BACKGROUND: Out of hospital cardiac arrest (OHCA) has a poor outcome. Recent non-randomized studies of ECLS (extracorporeal life support) in OHCA suggested further prospective multicenter studies to define population that would benefit from ECLS. We aim to perform a prospective randomized study comparing prehospital intraarrest hypothermia combined with mechanical chest compression device, intrahospital ECLS and early invasive investigation and treatment in all patients with OHCA of presumed cardiac origin compared to a standard of care. METHODS: This paper describes methodology and design of the proposed trial. Patients with witnessed OHCA without ROSC (return of spontaneous circulation) after a minimum of 5 minutes of ACLS (advanced cardiac life support) by emergency medical service (EMS) team and after performance of all initial procedures (defibrillation, airway management, intravenous access establishment) will be randomized to standard vs. hyperinvasive arm. In hyperinvasive arm, mechanical compression device together with intranasal evaporative cooling will be instituted and patients will be transferred directly to cardiac center under ongoing CPR (cardiopulmonary resuscitation). After admission, ECLS inclusion/exclusion criteria will be evaluated and if achieved, veno-arterial ECLS will be started. Invasive investigation and standard post resuscitation care will follow. Patients in standard arm will be managed on scene. When ROSC achieved, they will be transferred to cardiac center and further treated as per recent guidelines. PRIMARY OUTCOME: 6 months survival with good neurological outcome (Cerebral Performance Category 1-2). Secondary outcomes will include 30 day neurological and cardiac recovery. DISCUSSION: Authors introduce and offer a protocol of a proposed randomized study comparing a combined "hyperinvasive approach" to a standard of care in refractory OHCA. The protocol is opened for sharing by other cardiac centers with available ECLS and cathlab teams trained to admit patients with refractory cardiac arrest under ongoing CPR. A prove of concept study will be started soon. The aim of the authors is to establish a net of centers for a multicenter trial initiation in future. ETHICS AND REGISTRATION: The protocol has been approved by an Institutional Review Board, will be supported by a research grant from Internal Grant Agency of the Ministry of Health, Czech Republic NT 13225-4/2012 and has been registered under ClinicalTrials.gov identifier: NCT01511666.

2nd Department of Medicine 1st Faculty of Medicine Charles University Prague and General University Hospital Prague U Nemocnice 2 Prague 2 128 00 Czech Republic

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Goldberger JJ, Cain ME, Hohnloser SH, Kadish AH, Knight BP, Lauer MS, Maron BJ, Page RL, Passman RS, Siscovick D, Stevenson WG, Zipes DP. American Heart Association Council on Clinical Cardiology; American Heart Association Council on Epidemiology and Prevention; American College of Cardiology Foundation; Heart Rhythm Society. American Heart Association/american College of Cardiology Foundation/heart Rhythm Society scientific statement on noninvasive risk stratification techniques for identifying patients at risk for sudden cardiac death: a scientific statement from the American Heart Association Council on Clinical Cardiology Committee on Electrocardiography and Arrhythmias and Council on Epidemiology and Prevention. Heart Rhythm. 2008;5:e1–e21. PubMed

Zheng ZJ, Croft JB, Giles WH, Mensah GA. Sudden cardiac death in the United States, 1989 to 1998. Circulation. 2001;104:2158–2163. doi: 10.1161/hc4301.098254. PubMed DOI

Hazinski MF, Nolan JP, Billi JE, Böttiger BW, Bossaert L, de Caen AR, Deakin CD, Drajer S, Eigel B, Hickey RW, Jacobs I, Kleinman ME, Kloeck W, Koster RW, Lim SH, Mancini ME, Montgomery WH, Morley PT, Morrison LJ, Nadkarni VM, O’Connor RE, Okada K, Perlman JM, Sayre MR, Shuster M, Soar J, Sunde K, Travers AH, Wyllie J, Zideman D. Part 1: Executive summary: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Resuscitation. 2010;81(Suppl 1):e1–e25. PubMed PMC

