Objective

To evaluate the real-world safety and effectiveness of inhaled nitric oxide (INOflo^® for Inhalation 800 ppm) for perioperative pulmonary hypertension associated with cardiac surgery in Japan.

Methods

This was a prospective, non-interventional, all-case, post-marketing study of pediatric and adult patients who received perioperative INOflo with cardiac surgery from November 2015–December 2020. Safety and effectiveness were monitored from INOflo initiation to 48 h after treatment completion or withdrawal. Safety outcomes included adverse drug reactions, blood methemoglobin concentrations, and inspired nitrogen dioxide concentrations over time. Effectiveness outcomes included changes in central venous pressure among pediatrics, mean pulmonary arterial pressure among adults, and the partial pressure of arterial oxygen/fraction of inspired oxygen ratio (PaO₂/FiO₂) in both populations.

Results

The safety analysis population included 2,817 Japanese patients registered from 253 clinical sites (pediatrics, n = 1375; adults, n = 1442). INOflo was generally well tolerated; 15 and 20 adverse drug reactions were reported in 14 pediatrics (1.0%) and 18 adults (1.2%), respectively. No clinically significant elevations in blood methemoglobin and inspired nitrogen dioxide concentrations were observed. INOflo treatment was associated with significant reductions in both central venous pressure among pediatrics and mean pulmonary arterial pressure among adults, and significant improvements in PaO₂/FiO₂ among pediatrics and adults with PaO₂/FiO₂ ≤ 200 at baseline.

Conclusions

Perioperative INOflo treatment was a safe and effective strategy to improve hemodynamics and oxygenation in patients with pulmonary hypertension during cardiac surgery. These data support the use of INOflo for this indication in Japanese clinical practice.

中文翻译：

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心脏手术围手术期吸入一氧化氮治疗肺动脉高压的真实安全性和有效性：一项针对日本 2817 名患者的上市后研究

客观的

^{旨在评估吸入一氧化氮（INoflo ®}吸入 800 ppm）在日本治疗与心脏手术相关的围手术期肺动脉高压的现实安全性和有效性。

方法

这是一项前瞻性、非干预性、全病例、上市后研究，研究对象为 2015 年 11 月至 2020 年 12 月期间接受心脏手术的围手术期 INOflo 的儿童和成人患者。从 INOflo 开始到治疗完成后 48 小时监测安全性和有效性或撤回。安全性结果包括药物不良反应、血液高铁血红蛋白浓度和随时间变化的吸入二氧化氮浓度。有效性结果包括儿科中心静脉压的变化、成人平均肺动脉压以及两个人群的动脉氧分压/吸入氧分数比率（PaO ₂ /FiO _{2 ）。}

结果

安全性分析人群包括来自 253 个临床中心的 2,817 名日本患者（儿科，n = 1375；成人，n = 1442）。INOflo 总体耐受性良好；14 名儿童 (1.0%) 和 18 名成人 (1.2%) 分别报告了 15 起和 20 起药物不良反应。没有观察到血液高铁血红蛋白和吸入二氧化氮浓度有临床意义的升高。INOflo 治疗与儿科中心静脉压和成人平均肺动脉压显着降低相关，并且 基线时PaO ₂ /FiO ₂ ≤ 200的儿科和成人 PaO ₂ /FiO _{2显着改善。}

结论

围手术期 INOflo 治疗是改善心脏手术期间肺动脉高压患者的血流动力学和氧合的安全有效的策略。这些数据支持 INOflo 在日本临床实践中用于该适应症。