Nitric oxide via heart bypass fails to improve ventilator-free survival in infants undergoing heart surgery: JAMA

Australia: In children younger than 2 years undergoing cardiopulmonary bypass surgery for congenital heart disease, the use of nitric oxide via cardiopulmonary bypass did not significantly affect the number of ventilator-free days as compared to the standard care, states an article published in the Journal of the American Medical Association (JAMA). 

Globally, about 1.35 million babies are born with CHD each year and approximately 25% of them require corrective surgery during infancy. Low cardiac output syndrome occurs in 25% to 40% of children undergoing cardiopulmonary bypass surgery and is associated with higher mortality, prolonged mechanical ventilation, and unfavorable long-term outcomes.

Based on preclinical and clinical data, nitric oxide has been proposed as adjunctive therapy for children undergoing cardiopulmonary bypass surgery. It reduces postoperative low cardiac output syndrome, leading to improved recovery and a shorter duration of respiratory support. There is no evidence whether nitric oxide administered into the cardiopulmonary bypass oxygenator improves ventilator-free days (days alive and free from mechanical ventilation).

Luregn J. Schlapbach, The University of Queensland, Australia, and his team conducted The international NITRIC (Nitric Oxide During Cardiopulmonary Bypass to Improve Recovery in Infants With Congenital Heart Defects) trial to evaluate the effect of nitric oxide applied to the cardiopulmonary bypass oxygenator vs standard care on ventilator-free days in children undergoing surgery for CHD.

Researchers enrolled 1371 children, younger than 2 years undergoing CHD surgery for the trial in 6 pediatric cardiac surgical centers, with a 28-day follow-up. Patients were assigned to receive nitric oxide at 20 ppm delivered into the cardiopulmonary bypass oxygenator (n = 679) or standard care cardiopulmonary bypass without nitric oxide (n = 685).

The primary endpoint was the number of ventilator-free days from commencement of bypass until day 28. Secondary endpoints included a composite of low cardiac output syndrome, extracorporeal life support, or death; length of stay in the intensive care unit; length of stay in the hospital; and postoperative troponin levels

The study data showed,

• There was no significant difference in ventilator-free days between the nitric oxide and standard care groups, with a median of 26.6 days vs 26.4 days, respectively, for an absolute difference of −0.01 days.

• A total of 22.5% of the nitric oxide group and 20.9% of the standard care group developed low cardiac output syndrome within 48 hours, needed extracorporeal support within 48 hours, or died by day 28, for an adjusted odds ratio of 1.12.

• Other secondary outcomes were not significantly different between the groups.

The authors conclude that the result showed no difference in the ventilation needs of study participants who received nitric oxide and those who did not after heart surgery. The findings do not support the use of nitric oxide delivered into the cardiopulmonary bypass oxygenator during heart surgery.

Researchers will also analyze gene activation patterns in the study participants to find out which biological processes should be targeted in the future—including in terms of precision medicine. A follow-up study of the cohort into school age is proposed to understand the true long-term impact of nitric oxide gas intervention, the authors commented.

Reference:

Schlapbach LJ, Gibbons KS, Horton SB, et al. Effect of Nitric Oxide via Cardiopulmonary Bypass on Ventilator-Free Days in Young Children Undergoing Congenital Heart Disease Surgery: The NITRIC Randomized Clinical Trial. JAMA. Published online June 27, 2022. doi:10.1001/jama.2022.9376