Franěk O, Pokorná M, Sukupová P. Pre-hospital cardiac arrest in Prague, Czech Republic—The Utstein-style report. Resuscitation. 2010;81:831–835. doi: 10.1016/j.resuscitation.2010.03.005. PubMed DOI

Kirves H, Skrifvars MB, Vahakuopus M, Ekstrom K, Martikainen M, Castren M. Adherence to resuscitation guidelines during prehospital care of cardiac arrest patients. Eur J Emerg Med. 2007;14:75–81. doi: 10.1097/MEJ.0b013e328013f88c. PubMed DOI

Sunde K, Pytte M, Jacobsen D, Mangschau A, Jensen LP, Smedsrud C, Draegni T, Steen PA. Implementation of a standardised treatment protocol for post resuscitation care after out-of-hospital cardiac arrest. Resuscitation. 2007;73:29–39. doi: 10.1016/j.resuscitation.2006.08.016. PubMed DOI

Gaieski DF, Band RA, Abella BS, Neumar RW, Fuchs BD, Kolansky DM, Merchant RM, Carr BG, Becker LB, Maguire C, Klair A, Hylton J, Goyal M. Early goal-directed hemodynamic optimization combined with therapeutic hypothermia in comatose survivors of out-of-hospital cardiac arrest. Resuscitation. 2009;80:418–424. doi: 10.1016/j.resuscitation.2008.12.015. PubMed DOI

Deem S, Hurford WE. Respiratory controversies in the critical care setting. Should all patients be treated with hypothermia following cardiac arrest? Respir Care. 2007;52:443–450. PubMed

Wijdicks EF, Hijdra A, Young GB, Bassetti CL, Wiebe S. Practice parameter: prediction of outcome in comatose survivors after cardiopulmonary resuscitation (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006;67:203–210. doi: 10.1212/01.wnl.0000227183.21314.cd. PubMed DOI

Rossetti AO, Oddo M, Logroscino G, Kaplan PW. Prognostication after cardiac arrest and hypothermia: a prospective study. Ann Neurol. 2010;67:301–307. PubMed

Nielsen N, Friberg H, Gluud C, Herlitz J, Wetterslev J. Hypothermia after cardiac arrest shloud be further evaluated – A systematic review of randomised trials with meta-analysis and trial sequential analysis. Int J Cardiol. 2011;15(3):333–341. PubMed

Nielsen N, Sunde K, Hovdenes J, Riker RR, Rubertsson S, Stammet P, Nilsson F, Friberg H. Hypothermia Network. Adverse events and their relation to mortality in out-of-hospital cardiac arrest patients treated with therapeutic hypothermia. Crit Care Med. 2011;39:57–64. doi: 10.1097/CCM.0b013e3181fa4301. PubMed DOI

Nielsen N, Hovdenes J, Nilsson F, Rubertsson S, Stammet P, Sunde K, Valsson F, Wanscher M, Friberg H. Hypothermia Network. Outcome, timing and adverse events in therapeutic hypothermia after out-of-hospital cardiac arrest. Acta Aneasthesiol Scand. 2009;53:926–934. doi: 10.1111/j.1399-6576.2009.02021.x. PubMed DOI

Bělohlávek J, Šmíd O. Therapeutic hypothermia after cardiac arrest: why and for how long? Vnitr Lek. 2011;57:23–26. PubMed

Pfeifer R, Jung C, Purle S, Lauten A, Yilmaz A, Surber R, Ferrari M, Figulla HR. Survival does not improve when therapeutic hypothermia is added to post-cardiac arrest care. Resuscitation. 2011;82:1168–1173. doi: 10.1016/j.resuscitation.2011.05.024. PubMed DOI

Scolletta S, Taccone FS, Nordberg P, Donadello K, Vincent JL, Castren M. Intra-arrest hypothermia during cardiac arrest: a systematic review. Crit Care. 2012;16:R41. doi: 10.1186/cc11235. PubMed DOI PMC

