Intestinal Ischemia as a Stimulus for Systemic Inflammatory Response After Cardiac Arrest (TICA)
Out-of-hospital cardiac arrest (CA) is a leading public health problem causing nearly one third of a million deaths annually in the US, accounting for half of all cardiovascular deaths and surpassing deaths from stroke, heart failure, and breast and lung cancer combined. Twenty to fifty percent of CA patients (pts) can be resuscitated initially but many die before hospital discharge or suffer permanent neurologic damage. Therapeutic hypothermia (TH) improves survival and neurological outcomes. Despite aggressive, targeted post arrest management, including TH, approximately 50% of pts die before leaving the hospital due to global ischemia-reperfusion injury (IRI) known as the "post arrest syndrome", 1 which is a sepsis-like state characterized by elevated markers of cellular inflammation and injury. It is believed that TH works by decreasing the body's basal metabolic rate (BMR) and attenuating the systemic inflammatory response (SIR). However, specific triggers of the intense pro-inflammatory response are unclear. This "gap" in knowledge must be closed to identify targeted therapy to decrease IRI and improve outcomes.
Blood flow to the gut is decreased markedly and intestinal tissue becomes ischemic during CA and CPR, particularly when vasoconstrictor drugs such as epinephrine, are given. IRI of the intestine increases intestinal permeability leading to intestinal microbial translocation and endotoxin release that can stimulate and perpetuate systemic inflammation and cause subsequent multi-organ dysfunction. Endotoxin also increases body temperature and energy expenditure and may attenuate TH induced reductions in BMR and hence, decrease efficacy. The purpose of this novel pilot study is to detect systemic endotoxin release following CA in humans and determine association with cytokine activation, and BMR alterations during TH.
研究概览
详细说明
Hypothesis 1 Intestinal ischemia during and following Caridac Arrest leads to increased gut permeability and endotoxin release that stimulates the Systemic Inflammatory Response that is responsible for subsequent death and disability after resuscitation.
Hypothesis 2: Different degrees of systemic endotoxin activity variably affect Basic Metabolic Rate during Therapeutic Hypothermia
Serial samples of blood, stool and expired gas will be measured at predetermined timepoints after ROSC from cardiac arrest.
研究类型
注册 (实际的)
联系人和位置
学习地点
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Virginia
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Richmond、Virginia、美国、23298
- Virginia Commonwealth University
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
取样方法
研究人群
描述
Inclusion Criteria:
Adult, Cardiac Arrest with ROSC receiving Therapeutic Hypothermia-
Exclusion Criteria:
- Age < 18
- Cardiac Arrest of traumatic etiology
- Known to be pregnant
- Prisoner
学习计划
研究是如何设计的?
设计细节
- 观测模型:队列
- 时间观点:预期
队列和干预
团体/队列 |
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Cardiac Arrest patients undergoing Therapeutic Hypothermia
Cardiac Arrest subjects with Return Of Spontaneous Circulation (ROSC) and undergoing treatment with Therapeutic Hypothermia will undergo sampling of blood, stool, and expired gas data at physiologically predetermined time points.
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Detection of Endotoxin Activity
大体时间:48 hours
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Endotoxin activity will be measured by the Endotoxin Activity Assay and values . of >0.4 EA units will be used as the "cut-off" for the presence of pathological endotoxin.
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48 hours
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Detection of sCD14
大体时间:48 hours
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To demonstrate activation of endotoxin by the immune system and "upstream" physiologic changes necessary for systemic endotoxemia to occur
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48 hours
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Detection of stool lactoferrin and stool α1-antitrypsin
大体时间:48 hours
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To demonstrate evidence of intestinal inflammation and permeability that can lead to endotoxemia and "downstream" cellular inflammatory responses responsible for end organ damage
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48 hours
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Detection and quantification of inflammatory cytokines
大体时间:48 hours
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To demonstrate an association with the primary outcome
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48 hours
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BMR measurement elevation
大体时间:48 hours
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To determine its association with endotoxemia and cytokine.
BMR is being measured to determine if pts with higher levels of endotoxin and cytokines have higher BMR and therefore blunted therapeutic value of TH
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48 hours
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合作者和调查者
调查人员
- 首席研究员:Mary Ann Peberdy, M.D.、Virginia Commonwealth University
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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