Meprobamate Intoxication Research Articles

Overdose of meprobamate: plasma concentration and Glasgow Coma Scale

Meprobamate is a carbamate, main active metabolite of carisoprodol [1], used as an anxiolytic agent and prescribed in Europe and the USA. Carisoprodol is a prescribed centrally active muscle relaxant analgesic. Carisoprodol is extensively converted to meprobamate. Meprobamate plasmatic levels exceed those of carisoprodol 2.5 h after oral administration of 700 mg of carisoprodol to healthy volunteers [2]. Meprobamate is involved in 7% of psychotropic poisonings [3]. Meprobamate has a barbiturate-like mode of action at the GABAA receptor and at high concentrations is able to cause chloride ion infuse. Well-known toxic effects of a meprobamate overdose include central nervous system (CNS) depression, weakness, clonus and hyperactive reflexes, tachycardia, hypotension and respiratory depression. Meprobamate produces CNS-depressing symptoms [4]. Meprobamate intoxications are often serious and sometimes fatal (5%), resulting from haemodynamic disturbance and circulatory collapse, secondary to severe acute cardiac failure [3]. The mechanism of cardiac toxicity is unknown. An overdose of meprobamate results in coma, generally estimated by the Glasgow Coma Scale (GCS). Only one study, including few patients (n= 21), has evaluated the relationship between meprobamate plasmatic concentrations and GCS [5]. Classically, a nonsevere coma appears with meprobamate concentration between 60 and 120 mg l−1 and deep coma >120 mg l−1. We have studied the relationship between GCS and meprobamate plasma concentration in meprobamate intoxication and evaluated the pertinence of determining the meprobamate plasma level. We have reviewed all toxicological analyses made from January 2002 to September 2007. All patients with a plasma concentration of meprobamate higher than normal (>20 mg l−1) have been included. Blood samples were collected when the patient was admitted to the Emergency Department of the University Hospital. Meprobamate plasma concentrations and GCS were analysed. Meprobamate plasma concentrations were determined by a simplified, rapid and accurate gas chromatographic method [6], using a Delsi Instrument Series 30 gas chromatograph equipped with a flame ionization detector and split-splitless injection. GCS was classified into three groups: as severe group A (GCS 3–8); moderate group B (GCS 9–12); and mild group C (GCS 13–15). Statistical analysis was conducted using an analysis of variance (anova) and the Kruskal–Wallis test, with a level of significance P= 0.05. The research was conducted in compliance with the requirements of our Institutional Review Board. A total of 59 cases were collected. Mean age was 43 years (range 16–69) with a male : female ratio of 0.6. The mean plasma meprobamate concentration was 99.9 ± 13 mg l−1 (therapeutic range 10–25 mg l−1) with a maximal concentration of 271 mg l−1. Mean GCS was 7.1 ± 0.95 (range 3–15). The GCS partition was group A, n= 42; group B, n= 9; and group C, n= 8. In 87% of cases (n= 51), meprobamate had been ingested with concomitant drugs, mainly benzodiazepines (n= 35) or alcohol (n= 17). In 25 cases, the drug involved was the associated meprobamate/aceprometazine, brand name Mepronizine® in France. Meprobamate was the only drug detected in eight cases. Combination with tricyclic antidepressants was found in three cases. Concomitant ingestion of benzodiazepine was equally distributed among the three groups. Fifty-eight patients recovered. One fatal outcome was observed in a 57-year-old woman with a plasma level of meprobamate of 147 mg l−1, associated with a lethal concentration of propranolol of 1260 µg l−1, (therapeutic range 50–150 µg l−1). A high concentration of meprobamate was associated with low GCS (P= 0.0194) (Table 1). Table 1 Analysis by groups For patients with GCS = 3, meprobamate was detected in three cases, with a plasma concentration from 37 to 177 mg l−1. At a high level of consciousness (GCS = 15) a patient presented a meprobamate plasma concentration of 95 mg l−1. In the fatal case, the cause of death could not be attributed to meprobamate alone. According to the American Association of Poison Control Centers, propranolol is responsible for 71% of fatal β-blocker ingestion [7]. In our study, some interindividual variations were observed. Genetics differences have been studied only with carisoprodol. The study about CYP2C19 genotype and the pharmacokinetics of carisoprodol [8] concluded that there are no significant differences with respect to normal and nonfunctional CYP2C19 alleles in acute impairing effects of a single dose of carisoprodol. Conscious patients, with high meprobamate concentrations, are probably addicted to this drug. GCS, as a surrogate marker of meprobamate toxicity, is inferior to direct objective serum measurement and meprobamate levels, despite a high correlation based upon patient sample. Meprobamate concentration determination remains essential for the diagnosis of poisoning and ensures appropriate care of patients (electrocardiogram, intensive care). In our hospital, when meprobamate intoxication is suspected, we systematically determine the dosage of plasma meprobamate. This attitude may explain the absence of fatal outcomes.