Garrett JS, Studnek JR, Blackwell T, Vandeventer S, Pearson DA, Heffner AC, Reades R. The association between intra-arrest therapeutic hypothermia and return of spontaneous circulation among individuals experiencing out of hospital cardiac arrest. Resuscitation. 2011;82:21–25. doi: 10.1016/j.resuscitation.2010.09.473. PubMed DOI

Riter HG, Brooks LA, Pretorius AM, Ackermann LW, Kerber RE. Intra- arrest hypothermia: both cold liquid ventilation with perfluorocarbons and cold intravenous saline rapidly achieve hypothermia, but only cold liquid ventilation improves resumption of spontaneous circulation. Resuscitation. 2009;80:561–566. doi: 10.1016/j.resuscitation.2009.01.016. PubMed DOI PMC

Menegazzi JJ, Rittenberger JC, Suffoletto BP, Logue ES, Salcido DD, Reynolds JC, Sherman LD. Effects of pre‑arrest and intra- arrest hypothermia on ventricular fibrillation and resuscitation. Resuscitation. 2009;80:126–132. doi: 10.1016/j.resuscitation.2008.09.002. PubMed DOI PMC

Castrén M, Nordberg P, Svensson L, Taccone F, Vincent JL, Desruelles D, Eichwede F, Mols P, Schwab T, Vergnion M, Storm C, Pesenti A, Pachl J, Guérisse F, Elste T, Roessler M, Fritz H, Durnez P, Busch HJ, Inderbitzen B, Barbut D. Intra-arrest transnasal evaporative cooling: a randomized, prehospital, multicenter study (PRINCE: Pre-ROSC IntraNasal Cooling Effectiveness) Circulation. 2010;17(7):729–736. PubMed

Krep H, Mamier M, Breil M, Heister U, Fischer M, Hoeft A. Out-of hospital cardiopulmonary resuscitation with the AutoPulse system: a prospective observational study with a new load-distributing band chest compression device. Resuscitation. 2007;73:86–95. doi: 10.1016/j.resuscitation.2006.08.027. PubMed DOI

Hallstrom A, Rea TD, Sayre MR, Christenson J, Anton AR, Mosesso VN Jr, Van Ottingham L, Olsufka M, Pennington S, White LJ, Yahn S, Husar J, Morris MF, Cobb LA. Manual chest compression vs use of an automated chest compression device during resuscitation following out-of-hospital cardiac arrest: a randomized trial. JAMA. 2006;295:2620–2628. doi: 10.1001/jama.295.22.2620. PubMed DOI

Ong ME, Ornato JP, Edwards DP, Dhindsa HS, Best AM, Ines CS, Hickey S, Clark B, Williams DC, Powell RG, Overton JL, Peberdy MA. Use of an automated, load distributing band chest compression device for out-of-hospital cardiac arrest resuscitation. JAMA. 2006;295:2629–2637. doi: 10.1001/jama.295.22.2629. PubMed DOI

Lerner EB, Persse D, Souders CM, Sterz F, Malzer R, Lozano M Jr, Westfall M, Brouwer MA, van Grunsven PM, Whitehead A, Olsen JA, Herken UR, Wik L. Design of the Circulation improving resuscitation care (CIRC) trial: A new state of the art design for out-of hospital cardiac arrest research. Resuscitation. 2011;82:294–299. doi: 10.1016/j.resuscitation.2010.11.013. PubMed DOI

ZOLL Medical Corporation press release. CIRC (Circulation improving resuscitation care) trial concludes succesfully. USA: Chelmsford, MASS; 2011.

