Barbiturate coma for intracranial hypertension: clinical observations.

Dereeper E, Berre J, Vandesteene A, Lefranc F, Vincent JL.

Department of Anesthesiology, Erasme Hospital, Free University of Brussels, Belgium.

PURPOSE: To determine the neurologic outcome of patients with intracranial hypertension treated with barbiturate-induced coma. Materials and Methods: The records of 49 patients who were admitted to a 31-bed medicosurgical intensive care unit over a 5-year period in whom a barbiturate coma was induced to control intracranial hypertension were analyzed retrospectively. Analysis included assessment of the response to barbiturate coma and evaluation of the long-term neurologic outcome according to the Glasgow Outcome Scale (GOS). RESULTS: Intracranial hypertension was caused by head trauma in 28 patients and subarachnoid hemorrhage in 21 patients. Eight of the head trauma patients and 5 of the patients with subarachnoid hemorrhage survived their hospital stay. The survivors were younger than the nonsurvivors, and had a good neurologic status after 1 year (except for 2 patients who died 1 and 3 months after discharge, respectively). There was no significant difference in the Glasgow Coma Score (GCS) on admission between the survivors and the nonsurvivors. The long-term outcome at 1 year was markedly better in the patients who had experienced a subarachnoid hemorrhage than in the trauma patients. Copyright 2002, Elsevier Science (USA). All rights reserved.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12040550&dopt=Abstract barbiturate Butalbital Fioricet





Physiological comparison of alpha-ethyl-alpha-methyl-gamma-thiobutyrolactone with benzodiazepine and barbiturate modulators of GABAA receptors.

Mathews GC, Bolos-Sy AM, Covey DF, Rothman SM, Ferrendelli JA.

Department of Molecular Biology, Washington University School of Medicine, St Louis, MO 63110, USA.

The GABAA receptor/chloride ionophore (GABAR) is allosterically modulated by several classes of anticonvulsant agents, including benzodiazepines and barbiturates, and some alkyl-substituted butyrolactones. To test the hypothesis that the anticonvulsant butyrolactones act at a distinct positive-modulatory site on the GABAR, we examined the physiological effects of a butyrolactone, a benzodiazepine and a barbiturate on GABA-mediated currents in voltage-clamped neurons and cells transfected with various subunit combinations. The butyrolactone, alpha-ethyl-alpha-methyl-gamma-thiobutyrolactone (alpha EMTBL), altered the EC50 for GABA and changed the apparent cooperativity of GABA responses. In contrast, the benzodiazepine chlordiazepoxide altered the EC50 for GABA with no effect on apparent cooperativity. The barbiturate phenobarbital altered both the EC50 and the amplitude of the maximal GABA response without altering apparent cooperativity. The GABA-mediated effect of the barbiturate, but not the benzodiazepine, added to the maximal effect of the butyrolactone, supporting the hypothesis that butyrolactones do not exert their effect at the barbiturate effector site. Both alpha EMTBL and phenobarbital potentiated GABA currents in transfected cells containing the alpha 1 beta 2 and alpha 1 gamma 2 subunit combinations, as well as alpha 1 subunits alone. Chlordiazepoxide had the minimum requirement of an alpha subunit and a gamma subunit. Specific GABARs lacking benzodiazepine or barbiturate modulation were tested for modulation by alpha EMTBL. The alpha 6 beta 2 gamma 2 combination was modulated by the butyrolactone but not chlordiazepoxide. However, GABARs comprising rho1 subunits were sensitive to both phenobarbital and alpha EMTBL. Although the molecular determinants for alpha EMTBL action appear similar to the barbiturates, our data support the conclusion that alpha EMTBL interacts with GABARs in a distinct manner from barbiturates and benzodiazepines.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8734480&dopt=Abstract barbiturate Butalbital Fioricet





[Quantitative analysis of plasma concentration of barbiturate for diagnosis of brain death]

[Article in Japanese]

Saito T, Kurashima A, Oda T, Aoki S, Endo H, Nashimoto T, Yamada R.

Department of Neurosurgery, Nagano Red Cross Hospital, 5-22-1 Wakasato, Nagano 380-8582, Japan.