Severe Meprobamate Intoxication: In Death as in Life?

n unusual case is presented where a toxicological investigation conducted in one laboratory was important for the proper interpretation of postmortem toxicology findings in the same person, in a different laboratory, seven months later. The first incident, a minor motor vehicle accident, involved a severe meprobamate intoxication in which the person's blood concentration was 98 mg/L. In the second incident, a fatal house fire, the postmortem blood meprobamate concentration was 96 mg/L. Knowledge of the first toxicological investigation and circumstances surrounding the matter aided interpretation of the postmortem toxicology findings: that the very high blood meprobamate concentrations probably resulted from chronic abuse of the drug and not from a suicidal overdose.

Interpretation of blood glutethimide, meprobamate, and methyprylon concentrations in nonfatal and fatal intoxications involving a single drug.

We evaluated blood concentrations of three nonbarbiturate sedative-hypnotics in 19 nonfatal (NF) and five fatal (F) intoxications which were "pure" (i.e. which involved only one drug each): glutethimide, 4 (NF), 3 (F); meprobamate, 9 (NF), 1 (F); and methyprylon, 6 (NF), 1 (F). For each of the 24 cases, both a comprehensive toxicology panel (including blood and urine) and the clinical history established that only a single drug had been ingested. Blood drug concentrations showed statistically significant correlation with the level of consciousness for nonfatal meprobamate intoxication (p less than 0.01) and nonfatal methyprylon intoxication (p less than 0.05). Blood glutethimide concentrations did not show such correlation. Death was associated with a mean blood glutethimide concentration in excess of 4.0 mg/dL, a blood meprobamate concentration of 20.5 mg/dL, and a blood methyprylon concentration of 11.7 mg/dL. Interpretation of blood concentrations of these compounds is discussed, and physical findings and demographic data are presented.

Meprobamateの慢性中毒にみられるてんかん様けいれん発作について

The present author has studied from various viewpoint 14 patients who had epileptiform convulsive disorders under choronic Meprobamate intoxication and 47 additional cases which were already reported in Japanese and other languages.1) There were no specific convulsive predi sposition and family history in the author's cases. Remarkable personality disorder of these cases were often seen in the peoples who addicted any drugs and others. They had no intellectual defect.2) Generally, convulsive seizure broke out when one took Meprobamate more than 3g daily over one to several years.3) In the literature, ev ery other author understood that these convulsive seizures had occured only as abstinence syndrom. It is certain that the majorities of these convulsions occur as abstinence syndrom but others occur during the intake of this drug. Delirium or disturbance of alertness also would develop likeweise. The present author differentiated four types regardig to the occurrence of convulsive seizure as well as the intake of this drug. A: Convulsion precipitated by abrupt withdrawal. B: Convulsion which occured during intake of this drug. C: Convulsion which occured under marked consciousness disturbance. D: Convulsion which occured particularly during the treatment of marked consiousness disturbance. Clinical types mentioned above were not always same in one patient.4) A lmost all the convulsive seizures appeared to be of epileptic nature but they often came out in the form of status epilepticus.5) Neurological signs and s ymptoms such as fever, nausea, vomiting, shaking and ataxia would frequently accompanied convulsions.6) Before and after convulsion, the r e was stormy consciousness disturbance which was certainly different from initial and postical twilight state. Convulsive seizures associated with fever and neurological symptoms and severe consciousness disturbance tend to have the form of status epilepticus. Therefore these signs and symtoms suggest some serious oragnic brain damage. In this regard, the present author discovered in the literatures three cases, of whom two died during status epilepticus and the other got into comatose with fever from delirium.7) EEG finding s showed convulsive readiness under Meprobamate abuse, so it is quite natural that the convulsive seizure appears even under its abuse. Moreover, some focal signs in EEG suggest localized damage.8) It was not effective to gi ve Meprobamate for the treatment of abstinence syndrome. When, once convulsion and related disorder happened to occur, such disorders would reoccur short after re-use of Meprobamate. However, if a patient does not fall in abuse again, another convulsive disorder does not occur and clinical outcome is very favourable, so that it is not necessary to prolong anticonvulsant medication. These convulsive disorders do not look over as accidental outbursts in the patient with convulsive predisposition or as rebound phenomena after long abuse of Meprobamate that has mild anticonvulsant action.

