Department of Neurology (J.B.K., S.T.G., J.A.S., M.I.S., A.M., K.K., D.S., S.S., H.B.H.), University of Erlangen-Nuremberg, Germany.
Division of Brain Injury Outcomes, Johns Hopkins University, Baltimore, MD (W.Z., M.R., R.A., D.F.H.).
Stroke. 2022 Sep;53(9):2876-2886. doi: 10.1161/STROKEAHA.121.038455. Epub 2022 May 6.
In patients with intracerebral hemorrhage (ICH), the presence of intraventricular hemorrhage constitutes a promising therapeutic target. Intraventricular fibrinolysis (IVF) reduces mortality, yet impact on functional disability remains unclear. Thus, we aimed to determine the influence of IVF on functional outcomes.
This individual participant data meta-analysis pooled 1501 patients from 2 randomized trials and 7 observational studies enrolled during 2004 to 2015. We compared IVF versus standard of care (including placebo) in patients treated with external ventricular drainage due to acute hydrocephalus caused by ICH with intraventricular hemorrhage. The primary outcome was functional disability evaluated by the modified Rankin Scale (mRS; range: 0-6, lower scores indicating less disability) at 6 months, dichotomized into mRS score: 0 to 3 versus mRS: 4 to 6. Secondary outcomes included ordinal-shift analysis, all-cause mortality, and intracranial adverse events. Confounding and bias were adjusted by random effects and doubly robust models to calculate odds ratios and absolute treatment effects (ATE).
Comparing treatment of 596 with IVF to 905 with standard of care resulted in an ATE to achieve the primary outcome of 9.3% (95% CI, 4.4-14.1). IVF treatment showed a significant shift towards improved outcome across the entire range of mRS estimates, common odds ratio, 1.75 (95% CI, 1.39-2.17), reduced mortality, odds ratio, 0.47 (95% CI, 0.35-0.64), without increased adverse events, absolute difference, 1.0% (95% CI, -2.7 to 4.8). Exploratory analyses provided that early IVF treatment (≤48 hours) after symptom onset was associated with an ATE, 15.2% (95% CI, 8.6-21.8) to achieve the primary outcome.
As compared to standard of care, the administration of IVF in patients with acute hydrocephalus caused by intracerebral and intraventricular hemorrhage was significantly associated with improved functional outcome at 6 months. The treatment effect was linked to an early time window <48 hours, specifying a target population for future trials.
在颅内出血（ICH）患者中，存在脑室内出血是一个很有前途的治疗靶点。脑室内纤溶（IVF）降低了死亡率，但对功能障碍的影响仍不清楚。因此，我们旨在确定 IVF 对功能结果的影响。
这项个体参与者数据荟萃分析汇总了 2004 年至 2015 年期间 2 项随机试验和 7 项观察性研究中招募的 1501 名患者。我们比较了因 ICH 伴脑室内出血引起急性脑积水而接受外部脑室引流的患者中 IVF 与标准治疗（包括安慰剂）的效果。主要结局是 6 个月时用改良 Rankin 量表（mRS；范围：0-6，得分越低表示功能障碍越轻）评估的功能障碍，分为 mRS 评分：0-3 与 mRS：4-6。次要结局包括等级转换分析、全因死亡率和颅内不良事件。通过随机效应和双重稳健模型调整混杂因素和偏倚，计算比值比和绝对治疗效果（ATE）。
与标准治疗组 905 例相比，596 例接受 IVF 治疗的患者的 ATE 达到主要结局的比例为 9.3%（95%CI，4.4-14.1）。IVF 治疗在整个 mRS 估计值范围内都显著改善了结局，常见比值比为 1.75（95%CI，1.39-2.17），降低了死亡率，比值比为 0.47（95%CI，0.35-0.64），且未增加不良事件，绝对差异为 1.0%（95%CI，-2.7 至 4.8）。探索性分析表明，症状出现后≤48 小时进行早期 IVF 治疗与 ATE 相关，达到主要结局的比例为 15.2%（95%CI，8.6-21.8）。
与标准治疗相比，在因脑实质和脑室内出血引起的急性脑积水患者中使用 IVF 治疗与 6 个月时的功能结局改善显著相关。治疗效果与<48 小时的早期时间窗口相关，为未来的试验指定了一个目标人群。
