Wheeler Arthur, Steingrub Jay, Schmidt Gregory A, Sanchez Philip, Jacobi Judith, Linde-Zwirble Walter, Bates Becky, Qualy Rebecca L, Woodward Brad, Zeckel Michael
Vanderbilt Medical Center, Nashville, TN, USA.
Crit Care Med. 2008 Jan;36(1):14-23. doi: 10.1097/01.CCM.0000298309.73776.CB.
To compare characteristics and outcomes of patients treated with drotrecogin alfa (activated) (DrotAA) in clinical practice to those treated in a phase III randomized controlled trial (PROWESS).
Observational data were collected retrospectively from patients who received DrotAA as part of physician-directed treatment.
Intensive care units of five teaching institutions.
Patients were > or = 18 yrs old, had severe sepsis (confirmed/suspected infection with one or more sepsis-induced organ dysfunctions), and received DrotAA.
None.
Baseline demographics, severity of illness, time from organ dysfunction onset to DrotAA treatment, daily assessment of organ dysfunction, serious bleeding events, and in-hospital mortality were reported. Timing from severe sepsis documentation to start of DrotAA infusion was categorized: day 0 (same calendar day); day 1 (next calendar day); and day > or = 2 (second calendar day or later). Clinical practice patients (n = 274) were younger, had more comorbidities, had higher severity of illness (as measured by organ dysfunction or greater vasopressor/ventilator use), and received DrotAA later than PROWESS patients (all p < .05). Overall hospital mortality for clinical practice patients was 42%, compared with 37% for DrotAA-treated PROWESS patients with Acute Physiology and Chronic Health Evaluation II score > or = 25. Mortality for day 0, day 1, and day > or = 2 groups was 33%, 40%, and 52%, respectively. In PROWESS, the vast majority were treated on day 0 or day 1. Serious bleeding events during infusion were noted in 4.0% of clinical practice patients compared with 2.2% of PROWESS DrotAA-treated patients with Acute Physiology and Chronic Health Evaluation II score > or = 25.
Patients treated in clinical practice differed from those in PROWESS. Patients were younger, had more comorbidities, had greater severity of illness, and had longer mean time from severe sepsis onset to the start of DrotAA. Hospital mortality for patients treated within 1 day of severe sepsis onset was similar to DrotAA-treated PROWESS patients. While the low number of serious bleeding events precludes a definitive assessment, the observed incidence of serious bleeding events in clinical practice patients was numerically higher than in DrotAA-treated PROWESS patients.
比较在临床实践中接受活化蛋白C（DrotAA）治疗的患者与在一项III期随机对照试验（PROWESS）中接受治疗的患者的特征和结局。
从接受DrotAA作为医生指导治疗一部分的患者中回顾性收集观察数据。
五家教学机构的重症监护病房。
年龄≥18岁，患有严重脓毒症（确诊/疑似感染并伴有一种或多种脓毒症诱发的器官功能障碍），且接受了DrotAA治疗。
无。
报告了基线人口统计学资料、疾病严重程度、从器官功能障碍发作到接受DrotAA治疗的时间、器官功能的每日评估、严重出血事件和院内死亡率。从记录严重脓毒症到开始输注DrotAA的时间分为：第0天（同一日历日）；第1天（下一日历日）；以及第≥2天（第二日历日或更晚）。临床实践中的患者（n = 274）更年轻，合并症更多，疾病严重程度更高（以器官功能障碍或更多血管升压药/呼吸机使用情况衡量），且比PROWESS试验中的患者接受DrotAA治疗的时间更晚（所有p < 0.05）。临床实践患者的总体院内死亡率为42%，而急性生理与慢性健康状况评分II≥25分且接受DrotAA治疗的PROWESS患者的死亡率为37%。第0天、第1天和第≥2天组的死亡率分别为33%、40%和52%。在PROWESS试验中，绝大多数患者在第0天或第1天接受治疗。临床实践患者中4.0%在输注期间出现严重出血事件，而急性生理与慢性健康状况评分II≥25分且接受DrotAA治疗的PROWESS患者中这一比例为2.2%。
临床实践中治疗的患者与PROWESS试验中的患者不同。患者更年轻，合并症更多，疾病严重程度更高，且从严重脓毒症发作到开始使用DrotAA的平均时间更长。在严重脓毒症发作1天内接受治疗的患者院内死亡率与接受DrotAA治疗的PROWESS患者相似。虽然严重出血事件数量较少，无法进行确定性评估，但临床实践患者中观察到的严重出血事件发生率在数值上高于接受DrotAA治疗的PROWESS患者。
