title: Thiopentone and methohexital, but not pentobarbitone, reduce early focal cerebral ischemic injury in rats.
abstract: OBJECTIVE
  Although barbiturates are considered to be cerebral protectants, little is known regarding the relative efficacy of different barbiturates to reduce ischemic brain injury. In a model of middle cerebral artery occlusion (MCAo), we compared the relative effects of 1.0 and 0.4 burst-suppression doses of thiopentone, methohexital, and pentobarbitone on cerebral infarct.
  
  
  METHODS
  During isoflurane anesthesia, MCAo was achieved via a temporal craniotomy. Thirty minutes before MCAo the rats were randomized to receive one of the following which was maintained throughout the study. Halothane (n=20)-1.2 MAC halothane, thiopentone (n=20), methohexital (n=20), or pentobarbitone (n=20). The first ten animals in each barbiturate group received the respective barbiturate in a dose sufficient to maintain burst-suppression of the electroencephalogram (3-5 bursts x min(-1)). The subsequent ten animals in each barbiturate group received 40% of the burst-suppression dose. After 180 min of MCAo and 120 min of reperfusion, cerebral injury was assessed.
  
  
  RESULTS
  For the burst-suppression animals, injury volume (mm3, mean +/- SD) was less in the thiopentone group (88 +/- 14) than the halothane (133 +/- 17), methohexital (126 +/- 19), or pentobarbitone (130 +/- 17) groups (P <0.05). For 0.4 burst-suppression animals, injury volume was less for the methohexital group (70 +/- 22) than the halothane (124 +/- 24), thiopentone (118 +/- 15), or pentobarbitone (121 +/- 20) groups (P <0.05).
  
  
  CONCLUSIONS
  These data are inconsistent with the longstanding assumption that electrophysiologically comparable doses of the various classes of barbiturates have equivalent protective efficacy. They in turn suggest that mechanisms other than, or at least in addition to, metabolic suppression may contribute to the protective effect of barbiturates.
authors.affiliation: Department of Anesthesiology, Loma Linda University, Loma Linda, California 92354, USA. djcole@som.llu.edu
authors.forename: D J
authors.initials: DJ
authors.lastname: Cole
authors.forename: L M
authors.initials: LM
authors.lastname: Cross
authors.forename: J C
authors.initials: JC
authors.lastname: Drummond
authors.forename: P M
authors.initials: PM
authors.lastname: Patel
authors.forename: W K
authors.initials: WK
authors.lastname: Jacobsen
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D004569:Electroencephalography / Q000187:drug effects; D005609:Free Radicals; D018698:Glutamic Acid / Q000633:toxicity; D008297:Male; D008723:Methohexital / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000633:toxicity; D010424:Pentobarbital / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D013874:Thiopental / Q000627:therapeutic use*
chemical_list: D005609:Free Radicals; D009569:Nitric Oxide; D018698:Glutamic Acid; D008723:Methohexital; D010424:Pentobarbital; D013874:Thiopental; D002118:Calcium