Auditory and electroencephalographic effects of midazolam and alpha-hydroxy-midazolam in healthy subjects.

Aims: Whereas cortical EEG effects of benzodiazepines are well characterized, information about benzodiazepine effects in other areas of the central nervous system is sparse. This study investigated the action of midazolam and its active metabolite alpha-hydroxy-midazolam on different parts of the auditory pathway in six healthy volunteers in a randomized, double-blind, three-way cross-over study.

Methods: Acoustically evoked short (SLP) and middle (MLP) latency potentials, transitory evoked otoacoustic emissions (TEOAE), and EEG power spectra were analysed after short i.

[Syncopes from the neurologic viewpoint].

A syncope is defined as a sudden, temporary loss of consciousness, associated with loss of postural tone with spontaneous recovery. The incidence is high and the differential diagnosis broad; therefore, the first observations are essential for the management of the patient. In this review diseases will be described which manifest themselves with syncopes that fall under the auspices of either internal medicine or neurology.

Evaluation of the efficacy and safety of flumazenil in the treatment of portal systemic encephalopathy: a double blind, randomised, placebo controlled multicentre study.

Background: Portal systemic encephalopathy (PSE) is a complex neuropsychiatric syndrome associated with hepatic failure. Small scale studies have shown the benzodiazepine receptor antagonist flumazenil to be effective in ameliorating PSE.

Aims: To determine the efficacy of flumazenil in patients with non-comatous mild to moderate PSE (stages I to III) due to severe chronic liver disease.

Effect of flumazenil on the electroencephalogram of patients with portosystemic encephalopathy. Results of a double blind, randomised, placebo-controlled multicentre trial.

The efficacy of the benzodiazepine antagonist flumazenil has been assessed clinically in a double blind, randomised, placebo-controlled multicentre study in patients with grade I-III portosystemic encephalopathy. In an ancillary study reported here the effect of flumazenil on the electroencephalogram (EEG) was analysed in 32 patients who had EEG grading according to protocol. Following the baseline observation period, patients were randomised to receive (at 1 min interval) 3 sequential bolus injections of flumazenil (0.

Prolonged sedation due to accumulation of conjugated metabolites of midazolam.

Midazolam is a short-acting benzodiazepine routinely used in intensive-care medicine. Conjugates of its main metabolite, alpha-hydroxymidazolam, have been shown to accumulate in renal failure but have not previously been related to the prolonged sedative effects commonly observed in critically ill patients. We report five patients with severe renal failure who had prolonged sedation after administration of midazolam.

[Therapy of epilepsy: trends and effectiveness of new anticonvulsants].

New antiepileptic drugs such as vigabatrin, lamotrigine, gabapentin, oxcarbazepine and felbamate have been lately marketed. This article provides an overview, showing known modes of action, pharmacokinetics, efficacy, tolerability, interactions and indications. A table showing selected data of antiepileptic drugs is included.

[Sodium valproate--still a current antiepileptic agent?].

In Switzerland valproate is in use as an anticonvulsant drug since 25 years. On this occasion we present a synopsis of the state of knowledge about its mechanism of action, pharmacokinetics, clinical efficacy, side effects, drug interactions, and administration with respect to special clinical situations.

Computed tomography and magnetic resonance imaging in epileptic seizures.

In epileptic seizures, the sensitivity of CT and MRI depends on different underlying pathologies and varies according to the age of the patient and the type of seizure. The different modalities are discussed in detail.

[Epilepsy in middle and older age].

Single fits and epileptic illness are more frequent in advanced age; their occurrence reaches the same frequency as in the neonatal period. Their origin and the possibilities of treatment are tightly connected to the process of ageing, a fact that requires special consideration. The main reasons for new epileptic attacks in the group of age 65 or more are structural changes, i.

[Confusional states following administration of short-acting benzodiazepines (midazolam/triazolam)].

The authors report about six patients, who after the intake of Midazolam or Triazolam suffered from an oneiroid-confusional state in which they carried out complex acts and for which an anterograde amnesia existed. In addition to these drugs, one female patient was under the influence of alcohol and one male patient of Bromazepam. Two of the patients suffered of emotional conflicts.

Risks and benefits of therapy with flumazenil (Anexate) in mixed drug intoxications.

Flumazenil, the first specific benzodiazepine (BZD) antagonist, is one of the most innovative drugs to become available within the last few years. Flumazenil is indicated for the reversal of the centrally depressant effects of BZDs, in BZD-induced anaesthesia, in BZD sedation in intensive care and in patients comatose after drug overdoses including BZDs. A conference of experts experienced in the treatment of mixed drug overdoses by various means, including flumazenil, was held in order to try to reach a consensus regarding the safe use of flumazenil in this indication.

[Diagnostic and therapeutic aspects of the initial epileptic seizure].

