Predictors of methemoglobin formation in high-dose inhaled nitric oxide therapy: A retrospective cohort study

IF 3.8 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Nitric oxide : biology and chemistry Pub Date : 2026-02-01 Epub Date: 2025-11-20 DOI:10.1016/j.niox.2025.11.006

Talisa Bühl , Stefano Cenci , Stefano Gianni , Bijan Safaee Fakhr , Carlo Valsecchi , Binglan Yu , Edward A. Bittner , Lorenzo Berra

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引用次数: 0

Abstract

Background

High-dose inhaled nitric oxide (iNO), defined as doses exceeding 20 parts per million (ppm) and reaching up to 300 ppm, has demonstrated promising antimicrobial properties. However, elevated concentrations of nitric oxide (NO) can increase the formation of methemoglobin (MetHb), which can impair oxygen transport. Understanding factors influencing MetHb formation is essential to guide safe clinical use of iNO therapy.

Methods

We conducted a retrospective analysis of 660 high-dose iNO treatments administered to 71 individuals between April 2020 and January 2022 under three prospective protocols at a large academic medical center. The study protocols included healthy volunteers, non-pregnant patients with COVID-19 pneumonia, and pregnant patients with COVID-19 pneumonia. MetHb levels were recorded at baseline and post-treatment using CO-oximeter. Mixed-effects modeling was used to identify predictors of MetHb formation with repeated measures.

Results

iNO concentration was positively associated with MetHb formation, while COVID-19 pneumonia, older age, higher baseline MetHb, and increased respiratory rate were inversely associated. No significant associations were found for sex, race, or hemoglobin concentration. Nitrogen dioxide levels remained within normal ranges, and no systemic hypotension or toxicity were observed. In tachypneic patients with COVID-19 pneumonia, high-dose iNO reduced respiratory rate.

Conclusion

High-dose iNO up to 300 ppm was well tolerated across diverse patient populations. MetHb formation was influenced not only by iNO doses but also by individual physiological factors. These findings support the safety of high-dose iNO and provide a basis for individualized delivery strategies.

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高剂量吸入一氧化氮治疗中高铁血红蛋白形成的预测因素：一项回顾性队列研究。

背景：高剂量吸入一氧化氮（iNO），定义为剂量超过百万分之20 （ppm）并高达300 ppm，已显示出有希望的抗菌特性。然而，一氧化氮（NO）浓度升高会增加高铁血红蛋白（MetHb）的形成，从而损害氧气运输。了解影响甲基苯丙胺形成的因素对指导临床安全使用甲基苯丙胺治疗至关重要。方法：我们对一家大型学术医疗中心在2020年4月至2022年1月期间对71名患者进行的660次高剂量iNO治疗进行了回顾性分析。研究方案包括健康志愿者、未怀孕的COVID-19肺炎患者和怀孕的COVID-19肺炎患者。使用co -血氧仪记录基线和治疗后甲基苯丙胺水平。混合效应模型用于通过重复测量来确定甲氧麻黄形成的预测因子。结果：一氧化氮浓度与甲胺磷形成呈正相关，COVID-19肺炎与年龄、基线甲胺磷升高、呼吸频率增加呈负相关。未发现性别、种族或血红蛋白浓度有显著相关性。二氧化氮水平保持在正常范围内，未观察到全身性低血压或毒性。在COVID-19肺炎快速通气患者中，高剂量iNO可降低呼吸速率。结论：在不同的患者群体中，高达300ppm的高剂量iNO具有良好的耐受性。甲基苯丙胺的形成不仅受一氧化氮剂量的影响，还受个体生理因素的影响。这些发现支持了大剂量iNO的安全性，并为个体化给药策略提供了基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nitric oxide : biology and chemistry 生物-生化与分子生物学

CiteScore

7.50

自引率

7.70%

发文量

审稿时长

52 days

期刊介绍： Nitric Oxide includes original research, methodology papers and reviews relating to nitric oxide and other gasotransmitters such as hydrogen sulfide and carbon monoxide. Special emphasis is placed on the biological chemistry, physiology, pharmacology, enzymology and pathological significance of these molecules in human health and disease. The journal also accepts manuscripts relating to plant and microbial studies involving these molecules.