Dissertations in Health Sciences · Dissertations in Health Sciences ISBN 978-952-61-2078-2 ISSN...

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PUBLICATIONS OF THE UNIVERSITY OF EASTERN FINLAND

Dissertations in Health Sciences

ISBN 978-952-61-2078-2 ISSN 1798-5706



PAMELA HILTUNEN

OUT-OF-HOSPITAL CARDIAC ARREST IN FINLAND

Out-of-hospital Cardiac Arrest in Finland

PAMELA HILTUNEN

Out-of-hospital Cardiac Arrest in Finland

To be presented by permission of Health Sciences, University of Eastern Finland for public examination in Kuopio University Hospital, Kuopio, on Friday, April 29th 2016, at 12 noon

Publications of the University of Eastern Finland

Dissertations in Health Sciences Number 343

Centre for Prehospital Care, Institute of Clinical Medicine, Faculty of Health Sciences, Kuopio University Hospital,

Kuopio, 2016

Grano Oy Jyväskylä, 2016

Series Editors:

Professor Veli Matti Kosma, M.D., Ph.D. Institute of Clinical Medicine, Pathology

Faculty of Health Sciences

Professor Hannele Turunen, Ph.D. Department of Nursing Science


Associate Professor Tarja Malm, Ph.D. A.I. Virtanen Institute for Molecular Sciences


Professor Kai Kaarniranta, M.D., Ph.D. Institute of Clinical Medicine, Ophtalmology


Lecturer Veli-Pekka Ranta, Ph.D. School of Pharmacy


Distributor: University of Eastern Finland

Kuopio Campus Library P.O.Box 1627

FI-70211 Kuopio, Finland http://www.uef.fi/kirjasto

ISBN (print): 978-952-61-2078-2 ISBN (pdf): 978-952-61-2079-9

ISSN (print): 1798-5706 ISSN (pdf): 1798-5714

ISSN-L: 1798-5706

Author’s address: Centre for Prehospital Care, Institute of Clinical Medicine Kuopio University Hospital P.O.Box 100

FIN-70029 KYS FINLAND

Supervisors: Docent Jouni Kurola, M.D., Ph.D. Kuopio University Hospital KUOPIO FINLAND Helena Jäntti, M.D., Ph.D. Kuopio University Hospital KUOPIO FINLAND Docent Tom Silfvast, M.D., Ph.D Helsinki University Hospital HELSINKI FINLAND Reviewers: Docent Jouni Nurmi, M.D., Ph.D. Helsinki University Hospital

HELSINKI FINLAND Docent Olli Anttonen, M.D., Ph.D. Päijät-Häme Central Hospital

LAHTI FINLAND Opponent: Professor Klaus Olkkola, M.D., Ph.D. University of Helsinki HELSINKI FINLAND

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Hiltunen, Pamela Out-of-hospital Cardiac Arrest in Finland University of Eastern Finland, Faculty of Health Sciences Publications of the University of Eastern Finland. Dissertations in Health Sciences Number 343. 2016. 160 p. ISBN (print): 978-952-61-2078-2 ISBN (pdf): 978-952-61-2079-9 ISSN (print): 1798-5706 ISSN (pdf): 1798-5714 ISSN-L: 1798-5706 ABSTRACT Out-of-hospital cardiac arrest (OHCA) remains a major health challenge worldwide. Despite the development of medicine and prehospital care during the last decades, only a modest increase in survival has been reported, and overall survival has remained low. After cardiac arrest, there are only a few minutes for effective resuscitation. Optimisation of survival is ideally achieved by strengthening all links in the “chain of survival”: 1) early recognition of cardiac arrest, 2) early cardiopulmonary resuscitation, 3) early defibrillation and 4) post-resuscitation care. The aim of this prospective cohort study was to describe the epidemiology and outcomes of OHCA and study the elements of the “chain of survival” in Finland. The study area included southern and eastern Finland. For six months, data from all cases dispatched as cardiac arrests in the Emergency Medical Dispatch Centre inside the study area were collected to a combined database. Additionally, Emergency Medical Services (EMS) personnel documented all cardiac arrests according the Utstein template, and this information was linked to the database. Moreover, data for patients successfully resuscitated prehospitally and admitted to the intensive care unit (ICU) were collected for 12 months. This information also included the use of therapeutic hypothermia (TH) and involved nearly every ICU in Finland. This study found an incidence of EMS-attempted resuscitation of 51/100,000 inhabitants/year. The emergency medical dispatchers recognised 80.3% of cardiac arrests as the reason for the emergency call. One-third had a primary shockable rhythm, and more than half of the patients had a cardiac arrest of presumed cardiac origin. Nearly half of the patients received bystander cardiopulmonary resuscitation (CPR) before EMS arrival. Overall survival at one year was 13.4%, with 32.7% survival for patients resuscitated from shockable rhythms and 4.6% for patients resuscitated from non-shockable rhythms. A primary shockable rhythm, short delays from collapse to initiation of CPR and to EMS arrival on scene, the presence of an EMS physician during OHCA treatment and the use of TH for patients resuscitated from shockable rhythms were associated with improved survival. EMS personnel most commonly used endotracheal

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intubation as an airway technique. Endotracheal intubation was usually performed by an advanced life support (ALS) provider. Overall success rates of airway management for both basic level and ALS personnel were within acceptable levels. TH was widely implemented in intensive care units, and was also in use for patients with a non-shockable primary rhythm. Survival to hospital discharge among ICU-treated unconscious OHCA patients was 51.6% and was improved if TH was used for patients resuscitated from a shockable primary rhythm. TH was not associated with survival among patients with a non-shockable rhythm. Overall survival from OHCA was similar to that reported earlier from Finland. Survival was improved, however, among patients resuscitated from bystander-witnessed cardiac arrest with a primary shockable rhythm of presumed cardiac origin. These survival rates are also commendable when compared to studies from other countries. The ability of Finnish dispatchers to recognise cardiac arrest was high. Bystander CPR should be increased. Current national recommendations concerning airway management in OHCA seem practical and lead to desirable results. TH was used widely in Finland and was also used for patients resuscitated from non-shockable primary rhythms. National Library of Medicine Classification: WG 214, WG 205, WA 292, WF 145, WX 215, WA 900, W 84.7 Medical Subject Headings: Out-of-Hospital Cardiac Arrest; Airway Management; Cardiopulmonary Resuscitation; Emergency Medical Services; Intensive Care Units; Hypothermia, Induced; Incidence ; Survival Rate; Time-to-Treatment; Treatment Outcome ; Patient Outcome Assessment; Critical Pathways; Cohort Studies; Prospective Studies

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Hiltunen, Pamela Out-of-hospital Cardiac Arrest in Finland Itä-Suomen yliopisto, terveystieteiden tiedekunta Publications of the University of Eastern Finland. Dissertations in Health Sciences Nro.343. 160 s. TIIVISTELMÄ Sairaalan ulkopuolinen sydänpysähdys on merkittävä kansanterveydellinen ongelma. Huolimatta lääketieteen ja ensihoidon kehittymisestä, kokonaisselviytyminen on matala, joskin pientä parantumista on vuosikymmenien saatossa havaittu. Kun sydänpysähdys tapahtuu, on aikaa vain muutama minuutti tehokkaille elvytystoimille. Niin sanottu ”chain of survival” – ketjun vahvistaminen optimoi potilaan selviytymisen. Nämä ketjun osat ovat: 1) sydänpysähdyksen varhainen tunnistaminen, 2) varhain aloitettu painelu- tai/ja painelu-puhalluselvytys, 3) varhainen defibrillaatio ja 4) elvytyksenjälkeinen hoito. Tämän prospektiivisen kohorttitutkimuksen tarkoituksena oli kuvata sairaalan ulkopuolisen sydänpysähdyspotilaan epidemiologiaa ja hoitotuloksia sekä tarkastella ”chain of survival” ketjua ja sen osasten vaikutusta selviämiseen. Tutkimusalueena oli itäinen ja eteläinen Suomi. Tiedonkeruu kesti kuusi kuukautta, minkä aikana tutkimusalueen hätäkeskuksista kerättiin tietokantaan tiedot kaikista tehtävistä jotka koskivat sydänpysähdystä. Ensihoitohenkilöstö dokumentoi omalta osaltaan hoitamansa sydänpysähdyspotilaat ja nämä tiedot syötettiin yhteiseen tietokantaan. Niistä potilaista, jotka otettiin tehohoitoon, järjestettiin erillinen tiedonkeruu jota jatkettiin 12 kuukauden ajan, ja tässä keräyksessä olivat mukana lähes kaikki Suomen teho-osastot. Tässä tutkimuksessa todettiin ensihoitajien hoitamien elvytystapahtuminen ilmaantuvuudeksi 51/100,000 asukasta/vuosi. Hätäkeskuspäivystäjät tunnistivat 80.3% elottomuudesta hätäpuhelun soittohetkellä. Yhdellä kolmasosalla potilaista oli defibrilloitava rytmi tavattaessa, ja yli puolella potilaista arvioitiin olevan sydänperäinen taustasyy. Vajaa puolet potilaista sai maallikkoelvytystä ennen ensihoidon paikalle tuloa. Kokonaisselviytyminen vuoden kohdalla oli 13.4%, ja 32.7% niiden potilaiden osalta jotka oli elvytetty defibrilloitavasta alkurytmistä. Vastaava selviytymisluku ei-defibrilloitavista rytmeistä elvytetyillä oli 4.6%. Defibrilloitava alkurytmi, lyhyet viiveet sydänpysähdyksestä paineluelvytyksen aloittamiseen ja ensihoidon paikalle tuloon, ensihoitolääkärin osallistuminen hoitoon sekä hypotermiahoito teho-osastolla niille potilaille, jotka oli elvytetty defibrilloitavasta rytmistä, olivat yhteydessä potilaan selviytymiseen sekä elossa sairaalasta että 1 vuoden kohdalla. Ensihoitajat yleisimmin varmistivat ilmatien intubaatiolla ja suorittajana oli yleisimmin hoitotaso. Onnistumisprosentit olivat hyväksyttävällä tasolla sekä perus- että hoitotason ensihoitajilla. Terapeuttinen hypotermiahoito oli laajasti käytössä Suomen teho-osastoilla, ja myös potilaita, jotka oli elvytetty ei-defibrilloitavista rytmeistä, viilennettiin.

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Kokonaisselviytyminen niillä tajuttomilla potilailla, jotka otettiin sairaalaan tehohoitoon, oli 51.6%, ja hypotermiahoito vaikutti positiivisesti defibrilloitavista rytmeistä elvytettyjen ennusteeseen. Hypotermiahoidolla ei ollut vaikutusta ei-defibrilloitavista rytmeistä elvytettyjen potilaiden selviytymiseen. Kokonaisselviytyminen sairaalan ulkopuolisesta sydänpysähdyksestä oli samaa luokkaa kuin mitä aiemmin on Suomesta raportoitu. Selviytyminen oli kuitenkin parantunut niillä potilailla, joiden elottomuus oli nähty, joiden alkurytmi oli defibrilloitava sekä sydänpysähdyksen taustasyy oletetusti sydänperäinen. Näiden potilaiden selviytymisluvut olivat kansainvälisestikin tarkasteltuna hyviä. Hätäkeskuspäivystäjän kyky tunnistaa sydänpysähdys oli korkea. Maallikkoelvyttäjien antamaa elvytystä sydänpysähdystilanteessa tulisi lisätä. Nykyiset kansalliset suositukset hengitystien varmistamisesta sydänpysähdyksen yhteydessä ovat mielekkäät ja käytännölliset ja johtavat hyviin onnistumislukuihin. Terapeuttinen hypotermia oli laajassa käytössä Suomessa ja sitä käytettiin myös potilaille, joilla alkurytmi oli ei-defibrilloitava rytmi. Luokitus: WG 214, WG 205, WA 292, WF 145, WX 215, WA 900, W 84.7 Yleinen suomalainen asiasanasto: sydämenpysähdys; epidemiologia; akuuttihoito; ensihoito; elvytys; hypotermia; selviytyminen; hoitoketjut; kohorttitutkimus; seurantatutkimus

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To my mother Vaula

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Acknowledgements It feels somewhat surreal to write this page for my thesis as it took six years to finish this study. During this time, I have been blessed for crossing paths with so many people; those who have gave me their love, friendship and support during this journey. Some of them live literally on the other side of the world. I hope, although not mentioned, these people know in their hearts how grateful I am for them for entering and being in my life, sometimes just at the right moment when I was diving through the deepest oceans and storms with this thesis. My warmest appreciation and respect goes to Professor Esko Ruokonen. Many years ago I got a phone call from you asking whether I was interested in doing some research (with pigs first, of course). I thought about it thoroughly for couple of days, but finally said yes. Later on you guided me to the FINNRESUSCI project. You have inspired me with your passionate attitude towards science. I have always enjoyed listening to your lectures, making scientific research sound like a fascinating world that every doctor could (and should) easily join into. My supervisors Docent Jouni Kurola, Docent Tom Silfvast and Helena Jäntti, PhD. I somehow managed to have these amazing supervisors who helped me finalise this study. Jouni. You make my head spin around and around nearly every time we meet – your endless energy towards anything is unstoppable! I have strongly felt your support and presence close to me over these years. You have taught me so much, in research and clinically. Thank you; Tom, your sharp comments and simple suggestions for solutions have been most valuable. Sharing your extensive experience from prehospital work has helped me to look at things from the right perspective; Helena, my supervisor, my colleague, my friend. Your fantastic ability to simplify even difficult issues has led me out of many deadlocks. The word “resilience” gets its meaning from you! YOU are the heart of HEMS. Your steady, unwavering support and friendship have carried me along in science and also in my civilian life. Docent Markku Kuisma, co-author. You have provided me with prompt information when needed, with quick responses to any questions I have had, even the silly ones… It now feels crazy to remember but we two sat down 1,5 years ago in Toowoomba, Australia for two hours. You, while travelling, gave me your time to help me with this study. I never forget that day. It has also been a great pleasure to get to know you personally as well. Jukka Vaahersalo, MD, FINNRESUSCI researcher and co-author. Together we made it! With your kind permission as main author I have been able to use study IV as part of my thesis. Co-authors Juha Rutanen, PhD, Tuomas Oksanen, MD, Kirsi-Maija Kaukonen, PhD, Docent Jyrki Tenhunen, Professor Tero Ala-Kokko, Vesa Lund, PhD,

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Matti Reinikainen, PhD, Outi Kiviniemi, MD, Tero Varpula, PhD, Professor Ville Pettilä. Juha, your help especially in the very start of the study but also later, has been irreplaceable. Matti, with your guidance I overcame the “blank paper syndrome” and moved forward from page 1 in this thesis. Marjaana Tiainen, PhD, neurologist evaluating FINNRESUSCI patients’ neurological outcomes. Though extremely busy, you gave your time and help for this study. Docent Ari Uusaro. I can only imagine what has it been like to guide me when I was starting my research (with those pigs). I was totally unfamiliar with research nuances, and I was in the middle of it, like ground zero… I thank you for your patience and encouraging comments as a co-author, especially concerning my first published article. Your advice have helped me enormously with this study as well. Docent Olli Anttonen and Jouni Nurmi, my official reviewers. I read very carefully your insightful comments and thoughts. With them, I managed to improve my dissertation, which I was writing alone through the darkest and rainiest days at the end of last year, wondering to myself whether any of it would be even close to publishable. Docent David Laaksonen, thank you for editing the English. Marja-Leena Lamidi, your quick and prompt replies concerning my statistical problems over these years have been in great value. FH60 crew, all the doctors, flight paramedics and pilots. Whatever seems to happen to me, you stand beside me like rock to lean on. You encouraged me to write and finish this thesis, and never got tired listening to my endless talk about this project (or did you?). I feel privileged to fly and work with you. Thank you for being such an important part of my life. EMS doctors and paramedics inside the study area. Without your assistance with data collection this dissertation would never exist. I deeply thank each and every one of you for helping me to create this dissertation and hence, showing the status quo of management of out-of-hospital cardiac arrest patients in Finland. We share the same out-of-hospital world, which sometimes extends far beyond. It must have been a challenge to cope with this critical patient group, remember all the treatment given and write things down for FINNRESUSCI research purposes. Nina Nakari, research nurse. I am grateful for your help with prehospital data collection and handling in the HUS area. My sincerest thanks go to all the nurses and doctors participating in FINNRESUSCI data collection in 21 ICUs. This is very impressive and makes me very proud of the massive ICU network we have in Finnish ICUs. Research nurses Elina Halonen, Sari Rahikainen, Saija Rissanen. Thank you for your contribution.

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In 2014, I worked overseas in Australia for one year. The journey was unforgettable. Australia will always have a special place in my heart. I send my warmest greetings to all the people I was able to meet and work with. This research project has walked with me even there, down under. It sure has seen it all! I have desired many things and have craved to experience life as much as I can. By living so, it undoubtedly has leaded to limited time to spend with my friends. I have humbly noticed how those I need still seem to stay near. Petteri. With you the world has shown its humorous side, and the friendship we have has lasted since medical school. Thank you also for bringing Sari into my life. Sari. With you I double my joys and half the sorrows I’ve felt. Heli and Jari, Henna and Teemu, Teea. I thank you all for letting me leave medicine behind time to time. Anne, my sister-in-law, Eila and Jorma, my parents-in-laws. I am very fortunate to have you near my family and me. Thank you for your never-failing help and support for everything and also for looking after our children and never counting hours or kilometres. My sister Seidi and brother Ali. We all live apart, but it is always easy to call you whatever the issue would be. My father Matti. Your support for anything I have strived for in my life is invaluable. You never stop thinking positive, and I admire that attitude of yours. With your love I would and actually have moved mountains. My husband Jani. I assume neither of us knew how much work and time this dissertation would actually take. I often wished I had a magic wand to wipe away the sadness from your look when I was too focused to see anything else but this. Research work can be all-embracing and can make loved ones feel second best, which is untrue. I promise to give the best of me to our life that we still have ahead of us. I will never stop admiring your patience waiting for this dissertation to be finished. Our children Luka and Neela. Luka you once said: “Einstein has said that if you cannot explain difficult things with simple words, you have not understood it…” thank you for this advice, I have tried to keep it in mind when writing this thesis! Neela, you may be a small girl still, but inside you lives a soul beyond your years that I never stop admiring. Whatever I might yet achieve, you two will always be the best and most beautiful creations that I have brought into this world. My late mother Vaula. To my sorrow, we ran out of time for you to see me finish this dissertation. I still feel your presence and love around me, though. I know you would be proud of me. Luckily, for some reason, just before Christmas I printed out a version of this thesis to be sent to reviewers, and you and I sat down and briefly read through it together. I promise to continue to reflect on all those good things you showed and taught me. I dedicate this thesis to you; thank you for being the best äiti ever.

