Dellinger R P, Zimmerman J L, Taylor R W, Straube R C, Hauser D L, Criner G J, Davis K, Hyers T M, Papadakos P
University of Missouri, Columbia, USA.
Crit Care Med. 1998 Jan;26(1):15-23. doi: 10.1097/00003246-199801000-00011.
To evaluate the safety and physiologic response of inhaled nitric oxide (NO) in patients with acute respiratory distress syndrome (ARDS). In addition, the effect of various doses of inhaled NO on clinical outcome parameters was assessed.
Prospective, multicenter, randomized, double-blind, placebo-controlled study.
Intensive care units of 30 academic, teaching, and community hospitals in the United States.
Patients with ARDS, as defined by the American-European Consensus Conference, were enrolled into the study if the onset of disease was within 72 hrs of randomization.
Patients were randomized to receive placebo (nitrogen gas) or inhaled NO at concentrations of 1.25, 5, 20, 40, or 80 ppm.
Acute increases in PaO2, decreases in mean pulmonary arterial pressure, intensity of mechanical ventilation, and oxygenation index were examined. Clinical outcomes examined were the dose effects of inhaled NO on mortality, the number of days alive and off mechanical ventilation, and the number of days alive after meeting oxygenation criteria for extubation. A total of 177 patients were enrolled over a 14-month period. An acute response to treatment gas, defined as a PaO2 increase > or =20%, was seen in 60% of the patients receiving inhaled NO with no significant differences between dose groups. Twenty-four percent of placebo patients also had an acute response to treatment gas during the first 4 hrs. The initial increase in oxygenation translated into a reduction in the FIO2 over the first day and in the intensity of mechanical ventilation over the first 4 days of treatment, as measured by the oxygenation index. There were no differences among the pooled inhaled NO groups and placebo with respect to mortality rate, the number of days alive and off mechanical ventilation, or the number of days alive after meeting oxygenation criteria for extubation. However, patients receiving 5 ppm inhaled NO showed an improvement in these parameters. In this dose group, the percentage of patients alive and off mechanical ventilation at day 28 (a post hoc analysis) was higher (62% vs. 44%) than the placebo group. There was no apparent difference in the number or type of adverse events reported among those patients receiving inhaled NO compared with placebo. Four patients had methemoglobin concentrations >5%. The mean inspired nitrogen dioxide concentration in inhaled NO patients was 1.5 ppm.
From this placebo-controlled study, inhaled NO appears to be well tolerated in the population of ARDS patients studied. With mechanical ventilation held constant, inhaled NO is associated with a significant improvement in oxygenation compared with placebo over the first 4 hrs of treatment. An improvement in oxygenation index was observed over the first 4 days. Larger phase III studies are needed to ascertain if these acute physiologic improvements can lead to altered clinical outcome.
评估吸入一氧化氮（NO）对急性呼吸窘迫综合征（ARDS）患者的安全性及生理反应。此外，还评估了不同剂量吸入NO对临床结局参数的影响。
前瞻性、多中心、随机、双盲、安慰剂对照研究。
美国30家学术、教学及社区医院的重症监护病房。
符合美国-欧洲共识会议定义的ARDS患者，若疾病发作在随机分组后72小时内，则纳入本研究。
患者被随机分为接受安慰剂（氮气）或浓度为1.25、5、20、40或80 ppm的吸入NO。
检测动脉血氧分压（PaO₂）的急性升高、平均肺动脉压的降低、机械通气强度及氧合指数。所检测的临床结局包括吸入NO对死亡率的剂量效应、存活且脱离机械通气的天数以及达到拔管氧合标准后的存活天数。在14个月期间共纳入177例患者。接受吸入NO治疗的患者中，60%出现对治疗气体的急性反应，定义为PaO₂升高≥20%，各剂量组间无显著差异。24%的安慰剂组患者在最初4小时内也出现对治疗气体的急性反应。通过氧合指数测量，最初的氧合改善转化为治疗第1天FiO₂的降低以及治疗前4天机械通气强度的降低。在合并的吸入NO组和安慰剂组之间，死亡率、存活且脱离机械通气的天数或达到拔管氧合标准后的存活天数无差异。然而，接受5 ppm吸入NO治疗的患者在这些参数上有所改善。在该剂量组中，第28天（事后分析）存活且脱离机械通气的患者百分比（62%对44%）高于安慰剂组。与安慰剂组相比，接受吸入NO治疗的患者报告的不良事件数量或类型无明显差异。4例患者的高铁血红蛋白浓度>5%。吸入NO患者吸入的二氧化氮平均浓度为1.5 ppm。
从这项安慰剂对照研究来看，在所研究的ARDS患者群体中，吸入NO似乎耐受性良好。在机械通气保持不变的情况下，与安慰剂相比，吸入NO在治疗的前4小时与氧合的显著改善相关。在治疗的前4天观察到氧合指数有所改善。需要更大规模的III期研究来确定这些急性生理改善是否能导致临床结局改变。
