Early Combination Therapy of Ketamine and Midazolam in Patients with Refractory Status Epilepticus in Hemodynamic Unstable State
The use of anesthetics is inevitable to suppress seizure activity in refractory status epilepticus (RSE). Hypotension, which is a critical side effect observed when treating RSE using a higher dosage of anesthetics that enhance γ-aminobutyric acid (GABA) activity, often requires vasopressor agents. Concomitant treatment with N-methyl-D-aspartate (NMDA) receptor antagonists, such as ketamine, could be effective in prolonged refractory SE, while maintaining stable blood pressure owing to the blockage of catecholamine reuptake in the systemic circulation. We report two cases of patients who had RSE with hemodynamic instability treated promptly with an early combination of ketamine and low-dose midazolam. The combination treatment effectively suppressed epileptic discharge with less hemodynamic side effects; moreover, a low dose of midazolam was required when combined with ketamine therapy. The initial combination of a third-line therapy that blocks NMDA receptors with enhanced GABAergic activity could be useful in RSE. Further studies are necessary in many variable etiologies of SE.
Rhythmic sharp and waves on EEG disappeared within 24 hours of combination continuous midazolam and ketamine infusion, and autonomic dysfunctions were controlled. After continuous combination infusion for 48 hours, both regimens were tapered out with concomitant intravenous phenobarbital 20 mg/kg loading and a maintenance dose of 30 mg three times a day. Upon improvement of the EEG findings with recovered consciousness, the patient was treated with levetiracetam 750 mg, phenytoin 150 mg, lacosamide 150 mg, and phenobarbital 30 mg twice daily. The patient was successfully weaned off the ventilator on hospital day 8 and continued with physical therapy to return to her baseline (modified Rankin score improved from 5 to 1).
Conflicts of Interest
Conflict of Interest
The authors declare that they have no conflicts of interest.