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Biomedical subjects

R Askenasi

Publications and source records attributed to R Askenasi.

At least 19 recordsLinked to original sources
PubMed1992

Flumazenil in mixed benzodiazepine/tricyclic antidepressant overdose: a placebo-controlled study in the dog.

This study evaluates the cardiac and neurologic risks associated with the antagonization of the benzodiazepine component of mixed drug overdoses, when cyclic antidepressants are also implicated. Twenty-four mongrel dogs were anesthetized and ventilated. Electroencephalogram, electrocardiogram, and tidal carbon dioxide and arterial pressure were continuously recorded. Amitriptyline (1 mg/kg/min) associated with midazolam (1 mg/kg + 1 mg/kg/h) was infused in 12 of the dogs. Midazolam was replaced by saline in the other 12. Drug administration was continued until signs of cardiotoxicity (QRS prolongation greater than 120 milliseconds or sustained arrhythmias) occurred. At that moment, midazolam effects were suddenly reversed by administration of flumazenil 0.2 mg/kg in six dogs out of each group. Placebo was administered in the others. Reactions were observed for the next 120 minutes. Midazolam-induced sedation efficiently protects (P less than .02) against seizures due to amitriptyline toxicity. This protective effect is counteracted by flumazenil. Midazolam has limited influence on the cardiac toxic effects of amitriptyline. The bolus of flumazenil is, however, associated with a significant worsening of electrocardiogram disturbances, and two sudden deaths were recorded. The mechanism of this effect remains unclear, as it could be unrelated to the antagonization of midazolam sedation. Given the problem of extrapolating animal data to humans, these results suggest that bolus administration of high doses of flumazenil in mixed intoxication implicating benzodiazepine and cyclic antidepressants has the potential to precipitate convulsions and/or arrhythmias. A slowly titrated administration of the antidote, as usually recommended, could prevent these effects.

Amitriptyline↗
PubMed1992

Predicting severity of tricyclic antidepressant overdose.

The measurement of plasma concentration, a prolonged QRS interval, and level of consciousness have all been recommended as useful indicators of toxicity following tricyclic antidepressant overdose. The aims of this study were firstly, to determine the relative prognostic value of each of these indicators and secondly, to assess when a patient can be discharged safely from the intensive care unit. Data were evaluated on 67 patients with tricyclic antidepressant overdose from four centers. Plasma tricyclic antidepressant concentrations were measured, coma grade was evaluated using the Matthew-Lawson Coma Scale and a ECG was obtained from 23 patients on admission. Complications such as convulsions, hypotension, arrhythmias, and need for intubation and ventilation were recorded. Thirty patients developed complications and no patient died. Coma grade was the best predictor of outcome. The development of serious complications is unlikely in patients whose level of consciousness is grade II or less and who are admitted to hospital more than 6 h after overdose. Plasma tricyclic antidepressant concentration was of no additional value in predicting toxic complications or deciding when the patient could leave the intensive care unit. Our study suggests that an alert and orientated patient with a QRS duration less than 100 ms is the best indicator for safe transfer to a medical or psychiatric ward.

Adolescent↗
PubMed1992

Risks of flumazenil in mixed benzodiazepine-tricyclic antidepressant overdose: report of a preliminary study in the dog.

This preliminary study evaluates the cardiac and neurological risks associated with the sudden antagonism of benzodiazepine (BZD)--induced sedation in dogs intoxicated with tricyclic anti-depressants (TCA). Twelve dogs were anesthetized with midazolam and ventilated with room air. EEG, ECG, and arterial pressure were continuously recorded. An infusion of amitriptyline (6 dogs) or clomipramine (6 dogs) 1 mg/kg. min was maintained until signs of cardiotoxicity (QRS prolongation, hypotension or arrhythmias) occurred. The effects of a bolus of flumazenil 0.2 mg/kg were then observed until 120 minutes. In amitriptyline poisoning, BZD reversal was associated with development of convulsions in 3 dogs, with severe arrhythmias in 4 and with one death. In clomipramine intoxication, 2 dogs developed sudden fatal arrhythmias. These results show that BZD reversal may unmask the convulsant properties and increase the severity of arrhythmias induced by TCA.

Amitriptyline↗
PubMed1991

Efficacy of flumazenil in acute alcohol intoxication: double blind placebo-controlled evaluation.

