Cortical spreading depolarizations in the context of subarachnoid hemorrhage and the role of ketamine

Abstract

Delayed cerebral ischemia (DCI) is one of the main complications of spontaneous subarachnoid haemorrhage and one of its causes is the cortical spreading depolarizations (CSDs). Cortical spreading depolarizations are waves of neuronal and glial depolarizations in which there is loss of neuronal ionic homeostasis with potassium efflux and sodium and calcium influx. In damaged brain areas and brain areas at risk, such as those adjacent to subarachnoid haemorrhage (SAH), CSDs induce microvascular vasoconstriction and, therefore, hypoperfusion and spread of ischemia. Several studies have been devoted to minimize secondary injuries that occur hours to days after an acute insult. Ketamine, a drug until recently contraindicated in the neurosurgical population for potentially causing intracranial hypertension, has re-emerged as a potential neuroprotective agent due to its pharmacodynamic effects at the cellular level. These effects include anti-inflammatory mechanisms, and those of microthrombosis and cell apoptosis controls, and of modulation of brain excitotoxicity and CSDs. A literature review was performed at PubMed covering the period from 2002 to 2019. Retrospective studies confirmed the effects of ketamine on the control of CSDs and, consequently, of DCI in patients with SAH, but did not show improvement in clinical outcome. The influence of ketamine on the occurrence/development of DCI needs to be further confirmed in prospective randomized studies.