Disclosure. Co-investigators 1/23/2015

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The impact of chest compression fraction on clinical outcomes from shockable out-of-hospital cardiac arrest during the ROC PRIMED trial Sheldon Cheskes, MD CCFP(EM) FCFP Medical Director, Sunnybrook Centre for Prehospital Medicine Assistant Professor, Division of Emergency Medicine, University of Toronto Collaborating Investigator, Li Ka Shing Knowledge Institute, St. Michael s Hospital Co-Principal Investigator, Toronto RescuNet, Resuscitation Outcomes Consortium Disclosure Financial Disclosure: speaking honorarium and research funding, Zoll Medical Inc. Unlabeled/Unapproved Uses Disclosure: None Conflicts of Interest: AstraZeneca Brilinta Advisory Board Co-investigators Robert H. Schmiker Tom Rea Judy Powell Ian R. Drennan Peter Kudenchuck Christian Vaillancourt Ian Stiell Dion Stubb Noah Alexander Dan Davis William Conway Jim Christenson For the ROC Investigators 1

ROC Funding Partners Background The association between chest compression fraction (CCF) and survival from shockable out-of-hospital cardiac arrest (OHCA) remains uncertain Previous Resuscitation Outcomes Consortium (ROC) research shows association between CCF and survival from shockable OHCA but only assessed compressions up to the first prehospital rhythm analysis Recent observational study suggests an association between CCF and survival from shockable OHCA during prolonged resuscitations (> 20 mins) No large multicenter study has assessed the association between CCF and clinical outcomes accounting for time of ROSC and resuscitation length CCF During ROC PRIMED Purpose Examine the relationship between CCF and clinical outcomes in a secondary analysis of data from the ROC PRIMED trial Hypothesis Increases in CCF would be associated with improved clinical outcomes 2

Methods Secondary data analysis of cardiopulmonary resuscitation (CPR) quality data from all sites participating in the ROC PRIMED trial Adult, non-traumatic OHCA, presented in shockable rhythm and had CPR process measures for at least one shock Excluded cases of EMS witnessed arrest, PAD defibrillation prior to EMS arrival, missing regression variable data Methods Multivariable logistic regression adjusting for Utstein variables, ROC site, shock pause duration and compression rate to assess association between CCF and ROSC, survival to hospital discharge and neuro intact survival (MRS 3). Models constructed to assess association between CCF and survival to hospital discharge adjusting for length of EMS resuscitation and timing of ROSC (<5 mins, 5-10 mins). Due to potential confounding between CCF and cases that achieve early ROSC, we performed an analysis restricted to patients with no ROSC in the first 10 minutes of resuscitation. CCF During ROC PRIMED RESULTS 3

Consort Diagram of Study Population Study Cohort Baseline Characteristics Study Cohort CPR Quality Metrics 4

Unadjusted Association between CCF and Clinical Outcomes Logistic Regression Model (all cases) Logistic Regression Model (no ROSC first 10 mins) 5

Discussion Discussion Negative correlation between CCF and survival to hospital discharge No association between CCF and survival to hospital discharge for resuscitations with no ROSC in the first 10 mins of resuscitation Does this mean poor quality CPR (as measured by CCF) is what we should strive for?? Is there biological plausibility for our findings? Methodology - The devil is in the details Differences between Epistry CCF and PRIMED CCF Epistry CCF PRIMED CCF Methodology CPR to First Analysis* CPR Up to Time of ROSC or all CPR Process Data AE vs. AL and ITD No RCT? Impact of AE vs. AL and ITD N 506 2006 Distribution of Episodes 79% Data from 2 Sites Data from Whole Consortium Mean CCF 0.65 0.7 (median 0.75) % Cases with CPR Fraction <0.4 34% 2.8% Bystander CPR 1.14 (0.73 1.78) 1.35 (1.07 1.70) 6

Exploratory Analysis No relationship between CCF and survival for patients with STEMI vs. NSTEMI No relationship between CCF and survival for patient undergoing PCI and no PCI No relationship between CCF and survival for patients undergoing TH and no TH Appears to be relationship between CCF and survival for prolonged resuscitations (> 20 mins) FAQs!! No co-linearity between CPR quality metrics (VIF < 10) Model 2 (main model) fit well, based on Pearson Chi-Square goodness of fit p=0.26 Remove all CPR quality metrics from model resulted in no change in findings Ischemic preconditioning?? Limitations Short resuscitations limited by lack of CPR quality data No CPR quality data by bystanders prior to pad placement (is high quality bystander CPR as important as early EMS CPR?) Confounded by indication?? (resuscitation length) Optimized EMS systems for response time and CPR 7

Conclusions When adjusted for Utstein variables, CPR quality metrics and ROC site, CCF paradoxically was associated with lower odds of survival. For patients with no ROSC in first 10 minutes of resuscitation there was no relationship between CCF and clinical outcomes. Pre-shock pause strongly associated with survival (timing of CPR interruptions) Shorter resuscitations may confound results due to early defibrillation, lack of CPR quality data and EMS resuscitative strategies whereas longer resuscitations may benefit most from higher CCF. CCF is a complex measure and taken by itself may not be a consistent predictor of clinical outcome. High quality CPR with CCF > 80% should still be benchmark, particularly in longer resuscitations. Thank You! 8