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I am thankful for all the financial support received from EVO funding from Kuopio University Hospital, the Foundation of Emergency Medicine, the Finska Läkaresällskapet Foundation, the Päivikki and Sakari Sohlberg Foundation and the Finnish Society of Anesthesiologists. Kuopio, April 2016 Pamela Hiltunen

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List of original publications and studies This Dissertation is based on the following original publications and studies: I Hiltunen P, Kuisma M, Silfvast T, Rutanen J, Vaahersalo J, Kurola J. Regional variation and outcome of out-of-hospital cardiac arrest (ohca) in Finland – the Finnresusci study. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine 20:80, 2012. II Hiltunen P, Silfvast T, Jäntti H, Kuisma M, Kurola J and for the FINNRESUSCI Prehospital Study Group. Emergency dispatch process and patient outcome in bystander-witnessed out-of-hospital cardiac arrest with a shockable rhythm. European Journal of Emergency Medicine 22(4):266-72, 2015. IIII Hiltunen P, Jäntti H, Silfvast T, Kuisma M, Kurola J. Airway management in out-of-hospital cardiac arrest: current practises and outcomes. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine 2016. In press. IV Vaahersalo J, Hiltunen P, Tiainen M, Oksanen T, Kaukonen Kirsi-Maija, Kurola J, Ruokonen E, Tenhunen J, Ala-Kokko T, Lund V, Reinikainen M, Kiviniemi O, Silfvast T, Kuisma M, Varpula T, Pettilä V. Therapeutic hypothermia after out-of-hospital cardiac arrest in Finnish intensive care units: the FINNRESUSCI study. Intensive Care Medicine 39:836-837, 2013. The publications were adapted with the kind permission of the copyright owners.

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Contents 1 INTRODUCTION……………………………………………………………………………….1

2 REVIEW OF THE LITERATURE…………………………………………………………...…3 2.1 Prehospital emergency care……………………………………………………………..…..3 2.1.1 History and development…………………………………………………………..…3 2.1.2 Prehospital system in Finland……………………………………………………...…4 2.1.2.1 Short history of the development of prehospital care………………………4 2.1.2.2 Emergency Medical Service (EMS)……………………………………...……5 2.1.2.3 Emergency Medical Dispatch (EMD)……………………………………..….6 2.2 Epidemiology and outcome of out-of-hospital cardiac arrest (OHCA)……………..….7 2.2.1 Incidence and aetiology of OHCA………………………………………………..…..7 2.2.2 Indications for out-of-hospital resuscitation efforts……………………………..….9 2.2.3 Factors related to outcome in OHCA……………………………………………….10 2.2.4 Outcomes of OHCA worldwide and in Finland…………………………………...11 2.3 Chain of survival……………………………………………………………………………12 2.3.1 Role of the bystander – importance of the emergency call and CPR……….……13 2.3.2 Role of the dispatcher – recognition of OHCA…………………………………….13 2.3.3 Role of EMS – following resuscitation protocol……………………………………14 2.3.4 Role of EMS-physician in treatment of OHCA…………………………………….16 2.3.5 Post-resuscitation care after OHCA…………………………………………………16

3 AIMS OF THE STUDY……………………………………………………………………..….19

4 PATIENTS AND METHODS…………………………………………………………….…..21 4.1 Study area and description of EMS…………………………………………………….…21 4.2 Study setting and data collection…………………………………………………….……22 4.3 Ethical considerations………………………………………………………………….….. 27 4.4 Statistical methods……………………………………………………………………….….27

5 RESULTS………………………………………………………………………………………...29 5.1 Epidemiology and outcome………………………………………………………………..29 5.1.1 Epidemiology………………………………………………………………………….29 5.1.2 Patient outcome……………………………………………………………………….31 5.2 Factors related to survival………………………………………………………………….32 5.3 Elements of chain of survival………………………………………………………………33 5.3.1 Role of the EMD……………………………………………………………….……….33 5.3.2 Airway management process in OHCA……………………….……………………34 5.3.3 Therapeutic hypothermia in ICU………………………………………………….…35

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6 DISCUSSION………………………………………………………………………………….37 6.1 Main findings……………………………………………………………………………….37 6.1.1 Epidemiology and outcome…………………………………………………………37 6.1.2 Factors related to survival…………………………………………………………...37 6.1.3 Elements of chain of survival……………………………………………………….37 6.2. Incidence and outcomes in relation to previous studies……………………………….38 6.2.1 Incidence of OHCA…………………………………………………………………..38 6.2.2 Withholding resuscitation…………………………………………………………...39 6.2.3 Aetiology………………………………………………………………………………40 6.2.4 Increased survival rates and survival from shockable rhythms…………………41 6.2.5 Survival from non-shockable rhythms……………………………………………..42 6.2.6 Different EMS systems……………………………………………………………….42 6.3. Factors related to survival………………………………………………………………….43 6.3.1 Early provision of CPR……………………………………………………………….43 6.3.2 EMS arrival…………………………………………………………………………….43 6.3.3 EMS physician…………………………………………………………………………44 6.4 Different elements in OHCA..…………………………………………...…………………45 6.4.1 Dispatch process……………………………………………………………………….45 6.4.2 Airway management…………………………………………………………………..45 6.4.3 Therapeutic hypothermia……………………………………………………………..46 6.4.4 Cardiac arrest in special circumstances……………………………………………...47

7 LIMITATIONS OF THE STUDY…………………………………………………………….49

8 CONCLUSIONS………………………………………………………………………………..51

9 FUTURE IMPLICATIONS……………………………………………………………………53

10 REFERENCES………………………………………………………………………………….55 11 APPENDIX: Original publications I, II and IV Study III

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Abbreviations AED Automated external defibrillator ALS Advanced life support APACHE II Acute Physiology and Chronic Health Evaluation II Score BLS Basic life support BVM Bag-valve-mask CPC Cerebral Performance Category CRF Case Report Form CPR Cardiopulmonary resuscitation DNAR Do not attempt resuscitation EMD Emergency Medical Dispatch EMS Emergency Medical Services EMT Emergency Medical Technician ERC European Resuscitation Council ETI Endotracheal intubation ICU Intensive care unit PEA Pulseless electrical activity PCI Percutaneous Coronary Intervention ROSC Return of spontaneous circulation RCT Randomised controlled trial

T-CPR Telephone-guided cardiopulmonary resuscitation TH Therapeutic hypothermia

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OHCA Out-of-hospital cardiac arrest SAD Supraglottic airway device VF Ventricular fibrillation VT Ventricular tachycardia

Definitions

Considered for resuscitation Patient without of signs of circulation. Does not

include patients: - in whom resuscitation was not attempted (see below), or it was immediately discontinued after initial assessment (i.e. unwitnessed cardiac arrest with asystole, or pre-existing DNAR) - patients with clear secondary signs of death - patients with lethal trauma (e.g. decapitated body) - patients alive upon EMS arrival despite suspected OHCA at dispatch

Attempted resuscitation resuscitation continued with cardiopulmonary

resuscitation (CPR), early defibrillation and/or airway management

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1 INTRODUCTION In Europe, the annual incidence of Emergency Medical Services (EMS) -treated out-of-hospital cardiac arrest (OHCA) is approximately 38/100,000/year (Atwood et al. 2005). Without any resuscitation efforts, patients with a stopped heart will die. Some of these patients will undergo cardiopulmonary resuscitation (CPR) by bystanders before the EMS arrive and continue resuscitation efforts to restore life. International guidelines for CPR are published every five years, most recently in 2015 (Monsieurs et al. 2015). Nevertheless, despite these efforts, survival is poor, roughly 10% of all OHCAs (Berdowski et al. 2010, Ong et al. 2015). To optimise the “chain of survival”, the recognition of cardiac arrest, early activation of EMS, early CPR efforts provided by a caller or bystander, possibly with telephone-guided CPR (T-CPR), and early defibrillation are the key acts that need to be performed effectively and as rapidly as possible. Successful return of spontaneous circulation (ROSC) represents the first step of recovery from OHCA. Many complex pathophysiological changes commence after ROSC is achieved (Nolan et al. 2008). Post-resuscitation care plays an important role in patient outcome by providing support and treatment for multiple organs affected by cardiac arrest (Kirves et al. 2007, Sunde et al. 2007). The aim of this nationwide study was to prospectively study the epidemiology and outcomes of OHCA in Finland. Of all OHCA patients, patients with a witnessed cardiac arrest and a primary shockable rhythm (ventricular fibrillation or ventricular tachycardia) have the best prognosis. It is vital to recognise OHCA when the emergency call is processed. Additionally, the practice of EMS prehospital management of the airway in patients with OHCA is not known. We also studied the use and outcome of therapeutic hypothermia for resuscitated OHCA patients in Finnish intensive care units.

2 REVIEW OF THE LITERATURE 2.1 PREHOSPITAL EMERGENCY CARE 2.1.1 History and development In previous times, people who were injured or sick were transported to hospital by any vehicle available – by horses, farm machinery, taxicabs or simply by carrying them. No treatment was given during transport, and people capable of patient care were unavailable. It was not until in the late 1700s, when Napoleon’s chief military physician, surgeon Baron Larrey, recognised the need for better prehospital care and constructed horse-drawn “flying ambulances” for soldiers injured on the battlefield (Remba et al. 2010) (in fact, the word “ambulance” originates from Latin meaning to “walk, move or wander” about). He stressed that not only that these ambulances should transport patients rapidly, but they should also include medically trained personnel capable of care en route to the nearby hospital. Larrey established the theory of prehospital care, and he can be considered as the father of EMS in the modern era. Despite the efforts of Larrey, prehospital care for civilians remained practically undeveloped until wars in Korea, Vietnam and the Middle East. Many injured soldiers were rescued by medics who initiated ventilation support, performed external bleeding control and transfused fluids intravenously before arrival to hospital. These interventions saved many of the military personnel who normally would have died on the field. As a result, these experiences triggered prehospital systems established worldwide in civilian era. This development was more than welcome. In fact, for example in the 1950s in United States, the only requirements for an ambulance were that the patient was able to lie down during transportation. Moreover, over half of the ambulances were operated by morticians (McSwain 2005). Experienced physicians returning home from Korea and Vietnam claimed that soldiers were more likely to survive in a combat zone than a normal citizen on the street. An impressive report were published in United States in 1966 by researchers from the National Academy of Sciences (Howard 2000). It concluded that “…both the public and government were insensitive to the magnitude of the problem of accidental death and injury…” and that “most ambulances used in this country are unsuitable, have incomplete equipment, carry inadequate supplies, and are manned by untrained attendants”. Several guidelines were developed and recommendations were given. These publications lead departments in different areas worldwide to initiate training personnel to treat patients prehospitally, including those suffering from cardiac arrest. For example, in the late 1960s, a group of Seattle Fire Department personnel began a training course for firemen designed by dedicated physicians, many of them with wartime medical experience. These first trained paramedics started their work in the prehospital environment on March 7, 1970 and were instructed by law to have a physician with them on every emergency task. However, the governor of California Ronald Reagan signed the Wedworth Townsend Act of 1970 to become law. It had many important consequences in the future development of

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the EMS system in the US (Pozner et al. 2004). Importantly, it led paramedics to work without the presence of physicians, but still providing more advanced patient care than previously had been possible. Along with progress in “EMS infrastructure”, significant inventions and treatments have been developed. Major advances in the care of lifeless patients were brought into practice in the 1950s. The defibrillator was introduced as a tool for life-saving treatment of lethal ventricular arrhythmia (ZOLL et al. 1956) along with modern ventilation strategies (SAFAR, ESCARRAGA & CHANG 1959). In addition, William Kouwenhoven introduced external chest compressions in order to maintain even minor cardiac output during cardiac arrest (KOUWENHOVEN, JUDE & KNICKERBOCKER 1960). In the 1960s, the city of Belfast introduced the first mobile intensive care unit that was physician staffed and carried a defibrillator. This unit treated patients suffering chest pain or sudden cardiac arrest only (Pantridge, Geddes 1967). In the 1970s and 1980s, multiple EMS systems were founded internationally in a variety of ways. Mostly they were organised with at least two tiers, where emergency medical technicians (EMTs) represented the first tier (BLS) and paramedics the second tier (ALS). Additionally, some systems had physicians involved as a third tier. Eisenberg et al. reported encouraging results in 1980 showing that survival from cardiac arrest was improved if patient care was provided by ALS-level personnel (Eisenberg, Bergner & Hallstrom 1980, Eisenberg et al. 1980), which provided support for a two-tiered system at least in the prehospital setting. In Europe, prehospital care is typically physician led (Langhelle et al. 2004), whereas in the USA it is paramedic led (Pozner et al. 2004). Nowadays, EMS exists to fulfill the basic principles of first aid: Preserve Life, Prevent Further Injury, and Promote Recovery. This theme in medicine is illustrated by a “star of life”, and it includes six points that are used to describe high-quality prehospital care: (1) early detection, (2) early reporting, (3) early response, (4) good on-scene care, (5) care in transit and (6) transfer to definitive care. Many ways of coordinating EMS exist, and there is variability in this process of care (Roudsari et al. 2007). 2.1.2 Prehospital system in Finland 2.1.2.1 Short history of the development of prehospital care In 1877, the Finnish subsection of the Red Cross sent a unit to the Russo-Turkish War. This unit can be considered the first prehospital provider in Finland. Furthermore, the military developed prehospital care in the wars that Finland was involved in (the Finnish Civil War in 1918, World War II) similarly as in other countries worldwide. Especially after World War II, the Finnish Red Cross recognised the need for ambulance services and transportation for civilian emergencies. In 1953, the Chairman of the Finnish Red Cross, medical councilor Leo Kaprio, sent an enquiry for communities about how they organised prehospital transportation for patients. Of 486 communities, 411 did not have any transportation system. Thirty-three communities left the enquiry unanswered. When organised (75/486), the provider of the ambulance service was usually the rescue

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department. In a minority of communities, hospitals, private drivers (taxis), the Red Cross, or industries were the providers of this service. Nevertheless, these “ambulances” were also used to transport deceased people and served as taxis, with basically no medical equipment. The driver had no assisting personnel. In 1956, the Ministry of Health defined the minimum equipment for the ambulances. Gradually, improvements in education and equipment enabled ambulance personnel to better provide first aid (Järvinen 1998). Helsinki, the capital city of Finland, and its rescue department, initiated ambulance service in 1904. Moreover, the first physician-staffed ambulance, the Mobile Intensive Care Unit (MICU), was established in Helsinki in 1972 and has been in operation ever since. It was dispatched for high risk emergencies, and at first it also transported patients. At the end of 1980s this physician-staffed unit stopped transporting patients, improving availability for other emergency situations (Nyström 2005). In other parts of Finland, inspired by the experiences of the Helsinki MICU, other physician-staffed ambulances were founded (e.g. in Kuopio) but were soon stopped due to lack of support of local authorities. Finland did not have legislative guidance for EMS until in 1994 when the municipalities became responsible for organising the EMS in their area. The first helicopter EMS (HEMS) began in 1992 in the southern part of Finland (“Medi-Heli”) and was initially a strongly charity-based unit. In 2011, the legislation was revised. Instead of municipalities organising EMS, hospital districts became responsible for coordinating EMS, including dispatch criteria and administrative EMS medical director. New legislation also determined the minimum educational standards of basic-level and advanced-level ambulance personnel (Finlex 2011). 2.1.2.2 Emergency Medical Services (EMS) Nowadays EMS services are organised by 20 hospital districts. They can provide this service themselves or buy it from municipal services or private companies. The EMS system is three-tiered. By law, in every ambulance unit there must be at least one educated, professional health care provider. First responders and EMTs serve as the first tier, i.e. basic life support (BLS). First responders are usually voluntary personnel from the local fire brigade and have completed a short course for first responders. BLS personnel may also be practical nurses or registered nurses in prehospital emergency care. Advanced life support (ALS) units have at least one of the personnel who is a registered nurse (bachelor) in emergency care or a registered nurse with one year of additional education for prehospital care.

The first tier is capable of defibrillating and, in case of a cardiac arrest, to use bag-valve-mask ventilation (BVM) and a supraglottic airway device (SAD). In southern part of Finland, the first tier is also allowed to use endotracheal intubation (ETI) in cardiac arrest patients, if trained and experienced in the ETI procedure. Additionally, the first tier is allowed to start intravenous fluid administration and give medication by natural routes (orally, inhaled, intranasally, rectally) and, if registered nurses, also intravenously either independently or after consulting an EMS or other physician. Adrenalin can be administered intravenously in OHCA without consultation.

