Characterization of mitochondrial injury after cardiac arrest (COMICA).

INTRODUCTION: Mitochondrial injury post-cardiac arrest has been described in pre-clinical settings but the extent to which this injury occurs in humans remains largely unknown. We hypothesized that increased levels of mitochondrial biomarkers would be associated with mortality and neurological morbidity in post-cardiac arrest subjects. METHODS: We performed a prospective multicenter study of post-cardiac arrest subjects. Inclusion criteria were comatose adults who suffered an out-of-hospital cardiac arrest. Mitochondrial biomarkers were measured at 0, 12, 24, 36 and 48h after return of spontaneous circulation as well as in healthy controls. RESULTS: Out of 111 subjects enrolled, 102 had evaluable samples at 0h. Cardiac arrest subjects had higher baseline cytochrome c levels compared to controls (2.18ng/mL [0.74, 7.74] vs. 0.16ng/mL [0.03, 0.91], p<0.001), and subjects who died had higher 0h cytochrome c levels compared to survivors (3.66ng/mL [1.40, 14.9] vs. 1.27ng/mL [0.16, 2.37], p<0.001). There were significantly higher Ribonuclease P (RNaseP) (3.3 [1.2, 5.7] vs. 1.2 [0.8, 1.2], p<0.001) and Beta-2microglobulin (B2M) (12.0 [1.0, 22.9], vs. 0.6 [0.6, 1.3], p<0.001) levels in cardiac arrest subjects at baseline compared to the control subjects. There were no differences between survivors and non-survivors for mitochondrial DNA, nuclear DNA, or cell free DNA. CONCLUSIONS: Cytochrome c was increased in post- cardiac arrest subjects compared to controls, and in post-cardiac arrest non-survivors compared to survivors. Nuclear DNA and cell free DNA was increased in plasma of post-cardiac arrest subjects. There were no differences in mitochondrial DNA, nuclear DNA, or cell free DNA between survivors and non-survivors. Mitochondrial injury markers showed mixed results in the post-cardiac arrest period. Future research needs to investigate these differences.

Initial lactate and lactate change in post-cardiac arrest: a multicenter validation study.

OBJECTIVE: Rate of lactate change is associated with in-hospital mortality in post-cardiac arrest patients. This association has not been validated in a prospective multicenter study. The objective of the current study was to determine the association between percent lactate change and outcomes in post-cardiac arrest patients. DESIGN: Four-center prospective observational study conducted from June 2011 to March 2012. SETTING: The National Post-Arrest Research Consortium is a clinical research network conducting research in post-cardiac arrest care. The network consists of four urban tertiary care teaching hospitals. PATIENTS: Inclusion criteria consisted of adult out-of-hospital non-traumatic cardiac arrest patients who were comatose after return of spontaneous circulation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was survival to hospital discharge, and secondary outcome was good neurologic outcome. We compared the absolute lactate levels and the differences in the percent lactate change over 24 hours between survivors and nonsurvivors and between subjects with good and bad neurologic outcomes. One hundred patients were analyzed. The median age was 63 years (interquartile range, 50-75) and 40% were female. Ninety-seven percent received therapeutic hypothermia, and overall survival was 46%. Survivors and patients with good neurologic outcome had lower lactate levels at 0, 12, and 24 hours (p< 0.01). In adjusted models, percent lactate decrease at 12 hours was greater in survivors (odds ratio, 2.2; 95% CI, 1.1-6.2) and in those with good neurologic outcome (odds ratio, 2.2; 95% CI, 1.1-4.4). CONCLUSION: Lower lactate levels at 0, 12, and 24 hours and greater percent decrease in lactate over the first 12 hours post cardiac arrest are associated with survival and good neurologic outcome.

Body temperature changes are associated with outcomes following in-hospital cardiac arrest and return of spontaneous circulation.

INTRODUCTION: Spontaneous changes in body temperature after return of circulation (ROSC) from cardiac arrest are common, but the association of these changes with outcomes in hospitalized patients who survive to 24h post-ROSC is not known. We tested the hypothesis that adults who experience temperature lability in the first 24h have worse outcomes compared with those who maintain normothermia. MATERIALS AND METHODS: A prospective observational study from a multicenter registry of cardiac arrests (National Registry of Cardiopulmonary Resuscitation) from 355 US and Canadian hospitals. 14,729 adults with return of circulation from a pulseless cardiac arrest. We excluded those who died or were discharged before 24h post-event, those made Do-Not-Resuscitate (DNR) within 24h of event, those that had a preceding trauma, and those with multiple cardiac arrests. Finally, we included only subjects that had both a lowest (T(min)) and highest (T(max)) body temperature value recorded during the first 24-h after ROSC, resulting in a study sample of 3426 patients. RESULTS: After adjustment for potential covariates, there was a lower odds of survival in those having an episode of hypothermia (adjusted odds ratio [OR], 0.62; 95% confidence interval [CI], 0.48-0.80), those having an episode of hyperthermia (OR, 0.67; 95% CI, 0.48-0.80), and those having an episode of both (OR, 0.59; 95% CI, 0.39-0.91). Among those who survived to discharge, there was also a lower odds of favorable neurologic performance in those who had an episode of hyperthermia (OR, 0.71; 95% CI, 0.51-0.98). CONCLUSIONS: Episodes of temperature lability following in-hospital resuscitation from cardiac arrest are associated with lower odds of surviving to discharge. Hyperthermia is also associated with fewer patients leaving the hospital with favorable neurologic performance. Further studies should identify whether therapeutic control over changes in body temperature after in-hospital cardiac arrest improves outcomes.

Defibrillation.

The field of defibrillation is one of the most rapidly advancing areas in resuscitation. Defibrillation is also one of the most promising interventions for achieving improved survival from cardiac arrest. The purpose of this article is to provide an overview of the science and clinical applications of defibrillation.