Isoflurane suppresses cortical spreading depolarizations compared to propofol--implications for sedation of neurocritical care patients.
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.
Max Planck Institute for Neurological Research, 50931 Cologne, Germany; Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
Masatoshi
M
Takagaki
Max Planck Institute for Neurological Research, 50931 Cologne, Germany. Electronic address: delphfeuerstein@gmail.com.
Delphine
D
Feuerstein
Max Planck Institute for Neurological Research, 50931 Cologne, Germany; Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
Tetsuya
T
Kumagai
Max Planck Institute for Neurological Research, 50931 Cologne, Germany.
Markus
M
Gramer
Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
Toshiki
T
Yoshimine
Max Planck Institute for Neurological Research, 50931 Cologne, Germany.
Rudolf
R
Graf
D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects; D013181:Cortical Spreading Depression / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000473:pathology; D007530:Isoflurane / Q000494:pharmacology*; D017078:Laser-Doppler Flowmetry; D008297:Male; D011189:Potassium Chloride / Q000494:pharmacology; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D006993:Hypnotics and Sedatives; D011189:Potassium Chloride; D007530:Isoflurane; D015742:Propofol
CBF; CSD; Cerebral blood flow; Cortical spreading depression; DC; ICU; Intensive care unit; Isoflurane; LSF; MCAo; Propofol; ROI; Stroke; cerebral blood flow; cortical spreading depression; direct current; intensive care unit; laser speckle flowmetry; middle cerebral artery occlusion; region of interest