一氧化氮吸入治疗新生儿胎粪吸入综合征的随机对照研究

A randomized controlled study on the efficacy of inhaled nitric oxide in treatment of neonates with meconium aspiration syndrome

目的观察吸入低浓度一氧化氮（NO）治疗胎粪吸入综合征（MAS）的疗效和安全性。方法46名氧合指数（OI）≥15的重症MAS患儿入选试验，采用随机数字法随机分为NO组（NO，n=21）和对照组（C，n=25），所有患儿均在本院NICU接受机械通气同步间歇指令模式（SIMV）治疗。NO组吸入NO初始剂量15ppm，吸入1h如血氧饱和度（SpO2）提高〉10％，动脉血PaO2提高〉10mmHg（1mmHg=0．133kPa）判定为有效（否则判定为无效，增加吸入NO的浓度，最多不超过20ppm）。两组均监测0、1、24h的动脉血气和体循环血压、肺动脉压，记录吸氧浓度、氧合指数、呼吸机参数、呼吸机应用时间、氧暴露时间，吸入NO12—24h测定血高铁血红蛋白浓度。结果NO组和对照组在1h和24h，OI差异有统计学意义（F=181．77，P〈0．01）；NO组患儿在吸入NO后1h氧合指数即与0h时对照差异有统计学意义（F=35．27，P〈0．01），而对照组直至24h与0h比较，差异才有统计学意义（F=20．16，P〈0．01）；随着NO的持续吸入，NO组肺动脉压力逐渐下降，而体循环收缩压无明显改变（P〉0．05），两组间肺动脉压力在1h（t=2．41，P〈0．05）、24h（t=3．11，P〈0．01）差异均有统计学意义；血高铁血红蛋白浓度未发现异常增高；两组间住院天数（t=2．86，P〈0．05）、氧暴露时间（t=2．53，P〈0．05）、机械通气时间（t=2．41，P〈0．05）差异均有统计学意义，而死亡率（X^2=0．21，P〉0．05），和颅内出血的发生率（X^2=0．00，P〉0．05）差异无统计学意义。结论吸入NO治疗重症MAS能较迅速改善氧合，缩短呼吸机应用时间、氧暴露时间及住院天数，并未增加主要并发症的发生。

Objective Meconium aspiration syndrome （MAS） is a disease of the term and nearterm infant that is associated with considerable respiratory morbidity. The purpose of this study was to investigate effects of inhaled nitric oxide （iNO） in oxygenation and outcome of newborns with MAS. Methods Eligible patients diagnosed as severe MAS admitted consecutively to the neonatal intensive care unit （NICU） of Hebei Children＇s Hospital from January 2004 to June 2006 were included in the study. The patients with an oxygenation index （OI）≥ 15 were randomized in a nonblinded manner to receive either iNO （ NO group, n = 21 ） or no NO （ control group, n = 25 ）. Patients with an OI ≥ 15 after enrollment were treated with iNO at 15 ppm initially. The response to iNO was assessed according to the increase in arterial PaO2 and oxygen saturation（ SpO2 ）after exposure to the starting concentration for 60 minutes. A response of 10 mm Hg（1 mm Hg =0. 133 kPa） increase in PaO2 and a 10% increase in SpO2 was assessed responsive to iNO. All patients were treated in the same neonatal unit and received the same standard therapy throughout the study period. Arterial blood gas tensions, pulmonary arterial pressure and systemic arterial blood pressures were recorded at baseline, 1 hour, and 24 hours in all patients. Methemoglobin levels were obtained at 12-24 hours after inhaled NO treatment. Parameters of fraction of inspired oxygen （ FiO2 ）, OI, mortality, ventilation time, and incidence of intraventricular hemorrhage （IVH, grade Ⅲ-Ⅳ ） were recorded. Informed consent was obtained from parents before enrollment. The protocol and the informed consent forms were approved by the ethic committee of the hospital before patient enrollment. Results There was no significant difference in gestational age, birth weight, gender ratio, age at admission in hours, c-section delivery between the two groups, and no significant difference was found in respiratory mechanics parameters between the two groups at baseline. The duration of iNO was 34. 90 ± 16. 41 hours. At the beginning of the treatment, no significant differences were detected in the OI and PAP between the two groups. One hour later, OI and PAP of NO group decreased significantly （OI, F = 35.27, P 〈 0. 01, PAP, F=24. 30, P〈0.01）, while in control group the difference was not found until 24 hours （OI, F=20. 16, P 〈 0.01, PAP, F = 101.22, P 〈 0. 01 ）. There were significant differences in PAP at 1,24 hours between the two groups （ 1 h, t = 2.41, P 〈 0. 05 ; 24 h, t = 3.11, P 〈 0. 01 ）. The methemoglobin levels were normaL Compared to the controls, hospital stay （ t = 2. 86, P 〈 0.05 ）, duration of the need for oxygen supplement （ t = 2.53, P 〈 0. 05 ） and ventilation time were shorter （ t = 2. 41, P 〈 0.05 ）., whereas mortality （X^2 = 0. 21, P 〉 0. 05 ） and incidence of IVH （ X^2 = 0. 00, P 〉 0. 05 ） were not significantly different between the groups. Conclusions iNO could effectively improve the oxygenation and shorten the ventilation time and hospital stay without augmentation of risk of IVH and pneumothorax in these neonatal patients.