Departments of Neurology and Emergency Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, CR-127, Portland, OR 97239, USA.
Department of Neurology, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
J Stroke Cerebrovasc Dis. 2020 Jul;29(7):104916. doi: 10.1016/j.jstrokecerebrovasdis.2020.104916. Epub 2020 May 13.
BACKGROUND/OBJECTIVE: Malignant edema can be a life-threatening complication of large hemispheric infarction (LHI), and is often treated with osmotherapy. In this exploratory analysis of data from the GAMES-RP study, we hypothesized that patients receiving osmotherapy had symptomatic cerebral edema, and that treatment with intravenous (IV) glibenclamide would modify osmotherapy use as compared with placebo.
GAMES-RP was a phase 2 multi-center prospective, double blind, randomized, placebo-controlled study in LHI. Patients were randomized to IV glibenclamide (e.g. IV glyburide) or placebo. Cerebral edema therapies included osmotherapy and/or decompressive craniectomy at the discretion of the treating team. Total bolus osmotherapy dosing was quantified by "osmolar load". Radiographic edema was defined by dichotomizing midline shift at 24 h. Clinical changes were defined as any increase in NIHSS1a.
Osmotherapy was administered to 40 of the 77 patients at a median of 39 [27-55] h after stroke onset. The median baseline DWI lesion volume was significantly larger in the osmotherapy treated group (167 [146-211] mL v. 139 [112-170] mL; P=0.046). Adjudicated malignant edema (75% v. 16%; P<0.001) was more common in the osmotherapy treated group. There were no differences in the proportion of patients receiving osmotherapy or the median total osmolar load between treatment arms. Most patients (76%) had a decrease in consciousness (NIHSS item 1A ≥1) on the day they began receiving osmotherapy.
In the GAMES-RP trial, osmolar therapies were most often administered in response to clinical symptoms of decreased consciousness. However, the optimal timing of administration and impact on outcome after LHI have yet to be defined.
背景/目的：恶性水肿是大面积半球梗死（LHI）的一种危及生命的并发症，常采用渗透疗法进行治疗。在 GAMES-RP 研究数据的探索性分析中，我们假设接受渗透治疗的患者存在症状性脑水肿，与安慰剂相比，静脉（IV）格列本脲治疗会改变渗透治疗的使用。
GAMES-RP 是一项 2 期多中心前瞻性、双盲、随机、安慰剂对照研究，纳入 LHI 患者。患者被随机分为 IV 格列本脲（如 IV 格列吡嗪）或安慰剂组。脑水肿治疗包括渗透治疗和/或减压性颅骨切除术，由治疗团队决定。总推注渗透治疗剂量通过“渗透压负荷”进行量化。影像学水肿通过 24 小时中线移位的二分法定义。临床变化定义为 NIHSS1a 任何增加。
在发病后 39 [27-55] 小时中位数时，40 例（77 例中的 40 例）患者接受了渗透治疗。在接受渗透治疗的组中，基线 DWI 病变体积中位数明显更大（167 [146-211] mL 比 139 [112-170] mL；P=0.046）。在渗透治疗组中，更常见的是判定为恶性水肿（75%比 16%；P<0.001）。治疗组之间接受渗透治疗的患者比例或中位数总渗透压负荷没有差异。大多数患者（76%）在开始接受渗透治疗的当天意识下降（NIHSS 项目 1A ≥1）。
在 GAMES-RP 试验中，渗透压治疗最常用于治疗意识下降的临床症状。然而，LHI 后最佳给药时机和对结局的影响仍有待确定。
