Supplementary Material for: Effect of Fentanyl for Preterm Infants on Mechanical Ventilation: A Systematic Review and Meta-Analysis

<b><i>Introduction:</i></b> Because excessive physical stress is harmful, reducing pain and discomfort in premature neonates during mechanical ventilation is a major challenge for physicians. There are no consensus and systematic review on the use of fentanyl, the most commonly used pain reliever in preterm neonates during mechanical ventilation. We aim to compare the benefits and harms of fentanyl versus placebo or no drug for preterm neonates receiving mechanical ventilation. <b><i>Methods:</i></b> A systematic review of randomized controlled trials (RCTs) was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions. The systematic review was reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Scientific databases such as MEDLINE, Embase, CENTRAL, and CINAHL were searched. All preterm infants on mechanical ventilation and enrolled in an RCT of fentanyl versus control were included. <b><i>Results:</i></b> Of 256 reports initially retrieved, 4 reports met the eligibility criteria. Fentanyl was not associated with mortality risk compared to the control (risk ratio: 0.72, 95% confidence intervals [CIs]: 0.36–1.44). No increase in ventilation duration (mean difference [MD]: 0.04, 95% CIs: −0.63–0.71) and no effect on hospital stay length (MD: 4.00, 95% CIs: −7.12–15.12) were found. Fentanyl intervention does not affect any other morbidities, including bronchopulmonary dysplasia, periventricular leukomalacia, patent ductus arteriosus, intraventricular hemorrhage (IVH), severe IVH, sepsis, and necrotizing enterocolitis. <b><i>Conclusion:</i></b> The present systematic review and meta-analysis failed to demonstrate the benefit of administering fentanyl to preterm infants on mechanical ventilation in mortality and morbidities. Follow-up studies are required to investigate the long-term neurodevelopment of the children.

<b><i>引言：</i></b> 由于过度躯体应激可造成损害，因此在机械通气期间减轻早产新生儿的疼痛与不适，是临床医师面临的一项重大挑战。目前尚无针对芬太尼（fentanyl）——机械通气早产新生儿最常用的镇痛药物——应用的共识与系统评价。本研究旨在对比机械通气早产新生儿使用芬太尼与安慰剂或不使用药物的获益与风险。<b><i>方法：</i></b> 本研究依据《Cochrane干预性系统评价手册（Cochrane Handbook for Systematic Reviews of Interventions）》开展随机对照试验（randomized controlled trial, RCT）的系统评价，并遵循《系统评价与Meta分析优先报告条目（Preferred Reporting Items for Systematic Reviews and Meta-Analyses, PRISMA）》进行报告。检索了MEDLINE、Embase、CENTRAL及CINAHL等学术数据库，纳入所有接受机械通气且被纳入芬太尼与对照的随机对照试验的早产婴儿。<b><i>结果：</i></b> 初检共获得256篇文献，最终4篇符合纳入标准。与对照组相比，芬太尼未显著改变死亡风险（风险比：0.72，95%置信区间[CIs]：0.36~1.44）。未观察到通气时长增加（均数差[MD]：0.04，95%置信区间：−0.63~0.71），亦未对住院时长产生影响（均数差：4.00，95%置信区间：−7.12~15.12）。芬太尼干预对其他并发症亦无显著影响，包括支气管肺发育不良（bronchopulmonary dysplasia）、脑室周围白质软化（periventricular leukomalacia）、动脉导管未闭（patent ductus arteriosus）、脑室内出血（intraventricular hemorrhage, IVH）、重度脑室内出血、败血症（sepsis）及坏死性小肠结肠炎（necrotizing enterocolitis）。<b><i>结论：</i></b> 本项系统评价与Meta分析未能证实，机械通气早产新生儿使用芬太尼可改善死亡结局或并发症预后。未来仍需开展随访研究，以评估此类患儿的长期神经发育状况。