Inhaled nitric oxide as adjunctive therapy for severe malaria: a randomized controlled trial
Inhaled nitric oxide as adjunctive therapy for severe malaria: a randomized controlled trial
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DOI：
10.1186/s12936-015-0946-2
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发表时间：
2015-10-29
期刊：
影响因子：
3
通讯作者：
Kain, Kevin C.
中科院分区：
文献类型：
--
作者：
Hawkes, Michael T.;Conroy, Andrea L.;Kain, Kevin C.
背景：严重疟疾仍然是全球儿童死亡的主要原因。内皮一氧化氮减少与严重和致命的疟疾有关。假设辅助吸入一氧化氮(INO)可以改善非洲严重疟疾儿童的预后。方法：采用随机、盲法、安慰剂对照的方法，使用80ppm的iNO非呼吸面罩与室内空气安慰剂作为青蒿琥酯辅助治疗重症疟疾儿童的试验。主要结果是血管生成素-2(Ang-2)的纵向病程，血管生成素-2是疟疾严重程度和临床结果的内皮生物标志物。结果：180名儿童入选；88名儿童被分配到iNO组，92名儿童被分配到安慰剂组(均接受青蒿琥酯静脉注射)。入院72小时内测得的血管紧张素转换酶2水平在两组间无显著差异。两组48h死亡率相似[iNO组6/87(6.9%)vs安慰剂组8/92(8.7%)；OR 0.78，95%CI 0.26-2.3；p=0.65]。临床恢复时间和寄生虫清除动力学相似(p>；0.05)。在接受iNO治疗的患者中，有25%的患者出现了7%的高铁血红蛋白血症，并且没有后遗症。神经功能缺陷发生率(0.05)。结论：非呼吸机面罩在80ppm给予INO是安全的，但不影响循环Ang-2水平。为了达到生物学效果和改善临床结果，可能需要增强内皮细胞NO生物利用度的替代方法。
Background: Severe malaria remains a major cause of childhood mortality globally. Decreased endothelial nitric oxide is associated with severe and fatal malaria. The hypothesis was that adjunctive inhaled nitric oxide (iNO) would improve outcomes in African children with severe malaria.Methods: A randomized, blinded, placebo-controlled trial of iNO at 80 ppm by non-rebreather mask versus room air placebo as adjunctive treatment to artesunate in children with severe malaria was conducted. The primary outcome was the longitudinal course of angiopoietin-2 (Ang-2), an endothelial biomarker of malaria severity and clinical outcome.Results: One hundred and eighty children were enrolled; 88 were assigned to iNO and 92 to placebo (all received IV artesunate). Ang-2 levels measured over the first 72 h of hospitalization were not significantly different between groups. The mortality at 48 h was similar between groups [6/87 (6.9 %) in the iNO group vs 8/92 (8.7 %) in the placebo group; OR 0.78, 95 % CI 0.26-2.3; p = 0.65]. Clinical recovery times and parasite clearance kinetics were similar (p > 0.05). Methaemoglobinaemia > 7 % occurred in 25 % of patients receiving iNO and resolved without sequelae. The incidence of neurologic deficits ( 0.05).Conclusions: iNO at 80 ppm administered by non-rebreather mask was safe but did not affect circulating levels of Ang-2. Alternative methods of enhancing endothelial NO bioavailability may be necessary to achieve a biological effect and improve clinical outcome.