The anesthetic agent sevoflurane attenuates pulmonary acute lung injury by modulating apoptotic pathways

The objective of this study was to evaluate lung protection by the volatile anesthetic sevoflurane (SEVO), which inhibits apoptosis. Male Sprague-Dawley rats (250–280 g; n=18) were randomly divided into three groups. The LPS group received 5 mg/kg endotoxin (lipopolysaccharide), which induced acute lung injury (ALI). The control (CTRL) group received normal saline and the SEVO group received sevoflurane (2.5%) for 30 min after ALI was induced by 5 mg/kg LPS. Samples were collected for analysis 12 h after LPS. Lung injury was assessed by pathological observations and tissue wet to dry weight (W/D) ratios. Apoptotic index (AI) was determined by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and electron microscopy. Caspase-3 and cleaved-caspase-3 protein levels were determined by immunocytochemistry and western blotting, respectively. Bcl-xl levels were measured by western blotting and Bcl-2 levels by quantitative real-time polymerase chain reaction and western blotting. In the LPS group, W/D ratios, AI values, caspase-3 and cleaved-caspase-3 levels were significantly higher than in the CTRL group and lung injury was more severe. In the SEVO group, W/D ratios, AI, caspase-3 and cleaved-caspase-3 were lower than in the LPS group. Bcl-2 and Bcl-xl expression were higher than in the LPS group and lung injury was attenuated. Sevoflurane inhalation protected the lungs from injury by regulating caspase-3 activation and Bcl-xl and Bcl-2 expression to inhibit excessive cell apoptosis, and such apoptosis might be important in the pathogenesis of LPS-induced ALI.

Effects of sevoflurane on tight junction protein expression and PKC-alpha translocation after pulmonary ischemia-reperfusion injury

Pulmonary dysfunction caused by ischemia-reperfusion injury is the leading cause of mortality in lung transplantation. We aimed to investigate the effects of sevoflurane pretreatment on lung permeability, tight junction protein occludin and zona occludens 1 (ZO-1) expression, and translocation of protein kinase C (PKC)-alpha after ischemia-reperfusion. A lung ischemia-reperfusion injury model was established in 96 male Wistar rats following the modified Eppinger method. The rats were divided into four groups with 24 rats in each group: a control (group C), an ischemia-reperfusion group (IR group), a sevoflurane control group (sev-C group), and a sevoflurane ischemia-reperfusion group (sev-IR group). There were three time points in each group: ischemic occlusion for 45 min, reperfusion for 60 min and reperfusion for 120 min; and there were six rats per time point. For the 120-min reperfusion group, six extra rats underwent bronchoalveolar lavage. Mean arterial pressure (MAP) and pulse oxygen saturation (SpO2) were recorded at each time point. The wet/dry weight ratio and lung permeability index (LPI) were measured. Quantitative RT-PCR and Western blot were used to measure pulmonary occludin and ZO-1, and Western blot was used to measure cytosolic and membranous PKC-alpha in the lung. Lung permeability was significantly increased after ischemia-reperfusion. Sevoflurane pretreatment promoted pulmonary expression of occludin and ZO-1 after reperfusion and inhibited the translocation of PKC-alpha. In conclusion, sevoflurane pretreatment alleviated lung permeability by upregulating occludin and ZO-1 after ischemia-reperfusion. Sevoflurane pretreatment inhibited the translocation and activation of PKC-alpha, which also contributed to the lung-protective effect of sevoflurane.

Effect of Dexmedetomidine on Sevoflurane Requirements and Emergence Agitation in Children Undergoing Ambulatory Surgery

PURPOSE: Dexmedetomidine, a potent selective alpha2-adrenergic agonist, produces sedation and analgesia. This study was conducted to assess the effect of dexmedetomidine infusion on sevoflurane requirements, recovery profiles, and emergence agitation in children undergoing ambulatory surgery. MATERIALS AND METHODS: Forty children undergoing ambulatory hernioplasty or orchiopexy were randomized into two groups. The dexmedetomidine group (Group D, n=20) received dexmedetomidine 1 microg/kg, followed by 0.1 microg/kg/h until the end of surgery, whereas the saline group (Group S, n=20) received volume-matched normal saline. Sevoflurane was used for induction and maintenance of anesthesia and caudal block was performed in all children. End-tidal sevoflurane concentration (ET-sevo), the incidence of emergence agitation, pain scores, and sedation scores were recorded. Hemodynamic changes and other adverse effects were assessed in the perioperative period. RESULTS: ET-sevo of Group D was significantly reduced in 23.8-67% compared to Group S during surgery. The incidence of emergence agitation was lower in Group D than in Group S (5% vs. 55%, p=0.001). Postoperative pain was comparable, and discharge time was not different between the groups. Mean arterial pressure and heart rate were significantly lower in Group D during surgery. CONCLUSION: Intraoperative infusion of dexmedetomidine reduced sevoflurane requirements and decreased emergence agitation without delaying discharge in children undergoing ambulatory surgery. However, caution should be taken in regard to bradycardia and hypotension.

Comparison of sevoflurane and isoflurane in OPCAB surgery.

Maintenance of anaesthesia with volatile anaesthetic agents affects the perioperative course of patients undergoing off-pump coronary artery bypass (OPCAB) surgery. This facilitates adequate depth of anaesthesia, reduction in need of analgesic dosage, early extubation and transfer from Intensive Care Unit. We compared two volatile anaesthetic agents sevoflurane and isoflurane in terms of haemodynamic effects, amount of analgesic needed during surgery, quantity of agent needed for maintenance of anaesthesia and postoperative recovery in 40 patients undergoing OPCAB surgery. Anaesthesia was induced with fentanyl, midazolam and thiopentone, and vecuronium was used for muscle relaxation. An Octopus stabiliser was used and coronary anastomosis was performed using internal mammary artery and saphenous vein grafts. Routine monitoring was performed. The depth of anaesthesia was monitored using Bispectral index monitor. The inspired/expired concentration of anaesthetic agents to maintain the desired BIS and the amount of volatile anaesthetic agent needed was also noted. The amount of analgesic used intraoperatively was noted in both the groups. The 'time of awakening' defined as eye opening on verbal commands, and time of extubation were noted. There were no differences in haemodynamic parameters, depth of anaesthesia, and quantity of agent needed, but patients in isoflurane group required more intraoperative analgesics than sevoflurane group. Time of awakening (48+/-13 vs 114 +/- 21 mins; P < 0.001) and subsequent extubation (124 +/- 25 vs 177 +/- 36 mins, P<0.001) was earlier in sevoflurane group than isoflurane group. There was no evidence of perioperative myocardial infarction in both the groups. We conclude that sevoflurane and isoflurane can both be safely used in OPCAB surgery, but the awakening and extubation times are significantly less with sevoflurane.