The global COVID-19 pandemic has become the largest public health challenge of recent years. The incidence of COVID-19-related acute hypoxemic respiratory failure (AHRF) occurs in up to 15% of hospitalized patients. Antiviral drugs currently available to clinicians have little to no effect on mortality, length of in-hospital stay, the need for mechanical ventilation, or long-term effects. Inhaled nitric oxide (iNO) administration is a promising new non-standard approach to directly treat viral burden while enhancing oxygenation. Along with its putative antiviral affect in COVID-19 patients, iNO can reduce inflammatory cell-mediated lung injury by inhibiting neutrophil activation, lowering pulmonary vascular resistance and decreasing edema in the alveolar spaces, collectively enhancing ventilation/perfusion matching. This narrative review article presents recent literature on the iNO therapy use for COVID-19 patients. The authors suggest that early administration of the iNO therapy may be a safe and promising approach for the treatment of COVID-19 patients. The authors also discuss unconventional approaches to treatment, continuous versus intermittent high-dose iNO therapy, timing of initiation of therapy (early versus late), and novel delivery systems. Future laboratory and clinical research is required to define the role of iNO as an adjunct therapy against bacterial, viral, and fungal infections.

Background: Postoperative acute kidney injury (AKI) is a significant concern for cardiac surgery patients with chronic kidney disease (CKD). Effective pharmacologic interventions to mitigate these risks are urgently needed. This study aimed to evaluate the efficacy and safety of perioperative nitric oxide (NO) administration in preventing AKI and limiting CKD progression in patients undergoing cardiac surgery. Methods: A total of 136 patients with CKD undergoing elective cardiac surgery with cardiopulmonary bypass were randomized into two equal groups: the NO group (n = 68), receiving 80 parts per million NO during the intraoperative period and for 6 h postsurgery, and the control group (n = 68), receiving a sham treatment. The primary outcome was AKI incidence within 7 days postsurgery. Results: AKI incidence was significantly lower in the NO group (16 of 68 patients, 23.5%) compared to the control group (27 of 68 patients, 39.7%) with a relative risk of 0.59 (95% CI, 0.35 to 0.99; P = 0.043). Six months postsurgery, the glomerular filtration rate was higher in the NO group (50 ml · min ⁻¹ · 1.73 m ⁻² [45; 54]) compared to the control group (45 ml · min ⁻¹ · 1.73 m ⁻² [41; 51]; P = 0.038). Postoperative pneumonia was significantly less frequent in the NO group: 10 of 68 (14.7%) versus 20 of 68 (29.4%) with a relative risk of 0.5 (95% CI, 0.25 to 0.99; P = 0.039). NO administration was safe: methemoglobin and nitrogen dioxide levels remained within acceptable ranges, oxidative-nitrosyl stress did not increase, and there were no significant differences between the groups in blood transfusion requirements, platelet counts, or postoperative blood loss volumes Conclusions: Perioperative NO administration in CKD patients undergoing cardiac surgery with cardiopulmonary bypass is safe, reduces the incidence of AKI, and slows the progression of renal dysfunction.

Performing cardiac surgery under cardiopulmonary bypass (CPB) and circulatory arrest (CA) provokes the development of complications caused by tissue metabolism, microcirculatory disorders, and endogenous nitric oxide (NO) deficiency. This study aimed to investigate the potential mechanisms for systemic organoprotective effects of exogenous NO during CPB and CA based on the assessment of dynamic changes in glycocalyx degradation markers, deformation properties of erythrocytes, and tissue metabolism in the experiment. A single-center prospective randomized controlled study was conducted on sheep, n = 24, comprising four groups of six in each. In two groups, NO was delivered at a dose of 80 ppm during CPB (“CPB + NO” group) or CPB and CA (“CPB + CA + NO”). In the “CPB” and “CPB + CA” groups, NO supply was not carried out. NO therapy prevented the deterioration of erythrocyte deformability. It was associated with improved tissue metabolism, lower lactate levels, and higher ATP levels in myocardial and lung tissues. The degree of glycocalyx degradation and endothelial dysfunction, assessed by the concentration of heparan sulfate proteoglycan and asymmetric dimethylarginine, did not change when exogenous NO was supplied. Intraoperative delivery of NO provides systemic organoprotection, which results in reducing the damaging effects of CPB on erythrocyte deformability and maintaining normal functioning of tissue metabolism.

This study aimed to assess the safety and potential efficacy of high-dose inhaled nitric oxide therapy for the prevention of postoperative pneumonia in cardiac surgery patients. A prospective randomised controlled pilot study included 74 patients with moderate risk of postoperative pneumonia after elective cardiac surgery under cardiopulmonary bypass. Patients were randomised into two groups. The main group (NO-group) (n = 37) received inhaled nitric oxide at a dose of 200 ppm for 30 minutes 2 times a day for 5 days or until pneumonia developed. The control group received conventional postoperative care (n = 37). The primary endpoint was the incidence of postoperative pneumonia during in-hospital stay. Preventive nitric oxide inhalations were associated with a reduced incidence of postoperative nosocomial pneumonia (2 (5.4%) cases in the main group (NO-group) vs. 9 (24.3%) cases in the control group, p = 0.046; OR = 0.178, 95% CI = 0.036-0.89)). There was no decrease in either peak expiratory flow, or peak inspiratory flow in comparison with the preoperative values in the NO-group. Inhaled nitric oxide therapy is safe. It did not lead to an increase in the incidence of acute kidney injury. High-dose inhaled nitric oxide therapy is safe and effective for the prevention of postoperative nosocomial pneumonia in cardiac surgery.