Inhaled high dose nitric oxide is a safe and effective respiratory treatment in spontaneous breathing hospitalized patients with COVID-19 pneumonia,Nitric Oxide

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Inhaled high dose nitric oxide is a safe and effective respiratory treatment in spontaneous breathing hospitalized patients with COVID-19 pneumonia
Nitric Oxide ( IF 3.9 ) Pub Date : 2021-08-13 , DOI: 10.1016/j.niox.2021.08.003
Bijan Safaee Fakhr ₁ , Raffaele Di Fenza ₁ , Stefano Gianni ₁ , Steffen B Wiegand ₁ , Yusuke Miyazaki ₁ , Caio C Araujo Morais ₁ , Lauren E Gibson ₁ , Marvin G Chang ₁ , Ariel L Mueller ₁ , Josanna M Rodriguez-Lopez ₂ , Jeanne B Ackman ₃ , Pankaj Arora ₄ , Louie K Scott ₅ , Donald B Bloch ₆ , Warren M Zapol ₁ , Ryan W Carroll ₇ , Fumito Ichinose ₁ , Lorenzo Berra ₈ ,

Affiliation

Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, 55 Fruit St, Boston, MA, 02114, USA; Harvard Medical School, 25 Shattuck St, Boston, MA, 02115, USA.
Harvard Medical School, 25 Shattuck St, Boston, MA, 02115, USA; Pulmonary and Critical Care Medicine, Department of Medicine, Massachusetts General Hospital, 55 Fruit St, Boston, MA, 02114, USA.
Harvard Medical School, 25 Shattuck St, Boston, MA, 02115, USA; Division of Thoracic Imaging and Intervention, Department of Radiology, Massachusetts General Hospital, 55 Fruit St, Boston, MA, 02114, USA.
Division of Cardiovascular Disease, University of Alabama at Birmingham, Tinsley Harrison Tower, Suite 311, 1900 University Boulevard, Birmingham, AL, 35233, USA.
Critical Care Medicine, Department of Medicine, LSU Health Shreveport, 1501 Kings Hwy, Shreveport, LA, 71103, USA.
Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, 55 Fruit St, Boston, MA, 02114, USA; Harvard Medical School, 25 Shattuck St, Boston, MA, 02115, USA; Center for Immunology and Inflammatory Diseases and Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, 55 Fruit St, Boston, MA, 02114, USA.
Harvard Medical School, 25 Shattuck St, Boston, MA, 02115, USA; Division of Pediatric Critical Care Medicine, Department of Pediatrics, Massachusetts General Hospital, 55 Fruit St, Boston, MA, 02114, USA.
Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, 55 Fruit St, Boston, MA, 02114, USA; Harvard Medical School, 25 Shattuck St, Boston, MA, 02115, USA; Respiratory Care Services, Massachusetts General Hospital, 55 Fruit St, Boston, MA, 02114, USA.

Background

Inhaled nitric oxide (NO) is a selective pulmonary vasodilator. In-vitro studies report that NO donors can inhibit replication of SARS-CoV-2. This multicenter study evaluated the feasibility and effects of high-dose inhaled NO in non-intubated spontaneously breathing patients with Coronavirus disease-2019 (COVID-19).

Methods

This is an interventional study to determine whether NO at 160 parts-per-million (ppm) inhaled for 30 min twice daily might be beneficial and safe in non-intubated COVID-19 patients.

Results

Twenty-nine COVID-19 patients received a total of 217 intermittent inhaled NO treatments for 30 min at 160 ppm between March and June 2020. Breathing NO acutely decreased the respiratory rate of tachypneic patients and improved oxygenation in hypoxemic patients. The maximum level of nitrogen dioxide delivered was 1.5 ppm. The maximum level of methemoglobin (MetHb) during the treatments was 4.7%. MetHb decreased in all patients 5 min after discontinuing NO administration. No adverse events during treatment, such as hypoxemia, hypotension, or acute kidney injury during hospitalization occurred.

In our NO treated patients, one patient of 29 underwent intubation and mechanical ventilation, and none died. The median hospital length of stay was 6 days [interquartile range 4–8]. No discharged patients required hospital readmission nor developed COVID-19 related long-term sequelae within 28 days of follow-up.

Conclusions

In spontaneous breathing patients with COVID-19, the administration of inhaled NO at 160 ppm for 30 min twice daily promptly improved the respiratory rate of tachypneic patients and systemic oxygenation of hypoxemic patients. No adverse events were observed. None of the subjects was readmitted or had long-term COVID-19 sequelae.

中文翻译：

吸入高剂量一氧化氮是对 COVID-19 肺炎住院自主呼吸患者安全有效的呼吸治疗

背景

吸入一氧化氮 (NO) 是一种选择性肺血管扩张剂。体外研究报告称，NO 供体可以抑制 SARS-CoV-2 的复制。这项多中心研究评估了高剂量吸入 NO 在非插管自主呼吸的 2019 冠状病毒病 (COVID-19) 患者中的可行性和效果。

方法

这是一项干预性研究，旨在确定每天两次吸入 160 百万分之一 (ppm) 的 NO 30 分钟是否对未插管的 COVID-19 患者有益且安全。

结果

在 2020 年 3 月至 2020 年 6 月期间，29 名 COVID-19 患者总共接受了 217 次间歇性吸入 NO 治疗，持续 30 分钟，浓度为 160 ppm。呼吸 NO 会急剧降低呼吸急促患者的呼吸频率，并改善低氧血症患者的氧合。输送的最大二氧化氮水平为 1.5 ppm。治疗期间高铁血红蛋白 (MetHb) 的最高水平为 4.7%。停止 NO 给药后 5 分钟，所有患者的 MetHb 均下降。治疗期间未发生低氧血症、低血压、住院期间急性肾损伤等不良事件。

在我们接受 NO 治疗的患者中，29 名患者中有一名接受了插管和机械通气，没有人死亡。中位住院时间为 6 天 [四分位数范围 4-8]。在随访 28 天内，没有出院患者需要再次入院，也没有出现与 COVID-19 相关的长期后遗症。