Refractory and Super-refractory Status Epilepticus

Context: Refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE) are neurological emergencies withconsiderable mortality and morbidity. In this paper, we provide an overview of causes, evaluation, treatment, and consequences of RSEand SRSE, reflecting the lack of high-quality evidence to inform therapeutic approach. Sources: This is a narrative review based onpersonal practice and experience. Nevertheless, we searched MEDLINE (using PubMed and OvidSP vendors) and Cochrane centralregister of controlled trials, using appropriate keywords to incorporate recent evidence. Results: Refractory status epilepticus iscommonly defined as an acute convulsive seizure that fails to respond to two or more anti-seizure medications including at least one non-benzodiazepine drug. Super-refractory status epilepticus is a status epilepticus that continues for ≥24 hours despite anesthetic treatment,or recurs on an attempted wean of the anesthetic regimen. Both can occur in patients known to have epilepsy or de novo, with increasingrecognition of autoimmune and genetic causes. Electroencephalography monitoring is essential to monitor treatment response inrefractory/super-refractory status epilepticus, and to diagnose non-convulsive status epilepticus. The mainstay of treatment for thesedisorders includes anesthetic infusions, primarily midazolam, ketamine, and pentobarbital. Dietary, immunological, and surgicaltreatments are viable in selected patients. Management is challenging due to multiple acute complications and long-term adverseconsequences. Conclusions: We have provided a synopsis of best practices for diagnosis and management of refractory/super-refractory status epilepticus and highlighted the lack of sufficient high-quality evidence to drive decision making, ending with a brief forayinto avenues for future research.

Caspofungin.

Caspofungin is a new antifungal drug meant for intravenous use. It has been shown to be comparable to other antifungal agents such as amphotericin B and fluconazole for empirical therapy in febrile neutropenic patients, oropharyngeal/esophageal candidiasis and invasive aspergillosis. Its efficacy has also been documented in children in small uncontrolled trials. The biggest assets of caspofungin are its excellent tolerability/safety profile and minimal drug interactions.