粒细胞-巨噬细胞集落刺激因子（GM-CSF）在脓毒症诱导免疫抑制患者中的应用：GRID 随机对照试验。

Granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients presenting sepsis-induced immunosuppression: The GRID randomized controlled trial.

机构信息

Département d'Anesthésie Réanimation, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Lyon, France; CIRI-Centre International de Recherche en Infectiologie (Team PHE3ID), Univ Lyon, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS Lyon, 46 allée d'Italie, Lyon 69007, France; Université Lyon 1.

Département d'Anesthésie Réanimation, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Lyon, France; REA REZO Infections & Antibiorésistance en Réanimation, Hôpital Henry Gabrielle, Villa Alice, 20 route de Vourles, Saint Genis-Laval 69 230, France; CIRI-Centre International de Recherche en Infectiologie (Team PHE3ID), Univ Lyon, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS Lyon, 46 allée d'Italie, Lyon 69007, France.

出版信息

J Crit Care. 2023 Dec;78:154330. doi: 10.1016/j.jcrc.2023.154330. Epub 2023 May 31.

DOI:10.1016/j.jcrc.2023.154330

PMID:37267804

Abstract

PURPOSE

Septic shock is associated in some patients with a profound immunosuppression. We hypothesized that GM-CSF would reduce the occurrence of ICU-acquired infections in immunosuppressed septic patients.

METHODS

Randomized double-blind trial conducted between 2015 and 2018. Adult patients, admitted to ICU, with severe sepsis or septic shock presenting with sepsis-induced immunosuppression defined by mHLA-DR < 8000 ABC (antibodies bound per cell) at day 3 were included. Patients were randomized to receive GM-CSF 125 μg/m or placebo for 5 days at a 1:1 ratio. The primary outcome was the difference in the number of patients presenting≥1 ICU-acquired infection at day 28 or ICU discharge.

RESULTS

The study was prematurely stopped because of insufficient recruitment. A total of 98 patients were included, 54 in the intervention group and 44 in the placebo group. The two groups were similar except for a higher body mass index and McCabe score in the intervention group. No significant difference was observed between groups regarding ICU-acquired infection (11% vs 11%, p = 1.000), 28-day mortality (24% vs 27%,p = 0.900), or the number or localization of the ICU infections.

CONCLUSION

GM-CSF had no effect on the prevention of ICU-acquired infection in sepsis immunosuppression, but any conclusion is limited by the early termination of the study leading to low number of included patients.

摘要

目的

在一些患者中，感染性休克与严重的免疫抑制有关。我们假设 GM-CSF 可降低免疫抑制性感染性休克患者 ICU 获得性感染的发生。

方法

这是一项在 2015 年至 2018 年间进行的随机、双盲试验。纳入 ICU 收治的成年患者，其患有严重脓毒症或感染性休克，且在第 3 天存在由 mHLA-DR<8000 ABC（每个细胞结合的抗体）定义的脓毒症诱导的免疫抑制。患者随机接受 GM-CSF（125μg/m）或安慰剂治疗，疗程为 5 天，比例为 1:1。主要结局为第 28 天或 ICU 出院时出现≥1 例 ICU 获得性感染的患者人数差异。

结果

由于招募不足，该研究提前停止。共纳入 98 例患者，干预组 54 例，安慰剂组 44 例。两组除干预组的体重指数和 McCabe 评分较高外，其他方面均相似。两组 ICU 获得性感染（11%比 11%，p=1.000）、28 天死亡率（24%比 27%，p=0.900）或 ICU 感染的数量或部位无显著差异。