We present the concept of an 'epileptic syndrome' which is important for prognostic statements and the application of appropriate therapeutic measures. We then discuss the epileptic seizure and the assessment of suspected seizure, indications for admission to a hospital, diagnostic measures (EEG, CT scan, laboratory tests, lumbal puncture, MRI scan, PET scan, angiography), therapy and procedures for imminent status epilepticus. Finally, we try to answer the question whether anticonvulsant medication should be instituted after a first epileptic seizure.

Use of flumazenil in intoxicated patients with coma. A double-blind placebo-controlled study in ICU.

In a double-blind placebo-controlled prospective clinical trial we studied the efficacy and safety of the benzodiazepine antagonist, flumazenil. In 23 patients admitted to the Intensive Care Unit with coma due to overdose with benzodiazepines or other sedatives, flumazenil i.v.

Computed tomography, electroencephalography, and clinical features in the differential diagnosis of senile dementia. A prospective clinicopathologic study.

The accuracy of computed tomography, electroencephalography, and clinical features in the differential diagnosis of senile dementia was studied prospectively. Out of 50 demented patients, autopsy revealed 32 cases with either senile dementia of the Alzheimer's type (SDAT), multi-infarct dementia (MID), or a combination of both. Eighteen patients had dementia caused by other diseases.

[Epilepsy yesterday, today and tomorrow].

In this overview the current state of knowledge concerning epilepsy is presented: diagnosis, classification, etiology, pathogenesis and therapy. The change in these aspects during the past epochs of medical history is described. Suggestions as to future prospects are discussed.

Flumazenil (Anexate) in severe intoxication with carbamazepine (Tegretol).

In addition to the benzodiazepine antagonism we report, as a first observation, the effect of flumazenil on carbamazepine intoxication, where a mechanism other than benzodiazepine receptor antagonism must be supposed.

The clinical anti-convulsant effects of flumazenil, a benzodiazepine antagonist.

The clinical anti-convulsant effect of flumazenil in epilepsy has been demonstrated: (i) by acute i.v. administration under EEG control in an epileptic patient who had been previously heavily sedated with diazepam; (ii) in patients undergoing pharmaco-EEG studies whereby spike and wave counts were diminished following oral administration of 10 mg of flumazenil; and (iii) in a series of 27 epileptic patients treated chronically for periods of up to 42 months with flumazenil as monotherapy or as addition to basic therapy.

[Value of the EEG in the prognosis of post-anoxic coma following cardiocirculatory arrest].

The EEGs of 26 patients who remained at least 6 hours in coma after cardiovascular arrest were analyzed. The first EEG was recorded within few days after reanimation, classified in a 5-grade scale of increasingly severe impairment and compared with the final clinical outcome. On the basis of the present study and of a review of 408 EEG findings reported in similar investigations in the literature we conclude that the EEG can be useful in predicting the outcome of patients in postanoxic coma states: the EEG should be recorded at earliest 8-12 hours but within 2 days after reanimation, a barbiturate intoxication and hypothermia should be excluded.

Prognostic value of EEG in post-anoxic coma after cardiac arrest.

The authors themselves studied 26 patients. The EEGs were classified in terms of increasing severity in 5 categories. Incorporating over 400 cases from the literature, the authors correlated the initial EEG findings with the clinical outcome following cardiac arrest.

Benzodiazepine antagonist Ro 15-1788 in self-poisoning. Diagnostic and therapeutic use.

Thirteen patients with benzodiazepine overdosage received the specific benzodiazepine antagonist Ro 15-1788. Intravenous administration of 1.5 to 10 mg reversed the central nervous system depression induced by different benzodiazepine compounds within one to two minutes of injection.

Benzodiazepine antagonist (RO 15-1788) in ethanol intoxication: a pilot study.

In 1983, we reported on the excellent efficacy of the benzodiazepine antagonist RO 15-1788 in cases of acute intoxication with diazepam in intensive care medicine. Upon observing a positive effect in a patient who had taken alcohol as well as diazepam a study aiming at establishing the beneficial effect of RO 15-1788 in alcoholic intoxication was started. In the meantime, we discovered a significant amelioration of the cerebral disturbance in patients suffering from hepatic coma by the same benzodiazepine antagonist.

[Prolonged coma caused by diazepam sedation in ventilated patients. Diagnostic and therapeutic use of the benzodiazepine antagonist Ro 15-1788].

Repeated administration of diazepam in two ventilated patients had caused drug cumulation and coma over several days. In both cases central nervous depression could be demonstrated by the benzodiazepin antagonist Ro 15-1788 which induced reversal of coma. Estimation of plasma concentrations in a 70-year-old female patient 150 hours after the last administration showed a diazepam concentration of 437 ng/ml and a desmethyl-diazepam concentration of 483 ng/ml.