Effect of nitric oxide delivery via cardiopulmonary bypass circuit on postoperative oxygenation in adults undergoing cardiac surgery (NOCARD trial): a randomised controlled trial

BACKGROUND Cardiac surgery involving cardiopulmonary bypass induces a significant systemic inflammatory response, contributing to various postoperative complications, including pulmonary dysfunction, myocardial and kidney injuries. OBJECTIVE To investigate the effect of Nitric Oxide delivery via the cardiopulmonary bypass circuit on various postoperative outcomes. DESIGN A prospective, single-centre, double-blinded, randomised controlled trial. SETTING Rabin Medical Centre, Beilinson Hospital, Israel. PATIENTS Adult patients scheduled for elective cardiac surgery were randomly allocated to one of the study groups. INTERVENTIONS For the treatment group, 40 ppm of nitric oxide was delivered via the cardiopulmonary bypass circuit. For the control group, nitric oxide was not delivered. OUTCOME MEASURES The primary outcome was the incidence of hypoxaemia, defined as a p a O 2 /FiO 2 ratio less than 300 within 24 h postoperatively. The secondary outcomes were the incidences of low cardiac output syndrome and acute kidney injury within 72 h postoperatively. RESULTS Ninety-eight patients were included in the final analysis, with 47 patients allocated to the control group and 51 to the Nitric Oxide group. The Nitric Oxide group exhibited significantly lower hypoxaemia rates at admission to the cardiothoracic intensive care unit (47.1 vs. 68.1%), P = 0.043. This effect, however, varied in patients with or without baseline hypoxaemia. Patients with baseline hypoxaemia who received nitric oxide exhibited significantly lower hypoxaemia rates (61.1 vs. 93.8%), P = 0.042, and higher p a O 2 /FiO 2 ratios at all time points, F (1,30) = 6.08, P = 0.019. Conversely, this benefit was not observed in patients without baseline hypoxaemia. No significant differences were observed in the incidence of low cardiac output syndrome or acute kidney injury. No substantial safety concerns were noted, and toxic methaemoglobin levels were not observed. CONCLUSIONS Patients with baseline hypoxaemia undergoing cardiac surgery and receiving nitric oxide exhibited lower hypoxaemia rates and higher p a O 2 /FiO 2 ratios. No significant differences were found regarding postoperative pulmonary complications and overall outcomes. TRIAL REGISTRATION This trial was registered at ClinicalTrials.gov (NCT04807413).