*Department of Anesthesiology and Critical Care, Children's Hospital of Philadelphia †Department of Anesthesiology and Critical Care, Perelman School of Medicine at the University of Pennsylvania, Philadelphia ‡Department of Neural and Behavioral Sciences, Pennsylvania State University College of Medicine, Hershey, PA.
J Neurosurg Anesthesiol. 2017 Oct;29(4):439-447. doi: 10.1097/ANA.0000000000000365.
The use of isoflurane sedation for prolonged periods in the critical care environment is increasing. However, isoflurane-mediated neurotoxicity has been widely reported. The goal of the present study was to determine whether long-term exposure to low-dose isoflurane in mechanically ventilated rodents is associated with evidence of neurodegeneration or neuroinflammation.
Adult female Sprague-Dawley rats were used in this study. Experimental animals (n=11) were induced with 1.5% isoflurane, intubated, and given a neuromuscular blockade with α-cobratoxin. EEG electrodes were surgically implanted, subcutaneous precordial EKG Ag wire electrodes, and bladder, femoral artery, and femoral vein cannulas permanently placed. After these procedures, the isoflurane concentration was reduced to 0.5% and, in conjunction with the neuromuscular blockade, continued for 7 days. Arterial blood gases and chemistry were measured at 3 time points and core body temperature servoregulated and maintenance IV fluids were given during the 7 days. Experimental animals and untreated controls (n=9) were euthanized on day 7.
Immunohistochemical and cytochemical assays did not detect evidence of microgliosis, astrocytosis, neuronal apoptosis or necrosis, amyloidosis, or phosphorylated-tau accumulation. Blood glucose levels were significantly reduced on days 3/4 and 6/7 and partial pressure of oxygen was significantly reduced, but still within the normal range, on day 6/7. All other blood measurements were unchanged.
No neuropathologic changes consistent with neurotoxicity were detected in the brain after 1 week of continuous exposure to 0.5% isoflurane in healthy rats. These data suggest that even long exposures to low concentrations of isoflurane have no overt consequences on neuropathology.
在重症监护环境中，长时间使用异氟醚镇静的情况越来越多。然而，异氟醚介导的神经毒性已被广泛报道。本研究的目的是确定机械通气的啮齿动物长期暴露于低剂量异氟醚是否与神经退行性变或神经炎症的证据有关。
本研究使用成年雌性 Sprague-Dawley 大鼠。实验动物（n=11）用 1.5%异氟醚诱导，插管，并给予α-眼镜蛇毒素肌松。手术植入脑电图电极，皮下心前区 ECG Ag 线电极，以及膀胱、股动脉和股静脉插管永久放置。在这些程序之后，将异氟醚浓度降低至 0.5%，并与肌松一起持续 7 天。在 3 个时间点测量动脉血气和化学物质，调节核心体温并在 7 天内给予维持 IV 液。实验动物和未经处理的对照组（n=9）在第 7 天被安乐死。
免疫组织化学和细胞化学检测未检测到小胶质细胞增生、星形胶质细胞增生、神经元凋亡或坏死、淀粉样变性或磷酸化 tau 积累的证据。第 3/4 天和第 6/7 天血糖水平显著降低，第 6/7 天氧分压显著降低，但仍在正常范围内。所有其他血液测量均未改变。
在健康大鼠连续 1 周暴露于 0.5%异氟醚后，大脑中未发现与神经毒性一致的神经病理变化。这些数据表明，即使长时间暴露于低浓度的异氟醚也不会对神经病理学产生明显影响。
