Midazolam In Status Epilepticus Research Articles

Midazolam as an anticonvulsant antidote for organophosphate intoxication--A pharmacotherapeutic appraisal.

This review summarizes the therapeutic potential of midazolam as an anticonvulsant antidote for organophosphate (OP) intoxication. Benzodiazepines are widely used to treat acute seizures and status epilepticus (SE), a neurologic emergency of persistent seizures that can lead to severe neuronal damage or death. Midazolam is a benzodiazepine hypnotic with a rapid onset and short duration of action. Midazolam is considered the new drug of choice for persistent acute seizures and SE, including those caused by neurotoxic OPs and nerve agents. Midazolam is a positive allosteric modulator of synaptic γ-aminobutyric acid (GABA)A receptors in the brain. It potentiates GABAergic inhibition and thereby controls hyperexcitability and seizures. Midazolam is administered intravenously or intramuscularly to control acute seizures and SE. Due to its favorable pharmacokinetic features, midazolam is being considered as a replacement anticonvulsant for diazepam in the antidote kit for nerve agents. Clinical studies such as the recent Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART) trial have confirmed the anticonvulsant efficacy of midazolam in SE in prehospital settings. In experimental models, midazolam is effective when given at the onset of seizures caused by nerve agents. However, benzodiazepines are less effective at terminating seizures when given 30 min or later after OP exposure or seizure onset, likely because of internalization or downregulation of synaptic, but not extrasynaptic, GABAA receptors, which can lead to diminished potency and seizure recurrence.

Blood concentrations of midazolam in status epilepticus using an appropriate condition of HPLC

The aim of the present study was to determine an index to evaluate the efficacy and safety of midazolam (MDZ) to treat status epilepticus (SE). An original system was therefore developed to measure blood concentrations of MDZ and 1-hydroxymidazolam (1-OHMDZ) as the main metabolite on high-performance liquid chromatography. This system was established through inspection of chromatograms, calibration curves and coefficient of correlations of MDZ. The clinical course of 11 SE patients, ranging from 4 months to 10 years of age, are described. These patients were treated with MDZ and measured at each blood concentration of MDZ. Moreover, patients were evaluated on cranial computed tomography and magnetic resonance imaging and video electroencephalogram (EEG), and it was determined that their seizures disappeared in accordance with the disappearance of convulsions and interictal EEG findings. Reproducibility was good with this system. The standard curves of MDZ and 1-OHMDZ were almost straight, and the correlation coefficients of MDZ and 1-OHMDZ were r = 0.9999 and r = 0.9998, respectively. The convulsions in nine of 11 SE patients disappeared without side-effects and the blood concentrations of MDZ in all the patients were measured. The mean peak blood concentrations of MDZ and 1-OHMDZ were higher than those reported in other studies. The clinical utility of this system has been demonstrated. An index to evaluate the efficacy and safety of MDZ is necessary, and MDZ blood concentrations measured on the present original precise measuring system could help in establishing a plan to successfully treat SE.

Burst suppression on amplitude‐integrated electroencephalogram may be induced by midazolam: a report on three cases

Continuous amplitude-integrated electroencephalogram (aEEG) recording with a cerebral function monitor is a useful tool to evaluate prognoses following perinatal asphyxia in term infants. Drugs may change the pattern of the conventional EEG. This report presents three infants treated with midazolam for status epilepticus and repetitive seizures who proved resistant to other anticonvulsants (phenobarbitone, lidocaine). The infants developed burst suppression patterns on aEEG concurrent with high serum levels of midazolam (900-7093 microg l(-1)). Following discontinuation of midazolam treatment, serum levels normalized and background patterns returned to normal voltage traces. These findings indicated that midazolam can cause burst suppression on aEEG. Therefore, the prognostic value of aEEG is limited in case of high serum levels of midazolam. Serum levels of midazolam should be measured in infants who have burst suppression patterns on aEEG during midazolam treatment.

Intranasal Midazolam in Patients With Status Epilepticus

The patient in status epilepticus presents many challenges to the emergency physician. IV access is frequently difficult to achieve, and prolonged attempts at access can jeopardize the patient and endanger the caregiver. We present two cases in which the administration of intranasal midazolam appeared to successfully terminate status epilepticus. No adverse effects were noted. Studies are needed to clarify the safety, optimal dosing, and clinical utility of this treatment modality. [Kendall JL, Reynolds M, Goldberg R: Intranasal midazolam in status epilepticus. Ann Emerg Med March 1997;29:415-417.]