Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 273
- 试验地点
- 8
- 主要终点
- Change in short-term cognition as measured by continuous cognitive score
研究概览
简要总结
In this study the investigator will randomize 273 subjects to deep (<20°C), low (20.1°C-24°C), or moderate (24.1°C-28°C) hypothermia during aortic arch surgery with circulatory arrest. The primary purpose of this study is to determine the effect of deep vs low vs moderate hypothermia on neurocognitive function, brain functional connectivity, and leukocyte SUMOylation patterns after surgical circulatory arrest in participants.
详细描述
Purpose of the Study: Determine the effect of deep vs low vs moderate hypothermia on neurocognitive function, brain functional connectivity, and leukocyte SUMOylation patterns after surgical circulatory arrest.
Hypothesis
Deep hypothermia is superior to moderate hypothermia in reducing postoperative cognitive decline and preserving brain functional connectivity and that low hypothermia is non-inferior to deep hypothermia.
Design and Procedures: 273 informed and consenting patients who are scheduled for elective proximal aortic reconstructive surgery (ascending aorta + aortic valve or root) with concomitant proximal hemi- or total arch replacement via median sternotomy will be randomized to deep (<20°C), low (20.1°C-24°C), or moderate (24.1°C-28°C) hypothermia during circulatory arrest. Cognitive testing using a standard battery will occur preoperatively (baseline), at 4 weeks, and at 1 year after surgery. Neuroimaging procedures before surgery, and at 4 weeks and 1 year after surgery will consist of high-resolution anatomic, resting-state fMRI (rs-fMRI) and magnetic resonance spectroscopy (MRS) sequences. To characterize leukocyte activation, whole blood will be drawn at 5 time points: at baseline (prior to surgery), before circulatory arrest, 10 minutes after reperfusion, 10 minutes after CPB, and 4 hours after CPB.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients who are scheduled for elective proximal aortic reconstructive surgery (ascending aorta + aortic valve or root) with concomitant proximal hemi- or total arch replacement via median sternotomy
排除标准
- •< 18 years of age
- •History of symptomatic cerebrovascular disease, eg, prior stroke with residual deficit
- •Alcoholism (> 2 drinks/day)
- •Psychiatric illness (any clinical diagnoses requiring therapy)
- •Drug abuse (any illicit drug use in the past 3 months)
- •Hepatic insufficiency (liver function tests > 1.5 times the upper limit of normal)
- •Severe pulmonary insufficiency (requiring home oxygen therapy)
- •Renal failure (serum creatinine > 2.0 mg/dL)
- •Claustrophobic fear
- •Unable to read and thus unable to complete the cognitive testing
- •Pregnant women
- •Patients who score < 24 on a baseline Mini Mental State Examination (MMSE) or ≥ 27 on the baseline Center for Epidemiological Studies Depression (CES-D) scale
- •Patients who have pre-existing unsafe implants for 3 Tesla magnetic resonance imaging (MRI).
- •Patients who have received chemotherapy in the last 12 months.
- •Patients with COVID-19 diagnosis within the past 12 months
结局指标
主要结局
Change in short-term cognition as measured by continuous cognitive score
时间窗: From baseline to 4 weeks post-operatively
To characterize cognitive function over time while minimizing potential redundancy in the cognitive measures, a factor analysis will be performed on the cognitive test scores from baseline. A continuous change score will be calculated by subtracting the baseline cognitive index (the mean of the domain scores from factor analysis) from the follow-up cognitive index at 4 weeks.
次要结局
- Change in neurological function as measured by NIHSS(Assessed at baseline, post-op day 4, 4 weeks)
- Change in neuronal metabolism(From baseline to 4 weeks)
- Change in Duke Activity Status Index score(From baseline to 4 weeks postoperatively)
- Change in employment status(From baseline to 1 year postoperatively)
- Incidence of delirium(Up to post-operative day 3)
- Change in SUMO 2/3 levels(Pre-incision, before circulatory arrest, 10 minutes after reperfusion, 10 minutes after cardiopulmonary bypass, 4 hrs after cardiopulmonary bypass)
- Change in depression score(From baseline to 4 weeks postoperatively)
- Change in long-term cognition as measured by continuous cognitive score(From baseline to 1 year post-operatively)
- Change in resting-state functional connectivity(From baseline to 4 weeks post-operatively)
- Change in anxiety score(From baseline to 4 weeks postoperatively)
- Change in SF-36 score(From baseline to 1 year postoperatively)