Midazolam provides cytoprotective effect during corticosterone-induced damages in rat astrocytes by stimulating steroidogenesis.

Midazolam is a benzodiazepine derivative drug that has powerful anxiolytic, amnestic, hypnotic, and sedative properties. The cytoprotective effect of midazolam on brain astrocytes is poorly understood. This study aimed to investigate the cytoprotective effect of midazolam on astrocytes exposed to corticosterone, a stress-produced glucocorticoid. We found that midazolam stimulated pregnenolone and progesterone secretion in astrocytes in a dose-dependent manner. Midazolam protected astrocytes from corticosterone-induced damages in a dose-dependent manner. In addition, we demonstrated that progesterone reduced corticosterone-induced damages. Finally, we applied trilostane, an inhibitor of 3ß-hydroxysteroid dehydrogenase, to inhibit pregnenolone metabolism and found that pretreatment with trilostane significantly inhibited the cytoprotective effect of midazolam on corticosterone-induced cytotoxicity in rat astrocytes in a dose-dependent manner. Taken together, these results demonstrate that midazolam has cytoprotective effect on astrocytes. This is, at least partially, derived from midazolam-induced steroidogenesis including progesterone and downstream products in astrocytes. Our data provide new insights into the cytoprotective effect of midazolam.

Comparison of neonatal tolerance to thoracoscopic and open repair of esophageal atresia with tracheoesophageal fistula.

BACKGROUND: Advances in minimally invasive surgical techniques and neonatal intensive care for neonates have allowed for repair of the neonatal esophageal atresia with tracheoesophageal fistula (EA/TEF) to be approached endoscopically. However, thoracoscopic surgery in children is still performed in only a few centers throughout the world. The aim of this study was to compare the neonatal tolerance to the thoracoscopic repair (TR) and the open repair (OR) and also to discuss anesthetic management in thoracoscopic procedure. METHODS: We performed a prospective study enrolling newborns diagnosed with EA with distal TEF (type C) receiving the repair surgery between June 2009 and January 2012 in our institution. Data collected included the newborns' gestational age and weight at the time of the operation, operative time, parameters of intraoperative mechanical ventilation, oxygenation, end-tidal carbon dioxide (ETCO2), and analysis of blood gases. Time to extubation and length of stay were also recorded. RESULTS: Intravenous induction with muscle paralysis followed by pressure-control ventilation and tracheal intubation regardless of the position of the fistula can be performed uneventfully in EA/TEF newborns with no additional airway anomalies and large, pericarinal fistulas in our experiences. The thoracoscopic approach appeared to take longer than the open approach. During the procedure of repair, hypercarbia and acidosis developed immediately 1 hour after pneumothorax in both groups. CO2 insufflation did have additional influence on the respiratory function of the newborns in the TR group; values of PaCO2 and ETCO2 were higher in the TR group but the difference did not reach statistical significance. By the end of the procedure, values of PaCO2 and ETCO2 returned to the baseline levels while pH did not, but all parameters made no difference in the two groups. Besides, time to extubation was shorter in the TR group. CONCLUSIONS: Thoracoscopic repair of EA/TEF is comparable to the open repair, and is believed to be safe and tolerable in selected patients. A wider range of neonates may be acceptable for thoracoscopic EA/TEF repair with increasing surgical experience.