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.