Baquero Hernando, Soliz Amed, Neira Freddy, Venegas Maria E, Sola Augusto
Division of Neonatology, Universidad del Norte, Barranquilla, Colombia.
Pediatrics. 2006 Apr;117(4):1077-83. doi: 10.1542/peds.2005-0523.
Persistent pulmonary hypertension (PPHN) occurs in as many as 6.8 of 1000 live births. Mortality is approximately 10% to 20% with high-frequency ventilation, surfactant, inhaled nitric oxide, and extracorporeal membrane oxygenation but is much higher when these therapies are not available. Sildenafil is a phosphodiesterase inhibitor type 5 that selectively reduces pulmonary vascular resistance.
Our goal was to evaluate the feasibility of using oral sildenafil and its effect on oxygenation in PPHN.
This study was a proof-of-concept, randomized, masked study in infants >35.5 weeks' gestation and <3 days old with severe PPHN and oxygenation index (OI) >25 admitted to the NICU (Hospital Niño Jesús, Barranquilla, Colombia). The sildenafil solution was prepared from a 50-mg tablet. The first dose (1 mg/kg) or placebo was given by orogastric tube <30 minutes after randomization and every 6 hours. Preductal saturation and blood pressure were monitored continuously. OI was calculated every 6 hours. The main outcome variable was the effect of oral sildenafil on oxygenation. Sildenafil or placebo was discontinued when OI was <20 or if there was no significant change in OI after 36 hours.
Six infants with an OI of >25 received placebo, and 7 received oral sildenafil at a median age of 25 hours. All infants were severely ill, on fraction of inspired oxygen 1.0, and with similar ventilatory parameters. Intragastric sildenafil and placebo were well tolerated. In the treatment group, OI improved in all infants within 6 to 30 hours, all showed a steady improvement in pulse oxygen saturation over time, and none had noticeable effect on blood pressure; 6 of 7 survived. In the placebo group, 1 of 6 infants survived.
Oral sildenafil was administered easily and tolerated as well as placebo and improved OI in infants with severe PPHN, which suggests that oral sildenafil may be effective in the treatment of PPHN and underscores the need for a large, controlled trial.
持续性肺动脉高压（PPHN）在每1000例活产中发生率高达6.8例。采用高频通气、表面活性剂、吸入一氧化氮及体外膜肺氧合治疗时，死亡率约为10%至20%，但在无法获得这些治疗手段时死亡率会高得多。西地那非是一种5型磷酸二酯酶抑制剂，可选择性降低肺血管阻力。
我们的目标是评估口服西地那非治疗PPHN的可行性及其对氧合的影响。
本研究是一项概念验证性、随机、双盲研究，纳入了胎龄>35.5周且出生<3天、患有重度PPHN且氧合指数（OI）>25并入住新生儿重症监护病房（哥伦比亚巴兰基亚市Niño Jesús医院）的婴儿。西地那非溶液由50毫克片剂配制而成。首剂（1毫克/千克）或安慰剂在随机分组后<30分钟经口胃管给药，每6小时给药一次。持续监测导管前血氧饱和度和血压。每6小时计算一次OI。主要结局变量是口服西地那非对氧合的影响。当OI<20或36小时后OI无显著变化时，停用西地那非或安慰剂。
6例OI>25的婴儿接受了安慰剂，7例接受了口服西地那非，中位年龄为25小时。所有婴儿病情均严重，吸入氧分数为1.0，通气参数相似。胃内给予西地那非和安慰剂耐受性良好。治疗组中，所有婴儿在6至30小时内OI均有改善，所有婴儿的脉搏血氧饱和度随时间稳步提高，且无一例对血压有明显影响；7例中有6例存活。安慰剂组中，6例婴儿中有1例存活。
口服西地那非给药简便，耐受性与安慰剂相当，可改善重度PPHN婴儿的OI,这表明口服西地那非可能对PPHN治疗有效，并强调需要进行大规模对照试验。
