What is the Optimal Chest Compression Depth During Out-of-Hospital Cardiac Arrest Resuscitation of Adult Patients? Ian G. Stiell, Siobhan P. Brown, Graham Nichol, Sheldon Cheskes, Christian Vaillancourt, Clifton W. Callaway, Laurie J. Morrison, James Christenson, Tom P. Aufderheide, Daniel P. Davis, Cliff Free, Dave Hostler, John A. Stouffer and Ahamed H. Idris and the Resuscitation Outcomes Consortium (ROC) Investigators Circulation. published online September 24, 2014; Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 2014 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7322. Online ISSN: 1524-4539

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What is the Optimal Chest Compression Depth During Out-of-Hospital Cardiac Arrest Resuscitation of Adult Patients? Running title: Stiell et al.; CPR Compression Depth Ian G. Stiell, MD1; Siobhan P. Brown, PhD2; Graham Nichol, MD3; Sheldon Cheskes, MD4; Christian Vaillancourt, MD1; Clifton W. Callaway, MD5; Laurie J. Morrison, MD6; James Christenson, MD7; Tom P. Aufderheide, MD8; Daniel P. Davis, MD9; Cliff Free, EMT-P10; Dave Hostler, PhD5; John A. Stouffer, EMT-P11; Ahamed H. Idris, MD12 and the Resuscitation Outcomes Consortium (ROC) Investigators 1

Dept of Emergency Medicine and Ottawa Hospital Research Institute, University of Ot Otta Ottawa, tawa ta w , Ot wa Otta Ottawa, tawa wa, 2 ON, Canada; Clinical Trials Centre, Dept of Biostatistics, University of Washington Washington, onn, Se Sea Seattle, attl attl tle, e W e, WA; A; 3 Clinical Trials Centre, Dept of Biostatistics and Department of Medicine, University y ooff Wa Wash Washington; shin sh ingt in gton gt on;; on University of Washington-Harborview Center for Prehospital Emergency Care, Seattle, WA; 4Division of Emergency Medicine, Dept of Family and Community Medicine, University of Toronto and Rescu, Li Ka Shing Toronto, Shin ingg Knowledge Know Kn owle ow leedg d e Institute, Inst In s itute, St. Michael’s Hospital, T oron or o to, ON, Canada; 5De Dept p of Emergency Medicine Medicine, 6 Unniv iveers ersity of of P itttsbburrgh g , Pittsburgh, Pittsburgh g , PA; Division of University Pittsburgh, of E Emergency merge g ncy y Medi Medicine, diici c nee, De D Dept ept of Medicine, University of of Toronto Toronto and and nd Rescu, Res e cu u, Li Ka Ka Shing Shhin ing g Knowledge Know Kn owle ow l dg le dgee Institute, I stiitute, St. In St. Michael’s Mich Mi c ae ch aell’ss Hospital, Hosp Ho spit sp i al, Toronto, it Toro To ront ro nto, nt o ON, o, ON, N, Canada; Canad an nad a a; 7 Dept D De pt of Emergency Em merrgeenc ncy y Medicine, Mediccin Medi ne University ne, Uniive Un iverssity of of British Britiishh Columbia, Col olum ol umb um biaa, V Vancouver, an ncouv uvverr, BC BC,, Ca Can Canada; nada; nad da 8De Dept pt ooff Emergency Medicine, Medical College Wisconsin, Milwaukee, Em mergencyy Me M diccine,, M edi diccall Co Colleg egee off Wisc eg sco onsiin, M ilwa il w uk wa uke kee, WI; WI; 9De Dept eptt ooff Em Emergency mer e geenccy M Medicine, ediccin ne, 10 0 University California, Diego, CA; Univ Un i errsi iv sity ty ooff Cali C alifforn forn nia ia, Sa San Di Dieg ego, eg o, C A; Ca Camas ama mas F Fire ire ree Dept, Dep eptt, Camas, Cam mass, WA; WA; 11Ce Central Cent ntra nt rall W Washington ash shhin ngt g on on Unniv iver ersity ity,, Ellensburg, E leens El n buurg rg,, WA A; 122De University, WA; Depts Dept ptss of Emergency Eme merg rgen ency cy Medicine Medic icin inee and and Internal Inteern In rnal al Medicine, Med dic icin ne, e University Univeers rsity y of T Texas ex xas Southwestern Medical Center, Dallas, Soout u hw wes e te tern rn M edic ed ical al C ente en ter, r D r, alla al las, s, TX X

