Neurology India Medknow Publications on behalf of the Neurological Society of India ISSN: 0028-3886 EISSN: 1998-4022 Vol. 52, Num. 3, 2004, pp. 394-396

Neurology India, Vol. 52, No. 3, July-September, 2004, pp. 394-396

Letter To Editor

Intravenous valproate in post-anoxic myoclonic status epilepticus: A report of ten patients

Patel R, Jha S

Department of Neurology, Sanjay Gandhi PGIMS, Lucknow

Correspondence Address:Department of Neurology, Sanjay Gandhi PGIMS, Lucknow
sjha@sgpgi.ac.in

Code Number: ni04133

Sir,
Post-anoxic myoclonic status epilepticus (MSE) is difficult to treat. Valproate (VP) is an established antiepileptic drug (AED) with broad-spectrum efficacy in generalized and partial seizures.[1],[2] Clinical trials with intravenous VP have shown encouraging results in myoclonic epilepsy and status epilepticus.[3],[4] Intravenous VP has been shown to be effective in terminating MSE in a patient with juvenile myoclonic epilepsy.[5] We present our observations on the effect of intravenous VP in post-anoxic MSE.

We studied the efficacy of intravenous VP in 10 patients who developed MSE following anoxic cerebral injury in the peri- and postoperative (within 24-48 hrs) period. The clinical details, the primary disease for which the operation was done, and the type of anesthesia were recorded in all the patients. Informed consent was taken from the relatives for the drug administration. Initial loading dose of VP was 20 mg/kg at a rate of 20 mg/minute. This was followed by 10mg/kg bolus every 6 hours for 24 hours (the total dose in the first 24 hours: 60 mg/kg). Patients were then given a maintenance dose of 10 mg/kg every 6 hours till the patient was shifted to oral VP.[6],[7] The infusion was continued till MSE was terminated. The frequency of seizures and the time taken for the termination of MSE were noted. Metabolic (hepatic, renal and pancreatic function tests), hemodynamic (heart rate, blood pressure, respiratory rate and electrocardiographic changes) and hematological parameters were monitored. Arterial blood gases and oxygen saturation were also monitored. Serum valproate levels were not measured.

The clinical characteristics of the patients are given in [Table - 1]. There was a significant reduction in the frequency of seizures in all the 10 patients. MSE was terminated with intravenous VP alone in 6 patients and the time duration for the termination of MSE ranged between 2-10 hours. Four patients needed 30 mg/kg and 2 patients needed 40 mg/kg of VP to terminate MSE. An additional infusion of a second AED, intravenous diazepam or lorazepam, one each was required in 2 patients to terminate MSE. The time taken for the termination of MSE was 26 and 38 hours. The remaining 2 patients continued to have seizures, but with a reduced frequency (approx 25% reduction). During intravenous VP therapy, no adverse effects, including reaction at the infusion site, respiratory depression, cardiac arrhythmia or hypotension were observed. There was no change in hemodynamic parameters. Two patients died. Six patients recovered completely and 2 patients were left with significant neurological deficits. [Figure - 1a] [Figure - 1b]

Introduction of the parenteral form has facilitated the use of VP in situations like seizures in the operative or postoperative phase.[3],[5] Several advantages are evident with intravenous VP: a physiological pH, ready-to-use preparation, non-requirement of any organic solvent, no incompatibility with other intravenous solutions and high stability at room temperature.[8],[9] A high success rate of intravenous VP has been observed in various studies.[10],[11] Excellent control of myoclonus in a patient after cardio-pulmonary arrest, with intravenous VP has also been documented when other antiepileptics had failed.[12],[13] Similar results have been described in post-anoxic myoclonus.[13] It is well tolerated and safe in children with refractory epilepsy and in the elderly, even in the setting of concurrent hypotension, labile cardiovascular function or severe illness.[14],[15] Though the Food and Drug Authority recommends an infusion rate of 20 mg/min of intravenous VP, excellent tolerability has been reported with higher rates.[15]

Anoxic brain injury and MSE are life-threatening and notoriously refractory to AEDs. Their long duration is associated with poor outcome and high mortality, hence must be treated promptly. The available conventional intravenous AEDs may induce or exacerbate hypotension and cause respiratory depression requiring intensive monitoring. Hypotension associated with intravenous AED administration may adversely affect the general cardiovascular status by limiting the timely and adequate delivery of the AEDs (since these complications have to be managed by slowing the infusion rate).[14],[16] The mechanism postulated for the efficacy of intravenous VP is rapid penetration of the drug into the brain tissue.[8],[17] Recently, levetiracetam has been found to be effective in myoclonic epilepsy, which may emerge as an alternative therapy.[18]

Our observations with intravenous VP in post-anoxic MSE are preliminary and the study has many limitations. Continuous EEG monitoring was not done and serum valproate levels were not measured. Larger, multicentric and controlled studies are required for intravenous VP to be considered as first- line therapy for post-anoxic MSE.

REFERENCES

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