Nitric Oxide for Inhalation in the Acute Treatment of Sickle Cell Pain Crisis A Randomized Controlled Trial
Nitric Oxide for Inhalation in the Acute Treatment of Sickle Cell Pain Crisis A Randomized Controlled Trial
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DOI：
10.1001/jama.2011.235
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发表时间：
2011-03-02
影响因子：
120.7
通讯作者：
Casella, James F.
中科院分区：
文献类型：
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作者：
Gladwin, Mark T.;Kato, Gregory J.;Casella, James F.
在镰状细胞病（SCD）小鼠模型、急性胸综合征患者病例系列和2个小型安慰剂对照试验中，吸入一氧化氮已显示出治疗血管闭塞性疼痛危像（VOC）的有效性。目的探讨吸入一氧化氮气体是否能减少SCD患者在急诊科或医院就诊时的痛苦危机持续时间。设计、环境和参与者：前瞻性、多中心、双盲、随机、安慰剂对照的临床试验，在2004年10月5日至2008年12月22日期间，在11个中心对150名患有挥发性有机化合物SCD的参与者进行了长达72小时的吸入一氧化氮气体与吸入氮安慰剂的对照。干预措施：吸入一氧化氮气体vs吸入氮安慰剂。主要终点是疼痛危机的解决时间，定义为(1)停止静脉注射阿片类药物5小时；(2)通过视觉模拟疼痛量表评分6 cm或更低（0-10分）评估疼痛缓解；(3)行走能力；(4)患者和家属的决定，在医生的共识下，剩余的疼痛可以在家里管理。结果一氧化氮组和安慰剂组的主要终点无显著变化，危机解决的中位时间分别为73.0小时（95%可信区间[CI]， 46.0 ~ 91.0）和65.5小时（95% CI, 48.1 ~ 84.0） （P= 0.87）。次要结局指标无显著差异，包括住院时间、视觉模拟疼痛量表评分、阿片类药物累积使用和急性胸综合征发生率。吸入一氧化氮耐受性良好，严重不良事件未增加。静脉高铁血红蛋白浓度的增加证实了依从性和随机化，但在任何研究参与者中都不超过5%。治疗组血浆硝酸盐显著升高，但血浆或全血亚硝酸盐未见升高。结论在伴有VOC的SCD住院患者中，与安慰剂相比，吸入一氧化氮并没有缩短危机解决的时间。
Context Inhaled nitric oxide has shown evidence of efficacy in mouse models of sickle cell disease (SCD), case series of patients with acute chest syndrome, and 2 small placebo-controlled trials for treatment of vaso-occlusive pain crisis (VOC).Objective To determine whether inhaled nitric oxide gas reduces the duration of painful crisis in patients with SCD who present to the emergency department or hospital for care.Design, Setting, and Participants Prospective, multicenter, double-blind, randomized, placebo-controlled clinical trial for up to 72 hours of inhaled nitric oxide gas vs inhaled nitrogen placebo in 150 participants presenting with VOC of SCD at 11 centers between October 5, 2004, and December 22, 2008.Intervention Inhaled nitric oxide gas vs inhaled nitrogen placebo.Main Outcome Measures The primary end point was the time to resolution of painful crisis, defined by (1) freedom from parenteral opioid use for 5 hours; (2) pain relief as assessed by visual analog pain scale scores of 6 cm or lower (on 0-10 scale); (3) ability to walk; and (4) patient's and family's decision, with physician consensus, that the remaining pain could be managed at home.Results There was no significant change in the primary end point between the nitric oxide and placebo groups, with a median time to resolution of crisis of 73.0 hours (95% confidence interval [CI], 46.0-91.0) and 65.5 hours (95% CI, 48.1-84.0), respectively (P=.87). There were no significant differences in secondary outcome measures, including length of hospitalization, visual analog pain scale scores, cumulative opioid usage, and rate of acute chest syndrome. Inhaled nitric oxide was well tolerated, with no increase in serious adverse events. Increases in venous methemoglobin concentration confirmed adherence and randomization but did not exceed 5% in any study participant. Significant increases in plasma nitrate occurred in the treatment group, but there were no observed increases in plasma or whole blood nitrite.Conclusion Among patients with SCD hospitalized with VOC, the use of inhaled nitric oxide compared with placebo did not improve time to crisis resolution.