Shah P S, Ohlsson A
University of Toronto, Department of Paediatrics, Rm 775A, 600 University Avenue, Toronto, Ontario, Canada, M5G 1XB.
Cochrane Database Syst Rev. 2007 Jul 18(3):CD005494. doi: 10.1002/14651858.CD005494.pub2.
Persistent pulmonary hypertension in neonates (PPHN) is associated with high mortality. Currently, the therapeutic mainstay for PPHN is assisted ventilation and administration of inhaled nitric oxide (iNO). However, nitric oxide is costly and may not be appropriate in resource-poor settings. Approximately 30% of patients fail to respond to iNO. High concentrations of phosphodiesterases in the pulmonary vasculature has led to the use of phosphodiesterase inhibitors such as sildenafil or milrinone.
To assess the efficacy and safety of Sildenafil in the treatment of persistent pulmonary hypertension in neonates.
MEDLINE, EMBASE, CINAHL databases were searched from their inception until March 2007; the Cochrane Central Register of Controlled Trials, the Cochrane Library, the reference lists of identified trials, and abstracts of meetings were searched without any language restriction.
Randomized or quasi-randomized controlled trials of Sildenafil compared with placebo or other pulmonary vasodilators, irrespective of dose, route and duration of administration in neonates with PPHN, were included if the trial reported any of the pre-specified outcomes.
The methodological quality of the trials was assessed regarding how bias at study entry, study intervention and outcomes measurement was minimized. Data on relevant outcomes were extracted and the effect size was estimated and reported as relative risk (RR), risk difference (RD) and weighted mean difference (MD) as appropriate. The I-squared (I(2)) test of heterogeneity was applied.
Two small eligible trials (one full article and one abstract) were identified. The methodological quality of the trial presented in the full article was good. Information provided in the abstract was limited. The total number of enrolled patients in the two studies was 37. Both studies were performed in resource-limited settings where iNO and high frequency ventilation are not available. Both studies reported statistically significant improvement in oxygenation (reduction in oxygenation index) in the Sildenafil group. One study reported what would be, if replicated, a strongly protective effect on mortality (RR 0.17, 95% CI 0.03, 1.09) favoring the Sildenafil group. However, this result needs to be replicated in larger studies. No clinically important side effects were reported.
AUTHORS' CONCLUSIONS: The safety and effectiveness of sildenafil in the treatment of PPHN has not yet been established and its use should be restricted within the context of randomized controlled trials. Further randomized controlled trials of adequate power comparing Sildenafil with other pulmonary vasodilators are needed in moderately ill infants with PPHN.
新生儿持续性肺动脉高压（PPHN）与高死亡率相关。目前，PPHN的主要治疗方法是辅助通气和吸入一氧化氮（iNO）。然而，一氧化氮成本高昂，在资源匮乏地区可能并不适用。约30%的患者对iNO无反应。肺血管中高浓度的磷酸二酯酶促使人们使用磷酸二酯酶抑制剂，如西地那非或米力农。
评估西地那非治疗新生儿持续性肺动脉高压的疗效和安全性。
检索MEDLINE、EMBASE、CINAHL数据库，时间跨度从建库至2007年3月；检索Cochrane对照试验中央注册库、Cochrane图书馆、已识别试验的参考文献列表以及会议摘要，无语言限制。
纳入西地那非与安慰剂或其他肺血管扩张剂对比的随机或半随机对照试验，无论剂量、给药途径和疗程如何，只要试验报告了任何预先指定的结局，且试验对象为患有PPHN的新生儿。
评估试验的方法学质量，看其如何将研究入组、研究干预和结局测量时的偏倚降至最低。提取相关结局的数据，并酌情估计效应量，以相对危险度（RR）、危险度差值（RD）和加权均数差值（MD）报告。应用I²检验评估异质性。
识别出两项小型合格试验（一篇全文和一篇摘要）。全文发表的试验方法学质量良好。摘要提供的信息有限。两项研究纳入的患者总数为37例。两项研究均在无法获得iNO和高频通气的资源有限地区开展。两项研究均报告西地那非组的氧合情况（氧合指数降低）有统计学显著改善。一项研究报告了若能重复，西地那非组对死亡率有强烈的保护作用（RR 0.17，95%CI 0.03，1.09）。然而，这一结果需要在更大规模的研究中重复验证。未报告具有临床重要意义的副作用。
西地那非治疗PPHN的安全性和有效性尚未确立，其使用应限制在随机对照试验范围内。对于中度患病的PPHN婴儿，需要开展更多有足够效力的随机对照试验，将西地那非与其他肺血管扩张剂进行比较。
