Department of Paediatrics, Aarhus University Hospital, Aarhus N, Denmark.
Aarhus University Group for Understanding Systematic Reviews and Metaanalyses in Translational Preclinical Science, Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark.
Pediatr Res. 2022 Jun;91(7):1654-1661. doi: 10.1038/s41390-021-01656-7. Epub 2021 Jul 19.
Hypoxic-ischemic encephalopathy (HIE) is a major contributor to death and disability worldwide. Remote ischemic postconditioning (RIPC) may offer neuroprotection but has only been tested in preclinical models. Various preclinical models with different assessments of outcomes complicate interpretation. The objective of this systematic review was to determine the neuroprotective effect of RIPC in animal models of HIE.
The protocol was preregistered at The International Prospective Register of Systematic Reviews (PROSPERO) (CRD42020205944). Literature was searched in PubMed, Embase, and Web of Science (April 2020). A formal meta-analysis was impossible due to heterogeneity and a descriptive synthesis was performed.
Thirty-two papers were screened, and five papers were included in the analysis. These included three piglet studies and two rat studies. A broad range of outcome measures was assessed, with inconsistent results. RIPC improved brain lactate/N-acetylaspartate ratios in two piglet studies, suggesting a limited metabolic effect, while most other outcomes assessed were equally likely to improve or not.
There is a lack of evidence to evaluate the neuroprotective effect of RIPC in HIE. Additional studies should aim to standardize methodology and outcome acquisition focusing on clinically relevant outcomes. Future studies should address the optimal timing and duration of RIPC and the combination with therapeutic hypothermia.
This systematic review summarizes five preclinical studies that reported inconsistent effects of RIPC as a neuroprotective intervention after hypoxia-ischemia. The heterogeneity of hypoxia-ischemia animal models employed, mode of postconditioning, and diverse outcomes assessed at varying times means the key message is that no clear conclusions on effect can be drawn. This review highlights the need for future studies to be designed with standardized methodology and common clinically relevant outcomes in models with documented translatability to the human condition.
缺氧缺血性脑病（HIE）是全球范围内导致死亡和残疾的主要原因。远程缺血后处理（RIPC）可能具有神经保护作用，但仅在临床前模型中进行了测试。各种具有不同结局评估的临床前模型使得解释变得复杂。本系统评价的目的是确定 RIPC 在 HIE 动物模型中的神经保护作用。
该方案在国际前瞻性系统评价登记处（PROSPERO）（CRD42020205944）预先注册。在 2020 年 4 月，在 PubMed、Embase 和 Web of Science 中搜索文献。由于异质性，无法进行正式的荟萃分析，因此进行了描述性综合分析。
筛选出 32 篇论文，其中 5 篇论文纳入分析。这些研究包括 3 项仔猪研究和 2 项大鼠研究。评估了广泛的结局指标，但结果不一致。在两项仔猪研究中，RIPC 改善了脑乳酸/N-乙酰天冬氨酸比值，表明具有有限的代谢作用，而评估的大多数其他结局则同样可能改善或不改善。
目前尚无证据评估 RIPC 在 HIE 中的神经保护作用。额外的研究应旨在标准化方法和结局获取，重点关注临床相关结局。未来的研究应解决 RIPC 的最佳时机和持续时间以及与治疗性低温的联合应用。
本系统评价总结了 5 项临床前研究，这些研究报告了 RIPC 作为缺氧后缺血性神经保护干预的作用不一致。所采用的缺氧缺血性动物模型的异质性、后处理方式以及在不同时间评估的多样化结局意味着关键信息是，不能从这些研究中得出关于效果的明确结论。本综述强调了未来研究的必要性，即在具有明确可转化为人类疾病模型的标准化方法和常见临床相关结局的情况下进行设计。
