The detrimental effects of intestinal injury mediated by inflammation are limited in cardiac arrest patients: A prospective cohort study.

Background: Ischaemic intestines could be a driver of critical illness through an inflammatory response. We have previously published reports on a biomarker for intestinal injury, plasma Intestinal Fatty Acid Binding Protein (IFABP), and inflammatory biomarkers after out-of-hospital cardiac arrest (OHCA). In this post-hoc study we explored the potential indirect effects of intestinal injury mediated through the inflammatory response on organ dysfunction and mortality. Methods: We measured IFABP and twenty-one inflammatory biomarkers in 50 patients at admission to intensive care unit after OHCA. First, we stratified patients on median IFABP and compared biomarkers between "low" and "high" IFABP. Second, by causal mediation analysis, we assessed effects of IFABP through the two most important inflammatory biomarkers, interleukin (IL)-6 and terminal complement complex (TCC), on day two circulatory variables, Sequential Organ Failure Assessment (SOFA)-score, and 30-day mortality. Results: Cytokines and complement activation were higher in the high IFABP group. In mediation analysis, patients on the 75th percentile of IFABP, compared to the 25th percentile, had 53% (95% CI, 33-74; p < 0.001) higher risk of dying, where 13 (95% CI, 3-23; p = 0.01) percentage points were mediated through an indirect effect of IL-6. Similarly, the indirect effect of IFABP through IL-6 on SOFA-score was significant, but smaller than potential other effects. Effects through IL-6 on circulatory variables, and all effects through TCC, were not statistically significant and/or small. Conclusion: Effects of intestinal injury mediated through inflammation on organ dysfunction and mortality were limited. Small, but significant, effects through IL-6 were noted.Trial registration: ClinicalTrials.gov: NCT02648061.

Intestinal injury in cardiac arrest is associated with multiple organ dysfunction: A prospective cohort study.

BACKGROUND: The impact of intestinal injury in cardiac arrest is not established. The first aim of this study was to assess associations between clinical characteristics in out-of-hospital cardiac arrest (OHCA) and a biomarker for intestinal injury, Intestinal Fatty Acid Binding Protein (IFABP). The second aim was to assess associations between IFABP and multiple organ dysfunction and 30-day mortality. METHODS: We measured plasma IFABP in 50 patients at admission to intensive care unit (ICU) after OHCA. Demographic and clinical variables were analysed by stratifying patients on median IFABP, and by linear regression. We compared Sequential Organ Failure Assessment (SOFA) score, haemodynamic variables, and clinical-chemistry tests at day two between the "high" and "low" IFABP groups. Logistic regression was applied to assess factors associated with 30-day mortality. RESULTS: Several markers of whole body ischaemia correlated with intestinal injury. Duration of arrest and lactate serum concentrations contributed to elevated IFABP in a multivariable model (p < 0.01 and p = 0.04, respectively). At day two, all seven patients who had died were in the "high" IFABP group, and all six patients who had been transferred to ward were in the "low" group. Of patients still treated in the ICU, the "high" group had higher total, renal and respiratory SOFA score (p < 0.01) and included all patients receiving inotropic drugs. IFABP predicted mortality (OR 16.9 per standard deviation increase, p = 0.04). CONCLUSION: Cardiac arrest duration and lactate serum concentrations were risk factors for intestinal injury. High levels of IFABP at admission were associated with multiple organ dysfunction and mortality. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02648061.

REBOARREST, resuscitative endovascular balloon occlusion of the aorta in non-traumatic out-of-hospital cardiac arrest: a study protocol for a randomised, parallel group, clinical multicentre trial.

BACKGROUND: Survival after out-of-hospital cardiac arrest (OHCA) is poor and dependent on high-quality cardiopulmonary resuscitation. Resuscitative endovascular balloon occlusion of the aorta (REBOA) may be advantageous in non-traumatic OHCA due to the potential benefit of redistributing the cardiac output to organs proximal to the aortic occlusion. This theory is supported by data from both preclinical studies and human case reports. METHODS: This multicentre trial will enrol 200 adult patients, who will be randomised in a 1:1 ratio to either a control group that receives advanced cardiovascular life support (ACLS) or an intervention group that receives ACLS and REBOA. The primary endpoint will be the proportion of patients who achieve return of spontaneous circulation with a duration of at least 20 min. The secondary objectives of this trial are to measure the proportion of patients surviving to 30 days with good neurological status, to describe the haemodynamic physiology of aortic occlusion during ACLS, and to document adverse events. DISCUSSION: Results from this study will assess the efficacy and safety of REBOA as an adjunctive treatment for non-traumatic OHCA. This novel use of REBOA may contribute to improve treatment for this patient cohort. TRIAL REGISTRATION: The trial is approved by the Regional Committee for Medical and Health Research Ethics in Norway (reference 152504) and is registered at ClinicalTrials.gov (reference NCT04596514) and as Universal Trial Number WHO: U1111-1253-0322.