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.

Efficacy of defibrillator pads placement during ventricular arrhythmias, a before and after analysis.

BACKGROUND: European resuscitation guidelines describe several acceptable placements of defibrillator pads during resuscitation of cardiac arrest. However, no clinical trial has compared defibrillation efficacy between any of the different pad placements. Houston Fire Department emergency medical system (EMS) used anterior-posterior (AP) defibrillator pad placement before becoming a study site in the circulation improving resuscitation care trial (CIRC). During CIRC, Houston Fire EMS used sternal-apical (SA) pad placement. METHODS: Data from electronic defibrillator records was compared between a pre-CIRC dataset and patients in the CIRC trial receiving manual cardiopulmonary resuscitation (CPR). Only shocks from patients with initial ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) were included. Measured outcome was defibrillation efficacy, defined as termination of VF/VT. The general estimatingequations model was used to study the association between defibrillation efficacy rates in the AP vs SA group. RESULTS: In the pre-CIRC dataset, 207 included patients received 1023 shocks with AP pad placement, compared with 277 patients from the CIRC trial who received 1020 shocks with SA pad placement. There was no significant difference in defibrillation efficacy between AP and SA pads placement (82.1 % vs 82.2 %, p = 0.98). CONCLUSION: No difference was observed in defibrillation efficacy between AP and SA pad placement in this study. A randomized clinical trial may be indicated.

Survival to hospital discharge with biphasic fixed 360 joules versus 200 escalating to 360 joules defibrillation strategies in out-of-hospital cardiac arrest of presumed cardiac etiology.

INTRODUCTION: Guidelines recommend constant or escalating energy levels for shocks after the initial defibrillation attempt. Studies comparing survival to hospital discharge with escalating vs fixed high energy level shocks are lacking. We compared survival to hospital discharge for 200 J escalating to 360 J vs fixed 360 J in patients with initial ventricular fibrillation/pulseless ventricular tachycardia in a post-hoc analysis of the Circulation Improving Resuscitation Care trial database. METHODS AND RESULTS: Pre-shock rhythm, rhythm 5 s after shock, shock energy levels, termination of ventricular fibrillation/pulseless ventricular tachycardia (TOF), and survival to hospital discharge were recorded. Association between defibrillation strategy and survival to hospital discharge was investigated with multivariable logistic regression. The escalating energy group included 260 patients and 883 shocks vs 478 patients and 1736 shocks in the fixed-high energy group. There was no difference in survival to hospital discharge between escalating (70/255 patients, 28%) and fixed energy group (132/478 patients, 28%) (unadjusted OR 1.00, 95% CI 0.72-1.42 and adjusted OR 0.81, 95% CI 0.54-1.22, p = 0.32). First shock TOF was 86% in the escalating group compared to 83% in the fixed-high group, p = 0.27. CONCLUSION: There was no difference in survival to hospital discharge or the frequency of TOF between escalating energy and fixed-high energy group. ClinicalTrials.gov Identifier: NCT00597207.

Transthoracic impedance used to evaluate performance of cardiopulmonary resuscitation during out of hospital cardiac arrest.

INTRODUCTION: There is a need to measure cardiopulmonary resuscitation (CPR) in order to document whether ambulance personnel follow CPR guidelines. Our goal was to do this using defibrillator technology based on changes in transthoracic impedance (TTI) produced by chest compressions and ventilations. METHODS: 122 incidents of out-of-hospital cardiac arrest between May 2003 and February 2004 were analysed based on data recorded from defibrillators in Oslo EMS. New software was used to analyze chest compressions and ventilations based on changes in thoracic impedance between the defibrillator pads, as well as ECG and other event data. RESULTS: In total, 25+/-14% (varying from 76% to 3%) of the time chest compressions were not performed on patients without spontaneous circulation (NFR=No Flow Ratio). When adjusting for time spent on analysis of ECG, pulse check and defibrillation, NFR was 20+/-13% (varying from 70% to 3%). Mean compressions delivered per minute was 87+/-16 and the compression rate during active compressions was 117+/-9min(-1). Individual variation was 31-117min(-1) (mean) and 95-144min(-1) (active periods). A mean of 14+/-3ventilations/min was recorded, varying from 8 to 26min(-1). Compared with the rest of the episode, the first 5min had a significantly higher proportion of time without chest compressions; 30+/-17% (p<0.001) and significantly lower mean compression and ventilation rates; 80+/-19min(-1) and 12+/-4min(-1), respectively (p<0.001 in both cases). CONCLUSIONS: Core CPR values can be measured from TTI signals by using a standard defibrillator and new software. NFR was 25% (20% adjusted) with great rescuer variability.

Haemodynamic outcomes during piston-based mechanical CPR with or without active decompression in a porcine model of cardiac arrest.

BACKGROUND: Experimental active compression-decompression (ACD) CPR is associated with increased haemodynamic outcomes compared to standard mechanical chest compressions. Since no clinically available mechanical chest compression device is capable of ACD-CPR, we modified the LUCAS 2 (Physio-Control, Lund, Sweden) to deliver ACD-CPR, hypothesising it would improve haemodynamic outcomes compared with standard LUCAS CPR on pigs with cardiac arrest. METHODS: The modified LUCAS delivering 5 cm compressions with or without 2 cm active decompression above anatomical chest level was studied in a randomized crossover design on 19 Norwegian domestic pigs. VF was electrically induced and untreated for 2 min. Each pig received ACD-CPR and standard mechanical CPR in three 180-s. phases. We measured aortic, right atrial, coronary perfusion, intracranial and oesophageal pressure, cerebral and carotid blood flow and cardiac output. Two-sided paired samples t-test was used for continuous parametric data and Wilcoxon test for non-parametric data. P < 0.05 was considered significant. RESULTS: Due to injuries/device failure, the experimental protocol was completed in nine of 19 pigs. Cardiac output (l/min, median, (25, 75-percentiles): 1.5 (1.1, 1.7) vs. 1.1 (0.8, 1.5), p < 0.01), cerebral blood flow (AU, 297 vs. 253, mean difference: 44, 95% CI; 14-74, p = 0.01), and carotid blood flow (l/min, median, (25, 75-percentiles): 97 (70, 106) vs. 83 (57, 94), p < 0.01) were higher during ACD-CPR compared to standard mechanical CPR. Coronary perfusion pressure (CPP) trended towards higher in end decompression phase. CONCLUSION: Cardiac output and brain blood flow improved with mechanical ACD-CPR and CPP trended towards higher during end-diastole compared to standard LUCAS CPR.