Address for Correspondence: Ian G. Stiell, MD Ottawa Hospital Research Institute Clinical Epidemiology Unit, Office F657, The Ottawa Hospital, Civic Campus 1053 Carling Avenue Ottawa, Ontario, Canada, K1Y 4E9 Tel: 613-798-5555 x18683 Fax: 613-761-5351 E-mail: [email protected]

Journal Subject Code: Treatment:[25] CPR and emergency cardiac care

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Abstract

Background—The 2010 AHA guidelines suggested an increase in CPR compression depth with a target greater than 50 mm and no upper limit. This target is based upon limited evidence and we sought to determine the optimal compression depth range. Methods and Results—We studied emergency medical services treated out-of-hospital cardiac arrest (OHCA) patients from the Resuscitation Outcomes Consortium ROC PRIMED clinical trial and Epistry - Cardiac Arrest database. We calculated adjusted odds ratios for survival to hospital discharge, one-day survival, and any return of circulation (ROSC). We included 9,136 compression adult patients from 9 U.S. and Canadian cities that had mean age 67.5 years; mean mea eaan co comp mpre mp ress re ssio ss ion io depth 41.9 mm; and had ROSC 31.3%, one-day survival 22.8%, and survival to hospital discharge 1.08) disc chaarg rgee 7.3%. 7 3% 7. 3 . For For survival to discharge, the adjusted ad dju just s ed odds ratios were wer erre 1.04 1 04 (95% CI 1.00, 1.08 1. for within fo or each ea 5 mm mm increment incr in crem em men nt inn compression com ompr p es pr essi sionn depth, si dep e th, 1.45 1.4 45 (1.20, (1 1.2 .20, 0, 1.76) 1.776) 6) for for ccases asees w as ithi it hinn 20 hi 22005 05 ddepth epth ep th range mm), 1.08) minutes depth range ang ngee (> ((>38 38 m m , and m) and 11.05 .005 05 ((1.03, 1.03 03,, 1. 03 .08 0 ) ffor or per ppercent ercen entt of of m inut utess inn de ept p h ra ang ngee (10% (10% % cchange). hang ha ngge) e).. Covariate-adjusted maximum survival 45.6 mm Cova Co vari va riat ri atee-ad at e-ad adju just ju sted st ed spline spl plin inee curves in curv cu rves rv es revealed reve re veal ve aled al ed that tha hatt th thee ma maxi ximu xi mum mu m su surv rviv rv ival iv al iiss at a ddepth epth ep th ooff 45 .66 m m (15 mm interval with highest survival between 40.3 to 55.3) with no differences between males and females. Conclusions—This large study of OHCA patients demonstrated that increased CPR compression depth is strongly associated with better survival. Our adjusted analyses, however, found maximum survival was in the depth interval of 40.3 to 55.3 mm (peak 45.6 mm), suggesting that the 2010 AHA CPR guideline target may be too high. Clinical Trial Registration Information—clinicaltrials.gov. Identifier: NCT00394706.

