Effects of Dexmedetomidine on Brain and Inflammatory Outcomes In Pediatric Cardiac Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

ABSTRACT

OBJECTIVE: Dexmedetomidine use decreases adverse neurocognitive outcomes in adults undergoing cardiovascular surgery, but its effect has been unclear in children with congenital heart disease. METHODS: The authors conducted a systematic review using the PubMed, Embase, and Cochrane Library databases for randomized controlled trials (RCTs) that compared intravenous dexmedetomidine with normal saline during pediatric cardiac surgery under anesthesia. Published randomized controlled trials that evaluated children aged <18 years who underwent congenital heart surgery were included. Nonrandomized trials, observational studies, case series and case reports, editorials, reviews, and conference papers were excluded. The quality of the included studies was assessed using the Cochrane revised tool for assessing risk-of-bias in randomized trials. Meta-analysis was performed to estimate the effects of intravenous dexmedetomidine on brain markers (neuron-specific enolase [NSE], S-100ß protein) and inflammatory markers (interleukin-6, tumor necrosis factor [TNF]-α, nuclear factor kappa-B [NF-κB]) during and after cardiac surgery, using random-effect models for standardized mean difference (SMD). RESULTS: Seven RCTs involving 579 children were eligible for the following meta-analyses. Most children underwent cardiac surgery for atrial or ventricular septum defects. Pooled analyses (5 treatment groups in 3 RCTs with 260 children) showed that dexmedetomidine use was associated with reduced serum levels of NSE (pooled SMD, -0.54; 95% CI, -0.96 to -0.12) and S-100ß (pooled SMD, -0.85; 95% CI, -1.67 to -0.04) within 24 hours after the surgery. Also, dexmedetomidine use was associated with reduced levels of interleukin-6 (pooled SMD, -1.55; 95% CI, -2.82 to -0.27; 4 treatment groups in 2 RCTs with 190 children). In contrast, the authors observed similar levels of TNF-α (pooled SMD, -0.07; 95% CI, -0.33 to 0.19; 4 treatment groups in 2 RCTs with 190 children) and NF-κB (pooled SMD, -0.27; 95% CI, -0.62 to 0.09; 2 treatment groups in 1 RCT with 90 children) between the dexmedetomidine and control groups. CONCLUSIONS: The authors' findings support the effect of dexmedetomidine on reductions in brain markers among children who undergo cardiac surgery. Further studies would be needed to elucidate its clinically meaningful effects using cognitive functions in the long term, and its effects among children who undergo more complex cardiac surgeries.