Presurgical Use of Hypoxic Mixture for Systemic Perfusion Improvement in Neonates With Complex Congenital Heart Disease: A Systematic Review and Meta-Analysis.

Oxygen therapy is essential for the survival of preterm babies and critically ill newborns; however, it has the potential to cause harm through hypoxemia or hyperoxemia. Newborns with complex congenital heart diseases (CHD) suffer from oxygen fluctuations due to the disease and its treatments, altering pre and postnatal development. The objective of this study is to evaluate the evidence for using a hypoxic mixture to decrease pulmonary over-circulation and improve systemic perfusion before surgical interventions in newborns with complex CHD that course with pulmonary over-circulation and systemic hypoperfusion. A search was conducted in PubMed, EMBASE, LILACS, Scielo, Taylor and Francis, SAGE, and Science Direct databases from 2000 to 2022 by two independent authors, including articles with hypoxic mixture treatment in observational studies or trials, with pre-treatment and post-treatment measurements in the same patient, or two groups or more comparisons. Six articles were selected, with a total of 75 patients. The primary outcome was improved systemic circulation and decreased pulmonary over-circulation measured directly with Qp/Qs and indirectly with oxygen saturation and cerebral near-infrared spectroscopy (NIRS). In addition, we performed a meta-analysis for oxygen saturation and cerebral NIRS. Oxygen saturation was the value uniformly reported; three studies reported a significantly lower oxygen saturation after the hypoxic mixture. The cerebral NIRS was measured in 4 studies, with inconsistent results. After using the hypoxic mixture, the Qp/Qs calculation was lower in the two studies but was not statistically significant. The meta-analysis for oxygen saturation showed a fixed effect post-hypoxic therapy of -0.7 (-1.06; -0.35), p < 0.001. The meta-analysis of two studies that measured cerebral NIRS did not show a statistically significant difference at 12 and 24 hours. In conclusion, this is the first systematic review and meta-analysis regarding the pre-operative use of hypoxic gas mixtures for newborns with complex congenital heart disease. Treatment results in lower oxygen saturations, but there is a lack of evidence of improvement in systemic perfusion. The utilization of this therapy is controversial, and better evidence is necessary.