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The second tier (ALS level) works more independently than the first tier. Instructions are given locally by the EMS medical coordinator and vary. The ALS level can use ETI as a first-line choice in case of a cardiac arrest. Moreover, ALS level is trained for intubating also in non-arrest situations, but nationwide recommendations follow Scandinavian guidelines in which performing ETI for an unconscious patient is a procedure that a prehospital physician performs (Berlac et al. 2008). Physician-staffed units represent the third tier and are available 24/7. One ground unit exists in the capital city, Helsinki, with an additional five HEMS units nationwide. There are also two helicopter unit staffed with nurses only, one of which is funded by local charity. Two cities, Pori and Lahti, provide physician-staffed ground unit EMS for limited hours of the day. HEMS is coordinated by FinnHEMS, which is the national administrative unit for HEMS and is owned by the five university hospital districts. Funding comes from the state via the Ministry of Social Affairs and Health. Physician staffed units are dispatched simultaneously in areas where they are available, for high-risk trauma and non-trauma cases. They are involved in treatment for critically injured or sick patients and, additionally, give instructions and advice via telephone if needed. Physicians are consultants in anaesthesiology and intensive care or in their final stage of specialisation. In 2015, HEMS covered 60% of the Finnish population within a 30-minute response time (personal communication, Jukka Pappinen, FinnHEMS). The aforementioned physician-staffed ground unit operating in Helsinki also reaches all cardiac arrest patients in Helsinki within a 30-minute response time. 2.1.2.3 Emergency Medical Dispatch (EMD) Emergency dispatch centres in Finland were first established in the late 1950s and were community-based and operating as part of rescue department services. Police, the rescue department and the ambulance service all had separate dispatch numbers. By 1954, Helsinki had installed 600 emergency phones inside the city area, and these calls were answered by Helsinki dispatch centre provided by Helsinki telephone company. Legislation in 1976 required municipalities to be responsible for the organisation of emergency calls. As a result, Finland initially had 58 dispatch centres based on the existing telephone network. No uniform number to call for help existed, and people answering the calls were untrained dispatchers, often former firemen or police personnel. At first, there was a variety of ways to alert ambulances. One could call to a dispatch centre, who only transmitted the request for an ambulance to the provider and did not do any assessment of need for transportation overall nor gave any instructions to the caller. The emergency number in Finland is “112”, the official emergency number inside the European Union, and was adopted for use in the early 1990s. The system of dispatch centres was established in 2001 due to new legislation. Prior to this, in 1996 authorities combined four dispatch centers for a four-year period to test the liaison of rescue and police dispatch centres. The aim was to optimise the dispatching organisation. The results

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were encouraging. The goal was to reduce the large amount of dispatch centres Finland had at that time. Between 2001-2005 a nationwide reorganisation was established, and nowadays only six dispatch centres exists. These are combined centres for EMS, police and fire and rescue services. Little by little, dispatchers were trained for their role, first through different courses 2-4 weeks in duration and organised by rescue departments. Modern Emergency Medical Dispatcher (EMD) training contains 1,5 years of formal education in emergency-telephone-call processing and dispatching, and was started in 1997. Since then, medical call processing and dispatching have been based on the patient’s chief complaint and the patient’s current condition according to uniform national emergency medical dispatch guidelines given by Ministry of Social Affairs and Health. These criteria-based dispatch guidelines are based on those developed in 1990 by the King County Emergency Medical Services Division (King County Government Health Services 2015). Dispatchers play an important role in patient care in the prehospital setting. They gather information on the patient’s condition and location, decide what kind of response is needed and communicate with the dispatched units. In case of a cardiac arrest, they also give T-CPR instructions. By law, only the emergency dispatch centre can take and process emergency calls in Finland. 2.2 EPIDEMIOLOGY AND OUTCOME OF OUT-OF-HOSPITAL CARDIAC ARREST (OHCA) In 1991, a statement was issued to establish uniform terms and definitions for OHCA and resuscitation. Reports from different countries and different systems were infrequently compatible. To improve comparability, an “Utstein-style template” was developed (Cummins et al. 1991). The first meeting was held at Utstein Abbey, in Norway in 1990 by the European Resuscitation Council, which was founded one year earlier. The goal was to be able to compare cardiac arrest reports more reliably and share information internationally. Since then, the Utstein template has been updated (Jacobs et al. 2004, Perkins et al. 2015), and it has been used widely in published outcome studies of cardiac arrest. According to Utstein definitions, cardiac arrest is a lack of cardiac mechanical activity that is confirmed by the absence of signs of circulation and, in case of OHCA, occurring in an out-of-hospital environment. The patient is unresponsive, not breathing or with agonal respirations and has no pulse. Convulsions may occur. Death will follow if arrest is untreated. The World Health Organisation (WHO) defines cardiac death as sudden if it is manifested within 1 hour of the onset of symptoms (WHO Scientific Group 1985). Additionally, especially in scientific studies other definitions are also in use (Zipes et al. 2006) in which cardiac arrest is sudden if it results within minutes after the onset of symptoms and is unexpected. 2.2.1 Incidence and aetiology of OHCA The overall incidence of OHCA globally has been reported to be between 37 and 121 alle nelinkertainen per 100,000 habitants/year (Berdowski et al. 2010). In Finland, earlier

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studies reported the incidence of OHCA in the cities of Helsinki and Tampere to be between 80-113 per 100,000 habitants/year (Silfvast 1990, Kuisma, Määttä 1996, Kämäräinen et al. 2007). The situation across the country has been unknown. Table 1. Incidence and demography of out-of-hospital cardiac arrest (OHCA) in earlier studies from Finland in the cities of Helsinki and Tampere in 1987, 1994 and 2004, respectively. Incidence is reported per 100,000 inhabitants/year. *EMS-witnessed OHCAs included.

Community Populati

on served

OHCA considered for resuscitation

OHCA incidence considered for resuscitation

EMS-treated OHCA incidence

Primary shockable rhythm (%)

Bystander CPR (%)

Overall survival to hospital discharge (%)

Survival from witnessed primary shockable rhythm (%)

Helsinki 1987 (Silfvast)

500 000

563

113

53

62

Not reported

not reported

27*

Helsinki 1994 (Kuisma)

516 000

412

80

67

37

22

13

32

Tampere 2004 (Kämäräinen)

203 000

191

94

46

30

31

13

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Variation in incidence exist between countries and communities (Atwood et al. 2005, Fredriksson, Herlitz & Nichol 2003). There may be many reasons for this, including inclusion and exclusion criteria of studies and data collection (Fredriksson, Herlitz & Nichol 2003, Nishiyama et al. 2014). To overcome this variation, a common dataset has been established (Wnent et al. 2015), European Registry of Cardiac arrest, “EuReCa”. It may help to find explanations for reported differences in epidemiology, treatment and outcome in OHCA. The majority of OHCAs are of cardiac origin, and this patient group is also associated with a more favourable outcome (Ong et al. 2015, Kuisma, Määttä 1996, Pell et al. 2003, Franek, Pokorna & Sukupova 2010). There has been a debate on the difficulty and, on the other hand, the importance of defining the term “cardiac origin” and its use in practice (Eisenberg, Bergner & Hearne 1980). A report from Finland showed significant differences in causes of death from unsuccessful prehospital resuscitation followed by autopsy or no autopsy (Virkkunen et al. 2008). Nevertheless, most often the assessment of the origin of the cardiac arrest in OHCA studies relies only on EMS personnel treating the patient before hospital phase. Understandably, this may vary because of individual judgement or personal opinion. Besides intracardial causes, Kuisma and Alaspää reported in 1997 that 34.1% of OHCA patients had a cardiac arrest of non-cardiac origin. The most common causes were trauma, non-traumatic bleeding and intoxication (Kuisma, Alaspää 1997). This patient group may receive resuscitation efforts that differ from standard protocol (Monsieurs et al. 2015).

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Verifying the cause of cardiac arrest by autopsy for outcome reports is challenging and costly. The overall number of autopsies has been decreasing over the last decades (Marwick 1995), also in Finland (Tilastokeskus 2014a). In an earlier report from Finland in 1991, an autopsy was performed in 39% of the patients who died after unsuccessful resuscitation efforts in a prehospital setting (Silfvast 1991). Moreover, many factors may play a role in causing lethal arrhythmias. Therefore, it has been agreed that cardiac arrest should be considered of cardiac origin unless it is known or likely to have been caused by trauma, submersion, drug overdose, asphyxia, exsanguination, or any other non-cardiac cause as best determined by rescuers (Cummins et al. 1991, Jacobs et al. 2004). Ischaemic heart disease represents the leading cause of death in the world (Murray, Lopez 1997, Newton et al. 2015). On initial evaluation, about 25-30% of OHCA patients have ventricular fibrillation (VF), but the incidence of VF has been declining over the past decades (Cobb et al. 2002, Väyrynen et al. 2011). There may be multiple reasons for this decline, but probably most importantly it is due to enhanced treatment of coronary artery disease and its risk factors (hypercholesterolemia, hypertension, etc.). One interesting potential cause could be urbanisation and an increasing number of single-person households. Most cardiac arrests occur at home, and if unwitnessed, prognosis is understandably poor (Väyrynen et al. 2011). In general, patients with VF have a better outcome than patients with non-shockable rhythms (Nichol et al. 2008, Holmgren et al. 2010). Even so, survival is still highly dependent on a short time from collapse to defibrillation (Weaver et al. 1986). On average, each non-treated minute means 7% to 10% reduction in likelihood of survival for an OHCA patient in VF (Cummins et al. 1991).

2.2.2 Indications for out-of-hospital resuscitation efforts There are two main questions that challenge health care providers especially in the EMS world: when to start and when to stop cardiopulmonary resuscitation? Cardiac arrest is a life-threatening condition that will lead to death within minutes without interventions. Understandably, it is impossible to gain 100% survival for these patients. Patients should have a reversible, treatable cause for cardiac arrest and the capability to recover from resuscitation in the post-resuscitation phase. In other words, not all patients benefit nor are entitled for resuscitation efforts. Resuscitation is considered to be inappropriate if it is clear that it will be futile or is against the wishes of the patient. However, current practices and legislation vary internationally. For example, in South Korea it is not possible for EMS crews to withhold prehospital resuscitation, and they cannot stop resuscitation without declaration of death by a physician, requiring mandatory transportation to hospital for patients with ongoing resuscitation (Ahn et al. 2010). Similar practices exist in many East Asian countries (Kajino et al. 2008), giving the possibility not to initiate resuscitation only in obvious cases of death, e.g. asystole and the presence of decapitation, decomposition, dependent lividity, presence of brain matter from a head wound and rigor mortis. Interventions must be performed rapidly and efficiently. Otherwise a good neurological outcome is unachievable. However, the decision to start or discontinue resuscitation efforts in prehospital setting is challenging due to lack of information about the overall

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health status of the patient, including what actually was the situation just prior to the cardiac arrest. Nevertheless, if the cardiac arrest was not seen or heard, and the patient is found without a palpable pulse and having asystole as the primary rhythm, he can be considered to be dead and resuscitation attempts can be withheld, which is the practice in the Finnish EMS system. Functional and sensitive prediction rules for termination of resuscitation efforts for EMS personnel have been published (Morrison et al. 2006). The ERC Guidelines include a chapter concerning the ethics of resuscitation and end-of-life decisions and when withholding or withdrawing CPR should be considered (Bossaert et al. 2015). In unclear situations, which OCHA mainly is at the initial phase, it is reasonable to start resuscitation efforts, and when further information of patient’s previous medical history or underlying cause (e.g., primary rhythm, time intervals from emergency call to EMS arrival, witnessed vs. found, end-stage cancer) is gathered, termination of resuscitation can be established shortly after arrival on the scene. Nevertheless, in the end this decision is based on the judgment of unresponsiveness of individuals to advanced cardiac life support (Monsieurs et al. 2015). It has been said that critical care is a method to remove a temporary threat to life, and in many ways this same definition also applies to resuscitation. 2.2.3 Factors related to outcome in OHCA Even for a young, previously healthy patient, after cardiac arrest there are only minutes to spend for effective resuscitation before irreversible cerebral and cardiac changes occur, resulting in either patient death or making recovery to or near his previous functional capacity impossible. Unfortunately, survival is achieved only for a small minority of people. Studying factors that may influence the positive outcome among these patients is vital. On the other hand, knowledge and recognition of these factors will help health care personnel to make a decision to withhold or not to even initiate resuscitation efforts in obviously futile situations. Before modern cardiopulmonary resuscitation was adopted in 1960s, very few patients survived cardiac arrest (Cooper, Cooper & Cooper 2006). Furthermore, factors that may have had influence on outcome were not properly identified or documented. However, in 1976 Mickey Eisenberg and his colleagues initiated the Project Restart study to determine factors associated with successful resuscitation in prehospital setting (Eisenberg, Bergner & Hallstrom 1979). They concluded that four factors had a significant association with better survival rates: paramedic (not EMT) service, time from collapse to initiation of CPR, rapid transport time to definitive care and bystander-initiated CPR. Interestingly, initial rhythm alone was not associated with better outcome. On the other hand, only 50% of the cardiac arrests were overall even monitored, and of these patients, 64% had ventricular fibrillation (VF) as first documented rhythm. Time from the collapse to defibrillation, when performed, was also not documented. Eisenberg reported that CPR initiated within four minutes and rapid transportation to definitive care, the latter performed more rapidly by paramedics than emergency medical technicians (EMTs), were associated with survival. The study group suggested citizen training for providing CPR for a patient, thus

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buying time until definitive care reaches the patient, and indeed both Seattle and King County took CPR into their programme for citizen education. Eisenberg at his colleagues indeed led the EMS world towards meaningful things in OHCA care. According to Sasson (Sasson et al. 2010), the associations between key predictors and survival have been stable for over a decade. These key predictors are: initial cardiac rhythm, provision of CPR, arrest witnessed by a bystander or EMS, or the return of spontaneous circulation. The most important factor affecting survival is time from collapse to initiation of resuscitation efforts (Eisenberg, Bergner & Hallström 1979). Early chest compressions from the beginning of collapse have been shown to have a positive effect on outcome in other studies as well (Holmberg et al. 2001, Nordberg et al. 2009). Additionally, patient survival has been linked to the quality of CPR; suboptimal chest compression reduces survival to discharge after OHCA up to 30% (Stiell et al. 2012). Another study including patients with in-hospital cardiac arrests showed that higher chest compression rates correlated with higher rates of ROSC (Abella et al. 2005). Shockable rhythms - ventricular fibrillation (VF) and ventricular tachycardia (VT), have been associated with a more favourable outcome than other rhythms (Cummins et al. 1991, Herlitz et al. 2005). As a result, the best prognosis is among those people whose cardiac arrest has been witnessed, whose cause of arrest is of cardiac origin and in whom VF/VT is the primary rhythm (Pell et al. 2003). Actually, the best results have been achieved from casinos where non-medical personnel, security officers, were trained to use defibrillator and succeeded in defibrillating VF patients within approximately four minutes of collapse. Overall survival from hospital discharge was 38%, and 59% among patients having VF as an initial rhythm (Valenzuela et al. 2000). 2.2.4 Outcomes of OHCA worldwide and in Finland Reported outcomes for OHCA have been poor – 10.7% for all initial rhythms. For VF, survival improved up to 21.2% (Atwood et al. 2005). Nevertheless, a small improvement in overall OHCA survival rates has been seen over the last few decades. A meta-analysis published in 2010 showed survival rates to be between 6.7% and 8.4% (Sasson et al. 2010) despite of many advances in treatment and practices over time. In this meta-analysis, bystander CPR and shockable rhythms were positive predictors of survival, well-known factors affecting patient outcome. A recent ROC report concluded that OHCA patients survival had increased (Daya et al. 2015) slightly, from 8.2% to 10.4% between 2006 and 2010 in US and Canadian sites. One explanation for this modest improvement may be the simultaneous decrease of three known predictors of survival: shockable initial rhythm, cardiac arrest of cardiac origin and public location. In a review, Savastano et al. reported a significant decrease in mortality over three different time periods, with a survival rate at hospital discharge of 9.2% after the year 2005.

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Figure 1. Rate of survival to hospital discharge after OHCA in the three periods. OHCA, out-of-hospital cardiac arrest. According to Savastano et al. 2014.

In Finland, overall OHCA survival to hospital discharge has been reported to be 13% (Table 1). These studies included only single EMS providers covering the city areas of Helsinki and Tampere. However, it seems that when comparing patients whose cardiac arrest was witnessed, of presumed cardiac origin, and with an initial shockable rhythm, the prognosis of this patient group has improved in Finland (Silfvast 1990, Kuisma, Määttä 1996, Kämäräinen et al. 2007, Kuisma, Alaspää 1997). This improvement has also been noted in other countries (Iwami et al. 2009). 2.3 CHAIN OF SURVIVAL The “chain of survival” remains a model of resuscitation throughout the world. This concept was established in 1991, and it means all actions linked with survival in patients with cardiac arrest (Cummins et al. 1991). Initially this chain involved 1) recognition of early warning signs, 2) activation of the emergency medical system, 3) basic cardiopulmonary resuscitation, 4) defibrillation, 5) intubation, and 6) intravenous administration of medications. Research on different factors affecting survival has modified this chain over the years. In 2010 this sequence had four links: 1) early recognition of those at risk of cardiac arrest, 2) early provision of CPR, 3) early defibrillation, and 4) post-resuscitation care (Nolan et al. 2010). Updated resuscitation guidelines in 2015 stress the importance of interactions between the emergency medical dispatcher, the bystander who provides CPR and the early use of automated external defibrillators in patient survival from OHCA (Nolan et al. 2015). In 1992, an International Liaison Committee on Resuscitation (ILCOR) was formed to have liaison between resuscitation organisations worldwide (ILCOR 2015). The European Resuscitation Council represents one of the member organisations. ILCOR offers a forum for discussion of different aspects of resuscitation worldwide, provides a mechanism for collecting and sharing data on different topics and points to areas where further research is needed. It also provides statements on different issues in regard to resuscitation. A massive review on resuscitation and closely related issues is performed regularly by the

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ILCOR and is followed by ERC guidelines every five years, based on evidence whenever possible, and if sufficiently strong evidence is lacking, on consensus of available scientific evidence and experts’ opinion and best practice. 2.3.1 Role of the bystander – importance of the emergency call and CPR In cardiac arrest, it is essential that a bystander who witnesses the arrest identifies this life-threatening situation and makes the emergency call. More ideal would be the citizen’s capability, with training, to recognise people at risk of cardiac arrest and call for help before the cardiac arrest even occurs. ERC recommends that citizens should be trained to give standard CPR that includes compressions and ventilation, or alternatively, to learn compression-only CPR (Monsieurs et al. 2015). Delays may occur if the bystander calls to a relative or friend first instead of making an immediate call to an emergency dispatch centre. Training increases the actions of a bystander to initiate and perform CPR (Cave et al. 2011). It has been shown in studies that bystander CPR (Sasson et al. 2010) improves outcome. Unfortunately, many people having a cardiac arrest will not receive any bystander resuscitation efforts. According to studies lack of bystander CPR is approximately one fourth of all OHCA events (Nichol et al. 2008), ranging from 1% (Ong et al. 2011) to 40% (Ong et al. 2015). Efforts made to increase these rates are crucial for OHCA patient management. 2.3.2 Role of the dispatcher – recognition of OHCA The effectiveness of many interventions in OHCA relies on the rapid response of EMS activation. Dispatchers play a major role in this entity when taking emergency calls. Cardiac arrest represents only a minority of medical emergencies. In addition, dispatch centres in Finland are combined centres for EMS, police and fire and rescue services. In other words, dispatchers also receive many non-medical or non-urgent medical calls. Nonetheless, they should rapidly and correctly identify this critical patient group, activate an adequate EMS response, and simultaneously initiate telephone-guided cardiopulmonary resuscitation orders (T-CPR). Thus, early recognition of cardiac arrest is the first link in the chain of survival (Monsieurs et al. 2015, Bobrow, Panczyk & Subido 2012) and has been shown to improve patient survival (Berdowski et al. 2009, Rea et al. 2001). To recognise OHCA by telephone assessment is a challenging task. A recent review by Vaillancourt et al showed that the sensitivity of telephone assessment of the patient as unconscious and with no or abnormal breathing varied (38-97%), but were reliable in OHCA (Vaillancourt et al. 2011). Dispatchers confront many barriers during the emergency call, affecting their recognition of OHCA, ie. caller’s physical and emotional proximity (Alfsen et al. 2015). If the caller describes the patient as breathing normally, dispatchers rarely give T-CPR. It seems important that the protocol includes the question “is patient breathing normally?” If the answer is no, and the patient is not conscious, the dispatcher should treat the situation as cardiac arrest (Berdowski et al. 2009). Agonal breathing has been shown to mislead dispatchers to believe patient is alive, leaving true cardiac arrest patients unrecognised (Bang, Herlitz & Martinell 2003). Additionally, recognition takes 1-4 minutes (Culley et al. 1991, Heward, Donohoe & Whitbread 2004).

