No additional neuroprotection provided by barbiturate-induced burst suppression under mild hypothermic conditions in rats subjected to reversible focal ischemia.
OBJECTIVE
Mild-to-moderate hypothermia is increasingly used for neuroprotection in humans. However, it is unknown whether administration of barbiturate medications in burst-suppressive doses-the gold standard of neuroprotection during neurovascular procedures-provides an additional protective effect under hypothermic conditions. The authors conducted the present study to answer this question.


METHODS
Thirty-two Sprague-Dawley rats were subjected to 90 minutes of middle cerebral artery occlusion and randomly assigned to one of four treatment groups: 1) normothermic controls; 2) methohexital treatment (burst suppression); 3) induction of mild hypothermia (33 degrees C); and 4) induction of mild hypothermia plus methohexital treatment (burst suppression). Local cerebral blood flow was continuously monitored using bilateral laser Doppler flowmetry and electroencephalography. Functional deficits were quantified and recorded during daily neurological examinations. Infarct volumes were assessed histologically after 7 days. Methohexital treatment, mild hypothermia, and mild hypothermia plus methohexital treatment reduced infarct volumes by 32%, 71%, and 66%, respectively, compared with normothermic controls. Furthermore, mild hypothermia therapy provided the best functional outcome, which was not improved by additional barbiturate therapy.


CONCLUSIONS
The results of this study indicate that barbiturate-induced burst suppression is not required to achieve maximum neuroprotection under mild hypothermic conditions. The magnitude of protection afforded by barbiturates alone appears to be modest compared with that provided by mild hypothermia.
Westermaier
T
T
Department of Neurosurgery and Institute for Surgical Research, Klinikum Grosshadern, Ludwig Maximilians University, Munich, Germany.
Zausinger
S
S
Baethmann
A
A
Steiger
H J
HJ
Schmid-Elsaesser
R
R
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000098:blood supply / Q000601:surgery; D002544:Cerebral Infarction / Q000188:drug therapy / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000502:physiology; D004569:Electroencephalography / Q000187:drug effects; D016894:Endarterectomy, Carotid; D007036:Hypothermia, Induced; D007430:Intraoperative Care / Q000379:methods; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000503:physiopathology; D017078:Laser-Doppler Flowmetry; D008297:Male; D008723:Methohexital / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D015430:Weight Gain / Q000187:drug effects
D018686:Anesthetics, Intravenous; D008723:Methohexital