Intestinal Ischemia as a Stimulus for Systemic Inflammatory Response After Cardiac Arrest

Completed

• Conditions: Reperfusion Injury; Cardiac Arrest

• Registration Number: NCT01944605
• Lead Sponsor: Virginia Commonwealth University

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study Start: 2013-09
• Study First Submitted: 2013-09-12
• Study First Submitted QC: 2013-09-12
• Study First Posted: 2013-09-17
• Primary Completion: 2014-03-30
• Study Completion: 2014-03-30
• Status Verified: 2017-10
• Last Update Submitted: 2017-10-05
• Last Update Posted: 2017-10-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

Adult, Cardiac Arrest with ROSC receiving Therapeutic Hypothermia-

Exclusion Criteria

• Age < 18
• Cardiac Arrest of traumatic etiology
• Known to be pregnant
• Prisoner

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Detection of Endotoxin Activity	48 hours	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.

Secondary Outcome Measures

Name	Time	Method
Detection of sCD14	48 hours	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	48 hours	To demonstrate evidence of intestinal inflammation and permeability that can lead to endotoxemia and "downstream" cellular inflammatory responses responsible for end organ damage
BMR measurement elevation	48 hours	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
Detection and quantification of inflammatory cytokines	48 hours	To demonstrate an association with the primary outcome

Trial Locations

Locations (1)

Virginia Commonwealth University; 🇺🇸 Richmond, Virginia, United States