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Despite these difficulties and challenges, the correct recognition of an OHCA has been reported to be as high as 70-83% (Garza et al. 2003, Kuisma et al. 2005, Nurmi et al. 2006). After recognising a cardiac arrest, T-CPR instructions are given for those willing to perform chest compressions. In Finland, T-CPR instructions are given unless CPR is already ongoing or the caller says he or she knows how to perform cardiopulmonary resuscitation. Rather than asking whether the caller would like to try CPR, the dispatcher should encourage the caller by saying: “We need to start CPR. I will help you.” It has been shown that CPR before EMS arrival improves survival, and therefore the guidance of dispatcher for bystander to provide CPR for a lifeless patient of great importance (Lerner et al. 2012). Unfortunately, rates of T-CPR offered has been shown to be low (Rea et al. 2001, Kuisma et al. 2005). In a study from South Korea, only 5.2% of OHCA patients received CPR before EMS arrival. T-CPR-instructions were given in 24.2% of the cases (Song et al. 2013). On the other hand, Bohm et al reported that sometimes dispatchers may not offer T-CPR instructions for suitable cases (Bohm et al. 2007). The same study reported also that bystanders seem to be motivated and willing to give CPR to a lifeless patient. In summary, dispatchers should always start the call by excluding cardiac arrest as a cause for the call and provide prearrival CPR instructions in case of cardiac arrest. This strengthens the Chain of Survival and helps save lives from OHCA (Lerner et al. 2012). 2.3.3 Role of EMS – following resuscitation protocol The cardiac arrest patient needs immediate treatment after collapse. Treatment can be partly provided by bystanders (CPR, even early defibrillation), but it is mainly in the hands of EMS personnel. Their role is to resuscitate according to a set protocol in concordance with guidelines. Major interventions include continuing and assuring good quality CPR, early monitoring of the initial rhythm and defibrillation of a shockable rhythm, airway management, opening intravenous access and administration of vasoactive drugs. When arriving to a patient side, EMS personnel assess the patient’s status by responsiveness of the patient (shaking, pain stimuli) and opening the airway. If the patient is not awake and is not breathing normally, patient is considered to be in cardiac arrest, and chest compressions are initiated unless the bystander CPR is already ongoing. Rapid assessment of carotid pulse by ALS personnel is allowed, but should not exceed 10 seconds. Continuous CPR is important throughout the resuscitation. Ideally, this is initiated by a bystander immediately after the collapse. CPR enables limited, but critical blood circulation to the heart and brain. By increasing the intrathoracic pressure and directly compressing the heart (KOUWENHOVEN, JUDE & KNICKERBOCKER 1960), CPR aims to offer sufficient oxygen delivery to vital organs during the resuscitation period. The American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care pointed out five critical components of high-quality CPR: minimal interruptions in chest compressions, compressions of adequate rate and depth,

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avoidance of leaning between compressions and avoidance of excessive ventilation (Meaney et al. 2013). Nevertheless, providing good quality CPR is challenging even for EMS personnel (Wik et al. 2005). Unfortunately, even when performed properly, chest compressions produce systolic arterial pressure peaks of 60-80mmHg maximum (Paradis et al. 1989). In addition, heterogeneity among patients has been reported, which makes optimal depth and compression rate challenging for rescuers to perform (Sainio et al. 2015). Monitoring the rhythm and diagnosing the initial shockable rhythm to be treated with defibrillation is of great importance in the early resuscitation phase. Defibrillation is one of the few interventions that has been shown to improve outcome from cardiac arrest with VF/VT, but for each passing minute untreated, the likelihood for VF patient to survive decreases 7% to 10% (Cummins et al. 1991). Emphasis on the importance of minimally interrupted chest compressions while EMS personnel apply, charge and deliver defibrillator shock is recognised in the ERC guidelines in 2010 (Nolan et al. 2010). Use of an automatic electric defibrillator (AED) in public settings (airport, casinos, sport facilities) may increase survival of VF patients (Hallstrom et al. 2004), but a sufficient amount of trained non-EMS rescuers and AEDs need to be available this to be successful. Sufficient oxygenation and ventilation are crucial in the management of OHCA. Bag-valve-mask ventilation (BVM) is a basic skill for all healthcare, EMS and rescue personnel. On the other hand, studies have shown that BVM is demanding (Kurola et al. 2004) and one of the major disadvantages is an increased risk of aspiration (Stone, Chantler & Baskett 1998). Advanced airway interventions such as ETI and different supraglottic airway devices are commonly used by EMS personnel in patients having a cardiac arrest. ETI was introduced to EMS in the 1970s (Stewart et al. 1984), and has been the golden standard for advanced airway management (Deakin et al. 2010). A cuffed tube positioned in the trachea beyond the vocal cords protects the lungs from aspiration and provides efficient gas exchange. ETI is, on the other hand, a highly technical skill and a person needs to train this skill regularly (Nolan, Soar 2008). If done improperly, ETI insertion may have catastrophic consequences (Hasegawa et al. 2012, Mort 2004). To date, there is no strong evidence of the superiority of ETI in cardiac arrest, although a recent meta-analysis indicates that non-traumatic OHCA patients who receive ETI have improved outcomes when compared to those with SGA placement (Benoit et al. 2015). Supraglottic airway devices (SADs) are inserted above the vocal cords, and their placement does not involve laryngoscopy, which makes them easier for users with limited experience. A number of different SADs have been introduced, for example laryngeal tubes (LTs), laryngeal mask airways (LMAs) and iGels. SADs were originally introduced in the operating theatre to be used for electively anaesthetised patients, but in time they also gained popularity in the prehospital emergency setting. Initially SADs served as backup plan for emergency airways, but they are nowadays used worldwide as both a primary and secondary airway device (Berlac et al. 2008). They are easy to use, and their placement enables simultaneous chest compressions. Successful insertion rates have been reported to be high among EMS personnel (Schalk et al. 2010).

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In conclusion, there is no high-quality evidence to support the use of any specific advanced airway technique (Bernhard, Benger 2015). ERC guidelines recommend ETI as the most reliable airway device. However, ETI is not recommended unless highly skilled individuals are available to perform this technique with minimal interruption to chest compressions (Nolan et al. 2010). Guidelines for managing the airway in the prehospital phase assume a certain level of education and training for safe use of any specific technique (Berlac et al. 2008). 2.3.4 Role of EMS-physician in treatment of OHCA There are no convincing high quality studies showing that the presence of an EMS physician decreases overall mortality or morbidity of prehospital-treated patients – in fact, same implies with any of the elements of advanced cardiac life support (ALS). The available evidence is somewhat confusing. A recent meta-analysis reported that EMS physician-guided CPR was significantly associated with improved outcomes compared to paramedic-guided CPR, with nearly twice as many patients alive at hospital discharge in the EMS-physician-guided CPR group (Böttiger et al. 2016). One cohort study published in 2015 from the USA showed that BLS-treated OHCA survival was better than ALS-treated OHCA (excluding OHCA treated by EMS physicians) (Sanghavi et al. 2015). A meta-analysis in 2011demonstrated that ALS increased the probability of survival in non-trauma cardiac arrest patients at hospital discharge by almost 47% compared to BLS (Bakalos et al. 2011). In addition, a review by Timmermann et al. (Timmermann, Russo & Hollmann 2008) suggests that some patients benefit from the EMS-physician care. Another review found few controlled studies that indicated improved survival with physician treatment in trauma and, with more limited evidence, cardiac arrest (Botker, Bakke & Christensen 2009). A retrospective study showed increased survival with prehospital care provided by specialists in anaesthesiology compared to EMTs or paramedics, especially in patients with cardiac arrest, patients in need of respiratory support and trauma patients (Mikkelsen et al. 2015). However, a study from Norway showed no difference in OHCA outcome between physician-staffed and paramedic-staffed ambulances (Olasveengen et al. 2009), although compliance with guidelines was better when an EMS physician was involved. In the end, Timmermann et al. claimed that no prospective, randomised double-blinded trial would ever be done from this topic. It would require thousands of patients and withholding EMS-physician care would be ethically and legally problematic in areas they already existed. Finally, Böttiger et al point out that via natural EMS system change from paramedics to EMS physicians or vice versa would give the opportunity to compare paramedic-guided CPR with EMS-physician-guided CPR (Böttiger et al. 2016). 2.3.5 Post-resuscitation care after OHCA Coronary heart disease is the most common cause for cardiac arrest in prehospital setting. However, it is neurological injury that kills two thirds of the patients successfully resuscitated from OHCA (Laver et al. 2004). To prevent neurological damage to brain tissue, mild therapeutic hypothermia (MTH) was introduced in 1950s by Benson et al. (BENSON et al. 1959). They reported better neurological survival (50% vs 14%) if OHCA

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patient was treated with hypothermia. Hypothermia reduces oxygen consumption and metabolism at the cellular level and protects tissues from ischaemia (Wong 1983). Unfortunately, it took nearly 50 years until two landmark studies were published in 2000 and 2002 showing improved survival among patients who were successfully resuscitated from VF and treated with MTH in intensive care units (Zeiner et al. 2000, Bernard et al. 2002). Although not scientifically proven, guidelines were made to recommend MTH for OHCA due to any arrhythmia for patients undergoing active treatment post-resuscitation (Castren et al. 2009). Initiation of hypothermia in prehospital phase has also been used and studied in many countries and EMS systems (Kämäräinen et al. 2009, Suffoletto et al. 2008), but evidence does not show improved outcomes (Hunter et al. 2014, Huang et al. 2015, Kim et al. 2014).

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3 AIMS OF THE STUDY The objective of this study was to report on the epidemiology, clinical course and outcomes of out-of-hospital cardiac arrest in Finland. The specific aims were: 1. To describe the epidemiology and outcome of out-of-hospital cardiac arrest in Finland (Studies I and IV) 2. To evaluate the factors related to survival from out-of-hospital cardiac arrest (Studies I, II, III, IV) 3. To study the elements of chain of survival in out-of-hospital cardiac arrest (I, II, III, IV)

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4 PATIENTS AND METHODS 4.1 STUDY AREA AND DESCRIPTION OF EMS Finland, located in the northern corner of Europe, is the most sparsely populated country in the European Union. Its geographic area is 337,000 km2 with average population density of 17 inhabitants/km2, with over 500,000 people living in the capital city of Helsinki. The FINNRESUSCI prehospital study area covered eastern and southern parts of Finland with overall population of 2,644,200 (49.1% of the total Finnish population). The study area included two hospital districts with its two university and six central hospitals (Studies I-III). We divided 120 municipalities into urban, semi-urban and rural areas according to existing criteria (Tilastollinen kuntaryhmitys). In addition, for resuscitated patients admitted to the ICU (Study IV), 21 intensive care units around Finland participated (21/22 of all ICUs), representing 98% of the Finnish adult population lived in the area (ICU-treated study group). There are eight regional dispatch centres located inside the study area. Trained dispatchers answered emergency calls. Medical call processing and medical priority criteria are described in the dispatcher’s guidebook. They are based on the patient’s chief complaint and on the patient’s current condition. EMS calls are prioritised into four categories A, B, C and D, where A represents the highest medical urgency. Dispatcher needs to identify the address of the emergency. If the patient is not on the phone, every emergency call is started by excluding cardiac arrest as a reason for the call. If patient is not awake and is not breathing normally, they continue processing the call as a cardiac arrest, alerting the closest and the most appropriate units to the patient site (two EMS units). An EMS physician is also dispatched simultaneously with other EMS units if the cardiac arrest occurs inside their operating area (30 minutes response time). The dispatcher then starts to give T-CPR instructions to the caller unless CPR is already being performed or the caller knows how to administer CPR. These T-CPR instructions have included only chest compressions since 2000 unless the patient is a child or cardiac arrest is probably caused by drowning or choking. As described earlier, Finland has a three-tiered EMS system. Basically, the first tier is capable of initiating first aid with basic measurements (blood pressure, oxygen administration, blood glucose) and, in case of a cardiac arrest, start CPR with defibrillation if needed and administer intravenous drugs, if a person with a healthcare background is providing patient care. Depending on local practices and guidance from the medical coordinator, the first tier is also trained in the use of some advanced airway device, mainly a SAD. In southern part of Finland, the first tier may also use the ETI technique, if

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sufficiently trained and experienced. The second tier works more independently and is allowed to perform intubation as a first-choice airway technique for a lifeless patient. EMS physicians represent the third tier and have, naturally, all advanced airway techniques in use.

Table 2. Description of the 3-tiered EMS system in Finland and airway devices in use for OHCA patients. EMS, Emergency Medical Service, OHCA, out-of-hospital cardiac arrest, SAD, supraglottic airway device, ETI, endotracheal intubation, EMT, Emergency Medical Technicians. National recommendations for prehospital care in OHCA have been published (Silfvast 2009). The Finnish Medical Society Duodecim first published recommendations regarding OHCA in 2002, again in 2006 (Suomalaisen Lääkäriseuran Duodecimin et al. 2011), and most recently in 2016 (Käypä Hoito 2016). EMS providers represented different organisations. Physician-staffed units were organised by hospital districts. In 2010 when data was collected, municipalities were responsible for organising the prehospital care. Providers inside the study area were either communities themselves, or contract was made together with other communities, rescue departments or private ambulances. Since April 2011, hospital districts have been responsible for organising and coordinating prehospital service inside their area (Finlex 2011). Each EMS has their own medical coordinator in every hospital district, resulting in variation in local practices and recommendations. 4.2 STUDY SETTING AND DATA COLLECTION This study was a prospective observational cohort study. All patients who fulfilled the criteria of suspected OHCA according to uniform national emergency medical dispatch policy were included regardless of aetiology, as were the patients who were identified as

Tier

Staff

Background/education

Airway technique in OHCA

First tier • First responders

• Basic-EMT

• Formal training in SAD use, not necessarily with healthcare educational background

• Firefighter-EMT • Practical nurse in

prehospital emergency care

• SAD in eastern part of Finland

• SAD/ETI in southern part of Finland

Second tier

• Advanced level

• Registered nurse (bachelor) in emergency care

• ETI/SAD

• ETI/SAD

Third tier • EMS physicians • >90% anaesthesiologists or residents in anaesthesiology

• ETI

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OHCA by EMS crews or who developed OHCA before arrival at the hospital (prehospital study group, Studies I-III). Additionally, all adult OHCA patients who were successfully resuscitated from out-of-hospital cardiac arrest and who were admitted to intensive care units in Finland were collected (ICU-treated study group, Study IV). Data was collected between March 1, 2010 and August 31, 2010. Additionally, data from ICU-treated OHCA patients was collected for 12 months from March 1 2010 to February 28, 2011. All OHCAs considered for resuscitation (excluding patients with secondary death marks or lethal trauma) were collected for Study I (1042 patients). Reasons for withholding resuscitation efforts were reported, and further analysis was made of patients who underwent attempted resuscitation (671patients). In Study III, the same patient group was analysed regarding the airway management process (614 patients). Study II was a substudy in which patients who experienced bystander-witnessed cardiac arrest with an initial shockable rhythm (164 patients) were further evaluated. Study IV included patients successfully resuscitated from OHCA and who were admitted to Finnish ICUs (548 patients) nationwide.

Table 3. Description of individual studies (I-IV) emboding the present thesis with inclusion and exclusion criterias. OHCA, out-of-hospital cardiac arrest, ICU, intensive care unit.

Description

Study I Epidemiology and outcomes

Study II Dispatch recognition

Study III Airway management

Study IV Hypothermia in ICUs

Inclusion criteria

-All OHCAs with attempted resuscitation**

-Witnessed OHCAs with shockable rhythm

-All OHCAs with attempted resuscitation

-All adult OHCAs successfully resuscitated and admitted to ICU***

Exclusion criteria*

-Resuscitation not attempted

-Witnessed by EMS -Non-shockable rhythm

-Resuscitation not attempted -No need for airway intervention

-In-hospital cardiac arrest -Patient awake -Duplicate ICU treatment

n 671 164 614 504 *Missing or incomplete data was an exclusion criterion for all studies.

**OHCAs considered for resuscitation included in incidence calculation and for describing patient group for withdrawn resuscitation efforts. Excluded from further analysis.

***Patients awake in the ICU were used in the calculation of incidence, but were excluded from the mortality analysis.

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Figure 2. Flow diagram of patients in Studies I, II and III. OHCA, out-of-hospital cardiac arrest; EMS, Emergency Medical Services.

