Department of Anesthesiology, Rigshospitalet, University of Copenhagen, Anestheisa, Juliane Marie Centre, Copenhagen, 2100, Denmark.
Anesth Analg. 2011 Jun;112(6):1411-21. doi: 10.1213/ANE.0b013e31820bd185. Epub 2011 Mar 3.
Acute hypoxemic respiratory failure, defined as acute lung injury and acute respiratory distress syndrome, are critical conditions associated with frequent mortality and morbidity in all ages. Inhaled nitric oxide (iNO) has been used to improve oxygenation, but its role remains controversial. We performed a systematic review with meta-analysis and trial sequential analysis of randomized clinical trials (RCTs). We searched CENTRAL, Medline, Embase, International Web of Science, LILACS, the Chinese Biomedical Literature Database, and CINHAL (up to January 31, 2010). Additionally, we hand-searched reference lists, contacted authors and experts, and searched registers of ongoing trials. Two reviewers independently selected all parallel group RCTs comparing iNO with placebo or no intervention and extracted data related to study methods, interventions, outcomes, bias risk, and adverse events. All trials, irrespective of blinding or language status were included. Retrieved trials were evaluated with Cochrane methodology. Disagreements were resolved by discussion. Our primary outcome measure was all-cause mortality. We performed subgroup and sensitivity analyses to assess the effect of iNO in adults and children and on various clinical and physiological outcomes. We assessed the risk of bias through assessment of trial methodological components. We assessed the risk of random error by applying trial sequential analysis.
We included 14 RCTs with a total of 1303 participants; 10 of these trials had a high risk of bias. iNO showed no statistically significant effect on overall mortality (40.2%versus 38.6%) (relative risks [RR] 1.06, 95% confidence interval [CI] 0.93 to 1.22; I² = 0) and in several subgroup and sensitivity analyses, indicating robust results. Limited data demonstrated a statistically insignificant effect of iNO on duration of ventilation, ventilator-free days, and length of stay in the intensive care unit and hospital. We found a statistically significant but transient improvement in oxygenation in the first 24 hours, expressed as the ratio of Po₂ to fraction of inspired oxygen (mean difference [MD] 15.91, 95% CI 8.25 to 23.56; I² = 25%). However, iNO appears to increase the risk of renal impairment among adults (RR 1.59, 95% CI 1.17 to 2.16; I² = 0) but not the risk of bleeding or methemoglobin or nitrogen dioxide formation.
iNO cannot be recommended for patients with acute hypoxemic respiratory failure. iNO results in a transient improvement in oxygenation but does not reduce mortality and may be harmful.
急性低氧性呼吸衰竭，定义为急性肺损伤和急性呼吸窘迫综合征，是与各年龄段频繁死亡率和发病率相关的危急情况。吸入一氧化氮（iNO）已被用于改善氧合作用，但它的作用仍然存在争议。我们进行了一项系统评价，对随机临床试验（RCTs）进行了荟萃分析和试验序贯分析。我们检索了 CENTRAL、Medline、Embase、国际 Web of Science、LILACS、中国生物医学文献数据库和 CINHAL（截至 2010 年 1 月 31 日）。此外，我们还手动检索了参考文献列表，联系了作者和专家，并检索了正在进行的试验登记册。两位审稿人独立选择了所有比较 iNO 与安慰剂或无干预的平行组 RCT，并提取了与研究方法、干预措施、结局、偏倚风险和不良事件相关的数据。所有试验，无论是否存在盲法或语言状态，均被纳入。检索到的试验均采用 Cochrane 方法进行评估。通过讨论解决了分歧。我们的主要结局测量指标是全因死亡率。我们进行了亚组和敏感性分析，以评估 iNO 在成人和儿童以及各种临床和生理结局中的作用。我们通过评估试验方法学组成部分来评估偏倚风险。我们通过应用试验序贯分析来评估随机错误的风险。
我们纳入了 14 项 RCT，共纳入 1303 名参与者；其中 10 项试验存在较高的偏倚风险。iNO 对总体死亡率无统计学显著影响（40.2%比 38.6%）（相对风险[RR]1.06，95%置信区间[CI]0.93 至 1.22；I²=0），并且在几个亚组和敏感性分析中也无统计学显著影响，表明结果可靠。有限的数据表明，iNO 对通气时间、无呼吸机天数和 ICU 及医院住院时间的影响无统计学意义。我们发现，在最初 24 小时内，氧合作用有统计学显著但短暂的改善，表现为氧分压与吸入氧分数的比值（平均差异[MD]15.91，95%CI8.25 至 23.56；I²=25%）。然而，iNO 似乎会增加成人肾功能损害的风险（RR1.59，95%CI1.17 至 2.16；I²=0），但不会增加出血或高铁血红蛋白或二氧化氮形成的风险。
不能推荐 iNO 用于急性低氧性呼吸衰竭患者。iNO 可导致氧合作用短暂改善，但不能降低死亡率，并且可能有害。
