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与米力农用于感染性休克儿童相关的微循环、内皮及糖萼变化

Microcirculation, endothelium and glycocalyx changes associated with the use of milrinone in children with septic shock.

作者信息

Sarta-Mantilla Mauricio, Fernández-Sarmiento Jaime, Acevedo Lorena, Mulett Hernando, Nieto Andres, Lucena Natalia, Lancheros Jeisson, Duque Catalina

机构信息

Department of Pediatrics and Intensive Care, Fundación Cardioinfantil-Instituto de Cardiología, Bogotá, Colombia.

Department of Pediatrics and Intensive Care, Universidad del Rosario, Bogotá, Colombia.

出版信息

Transl Pediatr. 2024 May 31;13(5):727-737. doi: 10.21037/tp-23-619. Epub 2024 May 27.

DOI:10.21037/tp-23-619
PMID:38840690
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11148745/
Abstract

BACKGROUND

The goal of fluid resuscitation and the use of inotropes in septic shock has traditionally focused on improving blood pressure and cardiac output, without considering the microcirculatory changes. Reaching macrocirculatory goals but with persistent microcirculatory abnormalities (hemodynamic incoherence) in septic shock has been associated with greater organ dysfunction and mortality. The objective of this study was to evaluate the microcirculation (flow and capillary density) and endothelial glycocalyx changes associated with the use of milrinone in children with septic shock, as well as their relationship with clinical variables and organ dysfunction.

METHODS

A prospective cohort study from February 2022 to January 2023 at a university hospital (Fundación Cardioinfantil-Instituto de Cardiología). Sublingual video microscopy was used to evaluate capillary density, microvascular flow rates and perfused boundary region (PBR-inverse parameter of glycocalyx thickness-abnormal if >2.0 microns). The primary outcome was the association between microcirculation and endothelial glycocalyx changes related to the use of milrinone.

RESULTS

A total of 140 children with a median age of two years [interquartile range (IQR) 0.58-12.1] were included. About 57.9% (81/140) of the patients received milrinone infusions. Twenty-four hours after receiving milrinone, the patients maintained functional capillary density (P<0.01) and capillary recruitment capacity (P=0.04) with no changes in capillary blood volume versus those who did not receive milrinone. Children under two years old who received milrinone had better 4-6-micron capillary density than older children [odds ratio (OR) 0.33; 95% confidence interval (95% CI): 0.12-0.89; P=0.02] and less endothelial glycocalyx degradation [adjusted OR (aOR) 0.34 95% CI: 0.11-0.99; P=0.04]. These changes persisted despite elevated ferritin (aOR 0.41; 95% CI: 0.18-0.93; P=0.03). Prolonged capillary refill and elevated lactate were correlated with microcirculation changes in both groups. The patients who died had the highest PBR levels (P=0.04).

CONCLUSIONS

Children with septic shock who receive milrinone infusions have microcirculation changes compared with those who do not receive them. The group that received milrinone was found to maintain functional capillary density and capillary recruitment capacity and have less endothelial glycocalyx degradation 24 hours after administration. These changes were present despite the inflammatory response and were more significant in those under two years of age.

摘要

背景

传统上,脓毒症休克患者的液体复苏和使用血管活性药物的目标主要是提高血压和心输出量,而未考虑微循环变化。在脓毒症休克中,尽管达到了大循环目标,但仍存在持续的微循环异常(血流动力学不协调),这与更严重的器官功能障碍和死亡率相关。本研究的目的是评估米力农对脓毒症休克患儿微循环(血流和毛细血管密度)及内皮糖萼的影响,以及它们与临床变量和器官功能障碍的关系。

方法

2022年2月至2023年1月在一家大学医院(Fundación Cardioinfantil-Instituto de Cardiología)进行的一项前瞻性队列研究。采用舌下视频显微镜评估毛细血管密度、微血管血流速度和灌注边界区域(PBR,糖萼厚度的反向参数,若>2.0微米则异常)。主要结局是与米力农使用相关的微循环和内皮糖萼变化之间的关联。

结果

共纳入140例中位年龄为2岁[四分位间距(IQR)0.58 - 12.1]的儿童。约57.9%(81/140)的患者接受了米力农输注。在接受米力农24小时后,与未接受米力农的患者相比,这些患者的功能性毛细血管密度(P<0.01)和毛细血管募集能力(P = 0.04)得以维持,且毛细血管血容量无变化。接受米力农的2岁以下儿童的4 - 6微米毛细血管密度优于大龄儿童[比值比(OR)0.33;95%置信区间(95%CI):0.12 - 0.89;P = 0.02],内皮糖萼降解程度更低[校正OR(aOR)0.34,95%CI:0.11 - 0.99;P = 0.04]。尽管铁蛋白升高,但这些变化仍然存在(aOR 0.41;95%CI:0.18 - 0.93;P = 0.03)。两组中,毛细血管再充盈时间延长和乳酸升高均与微循环变化相关。死亡患者的PBR水平最高(P = 0.04)。

结论

与未接受米力农输注的脓毒症休克患儿相比,接受米力农输注的患儿出现了微循环变化。接受米力农的组在给药24小时后维持了功能性毛细血管密度和毛细血管募集能力,且内皮糖萼降解程度更低。尽管存在炎症反应,这些变化仍然存在,且在2岁以下儿童中更为显著。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b5d/11148745/16130d797ccd/tp-13-05-727-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b5d/11148745/2fa9820b8e7f/tp-13-05-727-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b5d/11148745/62ed612017ac/tp-13-05-727-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b5d/11148745/16130d797ccd/tp-13-05-727-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b5d/11148745/2fa9820b8e7f/tp-13-05-727-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b5d/11148745/62ed612017ac/tp-13-05-727-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b5d/11148745/16130d797ccd/tp-13-05-727-f3.jpg

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