Key words: cardiac arrest, cardiopulmonary resuscitation, emergency medical services, compression depth

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Introduction Out-of-hospital cardiac arrest (OHCA) leads to an estimated 330,000 deaths each year in the United States and Canada.1 While overall survival for treated OHCA is low, hospital discharge rates vary from 3.0% to 16.3%.1 This variation in survival can be partly attributed to local differences in the five key links in the chain of survival: rapid emergency medical services (EMS) access, early cardiopulmonary resuscitation (CPR), early defibrillation, early advanced cardiac life support (ACLS), and effective post-resuscitation care.2-6 Considerable efforts by communities and hospitals to strengthen these links have led to only modestly better survival rates in recent years.1 In recent years, those involved in cardiac resuscitation have recognized th that hatt tthe hee qquality, uali ua lity li ty, quantity, and timeliness of CPR are key determinants for survival from cardiac arrest and that delivery de eliive very ry ooff ch ches chest st com ccompressions ompressions is often poor.7;8 Recent Rec ecent technological technologi giica c l ad adv advances va vances now allow the 9 11 9-11 ddetailed deta e ail i ed measu measurement ureement nt and nd rreview eviiew ev iew off kkey ey y com compression mpresssiion pparameters. aram aram met e errs..9-1 Using U singg this this his technology, tech te chno ch noolo ogy gy,,

Christenson Ch hri r st sten e so en son n and and Va V Vaillancourt ail illlancou nco rt ddemonstrated emon em onst sttra rate tedd an te n as aassociation sociaatio soc atio on be betw between tweeen tw een ou ooutcomes tcoomees of o O OHCA HCA pa HCA ppatients tiien nts t and the proportion prop porrtiion n ooff ea each ch rresuscitation esus es ussci cita taati t on nm minute in nut utee du duri during r ng ri n w which hich hi ch ccompressions ompr om pres pr essi es sion si onss we on were re ddelivered eliv el i ered (ches iv (chest s compression fraction).12;13. Cheskes found that longer perishock and preshock pauses were independently associated with a decrease in survival to hospital discharge in patients presenting in a shockable rhythm.14 Idris described an association between chest compression rate and return of spontaneous circulation.15 Chest compression depth is another aspect of CPR for which data are limited. Current CPR guidelines for compression rate and depth have been, for the most part, derived with relatively little robust human data to support them.3;16 The 2005 guidelines recommended a depth range of 38-50 mm whereas the new 2010 guidelines recommend a depth of at least 50 mm (2

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inches) with no upper limit specified. For compression depth, clinical studies to date have been small with insufficient power to evaluate clinically important outcomes.7;17-22 Our group studied 1,029 OHCA cases and found lower than recommended compression depth in half of patients by 2005 guideline standards and almost all by 2010 standards as well as an inverse association between compression depth and rate.23 We found a strong association between survival outcomes and increased compression depth but no clear evidence to support or refute the 2010 recommendations of greater than 50 mm. Our objective for the current study was to determine the optimal compression depth for adults in a large sample of OHCA patients.

Methods Design and Setting Th he Resuscitation Resu Re susc scit sc itaatio it on Outcomes Outcomes Consortium (ROC) (ROC C) iiss comprised off 10 1 U .S S. and Canadian The U.S. uuniversities niv ver e sities and ndd their their rregional eg gio iona nall EMS na EM MS systems syysttemss aand nd ha has a man m mandate anda ndate ate tto o con conduct ondu d ct llarge du arrge ccontrolled onntr troolleed tr ttrials iaals off prehospital preeho h sp spit ital it al interventions interrve venntiions n for for o cardiac card ca rdia rd iacc arrest arre ar resst and re and trauma. trrau rauma. uma. This Thiis study sttuddy represents reeprres esen e ts en t an an analysis anaalys ysis ys is ooff consecutive OHCA OHCA A cases cas a es e prospectively pro rosp sppec ecti tive v ly ve y gathered gat athe here he redd inn the re the recent rec ecen entt ROC en ROC Prehospital Preh Pr ehos eh ospi os p taal Resuscitation pi Resu Re susc su s itation Impedance Valve and Early Versus Delayed Analysis (PRIMED) Trial or in the ROC EpistryCardiac Arrest.24 The ROC PRIMED Trial used a partial factorial design whereby most patients were randomized to two concurrent protocols. The first protocol compared early rhythm analysis versus later rhythm analysis and the second protocol compared use of an impedance threshold device (ITD) versus use of a sham ITD. The ROC Epistry is a prospective multicenter observational registry of OHCA in EMS agencies and receiving institutions and includes patient outcomes and electronic data on CPR process.25 The ROC EMS network consists of 36,000 EMS professionals within 260 EMS agencies,

