Max Planck Institute for Neurological Research, 50931 Cologne, Germany; Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
Max Planck Institute for Neurological Research, 50931 Cologne, Germany.
Exp Neurol. 2014 Feb;252:12-7. doi: 10.1016/j.expneurol.2013.11.003. Epub 2013 Nov 15.
Sedatives in the neurointensive care unit can strongly influence patients' risks of developing secondary brain damage. In particular, isoflurane, a volatile anesthetic, has been recently re-introduced to the neurointensive care unit, and first clinical studies suggest beneficial effects due to elevation of cerebral blood flow and reduction of metabolism. In contrast, propofol is a commonly used intravenous sedative that reduces cerebral blood flow and intra-cranial pressure. We have here studied the influence of these two sedatives on the occurrence of cortical spreading depolarizations (CSDs), which have emerged over the last decade as a major mechanism of delayed brain injury in stroke and brain trauma, constituting a substantial vascular and metabolic threat to peri-infarct tissue and being associated with poor patient outcome. Two experimental models were tested in Wistar rats anesthetized either with isoflurane or with propofol: KCl-evoked CSDs (n=10) and spontaneous CSDs after occlusion of the middle cerebral artery (n=14). Spatiotemporal patterns of CSD waves were observed by real-time laser speckle imaging of regional cerebral blood flow changes associated with the CSDs. During 30 min of cortical KCl application, 5.2±0.7 CSDs were induced under isoflurane compared to 10.2±1.8 CSDs under propofol (p<0.001). After focal ischemia, 2.43±1.0 CSDs/h emerged spontaneously under isoflurane versus 6.83±2.5 CSDs/h under propofol (p<0.001). Furthermore, baseline blood flow and glycemia were much higher under isoflurane compared to propofol, which may set the tissue in better metabolic conditions to recover from the occurrence of CSD waves. We conclude that isoflurane, in comparison to propofol, decreases the occurrence of CSDs and may improve recovery from these metabolically demanding waves. To reduce CSD induced secondary tissue damage, we suggest isoflurane to be favored over propofol to sedate acute stroke and trauma patients in the neurointensive care unit.
神经重症监护病房中的镇静剂会强烈影响患者发生继发性脑损伤的风险。特别是，异氟醚作为一种挥发性麻醉剂，最近重新被引入神经重症监护病房，初步临床研究表明其具有升高脑血流和降低代谢的有益作用。相比之下，丙泊酚是一种常用的静脉镇静剂，可降低脑血流和颅内压。我们在这里研究了这两种镇静剂对皮质扩散性去极化（CSD）发生的影响，CSD 在过去十年中已成为中风和脑外伤中迟发性脑损伤的主要机制，对梗塞周围组织构成实质性的血管和代谢威胁，并与患者预后不良相关。我们在使用异氟醚或丙泊酚麻醉的 Wistar 大鼠中测试了两种实验模型：氯化钾诱发的 CSD（n=10）和大脑中动脉闭塞后自发的 CSD（n=14）。通过实时激光散斑成像观察与 CSD 相关的局部脑血流变化来观察 CSD 波的时空模式。在皮质氯化钾应用 30 分钟期间，异氟醚下诱导 5.2±0.7 次 CSD，而丙泊酚下诱导 10.2±1.8 次 CSD（p<0.001）。在局灶性缺血后，异氟醚下自发出现 2.43±1.0 CSD/h，而丙泊酚下自发出现 6.83±2.5 CSD/h（p<0.001）。此外，异氟醚下的基线血流和血糖水平明显高于丙泊酚，这可能使组织处于更好的代谢状态，从而从 CSD 波的发生中恢复。我们得出结论，与丙泊酚相比，异氟醚可降低 CSD 的发生，并可能改善这些代谢需求波的恢复。为了减少 CSD 引起的继发性组织损伤，我们建议在神经重症监护病房中使用异氟醚来镇静急性中风和创伤患者，而不是丙泊酚。
