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.
Panoramica dello studio
Stato
Condizioni
Descrizione dettagliata
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.
Tipo di studio
Iscrizione (Effettivo)
Contatti e Sedi
Luoghi di studio
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Virginia
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Richmond, Virginia, Stati Uniti, 23298
- Virginia Commonwealth University
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Metodo di campionamento
Popolazione di studio
Descrizione
Inclusion Criteria:
Adult, Cardiac Arrest with ROSC receiving Therapeutic Hypothermia-
Exclusion Criteria:
- Age < 18
- Cardiac Arrest of traumatic etiology
- Known to be pregnant
- Prisoner
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Modelli osservazionali: Coorte
- Prospettive temporali: Prospettiva
Coorti e interventi
Gruppo / Coorte |
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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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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Detection of Endotoxin Activity
Lasso di tempo: 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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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Detection of sCD14
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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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Collaboratori e investigatori
Sponsor
Collaboratori
Investigatori
- Investigatore principale: Mary Ann Peberdy, M.D., Virginia Commonwealth University
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Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- HM15326
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Prove cliniche su Lesioni da riperfusione
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Hospital Universitari Son DuretaEspen; This research prize was funded by Nestle Nutrition Institute and by Fresenius...CompletatoTrauma da moderato a grave, come definito da an | Injury Severity Score (ISS) > 12 punti sono stati inclusi nello studio.Spagna