A pragmatic approach to intravenous anaesthetics and electroencephalographic endpoints for the treatment of refractory and super-refractory status epilepticus in critical care

Abstract

Status epilepticus is a common neurological emergency, with overall mortality around 20%. Over half of cases are first time presentations of seizures. The pathological process by which spontaneous seizures are generated arises from an imbalance in excitatory and inhibitory neuronal networks, which if unchecked, can result in alterations in intracellular signalling pathways and electrolyte shifts, which bring about changes in the blood brain barrier, neuronal cell death and eventually cerebral atrophy. This narrative review focusses on the treatment of status epilepticus in adults. Anaesthetic agents interrupt neuronal activity by enhancing inhibitory or decreasing excitatory transmission, primarily via GABA and NMDA receptors. Intravenous anaesthetic agents are commonly used as second or third line drugs in the treatment of refractory status epilepticus, but the optimal timing and choice of anaesthetic drug has not yet been established by high quality evidence. Titration of antiepileptic and anaesthetic drugs in critically ill patients presents a particular challenge, due to alterations in drug absorbtion and metabolism as well as changes in drug distrubution, which arise from fluid shifts and altered protein binding. Furthermore, side effects associated with prolonged infusions of anaesthetic drugs can lead to multi-organ dysfunction and a need for critical care support. Electroencelography can identify patterns of burst suppression, which may be a target to guide weaning of intravenous therapy. Continuous elctroencephalography has the potential to directly impact clinical care, but despite its utility, major barriers exist which have limited its widespread use in clinical practice. A flow chart outlining the timing and dosage of anaesthetic agents used at our institution is provided.

Review and Updates on the Treatment of Refractory and Super Refractory Status Epilepticus

“…Clear treatment goals incorporating the risks and benefits of continuous anesthetic therapy should be defined early on using an interdisciplinary approach. It is particularly essential to bridge the gap between electrophysiologist and bedside clinician when treating patients with SE [ 17 ].…”

“…Traditionally, both midazolam and propofol have been used for decades as first-line continuous anesthetics for RSE and SRSE [ 18 ]. When one agent is initiated and up titrated without achieving therapeutic goals, the addition of another agent should be considered [ 17 , 31 ]. Additionally, clinicians should consider inhaled anesthetics such as isoflurane and desflurane in prolonged cases of SRSE [ 32 ].…”

To Wean or Not to Wean: Machine Learning to the Rescue

“…Therapeutic coma induced with IVAD is widely considered a standard of care in the treatment of certain types of RSE. 11 - 13 However, complications associated with IVAD in the treatment of RSE are also well recognized. Several studies have noted the increased risk of morbidity and mortality associated with TC induced by IVAD used to treat RSE.…”

Status epilepticus special edition

“…Prisco and a team of co-authors including neuro-intensivists, anaesthetists, neurologists, neurophysiologists and pharmacists then consider the options for people with refractory and super-refractory status epilepticus -those in whom neither first nor second line agents have aborted seizures [7]. They highlight how important it is to ensure systemic aspects are addressed and that continuous electroencephalographic monitoring may offer additional benefits to patient care.…”

“…They highlight how important it is to ensure systemic aspects are addressed and that continuous electroencephalographic monitoring may offer additional benefits to patient care. A flow chart of the intravenous anaesthetic protocol used on for status epilepticus on the Neuro-intensive care Unit in Oxford, UK, is also provided [7].…”