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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

中文翻译：

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静脉输注格列本脲的2期前瞻性，双盲，随机，安慰剂对照研究中的针对恶性脑水肿的渗透疗法。

背景/目的恶性水肿可能是威胁生命的大半球性脑梗塞（LHI）并发症，通常采用渗透疗法进行治疗。在对来自GAMES-RP研究的数据进行的探索性分析中，我们假设接受渗透治疗的患者患有症状性脑水肿，与安慰剂相比，静脉注射（IV）格列本脲治疗会改变渗透治疗的使用。方法GAMES-RP是LHI的2期多中心前瞻性，双盲，随机，安慰剂对照研究。患者被随机分为静脉注射格列本脲（如静脉注射格列本脲）或安慰剂。脑水肿治疗包括由治疗团队自行决定的渗透疗法和/或减压颅骨切除术。通过“渗透压负荷”定量总推注渗透疗法剂量。放射线水肿定义为在24小时将中线移位二分。临床变化定义为NIHSS1a升高。结果77例患者中有40例在中风发作后中位39 [27-55] h接受了渗透治疗。在渗透治疗组中，中位基线DWI病变体积明显更大（167 [146-211] mL对139 [112-170] mL； P = 0.046）。在渗透疗法治疗组中，恶性水肿的判定更为常见（75％vs. 16％； P <0.001）。两组之间接受渗透疗法的患者比例或总渗透压中位数无差异。大多数患者（76％）在开始接受渗透治疗的那天意识降低（NIHSS项目1A≥1）。结论在GAMES-RP试验中，渗透压疗法最常用于应对意识下降的临床症状。但是，LHI后的最佳给药时机及其对结果的影响尚待确定。