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provides coverage to an estimated 24 million persons from urban, suburban, and rural communities, and transports patients to 287 different hospitals.26 This analysis included OHCA patients treated by EMS and for whom electronic compression depth data were available. Sites that did not have the technical capacity to measure compression depth were not included and, hence, this study included data from 95 participating EMS agencies affiliated with nine U.S. and Canadian ROC sites. At the time of data collection, OHCA patients were being treated according to the 2005 guideline standards for compression depth (38-50 mm). Population We included all persons from the ROC PRIMED Trial or the ROC Epistry, aged 18 or older, who suffered non-traumatic cardiopulmonary arrest outside of the hospital within in n tthe h ccatchment he atch at chme ch m nt me area of a participating ROC EMS agency and were treated with defibrillation and/or delivery of ch hes estt co comp mpre mp r ssio re io ons ns by EMS providers. We included includ udeed patients withh anyy in ud ini itial cardiac rhythm. We chest compressions initial ex xcllud u ed patients patieentts who who did did not not have havve ha ve attempts atttem mptss at at resuscitation reesuusciita itatio ationn by EMS, EMS, MS with wi h an an obvious obvi ob v ous vi ous ca aus usee ooff excluded cause arrreestt, wh whos osee ar os arr ressts sts were were r EMS MS w itnnes it nessed ssed ed,, wh whoo re eceiv ved d a sshock hock ho ck k ffrom rom ro m a by byst s an st ande deer app aapplied pplieed AE AED, D arrest, whose arrests witnessed, received bystander ho hhad ad m o e th or than a 5m an i ut in utes es ooff EM EMS S CPR C R be CP befo fore fo ree tthe h ppads he adss we ad were r aapplied. re ppli pp lied li ed. We also ed and anyone w who more minutes before excluded patients for who at least one minute of electronic CPR compression depth data was not available. These data may have been unavailable because some EMS agencies do not use defibrillators with accelerometers capable of measuring compression depth or because of inadvertent failure to capture and transmit the data. The ROC PRIMED Trial and the ROC Epistry were reviewed and approved by the appropriate local institutional review boards (U.S.) or research ethics boards (Canada) without the need for informed consent from subjects. Strict confidentiality was maintained at all times and no personal identifiers were retained in the database.

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Data Collection The characteristics of chest compressions were measured via an accelerometer interface between the rescuer and the patient’s chest using commercially available defibrillators. Tracings were acquired and downloaded from Phillips (N=1,869; Andover, MA, USA) and ZOLL (N=7,246; Chelmsford, MA, USA) defibrillators.10;27 CPR process measures, including compression rate, chest compression fraction, and compression depth, were calculated by proprietary automated external defibrillator analytic software. Chest compression fraction was defined as the proportion of resuscitation time without spontaneous circulation during which chest compressions were administered. Compression depth was defined as the posterior depression of the anterior chest wall in mm. The mean compression values for all minute intervals were averaged ed d ffor o eeach or achh ac patient using all available minutes in the first 10 minutes after pads were placed. For co omp mpre ress re ssio ionn ddepth, io ept pthh, pt h, we defined within recommended recommeende nded range as per peer thee 2005 20005 international 20 compression gguidelines uid del e ines wit th an an aaverage veeraagee ddepth epth ep th ooff at le east 38 8 mm. m W m. des scri r beed th ri thee case case aass “w “wit ithi it hinn hi with least Wee de described “within eco comm mmen mm ende dedd de de eptth” iiff th thee mean mean ddepth epth epth hw as 338 8 mm orr mo mor re ffor re o m or oree tthan or haan an 660% 0% ooff minutes minnut nutes t es recommended depth” was more more ecorded. recorded. Patient and clinical data were abstracted from EMS and hospital records using standardized definitions for patient characteristics, EMS process, and outcome at hospital discharge. Data were abstracted locally, coded without personal health information, and transmitted to the data coordinating center electronically. Site-specific quality assurance included initial EMS provider training in data collection, and continuing education of EMS providers. The data coordinating center assured the quality of the data by a variety of techniques.1 Outcome Measures The primary outcome was survival to hospital discharge, defined as discharged alive from