Nolan JP, Soar J, Zideman DA, Biarent D, Bossaert LL, Deakin C, Koster RW, Wyllie J, Böttiger B. ERC Guidelines Writing Group. European Resuscitation Council Guidelines for Resuscitation 2010. Executive summary. Resuscitation. 2010;81:1219–1276. doi: 10.1016/j.resuscitation.2010.08.021. PubMed DOI

Mégarbane B, Leprince P, Deye N, Résière D, Guerrier G, Rettab S, Théodore J, Karyo S, Gandjbakhch I, Baud FJ. Emergency feasibility in medical intensive care unit of extracorporeal life support for refractory cardiac arrest. Intensive Care Med. 2007;33:758–764. doi: 10.1007/s00134-007-0568-4. PubMed DOI

Massetti M, Tasle M, Le Page O, Deredec R, Babatasi G, Buklas D, Thuaudet S, Charbonneau P, Hamon M, Grollier G, Gerard JL, Khayat A. Back from irreversibility: extracorporeal life support for prolonged cardiac arrest. Ann Thorac Surg. 2005;79:178–183. doi: 10.1016/j.athoracsur.2004.06.095. PubMed DOI

Chen JS, Ko WJ, Yu HY, Lai LP, Huang SC, Chi NH, Tsai CH, Wang SS, Lin FY, Chen YS. Analysis of the outcome for patients experiencing myocardial infarction and cardiopulmonary resuscitation refractory to conventional therapies necessitating extracorporeal life support rescue. Crit Care Med. 2006;34:950–957. doi: 10.1097/01.CCM.0000206103.35460.1F. PubMed DOI

Chen YS, Lin JW, Yu HY, Ko WJ, Jerng JS, Chang WT, Chen WJ, Huang SC, Chi NH, Wang CH, Chen LC, Tsai PR, Wang SS, Hwang JJ, Lin FY. Cardiopulmonary resuscitation with assisted extracorporeal life-support versus conventional cardiopulmonary resuscitation in adults with inhospital cardiac arrest: an observational study and propensity analysis. Lancet. 2008;372:554–561. doi: 10.1016/S0140-6736(08)60958-7. PubMed DOI

Liu Y, Cheng YT, Chang JC, Chao SF, Chang BS. Extracorporeal membrane oxygenation to support prolonged conventional cardiopulmonary resuscitation in adults with cardiac arrest from acute myocardial infarction at a very low-volume centre. Interact Cardiovasc Thorac Surg. 2011;12:389–393. doi: 10.1510/icvts.2010.256388. PubMed DOI

Morimura N, Sakamoto T, Nagao K, Asai Y, Yokota H, Tahara Y, Atsumi T, Nara S, Hase M. Extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest: A review of the Japanese literature. Resuscitation. 2011;82:10–14. doi: 10.1016/j.resuscitation.2010.08.032. PubMed DOI

Le Guen M, Nicolas-Robin A, Carreira S, Raux M, Leprince P, Riou B, Langeron O. Extracorporeal life support following out-of-hospital refractory cardiac arrest. Crit Care. 2011;15:R29. doi: 10.1186/cc9976. PubMed DOI PMC

Morris MC, Wernovsky G, Nadkarni VM. Survival outcomes after extracorporeal cardiopulmonary resuscitation instituted during active chest compressions following refractory in-hospital pediatric cardiac arrest. Pediatr Crit Care Med. 2004;5:440–446. doi: 10.1097/01.PCC.0000137356.58150.2E. PubMed DOI

Thiagarajan RR, Laussen PC, Rycus PT, Bartlett RH, Bratton SL. Extracorporeal Membrane Oxygenation to Aid Cardiopulmonary Resuscitation in Infants and Children. Circulation. 2007;116:1693–1700. doi: 10.1161/CIRCULATIONAHA.106.680678. PubMed DOI

Kane DA, Thiagarajan RR, Wypij D, Scheurer MA, Fynn-Thompson F, Emani S, del Nido PJ, Betit P, Laussen PC. Rapid-response extracorporeal membrane oxygenation to support cardiopulmonary resuscitation in children with cardiac disease. Circulation. 2010;122(11 Suppl):S241–S248. PubMed

Lebreton G, Pozzi M, Luyt CE, Chastre J, Carli P, Pavie A, Leprince P, Vivien B. Out-of-hospital extra-corporeal life support implantation during refractory cardiac arrest in a half-marathon runner. Resuscitation. 2011;82:1239–1242. doi: 10.1016/j.resuscitation.2011.04.002. PubMed DOI

