Werdan Karl, Pilz Günter, Bujdoso Oskar, Fraunberger Peter, Neeser Gertraud, Schmieder Roland Erich, Viell Burkhard, Marget Walter, Seewald Margret, Walger Peter, Stuttmann Ralph, Speichermann Norbert, Peckelsen Claus, Kurowski Volkhard, Osterhues Hans-Heinrich, Verner Ljiljana, Neumann Roswita, Müller-Werdan Ursula
Department of Medicine III, University Hospital, Martin-Luther-University Halle-Wittenberg, Germany.
Crit Care Med. 2007 Dec;35(12):2693-2701.
Intravenous immunoglobulin as an adjunctive treatment in sepsis was regarded as promising by a Cochrane meta-analysis of smaller trials. In this phase III multicenter trial, we assessed whether intravenous immunoglobulin G (ivIgG) reduced 28-day mortality and improved morbidity in patients with score-defined severe sepsis.
Randomized, double-blind, placebo-controlled, multicenter trial.
Twenty-three medical and surgical intensive care units in university centers and large teaching hospitals.
Patients (n = 653) with score-defined sepsis (sepsis score 12-27) and score-defined sepsis-induced severity of disease (Acute Physiology and Chronic Health Evaluation II score 20-35).
Patients were assigned to receive either placebo or ivIgG (day 0, 0.6 g/kg body weight; day 1, 0.3 g/kg body weight).
The prospectively defined primary end point was death from any cause after 28 days. Prospectively defined secondary end points were 7-day all-cause mortality, short-term change in morbidity, and pulmonary function at day 4. Six hundred fifty-three patients from 23 active centers formed the intention-to-treat group, 624 patients the per-protocol group (placebo group, n = 303; ivIgG group, n = 321). The 28-day mortality rate was 37.3% in the placebo group and 39.3% in the ivIgG group and thus not significantly different (p = .6695). Seven-day mortality was not reduced, and 4-day pulmonary function was not improved. Drug-related adverse events were rare in both groups. Exploratory findings revealed a 3-day shortening of mechanical ventilation in the surviving patients and no effect of ivIgG on plasma levels of interleukin-6 and tumor necrosis factor receptors I and II.
In patients with score-defined severe sepsis, ivIgG with a total dose of 0.9 g/kg body weight does not reduce mortality.
一项对较小规模试验的Cochrane荟萃分析认为，静脉注射免疫球蛋白作为脓毒症的辅助治疗手段很有前景。在这项III期多中心试验中，我们评估了静脉注射免疫球蛋白G（ivIgG）是否能降低评分定义的严重脓毒症患者的28天死亡率并改善发病率。
随机、双盲、安慰剂对照、多中心试验。
大学中心和大型教学医院的23个内科和外科重症监护病房。
评分定义的脓毒症（脓毒症评分12 - 27）和评分定义的脓毒症诱发疾病严重程度（急性生理与慢性健康状况评分II 20 - 35）患者（n = 653）。
患者被分配接受安慰剂或ivIgG（第0天，0.6 g/kg体重；第1天，0.3 g/kg体重）。
预先定义的主要终点是28天后任何原因导致的死亡。预先定义的次要终点是7天全因死亡率、发病率的短期变化以及第4天的肺功能。来自23个活跃中心的653名患者组成意向性治疗组，624名患者组成符合方案组（安慰剂组，n = 303；ivIgG组，n = 321）。安慰剂组的28天死亡率为37.3%，ivIgG组为39.3%，因此无显著差异（p = 0.6695）。7天死亡率未降低，第4天的肺功能未改善。两组药物相关不良事件均罕见。探索性结果显示，存活患者机械通气时间缩短了3天，且ivIgG对白细胞介素-6和肿瘤坏死因子受体I及II的血浆水平无影响。
在评分定义的严重脓毒症患者中，总剂量为0.9 g/kg体重的ivIgG不能降低死亡率。
