Division of Neurocritical Care, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
JAMA Neurol. 2022 Sep 1;79(9):856-868. doi: 10.1001/jamaneurol.2022.1991.
IMPORTANCE: Patients who survive severe intracerebral hemorrhage (ICH) and intraventricular hemorrhage (IVH) typically have poor functional outcome in the short term and understanding of future recovery is limited. OBJECTIVE: To describe 1-year recovery trajectories among ICH and IVH survivors with initial severe disability and assess the association of hospital events with long-term recovery. DESIGN, SETTING, AND PARTICIPANTS: This post hoc analysis pooled all individual patient data from the Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage phase 3 trial (CLEAR-III) and the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation (MISTIE-III) phase 3 trial in multiple centers across the US, Canada, Europe, and Asia. Patients were enrolled from August 1, 2010, to September 30, 2018, with a follow-up duration of 1 year. Of 999 enrolled patients, 724 survived with a day 30 modified Rankin Scale score (mRS) of 4 to 5 after excluding 13 participants with missing day 30 mRS. An additional 9 patients were excluded because of missing 1-year mRS. The final pooled cohort included 715 patients (71.6%) with day 30 mRS 4 to 5. Data were analyzed from July 2019 to January 2022. EXPOSURES: CLEAR-III participants randomized to intraventricular alteplase vs placebo. MISTIE-III participants randomized to stereotactic thrombolysis of hematoma vs standard medical care. MAIN OUTCOMES AND MEASURES: Primary outcome was 1-year mRS. Patients were dichotomized into good outcome at 1 year (mRS 0 to 3) vs poor outcome at 1 year (mRS 4 to 6). Multivariable logistic regression models assessed associations between prospectively adjudicated hospital events and 1-year good outcome after adjusting for demographic characteristics, ICH and IVH severity, and trial cohort. RESULTS: Of 715 survivors, 417 (58%) were male, and the overall mean (SD) age was 60.3 (11.7) years. Overall, 174 participants (24.3%) were Black, 491 (68.6%) were White, and 49 (6.9%) were of other races (including Asian, Native American, and Pacific Islander, consolidated owing to small numbers); 98 (13.7%) were of Hispanic ethnicity. By 1 year, 129 participants (18%) had died and 308 (43%) had achieved mRS 0 to 3. In adjusted models for the combined cohort, diabetes (adjusted odds ratio [aOR], 0.50; 95% CI, 0.26-0.96), National Institutes of Health Stroke Scale (aOR, 0.93; 95% CI, 0.90-0.96), severe leukoaraiosis (aOR, 0.30; 95% CI, 0.16-0.54), pineal gland shift (aOR, 0.87; 95% CI, 0.76-0.99]), acute ischemic stroke (aOR, 0.44; 95% CI, 0.21-0.94), gastrostomy (aOR, 0.30; 95% CI, 0.17-0.50), and persistent hydrocephalus by day 30 (aOR, 0.37; 95% CI, 0.14-0.98) were associated with lack of recovery. Resolution of ICH (aOR, 1.82; 95% CI, 1.08-3.04) and IVH (aOR, 2.19; 95% CI, 1.02-4.68) by day 30 were associated with recovery to good outcome. In the CLEAR-III model, cerebral perfusion pressure less than 60 mm Hg (aOR, 0.30; 95% CI, 0.13-0.71), sepsis (aOR, 0.05; 95% CI, 0.00-0.80), and prolonged mechanical ventilation (aOR, 0.96; 95% CI, 0.92-1.00 per day), and in MISTIE-III, need for intracranial pressure monitoring (aOR, 0.35; 95% CI, 0.12-0.98), were additional factors associated with poor outcome. Thirty-day event-based models strongly predicted 1-year outcome (area under the receiver operating characteristic curve [AUC], 0.87; 95% CI, 0.83-0.90), with significantly improved discrimination over models using baseline severity factors alone (AUC, 0.76; 95% CI, 0.71-0.80; P < .001). CONCLUSIONS AND RELEVANCE: Among survivors of severe ICH and IVH with initial poor functional outcome, more than 40% recovered to good outcome by 1 year. Hospital events were strongly associated with long-term functional recovery and may be potential targets for intervention. Avoiding early pessimistic prognostication and delaying prognostication until after treatment may improve ability to predict future recovery.
