Cortical spreading depolarization and ketamine: a short systematic review

Cortical spreading depolarization (SD) describes pathological waves characterized by an almost complete sustained depolarization of neurons and astrocytes that spreads throughout the cortex. In this study, we carried out a qualitative review of all available evidence, clinical and preclinical, on the use of ketamine in SD. We performed a systematic review of Medline, with no restrictions regarding publishing date or language, in search of articles reporting the use of ketamine in SD. The search string was composed of “ketamine,” “spreading,” “depolarization,” and “depression” in both (AND) and (OR) combinations. Twenty studies were included in the final synthesis. Many studies showed that ketamine effectively blocks SD in rats, swine, and humans. The first prospective randomized trial was published in 2018. Ten patients with severe traumatic brain injury or subarachnoid hemorrhage were enrolled, and ketamine showed a significant, dose-dependent effect on the reduction of SD. The available evidence from preclinical studies is helping to translate the role of ketamine in blocking spreading depolarizations to clinical practice, in the settings of migraine with aura, traumatic brain injury, subarachnoid hemorrhage, and hemorrhagic and ischemic stroke. More randomized controlled trials are needed to determine whether interrupting the ketamine-blockable SDs effectively leads to an improvement in outcome and to assess the real occurrence of adverse effects.