Efficacy of five days' barbiturate anesthesia in the treatment of intractable epilepsies in children.

Rantala H, Saukkonen AL, Remes M, Uhari M.

Department of Pediatrics, University of Oulu, Finland. Heikki.Rantala oulu.fi

PURPOSE: To analyze the efficacy of barbiturate anesthesia in the treatment of intractable epilepsies in childhood. METHODS: Anesthesia for 4-5 days with thiopentone sodium was used to treat children with intractable epilepsy in the Department of Pediatrics, Oulu, Finland, from November 1980 through December 1995. The number of epileptic seizures, the number and dosage of antiepileptic drugs (AEDs), and psychomotor development before and after anesthesia were compared. RESULTS: Fifty-four children with intractable epilepsy were treated with barbiturate anesthesia. Twenty-four children had infantile spasms; 22, Lennox-Gastaut syndrome; seven, complex partial epilepsy; and one, myoclonic epilepsy. Twenty-four (44.4%) children had complications during the anesthesia. The seizures recurred in 53 of the 54 patients in a median time of 12 days after the anesthesia. In 42 (78%) children, the seizure frequency returned to a level equal to or higher than that before the anesthesia in a median time of 211 days. The number of AEDs was significantly greater after than before the anesthesia (6.33 vs. 4.8; p < 0.001). Seventeen (32.5%) children were treated surgically after the anesthesia. CONCLUSIONS: Although the seizures are eliminated or the seizure frequency decreases for a short period after the barbiturate anesthesia, the anesthesia does not change the long-term outcome and is therefore inefficient in the treatment of childhood intractable epilepsies.

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Pentobarbital modulatory effect on GABA binding sites in developing chick optic lobe.

Fiszer de Plazas S, Viapiano MS, Mitridate de Novara A.

Instituto de Biologia Celular y Neurociencias, Facultad de Medicina, Universidad de Buenos Aires, Argentina.

Barbiturates are allosteric modulators of the CNS GABAA receptor, increasing [3H]-GABA binding to its receptor sites. In the present work we have studied the modulatory effect of the barbiturate pentobarbital on low-affinity GABA binding sites during ontogenetic development of the chick optic lobe. Our results indicate that [3H]-GABA binding enhancement by pentobarbital shows a differential profile during development, following a two-component enhancement model at early stages of development and a single-component enhancement model in the adult stage. Kinetic analysis performed at different stages of development showed that barbiturate enhancement was invariably due to an increase in [3H]-GABA binding affinity, while maximal binding capacity remained unchanged. Using GABA antagonists, picrotoxinin and bicuculline, convulsant sensitivity of high-affinity barbiturate modulatory sites was found at early stages. These data suggest that barbiturate action displays receptor heterogeneity during development, with high- and low-affinity modulatory sites only at early stages, while the high-affinity sites disappear between hatching and adulthood. Kinetic data indicate that both barbiturate modulatory sites are coupled to the GABAA receptor at early stages. The presence of high-affinity modulatory sites at early stages and at hatching suggests a major role during visual pathway maturation.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8770651&dopt=Abstract barbiturate Butalbital Fioricet





Effect of barbiturates on hydroxyl radicals, lipid peroxidation, and hypoxic cell death in human NT2-N neurons.

Almaas R, Saugstad OD, Pleasure D, Rootwelt T.

Department of Pediatric Research, National Hospital, Oslo, Norway. runar.almaas klinmed.uio.no

BACKGROUND: Barbiturates have been shown to be neuroprotective in several animal models, but the underlying mechanisms are unknown. In this study, the authors investigated the effect of barbiturates on free radical scavenging and attempted to correlate this with their neuroprotective effects in a model of hypoxic cell death in human NT2-N neurons. METHODS: Hydroxyl radicals were generated by ascorbic acid and iron and were measured by conversion of salicylate to 2,3-dihydroxybenzoic acid. The effect of barbiturates on lipid peroxidation measured as malondialdehyde and 4-hydroxynon-2-enal was also investigated. Hypoxia studies were then performed on human NT2-N neurons. The cells were exposed to 10 h of hypoxia or combined oxygen and glucose deprivation for 3 or 5 h in the presence of thiopental (50-600 microM), methohexital (50-400 microM), phenobarbital (10-400 microM), or pentobarbital (10-400 microM), and cell death was evaluated after 24 h by lactate dehydrogenase release. RESULTS: Pentobarbital, phenobarbital, methohexital, and thiopental dose-dependently inhibited formation of 2,3-dihydroxybenzoic acid and iron-stimulated lipid peroxidation. There were significant but moderate differences in antioxidant action between the barbiturates. While phenobarbital (10-400 microM) and pentobarbital (10-50 microM) increased lactate dehydrogenase release after combined oxygen and glucose deprivation, thiopental and methohexital protected the neurons at all tested concentrations. At a higher concentration (400 microM), pentobarbital also significantly protected the neurons. At both 50 and 400 microM, thiopental and methohexital protected the NT2-N neurons significantly better than phenobarbital and pentobarbital. CONCLUSIONS: Barbiturates differ markedly in their neuroprotective effects against combined oxygen and glucose deprivation in human NT2-N neurons. The variation in neuroprotective effects could only partly be explained by differences in antioxidant action.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10719955&dopt=Abstract barbiturate Butalbital Fioricet





Analysis of barbiturates by micro-high-performance liquid chromatography with post-column photochemical derivatization.

Garcia-Borregon PF, Lores M, Cela R.

Dpto. Quimica Analitica, Nutricion y Bromatologia, Facultad de Quimica, Universidad de Santiago de Compostela, Spain.

This study attempts to combine the advantages of microcolumn high-performance liquid chromatography (micro-HPLC) with those of post-column photochemical derivatization in barbiturate analysis. Some barbiturates are photochemically unstable, leading to photoproducts that show maximum absorption at 270 nm and not the typical one at approximately 220 nm. For this purpose, a laboratory-built photoreactor has been developed to work with micro-HPLC instruments. Its performance is satisfactory in the forensic analysis of barbiturates.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10722060&dopt=Abstract barbiturate Butalbital Fioricet