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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During a nine-month period we have treated 46 patients with status epilepticus with intravenous application of diazepam or midazolam. The initial doze od diazepam was 10 mg (rate: 2-5 mg/min) and of midazolam 15 mg (rate: 5 mg/min). Diazepam was effective in 26 and ineffective in 15 patients. Midazolam stopped status in 4 out of 7 patients. Both drugs were more effective when they were administered at the beginning of status. After the initial termination of status and recovering of consciousness, seizures returned in 10 patients (22%). In the group treated with diazepam, 4 patients had sudden apnea and 6 respiratory depression (totally 10 out of 41). In the group treated with midazolam, 3 had apnea and 2 respiratory depression (totally 5 out of 7). All patients with apnea or respiratory depression received higher doses of both drugs at the higher rates than the others. We conclude that the efficacy of the therapy is moderate while the frequency of serious complications is high. In status epilepticus, where the life of patient is in danger, drugs with such activity are of limited value.
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PMID:[Efficacy of therapy, recurrence of seizures and respiratory complications in the treatment of status epilepticus by intravenous administration of diazepam or midazolam]. 130 8

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.
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PMID:Flumazenil in mixed benzodiazepine/tricyclic antidepressant overdose: a placebo-controlled study in the dog. 158 24

The anticonvulsant effects and duration of protective action of midazolam against Metrazol induced seizures were studied in 528 rats aged 7,12,18,25 and 90 days. The doses of 0.025, 0.05, 0.25, 0.5 and 1.0 mg/kg were administered immediately before Metrazol (100 mg/kg in all but 18-day-old animals where 90 mg/kg were given) for detection of antimetrazol activity at all age groups. The doses of 0.05, 0.25, and/or 0.5 mg/kg were used to study the time course of the protective action of midazolam. Each experimental group consisted of eight animals. Dose-dependent antimetrazol effects of midazolam till now described only in adult animals were demonstrated at all developmental stages studied. There were no qualitative differences in these effects among age groups studied. Midazolam action was better expressed against major Metrazol seizures than against minimal Metrazol seizures. Duration of the protective action depended on the dose tested at all developmental stages, as a rule, lasted longer in young animals than in adult rats. Only quantitative changes of action were found.
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PMID:The effect of ontogenetic development on the anticonvulsant activity of midazolam. 158

In an open, prospective clinical trial, midazolam anaesthesia was compared with thiopental (plus suxamethonium chloride as a muscle relaxant) to clinically evaluate the former as an anaesthetic and a muscle relaxant during electroconvulsive therapy (ECT). Twelve depressed patients underwent a course of ECT, receiving midazolam or thiopental anaesthesia alternatively. Significant differences were found in seizure duration between the two anaesthetics. Midazolam shortened the seizures to a duration that was not therapeutically desirable. There were no differences in stimulus parameters between the two groups. The muscle relaxant effect of midazolam failed to provide optimal paralysis. Thus, midazolam anaesthesia offers no advantage over standard anaesthetic agents for ECT.
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PMID:Midazolam shortens seizure duration following electroconvulsive therapy. 161 82

Midazolam (Versed), the first water-soluble benzodiazepine, has had widespread acceptance as a parenteral anxiolitic agent. Its antiepileptic properties were studied in adult patients with good results. Midazolam was administered intramuscularly to 48 children, ages 4 months to 14 years, with 69 epileptic episodes of various types. In all but 5 epileptic episodes, seizures stopped 1-10 min after injection. These results suggest that midazolam administered intramuscularly may be useful in a variety of epileptic seizures during childhood, specifically when attempts to introduce an intravenous line in convulsing children are unsuccessful.
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PMID:Midazolam in treatment of epileptic seizures. 162 19

The effect of intrathecal administration of antiepileptic drugs on electroshock-induced convulsions (maximal electroshock seizure, MES test) was investigated in an experimental study in rats. Drugs tested were phenobarbital sodium (50-800 micrograms), sodium valproate (50-6,400 micrograms) and midazolam (50-250 micrograms), delivered into the cerebrospinal fluid via a catheter placed in the upper cervical intrathecal space. Control animals were tested with saline. The animals were tested in the MES test 30 min after drug administration. Phenobarbital sodium showed a dose-related protective effect on the tonic phase of the convulsion, with a 50% effect at a dose of 200 micrograms. Sodium valproate showed a less protective effect, even when reaching doses that produced neurological symptoms. Midazolam protected at a high dose but produced a severe decrease in motor activity. The results indicate the feasibility to treat experimental convulsions by means of intrathecal injection of antiepileptic drugs.
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PMID:Intrathecal antiepileptic drugs in experimental epilepsy. 181 35

