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小儿心脏手术中使用甲泼尼龙:证据充分吗?

Methylprednisolone in Pediatric Cardiac Surgery: Is There Enough Evidence?

作者信息

van Saet Annewil, Zeilmaker-Roest Gerdien A, Stolker Robert J, Bogers Ad J J C, Tibboel Dick

机构信息

Department of Anesthesiology, Erasmus Medical Center, Rotterdam, Netherlands.

Department of Intensive Care and Pediatric Surgery, Erasmus Medical Center, Rotterdam, Netherlands.

出版信息

Front Cardiovasc Med. 2021 Sep 22;8:730157. doi: 10.3389/fcvm.2021.730157. eCollection 2021.

DOI:10.3389/fcvm.2021.730157
PMID:34631828
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8492975/
Abstract

Corticosteroids have been used to decrease the inflammatory response to cardiac surgery and cardiopulmonary bypass in children for decades. Sparse information is present concerning the pharmacokinetics and pharmacodynamics of corticosteroids in the context of pediatric cardiac surgery. There is large interindividual variability in plasma concentrations, with indications for a larger volume of distribution in neonates compared to other age groups. There is ample evidence that perioperative use of MP leads to a decrease in pro-inflammatory mediators and an increase in anti-inflammatory mediators, with no difference in effect between doses of 2 and 30 mg/kg. No differences in inflammatory mediators have been shown between different times of administration relative to the start of surgery in various studies. MP has been shown to have a beneficial effect in certain subgroups of patients but is also associated with side effects. In lower risk categories, the balance between risk and benefit may be shifted toward risk. There is limited information on short- to medium-term outcome (mortality, low cardiac output syndrome, duration of mechanical ventilation, length of stay in the intensive care unit or the hospital), mostly from underpowered studies. No information on long-term outcome, such as neurodevelopmental outcome, is available. MP may provide a small benefit that is easily abolished by patient characteristics, surgical techniques, and perfusion management. The lack of evidence leads to large differences in practice between and within countries, and even within hospitals, so there is a need for adequately powered randomized studies.

摘要

几十年来,皮质类固醇一直被用于减轻儿童心脏手术和体外循环的炎症反应。关于小儿心脏手术中皮质类固醇的药代动力学和药效学的信息稀少。血浆浓度存在很大的个体间差异,与其他年龄组相比,新生儿的分布容积更大。有充分证据表明,围手术期使用甲泼尼龙(MP)可导致促炎介质减少和抗炎介质增加,2mg/kg和30mg/kg剂量之间的效果无差异。在各种研究中,相对于手术开始的不同给药时间,炎症介质方面未显示出差异。MP已被证明在某些患者亚组中有有益作用,但也与副作用相关。在低风险类别中,风险与益处之间的平衡可能会转向风险。关于短期至中期结局(死亡率、低心排血量综合征、机械通气时间、重症监护病房或医院住院时间)的信息有限,大多来自样本量不足的研究。没有关于长期结局(如神经发育结局)的信息。MP可能提供的微小益处很容易被患者特征、手术技术和灌注管理所抵消。证据的缺乏导致不同国家之间、国家内部甚至医院内部在实践中存在很大差异,因此需要进行样本量充足的随机研究。

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Cochrane Database Syst Rev. 2020 Oct 12;10(10):CD013101. doi: 10.1002/14651858.CD013101.pub2.
2
Perioperative Corticosteroid Therapy in Children Undergoing Cardiac Surgery: A Systematic Review and Meta-Analysis.接受心脏手术儿童的围手术期皮质类固醇治疗:系统评价与荟萃分析
Front Pediatr. 2020 Jul 24;8:350. doi: 10.3389/fped.2020.00350. eCollection 2020.
3
Transitioning from Basic toward Systems Pharmacodynamic Models: Lessons from Corticosteroids.从基础到系统药效动力学模型的转变:皮质类固醇的经验教训。
Pharmacol Rev. 2020 Apr;72(2):414-438. doi: 10.1124/pr.119.018101.
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Rationale and design of the STeroids to REduce Systemic inflammation after infant heart Surgery (STRESS) trial.STeroids 降低婴儿心脏手术后全身炎症反应(STRESS)试验的原理和设计。
Am Heart J. 2020 Feb;220:192-202. doi: 10.1016/j.ahj.2019.11.016. Epub 2019 Dec 9.
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Population Pharmacokinetic/Pharmacodynamic Modeling of Methylprednisolone in Neonates Undergoing Cardiopulmonary Bypass.心脏体外循环术新生儿中甲基强的松龙的群体药代动力学/药效学模型研究。
CPT Pharmacometrics Syst Pharmacol. 2019 Dec;8(12):913-922. doi: 10.1002/psp4.12470. Epub 2019 Oct 23.
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Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass: Randomized Controlled Trial.新生儿体外循环中皮质类固醇治疗的随机对照试验。
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