Treatment of refractory status epilepticus with propofol: clinical and pharmacokinetic findings.

Stecker MM, Kramer TH, Raps EC, O'Meeghan R, Dulaney E, Skaar DJ.

Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia 19104, USA.

PURPOSE: We compared propofol with high-dose barbiturates in the treatment of refractory status epilepticus (RSE) and propose a protocol for the administration of propofol in RSE in adults, correlating propofol's effect with plasma levels. METHODS: Sixteen patients with RSE were included; 8 were treated primarily with high-dose barbiturates and 8 were treated primarily with propofol. RESULTS: Both groups of patients had multiple medical problems and a subsequent high mortality. A smaller but not statistically significant fraction of patients had their seizures controlled with propofol (63%) than with high-dose barbiturate therapy (82%). The time from initiation of high-dose barbiturate therapy to attainment of control of RSE was longer (123 min) than the time to attainment of seizure control in the group receiving propofol (2.6 min, p = 0.002). Plasma concentrations of propofol associated with control of SE were 14 microM +/- 4 (2.5 microg/ml). Recurrent seizures were common when propofol infusions were suddenly discontinued but not when the infusions were gradually tapered. CONCLUSIONS: If used appropriately, propofol infusions can effectively and quickly terminate many but not all episodes of RSE. Propofol is a promising agent for use in treating RSE, but more studies are required to determine its true value in comparison with other agents.

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Relapse and survival after barbiturate anesthetic treatment of refractory status epilepticus.

Krishnamurthy KB, Drislane FW.

Department of Neurology, Beth Israel Hospital, Boston, Massachusetts 02215, USA.

PURPOSE: Pentobarbital is standard treatment for refractory status epilepticus (SE) and is almost uniformly effective, but the morbidity of treatment and the mortality of refractory SE are high. Recurrence of SE after pentobarbital discontinuation may predict a worsened outcome. We sought to determine the optimal use of barbiturate anesthetic treatment of refractory SE. METHODS: We reviewed 44 episodes of barbiturate anesthetic treatment for refractory SE in 40 patients, seeking factors predicting freedom from relapse to clinical or electrographic SE after treatment and predicting survival. RESULTS: Eight of 9 patients with relapse of seizures after barbiturate treatment died, whereas only 9 of 26 with persistently controlled seizures died (p < 0.005). Both likelihood of relapse and survival correlated strongly with etiology, with 19 of 20 patients with chronic epilepsy, infections, or focal lesions having good control as compared with 2 of 9 with multiple medical problems (p < 0.001). Treatment delay did not predict a worsened outcome. Hypotension caused dose reduction but never required treatment discontinuation. Patients with more prolonged treatment and those receiving phenobarbital (PB) at the time of pentobarbital taper were less likely to relapse. CONCLUSIONS: Relapse of SE after barbiturate anesthetic treatment is a poor prognostic sign and should be prevented, if possible. Etiology was the primary predictor of outcome, but more prolonged treatment and the use of PB during pentobarbital withdrawal appeared to provide protection against relapse.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8814099&dopt=Abstract barbiturate Butalbital Fioricet





Are suicide rates in Sweden associated with changes in the prescribing of medicines?

Carlsten A, Allebeck P, Brandt L.

Pharmacy Department, Sahlgrenska University Hospital, Goteborg, Sweden.

A key issue in the debate on suicide prevention is the extent to which suicide rates are affected by the availability of means of committing suicide. The aim of this study was to analyse the changes in rates of suicides committed by poisoning in Sweden between 1969 and 1992, and to determine to what extent these were associated with changes in the prescribing of medicines. We compared suicide rates from 1969 to 1992 with trends in the sales of antidepressants, barbiturates, neuroleptics and analgesics during the same period. The incidence of suicide by poisoning decreased during the 1970s, especially in younger and middle-aged men. This was mainly due to a decrease in suicides by barbiturate poisoning, which closely followed a decrease in sales of barbiturates. Sales of analgesics and antidepressants increased during the study period, and so did the rates of suicide using these drugs. We conclude that the availability of medicines is an important factor influencing suicide rates, and that changes in the prescribing of medicines may influence suicide rates.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8883569&dopt=Abstract barbiturate Butalbital Fioricet





Inhibition of gap junctional intercellular communication by barbiturates in long-term primary cultured rat hepatocytes is correlated with liver tumour promoting activity.

Ren P, Ruch RJ.

Department of Pathology, Medical College of Ohio, Toledo 43699, USA.

Rodent liver tumor formation can be promoted by certain barbiturates and this may involve their ability to inhibit hepatocyte gap junctional intercellular communication (GJIC). In order to address the mechanisms and specificity of action of barbiturates on hepatocyte gap junctions, we have compared the effects of liver tumor-promoting barbiturates (phenobarbital, sodium barbital and amobarbital: PB, SB and AB, respectively) and a non-liver tumor-promoting barbiturate (barbituric acid: BA) on primary cultured rat hepatocyte GJIC and connexin32 (Cx32) expression after short (1-24 h) and long (2-14 days) treatment. GJIC was evaluated by fluorescent dye microinjection (dye-coupling); Cx32 expression was monitored by Northern blot, Western blot and immunohistochemistry. Both parameters were maintained at high levels over 14 days by coculture of the cells with WB-F344 rat liver epithelial cells in the presence of dexamethasone. Treatment with PB (2 mM) for 1 h sharply reduced dye-coupling from approximately 90-30%, but the cells fully recovered by 24 h. No inhibition was seen with the other barbiturates over this 1-day treatment period. Longer treatments (2-14 days) with the promoters PB, SB and AB, however, gradually reduced hepatocyte dye-coupling to approximately 30-50%. The non-promoter, BA, did not affect hepatocyte GJIC. These decreases in hepatocyte dye-coupling occurred without changes in Cx32 or gap junction expression. Dye-coupling of WB-F344 cells and expression of their predominant gap junction protein, connexin43 (Cx43), were also not affected. Thus, the inhibition of GJIC was specific to liver tumor promoting barbiturates in hepatocytes, was time-dependent and was not due to altered Cx32 expression.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8895477&dopt=Abstract barbiturate Butalbital Fioricet