Efficacy and safety of inhaled nitric oxide administered during cardiopulmonary bypass for pediatric cardiac surgery: a systematic review and meta-analysis

Cardiopulmonary bypass (CPB) utilized for cardiac surgeries has been associated with significant mortality and adverse outcomes. The benefits of incorporating nitric oxide (NO) into the CPB circuit have been reported in terms of reduced inflammation, enhanced dynamic circulation, oxygenation, and end-organ function. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of inhaled NO introduced to the CPB circuit among pediatric patients undergoing various cardiac surgeries. METHODS: A systematic literature search was conducted on 26 July 2022, using the electronic databases of PubMed, Cochrane, Scopus, and Web of Science to include randomized controlled trials, with no restriction regarding the date of study conduction. The quality of studies was assessed using the Cochrane tool. RevMan 5.3 software was used to analyze data in the inverse variance method, with pooling data as mean difference (MD), risk ratio, and 95% CI. RESULTS: Six trials were included comprising 1666 children who had undergone the interventions of interest. All studies amenable to assessment were of good quality. NO was significantly superior to the control treatments regarding ventilation time (MD=−8.34; 95% CI [−14.50 to −2.17], P=0.008), postoperative interleukin-6 (IL-6) levels (MD=−0.50; 95% CI [−0.54 to −0.46], P<0.001), 24-h IL-6 levels (MD=−0.30; 95% CI [−0.32 to −0.20], P<0.001), and 24-h tumor necrosis factor-alpha (TNF-α) levels (MD=−1.72; 95% CI [−3.44 to −1.00], P=0.05). The side effects of NO and the control treatments were comparable (P=0.9). CONCLUSION: NO administered as part of the CPB circuit during cardiac surgeries is efficacious in terms of reducing ventilation time, postoperative IL-6, and TNF-α levels compared to control, with a comparable safety profile.