Adverse events and clinical outcome associated with drotrecogin alfa-activated: A single-center experience of 498 patients over 8 years

Purpose Licensed in 2002 for severe sepsis, drotrecogin alfa-activated (DAA) remains a much debated therapy particularly with respect to outcomes and a potentially increased risk of serious bleeding events (SBEs). Recent publications have suggested a significantly increased incidence of SBEs and death in those with baseline bleeding risks (BBRs). Our center is one of the highest prescribers of DAA worldwide; we describe our experience of SBEs and other clinical outcomes. Methods Prospectively collected data using a clinical guideline audit tool and database to track outcome and adverse events of DAA-treated severe sepsis patients were analyzed. Results Four hundred ninety-eight patients received DAA over an 8-year period. Hospital, critical care, and 28-day mortalities were 46.2%, 39.6%, and 35.1%, respectively. Contraindications were identified for 40 (8.0%) patients, of whom 24 (4.8%) had BBRs. Hospital mortality was 47.5% (19/40) for patients with any contraindication and 45.8% (11/24) for those with a BBR. Seventy-six (15.3%) bleeding events were reported; 22 (4.4%) were considered serious. Hospital mortality was 60.5% for patients with any bleeding event and 77.3% for those with SBEs. Conclusions This large single-center case series demonstrates that DAA has an incidence of SBEs similar to initial clinical trials. As expected, SBEs were associated with a poor outcome.

目的 活化蛋白C（DAA）于2002年被批准用于治疗严重脓毒症，它仍然是一种备受争议的疗法，尤其是在治疗效果以及可能增加严重出血事件（SBEs）风险方面。近期的文献表明，在有基线出血风险（BBRs）的患者中，SBEs的发生率和死亡率显著增加。我们中心是全球使用DAA处方量最高的机构之一；我们描述了我们在SBEs和其他临床结果方面的经验。 方法 使用临床指南审核工具和数据库前瞻性收集的数据，对接受DAA治疗的严重脓毒症患者的治疗结果和不良事件进行了分析。 结果 在8年期间，498名患者接受了DAA治疗。医院死亡率、重症监护病房死亡率和28天死亡率分别为46.2%、39.6%和35.1%。40名（8.0%）患者存在禁忌证，其中24名（4.8%）有BBRs。有任何禁忌证的患者医院死亡率为47.5%（19/40），有BBRs的患者医院死亡率为45.8%（11/24）。报告了76例（15.3%）出血事件；其中22例（4.4%）被视为严重出血事件。有任何出血事件的患者医院死亡率为60.5%，有SBEs的患者医院死亡率为77.3%。 结论 这个大型单中心病例系列表明，DAA的SBEs发生率与初始临床试验相似。正如预期的那样，SBEs与不良预后相关。