Abstract
Purpose
Although barbiturates are considered to be cerebral protectants, little is known regarding the relative efficacy of different barbiturates to reduce ischemie 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·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.
Résumé
Objectif
Bien que les barbituriques soient considérés comme des protecteurs cérébraux, on en sait peu sur leur efficacité relative à réduire la lésion cérébrale ischémique. Nous avons comparé, chez un modèle d’occlusion de l’artère cérébrale moyenne (OACM), les effets relatifs de doses de thiopental, méthohexital et pentobarbital, capables de suppression totale et à 40 % (1,0 et 0,4) des bouffées du tracé électroencéphalographique (EEG), sur l’infarctus cérébral.
Méthode
Pendant l’anesthésie à l’isoflurane, l’OACM a été provoquée au moyen d’une craniotomie temporale. Trente minutes avant l’occlusion, les rats ont été randomisés et ont reçu un des médicaments suivants, thérapie maintenue tout au long de l’étude : 1,2 CAM d’halothane (n = 20), du thiopental (n = 20), du méthohexital (n = 20) ou du pentobarbital (n = 20). Les dix premiers animaux de chaque groupe barbiturique ont reçu une dose du médicament suffisante pour maintenir la suppression des bouffées du tracé EEG (3–5·min−1). Les dix animaux suivants de chaque groupe barbiturique ont reçu 40 % de la dose causant la suppression des bouffées. On a évalué la lésion cérébrale après 180 min d’OACM suivie de 120 min de reperfusion.
Résultats
Pour les animaux chez qui il y a eu suppression des bouffées du tracé EEG, le volume lésionnel (mm3, moyenne ± écart type) a été plus bas avec le thiopental (88 ± 14) qu’avec l’halothane (133 ± 17), le méthohexital (126 ± 19) ou le pentobarbital (130 ± 17) (P < 0,05). Pour une suppression à 40 %, le volume lésionnel a été moindre avec le méthohexital (70 ± 22) qu’avec l’halothane (124 ± 24), le thiopental (118 ± 15) ou le pentobarbital (121 ± 20) (P < 0,05).
Conclusion
Ces données contredisent l’hypothèse de longue date voulant que des doses comparables, au plan électrophysiologique, de diverses classes de barbituriques présentent une efficacité protectrice équivalente. Elles évoquent, par ailleurs, que des mécanismes de suppression métabolique différents, ou tout au moins additionnels, peuvent contribuer à l’effet protecteur des barbituriques.
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Support for this study was provided by the Department of Anesthesiology, Loma Linda University-School of Medicine.
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Cole, D.J., Cross, L.M., Drummond, J.C. et al. Thiopentone and methohexital, but not pentobarbitone, reduce early focal cerebral ischemic injury in rats. Can J Anesth 48, 807–814 (2001). https://doi.org/10.1007/BF03016699
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DOI: https://doi.org/10.1007/BF03016699