Generalized tonic-clonic seizures are a neurologic emergency. Duration of ictal activity has been associated with neurologic sequelae. The purpose of this study was to determine if midazolam, a short-acting benzodiazepine, could effectively ablate ictal activity in an animal model without significant cardiorespiratory compromise. Ten domestic swine (10 to 20 kg) were ventilated and hemodynamically monitored. Bifrontal craniotomies were performed and electrocortical activity was recorded throughout the experiment. Pentylenetetrazol (100 mg/kg) was administered iv to induce seizures. Midazolam (0.1 mg/kg) was administered iv and serum levels were drawn at 1, 2, 5, 10, 15, and 20 min after administration. There was no significant difference between the baseline and postmidazolam vital signs. Seizure activity was seen periodically as generalized spikes, as well as individual spikes for 29 +/- 5 sec after midazolam administration. A period of attenuation of 24 +/- 7 sec was seen before returning to baseline electrocortical activity. Our study demonstrates that midazolam effectively ablated induced ictal activity without significant cardiorespiratory depression and with similar EEG effect as other benzodiazepines.
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PMID:Intravenous midazolam suppression of pentylenetetrazol-induced epileptogenic activity in a porcine model. 210 74

We have recently detected low basal levels of c-fos protein-like immunoreactivity in adult mammalian neurons. Here we report that generalized tonic-clonic seizures in mice are associated with a massive increase in c-fos protein-like immunoreactivity in the cingulate and piriform cortices and the dentate gyrus 1 h after injection of pentylenetetrazol. Midazolam, which prevented the pentylenetetrazol seizures also prevented the increase in c-fos protein-like immunoreactivity. These results suggest that seizure activity induces the formation of c-fos proteins in selective brain regions, and raise the possibility that c-fos proteins play as yet undetermined physiological and/or pathological roles in the mature brain.
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PMID:Generalized seizures induce c-fos protein(s) in mammalian neurons. 244 34

Midazolam meleate, a water soluble 1,4 benzodiazepine, was used intravenously in 20 patients suffering seizures, of whom 12 were in status epilepticus. In all cases, midazolam in a dose of 2.5-15 mg rapidly terminated the seizure. There were no complications from the use of midazolam. The causes of the seizures were varied but alcohol-withdrawal seizures were the single largest cause. Thirteen patients were taking some form of anticonvulsant medication but only three were in the therapeutic range. Midazolam is seen to be an effective agent in the emergency treatment of seizures.
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PMID:Midazolam: an effective intravenous agent for seizure control. 368 42

In the past decade, several new antiepileptic drugs have been tested. Most recently, 5 new antiepileptic drugs have been launched onto European and US markets. These include vigabatrin, oxcarbazepine and lamotrigine in Europe, and felbamate and gabapentin in the US. In addition to these, 3 additional drugs are in the clinical investigational stage: flunarizine, fosphenytoin and stiripentol. A fourth agent is midazolam, which was originally introduced in 1986, but recently has shown effectiveness in the treatment of status epilepticus. Flunarizine is a selective calcium channel blocker that has shown anticonvulsant properties in both animal and human studies. It is a long-acting anticonvulsant that clinical studies have shown to have effects similar to those of phenytoin and carbamazepine in the treatment of partial, complex partial and generalised seizures. Fosphenytoin was developed to eliminate the poor aqueous solubility and irritant properties of intravenous phenytoin. It is rapidly converted to phenytoin after intravenous or intramuscular administration. In clinical studies, this prodrug showed minimal evidence of adverse events and no serious cardiovascular or respiratory adverse reactions. It may have a clear advantage over the present parenteral formulation of phenytoin. Midazolam is a benzodiazepine that is more potent than diazepam as a sedative, muscle relaxant and in its influence on electroencephalographic measures. It has been shown to be an effective treatment for refractory seizures in status epilepticus. Stiripentol has anticonvulsant properties as well as the ability to inhibit the cytochrome P450 system. There are significant metabolic drug interactions between stiripentol and phenytoin, carbamazepine and phenobarbital (phenobarbitone). Stiripentol has been studied in patients with partial seizures, refractory epilepsy and refractory absence seizures with some efficacious results.
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PMID:New anticonvulsant drugs. Focus on flunarizine, fosphenytoin, midazolam and stiripentol. 752 21


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