Efficacy and Safety of Ketamine in Refractory/Super-refractory Nonconvulsive Status Epilepticus: Single-Center Experience

Refractory/super-refractory nonconvulsive status epilepticus (r/srNCSE) is an acute life-threatening neurocritical entity with significant morbidity. Failure to control SE in its earlier stages leads to multiple molecular alterations in the brain such as downregulation of GABA-A and upregulation of NMDA receptors. Recently ketamine, an NMDA receptor antagonist, has gained increased attention as a therapeutic choice in controlling refractory/super-refractory SE. We aimed to analyze the efficacy and safety profile of ketamine in our center. We retrospectively identified all the patients with nonconvulsive SE who received ketamine during their follow-up in our neurological intensive care unit between 2009 and 2019. Information about demographic, clinical, and laboratory findings; concurrent antiseizure and anesthetic medications; time of initiation, dose and duration of ketamine infusion; any adverse effects and finally prognosis were collected. The effect of day of ketamine initiation and duration of infusion on ketamine efficacy were analyzed statistically. Seven patients (4 males, 3 females; age: 44-86 years) were included in the study. Encephalitis was the most common etiology. Concurrent antiseizure medications varied between 2 and 5. Six patients received midazolam before/during ketamine infusion. Ketamine was initiated 2 to 7 days after the onset of EEG monitoring and lasted 3 to 24 days with a maximum infusion dose ranging between 1 to 5 mg/kg/h. It was definitely effective in 4 patients, and possibly effective in an additional patient. Earlier initiation was correlated with higher efficacy ( P = .047). There was a trend toward higher efficacy with longer duration of infusion ( P = .285). Overall prognosis was poor with 29% mortality rate. Temporary hepatic failure occurred in 1 patient. Ketamine appears to be a promising drug in r/srNCSE. Earlier and prolonged infusion, as well as combination with benzodiazepines may increase its efficacy. Adverse events are rarely observed.

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Nonconvulsive Status Epilepticus after Subarachnoid Hemorrhage

Neurosurgery ◽

10.1097/00006123-200211000-00006 ◽

2002 ◽

Vol 51 (5) ◽

pp. 1136-1144 ◽

Cited By ~ 142

Author(s):

Lyle J. Dennis ◽

Jan Claassen ◽

Lawrence J. Hirsch ◽

Ronald G. Emerson ◽

E. Sander Connolly ◽

...

Keyword(s):

Status Epilepticus ◽

Subarachnoid Hemorrhage ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Neurological Deterioration ◽

Nonconvulsive Status Epilepticus ◽

Neurological Intensive Care Unit ◽

Computed Tomographic ◽

Neurological Intensive Care ◽

Electrographic Seizures ◽

Prolonged Coma

Abstract OBJECTIVE Although in-hospital seizures have been reported for 3 to 24% of patients with aneurysmal subarachnoid hemorrhage (SAH), nonconvulsive status epilepticus (NCSE) has not been previously described. We sought to determine the frequency and clinical features of NCSE among comatose patients with SAH. METHODS Between November 1997 and February 2000, we performed continuous electroencephalographic (cEEG) monitoring for at least 24 hours for all patients with aneurysmal SAH who were treated in our neurological intensive care unit and exhibited unexplained coma or neurological deterioration. NCSE was diagnosed when cEEG monitoring demonstrated continuous or repetitive electrographic seizures exceeding 1 hour in duration. Refractory NCSE was treated aggressively with intravenous anticonvulsant administration and continuous-infusion midazolam therapy. RESULTS Of 233 patients with SAH who survived the first 48 hours of hospitalization, 101 were stuporous or comatose at some point during their hospitalization. Twenty-six of those patients underwent cEEG monitoring, and eight were diagnosed as having NCSE, an average of 18 days (range, 5–38 d) after SAH. All eight patients were receiving prophylactic anticonvulsant therapy. Four patients were persistently comatose and four demonstrated deterioration to stupor or coma; only one exhibited overt tonicoclonic activity. A worst Hunt and Hess grade of IV or V, older age, ventricular drainage, and cerebral edema on computed tomographic scans were identified as risk factors for NCSE (all P < 0.01). NCSE was successfully terminated for five patients (63%), but only one experienced clinical improvement, which was transient; all eight patients eventually died after a period of prolonged coma. CONCLUSION cEEG monitoring detected NCSE for 8% of patients with SAH and otherwise unexplained coma or neurological deterioration. The seizures were highly refractory to therapy, and the prognosis for these patients was extremely poor. Routine postoperative cEEG monitoring of patients with SAH who are at high risk for NCSE, allowing earlier diagnosis and treatment, offers the best chance of improving the outcomes for patients with this disorder.

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