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

Lara Prisco, Mario Ganau, Sidra Aurangzeb, Olivia Moswela, Claire Hallett, Simon Raby, Karina Fitzgibbon, Christopher Kearns, Arjune Sen

Journal: Seizure 2020;75():153-164

PMID: 31623937

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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.

Address: Neurosciences Intensive Care Unit, John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Anaesthesia Neuroimaging Research Group, Wellcome Centre for Integrative Neuroimaging, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK; Oxford Epilepsy Research Group, Nuffield Department of Clinical Neurosciences, University of Oxford, UK. Electronic address: [email protected].; Department of Neurosurgery, John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.; Oxford Epilepsy Research Group, Nuffield Department of Clinical Neurosciences, University of Oxford, UK; Department of Clinical Neurology, John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Department of Clinical Neurophysiology, John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.; Pharmacy Department, John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.; Neurosciences Intensive Care Unit, John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.; Oxford Epilepsy Research Group, Nuffield Department of Clinical Neurosciences, University of Oxford, UK; Department of Clinical Neurology, John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

DOI: 10.1016/j.seizure.2019.09.011

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MeSH Terms: Anesthetics, Intravenous, Anticonvulsants, Critical Care, Drug Resistant Epilepsy, Electroencephalography, Endpoint Determination, Humans, Status Epilepticus, Treatment Outcome