Department of Neurology, 71044Xuanwu Hospital, Capital Medical University, Beijing, China.
Beijing Institute of Brain Disorders, Capital Medical University, Beijing, China.
Int J Stroke. 2022 Apr;17(4):425-433. doi: 10.1177/17474930211006580. Epub 2021 Apr 7.
Remote ischemic conditioning can promote hematoma resolution, attenuate brain edema, and improve neurological recovery in animal models of intracerebral hemorrhage.
This study aimed to evaluate the safety and preliminary efficacy of remote ischemic conditioning in patients with intracerebral hemorrhage.
In this multicenter, randomized, controlled trial, 40 subjects with supratentorial intracerebral hemorrhage presenting within 24-48 h of onset were randomly assigned to receive medical therapy plus remote ischemic conditioning for consecutive seven days or medical therapy alone. The primary safety outcome was neurological deterioration within seven days of enrollment, and the primary efficacy outcome was the changes of hematoma volume on CT images. Other outcomes included hematoma resolution rate at 7 days ([hematoma volume at 7 days - hematoma volume at baseline]/hematoma volume at baseline), perihematomal edema (PHE), and functional outcome at 90 days.
The mean age was 59.3 ± 11.7 years and hematoma volume was 13.9 ± 4.5 mL. No subjects experienced neurological deterioration within seven days of enrollment, and no subject died or experienced remote ischemic conditioning-associated adverse events during the study period. At baseline, the hematoma volumes were 14.19 ± 5.07 mL in the control group and 13.55 ± 3.99 mL in the remote ischemic conditioning group, and they were 8.54 ± 3.99 mL and 6.95 ± 2.71 mL at seven days after enrollment, respectively, which is not a significant difference ( > 0.05 each). The hematoma resolution rate in the remote ischemic conditioning group (49.25 ± 9.17%) was significantly higher than in the control group (41.92 ± 9.14%; MD, 7.3%; 95% CI, 1.51-13.16%; = 0.015). The absolute PHE volume was 17.27 ± 8.34 mL in the control group and 12.92 ± 7.30 mL in the remote ischemic conditioning group at seven days after enrollment, which is not a significant between-group difference ( = 0.087), but the relative PHE in the remote ischemic conditioning group (1.77 ± 0.39) was significantly lower than in the control group (2.02 ± 0.27; MD, 0.25; 95% CI, 0.39-0.47; = 0.023). At 90-day follow-up, 13 subjects (65%) in the remote ischemic conditioning group and 12 subjects (60%) in the control group achieved favorable functional outcomes (modified Rankin Scale score ≤ 3), which is not a significant between-group difference ( = 0.744).
Repeated daily remote ischemic conditioning for consecutive seven days was safe and well tolerated in patients with intracerebral hemorrhage, and it may be able to improve hematoma resolution rate and reduce relative PHE. However, the effects of remote ischemic conditioning on the absolute hematoma and PHE volume and functional outcomes in this patient population need further investigations. http://www.clinicaltrials.gov. Unique identifier: NCT03930940.
远程缺血预处理可促进脑出血动物模型血肿吸收、减轻脑水肿和改善神经功能恢复。
本研究旨在评估远程缺血预处理治疗脑出血患者的安全性和初步疗效。
本多中心、随机、对照试验纳入发病后 24-48 小时内的幕上脑出血患者 40 例，随机分为连续 7 天接受药物治疗加远程缺血预处理组或单纯药物治疗组。主要安全性结局为入组后 7 天内神经功能恶化，主要疗效结局为 CT 图像上血肿体积的变化。其他结局包括第 7 天血肿清除率[（第 7 天血肿体积-基线血肿体积）/基线血肿体积]、血肿周围水肿（perihematomal edema，PHE）和 90 天的功能结局。
患者平均年龄为 59.3±11.7 岁，血肿体积为 13.9±4.5ml。入组后 7 天内无受试者出现神经功能恶化，研究期间无受试者死亡或出现与远程缺血预处理相关的不良事件。基线时，对照组血肿体积为 14.19±5.07ml，远程缺血预处理组为 13.55±3.99ml，入组后第 7 天分别为 8.54±3.99ml 和 6.95±2.71ml，差异无统计学意义（均 > 0.05）。远程缺血预处理组（49.25%±9.17%）的血肿清除率明显高于对照组（41.92%±9.14%；MD，7.3%；95%CI，1.51-13.16%； = 0.015）。入组后第 7 天，对照组 PHE 绝对体积为 17.27±8.34ml，远程缺血预处理组为 12.92±7.30ml，两组间差异无统计学意义（ = 0.087），但远程缺血预处理组的相对 PHE（1.77±0.39）明显低于对照组（2.02±0.27；MD，0.25；95%CI，0.39-0.47； = 0.023）。90 天随访时，远程缺血预处理组 13 例（65%）和对照组 12 例（60%）患者功能结局良好（改良 Rankin 量表评分≤3），两组间差异无统计学意义（ = 0.744）。
连续 7 天每日重复远程缺血预处理治疗脑出血患者安全且耐受良好，可能提高血肿清除率并降低相对 PHE。然而，这种处理方法对该患者人群的绝对血肿和 PHE 体积以及功能结局的影响还需要进一步研究。http://www.clinicaltrials.gov。注册号：NCT03930940。
