Efficacy of different analgesic or sedative drug therapies in pediatric patients with congenital heart disease undergoing surgery: a network meta-analysis.

BACKGROUND: Surgery is an effective therapy for congenital heart disease (CHD) and the management after surgery poses challenges for the clinical workers. We performed this network meta-analysis to enhance the corresponding evidence with respect to the relative efficacy of different drug treatments applied after the CHD surgery. METHODS: Embase and PubMed were systematically retrieved to identify all published controlled trials investigating the effectiveness of drugs for patients up to 25 August, 2018. Mean differences (MD), odds ratios and their 95% credible intervals (CrIs) were used to evaluate multi-aspect comparisons. Surface under cumulative ranking curve (SUCRA) was used to analyze the relative ranking of different treatments in each endpoint. RESULTS: Compared to saline, all the drugs achieved better preference under the efficacy endpoints except fentanyl in JET. As for ventilator time, all drugs were more effective than saline while only the difference of dexmedetomidine was statistically obvious (MD = 6.92, 95% CrIs 1.77-12.54). Under the endpoint of ICU time, dexmedetomidine was superior to saline as well (MD = 1.26, 95% CrIs 0.11-2.45). When all the endpoints were taken into consideration and with the help of ranking probabilities and SUCRA values, fentanyl combined with dexmedetomidine was one of the recommended drugs due to its shorter time on ventilator and stay in hospital as well as lower mortality. CONCLUSIONS: Overall, based on the comprehensive consideration of all the endpoints, fentanyl combined with dexmedetomidine was considered to be the best-recommended clinical interventions among all the methods.

Cytosolic HMGB1 Mediates Autophagy Activation in an Emulsified Isoflurane Anesthesia Cell Model.

Inhalation anesthetic isoflurane may cause an increased risk of cognitive impairment. Previous studies have indicated that this cognitive decline is associated with neuroinflammation mediated by high mobility group box 1 (HMGB1). HMGB1 is released from cells and acts as a damage-associated molecule in neurodegenerative diseases. However, the effect of intracellular HMGB1 during emulsified isoflurane (EI) exposure is poorly understood. The purpose of this study was to investigate the effect of autophagy on neuroprotection, evaluate variation of HMGB1, and determine its role in autophagic flux after EI exposure in vitro. We observed that EI decreased cell viability in a concentration-dependent manner, accompanied by an increase in autophagic flux. EI exposure also elevates the HMGB1 level in cytoplasm. Further, cytosolic HMGB1 was necessary for autophagy by perturbing the beclin1-Bcl-2 interaction. Most importantly, autophagy induction by rapamycin alleviated EI-provoked cell injury, and HMGB1 knockdown induced autophagy inhibition, which exacerbated cell damage. Based on these findings, we propose that autophagic flux is sustained and upregulated in response to EI exposure by increased cytosolic HMGB1, and that autophagy activation serves as a protective mechanism against EI-induced cytotoxicity. Thus, the complex roles of HMGB1 make it pivotal in reducing EI-induced neuronal damage.