吸入一氧化氮治疗早产儿低氧性呼吸衰竭的初步研究

A pilot study of inhaled nitric oxide in premature neonates with hypoxic respiratory failure

目的观察吸入一氧化氮（nitric oxide，NO）救治早产儿低氧性呼吸衰竭的安全性及有效性。方法两家三级医院新生儿重症监护病房2002年10月至2005年6月入住的胎龄小于35周早产儿，患呼吸窘迫综合征（respiratory distress syndrome，RDS）常规机械通气和（或）肺表面活性物质治疗2h后仍存在低氧性呼吸衰竭（FiO2≥0．4，PaO2〈50mm Hg，SpO2〈85％）者入选，分为常规治疗组（对照组，n=11）和吸入NO组（NO组，n=12）。监测肺动态顺应性（dynamic compliance，Cdyn）、气道阻力（airway resistance，RAW）、潮气量（tidal volume，VT）、氧合指数（oxygenation index，OI）和动脉血氧分压／肺泡氧分压（arterial—to-alveolar partial pressure of oxygen，a／A）。结果在治疗起始时NO组OI值（26．9±11．2）较对照组（13．7±6．5）高（P〈0．05），在治疗1h两组间差异无统计学意义，并保持至治疗72h（P〉0．05）。NO组OI值随治疗时间延长而不断降低；而对照组OI值在各时间点差异均无统计学意义。NO组起始a／A（0．08±0．03）较对照组（0．13±0．03）低（P〈0．01），两组a／A值逐渐升高，在治疗1h后两组间差异无统计学意义，直到治疗72h。NO组和对照组1、6、12、24、48、72h与0h相比，a／A值在1h起即比0h升高，到48h差异出现统计学意义（P〈0．05），并直至72h。吸入NO并未增加颅内出血、肺出血和慢性肺疾病的发生率。结论RDS早产儿吸入NO可能改善氧合和气体交换，且并未增加不良反应的发生，为多中心大样本随机对照研究提供了实验依据。

Objective To investigate the safety and efficacy of inhaled nitric oxide （NO） in premature infants with hypoxic respiratory failure （HRF）. Methods From Oct. 2002 to Jun. 2005, 23 premature neonates （gestational age 〈35 weeks） with respiratory distress syndrome （RDS） who were treated with mechanical ventilation and/or pulmonary surfactant for two hours and still with HRF （FiO2≥0.4, PaO2 〈50 mm Hg, SpO2〈85%） were allocated to a group with inhaled nitric oxide （NO group, n=12） and control group （n=11）. NO was given at 5-10 parts per million （ppm） initially followed by 2-5 ppm for maintenance. The arterial-to-alveolar partial pressure of oxygen （a/A ratio）, oxygenation index （OI）, dynamic compliance （Cdyn）, airway resistance （RAW） and tidal volume （VT） were monitored. Results At the beginning of the treatment, the OI of NO group （26.9±11.2） was higher than that of the control group （13. 7±6.5）, P〈0. 05; One hour later, there was no difference between two groups, and lasting to 72 hours（P〉0.05）. The a/A ratio of both groups had gradually increased, and OI of NO group decreased as time went by, while the OI of control group did not change at all. The incidence of intraventricular hemorrhage （IVH） of NO group was similar to that of control group. No significant difference was detected in the major complications and survival between the two groups. Conclusions Inhaled nitric oxide is safe for premature neonates with HRF. Results from this study was helpful for further randomized, controlled trial with large samples.