院外心脏骤停患者接受院前大剂量糖皮质激素治疗后的炎症反应：STEROHCA 试验的一个子研究。

Inflammatory response after prehospital high-dose glucocorticoid to patients resuscitated from out-of-hospital cardiac arrest: A sub-study of the STEROHCA trial.

机构信息

Department of Cardiology, Rigshospitalet - Copenhagen University Hospital, Copenhagen, Denmark.

出版信息

Resuscitation. 2024 Sep;202:110340. doi: 10.1016/j.resuscitation.2024.110340. Epub 2024 Jul 31.

DOI:10.1016/j.resuscitation.2024.110340

PMID:39094677

Abstract

BACKGROUND

The post-cardiac arrest syndrome (PCAS) after out-of-hospital cardiac arrest (OHCA) is characterized by a series of pathological events, including inflammation. In the randomized "STERoid for OHCA" (STEROHCA) trial, prehospital high-dose glucocorticoid decreased interleukin (IL) 6 and C-reactive protein levels following resuscitated OHCA. The aim of this predefined sub-study was to assess the inflammatory response the first three days of admission.

METHODS

The STEROHCA trial enrolled 137 OHCA patients randomized to either a single prehospital injection of methylprednisolone 250 mg or placebo. Inflammatory markers, including pro- and anti-inflammatory cytokines, were analyzed in plasma samples, from 0-, 24-, 48-, and 72 h post-admission. Mixed-model analyses were applied using log-transformed data to assess group differences.

RESULTS

The 137 patients included in this sub-study had a median age of 67 years (57 to 74), and the 180-day survival rates were 75% (n = 51/68) and 64% (n = 44/69) in the glucocorticoid and placebo group, respectively. A total of 130 (95%) patients had at least one plasma sample available. The anti-inflammatory cytokine IL-10 was increased at hospital admission in the glucocorticoid group (ratio 2.74 (1.49-5.05), p = 0.006), but the intervention showed the strongest effect after 24 h, decreasing pro-inflammatory levels of IL-6 (ratio 0.06 (0.03-0.10), p < 0.001), IL-8 (ratio 0.53 (0.38-0.75), p < 0.001), macrophage chemokine protein-1 (MCP-1, ratio 0.02 (0.13-0.31), p < 0.001), macrophage inflammatory protein-1-beta (MIP-1b, ratio 0.28 (0.18-0.45), p < 0.001), and tumor necrosis factor-α (TNF-α, ratio 0.6 (0.4-0.8), p = 0.01).

CONCLUSION

Administering high-dose glucocorticoid treatment promptly after resuscitation from OHCA influenced the inflammatory response with a reduction in several systemic proinflammatory cytokines after 24 h.

TRIAL REGISTRATION

EudraCT number: 2020-000855-11; submitted March 30, 2020. URL: https://www.

CLINICALTRIALS

gov; Unique Identifier: NCT04624776.

摘要

背景

院外心脏骤停（OHCA）后的心脏骤停后综合征（PCAS）的特征是一系列病理事件，包括炎症。在随机的“STERoid for OHCA”（STEROHCA）试验中，院前大剂量糖皮质激素可降低复苏后 OHCA 患者的白细胞介素（IL）6 和 C 反应蛋白水平。本预定义亚研究的目的是评估入院后前三天的炎症反应。

方法

STEROHCA 试验纳入了 137 名 OHCA 患者，随机分为单剂院前注射甲泼尼龙 250mg 或安慰剂。在入院后 0、24、48 和 72 小时，分析了包括促炎和抗炎细胞因子在内的血浆样本中的炎症标志物。采用对数转换数据的混合模型分析评估组间差异。

结果

本亚研究纳入的 137 例患者的中位年龄为 67 岁（57 至 74 岁），糖皮质激素组和安慰剂组的 180 天生存率分别为 75%（n=51/68）和 64%（n=44/69）。共有 130 名（95%）患者至少有一份血浆样本可用。糖皮质激素组入院时抗炎细胞因子 IL-10 增加（比值 2.74（1.49-5.05），p=0.006），但干预在 24 小时后效果最强，降低了促炎水平的 IL-6（比值 0.06（0.03-0.10），p<0.001）、IL-8（比值 0.53（0.38-0.75），p<0.001）、巨噬细胞趋化因子蛋白-1（MCP-1，比值 0.02（0.13-0.31），p<0.001）、巨噬细胞炎性蛋白-1-beta（MIP-1b，比值 0.28（0.18-0.45），p<0.001）和肿瘤坏死因子-α（TNF-α，比值 0.6（0.4-0.8），p=0.01）。