Arlt M, Philipp A, Voelkel S, Graf BM, Schmid C, Hilker M. Out-of-hospital extracorporeal life support for cardiac arrest-A case report. Resuscitation. 2011;82:1243–1245. doi: 10.1016/j.resuscitation.2011.03.022. PubMed DOI

Peek GJ. Community extracorporeal life support for cardiac arrest - when should it be used? Resuscitation. 2011;82:1117. doi: 10.1016/j.resuscitation.2011.06.006. PubMed DOI

Haneya A, Philipp A, Diez C, Schopka S, Bein T, Zimmermann M, Lubnow M, Luchner A, Agha A, Hilker M, Hirt S, Schmid C, Müller T. A 5-year experience with cardiopulmonary resuscitation using extracorporeal life support in non-postcardiotomy patients with cardiac arrest. Resuscitation. 2012;20 In press [Epub ahead of print] PubMed

Jaski BE, Ortiz B, Alla KR, Smith SC Jr, Glaser D, Walsh C, Chillcott S, Stahovich M, Adamson R, Dembitsky W. A 20-year experience with urgent percutaneous cardiopulmonary bypass for salvage of potential survivors of refractory cardiovascular collapse. J Thorac Cardiovasc Surg. 2010;139:753–757. doi: 10.1016/j.jtcvs.2009.11.018. PubMed DOI

ECC Committee, Subcommittee and Task Force of the American Heart Association. 2005 American Heart Association Guidelines for Cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2005;112(suppl IV):IV1-203. PubMed

Frederiksson M, Aune S, Bang A, Thoren AB, Lindqvist J, Karisson T, Herlitz J. Cardiac arrest outside and inside hospital in a community: mechanisms behind the differences in outcome and outcome in relation to time of arrest. Am Heart J. 2010;159:749–756. doi: 10.1016/j.ahj.2010.01.015. PubMed DOI

Kagawa E, Inoue I, Kawagoe T, Ishihara M, Shimatani Y, Kurisu S, Nakama Y, Dai K, Takayuki O, Ikenaga H, Morimoto Y, Ejiri K, Oda N. Assessment of outcomes and differences between in- and out-of-hospital cardiac arrest patients treated with cardiopulmonary resuscitation using extracorporeal life support. Resuscitation. 2010;81:968–973. doi: 10.1016/j.resuscitation.2010.03.037. PubMed DOI

Fox KA, Dabbous OH, Goldberg RJ, Pieper KS, Eagle KA, Van de Werf F, Avezum A, Goodman SG, Flather MD, Anderson FA Jr, Granger CB. Prediction of risk of death and myocardial infarction in the six months after presentation with acute coronary syndrome: prospective multinational observational study (GRACE) BMJ. 2006;333:1091–1096. doi: 10.1136/bmj.38985.646481.55. PubMed DOI PMC

Hamm CW, Bassand JP, Agewall S, Bax J, Boersma E, Bueno H, Caso P, Dudek D, Gielen S, Huber K, Ohman M, Petrie MC, Sonntag F, Uva MS, Storey RF, Wijns W, Zahger D, Bax JJ, Auricchio A, Baumgartner H, Ceconi C, Dean V, Deaton C, Fagard R, Funck-Brentano C, Hasdai D, Hoes A, Knuuti J, Kolh P. ESC Committee for Practice Guidelines et al.ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC) Eur Heart J. 2011;32:2999–3054. PubMed

Belohlavek J, Rohn V, Tosovsky J, Kunstyr J, Semrad M, Horak J, Lips M, Mlejnsky F, Vykydal I, Balík M, Stritesky M, Mrazek V, Klein A, Linhart A, Lindner J. A review of a newly established ECMO program in university affiliated cardiac center. J Cardiovasc Surg. 2011;52:445–451. PubMed