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hospital after the index OHCA. Patients who were transferred to another acute care facility (e.g. to undergo implantable cardioverter defibrillator placement) were considered to still be hospitalized. Patients were considered discharged if transferred to a non-acute ward or facility. The secondary outcomes were survival to the next calendar day and return of spontaneous circulation (ROSC). Survival for one day meant that the patient was still alive one day past the date of the event. Return of spontaneous circulation refers to the presence of a palpable pulse for any duration of time prior to arrival at hospital. Data were abstracted from collated EMS and hospital source documents. Statistical Analysis packages (SAS, All statistical analyses were performed with commercially available statistical pa acka acka kagges ges (S (SAS AS,, version 9.1.3, Cary, NC; R, version 2.14.1, Vienna, Austria). Summary results are presented as mean characteristics me an (±SD) (±S ±SD) D) or or median meddian (IQR). To test differences me differencees inn baseline char arrac a teeri rist stic st i s between subjects who used w hoo did and did did not no ot survive suurv vive ive to discharge, dissch harrge ge, likelihood likkeliho ke oodd ratio raatiio chi-squared chich i sq isqua uaareed ttests esstss orr t-tests t-t -tes ests es tss were werre us sed d as appropriate. Analysis wass us mean depths study appr ap prop pr opri op riat atee. e. A naaly ysi siss off vvariance a ia ar ianc ncce wa w used ed tto o ccompare om mpare paree m eann co ea ccompression mpre mp ress re sssio on de dept pths pt hs aacross crooss st stud uddy sites. depth and tested with ites. The association asssoc ocia i ti ia tion o between on bet e we ween en de dept p h an pt nd ra rate t ccategories te a eg at egor orie or i s wa wass te est sted ed w ithh a likelihood it likkel li elih ih hoo oodd ra rratio tio chisquared test.. The association between compression depth (evaluated separately with four approaches) and outcomes of interest was quantified using multivariate logistic regression with the Huber-White sandwich standard error .28 The key covariates/potential confounders assessed were age, sex, public location, bystander witnessed arrest, bystander CPR, EMS response time, CPR fraction, compression rate, site, and device manufacturer. We did not include cardiac rhythm as this is potentially a path variable. Smoothing splines were used to explore the relationship between average compression depth and outcome with a goal of finding the optimal 15 mm interval for depth.29 Smoothing splines were creating by including the b-spline basis for a

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natural cubic spline of depth in a logistic regression model in place of the other depth measures. Four degrees of freedom were used in the unadjusted models and five in the adjusted.

Results During the study period from June 2007 to December 2010, EMS agencies in the 10 participating ROC sites treated 27,986 cases of cardiac arrest. Of these patients, all but 9,266 were excluded for the reasons indicated in Figure 1; another 130 cases had missing data leaving a final study group of 9,136 patients. The most common reason for exclusion was missing time from 911 call to EMS arrival (65 cases); missing subject age was the next most common (n=35). The other 30 subjects ubjects were missing various covariates used in the regression models. The patients pattieentts in the the final fin inal study tudy cohort were similar in terms of clinical significance for characteristics and outcomes to those British more were hosse excluded, excl excl clud udeed, except ud exce ex cept that none were from Briti tissh Columbia and ti d mor oree w ere from Toronto, and they lower hey y had a low werr survival suurvi urvi viva vaal rate rate (Supplemental (Su upp pple leementtall Table Taable 1). 1). ) The study were OHCA cases T hee ppatients atie at ieentts in n tthe he stu he tu udy w eree ty er ttypical pica pi cal off O ca HCA A ca cas ses wi ses with th h oonly nlyy 13 nl 113% % fr from om m a ppublic ubli ubli lc location, bystander witnessed, CPR, having advanced ocation, 44% % by byst stan st ande an d r wi de witn tnes tn esse sed, se d 442% d, 2% % bbystander ysta ys tand ta nder nd err C PR R, 99 99% % ha havi ing aan n ad adva vaanc nced ed llife i e support if EMS crew in attendance (Table 1). The mean values for CPR process measures were compression rate 108 (SD 16) per minute and chest compression fraction 0.68 (SD 0.15). Of all patients, 31.3% had ROSC, 22.8% survived one day, and 7.3% survived to hospital discharge. Table 2 displays compression depth data which was available per case for a median of 7 minutes (IQR of 5-10). The overall median chest compression depth was 41 mm (IQR 35-48) and 36% of cases had a mean value less than 38 mm. In addition, we calculated that 40% of cases were not within the 2005 recommended range for depth. We also found (Supplemental Table 2) that compression rate and depth were inversely related (P< 0.001) such that 53% of

