title: Electroencephalographic burst suppression is not required to elicit maximal neuroprotection from pentobarbital in a rat model of focal cerebral ischemia.
abstract: BACKGROUND
  Barbiturates have previously been demonstrated to reduce focal cerebral ischemic brain damage. However, the dose of drug required to elicit maximal neuroprotection has not been defined. The authors' hypothesized that doses of pentobarbital substantially lower than those required to cause electroencephalographic burst suppression would result in maximal magnitudes of reduction of cerebral infarct volume.
  
  
  METHODS
  Wistar rats underwent 90 min of filament occlusion of the middle cerebral artery while either awake (control), or anesthetized with intravenous sodium pentobarbital administered to preserve an active electroencephalogram (15-23 mg.kg-1.h-1) or a pattern of burst suppression (45-60 mg.kg-1.h-1; n = 17). During ischemia and for the first 6 h of recirculation, brain temperature was rigorously controlled at 38.0 +/- 0.2 degrees C. Rats were allowed a recovery interval of 7 days after which neurologic function and cerebral infarct volume were assessed. In nonischemic rats undergoing a similar anesthetic protocol, the cerebral metabolic rate of glucose utilization was measured at each anesthetic depth.
  
  
  RESULTS
  Relevant physiologic values were similar between groups. Total infarct volume (mean +/- SD) was smaller in the active electroencephalogram group than in the control group (124 +/- 68 mm3 versus 163 +/- 66 mm3; P < 0.05). Increasing the dose of pentobarbital (burst suppression) did not further decrease infarct volume (128 +/- 54 mm3). Neurologic score and infarct volume were positively correlated (P < 0.001). Cerebral metabolic rate of glucose utilization was reduced by 56% in the burst suppression group versus 43% in the active electroencephalogram pentobarbital group (P < 0.001).
  
  
  CONCLUSIONS
  Sodium pentobarbital administered at either dose (active electroencephalogram or burst suppression) resulted in an approximately equal to 25% reduction of cerebral infarct size, indicating that burst suppression is not required to elicit maximal neuroprotective efficacy.
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710, USA. warne002@mc.duke.edu
authors.forename: D S
authors.initials: DS
authors.lastname: Warner
authors.forename: S
authors.initials: S
authors.lastname: Takaoka
authors.forename: B
authors.initials: B
authors.lastname: Wu
authors.forename: P S
authors.initials: PS
authors.lastname: Ludwig
authors.forename: R D
authors.initials: RD
authors.lastname: Pearlstein
authors.forename: A D
authors.initials: AD
authors.lastname: Brinkhous
authors.forename: F
authors.initials: F
authors.lastname: Dexter
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D004569:Electroencephalography / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010424:Pentobarbital / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018696:Neuroprotective Agents; D010424:Pentobarbital; D005947:Glucose