一氧化氮吸人治疗成人及儿童急性呼吸窘迫综合征和急性肺损伤的荟萃与序贯分析综述

背景急性肺损伤及急性呼吸窘迫综合征引起的急性低氧性呼吸衰竭是导致各个年龄段高死亡率及发病率的危重病。一氧化氮（nitric oxide，NO）吸入能否改善氧合作用仍有争议。本文就各随机临床试验（randomized clinical trials, RCTs）的荟萃及序贯分析作此综述。文献来自对CENTRAL、Medline、Embase以及联网CENTRAL, Medline, Embase 以及联网Science, LILACS, the Chinese Biomedical Literature数据库（更新至2010年1月31日）。同时查阅了参考文献，联系了作者及专家并跟踪了最新研究。两位研究员独立比较了各项RCTs实验中NO吸入治疗与对照组间的实验方法、干预方式、结果、偏倚因素以及相反意见。入选各双盲类型及语种的研究。回顾性研究参考循证医学。在讨论部分解决不一致的结果。初级转归指标为整体死亡率。有亚组及敏感度分析评估NO吸入治疗对于儿童及成人的临床及生理学转归09作用。使用实验方法学评估偏倚因素。使用试验性序列分析评估随机误差。结果研究包括了14项RCTs，共计1303例患者。其中10项偏倚风险较高。iNO在整体死亡率的改善中无显著性统计差异（40.2％vs 38．6％）[相对危险度（relativerisks，RR）1．06，95％可信区间（confidence interval，CI）为0．93-1．22，I^2=0]，一些亚组及灵敏度分析则显示较强劲的结果。有限的数据显示iNO在改善通气时间、有助脱机、减少ICU及住院时间方面并无优势。我们发现iNO在改善第一个24小时的氧合、减少吸入氧浓度方面有统计学差异[平均差（mean difference，MD）15．91，95％CI为8．25-23．56，I^2=25％]。然而，iNO是增加成人肾损伤的危险因素（RR1．59，95％CI1．17-2．16；I^2=0），但不增加出血风险及形成高铁血红蛋白症和二氧化氮的风险。结论不推荐使用iNO治疗急性缺氧性呼吸衰竭。iNO能暂时改善氧合但不能降低死亡率并有可能对人体有害。

BACKGROUND： 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 C^hrane 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. RESULTS： We included 14 RCTs with a total of 1303 participants; 10 of these trials had a high risk of bias, iNOshowed no statistically significant effect on overall mortality （40.2% versus 38.6%） （relative risks ERR] 1.06, 95% confidence interval [CI] 0.93 to 1.22; I^2 = 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 to23.56; I^2 = 25%）. However, iNO appears to increase the risk of renal impairment among adults （RR 1.59, 95% CI 1. 17 to 2.16; I^2 = 0） but not the risk of bleeding or methemoglobin or nitrogen dioxide formation. CONCLUSIONS： 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.