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cases with compression rate >120 also had depth 50 mm.19 Babbs examined a library of prehospital CPR process data and found, in 101 patients with depth >51 mm, a higher rate of electrical conversion but no difference in ROSC or other clinical outcomes.22 Subsequent to the 2010 CPR guidelines, our group published a specific compression de ept pthh anal aanalysis nal alys y is ys is ooff 1,029 1,0 9 OHCA cases from the RO 1,02 ROC C Epistry.23 W Wee foun found un nd a strong association depth bbetween etw ween survival surviv ival a outcomes al out utccome mess and and increased in ncr crea ease sed compression co ompreesssionn depth depth dep pth but but had had insufficient i sufffic in iciient ientt ppower ower tto owe o identify depth women. den enti tify ti fy tthe hee ooptimal ptim pt im mal al ccompression ompr om presssi s on de dept pth h fo forr adul aadult dul ultt me men orr w omen om e . en Limitations and and St Stre Strengths reng re ngth ng hs The study population represents a consecutive sample of cases from sites where compression depth could be measured and during a period when the 2005 guideline standards were in use. Regardless, we could detect no selection bias in our cases compared to those not included. Our records could not capture CPR data prior to the placement of accelerometer pads, a time period estimated to be less than 30 seconds (median 16 seconds, mean 29) and we did not examine data beyond 10 minutes of CPR. We did not have data for body size, firmness of the surface under the patient, leaning, or duty cycle, all possible confounders to the interpretation of compression depth data.33 We did, however, adjust for sex which may be considered a crude proxy for weight

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and found no difference between men and women. We had no measurements for children under age 18. We did not reliably capture data on whether or not device feedback was provided to providers. The major strengths of the study include a large sample of patients with all initial rhythms, from nine geographically disparate locations in the U.S. and Canada, and receiving use of devices from two different manufacturers. The overall survival to discharge proportion of 7.3% is quite reasonable, considering we excluded cases witnessed by EMS or that received bystander AED shocks. With 1,668 patients who received an average compression depth >50 mm, we were able to conduct robust analyses on clinically important outcomes and evaluate depth in a variety of ways. Clinical Implications This implications performing CPR. Th his sstudy tudy tu dy hhas as a nnumber um umber of important implication ons ffor on or those perf for o miing C PR. Our data clearly survival discharge are better when cl leaarl r y indicate te that thaat ROSC, R SC RO SC,, short-term shor sh ortt--te term rm survival, survi viivaal, aand nd su urv viv ival al tto o di disc scha h rg ha rgee ar re be bett tter tt er w h n he compression >50mm, co omp mpre ress re ssio io on depth deppthh is greater. de greeat aterr. Compared Comp Co mpar mp ared ed to to 2010 2010 1 Guideline Guiddeli deli line ne recommendation rec ecom ec om mme menndatio ationn of ddepth eptth > ep 50mm,, 50mm found within mm, with however, wee fo foun undd a pe un peak ak eeffect ffecct at ff a 445.6 5..6 mm w i hi it hinn an a iinterval nter nt erva er vall ooff 40 va 40.3 .3 tto o 55 55.3 .3 3m m, w ith similar results for both men and women. Hence, we believe that professional CPR providers must be mindful of achieving adequate compression depth but without going too deep. In the absence of other large studies, we anticipate that future recommendations for optimal compression depth for adults may be in the range of 40-55 mm. Providers must be cognizant of achieving proper compression depth along with other CPR process measures such as rate, fraction, and peri-shock pauses. Of note is that depth and rate are inversely related such that exceeding the target for one will likely lead to under-performance for the other. How best to assist EMS responders provide excellent CPR is unknown but presumably this includes a combination of good training, CPR