671 OHCA

1042 OHCA

Study I: Data of 671 patients for further

analysis

371 Resuscitation not attempted

Bystander-witnessed OHCA Shockable rhythm

507 Non-shockable primary rhythm OR EMS-witnessed OHCA

Study II: Data of 164 patients for further

anaylsis

30 no need for airway intervention 27 incomplete data

Airway intervention

Study III: Data of 614 patients for further

analysis

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Figure 3. Flow diagram of patients in Study IV OHCA, out-of-hospital cardiac arrest; ICU, intensive care unit. An interface was created between the dispatch centers’ combined database and the database of the Finnish Quality Consortium of Intensive Care (Intensium) (Studies I, II and III). This ensured the inclusion of all patients inside study area and provided a uniform database for this study. The EMS recorded patient data to case report forms (CRF) and faxed them to a research nurse who entered the data into the common FINNRESUSCI database, linking them to the dispatch data (Studies I, II and III). In addition, the data of study patients treated in ICUs was also collected via the Finnish Intensive Care

572 OHCA admissions in ICU

6 <18 years of age 18 duplicate ICU treatments

548 OHCA

Study IV: Data of 504 unconscious OHCAs for

further analysis

44 awake

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Consortium (FICC), to which all participating ICUs belonged (Study IV). All data was cross-checked by two research nurses. The National Institute for Health and Welfare administered the information about patients’ status at the time of hospital discharge and was categorised “alive” if patient was discharged from primary hospital either to a home or to a non-acute care facility. Data regarding survival after one year was obtained from the Finnish Population Information System (Tilastokeskus 2014b) available on December 31, 2009 (Studies I, II and II) and December 31, 2010 (Study IV). In addition, we reported the Pittsburgh Cerebral Performance Category (CPC) status 6-12 months after witnessed OHCA in patients with a shockable primary rhythm and from ICU-treated OHCA patients (Study II and IV). In short, CPC scores fall in five categories, where CPC 1-2 represents good neurological recovery, and 3-4-5 poor neurological outcome. One neurologist performed evaluation. Further analysis was made for patients with attempted resuscitation (Studies I-III) and for resuscitated patients admitted to the ICU (Study IV). Resuscitation was determined as “attempted” if EMS continued/initiated resuscitation procedures after arrival, excluding brief CPR efforts that were discontinued after assessing the situation to be futile for variety of reasons, e.g. pre-existing do not attempt resuscitation order (DNAR). EMS collected data according to Utstein template (Jacobs et al. 2004). The primary rhythm was reported as VF/VT (shockable rhythms), pulseless electrical activity (PEA) or asystole, or, if analysed with an automated external defibrillator (AED), as “schockable” or “another non-shockable” rhythm. When analysing the results, PEA and ASY rhythms were grouped together as “non-shockable rhythm”. Aetiology of cardiac arrest (estimated by EMS), primary rhythm, whether the CPR was provided on EMS arrival, if return of spontaneous circulation (ROSC) was achieved and if the patient was transported to a hospital were reported. The basic time points were: beginning of the emergency call, EMD dispatching the first EMS unit, EMS arrival on scene, initiation of chest compressions (by a bystander or EMS) and the time of first defibrillation. Time points were given in minutes. Time of the beginning of the emergency call and dispatching were electronically received from the dispatch centres, and other time points were estimated by EMS. Dispatch data was electronically transferred from the dispatch centre to the previously described common database, and it included the information on the beginning of the emergency call, dispatch codes (initial plus if it was changed by the dispatcher) and priority categories, dispatch times and units that were dispatched (Study II). We considered the emergency call recognised as cardiac arrest if the dispatcher initially coded the mission as cardiac arrest or changed the code as cardiac arrest before EMS entered the patient side. EMS reported whether the patient was having bystander CPR on scene and whether it was based on dispatcher’s guidance or not (Study II). The EMS crew documented the airway intervention in OHCA. They reported the first selected airway device and whether it was changed to another, and the education-level providing the final airway as well as the highest EMS provider on scene. Arrival time of an EMS physician was reported. Adverse effects associated with airway management were also studied, and multiple answers were allowed. Problems were reported as overall

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adverse effects during airway management process as well as the method of verifying the correct placement of the ET tube (Study III), not in relation to specific airway device if multiple was used. The basic data of patients treated in ICUs were collected using the Utstein template. In addition, the use of TH for cardiac arrest patients was reported as well as the reasons for withholding the TH for patients resuscitated from an initial shockable rhythm. 4.3 ETHICAL CONSIDERATIONS This study was a prospective study, and no interventions were done. The study protocol was approved by the Institutional Review Board of the Helsinki University Central Hospital (80/13/03/02/09, ClinicalTrials.gov ID NCT01295424) and, for data collected from ICUs, by the Ethics Committee of participating hospitals. At the time of discharge from the ICU, permission was asked to contact them via telephone after six-months/one year in order to do the survey of neurological recovery. 4.4 STATISTICAL METHODS This data was analysed using SPSS (SPSS, Chicago, Ill., USA) version 17.0 (Study I), 18.0 (Study II) and 19.0 (Study III and IV). Data was presented as medians with IQR or as frequencies and percentages (Studies I-IV). Association between categorical variables was assessed using cross tabulation and the chi-square test, and with ANOVA when variables were continuous (Studies I, II, III). In addition, variables recorded at time points were analysed according to the Kruskal-Wallis one-way ANOVA (Study I). The Kaplan-Meier estimator was used to assess the difference in patient survival between the municipalities (one-year follow-up) in Study I. A logistic regression model was used to determine factors related to survival (Studies I, II and III). Variables tested in study I were: primary rhythm, delay from collapse to initiation of CPR, cardiac arrest of cardiac origin, age, municipality type, gender, witnessed status of OHCA and location of OHCA. Variables tested in Study II were: type of municipality, EMS response time within 8 minutes, T-CPR instructions provided, emergency call processed within 2 minutes, CPR before EMS arrival, EMD-recognised OHCA (Study II). Variables tested in Study III were: gender, primary rhythm, location of cardiac arrest, witnessed, witnessed by EMS, presumed cardiac aetiology, whether OHCA was recognised by EMD, bystander CPR before EMS arrival, highest level EMS provider on the scene, ETI or SAD as a final airway technique, municipality type, and presence of an EMS physician in prehospital OHCA patient management. A P-value less than 0.05 was considered statistically significant (Studies I-III). In Study IV, groups were compared using the non-parametric Mann-Whitney U test for continuous data and Fisher’s exact test for proportions, when applicable. Unadjusted risk ratio differences for favourable outcome (CPC 1-2) for both shockable and non-shockable groups was calculated. Backwards logistic regression analysis was performed to evaluate

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independent factors associated with an unfavourable outcome (CPC 3-4-5), and higher APACHE II score (p=0.002) and higher age (p=0.008) were predictors for CPC 3-4-5. Other tested variables were site, use of TH, time to ROSC, witnessed arrest, bystander CPR, age, coronary artery disease (yes/no), primary rhythm (asystole or pulseless electrical activity), propensity score for TH, use of TH.

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5 RESULTS 5.1 EPIDEMIOLOGY AND OUTCOME 5.1.1 Epidemiology During the 6-month study period, dispatch centres received 885 338 emergency calls inside the study area. 237 295 of these calls were medical (26.8%), and they led to 186 420 EMS missions (78.6% of all medical calls). EMS considered resuscitation in 1042 patients, leading to an incidence of 78/100,000 inhabitants/year. EMS attempted resuscitation for 671 patients, corresponding incidence of 51/100,000 inhabitants/year. EMS withheld resuscitation for 371 of the patients, and the most common reason for this was “considered futile” (n=297, 80.1%). In addition, a pre-existing Do Not Attempt Resuscitation order was available for 71 patients. Table 4. Demographics of those patients whose resuscitation was NOT attempted. DNAR, do not attempt resuscitation. Reasons for withholding resuscitation attempts* Considered futile DNAR order

n (%) 297(80.1) 71(19.1)

Primary rhythm** Shockable*** Non-shockable Not monitored

1(0.3) 34(9.2) 333(89.8)

Dispatcher coded as cardiac arrest

128(34.5)

Total 371 *data available for 368 of the cases **data available for 362 of the cases ***90-year-old patient with severe systemic diseases

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Table 5. Patient characteristics and outcomes. *In two patients, the primary rhythm was not monitored. IQR, interquartile range, CPR, cardiopulmonary resuscitation, EMS, Emergency Medical Services. Patient characteristics and outcome

Study I n=671

Study II n=164

Study III n=614

Study IV n=504

Age, median (IQR), years

66(56-78)

64(56-76)

66(56-78)

63(54-72)

Male, n (%) 475(70.8) 131(79.9) 436(71.0) 380(75.4) Primary shockable rhythm n (%)

211(31.4)*

164(100)

183(29.8)*

281(55.8)

Aetiology of cardiac origin n (%)

361(53.8)

139(84.8)

324(52.8)

334(66.3)

Resuscitation Bystander CPR, n (%) Witnessed EMS-witnessed

317(47.2) 599(89.3) 140(20.9)

117(71.3) 164(100) NIL

298(48.5) 560(91.2) 117(19.1)

273(54.2) 448(88.9) NIL

Survived to hospital discharge, n (%)

133(19.8)

71(43.4)

109(17.8)

260(51.6)

Survival at one year, n (%) 90(13.4) 54(44.4) 86(14.0) 208(41.3)

In the prehospital study group, the primary rhythm was shockable for 211 patients (31.4%), and non-shockable for 458 patients (68.3%). Of these, 206 had a pulseless electrical activity (PEA), 223 asystole and 29 “other non-shockable” as the primary rhythm analysed by an AED. For two patients, the primary rhythm was not monitored. The presumed aetiology was of cardiac origin in 361 patients (53.8%). EMS personnel reported 129 cardiac arrests to be of unknown origin (19.2%), mainly in patients with a non-shockable rhythm (n=102, 79.1%). Additionally the study group included ten traumatic cardiac arrests, three eletrocutions and 24 submersions (3.6%). The majority of the patients were men. Home was the most probable environment for a cardiac arrest to occur. There were 63 OHCAs in extended care facilities. The collapse was mostly witnessed, usually by a relative or a bystander in 459 (68.4%), and by EMS in 140 (20.9%). In overall, the median time from collapse to initiation of CPR (provided by a bystander or EMS) was 3 minutes (IQR 0-9) and 10 minutes from collapse to first defibrillation for patients in shockable rhythm (IQR 6-14). During the one-year study period, 572 ICU admissions were conducted due to OHCA. The final analysis consisted of 504 unconscious patients. Of these, 281 (55.8%) were resuscitated from a shockable rhythm, and 223 (44.2%) from a non-shockable rhythm. The aetiology of cardiac arrest was reported to be cardiac in 334 (66.3%), and unknown in 55 (3.2%) of all patients. The median age was 63 years (IQR 54-72), and the median time to ROSC was 20 minutes (IQR 15-28). Bystander CPR was provided for 179 (63.7%) of the 281 patients with a primary shockable rhythm, and 94 (42.2%) of the 223 patients with a non-shockable rhythm (p<0.001). OHCA was more often witnessed in patients with a shockable rhythm (n=260 of 281, 92.5%) than in patients with a non-shockable primary rhythm (n=188 of 223, 84.3%, p=0.004).

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5.1.2 Patient outcome In the prehospital study group, 133 patients were alive at hospital discharge (19.8%). Of these, 33 patients were discharged home and 100 patients to another hospital or non-acute healthcare facility. Overall survival at one year was 13.4%. Of 140 patients with bystander-witnessed OHCA and a shockable primary rhythm of presumed cardiac origin, 64 (45.7%) were alive at hospital discharge, and 47 (33.6%) were still alive one year after OHCA. When evaluating this same patient group from urban areas, the numbers were 53.8% and 40.9%, respectively. Survival rates among patients with a non-shockable rhythm were lower: 8.5% (n=39) were alive at hospital discharge, and 4.6% (n=21) were alive after one year. Of the ten traumatic OHCAs, nine were declared dead on scene. One patient survived until hospital admission, but died a few hours later in the ICU. Of 63 OHCAs in extended care facilities, four patients (mean age 48 years) were still alive one year later. Survival to hospital admission was associated with municipality type, with more hospital admissions in more population-dense areas (urban 41.5%, semi urban 28.3%, rural 25.8%, p=0.001), but no difference in survival was found between municipality type at hospital discharge or one year after OHCA. Table 6. Survival in different patient groups (prehospital study group). EMS-witnessed OHCAs were excluded from the witnessed group. EMS, Emergency medical services. Patient group Alive at hospital discharge, % Alive in one year, %

All 19.8 13.4 Shockable primary rhythm 36.5

32.7

Non-shockable primary rhythm

8.5 4.6

Witnessed cardiac arrest with shockable rhythm of presumed cardiac origin

45.7 33.6

Witnessed cardiac arrest with shockable primary rhythm of presumed cardiac origin, urban areas

53.8 40.9

In Study II, survival among the 164 patients with a witnessed OHCA and a primary shockable rhythm was 43.4% (n=71) at hospital discharge, and at one year 32.9% (n=54). Of this patient subgroup, CPC status at 6-12 months was available for 51 of the 71 patients discharged alive from hospital, and for 37 of them, neurological outcome was good (CPC 1 or 2).

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Overall survival of ICU-treated unconscious patients resuscitated from any rhythm at hospital discharge was 51.6% (260/504). Of 281 patients resuscitated from a primary shockable rhythm, 186 were alive at hospital discharge (66.2%) and 160 at one year (56.9%), with favourable neurological outcome (CPC1-2) in 147 patients (52.9%). For the 223 patients with non-shockable rhythms, the corresponding figures were 74 (33.2%) and 48 (21.5%), with CPC 1-2 in 37 of the patients (17.1%), respectively. Table 7. Survival among the 504 ICU-treated patients. Patient group Alive at hospital

discharge (%) Alive at one year (%)

All 51.6 41.3 Patient with shockable primary rhythm

66.2 56.9

Patient with non- shockable primary rhythm

33.2 21.5

5.2 FACTORS RELATED TO SURVIVAL In Study I, regression analysis showed that shockable initial rhythm (p<0.001, OR 6.65. 95% CI 3.56-12.4), short delay from collapse to the beginning of CPR (p=0.001, OR 0.86, 95% 0.79-0.95), arrest of presumed cardiac origin (p=0.05, OR 2.0, 95% CI 1.06-3.9) and age (p<0.001, OR 0.97, 95% CI 0.95-0.98) were related to survival at one year. In addition, survival to hospital admission was associated with municipality type, with patients in urban municipalities more likely surviving than patients in semi-urban or rural areas (41.5% vs. 28.3% and 35.8%, p=0.001). For witnessed OHCAs with a primary shockable rhythm, an EMS response time (the time from the beginning of emergency call to EMS arrival on scene) less than 8 minutes was related to survival to hospital discharge (p=0.018, OR 2.82, 95% CI 1.19-6.67, Study II). In study III, a primary shockable rhythm (p<0.001, OR 5.23, 95% CI 3.05-8.98), the presence and involvement of an EMS physician in prehospital care (p<0.001, OR 5.05, 95% CI 2.94-8.68), and male gender (p=0.049, OR 1.80, 95% CI 1.00-3.22) were related to survival to hospital discharge. Moreover, a primary shockable rhythm (p<0.001, OR 6.96, 95% CI 3.61-13.44) and presence of an EMS physician (p=0.013, OR 2.57, 95% CI 1.22-5.43) were associated with survival at one year. In regression analysis, there was no association of OHCAs recognised by EMD or the technique used in airway management with increased survival. One-year neurological outcome (CPC 1-2) was significantly better among patients with a shockable primary rhythm if TH was provided (TH-treated 58.0% vs. no TH 22.5%,

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p<0.001). Finally, results showed no benefit of using TH for patients admitted to ICU after resuscitation from non-shockable rhythms (1-year CPC 1-2 19.4% in TH-treated group vs 16.0% in no TH-group, p=0.56). 5.3 ELEMENTS OF CHAIN OF SURVIVAL 5.3.1 Role of the EMD The EMD correctly recognised 82.3% of the OHCA patients when receiving an emergency call (135/164). When not recognised, 29 of them were dispatched as other high-priority calls (17.7%), the majority of them coded as “unconscious”. The median time processing the emergency call was one minute (IQR 1-2min), and in 90.7% of the calls an EMS unit was dispatched within 2 minutes (Study II). In 53 of the 164 patients, T-CPR instructions were provided (32.3%) and all of them also received bystander CPR. In addition, if OHCA was recognised by the EMD, bystander CPR was provided more often than when cardiac arrest was not recognised (102/135 (75.5%) vs. 15/29 (51.7%), p=0.01). Table 8. Age, sex, dispatch and EMS response times, CPR before EMS, ROSC and survival with CPC according to whether OHCA was recognised or not in the dispatch centre. EMS, Emergency Medical Services, CPR, cardiopulmonary resuscitation, ROSC, Return of Spontaneous Circulation, CPC, Cerebral Performance Categories. *dispatch times available in 151 cases. ** information not available in 2 patients who were discharged alive from hospital to their home countries.

***CPC available for 51 patients.

Recognised as OHCA

YES (n=135)

NO n=(29)

P value

Age (median) 63 (IQR 56 to 75)

67 (IQR 57.5 to 78)

0.083

Sex (%) Female

20

27.3

0.095

Dispatched within 2 minutes (%)*

88/127 (69.3%)

13/24 (54.2%)

0.149

EMS response < 9 minutes*

77/127 (60.6%)

12/24 (50.0%)

0.332

CPR before EMS

102/135 (75.6%)

15/29 (51.7%)

0.01

Sustained ROSC

83/135 (61.5%)

15/29 (51.7%)

0.331

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Alive at hospital discharge

60/135 (44.4%)

11/29 (37.9%)

0.521

Alive at one year**

46/133 (34.6%)

8/29 (27.6%)

0.469

CPC 1 or 2 after six months***

32/118 (27.1%)

5/26 (19.2%)

0.405

Home as place of OHCA

69/135 (51.1%)

14/29 (48.3%)

0.380

5.3.2 Airway management process in OHCA The final prehospital airway technique was ETI in 67.3% (413/614) of the patients, and SAD in 30.2% of the patients (188/614). The majority of the patients were treated with the initially selected airway technique only (554/614, 90.2%).

Table 9. ETI and SAD as final airway techniques and success rates. ETI, endotracheal intubation, SAD, supraglottic airway device, BLS, basic level support, ALS, advanced level support, EMS, Emergency Medical Service. Final airway technique n (%)

Overall success rate n (%)

Equal or less than two attempts n (%)

BLS as provider N (%)/EMS physician present n (%)

ALS as provider n (%)/EMS physician present n (%)

EMS physician as provider n (%)

ETI 413 (67.3) 384 (92.5) 353 (85.1) 82 (19.9)/18 (22.0)

264 (62.4)/32 (12.1)

67 (16.2)

SAD 188 (30.6) 164 (85.0) 155 (80.3) 129 (68.7)/1 (0.8)

57 (30.3)/3 (5.3) 2 (1.1)

In all, ETI was the final prehospital airway technique in 67.3% (n=413) and SAD in 30.2% (n=188). One patient was treated with cricothyrotomy, and six patients were treated with BVM only without any attempts to secure the airway (1.0%). Another six patients were successfully treated with BVM after failed advanced airway attempts. An EMS physician was present and involved in OHCA patient care in 249 (Study III) of the 614 patients (40.6%). When ALS or BLS performed airway management, a physician was present in 54 of the 532 patients (10.2%). Airway management was provided by EMS physicians in 70 of 614 OHCA patients (11.4%), including one successful cricothyrotomy after failed ETI and SAD attempts.

