Observed survival benefit of mild therapeutic hypothermia reanalysing the Circulation Improving Resuscitation Care trial.

BACKGROUND: Mild therapeutic hypothermia is argued being beneficial for outcome after cardiac arrest. MATERIALS AND METHODS: Retrospective analysis of Circulation Improving Resuscitation Care (CIRC) trial data to assess if therapeutic cooling to 33 ± 1 °C core temperature had an association with survival. Of 4231 adult, out-of-hospital cardiac arrests of presumed cardiac origin initially enrolled, eligibility criteria for therapeutic hypothermia were met by 1812. Logistic regression was undertaken in a stepwise fashion to account for the impact on outcome of each significant difference and for the variable of interest between the groups. RESULTS: Out-of- and in-hospital cooled were 263 (15%), only after admission cooled were 230 (13%) and not cooled were 357 (20%) patients. The group cooled out of- and in hospital had 98 (37%) survivors as compared to the groups cooled in hospital only [80 (35%)] and of those not cooled [68 (19%)]. After adjusting for known covariates (sex, age, witnessed cardiac arrest, no- and low-flow time, shockable initial rhythm, random allocation, bystander cardiopulmonary resuscitation and percutaneous coronary intervention), the odds ratio for survival comparing no cooling to out-of- plus in-hospital cooling was 0·53 [95% confidence interval (CI): 0·46-0·61, P < 0·001], and comparing to in-hospital cooling only was 0·67 (95% CI: 0·50-0·89, P = 0·006). CONCLUSION: Mild therapeutic hypothermia initiated out of hospital and/or in hospital was associated with improved survival within this secondary analysis of the CIRC cohort compared to no therapeutic hypothermia.

Why do some studies find that CPR fraction is not a predictor of survival?

INTRODUCTION: An 80% chest compression fraction (CCF) during resuscitation is recommended. However, heterogeneous results in CCF studies were found during the 2015 Consensus on Science (CoS), which may be because chest compressions are stopped for a wide variety of reasons including providing lifesaving care, provider distraction, fatigue, confusion, and inability to perform lifesaving skills efficiently. OBJECTIVE: The effect of confounding variables on CCF to predict cardiac arrest survival. METHODS: A secondary analysis of emergency medical services (EMS) treated out-of-hospital cardiac arrest (OHCA) patients who received manual compressions. CCF (percent of time patients received compressions) was determined from electronic defibrillator files. Two Sample Wilcoxon Rank Sum or regression determined a statistical association between CCF and age, gender, bystander CPR, public location, witnessed arrest, shockable rhythm, resuscitation duration, study site, and number of shocks. Univariate and multivariate logistic regressions were used to determine CCF effect on survival. RESULTS: Of 2132 patients with manual compressions 1997 had complete data. Shockable rhythm (p<0.001), public location (p<0.004), treatment duration (p<0.001), and number of shocks (p<0.001) were associated with lower CCF. Univariate logistic regression found that CCF was inversely associated with survival (OR 0.07; 95% CI 0.01-0.36). Multivariate regression controlling for factors associated with survival and/or CCF found that increasing CCF was associated with survival (OR 6.34; 95% CI 1.02-39.5). CONCLUSION: CCF cannot be looked at in isolation as a predictor of survival, but in the context of other resuscitation activities. When controlling for the effects of other resuscitation activities, a higher CCF is predictive of survival. This may explain the heterogeneity of findings during the CoS review.

Manual vs. integrated automatic load-distributing band CPR with equal survival after out of hospital cardiac arrest. The randomized CIRC trial.

OBJECTIVE: To compare integrated automated load distributing band CPR (iA-CPR) with high-quality manual CPR (M-CPR) to determine equivalence, superiority, or inferiority in survival to hospital discharge. METHODS: Between March 5, 2009 and January 11, 2011 a randomized, unblinded, controlled group sequential trial of adult out-of-hospital cardiac arrests of presumed cardiac origin was conducted at three US and two European sites. After EMS providers initiated manual compressions patients were randomized to receive either iA-CPR or M-CPR. Patient follow-up was until all patients were discharged alive or died. The primary outcome, survival to hospital discharge, was analyzed adjusting for covariates, (age, witnessed arrest, initial cardiac rhythm, enrollment site) and interim analyses. CPR quality and protocol adherence were monitored (CPR fraction) electronically throughout the trial. RESULTS: Of 4753 randomized patients, 522 (11.0%) met post enrollment exclusion criteria. Therefore, 2099 (49.6%) received iA-CPR and 2132 (50.4%) M-CPR. Sustained ROSC (emergency department admittance), 24h survival and hospital discharge (unknown for 12 cases) for iA-CPR compared to M-CPR were 600 (28.6%) vs. 689 (32.3%), 456 (21.8%) vs. 532 (25.0%), 196 (9.4%) vs. 233 (11.0%) patients, respectively. The adjusted odds ratio of survival to hospital discharge for iA-CPR compared to M-CPR, was 1.06 (95% CI 0.83-1.37), meeting the criteria for equivalence. The 20 min CPR fraction was 80.4% for iA-CPR and 80.2% for M-CPR. CONCLUSION: Compared to high-quality M-CPR, iA-CPR resulted in statistically equivalent survival to hospital discharge.

Design of the Circulation Improving Resuscitation Care (CIRC) Trial: a new state of the art design for out-of-hospital cardiac arrest research.

PURPOSE: Mechanical chest compression devices, such as the AutoPulse(®), have been developed to overcome problems associated with manual CPR (M-CPR). Animal and human studies have shown that AutoPulse CPR improves hemodynamic parameters over M-CPR. However, human studies conducted in the prehospital setting have conflicting results as to the AutoPulse's efficacy in improving survival. The Circulation Improving Resuscitation Care (CIRC) Trial is designed to evaluate the effectiveness of integrated AutoPulse-CPR (iA-CPR) (i.e., M-CPR followed by AutoPulse(®)-CPR) in a randomized controlled trial that addresses methodological issues that may have influenced the results of previous studies. METHODS: This paper describes the methodology of the CIRC trial. RESULTS: Unlike previous trials the CIRC trial studies iA-CPR where emphasis is placed on reducing "hands-off" time. The trial has six unique features: (1) training of all EMS providers in a standardized deployment strategy that reduces hands-off time and continuous monitoring for protocol compliance. (2) A pre-trial simulation study of provider compliance with the trial protocol. (3) Three distinct study phases (in-field training, run-in, and statistical inclusion) to minimize the Hawthorne effect and other biases. (4) Monitoring of the CPR process using either transthoracic impedance or accelerometer data. (5) Randomization at the subject level after the decision to resuscitate is made to reduce selection bias. (6) Use of the Group Sequential Double Triangular Test with sufficient power to determine superiority, inferiority, or equivalence. CONCLUSION: This unique, large, multicenter study comparing the effectiveness of iA-CPR to M-CPR will contribute to the science of the treatment of out-of-hospital cardiac arrest as well as to the design of future trials.