Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome: Results of a randomized phase II trial
Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome: Results of a randomized phase II trial
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DOI：
10.1097/00003246-199801000-00011
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发表时间：
1998-01-01
影响因子：
8.8
通讯作者：
Papadakos, P
中科院分区：
文献类型：
--
作者：
Dellinger, RP;Zimmerman, JL;Papadakos, P
目的：评价吸入一氧化氮（NO）治疗急性呼吸窘迫综合征（ARDS）的安全性和生理反应。此外，各种剂量的吸入NO对临床结果参数的影响进行了评估。设计：前瞻性，多中心，随机，双盲，安慰剂对照研究。设置：美国30所学术，教学和社区医院的重症监护室。患者：美国-欧洲共识会议定义的ARDS患者，如果疾病发作在随机化后72小时内，则入组研究。例患者随机接受安慰剂（氮气）或吸入浓度为1.25、5、20、40或80 ppm的NO。检测Pao（2）的急性增加、平均肺动脉压的降低、机械通气强度和氧合指数。临床结果检查吸入NO对死亡率的剂量效应，存活和关闭机械通气的天数，以及符合氧合标准拔管后的存活天数。在接受吸入NO的患者中，60%的患者对治疗气体有急性反应，定义为Pao（2）增加大于或等于20%，剂量组之间无显著差异。24%的安慰剂患者在最初4小时内对治疗气体也有急性反应。氧合的初始增加转化为治疗第一天Fio（2）的降低和治疗前4天机械通气强度的降低，通过氧合指数测量。在死亡率、脱离机械通气的存活天数或符合拔管氧合标准后的存活天数方面，合并吸入NO组和安慰剂组之间没有差异。然而，接受5 ppm吸入NO的患者显示这些参数的改善。在这个剂量组中，在第28天存活和脱离机械通气的患者百分比（事后分析）高于安慰剂组（62%对44%）。与安慰剂相比，吸入NO的患者报告的不良事件的数量或类型没有明显差异。4例患者高铁血红蛋白浓度> 5%。吸入NO患者的平均吸入二氧化氮浓度为1.5 ppm。结论：从这个安慰剂对照研究，吸入NO似乎是耐受性良好的ARDS患者研究的人口。在机械通气保持恒定的情况下，与安慰剂相比，吸入NO与治疗前4小时内氧合的显著改善相关。在前4天观察到氧合指数的改善。需要更大规模的III期研究来确定这些急性生理改善是否会导致临床结局的改变。
Objectives: 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.Design: Prospective, multicenter, randomized, double-blind, placebo-controlled study.Setting: Intensive care units of 30 academic, teaching, and community hospitals in the United States.Patients: 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.Interventions: Patients were randomized to receive placebo (nitrogen gas) or inhaled NO at concentrations of 1.25, 5, 20, 40, or 80 ppm.Measurements and Main Results: Acute increases in Pao(2) 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 Pao(2) increase greater than or equal to 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 Fio(2) 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.Conclusions: 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 improve ment 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.