biostudies-literatureAndreasen THDepartment of Neurosurgery research fundThe Novo Nordisk FoundationDoctor Sofus Carl Emil Friis and wife Olga Doris Friis grantSnedkermester Sophus Jacobsen og Hustru Astrid Jacobsens FondDanish Society for Anesthesiology and Intensive Care Medicine (DASAIM) Research Initiative 2021Merchant Jakob Ehrenreich and wife Grete Ehrenreich’s FoundationSundhedsdonationerKnud and Edith Eriksen’s Memorial FoundationThe A.P. Møller FoundationDagmar Marshall FoundationThe Danish Victims’ Foundationthe Research Board at Rigshospitalete101426https://www.ebi.ac.uk/biostudies/studies/S-EPMC12306330biostudies-literatureUnknown15(7)<h4>Introduction</h4>Cortical spreading depolarisation (SD) is a pathological wave of depolarisation in the cortex. SDs occur frequently after severe acute brain injury, and SDs in clusters can contribute to secondary brain damage in patients with severe acute brain injury through hypoperfusion and upregulation of cerebral metabolism in vulnerable brain tissue. Ketamine appears to inhibit SDs both in vitro and in patient series of severe acute brain injury. The KETA-BID trial aims to examine the efficacy and safety of S-ketamine for SDs in severe acute brain injury, as well as the feasibility of the trial design.<h4>Methods and analysis</h4>This randomised, blinded feasibility and pilot trial includes adults (≥ 18 years) undergoing a supratentorial craniotomy or craniectomy for severe acutBMJ openS-ketamine versus placebo for cortical spreading depolarisation in severe acute brain injury (KETA-BID): protocol for a pilot, randomised, blinded clinical trial.PMC1230633062786-202120-L-004120-610-001032024-0378NNF20OC0065750Olsen MHMoller KHauerberg JAndreasen THLindschou JFabricius MGluud CfalseS-ketamine versus placebo for cortical spreading depolarisation in severe acute brain injury (KETA-BID): protocol for a pilot, randomised, blinded clinical trial.<h4>Introduction</h4>Cortical spreading depolarisation (SD) is a pathological wave of depolarisation in the cortex. SDs occur frequently after severe acute brain injury, and SDs in clusters can contribute to secondary brain damage in patients with severe acute brain injury through hypoperfusion and upregulation of cerebral metabolism in vulnerable brain tissue. Ketamine appears to inhibit SDs both in vitro and in patient series of severe acute brain injury. The KETA-BID trial aims to examine the efficacy and safety of S-ketamine for SDs in severe acute brain injury, as well as the feasibility of the trial design.<h4>Methods and analysis</h4>This randomised, blinded feasibility and pilot trial includes adults (≥ 18 years) undergoing a supratentorial craniotomy or craniectomy for severe acut2025-01-01T00:00:00Z2025 Jul2026-03-31T11:03:50.06Z2025-08-27T03:11:09.34ZS-EPMC123063304072126310.1136/bmjopen-2025-101426