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.
This randomised, blinded feasibility and pilot trial includes adults (≥ 18 years) undergoing a supratentorial craniotomy or craniectomy for severe acute brain injury (ie, traumatic brain injury, aneurysmal subarachnoid haemorrhage or spontaneous intracerebral haemorrhage). During surgery, an electrocorticography (ECoG) strip is placed adjacent to injured brain tissue. Patients are continuously monitored throughout their stay at the neurointensive care unit and the neurosurgical step-down unit. In the case of an SD, physiological optimisation of intracranial pressure, brain tissue oxygen tension (PbtO2), core temperature and blood glucose is initiated. Participants developing SD clusters are randomised for continuous infusion with S-ketamine or matching placebo in a 1:1 allocation with full blinding of the treatment allocation. Infusion rates (ie, dose) and duration of trial medication are adjusted following a dosing algorithm according to SD occurrence. Surviving participants are followed until 6 months after the injury with recording of functional outcome. The primary outcome is occurrence of SDs per hour of monitoring after randomisation.
The Scientific Ethics Committee of the Capital Region of Denmark (H-21056972), the Danish Medicines Agency (EudraCT 2021-003716-12), as well as the Clinical Trials Information System (CTIS 2024-515315-22-00) approved this trial. This trial will provide insight into both SD and the clinical effects of ketamine following severe acute brain injury, presenting a potential new treatment for these patients. The findings will be submitted for publication in peer-reviewed publications.
Fatigue, depression, anxiety and cognitive difficulties are reported by 1/3 of patients following transient ischemic attack (TIA).
To explore the timeline and how the diagnosis impacts individuals experiencing lasting challenges after TIA. Furthermore, to identify what they believed facilitated return to everyday life.
Qualitative exploratory study with a phenomenological-hermeneutic approach.
Individual semi-structured interviews and thematic analysis.
Fifteen patients were included. Four themes were identified; (1) ‘They say it is transient – no, not for me’ where all participants described lasting challenges emphasizing invalidating fatigue and impaired social participation, (2) ‘I am a changed person; how does this impact my future?’ which reflects altered identity and elevated alertness to symptoms, (3) ‘Time has been my ally and new perspectives have evolved’ where most participants described improvement over time and a few considered the diagnosis a wake-up call to change lifestyle. Lastly (4) ‘What would have helped me recover?’ which unfolds that close, trustful relations influence positively. In addition, the system often failed to support. Participants described pressure to return to work and lack of trust and negative experiences when involving their general practitioner.
During the 4 months since diagnosis, participants experienced limitations impacting physical, psychological and social domains. They felt uninformed that lasting challenges could affect them. Different coping strategies were activated, and participants with close, supportive relations managed better. A pressure to return to work and a lack of trust in the general practitioner affected their recovery negatively. Overall, return to everyday life after TIA was considered stressful and appropriate support lacking.
To be able to support patients with challenges following TIA, we as healthcare professionals need to understand the identified impact and life changing circumstances. Currently the system seemingly is not able to provide timely, sufficient and competent support.
We know from the literature that up to 1/3 of patients following transient ischemic attack experience lasting challenges measured on a variety of questionnaires. This is paradoxical to a diagnosis defined by focal neurological symptoms that resolve within 24 h. It is unknown how patients with lasting challenges experience the timeline from diagnosis and until 4 months after, how the diagnosis impacts the lives of these individuals, and what they believe as beneficial in returning to their everyday life.
These participants with self-reported lasting challenges experienced substantial impacts on physical, psychological and social domains. Further, they felt alone with their struggles and when in need of support from the healthcare system, it failed to provide this. A pressure to return to work and a lack of trust in the general practitioner affected return to everyday life negatively, whereas close and supportive relations facilitated positively.
This study will have an impact on the healthcare professionals that provide support and the (limited) follow-up services to patients after TIA. These healthcare professionals are often specialized nurses who need to know what these patients experience and need in order to act upon their struggles and provide timely support.
The Standards of Reporting Qualitative Research (SRQR).
Patients with TIA was involved in planning this study. They participated in a panel to plan a prospective observational cohort study and emphasized the importance of exploring the subjective perspectives of impact and prognosis for those patients struggling in a longer term (through qualitative interviews).