Kunstyr J, Lipy M, Belohlavek J, Prskavec T, Mlejnsky F, Koucky M, Sebron V, Balik M. Spontaneous delivery during veno-venous extracorporeal membrane oxygenation in swine influenza-related acute respiratory failure. Acta Anaesthesiol Scand. 2010;54:1154–1155. doi: 10.1111/j.1399-6576.2010.02300.x. PubMed DOI

Belohlavek J, Rohn V, Jansa P, Tosovsky J, Kunstyr J, Semrad M, Horak J, Lips M, Mlejnsky F, Balik M, Klein A, Linhart A, Lindner J. Veno-arterial ECMO in severe acute right ventricular failure with pulmonary obstructive hemodynamic pattern. J Invasive Cardiol. 2010;22:365–369. PubMed

Rohn V, Spacek M, Belohlavek J, Tosovsky J. Cardiogenic Shock in Patient with Posterior Postinfarction Septal Rupture-Successful Treatment with Extracorporeal Membrane Oxygenation (ECMO) as a Ventricular Assist Device. J Card Surg. 2009;24:435–436. doi: 10.1111/j.1540-8191.2008.00710.x. PubMed DOI

Belohlavek J, Mlcek M, Huptych M, Svoboda T, Havranek S, Ostadal P, Boucek T, Kovarnik T, Mlejnsky F, Mrazek V, Belohlavek M, Aschermann M, Linhart A, Kittnar O. Coronary versus carotid blood flow and coronary perfusion pressure in a pig model of prolonged cardiac arrest treated by different modes of venoarterial ECMO and intraaortic balloon counterpulsation. Crit Care. 2012;16:R50. doi: 10.1186/cc11254. PubMed DOI PMC

Pokorna M, Necas E, Skripsky R, Kratochvil J, Andrlik M, Franek O. How accurately can the aetiology of cardiac arrest be established in an out-of-hospital setting? Analysis by “concordance in diagnosis crosscheck tables”. Resuscitation. 2011;82:391–397. doi: 10.1016/j.resuscitation.2010.11.026. PubMed DOI

Extracorporeal cardiopulmonary resuscitation versus standard treatment for refractory out-of-hospital cardiac arrest: a Bayesian meta-analysis

Effect of intra-arrest transport, extracorporeal cardiopulmonary resuscitation and immediate invasive assessment in refractory out-of-hospital cardiac arrest: a long-term follow-up of the Prague OHCA trial

Both decreased and increased grey-to-white matter attenuation ratio in the putamen and caudate on early head computed tomography differentiate patients with favorable and unfavorable outcomes after prolonged cardiac arrest-secondary analysis of the Prague OHCA study

Extracorporeal cardiopulmonary resuscitation for refractory OHCA: lessons from three randomized controlled trials-the trialists' view

Intraarrest transport, extracorporeal cardiopulmonary resuscitation, and early invasive management in refractory out-of-hospital cardiac arrest: an individual patient data pooled analysis of two randomised trials

Extracorporeal versus conventional cardiopulmonary resuscitation for refractory out-of-hospital cardiac arrest: a secondary analysis of the Prague OHCA trial

Effect of Intra-arrest Transport, Extracorporeal Cardiopulmonary Resuscitation, and Immediate Invasive Assessment and Treatment on Functional Neurologic Outcome in Refractory Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial

Electrocardiogram-synchronized pulsatile extracorporeal life support preserves left ventricular function and coronary flow in a porcine model of cardiogenic shock

Refractory Ventricle Arrhythmias Alternating with Pulseless Electrical Activity in a Young Woman Rescued by Extracorporeal Cardiopulmonary Resuscitation

Mechanical chest compressions in the coronary catheterization laboratory - do not hesitate to go step further!

Inducibility of ventricular fibrillation during mild therapeutic hypothermia: electrophysiological study in a swine model

Oxygenation, ventilation, and airway management in out-of-hospital cardiac arrest: a review

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ClinicalTrials.gov
NCT01511666