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.
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||Intestinal Ischemia as a Stimulus for Systemic Inflammatory Response After Cardiac Arrest|
- Detection of Endotoxin Activity [ Time Frame: 48 hours ] [ Designated as safety issue: No ]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.
- Detection of sCD14 [ Time Frame: 48 hours ] [ Designated as safety issue: No ]To demonstrate activation of endotoxin by the immune system and "upstream" physiologic changes necessary for systemic endotoxemia to occur
- Detection of stool lactoferrin and stool α1-antitrypsin [ Time Frame: 48 hours ] [ Designated as safety issue: No ]To demonstrate evidence of intestinal inflammation and permeability that can lead to endotoxemia and "downstream" cellular inflammatory responses responsible for end organ damage
- Detection and quantification of inflammatory cytokines [ Time Frame: 48 hours ] [ Designated as safety issue: No ]To demonstrate an association with the primary outcome
- BMR measurement elevation [ Time Frame: 48 hours ] [ Designated as safety issue: No ]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
Biospecimen Retention: Samples Without DNA
Blood plasma Blood serum Whole blood Stool Expired Gas
|Study Start Date:||September 2013|
|Estimated Study Completion Date:||July 2015|
|Estimated Primary Completion Date:||July 2015 (Final data collection date for primary outcome measure)|
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01944605
|Contact: Debra Spillmanfirstname.lastname@example.org|
|United States, Virginia|
|Virginia Commonwealth University||Recruiting|
|Richmond, Virginia, United States, 23298|
|Contact: Mary Ann Peberdy, MD 804-828-4571 email@example.com|
|Principal Investigator: Mary Ann Peberdy, MD|
|Sub-Investigator: Joseph Ornato, MD|
|Sub-Investigator: Renee Reid, MD|
|Sub-Investigator: Harinder DHindsa, MD|
|Sub-Investigator: Charlotte Roberts, ACNP|
|Sub-Investigator: Puneet Puri, MD|
|Sub-Investigator: Arun Sanyal, MD|
|Sub-Investigator: Antonio Abbate, MD|
|Sub-Investigator: Veronica Sikka, MD|
|Principal Investigator:||Mary Ann Peberdy, M.D.||Virginia Commonwealth University|