Defibrillation success during different phases of the mechanical chest compression cycle.

INTRODUCTION: Animal studies indicate higher termination of VF/VT (TOF) rates after shocks delivered during the decompression phase of the compression cycle for manual and mechanical CPR. We investigated TOF for shocks delivered in different compression cycle phases during load distributing band (LDB) mechanical CPR in the CIRC trial. METHODS: Shocks were retrospectively categorized as delivered during the compression, decompression, or relaxation phase of LDB compressions using transthoracic impedance data. Shocks delivered when the LDB device was paused, were used as controls. The first shock and the first up-to-three shocks (first shocks plus shocks two and three if given) from patients with initial VF/VT and LDB CPR prior to shock were grouped according to compression cycle phase. TOF rates for these groups versus the control group were analyzed using logistic regression for first shocks and the general estimating equations (GEE) model for the up-to-three shocks. Adjustments were made for bystander CPR, witnessed arrest, defibrillator shock energy and transthoracic impedance. RESULTS: Among 244 first shocks and 685 up-to-three shocks TOF success rates were lower (p<0.05 and p<0.02) for shocks given during the compression phase (72% and 71% respectively) than for control shocks given during compression pauses (86% and 82% respectively). Decompression and relaxation phase shocks had TOF rates not different from the controls. CONCLUSION: Shocks delivered in the compression phase of LDB chest compressions had lower TOF rates than shocks delivered while pausing the LDB device. More research is needed to see how defibrillation during chest compressions affect ROSC and survival.

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.

Pre-shock chest compression pause effects on termination of ventricular fibrillation/tachycardia and return of organized rhythm within mechanical and manual cardiopulmonary resuscitation.

BACKGROUND: Shorter manual chest compression pauses prior to defibrillation attempts is reported to improve the defibrillation success rate. Mechanical load-distributing band (LDB-) CPR enables shocks without compression pause. We studied pre-shock pause and termination of ventricular fibrillation/pulseless ventricular tachycardia 5s post-shock (TOF) and return of organized rhythm (ROOR) with LDB and manual (M-) CPR. METHODS: In a secondary analysis from the Circulation Improving Resuscitation Care trial, patients with initial shockable rhythm and interpretable post-shock rhythms were included. Pre-shock rhythm, pause duration (if any), and post-shock rhythm were obtained for each shock. Associations between TOF/ROOR and pre-shock pause duration, including no pause shocks with LDB-CPR, were analyzed with Chi-square test. A p-value <0.05 was considered statistically significant. RESULTS: For TOF and ROOR analyses we included 417 LDB-CPR patients with 1476 and 1438 shocks, and 495 M-CPR patients with 1839 and 1796 shocks, respectively. For first shocks with LDB-CPR, pre-shock pause was associated with TOF (p=0.049) with lowest TOF (77%) for shocks given without pre-shock compression pause. This association was not significant when all shocks were included (p=0.07) and not for ROOR. With M-CPR there were no significant associations between shock-related chest compression pause duration and TOF or ROOR. CONCLUSION: For first shocks with LDB-CPR, termination of fibrillation was associated with pre-shock pause duration. There was no association for the rate of return of organized rhythm. For M-CPR, where no shocks were given during continuous chest compressions, there were no associations between pre-shock pause duration and TOF or ROOR.

Minimizing pre-shock chest compression pauses in a cardiopulmonary resuscitation cycle by performing an earlier rhythm analysis.

BACKGROUND: Guidelines recommend 2min of CPR after defibrillation attempts followed by ECG analysis during chest compression pause. This pause may reduce the likelihood of return of spontaneous circulation (ROSC) and survival. We have evaluated the possibility of analysing the rhythm earlier in the CPR cycle in an attempt to replace immediate pre-shock rhythm analysis. METHODS AND RESULTS: The randomized Circulation Improving Resuscitation Care (CIRC) trial included patients with out of hospital cardiac arrest of presumed cardiac aetiology. Defibrillator data were used to categorize ECG rhythms as shockable or non-shockable 1min post-shock and immediately before next shock. ROSC was determined from end-tidal CO2, transthoracic impedance (TTI), and patient records. TTI was used to identify chest compressions. Artefact free ECGs were categorized during periods without chest compressions. Episodes without ECG or TTI data or with undeterminable ECG rhythm were excluded. Data were analyzed using descriptive statistics. Of 1657 patients who received 3409 analysable shocks, the rhythm was shockable in 1529 (44.9%) cases 1min post-shock, 13 (0.9%) of which were no longer shockable immediately prior to next possible shock. Of these, three had converted to asystole, seven to PEA and three to ROSC. CONCLUSION: While a shockable rhythm 1min post-shock was present also immediately before next possible defibrillation attempt in most cases, three patients had ROSC. Studies are needed to document if moving the pre-shock rhythm analysis will increase shocks delivered to organized rhythms, and if it will increase shock success and survival.

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.