Dexmedetomidine Versus Dexamethasone in Pediatric Cardiac Surgery with Cardiopulmonary Bypass: An Exploratory Randomized Controlled Trial of Inflammatory Biomarkers and Opioid Consumption.

Background/Objectives: Cardiopulmonary bypass (CPB) triggers a systemic inflammatory response in children undergoing congenital heart surgery. Although dexmedetomidine has been proposed as an alternative to corticosteroids, the two agents have not previously been directly compared in a pediatric randomized trial. This study aimed to compare the effects of dexmedetomidine and dexamethasone on inflammatory biomarkers and analgesic outcomes in children undergoing congenital heart surgery with CPB. Methods: In this prospective, randomized, controlled exploratory trial, 50 children aged 6 months to 18 years undergoing elective congenital heart surgery with CPB were randomized 1:1 to dexamethasone (n = 25) or dexmedetomidine (n = 25), using institutional regimens that were not equipotent anti-inflammatory doses. Serum interleukin-6 (IL-6) and interleukin-8 (IL-8) were measured at baseline, immediately after separation from CPB (post-CPB), and 12 h postoperatively. The primary endpoint was IL-6 at the two postoperative time points; IL-8 was a secondary biomarker outcome. Secondary outcomes also included Face, Legs, Activity, Cry, Consolability (FLACC) pain scores, fentanyl consumption, and time to first rescue analgesia. Effect estimates included Hodges-Lehmann (HL) median differences with 95% confidence intervals (CIs); a post hoc baseline-adjusted mixed-effects model of log-transformed concentrations served as a sensitivity analysis. Secondary and exploratory analyses were not adjusted for multiple comparisons. Results: All 50 randomized children were analyzed. Median IL-6 was lower in the dexmedetomidine group at 12 h (50 vs. 178 pg/mL; HL difference 86 pg/mL, 95% CI 59 to 144; p < 0.001); the post-CPB difference (46 vs. 77 pg/mL; HL difference 34 pg/mL, 95% CI 0 to 112; p = 0.045) was imprecise and not significant after post hoc Bonferroni correction for the two primary comparisons. In the post hoc baseline-adjusted sensitivity model, the ratio of geometric mean IL-6 concentrations (dexmedetomidine/dexamethasone) was 0.35 (95% CI 0.22 to 0.58; p < 0.001). Among secondary and exploratory outcomes, for which p-values are nominal, IL-8 was also lower post-CPB (159 vs. 381 pg/mL; p = 0.001) and at 12 h (120 vs. 311 pg/mL; p = 0.002). Dexmedetomidine was associated with lower intraoperative (83.0 ± 30.7 vs. 142.6 ± 51.7 µg; p < 0.001) and cumulative 24-h fentanyl consumption (53.8 ± 17.4 vs. 105.4 ± 32.8 µg; p < 0.001), analyzed in absolute units with incompletely documented intraoperative doses, and a longer time to first rescue analgesia (4.68 ± 0.73 vs. 1.84 ± 0.23 h; p < 0.001). Time to extubation did not differ significantly (median 2 vs. 1 h; p = 0.204). Intensive care unit length of stay, an exploratory outcome recorded in days, was distributed toward shorter stays with dexmedetomidine (median 2 [interquartile range 1-2] vs. 2 [2-3] days; p = 0.007). No pre-specified adverse events occurred in either group, although the trial was too small to exclude clinically important safety differences. Conclusions: In this exploratory trial of two non-equipotent institutional regimens, dexmedetomidine was associated with lower early postoperative IL-6 and IL-8 concentrations and lower opioid consumption than dexamethasone. These hypothesis-generating biomarker and analgesic signals do not demonstrate therapeutic superiority or patient-centered clinical benefit and require confirmation in larger, adequately powered multicenter trials.