The Safety and Efficacy of Glibenclamide in Managing Cerebral Edema After Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis
Background/Objectives: We sought to determine if glibenclamide, a sulfonylurea receptor 1-transient receptor potential melastatin 4 (SUR1-TRPM4) channel blocker, reduces cerebral edema and improves neurological functioning in aneurysmal subarachnoid hemorrhage (aSAH). Methods: Following Preferred Re...
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2025-06-01
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| author | Majd M. AlBarakat Rana B. Altawalbeh Khaled Mohamed Hamam Ahmed A. Lashin Ahmed Wadaa-Allah Ayah J. Alkrarha Mohamed Abuelazm James Robert Brašić |
| author_facet | Majd M. AlBarakat Rana B. Altawalbeh Khaled Mohamed Hamam Ahmed A. Lashin Ahmed Wadaa-Allah Ayah J. Alkrarha Mohamed Abuelazm James Robert Brašić |
| author_sort | Majd M. AlBarakat |
| collection | DOAJ |
| description | Background/Objectives: We sought to determine if glibenclamide, a sulfonylurea receptor 1-transient receptor potential melastatin 4 (SUR1-TRPM4) channel blocker, reduces cerebral edema and improves neurological functioning in aneurysmal subarachnoid hemorrhage (aSAH). Methods: Following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, a systematic search was conducted in PubMed, Cochrane Library, Web of Science, and SCOPUS for studies evaluating glibenclamide in aSAH patients. Primary outcomes included scores on the modified Rankin Scale (mRS) at discharge and the Subarachnoid Hemorrhage Early Brain Edema Score (SEBES) at ten days post-intervention. Secondary outcomes included adverse events, and safety and efficacy endpoints. Random-effects models were employed for meta-analyses. Results: Three studies utilizing oral glibenclamide (<i>n</i> = 245) met inclusion criteria. Oral glibenclamide demonstrated no significant improvements in mRS scores [MD −0.19 with 95% CI (−2.05, 1.66)] at discharge, [MD 0.06, (−0.60, 0.71)] at 3 months, and [MD 0.4, (−0.67, 0.87)] at 6 months; functional independence [risk ratio (RR) 1.05, (0.81, 1.36)]; independent ambulation [RR 1.07, (0.77, 1.48)]; mortality [RR 0.79, (0.42, 1.50)]; or delayed cerebral ischemia [RR 0.58, (0.31, 1.09]). Hypoglycemia risk was significantly higher in the glibenclamide group [RR 3.92, (1.14, 13.49)]. Conclusions: Oral glibenclamide offers a novel approach to addressing cerebral edema in aSAH but shows limited clinical efficacy in improving functional and neurological outcomes in subtherapeutic doses. Its safety profile is acceptable, though hypoglycemia risk necessitates careful monitoring. Further research is required to optimize dosing, timing of intervention, and patient selection to enhance therapeutic outcomes. By contrast, intravenous administration of therapeutic doses of glibenclamide offers a promising avenue for future studies in the management of aSAH by taking advantage of the favorable pharmacokinetics of this route of administration. |
| format | Article |
| id | doaj-art-b91e2d32545b40c7a703237dfe4ceb60 |
| institution | Kabale University |
| issn | 2076-3425 |
| language | English |
| publishDate | 2025-06-01 |
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| spelling | doaj-art-b91e2d32545b40c7a703237dfe4ceb602025-08-20T03:58:30ZengMDPI AGBrain Sciences2076-34252025-06-0115767710.3390/brainsci15070677The Safety and Efficacy of Glibenclamide in Managing Cerebral Edema After Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-AnalysisMajd M. AlBarakat0Rana B. Altawalbeh1Khaled Mohamed Hamam2Ahmed A. Lashin3Ahmed Wadaa-Allah4Ayah J. Alkrarha5Mohamed Abuelazm6James Robert Brašić7Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, JordanFaculty of Medicine, Jordan University of Science and Technology, Irbid 22110, JordanCollege of Health and Human Sciences, North Dakota State University, Fargo, ND 58102, USAFaculty of Medicine, Benha University, Benha 13511, EgyptDepartment of Biochemistry, Faculty of