Cornfield D N, Maynard R C, deRegnier R A, Guiang S F, Barbato J E, Milla C E
Division of Pulmonary and Critical Care Medicine, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Pediatrics. 1999 Nov;104(5 Pt 1):1089-94. doi: 10.1542/peds.104.5.1089.
Recent reports indicate that inhaled nitric oxide (iNO) causes selective pulmonary vasodilation, increases arterial oxygen tension, and may decrease the use of extracorporeal membrane oxygenation (ECMO) in infants with persistent pulmonary hypertension of the newborn (PPHN). Despite these reports, the optimal dose and timing of iNO administration in PPHN remains unclear.
To test the hypotheses that in PPHN 1) iNO at 2 parts per million (ppm) is effective at acutely increasing oxygenation as measured by oxygenation index (OI); 2) early use of 2 ppm of iNO is more effective than control (0 ppm) in preventing clinical deterioration and need for iNO at 20 ppm; and 3) for those infants who fail the initial treatment protocol (0 or 2 ppm) iNO at 20 ppm is effective at acutely decreasing OI.
A randomized, controlled trial of iNO in 3 nurseries in a single metropolitan area. Thirty-eight children, average gestational age of 37.3 weeks and average age <1 day were enrolled. Thirty-five of 38 infants had echocardiographic evidence of pulmonary hypertension. On enrollment, median OI in the control group, iNO at 0 ppm, (n = 23) was 33.1, compared with 36.9 in the 2-ppm iNO group (n = 15).
Initial treatment with iNO at 2 ppm for an average of 1 hour was not associated with a significant decrease in OI. Twenty of 23 (87%) control patients and 14 of 15 (92%) of the low-dose iNO group demonstrated clinical deterioration and were treated with iNO at 20 ppm. In the control group, treatment with iNO at 20 ppm decreased the median OI from 42.6 to 23.8, whereas in the 2-ppm iNO group with a change in iNO from 2 to 20 ppm, the median OI did not change (42.6 to 42.0). Five of 15 patients in the low-dose nitric oxide group required ECMO and 2 died, compared with 7 of 23 requiring ECMO and 5 deaths in the control group.
In infants with PPHN, iNO 1): at 2 ppm does not acutely improve oxygenation or prevent clinical deterioration, but does attenuate the rate of clinical deterioration; and 2) at 20 ppm acutely improves oxygenation in infants initially treated with 0 ppm, but not in infants previously treated with iNO at 2 ppm. Initial treatment with a subtherapeutic dose of iNO may diminish the clinical response to 20 ppm of iNO and have adverse clinical sequelae.
近期报告表明，吸入一氧化氮（iNO）可引起选择性肺血管舒张，提高动脉血氧张力，并可能减少新生儿持续性肺动脉高压（PPHN）患儿体外膜肺氧合（ECMO）的使用。尽管有这些报告，但PPHN中iNO给药的最佳剂量和时机仍不清楚。
检验以下假设：在PPHN中，1）百万分之二（ppm）的iNO可有效急性增加氧合指数（OI）所测量的氧合；2）早期使用2 ppm的iNO在预防临床恶化和避免使用20 ppm的iNO方面比对照组（0 ppm）更有效；3）对于那些初始治疗方案（0或2 ppm）失败的婴儿，20 ppm的iNO可有效急性降低OI。
在一个大都市地区的3个托儿所进行的一项关于iNO的随机对照试验。纳入了38名儿童，平均胎龄37.3周，平均年龄<1天。38名婴儿中有35名有肺动脉高压的超声心动图证据。入组时，对照组（0 ppm的iNO，n = 23）的中位OI为33.1，而2 ppm iNO组（n = 15）为36.9。
平均用2 ppm的iNO初始治疗1小时与OI的显著降低无关。23名对照组患者中有20名（87%）和低剂量iNO组的15名患者中有14名（92%）出现临床恶化，并接受了20 ppm的iNO治疗。在对照组中，用20 ppm的iNO治疗使中位OI从42.6降至23.8，而在iNO从2 ppm改为20 ppm的2 ppm iNO组中，中位OI没有变化（42.6至42.0）。低剂量一氧化氮组的15名患者中有5名需要ECMO，2名死亡，而对照组中23名需要ECMO的患者中有7名，5名死亡。
在PPHN婴儿中，iNO 1）：2 ppm时不能急性改善氧合或预防临床恶化，但可减缓临床恶化速度；2）20 ppm时可急性改善最初用0 ppm治疗的婴儿的氧合，但不能改善先前用2 ppm的iNO治疗的婴儿的氧合。用低于治疗剂量的iNO进行初始治疗可能会降低对20 ppm的iNO的临床反应，并产生不良临床后果。