Flumazenil acts as an antidote for pharmacological and toxic effects due to benzodiazepines. Several isolated observations and short uncontrolled series have also suggested a possible effect against the impairment of consciousness induced by pure alcohol intoxication. Patients admitted in the emergency department with coma related to acute alcohol (ALC) or pure benzodiazepine (BZD) intoxication were randomized and treated blindly with either placebo or 1 mg flumazenil. A modified Glasgow score was used to observe the evolution of consciousness. In the 18 ALC patients, 1 mg flumazenil was not more effective than placebo, whereas it appeared to be very active in the BZD group. However, an open administration of higher doses of flumazenil (2-5 mg) in 11 ALC patients, whose condition had not initially improved, was followed by clear improvement of consciousness in five of them. Flumazenil, administered at a dose usually active against BZD sedation, does not improve CNS depression induced by ALC intoxication. Higher doses could be more effective in some patients, but it should also be verified in a placebo-controlled trial.

Adolescent↗
PubMed1990

Current status of antidotal therapies in acute human intoxications.

The purpose of this work is a review of usefulness, indications and handling of some antidotes which are at our disposal for therapeutic use since several years, especially naloxone, flumazenil, Fab fragments of digoxin specific antibodies, hydroxocobalamine, 4-methyl-pyrazole, N-acetylcystein or the new metal chelators. Older clinically relevant substances are also reviewed.

Acute Disease↗
PubMed1990

Zolpidem intoxication mimicking narcotic overdose: response to flumazenil.

Zolpidem is a recently introduced sleep-inducer which is thought to act on the central-type benzodiazepine receptors. This observation is the first report of drug poisoning with this compound. The toxic response was characterized by the development of a profound but short-lasting coma, associated with pin-point pupils and respiratory depression, as observed in a narcotic overdose. These clinical signs were not influenced by the administration of naloxone, but responded dramatically to flumazenil. Some analytical data on zolpidem toxicokinetics are presented.

Adult↗
PubMed1988

Specific treatment of benzodiazepine overdose.

Intentional benzodiazepine (BZD) overdose is usually a benign condition frequently encountered in the emergency department of hospital. Twenty-one patients, who were suspected of BZD overdose, were treated with the antagonist of the central type BZD-receptors Ro 15-1788. Samples for toxicological analysis were taken before and after treatment. The patients were divided into three groups. In the first group (pure BZD overdose, n = 9), rapid and complete awakening was observed in all the patients (9/9) with 3.5 +/- 1.5 mg Ro 15-1788. In the second group of patients with multiple drugs poisoning (including BZD, n = 6), CNS depression improved in all the patients despite incomplete awakening. In the last group (n = 6), where no BZD were detected in toxicological samples, none of the comatous patients improved significantly during Ro 15-1788 administration, except one patient with pure ethanol intoxication. No undesirable effects are reported, except mild transitory withdrawal syndrome in three cases following rapid injection. This study supports the introduction of Ro 15-1788 as a useful antidote in the diagnosis and the treatment of drug-induced coma.

Adult↗
PubMed1988

Activated charcoal in tricyclic antidepressant poisoning.

Tricyclic antidepressants (TCA) bind to activated charcoal both in vitro and in vivo in healthy volunteers after a therapeutic dose of TCA. These findings provide a basis for the routine use of activated charcoal in TCA poisoning. The object of this study was to examine the effect of a single dose of 20 g of activated charcoal in overdose patients. Ninety-one patients from four centres with suspected TCA overdose were entered into a randomized study. Gastric lavage was performed on all patients. Thirty-four received 20 g of activated charcoal and 43 served as controls. Fourteen patients were excluded. Plasma drug concentrations were taken on admission and at 1, 2, 4, 8 and 24 h. The incidence of toxic symptoms was registered during 24 h. There was no significant difference in the area under the plasma drug concentration versus time curve, the peak plasma concentrations or plasma half-lives between the two groups. Toxic symptoms were more frequent in the non-treated groups although this difference was not statistically significant. In patients with TCA overdose initially treated with gastric lavage, a single dose of 20 g of activated charcoal had no effect on the systemic absorption or elimination of TCA.

Antidepressive Agents, Tricyclic↗
PubMed1987

Omental panniculitis: an unusual cause of acute appendiceal syndrome.

We report the case of a 41-year-old patient with no history of abdominal symptoms who presented with an acute painful syndrome of the right flank and iliac fossa suggesting acute appendicitis. The diagnosis of panniculitis of the great omentum was suggested preoperatively by the particular aspect of omental fat observed by abdominal sonography and computed tomography. A subvoval omentum resection was performed and the outcome was uneventful.

Adult↗
PubMed1986

Pneumococcal cellulitis.

A 42-year-old man with pneumonia was admitted for rhabdomyolysis. Streptococcus pneumoniae was isolated from the cellulitis surrounding the muscular necrosis. Subcutaneous localisation of S. pneumoniae in the course of a septicemia has never been described, although rhabdomyolysis may be associated with bacterial infections.

Adult↗