Cole F Sessions, Alleyne Claudia, Barks John D E, Boyle Robert J, Carroll John L, Dokken Deborah, Edwards William H, Georgieff Michael, Gregory Katherine, Johnston Michael V, Kramer Michael, Mitchell Christine, Neu Josef, Pursley DeWayne M, Robinson Walter, Rowitch David H
Department of Pediatrics, Division of Newborn Medicine, Washington University School of Medicine, and St. Louis Children’s Hospital, St. Louis, Missouri, USA.
NIH Consens State Sci Statements. 2010 Oct 29;27(5):1-34.
To provide healthcare providers, patients, and the general public with a responsible assessment of currently available data on the use of inhaled nitric oxide in early routine, early rescue, or later rescue regimens in the care of premature infants <34 weeks gestation who require respiratory support.
A non-Department of Health and Human Services, nonadvocate 16-member panel representing the fields of biostatistics, child psychology, clinical trials, ethics, family-centered care, neonatology, neurodevelopmental follow-up, nursing, pediatric epidemiology, neurobehavior, neurological surgery, neurology, and pulmonology, perinatology, and research methodology. In addition, 18 experts from pertinent fields presented data to the panel and conference audience.
Presentations by experts and a systematic review of the literature prepared by the Johns Hopkins University Evidence-based Practice Center, through the Agency for Healthcare Research and Quality. Scientific evidence was given precedence over anecdotal experience.
The panel drafted its statement based on scientific evidence presented in open forum and on published scientific literature. The draft statement was presented on the final day of the conference and circulated to the audience for comment. The panel released a revised statement later that day at http://consensus.nih.gov. This statement is a report of the panel and is not a policy statement of the NIH or the Federal Government.
(1) Taken as a whole, the available evidence does not support use of inhaled nitric oxide in early routine, early rescue, or later rescue regimens in the care of premature infants <34 weeks gestation who require respiratory support. (2) There are rare clinical situations, including pulmonary hypertension or hypoplasia, that have been inadequately studied in which inhaled nitric oxide may have benefit in infants <34 weeks gestation. In such situations, clinicians should communicate with families regarding the current evidence on its risks and benefits as well as remaining uncertainties. (3) Basic research and animal studies have contributed to important understandings of inhaled nitric oxide benefits on lung development and function in infants at high risk of bronchopulmonary dysplasia. These promising results have only partly been realized in clinical trials of inhaled nitric oxide treatment in premature infants. Future research should seek to understand this gap. (4) Predefined subgroup and post hoc analyses of previous trials showing potential benefit of inhaled nitric oxide have generated hypotheses for future research for clinical trials. Prior strategies shown to be ineffective are discouraged unless new evidence emerges. The positive results of one multicenter trial, which was characterized by later timing, higher dose, and longer duration of treatment, require confirmation. Future trials should attempt to quantify the individual effects of each of these treatment-related variables (timing, dose, and duration), ideally by randomizing them separately. (5) Based on assessment of currently available data, hospitals, clinicians, and the pharmaceutical industry should avoid marketing inhaled nitric oxide for premature infants <34 weeks gestation.
为医疗服务提供者、患者及公众提供关于吸入一氧化氮在孕周小于34周且需要呼吸支持的早产儿护理的早期常规、早期抢救或后期抢救方案中应用的现有数据的负责任评估。
一个由16名成员组成的小组，成员来自生物统计学、儿童心理学、临床试验、伦理学、以家庭为中心的护理、新生儿学、神经发育随访、护理、儿科流行病学、神经行为学、神经外科、神经病学、肺病学、围产医学和研究方法学领域，并非卫生与公众服务部成员，也无利益关联。此外，来自相关领域的18位专家向该小组及会议听众展示了数据。
专家的报告以及约翰·霍普金斯大学循证实践中心通过医疗保健研究与质量局编写的文献系统综述。科学证据优先于轶事经验。
该小组根据公开论坛上展示的科学证据和已发表的科学文献起草了声明。声明草案在会议最后一天公布，并分发给听众征求意见。当天晚些时候，该小组在http://consensus.nih.gov上发布了一份修订声明。本声明是该小组的报告，并非美国国立卫生研究院或联邦政府的政策声明。
（1）总体而言，现有证据不支持在孕周小于34周且需要呼吸支持的早产儿护理的早期常规、早期抢救或后期抢救方案中使用吸入一氧化氮。（2）存在一些罕见的临床情况，包括肺动脉高压或肺发育不全，对这些情况的研究尚不充分，吸入一氧化氮可能对孕周小于34周的婴儿有益。在这种情况下，临床医生应就其风险和益处以及尚存的不确定性与家庭进行沟通。（3）基础研究和动物研究有助于重要理解吸入一氧化氮对支气管肺发育不良高危婴儿肺部发育和功能的益处。这些有前景的结果在早产儿吸入一氧化氮治疗的临床试验中仅部分得以实现。未来研究应致力于理解这一差距。（4）先前试验的预定义亚组分析和事后分析显示吸入一氧化氮可能有益，这些分析为未来临床试验研究产生了假设。除非出现新证据，不鼓励采用已证明无效的先前策略。一项多中心试验的阳性结果，其特点是治疗时机较晚、剂量较高和疗程较长，需要得到证实。未来试验应尝试分别对这些与治疗相关的变量（时机、剂量和疗程）的个体效应进行量化，理想情况下通过分别随机化来实现。（5）基于对现有数据的评估，医院、临床医生和制药行业应避免将吸入一氧化氮用于孕周小于34周的早产儿的市场营销。
