Effect of esketamine vs dexmedetomidine adjunct to propofol sedation for pediatric 3Tesla magnetic resonance imaging: a randomized, double-blind, controlled trial.

BACKGROUND: Adequate sedation is essential for pediatric patients undergoing 3Tesla (T) magnetic resonance imaging (MRI). Using propofol alone is associated with patient arousing and adverse airway events. This study aimed to assess esketamine vs dexmedetomidine adjunct to propofol sedation for pediatric 3 T MRI. METHODS: In this randomized, double-blind, controlled trial, 114 pediatric patients aged between 6 months and 8 years were randomly assigned, in a 1:1 ratio, to the esketamine-propofol group or the dexmedetomidine-propofol group. Sedation was provided with esketamine or dexmedetomidine in combination with propofol titration. The primary outcome was the total dose of propofol. Secondary outcomes included propofol infusion dose, adverse events, time to emergence from sedation, and time to discharge from recovery room. RESULTS: A total of 111 patients completed this study (56 in the esketamine-propofol group and 55 in the dexmedetomidine-propofol group). All MRI procedures were successfully performed under sedation. The total median (IQR) dose of propofol was significantly lower in the esketamine-propofol group (159.8 [121.7, 245.2] µg/kg/min) than that in the dexmedetomidine-propofol group (219.3 [188.6, 314.8] µg/kg/min) (difference in medians [95% CI] = - 66.9 [- 87.8 to - 43.0] µg/kg/min, P < 0.0001). The use of esketamine resulted in a lower dose of propofol for titration (difference in medians [95% CI] = - 64.3 [- 75.9 to - 51.9] µg/kg/min), a shorter time to emergence (difference in means [95% CI] = - 9.4 [- 11.4 to - 7.4] min), and a reduced time to recovery room discharge (difference in means [95% CI] = - 10.1 [- 12.1 to - 8.2] min). In the dexmedetomidine-propofol group, 2 patients experienced upper airway obstruction and 6 patients had bradycardia. No episodes of oxygen desaturation or other adverse events were observed. CONCLUSIONS: Although both regimens provided effective sedation for pediatric 3 T MRI, the esketamine-propofol sedation reduced propofol requirement and facilitated recovery, without detection of increased adverse effects in the studied population. Trial registration Chinese Clinical Trial Registry (identifier: ChiCTR2100048477).

Dexmedetomidine Protects Cardiomyocytes against Hypoxia/Reoxygenation Injury by Suppressing TLR4-MyD88-NF-κB Signaling.

OBJECTIVE: We previously reported that dexmedetomidine (DEX) offers cardioprotection against ischemia/reperfusion injury in rats. Here, we evaluated the role of toll-like receptors 4- (TLR4-) myeloid differentiation primary response 88- (MyD88-) nuclear factor-kappa B (NF-κB) signaling in DEX-mediated protection of cardiomyocytes using in vitro models of hypoxia/reoxygenation (H/R). METHODS: The experiments were carried out in H9C2 cells and in primary neonatal rat cardiomyocytes. Cells pretreated with vehicle or DEX were exposed to hypoxia for 1 h followed by reoxygenation for 12 h. We analyzed cell viability and lactate dehydrogenase (LDH) activity and measured tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1ß mRNA levels, TLR4, MyD88, and nuclear NF-κB p65 protein expression and NF-κB p65 nuclear localization. TLR4 knock-down by TLR4 siRNA transfection and overexpression by TLR4 DNA transfection were used to further confirm our findings. RESULTS: DEX protected against H/R-induced cell damage and inflammation, as evidenced by increased cell survival rates, decreased LDH activity, and decreased TNF-α, IL-6, and IL-1ß mRNA levels, as well as TLR4 and NF-κB protein expression. TLR4 knock-down partially prevented cell damage following H/R injury, while overexpression of TLR4 abolished the DEX-mediated protective effects. CONCLUSIONS: DEX pretreatment protects rat cardiomyocytes against H/R injury. This effect is partly mediated by TLR4 suppression via TLR4-MyD88-NF-κB signaling.