SUCCESSFUL MANAGEMENT OF SEIZURES BY PROPHYLACTIC MIDAZOLAM DURING A CONCOMITANT ADMINISTRATION OF CARBAPENEM AND VALPROATE

Objectives: We have previously reported that the plasma concentration of valproate (VPA) was profoundly suppressed by a concomitant administration of carbapenem, beta-lactam antibiotic.

Methods: We report here the successful management of seizures by prophylactic continuous infusion of midazolam during a concomitant use of a carbapenem with valproate in a patient with severe epilepsy complicated by pneumonia.

Results: The patient was 23-years-old male with spastic quadriplegia, epilepsy and mental retardation resulting from the epileptic encephalopathy in childhood. His intractable seizures had been well controlled by VPA, phenytoin and carbamazepine. He was admitted to our hospital for the further evaluation of recurrent esophagitis. After the fiberscopic examination, he developed pneumonia due to pseudomonas aeruginosa: intravenous administration of cefepime and minomycin resulted in no improvement. According to the result of sensitivity test, antibiotics were changed to meropenem (MEPM), a newly developed carbapenem, and fosfomycin. Intravenous midazolam was continuously infused in order to prevent the recurrence of intractable seizure during the treatment of MEPM. He recovered fully by this agent: despite the drastic fall in plasma concentration of VPA (from 52 ìg/ml to 16 ìg/ml) during MEPM, he didn't develop seizures. Four months later, he developed pneumonia due to pseudomonas aeruginosa and was treated with MEPM without midazolam infusion: his plasma concentration of VPA was profoundly suppressed resulting in generalized tonic seizures. His seizure was successfully controlled by continuous infusion of midazolam.

Conclusion: In conclusion, continuous infusion of prophylactic midazolam appears to be useful for management of seizures when the concomitant use of carbapenem and VPA is unavoidable.