Preliminary assessment of inhaled nitric oxide for acute vaso-occlusive crisis in pediatric patients with sickle cell disease
Preliminary assessment of inhaled nitric oxide for acute vaso-occlusive crisis in pediatric patients with sickle cell disease
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DOI：
10.1001/jama.289.9.1136
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发表时间：
2003-03-05
影响因子：
120.7
通讯作者：
Brugnara, C
中科院分区：
文献类型：
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作者：
Weiner, DL;Hibberd, PL;Brugnara, C
血管闭塞是镰状细胞病痛苦危象和急性及慢性器官损伤的核心。血管张力、粘附、血小板活化和炎症的异常一氧化氮依赖性调节有助于血管闭塞的病理生理学。目的探讨吸入性一氧化氮（INO）治疗小儿血管闭塞危象的有效性和安全性。设计前瞻性、双盲、安慰剂对照、随机临床试验，1999年9月至2001年10月入组。研究对象：20例年龄在10 ~ 21岁的镰状细胞病和严重急性血管闭塞危象患者，随机接受INO治疗，（80 ppm，吸入氧气的最终浓度为21%; n=10）或安慰剂（21%吸入氧气; n=10）4小时。主要结果测量与吸入前疼痛相比，吸入4小时时疼痛的变化，测量10厘米视觉模拟量表（VAS）;次要结果的措施是疼痛超过6小时，肠外麻醉剂使用超过24小时，住院时间，血压，氧饱和度，和高铁血红蛋白concentration.Results吸入前VAS疼痛评分在INO和安慰剂组相似（P= 0.80）。4小时时VAS疼痛评分的降低在I NO组中为2.0 cm，在安慰剂组中为1.2 cm（P=37）。每小时疼痛评分的重复测量方差分析显示，INO组比安慰剂组减少1 cm/h（P=.02）。INO组6小时内的吗啡使用量显著减少（平均累积使用量，0.29 vs 0.44 mg/kg; P= 0.03），但在4小时（0.26 vs 0.32 mg/kg; P= 0.21）或24小时（0.63 vs 0.91 mg/kg; P= 0.15）内没有差异。INO组和安慰剂组的住院时间分别为78和100小时（P= 0.19）。结论本探索性研究的结果表明，INO可能是有益的急性血管闭塞危象。这些初步结果值得进一步调查。
Context Vaso-occlusion is central to the painful crises and acute and chronic organ damage in sickle cell disease. Abnormal nitric oxide-dependent regulation of vascular tone, adhesion, platelet activation, and inflammation contributes to the pathophysiology of vaso-occlusion. Nitric oxide may have promise as a mechanism-of-disease-based therapy for treatment of vaso-occlusion.Objective To explore the efficacy and safety of inhaled nitric oxide (INO) for treatment of vaso-occlusive crisis in pediatric patients.Design Prospective, double-blind, placebo-controlled, randomized clinical trial with enrollment between September 1999 and October 2001.Setting Urban, tertiary care children's hospital in the United States.Participants Twenty patients aged 10 to 21 years with sickle cell disease and severe acute vaso-occlusive crisis.Intervention Patients were randomly assigned to receive INO (80 ppm with 21% final concentration of inspired oxygen; n=10), or placebo (21% inspired oxygen; n=10) for 4 hours.Main Outcome Measures Change in pain at 4 hours of inhalation compared with preinhalation pain, measured on a 10-cm visual analog scale (VAS); secondary outcome measures were pain over 6 hours, parenteral narcotic use over 24 hours, duration of hospitalization, blood pressure, oxygen saturation, and methemoglobin concentration.Results Preinhalation VAS pain scores were similar in the INO and placebo groups (P=.80). The decrease in VAS pain scores at 4 hours was 2.0 cm in the I NO group and 1.2 cm in the placebo group (P=37). Repeated-measures analysis of variance for hourly pain scores showed a 1-cm/h greater reduction in the INO group than the placebo group (P=.02). Morphine use over 6 hours was significantly less in the INO group (mean cumulative use, 0.29 vs 0.44 mg/kg; P=.03) but was not different over 4 hours (0.26 vs 0.32 mg/kg; P=.21) or 24 hours (0.63 vs 0.91 mg/kg; P=.15). Duration of hospitalization was 78 and 100 hours in the INO and placebo groups, respectively (P=.19). No INO toxicity was observed.Conclusions Results of this exploratory study suggest that INO may be beneficial for acute vaso-occlusive crisis. These preliminary results warrant further investigation.