RESUMO
BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with a high incidence of long-term cognitive impairment, decreased quality of life (QoL), and psychiatric disorders. The effects of glibenclamide on such outcomes in the setting of aSAH are unknown. OBJECTIVE: To assess the impact of glibenclamide in patients with aSAH on cognitive performance, QoL, and emotional aspects. METHODS: Patients identified with aSAH were randomly allocated to receive 5 mg of glibenclamide for 21 days or placebo, starting within 96 hours of the ictus. After 6 months, patients were evaluated with Montreal Cognitive Assessment test (cognitive performance), Medical Outcomes Short-form Health Survey (QoL), and Hospital Anxiety and Depression Scale and Screen for Post-traumatic Stress Symptoms (emotional aspects). RESULTS: The mean Montreal Cognitive Assessment score was 22.5 ± 6.2. No statistically significant difference was found between groups, with a mean score of 21.7 ± 6.4 in the Glibenclamide group and 23.4 ± 6.2 in the placebo group (P = 0.392). A score <23 was observed in 16 patients (35.6%) and its frequency was similar between groups (P = 0.900). The most frequently impaired domains were Attention (N = 21/45; 46.7%) and Visuospatial (18/45; 40.0%). Impairment of each domain was similar between groups (P > 0.05). In each domain, the mean score was similar between groups (P > 0.05). The Hospital Anxiety and Depression Scale scores did not differ between groups (P > 0.05). The mean Screen for Post-traumatic Stress Symptoms score as well as the mean scores of its domains were similar between groups (P > 0.05). CONCLUSIONS: Glibenclamide did not improve cognitive performance, QoL, and emotional aspects after 6 months of follow-up of aSAH survivors.
RESUMO
BACKGROUND: Recent findings on the benefits of glibenclamide as a neuroprotective drug have started a new era for prospective studies on sulfonylureas. The effect of glibenclamide blocking the Sur1-Trpm4 channel was examined in models of subarachnoid hemorrhage and stroke, with findings of significantly reduced tight-junction abnormalities, resulting in less edema formation and considerably reduced transsynaptic apoptosis of hippocampal neurons and significantly ameliorated impairments in spatial learning. Based on these data, we plan a clinical trial to establish evidence of glibenclamide as an adjunct treatment in aneurysmal subarachnoid hemorrhage. METHODS: An estimated 80 patients meeting the inclusion criteria of radiological confirmatory evidence of an aneurysmal subarachnoid hemorrhage, age 18-70 years, and presentation of less than 96 h from the ictus will be allocated randomly into two groups, one receiving 5 mg daily oral intake of glibenclamide for 21 days and another control group receiving a placebo. The study's primary outcome is the modified Rankin scale (mRS) after 6 months, as favorable (mRS 0-2) or unfavorable (mRS 3-6). The secondary outcomes will be late cognitive status, assessed after 6 months by psychological tests (the Short Form Health Survey Questionnaire and the Montreal Cognitive Assessment), as well as death at 6 months, delayed cerebral ischemia and occurrence of serious adverse events due to study medication. DISCUSSION: There is a growing interest in the scientific community regarding glibenclamide in brain edema and traumatic brain injury, but with very little of this interest targeting spontaneous brain hemorrhage, especially aneurism rupture. Positive outcomes are expected for the treatment patients, especially in language and memory preservation, as has been shown in experimental models. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03569540 . Retrospectively registered on 26 June 2018.