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process debriefing, and possibly real-time feedback.34;35 Research Implications Clinical studies of CPR process are difficult to conduct yet are essential if we are to know the optimal targets and interplay amongst compression depth, compression rate, ventilations, compression fraction, duty cycle, and recoil. In addition, more data for children are required in order to understand the best CPR process parameters to optimize survival. Ultimately we need randomized intervention trials that evaluate the impact of different combinations of CPR process targets on patient survival.

Conclusions This large study of OHCA patients from a variety t of settings demonstrated that increased CPR compression co omp mpre ress re ssio ionn ddepth io ept pthh is pt i strongly associated with be better etter survival to ho hospital ospit ital al ddischarge. ischarge. An adjusted analysis, an nallys y is, however, howeeveer,, found fouund d maximum max axiimum imum survival suurvvivaal was was inn the th he mean mean ddepth eptth iinterval ntterrva vall of of 440.3 0.33 to 55. 0. 55.3 5.33 mm 5. (peak mm), suggesting 2010 AHA CPR guideline may high. pea eakk 45 445.6 .6 m m),, su m) uggges esti t ng ti n tthat hatt th ha thee 20 0100 A HA AC PR gu guid idel id elin ne ttarget arg get e m ay bbee to tooo hi high gh.. We We encourage the th he use u e of all us alll validated val alid al id dat ated ed strategies str trat ateg egie eg iess for ie for prehospital p eh pr ehos o pi pita tall and ta and in-hospital in-ho in hosp ho spit sp ital it al ccardiac arrdi diac ac aarrest r est rr resuscitations to assist rescuers to stay “within range” for key CPR parameters.

Acknowledgments: We gratefully acknowledge the tremendous effort and contribution of thousands of EMS providers and first responders who made this logistically challenging trial possible. We also thank Catherine Clement and Angela Marcantonio for their assistance with the manuscript as well as Tom Rea for insightful comments.

Funding Sources: The ROC is supported by a series of cooperative agreements to 10 regional clinical centers and one Data Coordinating Center (5U01 HL077863, HL077881,HL077871 HL077872, HL077866, HL077908, HL077867, HL077885, HL077887, HL077873, HL077865)

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from the National Heart, Lung and Blood Institute in partnership with the National Institute of Neurological Disorders and Stroke, U.S. Army Medical Research & Materiel Command, the Canadian Institutes of Health Research (CIHR) - Institute of Circulatory and Respiratory Health, Defence Research and Development Canada, the Heart and Stroke Foundation of Canada and the American Heart Association.

Conflict of Interest Disclosures: None.

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Table 1. Patient Characteristics. Characteristics Age - mean (SD) Male - n (%) Public location – n (%) Bystander witnessed – n (%) Bystander CPR – n (%) Site - n (%) Alabama Dallas/Fort Worth Milwaukee Ottawa Pittsburgh Portland San Diego Seattle/King County Toronto EMS Response Time from 911 call to scene – mean (SD) Time from 911 call to first EMS shock assessment – mean (SD) ALS scene LS first fir irst s on on sc cen e e – n (%) ALS scene ALS on on sc scen en ne – n (% ((%)) Number off responding units Number um resspo pond n in nd ng EM EMS S un unit itss*—m it —mean mea e n (S (SD) D D) EMS EM S Interventions Interventi tion onns Intubation attempted (%) Inttub u ation at attemp mptedd - n (% mp %) Shocks delivered (%) Sho hock ckss de ck deli live li vere reed - n (% %) Epinephrine (%) Epi pine n ph phri rin ne uuse s noted se not oted e - n (% %) CPR process measures meas me assur ures e es CPR first analysis CPR prior pri rior or tto o fi firs rstt an anal alys ysis is – n (%) (%) CPR fraction – mean (SD) Chest compression rate – mean (SD) Initial cardiac rhythm – n (%) VF/VF PEA Asystole AED no shock, no strip Cannot Determine/Missing Device - n (%) Philips Zoll Other Outcomes Any pre-hospital ROSC – n (%) Survived at least one day – n (%) Survived to hospital discharge – n (%)

