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Status epilepticus in children: aetiology, treatment, and outcome.

Eriksson KJ, Koivikko MJ.

Tampere University Hospital, Finland.

This retrospective study includes 65 children treated for status epilepticus at Tampere University Hospital in Finland. Aetiology of the condition, effectiveness of the treatment protocol, including short barbiturate anaesthesia to prevent prolonged status epilepticus episodes, and neurological outcome were evaluated. Symptomatic aetiology was present in 40% of status epilepticus episodes, and 37% of episodes were induced by fever. Neurological sequelae secondary to status epilepticus were identified in 15% of the cases and subsequent epilepsy in 23% during the mean follow-up time of 3.6 years. There were no status epilepticus-related deaths. The cut-off point of status epilepticus duration for significant risk for permanent neurological sequelae was 2 hours. Our treatment protocol, including short barbiturate anaesthesia in refractory cases, was able to abort status epilepticus in less than 2 hours in 75% of cases. We conclude that early and prompt use of barbiturate anaesthesia should be encouraged, and may explain our low morbidity figures.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9352725&dopt=Abstract barbiturate Butalbital Fioricet





Effect of altered tissue binding on the disposition of barbital in the isolated perfused rat liver: application of the axial dispersion model.

Chou CH, Rowland M.

School of Pharmacy and Pharmaceutical Sciences, University of Manchester, United Kingdom.

To examine the dependence of hepatic dispersion on tissue binding, the distribution kinetics of barbital under varying conditions of barbiturate perfusate concentrations was studied in the isolated perfused rat liver preparation (n = 5). The in situ liver was perfused in a single-pass mode with protein-free Krebs bicarbonate medium (15 mL/min). During steady-state infusion with various barbiturate concentrations (barbital, 1 g/L; butethal, 0.1, 1 g/L), a bolus containing [3H]water (cellular space marker) and [14C]barbital was injected into the portal vein. The recoveries of [3H]water and [14C]barbital were complete. The mean transit time and hence the volume of distribution for barbital in the absence of bulk barbiturate concentration (56 s and 1.24 mL/g) were about 2-fold higher than those for water (29 s and 0.58 mL/g), and they decreased progressively as the perfusate barbiturate concentration increased, indicating a decrease in tissue binding. However, the relative dispersion values (CV2H) of water (0.60) and barbital (0.66) were about the same magnitude and independent of the bulk concentration of barbiturate. The one-compartment dispersion model adequately described the data of barbital with a constant DN (dispersion number) value of 0.35. The results indicate that varying the tissue binding of barbital does not change the magnitude of DN; as such it offers a new experimental approach to examine the hepatic dispersion of solutes with a large distribution volume.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9383746&dopt=Abstract barbiturate Butalbital Fioricet





Orexinergic neurons and barbiturate anesthesia.

Kushikata T, Hirota K, Yoshida H, Kudo M, Lambert DG, Smart D, Jerman JC, Matsuki A.

Department of Anesthesiology, University of Hirosaki School of Medicine, Zaifu-cho 5, Hirosaki, Japan 036-8562. masuika cc.hirosaki-u.ac.jp

Orexins (OXs) regulate sleep with possible interactions with brain noradrenergic neurons. In addition, noradrenergic activity affects barbiturate anesthesia. As we have also recently reported that OXs selectively evoke norepinephrine release from rat cerebrocortical slices we hypothesized that barbiturate anesthesia may result from of an interaction with central orexinergic systems. To test this hypothesis, we performed a series of in vivo and in vitro studies in rats. In vivo, the effects of i.c.v. OX A, B and SB-334867-A (OX1 receptor antagonist) on pentobarbital, thiopental or phenobarbital-induced anesthesia times (loss of righting reflex) was assessed. In vitro effects of barbiturates and SB-334867-A on OX-evoked norepinephrine release from cerebrocortical slice was examined. In Chinese hamster ovary cells expressing human OX1/OX2 receptors OX A- and B-evoked increases in intracellular Ca2+ were measured with and without barbiturates. OX A and B significantly decreased pentobarbital, thiopental and phenobarbital anesthesia times by 15-40%. SB-334867-A increased thiopental-induced anesthesia time by approximately by 40%, and reversed the decrease produced by OX A. In vitro, all anesthetic barbiturates inhibited OX-evoked norepinephrine release with clinically relevant IC50 values. A GABAA antagonist, bicuculline, did not modify the inhibitory effects of thiopental and the GABAA agonist, muscimol, did not inhibit norepinephrine release. In addition there was no interaction of barbiturates with either OX1 or OX2 receptors. Collectively our data suggest that orexinergic neurons may be an important target for barbiturates, and GABAA, OX1 and OX2 receptors may not be involved in this interaction.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14580935&dopt=Abstract barbiturate Butalbital Fioricet





GC/MS confirmation of barbiturates in blood and urine.

Meatherall R.

Laboratory Medicine, St. Boniface General Hospital, Manitoba, Canada.

A gas chromatography-mass spectrometric method is described for the quantitative measurement of 6 commonly used barbiturates in blood and urine specimens. The targeted barbiturates are butalbital, amobarbital, pentobarbital, secobarbital, mephobarbital and phenobarbital. They are recovered along with the internal standard, tolybarb, from blood and urine using liquid extraction then alkalated to form the N-ethyl derivatives. The ethylated barbiturates have symmetrical peaks which are well separated from each other on a non-polar methylsilicone capillary column. The derivatives on a non-polar methylsilicone capillary column. The derivatives facilitate quantitations between 50 and 10,000 ng/mL. The day-to-day CVs for all 6 barbiturates were between 4 and 9% at 200 and 5000 ng/mL. The method has been extended for identifying other acidic drugs and drug metabolites. They are mainly non-steroidal anti-inflammatory drugs, diuretics, and anticonvulsants. An additional 83 compounds can be qualitatively identified.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9397563&dopt=Abstract barbiturate Butalbital Fioricet

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