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EMS reported adverse events in 27.2% of the patients (n=167). The most common reason was more than two attempts at securing an airway (8.1%). Regurgitation occurred in 7.2% of the patients, and difficult anatomy or impaired vision was reported in 29 patients (4.7%). An EMS physician successfully intubated eight patients after failed attempts by other EMS personnel. Capnometry or capnography was used to verify the correct ETI placement in 315 of the patients (76.3%), and nearly as often auscultation and observation of chest movements were used (68.0%). The tube was placed in visual control in most of the cases (86.2%). For four intubated patients, no records of ET tube placement confirmation were reported 5.3.3 Therapeutic hypothermia in ICU Of the 281 patients with a primary shockable rhythm, 241(85.8%) of them were treated with therapeutic hypothermia (TH). The corresponding figures for non-shockable rhythms were 70/223 patients (31.4%). High age and poor prognosis because of underlying diseases were the most common reported reasons for withholding TH in patients resuscitated from a primary shockable rhythm. Patients treated with TH were more likely to be younger (median age 62 vs 74, p<0.001), male (83.8% vs 70.0%, p=0.046), to have had bystander CPR in the prehospital phase (67.2% vs 42.5%, p=0.004) and to have presumed cardiac origin as the aetiology of OHCA (94.2% vs 80%, p=0.002).

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6 DISCUSSION 6.1 MAIN FINDINGS 6.1.1 Epidemiology and outcome In this study, the incidence of OHCAs considered for resuscitation was 78/100,000 inhabitants/year, with an incidence of EMS-attempted resuscitation of 51/100,000 inhabitants/year. EMS-attempted resuscitation was initiated mostly for patients whose collapse was witnessed. One-third had a primary shockable rhythm. Overall survival at one year for all events and for all rhythms was 13.4%, with a 32.7% 1-year survival for patients resuscitated from a shockable rhythm. Survival among patients resuscitated in urban areas from a witnessed OHCA of presumed cardiac origin with a shockable rhythm was improved when compared to earlier studies from Finland. The population-based incidence of adult ICU-treated OHCA was 13/100,000 inhabitants/year, the majority of whom were resuscitated from a shockable initial rhythm. Overall survival among ICU-treated, unconscious OHCA patients at hospital discharge was 51.6%. Survival from a non-shockable rhythm was poor in both prehospital and ICU-treated study groups. 6.1.2 Factors related to survival Factors related to improved survival were: a primary shockable rhythm, short delays from the emergency call to initiation of CPR and to EMS arrival on scene, the presence of an EMS physician during OHCA treatment in the prehospital phase and the use of TH for patients resuscitated from a shockable rhythm. The use of any advanced airway technique and the use of TH for non-shockable rhythms were not associated with survival. The recognition of OHCA by EMD, T-CPR instructions and bystander CPR before EMS arrival were also not associated with survival. 6.1.3 Elements of chain of survival The Finnish emergency medical dispatchers’ ability to recognise cardiac arrest as the reason for the emergency call was high, and the majority of the calls were processed within 2 minutes. T-CPR instructions were given for a minority of OHCA patients. In all, approximately half of the patients received bystander CPR. EMS personnel most often used ETI for cardiac arrest patients, with a high overall success rate. The provider was mostly ALS personnel, whereas BLS usually placed SADs. An EMS physician was physically present in one tenth of the situations where BLS or ALS managed the airway. In all, EMS physicians were present in nearly half of all OHCAs at some phase of the prehospital care. TH was used widely in Finnish ICUs for OHCA patients resuscitated from shockable rhythms, but it was also provided to one-third of patients with a non-shockable primary rhythm.

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6.2 INCIDENCE AND OUTCOMES IN RELATION TO PREVIOUS STUDIES 6.2.1 Incidence of OHCA The annual incidence of OHCA in Finland seems to be in concordance with many previously published studies (Kuisma, Määttä 1996, Kämäräinen et al. 2007, Franek, Pokorna & Sukupova 2010), but the incidence declined from 113/100,000 inhabitants/year to 78/100,000 inhabitants/year since the study from Helsinki in the late 1980s (Silfvast 1990). Atwood et al. reported the incidence of attempted resuscitations to be 38/100,000 inhabitants/year (Atwood et al. 2005). Despite the Utstein-style reporting system (Jacobs et al. 2004), considerable variation in incidence and outcome is seen among studies internationally (Atwood et al. 2005, Ong et al. 2015); according to Atwood, up to 6-fold. There are many explanations for this. Not all variables are collected, and interpretation and implementation of the template varies among registries in different countries (Pell et al. 2003). Table 10 shows the incidence and survival rates of OHCA in recent studies worldwide. It also demonstrates the difficulty of comparing incidences between studies due to differences in the definitions used, the study population and the patients included and the variables reported.

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Table 10. Incidence and survival rates of OHCA in Seattle, USA, Stavanger, Norway, London, UK and from Korea in addition to FINNRESUSCI study1. Mickey Eisenberg, personal communication 2015,2 (Lindner et al. 2011),3 (Fothergill et al. 2013),4 (Ahn et al. 2010). Incidence is reported per 100,000 inhabitants/year.

Community Inclusion criteria

Total population served

Incidence of OHCA considered for resuscitation

Incidence of EMS-attempted resuscitation efforts

Shockable primary rhythm, %

Overall survival to hospital discharge, %

Shockable primary rhythm, survival to hospital discharge, %

Shockable primary rhythm, witnessed status, cardiac origin, survival to hospital discharge

FINNRESUSCI Finland 2010

-all OHCAs

2,644,200 78 51 31 20 37 46

Seattle, USA 20131

-non-traumatic OHCAs -over 2 years of age

1,981,900 Not reported

57 24 21 50 62

Stavanger, Norway 2006-20082

-cardiac OHCA -over 18 years of age

314,000 Not reported

93 47 25 48 37

London, UK 2011-20123

bystander-witnessed OHCAs -cardiac origin -shockable rhythm

8,200,000 Not reported

51 35 32 32 32

Korea 2006-20074

-non-traumatic OHCA -cardiac OHCA

47,000,000 41 32 6 3 20

6.2.2 Withholding resuscitation EMS personnel withheld resuscitation after arriving to the patient’s side in 35.6% of the cases. The most commonly reported reason was futility of the situation (80.1%) due to e.g. long response times, non-witnessed cardiac arrest, or asystole as the primary rhythm. When EMS continued resuscitation after their arrival, the collapse was witnessed in approximately 9 out of every 10 cases (prehospital study group). Recent ERC guidelines advise to consider withholding CPR in children and adults when the safety of the provider cannot be assured, there are clear signs of mortal injury or secondary death marks, strong evidence that CPR would be against patient’s values or would be futile, or when asystole has continued for more than 20 minutes (Perkins et al. 2015). In Finland, medical directors in every district hospital give instructions to EMS personnel about these situations. Keeping in mind that the FINNRESUSCI study area was large and included many different EMS organisations, these instructions may have varied. In European countries,

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variability in withholding of resuscitation efforts exists – for example, not all countries in Europe allow limiting the treatment such as CPR prehospitally. An earlier study from Finland (Kämaräinen et al. 2007) found that EMS personnel withheld resuscitation in 98/191 (51.6%) of the OHCA patients. However, this number included 59 patients with signs of secondary death, and, additionally, 12 patients with massive trauma. This study was reported exactly how Utstein template guides to be included as considered for resuscitation: “all unresponsive, breathless and pulseless patients for whom the emergency personnel are called”. However, it is difficult to understand why patients who are obviously dead on EMS arrival with secondary death signs or with fatal trauma, should be classified as “considered for resuscitation” and to be included in data. This is somewhat confusing and has caused misunderstanding and even bias when reporting OHCA incidence and EMS rates of withheld resuscitation (Berdowski et al. 2010). New guidelines use the definition “EMS-attended”, which includes all patients with absence of signs of circulation (Perkins et al. 2015) and, patients with fatal trauma with signs of secondary death marks. These dead patients represent data of incidence of overall death outside hospital (with EMS response). Although the new term “EMS-attended” may more properly describe the components of healthcare system responding to OHCA, it still leaves open the possibility of misunderstanding. The patient group considered for resuscitation including only lifeless patients (with signs that indicates the patient is clearly dead on EMS arrival) whose resuscitation is either initiated or not by EMS, would more realistically describe the true decision-making process of resuscitation and also provide valuable data for organisations responsible for EMS. For example, if response times and delays increase and repeatedly cause situations where resuscitation efforts are considered to be of no benefit anymore, administration level is able to react on this by for example modifying/increasing EMS resources to shorten the response time for OHCA in their operating area. Finally, Berdowski et al. recommended that when reporting OHCAs, the study population should be clearly described (EMS-attended, treated by EMS, etc.) and inclusion and exclusion criteria explicitly noted. 6.2.3 Aetiology In this study, over half of the patients were evaluated to have a cardiac arrest of presumed cardiac origin. When analyzing the data for patients whose OHCA was classified as “unknown” (19.2%, n=129), this patient group consisted mostly of patients with a non-shockable primary rhythm (79.1%, n=102). In other words, there were 27 patients with shockable rhythm. Six of these patients survived to hospital discharge, and four patients were alive at one year. We did not want to make changes after EMS personnel evaluated the aetiology of OHCA, but instead instructed them to perform this evaluation according the Utstein template, where the intention has been to separate cardiac and non-cardiac arrests. The updated template recognises that trying to separate cardiac from non-cardiac causes may not be very useful and suggests that causes of cardiac arrest should fall into six

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categories: medical, traumatic, drug overdose, drowning, electrocution, or asphyxia (Perkins et al. 2015). “Medical” includes cases in which the cause of OHCA is presumed to be cardiac, but also includes other medical causes (e.g., anaphylaxis, asthma, gastrointestinal bleeding). In some cases, there is no obvious reason for cardiac arrest to occur. Hence, instead of trying to separate “cardiac” causes from all other OHCAs, the updated template recommends reporting all EMS-treated cardiac arrests that are bystander witnessed with a primary shockable rhythm. By doing this, uniform reporting might be improved and also more reliable. 6.2.4 Increased survival rates and survival from shockable rhythms In Finland, prior studies included OHCA patients from two cities and hence urban areas only (Silfvast 1990, Kuisma, Määttä 1996, Kämäräinen et al. 2007). To be able to more reliably compare FINNRESUSCI data to these previously published reports and whether the OHCA survival had improved, outcomes were also reported among OHCA patients treated in urban areas. This showed that the survival to hospital discharge among patients with bystander-witnessed OHCA with a primary shockable rhythm of presumed cardiac origin (the “golden standard” of Utstein) increased from 27% to 53.8% in two decades (1987-2010). This patient group has the best chance of all OHCAs for survival (Eisenberg, Bergner & Hallström 1979, Sasson et al. 2010) and was seen in this study also. A survival rate of 53.8% can be considered a good outcome. In a retrospective report from London, survival in this patient group increased from 12% (in 2007-2008) to 32% (in 2011-2012) (Fothergill et al. 2013) . Another study from Europe showed variation in survival rates from bystander-witnessed OHCA of cardiac aetiology resuscitated from a shockable rhythm ranging from 13% (Berlin) to 55% (Stavanger). The Stavanger data was unit based, not population based, but seven EMS systems have reported more than 30% survival in this patient group (Herlitz et al. 1999). In another study from Norway, survival from witnessed arrest with a shockable rhythm increased so that in the 2006-2008 time period, on average every second resuscitation attempt resulted in survival to hospital discharge (Lindner et al. 2011). Results of this study are not totally comparable to earlier reports in Finland because the study area and EMS were different, but the comparison represents the closest available for survival trends of OHCA patients in Finland. Increased overall survival from OHCA has also been reported from other countries (Lund-Kordahl et al. 2010, Adielsson et al. 2011). The ROC investigators recently reported improved survival from OHCA between 2006 and 2010 (Daya et al. 2015). The exact reason for this improvement was unknown, but according to authors may have been influenced by multiple factors, such as increased bystander CPR, minimising pauses in chest compressions and optimising the depth and rate of compression – overall by doing the right things at the right time during prehospital care of OHCA patient. It is possible that selection for resuscitation is performed more properly, i.e. patients with a better prognosis are recognised by EMS, and resuscitation efforts are focused on those patients that are more likely benefit from it and survive OHCA by withholding resuscitation in futile cases according to local EMS instructions. Accordingly, these same elements may partly apply when observing improved results also in Finland. The outcome of OHCA has improved when comparing patients before and after TH was thoroughly implemented in

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ICUs (Sunde et al. 2007, Reinikainen et al. 2012), which can be related also to a more standardised post-resuscitation care treatment protocol in the prehospital phase, after arrival to hospital and in ICUs. 6.2.5 Survival from non-shockable rhythms This study showed low survival rates for patients in the prehospital study group with primary non-shockable rhythms (8.5% to hospital discharge and 4.6% at one year), similar to other reports (Holmgren et al. 2010, Fischer, Fischer & Schuttler 1997). It seems that the prognosis of these patients has not changed over the years (Andrew et al. 2014). However, potential survivors do exist in this patient group, especially when advanced care is available at short notice, and ROSC is achieved without extensive delays (Herlitz et al. 2008, Väyrynen et al. 2008). According the ERC guidelines, reversible causes of cardiac arrest should be determined and treated during the early phase of resuscitation (Soar et al. 2015). This study reported survival to hospital discharge as the Utstein template recommends and, additionally at one year. To really survive OHCA means to survive not only alive, but also back to a functional and cognitive status at or near that which the patient had previously. For the prehospital study group, most patients with a primary shockable rhythm who survived to hospital discharge were alive one year after cardiac arrest (36.5% vs 32.7%), whereas survival from non-shockable rhythms decreased approximately 50% during the one-year follow-up (8.5% vs 4.6%). For ICU-treated patients, 66.2% (186/281) admitted to ICU and who were resuscitated from shockable rhythm, were alive at hospital discharge and 56.9% (160/281) were alive at one year. Corresponding numbers in the non-shockable patient group were 33.2% (74/223) and 21.5% (48/223). In other words, these figures show that prognosis of patients resuscitated from non-shockable rhythms remain poor not only in the pre- or in-hospital phase, but also after discharge. Reports on long-term follow-up after OHCA are scarce, especially if the primary rhythm is non-shockable. However, a study from Finland on patients resuscitated from a primary rhythm of pulseless electrical activity and with a 5-year follow-up showed that 7/10 of the patients were still alive one year after discharge (Saarinen et al. 2012). Another Finnish study restricted to patients who were resuscitated from VF demonstrated that when neurological recovery is achieved after resuscitation, it can be maintained for over a decade (Harve et al. 2007). 6.2.6 Different EMS systems Overall, comparison of different prehospital studies and their results internationally in studies is challenging due to different EMS systems with different levels of staff (EMTs, nurses, paramedics, paramedic-led or doctor-led EMS) in the regions they operate and different practices and protocols in each country, or even in each community inside the countries. These challenges also exist when FINNRESUSCI results are compared with previously published studies from Finland. The study areas were different. In some areas EMS system may function ideally with sufficient resources and may be able to rapidly respond when dispatched, reach more OHCA patients with more primary shockable rhythms and be more experienced with resuscitation, for which reasons they may achieve

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better OHCA patient outcome. On the other hand, there might be areas inside FINNRESUSCI study area and elsewhere in Finland, where the results treating OHCA patients are worse, but cannot be seen when results are pooled together. It should also be kept in mind, that although Finland basically has a doctor-led EMS system, from an operational point of view we still have areas where a trained EMS physician is unavailable for medical emergencies. This study showed that an urban municipality was associated with survival to hospital admission (urban 41.5%, semi urban 28.3%, rural 25.8%, p=0.001). Statistically municipality type did not associate with survival to hospital discharge or survival at one year. However, in urban areas the survival rates were nearly two-fold higher than those in rural areas (9.0% vs. 15.1%). There was no difference between municipalities in time to initiation of CPR or first defibrillation. Reasons for this observation of a difference in survival rates are difficult to explain, but the multiple factors mentioned in the previous paragraph may play a role. 6.3 FACTORS RELATED TO SURVIVAL 6.3.1 Early provision of CPR Bystander CPR has shown to improve outcome in previous studies (Sasson et al. 2010) and is of great importance to a victim experiencing cardiac arrest. In a Swedish study, when CPR was carried out by a bystander, it doubled the survival of an OHCA patient (Hasselqvist-Ax et al. 2015). Lindner reported that in the time period 2006-2008, 73% of the OHCA patients received CPR. In our study, bystander CPR was provided approximately to half of all patients (up to 71.3% in patients with a witnessed OHCA and a shockable rhythm), but was not related to survival in regression analysis. Instead, early provision of CPR by either a bystander or EMS after collapse was related to improved survival. The relation of bystander CPR with survival has been noted as early as in the late 1970s by Eisenberg et al. (Eisenberg, Bergner & Hearne 1980, Eisenberg, Bergner & Hallström 1979). Our study may have a lack of statistical power to show the benefit of bystander CPR. On the other hand, our study showed the importance of CPR to be given to a cardiac arrest patient as early as possible. In the prehospital patient group, the majority of the patients experienced a witnessed cardiac arrest, but half of them still did not receive CPR before EMS arrival. Hence, training bystanders and relatives to recognise cardiac arrest and immediately provide good-quality chest compressions should be further emphasised in Finland. 6.3.2 EMS arrival A short delay from collapse to EMS arrival at patient side was related to survival in this study. After determining the patient to be a cardiac arrest patient, EMS personnel provide chest compressions and simultaneously analyse the primary rhythm. If the rhythm is shockable, defibrillation is performed. These rapidly performed elements logically have a positive impact on outcome and have for decades been the backbone of cardiac arrest care in the prehospital environment. We did not separate the EMS units in this analysis into

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BLS or ALS units, keeping in mind that all first response and BLS units in Finland are capable of providing CPR, early defibrillation and airway management as earlier described. First response units have, additionally, AEDs in use. If a first response unit reaches the patient before trained EMS personnel, unit personnel are able to assess the rhythm and defibrillate it, if indicated. If dispatched as a cardiac arrest, a minimum of two units and, if available, an EMS physician unit are simultaneously dispatched. 6.3.3 EMS physician An EMS physician was involved in 40.6% of all OHCAs with attempted resuscitation efforts at some point in prehospital patient care. This presence was associated with increased survival to hospital discharge and at one year. To date, no randomised controlled studies exist on this topic. Bakalos et al. reported that in cardiac arrests, when the ALS provider is a physician, the probability of survival to hospital discharge increases (OR 2.047, 95% CI 1.593-2.631) (Bakalos et al. 2011). One reason for improved survival may be partly due to selection. In Finland, even when dispatched, EMS physicians can withdraw from an EMS assignment if they assess en route that the patient, for various reasons, probably would not benefit from their presence. They tend, reasonably, when attaching themselves to a task, to select OHCA patients with a good prognosis. When involved in the treatment, they may be follow the resuscitation protocol more thoroughly, including important elements such as good-quality chest compressions, timing of defibrillation, minimal pauses in chest compressions, and ideal oxygenation with a proper airway. Reversible or treatable causes behind cardiac arrest may be more actively assessed and diagnosed. If ROSC then is achieved, treatment of OHCA patient moves from a strict resuscitation protocol to a more challenging phase: treatment becomes more individualised depending on the patient’s medical history and background, and more extensive medical knowledge is needed to stabilise the patient. This will influence the treatment strategies when transporting the patient to hospital (e.g., myocardial infarction – existing or not, should patient receive thrombolysis immediately, or should a percutaneous coronary intervention (PCI) be performed. EMS physicians also represent an “extra resource” in treatment along with other EMS personnel, who also have one extra paramedic, nurse, or fireman with them. Increasing the number of personnel has been shown to have a positive effect on outcome in OHCA care prehospitally (Warren et al. 2015). The latest ERC guidelines (Soar et al. 2015) state that because of the inconsistent evidence, EMS physician involvement to OHCA patient care depends strongly on existing local policy, and no specific recommendations on this topic were made. In Finland, we have a three-tiered EMS system and a history of EMS physicians as part of our EMS system and in response to high-risk medical emergencies, including cardiac arrests. This assures that high-quality medical care reaches patients prehospitally. The results of this study also suggest that their presence during OHCA patient care is warranted.

