血管阻塞危象(VOC)在镰状细胞病(SCD)患者中很常见，10至14岁儿童VOC期间的平均住院时间为4.5天。根据该文的背景资料，20%的VOC住院患者得急性胸综合症(ACS)，这是一种有生命威胁的急性肺损伤，平均住院时间长达14天。“鉴于疼痛剧烈、发病率高、镰状细胞病中的VOC护理成本及当前治疗方案的缺乏等，鉴别和评价新的疗法尤为迫切，”文章作者表示。一氧化氮吸入是经食品和药品管理局批准、用于治疗新生儿低氧性呼吸衰竭的一种相对安全的药剂，在2次小型VOC安慰剂对照试验中显示了功效。
为进一步评价一氧化氮吸入的功效，匹兹堡大学的Mark T. Gladwin医学博士及其同事进行了阶段二随机安慰剂对照多中心试验。自2004年10月至2008年11月间，11个中心参与了试验，涉及150名患有血管阻塞危象的SCD患者。患者随机分组接受72小时一氧化氮气体吸入和氮安慰剂对照试验。主要结果测定是至疼痛危象消退的时间，界定标准为5小时不需要使用非口服(注射)阿片样物质；疼痛缓解程度根据视觉模拟疼痛量表(VAS)评分；能够步行；经患者和家人认定及医师意见一致，余痛可以在家里处理。
研究人员发现，根据治疗结果，VOC消退时间并无明显差异。至危象消退估计中位数(中点)时间分别为，一氧化氮吸入组73小时，安慰剂组65.5小时。而且，根据治疗结果，其他分析也无明显差异，包括中位住院时间(一氧化氮吸入与安慰剂之比为4.1：3.1天)、24小时平均VAS分值和阿片样物质平均总用量等。两个小组间，参与者在整个研究期内患上ACS而需要输血的比例并无差异，吸入气体研究期间ACS患者严重不良事件报告也无区别。
患者对一氧化氮吸入很耐受，无严重不良事件增加。
“总之，研究结果表明，本次研究所用的一氧化氮吸入剂量及给药方式并未减少镰状细胞病中的VOC严重性。这些结果突出表明，在有足够的SCD患者，迅速试验有前途的疗法提供足够动力的情况下，需要新的药剂及用于VOC研究的耐用的临床试验仪器，”作者最后总结道。
医脉通推荐英文摘要：
JAMA. 2011;305(9):893-902. doi: 10.1001/jama.2011.235
Nitric Oxide for Inhalation in the Acute Treatment of Sickle Cell Pain Crisis
Gladwin MT, Kato GJ, Weiner D, Onyekwere OC, Dampier C
(Division of Pulmonary, Allergy, and Critical Care Medicine (Dr Gladwin and Ms Hildesheim) and Vascular Medicine Institute (Drs Gladwin and Krishnamurti), University of Pittsburgh, Pittsburgh, Pennsylvania)
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.
更多阅读
Nitric oxide does not appear to improve treatment of sickle cell pain-attacks
Study finds nitric oxide does not help sickle cell pain crisis
(本网站所有内容，凡注明来源为“医脉通”，版权均归医脉通所有，未经授权，任何媒体、网站或个人不得转载，否则将追究法律责任，授权转载时须注明“来源：医脉通”。本网注明来源为其他媒体的内容为转载，转载仅作观点分享，版权归原作者所有，如有侵犯版权，请及时联系我们。)
