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

NCT ID: NCT01944605

Last Updated: 2017-10-06

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 40 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2013-09-30
• Study Completion Date: 2014-03-30

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.

Conditions

Cardiac Arrest; Reperfusion Injury

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

Adult, Cardiac Arrest with ROSC receiving Therapeutic Hypothermia-

Exclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

American Heart Association

OTHER

Sponsor Role: collaborator

Virginia Commonwealth University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mary Ann Peberdy, M.D.

Role: PRINCIPAL_INVESTIGATOR

Virginia Commonwealth University

Locations

Virginia Commonwealth University

Richmond, Virginia, United States

Countries

United States

Other Identifiers

HM15326

Identifier Type: -

Identifier Source: org_study_id