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6.4. DIFFERENT ELEMENTS IN OHCA 6.4.1 Dispatch process The updated resuscitation guidelines from 2015 stress the importance of interactions between the EMD, the bystander who provides CPR and the early use of automated external defibrillator in patient survival from OHCA (Nolan et al. 2015). Accordingly, the updated Utstein statement recommends that dispatch information be included in outcome reports on OHCA (Perkins et al. 2015) due to increasing knowledge on the factors affecting OHCA patient outcome (including EMD-assisted CPR). This study showed a high OHCA recognition rate by the Finnish EMD (82%). This was not associated with increased survival to hospital discharge. Even when coded as a “non-arrest” event, they were still usually coded as “unconscious”, thus receiving the highest priority anyway. Bystander CPR was performed more often for patients whose cardiac arrest was recognised by EMD. This did not have effect on survival, although as mentioned earlier, bystander CPR has shown to have positive impact on outcome in many other studies. Our study may lack the statistical power to show the effects of bystander CPR or EMD recognition of OHCA on the outcome. ROSC and survival to hospital discharge and one year were nevertheless worse if OHCA was not recognised, even though the results did not reach statistical significance. T-CPR instructions were given in a third of the emergency calls. Finnish dispatcher protocol includes T-CPR instructions if the caller is willing and does not know how to give CPR, unless CPR is already ongoing. Guidelines for T-CPR-instructions are being published (Lerner et al. 2012). 6.4.2 Airway management This study showed high overall success rates for ETI (92.5%) and SAD (85.0%) placement performed by BLS or ALS personnel. ETI was the most coomonly used airway technique. Adverse effects were observed in a fourth of the placements. In different EMS systems, different practices are in use (McMullan et al. 2014, Tanabe et al. 2013). It seems that current recommendations in use in Finland where all EMS providers are trained to use some advanced airway device lead to desirable results. Success rates for both ETI and SAD placements were comparable to other studies (Diggs, Yusuf & De Leo 2014, Sunde et al. 2012). However, success rates for SADs were lower than for ETIs. Are certain SADs more difficult to insert than others? Sunde reported a high insertion-related problem (52.7%) in laryngeal tube placements (Sunde et al. 2012). We grouped different SADs, making comparison of different devices impossible. SADs were mostly placed by BLS personnel. Although success rates were within acceptable limits, we may need to evaluate the need for extra training of BLS personnel. In the end, EMS personnel succeeded with the airway techniques they used surprisingly well in OHCAs. They had an EMS physician present in only every tenth ETI. In a questionnaire survey from Finland, the annual mean frequency for EMS personnel to

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perform ETI was 2 (range 0-16, n=185), and SAD 1 (0-20, n=22). This survey was from Northern Finland but gives some reference of the low frequency of airway management for individual EMS personnel. ETI or SAD placements is more difficult to perform for a non-arrest patient with laryngeal reflexes, which is why it is nationally agreed that ETI or SAD placement be reserved to experienced EMS physicians comfortable with working in a prehospital setting with limited resources and equipment. Ultimately, the optimal airway technique may not be a specific airway device, but instead may depend on the background and skill level of the provider (Soar, Nolan 2013). The key to success in this crucial procedure is the principle that whatever technique is chosen, the personnel should be properly trained and familiar with the equipment. 6.4.3 Therapeutic hypothermia In the latest guidelines (Monsieurs et al. 2015), the ERC collaborated with the European Society of Intensive Care Medicine to establish post-resuscitation care guidelines. One section has been dedicated to this important topic, which is recognised as a vital link in the Chain of Survival (Nolan et al. 2015). It includes urgent coronary catheterisation and PCI for patients with coronary heart disease as the cause of cardiac arrest, temperature-targeted (optionally to target a temperature of 36 degrees) management, and rehabilitation after survival from OHCA. The guidelines recommend that sufficient time be given to allow neurological recovery to occur before prognostication and a multimodal approach when assessing the prognosis of cardiac arrest patients (Sandroni et al. 2014). The FINNRESUSCI study showed that when an OHCA patient was admitted to a Finnish ICU, he/she most often was resuscitated from a witnessed cardiac arrest with a shockable rhythm. Bystander CPR was provided slightly more often than in the prehospital study group. OHCA patients in the ICU represent a highly selected patient population, exluding patients with a very poor prognosis and, on the other hand, conscious patients in stable condition who can be treated in other wards. In his dissertation, Tuomas Oksanen concluded that TH was implemented rapidly in Finland compared to other countries (Oksanen 2015). This study showed that TH was used widely in Finnish ICUs. Of patients with a shockable primary rhythm, 85.8% received TH. Additionally, 31.4% of patients with a primary non-shockable rhythm were also treated with TH. Scandinavian guidelines from 2009 recommended using TH for all primary rhythms if the patient is admitted to the ICU after OHCA (Castren et al. 2009) and active treatment is continued. We were unable to analyse some variables of interest concerning patients treated in the ICU, for example dispatch records. In this study, of those OHCA patients admitted to hospital and treated with TH, survival and neurological outcome was favourable only for those with a primary shockable rhythm. TH did not have positive impact on survival in the non-shockable patient group. In landmark studies on TH in the beginning of the 2000s (Zeiner et al. 2000, Bernard et al. 2002) survival and neurological recovery was reported in patients with a shockable primary rhythm, but neither study included patients with non-shockable rhythms. A short

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time to ROSC and bystander-provided CPR may be more important factors than TH among survivors in this patient group (Väyrynen et al. 2008). A systematic review by the Cochrane Collaboration concluded that TH seems to improve survival and neurologic outcome in cardiac arrest (Arrich et al. 2012). Preventing patients from becoming febrile may be sufficient to prevent adverse neurological injuries, although in many animal and human studies mild induced hypothermia protects neurons and prevents global cerebral hypoxic-ischaemic injury (Froehler, Geocadin 2007). On the other hand, what is found in experimental studies does not always carry clinical significance. A recent randomised controlled trial showed no difference in survival and neurological outcome for OHCA patients with a targeted temperature of 33 degrees compared to that of 36 degrees (Nielsen et al. 2013). ERC guidelines in 2015 prefer term targeted temperature management (TTM) over TH, and concludes by recommending TTM (33 to 36 degrees) for at least 24 hours in adults after OHCA with a primary shockable rhythm. The guidelines also suggest TTM for non-shockable rhythms but qualify it as a weak recommendation due to low-quality evidence (Nolan et al. 2015). In addition, for resuscitated patients, prehospital cooling has not been shown to benefit OHCA patients (Hunter et al. 2014). Finally, hypothermia alone is never sufficient for patients recovering from OHCA; it includes high-quality treatment from the very beginning of cardiac arrest, before, during and after intensive care. 6.4.4 Cardiac arrest in special circumstances The most recent ERC guidelines have some new elements compared to previously published guidelines (Soar et al. 2010) for cardiac arrest in special circumstances (Truhlar et al. 2015). Firstly, although mortality is high among traumatic cardiac arrest patients, there may be reversible, treatable causes (cardiac tamponade, tension pneumothorax) behind the arrest. Hence, a new treatment algorithm for this patient group has been developed. Especially in penetrating traumas leading to a cardiac arrest, the prognosis is not necessarily futile; in fact, in a London HEMS study survival was reported to be 18% (Davies, Lockey 2011). Secondly, for a highly-selected patient group, i.e. patients with a primary shockable rhythm and witnessed OHCA, and where the rescue PCI team is experienced and the protocol is well-planned in both outside and inside hospital, transportation with ongoing CPR can be considered from the scene to the catheterisation laboratory. If this decision is made, the use of a mechanical chest compression device is recommended throughout resuscitation. Thirdly, in pulmonary embolism, extracorporeal life support (ECLS) can be considered as a rescue therapy if resuscitation efforts are unsuccessful.

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7 LIMITATIONS OF THE STUDY Data collection for the prehospital phase of the study was a major challenge. The prehospital setting in geographically extensive area with different EMS organisations and hundreds of EMS providers with limited research resources was a difficult combination. EMS personnel are a heterogeneous group with different educational backgrounds, and not all are comfortable with data collection for research purposes. In addition, limited time is available when treating a cardiac arrest patient, and many procedures occur simultaneously, making observation of e.g. time points difficult. Understandably, patient care comes first and filling in case report forms and other papers when there is time to do so. Information was missing in some CRFs, resulting in exclusion of patients because of insufficient data. Moreover, data input in CRFs may be partly inaccurate, but this same bias, is presumably present in all prehospital studies or studies on critical care patients in general. Despite our efforts, there may be some cardiac arrests not reported and included in the FINNRESUSCI study. For analysis of survival rates, hospital discharge was defined as discharge from the primary hospital, and included patients transferred to another hospital or non-acute health care facility (n=100). Because of the wide study area and limited resources, it was impossible to follow up these patients at this phase. One reason why survival status at one year was reported was to increase the reliability of the data for survival rates. The quality of bystander CPR was not evaluated. Information on possible T-CPR instructions was given by EMS personnel, not by EMD. Airway management data was not collected as thoroughly as recommended by Sollid et al. (Sollid et al. 2009). Therefore, we were unable to report whether the provider of airway management changed during the process. On the other hand, the CRF was quite long, and decisions had to be made on the extent of data collection. TH use was not randomised, but was in the hands of the clinician. Bias between TH-treated and non TH-treated groups due to unknown variables and residual confounding after multivariate adjustment are also possible, as in all observational studies. Despite these limitations, FINNRESUSCI study is the first comprehensive observational study from Finland on OHCA patients, including different geographical areas and multiple EMS organisations and EMS providers. In addition, we reported TH use and outcomes from nearly every ICU in Finland. This study thus represents the status quo of epidemiology and outcomes of patients with OHCA treated in Finland.

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8 CONCLUSIONS Based on the current studies, the following conclusions can be drawn:

1. The incidence of OHCA with attempted resuscitation in Finland was 51/100,000 inhabitants/year, with one-third of the patients having a shockable primary rhythm. The incidence of OHCA has decreased over time. Overall survival from OHCA remained similar to previous reports from Finland, but survival for patients resuscitated from bystander-witnessed cardiac arrest with a shockable rhythm has improved.

2. A primary shockable rhythm, short delays from collapse to initiation of CPR and EMS arrival, involvement of an EMS physician in patient care and the use of TH for patients resuscitated from a shockable rhythm were associated with improved survival.

3. The recognition rate of cardiac arrest by the EMD was high (82%) and comparable to other studies. Most patients in this study suffered witnessed cardiac arrest, but less than half received bystander CPR. Airway management was usually performed by advanced level EMS personnel with ETI. TH was widely used in Finnish ICUs and was also used for one-third of patients resuscitated from a non-shockable rhythm.

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9 FUTURE IMPLICATIONS Early recognition of patients in cardiac arrest is crucial. Reasons for not recognising this life-threatening condition by the dispatcher should be further evaluated. Reasons for bystanders not giving cardiopulmonary resuscitation should also be studied. This simple technique, which has no costs and can be performed by almost anyone, even children (Abelairas-Gomez et al. 2014), has been shown to double the survival rates of OHCA patients (Hasselqvist-Ax et al. 2015). The public should be trained. CPR education should be extended to school curricula and workplaces. Resuscitation courses should ideally be inexpensive and available for everyone interested. How funding for widespread CPR education would be provided and whether laypersons would actually provide CPR in real life is uncertain. Location of nearby rescuers (professionals and trained volunteers) already trained in CPR via a mobile-phone positioning system is another possibility. They could then be guided to the patient side and possibly to use the nearest public AED. This idea has been tested in Stockholm with encouraging results – although not shown to increase survival rates, bystander CPR increased from 47.8% to 61.6% (Ringh et al. 2015). Other possibilities include development assisting tools for bystanders and dispatchers to identify cardiac arrest, for example with a mobile phone application (Syväoja et al. 2014). This is a fascinating idea that may be worthwhile developing and testing in real-life situations. The optimal airway technique in OHCA remains undetermined. At least two randomised controlled trials are currently in progress and may help resolve this important issue. Another topic that would be interesting to study further would be the influence on outcome when an EMS physician involved in OHCA patient care. Is the reason simply the selection of patients with presumed better prognosis, or is it the medical expertise brought to the patient side outside the hospital that increase the survival rates? Mickey Eisenberg, medical director of King County Emergency Medical Services, which has one of the world’s best survival rates in OHCA, has always considered the management of cardiac arrest to be the best surrogate for an entire system’s performance (“it takes a system to save a victim”) (Eisenberg 2013). Indeed, when monitoring the system, the whole “chain of survival” should be a continuous process. A national registry for OHCA data should be developed in Finland. It would provide a common database for future research and a tool to assess the effectiveness of EMS. The Resuscitation Academy programme, originating from King County EMS and established in 2009, will be organised for the first time in Finland in April 2016. It contains ten steps that will help to increase survival from cardiac arrest in communities (Eisenberg). Bringing this concept also to Finland is more than welcome. Additionally, efforts to establish a uniform European cardiac registry have recently been made (Wnent et al. 2015). In addition to the Utstein template, it should also contain some other variables related to critical interventions (i.e. airway management process).

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Moreover, further study of patients whose resuscitation efforts were withheld would be interesting. Does this patient group include patients whose cardiac arrest remained unrecognised by the bystander or dispatcher? What were the reasons why resuscitation was considered futile – e.g. if response times were too long, a closer examination of available resources or geographical location at the time of emergency call would be important to evaluate whether there ever was even a theoretical possibility for EMS to save the patient.

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10 REFERENCES

Abelairas-Gomez, C., Rodriguez-Nunez, A., Casillas-Cabana, M., Romo-Perez, V. & Barcala-Furelos, R. 2014, "Schoolchildren as life savers: at what age do they become strong enough?", Resuscitation, vol. 85, no. 6, pp. 814-819.

Abella, B.S., Sandbo, N., Vassilatos, P., Alvarado, J.P., O'Hearn, N., Wigder, H.N., Hoffman, P., Tynus, K., Vanden Hoek, T.L. & Becker, L.B. 2005, "Chest compression rates during cardiopulmonary resuscitation are suboptimal: a prospective study during in-hospital cardiac arrest", Circulation, vol. 111, no. 4, pp. 428-434.

Adielsson, A., Hollenberg, J., Karlsson, T., Lindqvist, J., Lundin, S., Silfverstolpe, J., Svensson, L. & Herlitz, J. 2011, "Increase in survival and bystander CPR in out-of-hospital shockable arrhythmia: bystander CPR and female gender are predictors of improved outcome. Experiences from Sweden in an 18-year perspective", Heart (British Cardiac Society), vol. 97, no. 17, pp. 1391-1396.

Ahn, K.O., Shin, S.D., Suh, G.J., Cha, W.C., Song, K.J., Kim, S.J., Lee, E.J. & Ong, M.E. 2010, "Epidemiology and outcomes from non-traumatic out-of-hospital cardiac arrest in Korea: A nationwide observational study", Resuscitation, vol. 81, no. 8, pp. 974-981.

Alfsen, D., Moller, T.P., Egerod, I. & Lippert, F.K. 2015, "Barriers to recognition of out-of-hospital cardiac arrest during emergency medical calls: a qualitative inductive thematic analysis", Scandinavian journal of trauma, resuscitation and emergency medicine, vol. 23, no. 1, pp. 70.

Andrew, E., Nehme, Z., Lijovic, M., Bernard, S. & Smith, K. 2014, "Outcomes following out-of-hospital cardiac arrest with an initial cardiac rhythm of asystole or pulseless electrical activity in Victoria, Australia", Resuscitation, vol. 85, no. 11, pp. 1633-1639.

Arrich, J., Holzer, M., Havel, C., Mullner, M. & Herkner, H. 2012, "Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation", The Cochrane database of systematic reviews, vol. 9, pp. CD004128.

Atwood, C., Eisenberg, M.S., Herlitz, J. & Rea, T.D. 2005, "Incidence of EMS-treated out-of-hospital cardiac arrest in Europe", Resuscitation, vol. 67, no. 1, pp. 75-80.