重要性：存活严重颅内出血 (ICH) 和脑室内出血 (IVH) 的患者在短期内功能预后较差，对未来恢复的理解有限。
目的：描述初始严重残疾的 ICH 和 IVH 幸存者的 1 年恢复轨迹，并评估医院事件与长期恢复的关系。
设计、地点和参与者：该事后分析汇总了美国、加拿大、欧洲和亚洲多个中心的 Clot Lysis:Evaluating Accelerated Resolution of Intraventricular Hemorrhage 3 期试验 (CLEAR-III) 和 Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation 3 期试验 (MISTIE-III) 的所有患者的个体数据。患者于 2010 年 8 月 1 日至 2018 年 9 月 30 日入组，随访时间为 1 年。999 名入组患者中，30 天改良Rankin 量表评分 (mRS) 为 4 至 5 分，排除 13 名 30 天 mRS 缺失的患者后，724 名患者存活。另外 9 名患者因缺失 1 年 mRS 而被排除。最终纳入了 715 名患者 (71.6%)，30 天 mRS 为 4 至 5 分。数据于 2019 年 7 月至 2022 年 1 月进行分析。
暴露因素：CLEAR-III 组患者随机分为脑室内阿替普酶与安慰剂组。MISTIE-III 组患者随机分为血肿立体定向溶栓与标准药物治疗组。
主要结局和测量指标：主要结局为 1 年 mRS。将患者分为 1 年时的良好结局 (mRS 0 至 3) 和不良结局 (mRS 4 至 6)。多变量逻辑回归模型评估了前瞻性调整的医院事件与治疗后 1 年的良好结局之间的关系，调整了人口统计学特征、ICH 和 IVH 严重程度以及试验队列。
结果：715 名幸存者中，417 名(58%)为男性，平均年龄 (标准差) 为 60.3(11.7)岁。总体而言，174 名参与者(24.3%)为黑人，491 名(68.6%)为白人，49 名(6.9%)为其他种族(包括亚洲人、美国原住民和太平洋岛民，由于人数较少，合并统计)；98 名(13.7%)为西班牙裔。随访 1 年时，129 名患者(18%)死亡，308 名患者(mRS 0 至 3)达到良好结局。在合并队列的调整模型中，糖尿病(aOR，0.50；95%CI，0.26-0.96)、美国国立卫生研究院卒中量表(aOR，0.93；95%CI，0.90-0.96)、严重白质疏松(aOR，0.30；95%CI，0.16-0.54)、松果体移位(aOR，0.87；95%CI，0.76-0.99)、急性缺血性卒中(aOR，0.44；95%CI，0.21-0.94)、胃造口术(aOR，0.30；95%CI，0.17-0.50)和 30 天持续脑积水(aOR，0.37；95%CI，0.14-0.98)与恢复不良相关。ICH(aOR，1.82；95%CI，1.08-3.04)和 IVH(aOR，2.19；95%CI，1.02-4.68)在 30 天内缓解与恢复至良好结局相关。在 CLEAR-III 模型中，脑灌注压小于 60 mm Hg(aOR，0.30；95%CI，0.13-0.71)、脓毒症(aOR，0.05；95%CI，0.00-0.80)和延长机械通气(aOR，95%CI，92-1.00 每增加 1 天)，以及在 MISTIE-III 中，需要颅内压监测(aOR，0.35；95%CI，0.12-0.98)是预后不良的其他因素。30 天事件基础模型强烈预测 1 年结局(AUC，0.87；95%CI，0.83-0.90)，与仅使用基线严重程度因素的模型相比，具有显著改善的区分能力(AUC，0.76；95%CI，0.71-0.80；P < .001)。
结论和意义：在初始功能预后较差的严重 ICH 和 IVH 幸存者中，超过 40%的患者在 1 年内恢复良好。医院事件与长期功能恢复密切相关，可能是潜在的干预靶点。避免早期悲观的预后预测，并在治疗后延迟预后预测，可能会提高预测未来恢复的能力。
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