Organ transplantation from brain death patients started in Japan in 1997. However it is difficult to diagnose brain death in patients treated with barbiturate therapy. In this study, the influence of long continuous administration of barbiturate on diagnosis of brain death was investigated by measuring plasma concentration of barbiturate. In 15 patients treated with barbiturate therapy, plasma concentrations of thiamylal were measured by liquid chromatographic apparatus every day until it's level decreased below 0.1 microgram/ml after cessation of continuous administration. At the same time, plasma thiamylal levels were checked on the day when burst-suppression (b-s) pattern had disappeared in 9 cases, light reflex of pupil appeared in 7 cases and spontaneous respiration had been detected by trigger lamp in 11 cases. The plasma concentrations of thiamylal on the day when b-s pattern had disappeared differed clearly among the cases in the range of 8.8 to 37.9 micrograms/ml. Those cases in which light reflex of the pupil had been recognized were also different in the range of 17.8 to 57.8 micrograms/ml. The cases in which spontaneous respiration had been detected were in the range of 4.4 to 23.0 micrograms/ml. These concentrations varied about 4, 3 and 5 times among the cases examined. The intervals between cessation of continuous administration of thiamylal and the decrease of plasma concentration to below 0.1 microgram/ml also varied from 2 to 14 days from case to case. The minimum concentration of thiamylal on the day when b-s pattern had disappeared, light reflex of the pupil had been recognized and spontaneous respiration had been detected was 8.8, 17.8 and 4.4 micrograms/ml respectively. These results suggest that diagnosis of brain death in patients treated with barbiturate therapy is able to be made when the plasma thiamylal level is below 4.4 micrograms/ml.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12094685&dopt=Abstract barbiturate Butalbital Fioricet





Neurotoxic effects of carambola in rats: the role of oxalate.

Chen CL, Chou KJ, Wang JS, Yeh JH, Fang HC, Chung HM.

Division of Nephrology, Kaohsiung Veterans General Hospital, 386 Ta-Chung 1st Road, Kaohsiung, Taiwan.

BACKGROUND AND PURPOSE: Carambola (star fruit) has been reported to contain neurotoxins that cause convulsions, hiccups, or death in uremic patients, and prolong barbiturate-induced sleeping time in rats. The constituent responsible for these effects remains uncertain. Carambola contains a large quantity of oxalate, which can induce depression of cerebral function and seizures. This study was conducted to investigate the role of oxalate in carambola toxicity in rats. MATERIALS AND METHODS: The effects on barbiturate-induced sleeping time and death caused by intraperitoneal administration of carambola juice were observed in Sprague-Dawley rats. To obtain a dose-dependent response curve and evaluate the lethal dose, rats were treated with serial amounts of pure carambola juice diluted with normal saline in a volume of 1:1. To test the role of oxalate in the neurotoxic effect of carambola, either 5.33 g/kg carambola after oxalate removal or 5.33 g/kg of pure carambola juice diluted with normal saline were administered intraperitoneally, while the control group was given normal saline before pentobarbital injection. The effects of carambola and oxalate-removed carambola on barbiturate-induced sleeping time were compared with those of saline. To assess the lethal effect of oxalate in carambola, we gave rats chemical oxalate at comparable concentrations to the oxalate content of carambola. RESULTS: Carambola juice administration prolonged barbiturate-induced sleeping time in a dose-dependent manner. The sleeping time of rats that received normal saline and 1.33 g/kg, 2.67 g/kg, 5.33 g/kg, and 10.67 g/kg of carambola juice were 66 +/- 16.6, 93.7 +/- 13.4, 113.3 +/- 11.4, 117.5 +/- 29.0, and 172.5 +/- 38.8 minutes, respectively. The three higher-dose groups had longer sleeping times than controls (p < 0.05 or 0.005). This effect was eliminated after the removal of oxalate from carambola juice. Four of eight rats in the 10.67-g/kg group and all rats in the 21.33 g/kg and chemical oxalate groups died after seizure. Lethal doses of carambola juice were rendered harmless by the oxalate removal procedure. CONCLUSIONS: Oxalate is a main constituent of carambola neurotoxicity. This finding suggests that patients with carambola intoxication should be treated for oxalate toxicosis.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12101851&dopt=Abstract barbiturate Butalbital Fioricet