Science, Ain Shams University, Abbassia, Cairo 1181, EgyptFaculty of Medicine, Jordan University of Science and Technology, Irbid 22110, JordanFaculty of Medicine, Tanta University, Tanta 31527, EgyptDepartment of Psychiatry, New York City Health and Hospitals/Bellevue, New York, NY 10016, USABackground/Objectives: We sought to determine if glibenclamide, a sulfonylurea receptor 1-transient receptor potential melastatin 4 (SUR1-TRPM4) channel blocker, reduces cerebral edema and improves neurological functioning in aneurysmal subarachnoid hemorrhage (aSAH). Methods: Following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, a systematic search was conducted in PubMed, Cochrane Library, Web of Science, and SCOPUS for studies evaluating glibenclamide in aSAH patients. Primary outcomes included scores on the modified Rankin Scale (mRS) at discharge and the Subarachnoid Hemorrhage Early Brain Edema Score (SEBES) at ten days post-intervention. Secondary outcomes included adverse events, and safety and efficacy endpoints. Random-effects models were employed for meta-analyses. Results: Three studies utilizing oral glibenclamide (<i>n</i> = 245) met inclusion criteria. Oral glibenclamide demonstrated no significant improvements in mRS scores [MD −0.19 with 95% CI (−2.05, 1.66)] at discharge, [MD 0.06, (−0.60, 0.71)] at 3 months, and [MD 0.4, (−0.67, 0.87)] at 6 months; functional independence [risk ratio (RR) 1.05, (0.81, 1.36)]; independent ambulation [RR 1.07, (0.77, 1.48)]; mortality [RR 0.79, (0.42, 1.50)]; or delayed cerebral ischemia [RR 0.58, (0.31, 1.09]). Hypoglycemia risk was significantly higher in the glibenclamide group [RR 3.92, (1.14, 13.49)]. Conclusions: Oral glibenclamide offers a novel approach to addressing cerebral edema in aSAH but shows limited clinical efficacy in improving functional and neurological outcomes in subtherapeutic doses. Its safety profile is acceptable, though hypoglycemia risk necessitates careful monitoring. Further research is required to optimize dosing, timing of intervention, and patient selection to enhance therapeutic outcomes. By contrast, intravenous administration of therapeutic doses of glibenclamide offers a promising avenue for future studies in the management of aSAH by taking advantage of the favorable pharmacokinetics of this route of administration.https://www.mdpi.com/2076-3425/15/7/677calcium channel blockerclinical trialsendotheliumfunctional independencehypoglycemiamorbidity |
| spellingShingle | Majd M. AlBarakat Rana B. Altawalbeh Khaled Mohamed Hamam Ahmed A. Lashin Ahmed Wadaa-Allah Ayah J. Alkrarha Mohamed Abuelazm James Robert Brašić The Safety and Efficacy of Glibenclamide in Managing Cerebral Edema After Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis Brain Sciences calcium channel blocker clinical trials endothelium functional independence hypoglycemia morbidity |
| title | The Safety and Efficacy of Glibenclamide in Managing Cerebral Edema After Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis |
| title_full | The Safety and Efficacy of Glibenclamide in Managing Cerebral Edema After Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis |
| title_fullStr | The Safety and Efficacy of Glibenclamide in Managing Cerebral Edema After Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis |
| title_full_unstemmed | The Safety and Efficacy of Glibenclamide in Managing Cerebral Edema After Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis |
| title_short | The Safety and Efficacy of Glibenclamide in Managing Cerebral Edema After Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis |
| title_sort | safety and efficacy of glibenclamide in managing cerebral edema after aneurysmal subarachnoid hemorrhage a systematic review and meta analysis |
| topic | calcium channel blocker clinical trials endothelium functional independence hypoglycemia morbidity |
| url | https://www.mdpi.com/2076-3425/15/7/677 |
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