Division of Burns, Critical Care, and Trauma, Department of Surgery, Weill Cornell Medical College, New York, New York, USA.
Surg Infect (Larchmt). 2011 Dec;12(6):443-9. doi: 10.1089/sur.2011.133.
Septic shock causing or complicating critical surgical illness results in high mortality. Drotrecogin alfa (activated), known also as recombinant human activated protein C (rhAPC) has become controversial as therapy, owing to persisting questions of efficacy and safety. We hypothesized rhAPC to be effective therapy for critically ill surgical patients with septic shock.
Open-label therapy with rhAPC (by predefined criteria) of 108 critically ill surgical patients. Treated patients were matched individually in prospect for age, gender, Acute Physiology and Chronic Health Evaluation (APACHE)-II and -III scores, site of infection, and organism (0-2 points each, maximum 12 points) with 108 patients from our 15,000-patient surgical intensive care unit database who did not receive rhAPC. No match was accepted if <6 points. Multiple organ dysfunction (MOD) scores and data regarding cortisol concentrations, bleeding complications, and transfusion requirements were collected. The primary endpoint was 28-day mortality, with mortality for hospitalization and resolution of organ dysfunction as secondary endpoints. Statistical analyses included ANOVA, c statistic, binary logistic regression, and Kaplan-Meier time-to-event and Cox proportional hazards analyses; α=0.05.
The mean match score was 9.2±0.1 points (range, 6-12 points). Patients were well matched by all criteria, including baseline MOD score (9.5±0.7 vs. 9.8±0.3 points, p=0.66). Mean age was 68.1±1.1 years (p=0.49), Mean APACHE-III score was 99.6±1.5 points (p=0.87). Mean time to rhAPC administration was 25±3 h. Survival at 28 days after rhAPC was 71.3% vs. 49.1% (p=0.001); hospital survival was 57.4% vs. 40.7% (p=0.02). By logistic regression, rhAPC therapy resulted in improved 28-day survival (OR 2.57, 95% CI 1.46-4.52, p=0.001) (model χ2 11.244, p=0.001); and hospital survival (OR 1.96, 95% CI 1.14-3.36, p=0.015) (model χ2 6.03, p=0.014). The MOD score decreased significantly (p=0.012) during rhAPC therapy.
Therapy with rhAPC appeared to improve survival in surgical ICU patients with life-threatening infection characterized by septic shock and organ dysfunction.
脓毒性休克导致或并发危急手术疾病会导致高死亡率。已被证明具有争议的重组人活化蛋白 C（rhAPC），又称凝血酶原片段 12（Drotrecogin alfa [activated]），其疗效和安全性仍存在争议。我们假设 rhAPC 对患有脓毒性休克的危重症手术患者是一种有效的治疗方法。
对 108 名危重症手术患者进行 rhAPC（根据预设标准）的开放性标签治疗。根据年龄、性别、急性生理学和慢性健康评估（APACHE）-II 和 -III 评分、感染部位和病原体（每项 0-2 分，最高 12 分）对治疗患者进行个体化前瞻性匹配，与我们的 15000 例外科重症监护病房数据库中未接受 rhAPC 的 108 名患者进行匹配。如果匹配分数 <6 分，则不接受匹配。收集了多器官功能障碍（MOD）评分以及皮质醇浓度、出血并发症和输血需求的数据。主要终点是 28 天死亡率，次要终点为住院死亡率和器官功能障碍的缓解。统计分析包括方差分析、c 统计量、二项逻辑回归、Kaplan-Meier 时间事件和 Cox 比例风险分析；α=0.05。
平均匹配分数为 9.2±0.1 分（范围 6-12 分）。所有标准均对患者进行了很好的匹配，包括基线 MOD 评分（9.5±0.7 分 vs. 9.8±0.3 分，p=0.66）。平均年龄为 68.1±1.1 岁（p=0.49），平均 APACHE-III 评分为 99.6±1.5 分（p=0.87）。rhAPC 给药的平均时间为 25±3 小时。rhAPC 治疗后 28 天的生存率为 71.3% vs. 49.1%（p=0.001）；住院生存率为 57.4% vs. 40.7%（p=0.02）。通过逻辑回归，rhAPC 治疗可提高 28 天生存率（OR 2.57，95%CI 1.46-4.52，p=0.001）（模型 χ2 11.244，p=0.001）；和住院生存率（OR 1.96，95%CI 1.14-3.36，p=0.015）（模型 χ2 6.03，p=0.014）。在 rhAPC 治疗期间，MOD 评分显著下降（p=0.012）。
rhAPC 治疗似乎可改善以脓毒性休克和器官功能障碍为特征的危及生命感染的外科重症监护病房患者的生存率。
