Thiopentone and methohexital, but not pentobarbitone, reduce early focal cerebral ischemic injury in rats

Abstract

P Pu ur rp po os se e: : 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.M Me et th ho od ds s: : 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 (35 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.R Re es su ul lt ts s: : For the burst-suppression animals, injury volume (mm 3 , 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).C Co on nc cl lu us si io on ns s: : 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.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 docclusion de lartère 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 linfarctus cérébral.Méthode : Pendant lanesthésie à lisoflurane, lOACM a été provoquée au moyen dune craniotomie temporale. Trente minutes avant locclusion, les rats ont été randomisés et ont reçu un des médica-ments suivants, thérapie maintenue tout au long de létude : 1,2 CAM dhalothane (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 (35·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 dOACM suivie de 120...

Thiopental Inhibits Global Protein Synthesis by Repression of Eukaryotic Elongation Factor 2 and Protects from Hypoxic Neuronal Cell Death

“…In our present experiments we also noted that the oxy-derivate of thiopental, pentobarbital, displayed a significantly reduced ability to induce phosphorylation of eEF2, translational repression and protection from ischemic cell death (Matjaz Humar, unpublished data). These findings are consistent with studies conducted in laboratory animals [64], [65], suggesting that the neuroprotective capacity of thiopental is superior to pentobarbital. In some of these studies neuroprotection by thiopental was associated with reduced radical formation, lipid peroxidation, and inflammation [40]–[42].…”

Neuroprotective effects of anesthetic agents

“…These data were confirmed in a similar study conducted by Schmid-Elsaesser and colleagues [48]. Another interesting finding is that electrophysiologically comparable doses of the various classes of barbiturates (i.e., thiopental, methohexital, and pentobarbital) can have different neuroprotective efficacy in a model of focal ischemia, suggesting that mechanisms other than, or at least in addition to, metabolic suppression may contribute to the protective effect of barbiturates [49].…”

Management of traumatic brain injury: some current evidence and applications

“…It is also important to remember that mechanisms other than, or at least in addition to, metabolic suppression may contribute to the protective effect of barbiturates, as a differential effect between thiopental, methohexital and pentobarbital has been described. 16 …”