CCM:新斯的明作为辅助治疗在感染性休克中对减轻促炎细胞因子作用：一项随机对照试验

Abstract

Objective: The cholinergic anti-inflammatory pathway (ChAP) is the key regulator of the dysregulated cytokine storm in sepsis, with acetylcholine acting on alpha-7 nicotinic acetylcholine receptors (α7nAChRs) to suppress excessive inflammation. The objective of this study was to evaluate whether neostigmine administration modulates the inflammatory response in sepsis by enhancing cholinergic anti-inflammatory activity.

目的：胆碱能抗炎通路（ChAP）是调控脓毒症中失调的细胞因子风暴的关键机制，乙酰胆碱通过作用于α7烟碱型乙酰胆碱受体（α7nAChRs）抑制过度炎症反应。本研究旨在评估新斯的明是否通过增强胆碱能抗炎活性来调节脓毒症患者的炎症反应。

Design: A single-center, prospective, randomized, double-blinded, placebo-controlled study.

设计：单中心、前瞻性、随机、双盲、安慰剂对照试验。

Setting: One adult ICU at a tertiary academic medical institution.

场所：某三级学术医疗机构的一个成人重症监护室（ICU）。

Intervention: Patients were randomized to receive neostigmine at a fixed rate of 0.2 mg/hr (2 mL/hr) or placebo. Study drug was administered for 5 days.

干预措施：患者被随机分配接受固定速率（0.2 mg/h，即2 mL/h）的新斯的明或安慰剂输注，疗程为5天。

Measurements and results: The primary outcome measure was decrease in tumor necrosis factor-alpha levels, in patients treated with neostigmine adjuvant therapy vs. the standard therapy. The secondary outcomes were hemodynamic parameters, septic shock reversal, changes in procalcitonin levels, and organ failure scores. The mean tumor necrosis factor-alpha levels were significantly lower in the neostigmine group (40 ± 36 pg/mL, mean ± sd) on day 5 as compared with the control group (67 ± 43 pg/mL; p = 0.002). There was a significant reduction in Sequential Organ Failure Assessment scores from day 1 to day 5 (p < 0.001) and 28-day mortality was also lower in the neostigmine group (26%) as compared with control group (54%, p = 0.02).

测量指标与结果：主要结局指标为新斯的明辅助治疗组与标准治疗组相比肿瘤坏死因子-α（TNF-α）水平的下降幅度。次要结局包括血流动力学参数、感染性休克逆转情况、降钙素原水平变化及器官衰竭评分。第5天时，新斯的明组的平均TNF-α水平显著低于对照组（40±36 pg/mL vs. 67±43 pg/mL；p=0.002）。序贯器官衰竭评估（SOFA）评分从第1天到第5天显著降低（p<0.001），且新斯的明组的28天死亡率亦低于对照组（26% vs. 54%；p=0.02）。

Conclusions: The neostigmine infusion modulates the ChAP by potentiating the acetylcholine release leading to reduced systemic inflammation and decreased cytokine levels in septic shock patients. (Clinical Trial Registry of India number: CTRI/2023/07/ 055054).

结论：新斯的明输注可通过促进乙酰胆碱释放来增强胆碱能抗炎通路活性，从而减少脓毒性休克患者的全身炎症反应并降低细胞因子水平。（印度临床试验注册号：CTRI/2023/07/055054）