Nitric oxide administration during CPB does not enhance neurodevelopmental or health-related quality of life outcomes: JAMA

The findings were published online in JAMA Network Open on February 5, 2025.

Children having congenital heart defects who undergo CPB surgery are at risk for delayed or impaired neurodevelopmental outcomes. CPB is known to contribute to systemic inflammatory responses and cerebral injury, which may affect long-term neurodevelopment in children with congenital heart conditions. The researchers note that NO addition to the CPB oxygenator may lower systemic inflammation due to CPB and enhance recovery from surgery, including improved neurodevelopmental outcomes.

Against the above background, Debbie A. Long, School of Nursing, Centre for Healthcare Transformation, Queensland University of Technology, Brisbane, Australia, and colleagues set out to investigate neurodevelopment, HRQOL, and factors linked with impaired neurodevelopment at 12 months post-surgery in infants who were administered CPB with NO or standard CPB.

For this purpose, the researchers conducted a double-masked randomized clinical trial in 6 centers in Australia, New Zealand, and the Netherlands between 2017 and 20021. A preplanned prospective follow-up 12 months postrandomization was completed on August 5, 2022. The cohort comprised 1364 infants younger than 2 years who underwent open heart surgery with CPB for congenital heart disease.

The intervention group was administered NO 20 ppm in the cardiopulmonary bypass oxygenator, while the control group received standard CPB.

The study's primary outcome was neurodevelopment, measured by the total score on the Ages and Stages Questionnaire, Third Edition (ASQ-3). Secondary outcomes included Health-Related Quality of Life (HRQOL) and functional status, assessed using the Pediatric Quality of Life Inventory (PedsQL) and modified Pediatric Overall Performance Category (mPOPC) scores, respectively. Sensitivity analyses were conducted to model outcomes for patients lost to follow-up.

The study led to the following findings:

• Out of 1318 infants alive 12 months after randomization, follow-up was completed for 927 infants, with 462 in the NO group and 465 in the standard care group.
• The median age at follow-up was 16.6 months, and the median time since randomization was 12.7 months; 516 participants (55.7%) were male.
• There were no differences between the NO and standard care groups in the ASQ-3 total score (mean [SD]: 196.6 versus 198.7, respectively; adjusted mean difference, −2.24).
• There were no differences in secondary outcomes between the two groups.
• Prematurity (gestational age <37 weeks), univentricular lesions, congenital syndromes, and longer ICU stays were associated with lower ASQ-3 total scores in adjusted multivariable analyses.

"In the randomized controlled trial involving infants undergoing open-heart surgery for congenital heart defects, the administration of nitric oxide via cardiopulmonary bypass did not lead to improvements in neurodevelopmental outcomes or health-related quality of life at 12 months post-surgery," the researchers wrote.

"Future research should focus on more homogenous cohorts with higher RACHS scores and investigate higher-dose or alternative therapeutic approaches to enhance neurodevelopment in children with congenital heart disease," they concluded.

Reference:

Long DA, Gibbons KS, Horton SB, et al. Neurodevelopmental Outcomes After Nitric Oxide During Cardiopulmonary Bypass for Open Heart Surgery: A Randomized Clinical Trial. JAMA Netw Open. 2025;8(2):e2458040. doi:10.1001/jamanetworkopen.2024.58040