Associate Professor of Neonatology, KMCH Institute of Health Sciences and Research, Coimbatore, Tamil Nadu, India.
Consultant Neonatologist, Ankura Hospital for Women and Children, Hyderabad, India.
J Neonatal Perinatal Med. 2022;15(4):699-719. doi: 10.3233/NPM-221025.
Despite appropriate antibiotic therapy, the risk of mortality in neonatal sepsis still remains high. We conducted a systematic review to comprehensively evaluate different adjuvant therapies in neonatal sepsis in a network meta-analysis.
We included randomized controlled trials (RCTs) and quasi-RCTs that evaluated adjuvant therapies in neonatal sepsis. Neonates of all gestational and postnatal ages, who were diagnosed with sepsis based on blood culture or sepsis screen were included. We searched MEDLINE, CENTRAL, EMBASE and CINAHL until 12th April 2021 and reference lists. Data extraction and risk of bias assessment were performed in duplicate. A network meta-analysis with bayesian random-effects model was used for data synthesis. Certainty of evidence (CoE) was assessed using GRADE.
We included 45 studies involving 6,566 neonates. Moderate CoE showed IVIG [Relative Risk (RR); 95% Credible Interval (CrI): 1.00; (0.67-1.53)] as an adjunctive therapy probably does not reduce all-cause mortality before discharge, compared to standard care. Melatonin [0.12 (0-0.08)] and granulocyte transfusion [0.39 (0.19-0.76)] may reduce mortality before discharge, but CoE is very low. The evidence is also very uncertain regarding other adjunctive therapies to reduce mortality before discharge. Pentoxifylline may decrease the duration of hospital stay [Mean difference; 95% CrI: -7.48 days (-14.50-0.37)], but CoE is very low.
Given the biological plausibility for possible efficacy of these adjuvant therapies and that the CoE from the available trials is very low to low except for IVIG, we need large adequately powered RCTs to evaluate these therapies in sepsis in neonates.
尽管给予了适当的抗生素治疗，新生儿败血症的死亡率仍然居高不下。我们进行了一项系统评价，通过网络荟萃分析全面评估新生儿败血症的不同辅助治疗方法。
我们纳入了评估新生儿败血症辅助治疗的随机对照试验（RCT）和准 RCT。所有胎龄和出生后年龄的新生儿，基于血培养或败血症筛查诊断为败血症的新生儿均纳入研究。我们检索了 MEDLINE、CENTRAL、EMBASE 和 CINAHL，检索时间截至 2021 年 4 月 12 日，并对参考文献列表进行了检索。数据提取和偏倚风险评估均由两人独立进行。采用贝叶斯随机效应模型的网络荟萃分析进行数据综合。使用 GRADE 评估证据确定性（CoE）。
我们纳入了 45 项研究，涉及 6566 名新生儿。中等 CoE 表明，与标准治疗相比，IVIG[相对风险（RR）；95%可信区间（CrI）：1.00；（0.67-1.53）]作为辅助治疗可能并不能降低出院前的全因死亡率。褪黑素[0.12（0-0.08）]和粒细胞输注[0.39（0.19-0.76）]可能降低出院前的死亡率，但 CoE 非常低。关于其他辅助治疗以降低出院前死亡率的证据也非常不确定。己酮可可碱可能会缩短住院时间[均数差；95%CrI：-7.48 天（-14.50-0.37）]，但 CoE 非常低。
鉴于这些辅助治疗方法可能具有疗效的生物学合理性，且除 IVIG 外，现有试验的 CoE 非常低或低，我们需要开展大型、充分有力的 RCT 来评估这些疗法在新生儿败血症中的作用。