Resin Hemoperfusion For Acute Drug Intoxication

To the Editor.— In his latest contribution to the study of the treatment of severe drug intoxication, Dr Rosenbaum and associates 1 described ten hemoperfusions performed on eight patients. The procedure used a 650-gm column of Amberlite XAD-4 resin and was shown to be more effective than any known method of removing barbiturates and glutethimide from the blood of patients with drug overdoses. Previous publication by Rosenbaum and associates dating back to 1970 2-5 have established that this macroreticular resin is effective in the treatment of drug overdose with methaqualone, ethchlorvynol, and all intermediate and long-acting barbiturates or combinations thereof. No clinical data have been published regarding the effectiveness of this resin in the treatment of patients with meprobamate intoxication. We recently were asked to see a 35-year-old woman who had ingested 20 gm of meprobamate 12 hours prior to her transfer to Memorial Medical Center. During those first 12 hours

Accumulative prognostic index for patients with barbiturate, glutethimide and meprobamate intoxication.

Abstract To assess and update prognosis in a group of critically ill patients, repetitive measurements of physiologic status were made in 52 patients who were comatose and in shock after attempting suicide by ingesting large doses of barbiturate, glutethimide or meprobamate. Only three variables were needed to provide the prognostic information contained in all 25 variables measured. A momentary prognostic index, which estimates the patient's probability of survival on the basis of a single set of measurements, and an accumulative prognostic index, which takes into account previous sets of measurements, were derived. The accumulative prognostic index may provide a more realistic assessment of prognosis, for it de-emphasizes transient fluctuations in the patient's condition and emphasizes directional changes as a function of time. Formulas were derived that permit calculation of this index by the clinician with the use of a desk-top calculator.

Meprobamate Overdosage

Meprobamate intoxication is encountered frequently but is seldom a treatment problem. The relatively short duration of coma and low mortality are due to rapid endogenous metabolism of the drug. In most cases, only supportive therapy is needed. However, when intoxication is severe or is complicated by intercurrent illness or other drugs, treatment with forced diuresis or hemodialysis should be considered. In our experience, the best criteria of profound intoxication were the clinical state of the patient and a plasma meprobamate concentration approaching 20 mg/100 ml.

Meprobamate overdosage. Evaluation of its severity and methods of treatment

Meprobamate intoxication is encountered frequently but is seldom a treatment problem. The relatively short duration of coma and low mortality are due to rapid endogenous metabolism of the drug. In most cases, only supportive therapy is needed. However, when intoxication is severe or is complicated by intercurrent illness or other drugs, treatment with forced diuresis or hemodialysis should be considered. In our experience, the best criteria of profound intoxication were the clinical state of the patient and a plasma meprobamate concentration approaching 20 mg/100 ml.

Meprobamate poisoning treated by peritoneal dialysis

Summary A 2-year-old boy who accidentally ingested several drugs was successfully treated with peritoneal dialysis. Meprobamate was found to be dialyzable; and a peritoneal clearance, with a dialyzing volume of 500 ml., averaged 3.5 ml. per minute. Peritoneal dialysis appears to be a potentially useful technique in the treatment of meprobamate intoxication.

Treatment of meprobamate intoxication with the use of methyl phenidate: case report.

Treatment of meprobamate intoxication with the use of methyl phenidate: case report.

Death due to massive overdose of meprobamate.

This is the description of a case of acute meprobamate intoxication due to the ingestion of 47.6 grams of the drug with fatal outcome. We wish to emphasize that meprobamate should be used with the same careful consideration that any therapeutic agent deserves.

Withdrawal convulsions in dogs following chronic meprobamate intoxication.

Clinical evidence is accumulating that abrupt withdrawal of meprobamate (Miltown, Equanil) from patients who have been ingesting large amounts of this agent may be followed by major convulsions. Lemere 1 reported the case of a patient who had ingested 6.4 gm. of meprobamate daily for one month and had a convulsion 10 hours after discontinuation of the drug. Barsa and Kline 2 noted a single convulsion in 6 of 25 schizophrenic patients following withdrawal of meprobamate (2.4 gm. daily for nine months). Tucker and Wilensky 3 reported one grand mal seizure, following discontinuation of the drug, in 2 of 32 psychotic patients who had received 1.6 gm. of meprobamate, increasing to 4.8 gm., daily for three months. Two cases of this sort have also been observed at the U. S. Public Health Service Hospital, Lexington, Ky. 4 One patient, who had been taking 4.0 gm. of meprobamate daily for about