右美托咪定在改善感染性休克患者免疫麻痹中的作用：随机对照试验

Role of dexmedetomidine in modifying immune paralysis in patients with septic shock: randomized controlled trial.

作者信息

Elayashy Mohamed, Elsayed Eman A, Mukhtar Ahmed M, Kasem Sahar, Elmetwally Sara A, Habib Sara, Abdelfattah Walaa, Ghaith Doaa, Hussein Amr

机构信息

Department of Anesthesia and Intensive Care, Kasr Al-Ainy Faculty of Medicine, Cairo University, Cairo, Egypt.

Department of Clinical Pathology, Kasr Al-Ainy Faculty of Medicine, Cairo University, Cairo, Egypt.

出版信息

Intensive Care Med Exp. 2023 Sep 4;11(1):59. doi: 10.1186/s40635-023-00542-2.

DOI:10.1186/s40635-023-00542-2

PMID:37665397

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10477149/

Abstract

BACKGROUND

Immune paralysis can be defined as a hypoinflammatory state associated with the incapacity of the immune system to release proinflammatory mediators despite the clearance of pathogens by antimicrobials. Persistent immune paralysis leads to failure to eradicate primary infections with a substantial increase in the risk of multiorgan dysfunction and mortality. The state of immune paralysis is caused mainly by the diminished ability of monocytes to release proinflammatory cytokines in response to endotoxin. This phenomenon is known as endotoxin tolerance. This study aimed to assess the role of dexmedetomidine in modifying immune paralysis in septic shock patients.

METHODS

Twenty-four patients with septic shock were randomized into two groups of 12 patients. A continuous intravenous infusion of dexmedetomidine started at 0.15 µg kg hr and adjusted by 0.15 µg kg h to a maximum of 0.75 µg kg h (10 ml h), while midazolam was started at 1 mg h (2 mL hr) and adjusted by 1 mg h to a maximum of 5 mg h (10 mL h). All infusions were adjusted by increments of 2 mL/hr to maintain blinding. Serum levels of CD42a+/CD14+, HLADR+/CD14+, CRP, IL-6, IL-10 and TNF-α were measured at baseline (T1), 12 h (T2), and 24 h (T3).

RESULTS

Treatment with dexmedetomidine yielded no significant difference in CD42a+/CD14+, HLADR+/CD14, CD24b-MFI, HLADR-MFI, IL6 and TREM1 at all time points when compared with midazolam treatment. There was no significant difference in TLR levels between the two groups. Cardiac output in the dexmedetomidine group showed a significant decrease at 6, 12 and 24 h (P = 0.033, 0.021, and 0.005, respectively) compared with that in the midazolam group.

CONCLUSION

Our results indicated that dexmedetomidine did not affect CD42a+/CD14+ and HLA-DR+/CD14+ expression in septic patients. Furthermore, cytokine production and inflammatory biomarkers did not change with dexmedetomidine infusion. Trial registration Clinical trial.gov registry (NCT03989609) on June 14, 2019, https://register.

CLINICALTRIALS

gov .

摘要

背景

免疫麻痹可定义为一种低炎症状态，尽管抗菌药物已清除病原体，但免疫系统仍无法释放促炎介质。持续性免疫麻痹会导致原发性感染无法根除，多器官功能障碍和死亡率大幅增加。免疫麻痹状态主要是由于单核细胞对内毒素反应时释放促炎细胞因子的能力下降所致。这种现象被称为内毒素耐受。本研究旨在评估右美托咪定在改善脓毒性休克患者免疫麻痹中的作用。

方法

24例脓毒性休克患者被随机分为两组，每组12例。右美托咪定持续静脉输注起始剂量为0.15μg·kg·hr，以0.15μg·kg·h的幅度调整，最大剂量为0.75μg·kg·h（10ml·h），而咪达唑仑起始剂量为1mg·h（2mL·hr），以1mg·h的幅度调整，最大剂量为5mg·h（10mL·h）。所有输注均以2mL/hr的增量进行调整以维持盲法。在基线（T1）、12小时（T2）和24小时（T3）测量血清中CD42a+/CD14+、HLADR+/CD14+、CRP、IL-6、IL-10和TNF-α水平。

结果

与咪达唑仑治疗相比，右美托咪定治疗在所有时间点的CD42a+/CD14+、HLADR+/CD14、CD24b-MFI、HLADR-MFI、IL6和TREM1方面均无显著差异。两组之间的TLR水平无显著差异。与咪达唑仑组相比，右美托咪定组的心输出量在6小时、12小时和24小时时显著降低（P分别为0.033、0.021和0.005）。

结论

我们的结果表明，右美托咪定不影响脓毒症患者的CD42a+/CD14+和HLA-DR+/CD14+表达。此外，右美托咪定输注后细胞因子产生和炎症生物标志物未发生变化。试验注册于2019年6月14日在Clinical trial.gov注册（NCT03989609），https://register.CLINICALTRIALS: gov 。