血需求来评估安全性。使用Cox比例风险模型，全身肝素治疗与28天死亡率降低相关（695例中的307例[44.2%] vs. 695例中的279例[40.1%]；风险比0.85[95%置信区间（CI）0.73 - 1.00]；p = 0.05）。在疾病严重程度最高的四分位数（急性生理与慢性健康状况评分II 29 - 53分）中，肝素给药与28天死亡率在临床和统计学上显著降低相关[184例中的127例（69.0%） vs. 168例中的94例（56.0%）；风险比0.70（95%CI 0.54 - 0.92）；p = 0.01]。静脉注射普通肝素的使用与成功脱离机械通气相关[优势比为1.42（95%CI 1.13 - 1.80）；p = 0.003]，以及成功停用血管升压药/正性肌力药物支持[优势比为1.34（95%CI 1.06 - 1.71）；p = 0.01]。未发现大出血发生率或输血需求有显著差异。
对于诊断为脓毒性休克的患者，早期给予静脉注射治疗剂量的普通肝素可能与死亡率降低相关，尤其是在疾病严重程度较高的患者中。需要进行前瞻性随机试验来进一步明确该药物在脓毒症和脓毒性休克中的作用。