Total N=9,136 67.5 (16.4) 5857 (64%) 1161 (13%) 4065 (44%) 3633 (42%) 22 (0%) 272 (3%) 936 (10%) 1389 (15%) 596 (7%) 168 (2%) 842 (9%) 837 (9%) 4074 40074 (45%) (45 45%) %) 55.9 5. 9 (2.5 ((2.5) 2 5) 10.5 (3.5) 3274 (36%) 9049 (99%) 2.66 (0 2. (0.8) 0.8 .8) 8) 6747 667 47 ((74%) 744%) 3647 36 647 ((40%) 400%) 7923(87%) 7923(8 79 (87% %) 8409 8409 (92%) (92 92%) %) 0.68 (0.15) 108.3 (16.0) 2181 (24%) 1845 (20%) 4513 (49%) 583 (6%) 14 (0%) 1869 (20%) 7246 (79%) 21 (0%) 2861 (31.3%) 2081 (22.8%) 666 (7.3%)

*

Information was only available about the first four EMS units at the scene. Note: percentages are of cases with non-missing data.

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Table 2. Compression Depth Measures.

Chest compression depth* (mm) - median (Q1, Q3) - mean (SD) Compression Depth Category* - % (n) 51 mm Within Depth Range† - % (n) Percent of minutes in recommended range - mean (SD) * †

Total N=9,136 41 (35, 48) 41.9 (11.7) 36% (3334) 45% (4134) 18% (1668) 60% (5461) 61% (39%)

Average depth in mm for 10 minutes Average depth at least 38 mm for at least 60% of minutes with CPR process measures available.

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Table 3. Univariate Comparison of Clinical Characteristics of Patients Who Did and Did Not Survive to Hospital Discharge

Age - mean (SD) Male - n (%) Public location – n (%) Bystander witnessed – n (%) Bystander CPR – n (%) EMS Response Time from 911 call to scene – mean (SD) Time from 911 call to first EMS shock assessment – mean (SD) ALS first on scene – n (%) ALS on scene – n (%) Number of responding EMS units*—mean (SD) EMS Interventions Intubation attempted - n (%) Sho Shocks hock ckss delivered deeli live v re redd - n (%) E Epinephrine pinneph pi nephhri rine ne uuse see nnoted oted - n (%) CPR CP R proces process ss me meas measures asur as urres C CPR PR prior to fi first irsst an analysis nallysis is – n (%) %) CPR CPR PR fraction fracttio ionn – mea m mean ean (SD) (SD)) C Chest hest he st ccompression ompr om pres essi es sion si on rrate atee – me at mean ean ((SD) SD)) SD Ches Ch Chest estt co comp compression mpre ress ssiion ion dept ddepth ept pthh (m (mm) m) - m mean ean ((SD) SD)) SD Comp Co Compression mpre ress ssio ionn De D Depth pthh Category pt Cate Ca tego gory ry - % (n) (n) 51 mm Within Recommended Depth Range† - % (n) Percent of minutes in depth range - mean (SD) Initial cardiac rhythm – n (%) VF/VF PEA Asystole AED no shock, no strip Cannot Determine/Missing

Outcome p-value from Deaths Survivors Chi-squared or t-test N=8,470 N=666 68.2 (16.3) 58.8 (15.3)