Bakalos, G., Mamali, M., Komninos, C., Koukou, E., Tsantilas, A., Tzima, S. & Rosenberg, T. 2011, "Advanced life support versus basic life support in the pre-hospital setting: a meta-analysis", Resuscitation, vol. 82, no. 9, pp. 1130-1137.

Bang, A., Herlitz, J. & Martinell, S. 2003, "Interaction between emergency medical dispatcher and caller in suspected out-of-hospital cardiac arrest calls with focus on agonal breathing. A review of 100 tape recordings of true cardiac arrest cases", Resuscitation, vol. 56, no. 1, pp. 25-34.

Benoit, J.L., Gerecht, R.B., Steuerwald, M.T. & McMullan, J.T. 2015, "Endotracheal intubation versus supraglottic airway placement in out-of-hospital cardiac arrest: A meta-analysis", Resuscitation, vol. 93, pp. 20-26.

BENSON, D.W., WILLIAMS, G.R.,Jr, SPENCER, F.C. & YATES, A.J. 1959, "The use of hypothermia after cardiac arrest", Anesthesia and Analgesia, vol. 38, pp. 423-428.

Berdowski, J., Beekhuis, F., Zwinderman, A.H., Tijssen, J.G. & Koster, R.W. 2009, "Importance of the first link: description and recognition of an out-of-hospital cardiac arrest in an emergency call", Circulation, vol. 119, no. 15, pp. 2096-2102.

55

Berdowski, J., Berg, R.A., Tijssen, J.G. & Koster, R.W. 2010, "Global incidences of out-of-hospital cardiac arrest and survival rates: Systematic review of 67 prospective studies", Resuscitation, vol. 81, no. 11, pp. 1479-1487.

Berlac, P., Hyldmo, P.K., Kongstad, P., Kurola, J., Nakstad, A.R., Sandberg, M. & Scandinavian Society for Anesthesiology and Intensive Care Medicine 2008, "Pre-hospital airway management: guidelines from a task force from the Scandinavian Society for Anaesthesiology and Intensive Care Medicine", Acta Anaesthesiologica Scandinavica, vol. 52, no. 7, pp. 897-907.

Bernard, S.A., Gray, T.W., Buist, M.D., Jones, B.M., Silvester, W., Gutteridge, G. & Smith, K. 2002, "Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia", The New England journal of medicine, vol. 346, no. 8, pp. 557-563.

Bernhard, M. & Benger, J.R. 2015, "Airway management during cardiopulmonary resuscitation", Current opinion in critical care, vol. 21, no. 3, pp. 183-187.

Bobrow, B.J., Panczyk, M. & Subido, C. 2012, "Dispatch-assisted cardiopulmonary resuscitation: the anchor link in the chain of survival", Current opinion in critical care, vol. 18, no. 3, pp. 228-233.

Bohm, K., Rosenqvist, M., Hollenberg, J., Biber, B., Engerstrom, L. & Svensson, L. 2007, "Dispatcher-assisted telephone-guided cardiopulmonary resuscitation: an underused lifesaving system", European journal of emergency medicine: official journal of the European Society for Emergency Medicine, vol. 14, no. 5, pp. 256-259.

Bossaert, L.L., Perkins, G.D., Askitopoulou, H., Raffay, V.I., Greif, R., Haywood, K.L., Mentzelopoulos, S.D., Nolan, J.P., Van de Voorde, P., Xanthos, T.T. & ethics of resuscitation and end-of-life decisions section Collaborators 2015, "European Resuscitation Council Guidelines for Resuscitation 2015: Section 11. The ethics of resuscitation and end-of-life decisions", Resuscitation, vol. 95, pp. 302-311.

Botker, M.T., Bakke, S.A. & Christensen, E.F. 2009, "A systematic review of controlled studies: do physicians increase survival with prehospital treatment?", Scandinavian journal of trauma, resuscitation and emergency medicine, vol. 17, pp. 12-7241-17-12.

Bottiger, B.W., Bernhard, M., Knapp, J. & Nagele, P. 2016, "Influence of EMS-physician presence on survival after out-of-hospital cardiopulmonary resuscitation: systematic review and meta-analysis", Critical Care (London, England), vol. 20, no. 1, pp. 4-015-1156-6.

Castren, M., Silfvast, T., Rubertsson, S., Niskanen, M., Valsson, F., Wanscher, M., Sunde, K. & Task Force on Scandinavian Therapeutic Hypothermia Guidelines, Clinical Practice Committee Scandinavian Society of Anaesthesiology and Intensive care Medicine 2009, "Scandinavian clinical practice guidelines for therapeutic hypothermia and post-resuscitation care after cardiac arrest", Acta Anaesthesiologica Scandinavica, vol. 53, no. 3, pp. 280-288.

Cave, D.M., Aufderheide, T.P., Beeson, J., Ellison, A., Gregory, A., Hazinski, M.F., Hiratzka, L.F., Lurie, K.G., Morrison, L.J., Mosesso, V.N.,Jr, Nadkarni, V., Potts, J., Samson, R.A., Sayre, M.R., Schexnayder, S.M., American Heart Association Emergency Cardiovascular Care Committee, Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation, Council on Cardiovascular Diseases in the Young, Council on Cardiovascular Nursing & Council on Clinical Cardiology, and Advocacy Coordinating Committee 2011, "Importance and implementation of training

56

in cardiopulmonary resuscitation and automated external defibrillation in schools: a science advisory from the American Heart Association", Circulation, vol. 123, no. 6, pp. 691-706.

Cobb, L.A., Fahrenbruch, C.E., Olsufka, M. & Copass, M.K. 2002, "Changing incidence of out-of-hospital ventricular fibrillation, 1980-2000", JAMA : the journal of the American Medical Association, vol. 288, no. 23, pp. 3008-3013.

Cooper, J.A., Cooper, J.D. & Cooper, J.M. 2006, "Cardiopulmonary resuscitation: history, current practice, and future direction", Circulation, vol. 114, no. 25, pp. 2839-2849.

Culley, L.L., Clark, J.J., Eisenberg, M.S. & Larsen, M.P. 1991, "Dispatcher-assisted telephone CPR: common delays and time standards for delivery", Annals of Emergency Medicine, vol. 20, no. 4, pp. 362-366.

Cummins, R.O., Ornato, J.P., Thies, W.H. & Pepe, P.E. 1991, "Improving survival from sudden cardiac arrest: the "chain of survival" concept. A statement for health professionals from the Advanced Cardiac Life Support Subcommittee and the Emergency Cardiac Care Committee, American Heart Association", Circulation, vol. 83, no. 5, pp. 1832-1847.

Davies, G.E. & Lockey, D.J. 2011, "Thirteen survivors of prehospital thoracotomy for penetrating trauma: a prehospital physician-performed resuscitation procedure that can yield good results", The Journal of trauma, vol. 70, no. 5, pp. E75-8.

Daya, M.R., Schmicker, R.H., Zive, D.M., Rea, T.D., Nichol, G., Buick, J.E., Brooks, S., Christenson, J., MacPhee, R., Craig, A., Rittenberger, J.C., Davis, D.P., May, S., Wigginton, J., Wang, H. & Resuscitation Outcomes Consortium Investigators 2015, "Out-of-hospital cardiac arrest survival improving over time: Results from the Resuscitation Outcomes Consortium (ROC)", Resuscitation, vol. 91, pp. 108-115.

Deakin, C.D., Nolan, J.P., Soar, J., Sunde, K., Koster, R.W., Smith, G.B. & Perkins, G.D. 2010, "European Resuscitation Council Guidelines for Resuscitation 2010 Section 4. Adult advanced life support", Resuscitation, vol. 81, no. 10, pp. 1305-1352.

Diggs, L.A., Yusuf, J.E. & De Leo, G. 2014, "An update on out-of-hospital airway management practices in the United States", Resuscitation, vol. 85, no. 7, pp. 885-892.

Eisenberg, M. 10 Steps for Improving Survival from Sudden Cardiac Arrest, http://www.resuscitationacademy.com/downloads/ebook/TenStepsforImprovingSurvivalFromSuddenCardiacArrest-RA-eBook-PDFFinal-v1_2.pdf edn, Resuscitation Academy.

Eisenberg, M."It takes a system to save a victim", Resuscitation, vol. 84, no. 8, pp. 1013-1014. Eisenberg, M., Bergner, L. & Hallstrom, A."Paramedic programs and out-of-hospital

cardiac arrest: I. Factors associated with successful resuscitation", American Journal of Public Health, vol. 69, no. 1, pp. 30-38.

Eisenberg, M.S., Bergner, L. & Hallstrom, A."Out-of-hospital cardiac arrest: improved survival with paramedic services", Lancet (London, England), vol. 1, no. 8172, pp. 812-815.

Eisenberg, M.S., Bergner, L. & Hearne, T."Out-of-hospital cardiac arrest: a review of major studies and a proposed uniform reporting system", American Journal of Public Health, vol. 70, no. 3, pp. 236-240.

Eisenberg, M.S., Copass, M.K., Hallstrom, A., Cobb, L.A. & Bergner, L."Management of out-of-hospital cardiac arrest. Failure of basic emergency medical technician services", Jama, vol. 243, no. 10, pp. 1049-1051.

57

Finlex 2011, Sosiaali- ja terveysministeriön asetus ensihoitopalvelusta [Homepage of Finlex Data Bank], [Online]. Available: http://www.finlex.fi/fi/laki/alkup/2011/20110340.

Fischer, M., Fischer, N.J. & Schuttler, J. 1997, "One-year survival after out-of-hospital cardiac arrest in Bonn city: outcome report according to the 'Utstein style'", Resuscitation, vol. 33, no. 3, pp. 233-243.

Fothergill, R.T., Watson, L.R., Chamberlain, D., Virdi, G.K., Moore, F.P. & Whitbread, M. 2013, "Increases in survival from out-of-hospital cardiac arrest: a five year study", Resuscitation, vol. 84, no. 8, pp. 1089-1092.

Franek, O., Pokorna, M. & Sukupova, P. 2010, "Pre-hospital cardiac arrest in Prague, Czech Republic--the Utstein-style report", Resuscitation, vol. 81, no. 7, pp. 831-835.

Fredriksson, M., Herlitz, J. & Nichol, G. 2003, "Variation in outcome in studies of out-of-hospital cardiac arrest: a review of studies conforming to the Utstein guidelines", The American Journal of Emergency Medicine, vol. 21, no. 4, pp. 276-281.

Froehler, M.T. & Geocadin, R.G. 2007, "Hypothermia for neuroprotection after cardiac arrest: mechanisms, clinical trials and patient care", Journal of the neurological sciences, vol. 261, no. 1-2, pp. 118-126.

Garza, A.G., Gratton, M.C., Chen, J.J. & Carlson, B. 2003, "The accuracy of predicting cardiac arrest by emergency medical services dispatchers: the calling party effect", Academic emergency medicine : official journal of the Society for Academic Emergency Medicine, vol. 10, no. 9, pp. 955-960.

Hallstrom, A.P., Ornato, J.P., Weisfeldt, M., Travers, A., Christenson, J., McBurnie, M.A., Zalenski, R., Becker, L.B., Schron, E.B., Proschan, M. & Public Access Defibrillation Trial Investigators 2004, "Public-access defibrillation and survival after out-of-hospital cardiac arrest", The New England journal of medicine, vol. 351, no. 7, pp. 637-646.

Harve, H., Tiainen, M., Poutiainen, E., Maunu, M., Kajaste, S., Roine, R.O. & Silfvast, T. 2007, "The functional status and perceived quality of life in long-term survivors of out-of-hospital cardiac arrest", Acta Anaesthesiologica Scandinavica, vol. 51, no. 2, pp. 206-209.

Hasegawa, K., Shigemitsu, K., Hagiwara, Y., Chiba, T., Watase, H., Brown, C.A.,3rd, Brown, D.F. & Japanese Emergency Medicine Research Alliance Investigators 2012, "Association between repeated intubation attempts and adverse events in emergency departments: an analysis of a multicenter prospective observational study", Annals of Emergency Medicine, vol. 60, no. 6, pp. 749-754.e2.

Hasselqvist-Ax, I., Riva, G., Herlitz, J., Rosenqvist, M., Hollenberg, J., Nordberg, P., Ringh, M., Jonsson, M., Axelsson, C., Lindqvist, J., Karlsson, T. & Svensson, L. 2015, "Early cardiopulmonary resuscitation in out-of-hospital cardiac arrest", The New England journal of medicine, vol. 372, no. 24, pp. 2307-2315.

Herlitz, J., Bahr, J., Fischer, M., Kuisma, M., Lexow, K. & Thorgeirsson, G. 1999, "Resuscitation in Europe: a tale of five European regions", Resuscitation, vol. 41, no. 2, pp. 121-131.

Herlitz, J., Engdahl, J., Svensson, L., Angquist, K.A., Young, M. & Holmberg, S. 2005, "Factors associated with an increased chance of survival among patients suffering from an out-of-hospital cardiac arrest in a national perspective in Sweden", American Heart Journal, vol. 149, no. 1, pp. 61-66.

58

Herlitz, J., Svensson, L., Engdahl, J. & Silfverstolpe, J. 2008, "Characteristics and outcome in out-of-hospital cardiac arrest when patients are found in a non-shockable rhythm", Resuscitation, vol. 76, no. 1, pp. 31-36.

Heward, A., Donohoe, R.T. & Whitbread, M. 2004, "Retrospective study into the delivery of telephone cardiopulmonary resuscitation to "999" callers", Emergency medicine journal : EMJ, vol. 21, no. 2, pp. 233-234.

Holmberg, M., Holmberg, S., Herlitz, J. & Swedish Cardiac Arrest Registry 2001, "Factors modifying the effect of bystander cardiopulmonary resuscitation on survival in out-of-hospital cardiac arrest patients in Sweden", European heart journal, vol. 22, no. 6, pp. 511-519.

Holmgren, C., Bergfeldt, L., Edvardsson, N., Karlsson, T., Lindqvist, J., Silfverstolpe, J., Svensson, L. & Herlitz, J. 2010, "Analysis of initial rhythm, witnessed status and delay to treatment among survivors of out-of-hospital cardiac arrest in Sweden", Heart (British Cardiac Society), vol. 96, no. 22, pp. 1826-1830.

Howard, J.M. 2000, "Historical background to accidental death and disability: the neglected disease of modern society", Prehospital emergency care: official journal of the National Association of EMS Physicians and the National Association of State EMS Directors, vol. 4, no. 4, pp. 285-289.

Huang, F.Y., Huang, B.T., Wang, P.J., Zuo, Z.L., Heng, Y., Xia, T.L., Gui, Y.Y., Lv, W.Y., Zhang, C., Liao, Y.B., Liu, W., Chen, M. & Zhu, Y. 2015, "The efficacy and safety of prehospital therapeutic hypothermia in patients with out-of-hospital cardiac arrest: A systematic review and meta-analysis", Resuscitation, vol. 96, pp. 170-179.

Hunter, B.R., O'Donnell, D.P., Allgood, K.L. & Seupaul, R.A. 2014, "No benefit to prehospital initiation of therapeutic hypothermia in out-of-hospital cardiac arrest: a systematic review and meta-analysis", Academic emergency medicine : official journal of the Society for Academic Emergency Medicine, vol. 21, no. 4, pp. 355-364.

ILCOR 2015, ILCOR. Available: http://www.ilcor.org/home/. Intensium, Intensium. Available: http://www.intensium.fi/web/english/. Iwami, T., Nichol, G., Hiraide, A., Hayashi, Y., Nishiuchi, T., Kajino, K., Morita, H.,

Yukioka, H., Ikeuchi, H., Sugimoto, H., Nonogi, H. & Kawamura, T. 2009, "Continuous improvements in "chain of survival" increased survival after out-of-hospital cardiac arrests: a large-scale population-based study", Circulation, vol. 119, no. 5, pp. 728-734.

Jacobs, I., Nadkarni, V., Bahr, J., Berg, R.A., Billi, J.E., Bossaert, L., Cassan, P., Coovadia, A., D'Este, K., Finn, J., Halperin, H., Handley, A., Herlitz, J., Hickey, R., Idris, A., Kloeck, W., Larkin, G.L., Mancini, M.E., Mason, P., Mears, G., Monsieurs, K., Montgomery, W., Morley, P., Nichol, G., Nolan, J., Okada, K., Perlman, J., Shuster, M., Steen, P.A., Sterz, F., Tibballs, J., Timerman, S., Truitt, T., Zideman, D. & International Liason Committee on Resusitation 2004, "Cardiac arrest and cardiopulmonary resuscitation outcome reports: update and simplification of the Utstein templates for resuscitation registries. A statement for healthcare professionals from a task force of the international liaison committee on resuscitation (American Heart Association, European Resuscitation Council, Australian Resuscitation Council, New Zealand Resuscitation Council, Heart and Stroke Foundation of Canada, InterAmerican Heart

59

Foundation, Resuscitation Council of Southern Africa)", Resuscitation, vol. 63, no. 3, pp. 233-249.

Järvinen, A. 1998, Hoitaja vai kuljettaja? : suomalaisen sairaankuljetuksen ja ensihoidon historia, Suomen Ensihoidon Tiedotus, Espoo.

Kajino, K., Iwami, T., Daya, M., Nishiuchi, T., Hayashi, Y., Ikeuchi, H., Tanaka, H., Shimazu, T. & Sugimoto, H. 2008, "Subsequent ventricular fibrillation and survival in out-of-hospital cardiac arrests presenting with PEA or asystole", Resuscitation, vol. 79, no. 1, pp. 34-40.

Kämäräinen, A., Virkkunen, I., Tenhunen, J., Yli-Hankala, A. & Silfvast, T. 2009, "Prehospital therapeutic hypothermia for comatose survivors of cardiac arrest: a randomized controlled trial", Acta Anaesthesiologica Scandinavica, vol. 53, no. 7, pp. 900-907.

Kämäräinen, A., Virkkunen, I., Yli-Hankala, A. & Silfvast, T. 2007, "Presumed futility in paramedic-treated out-of-hospital cardiac arrest: an Utstein style analysis in Tampere, Finland", Resuscitation, vol. 75, no. 2, pp. 235-243.

Käypä Hoito 2016, 02/03/2016-last update, Elvytys Käypä Hoito [Homepage of Duodecim], [Online]. Available: http://www.kaypahoito.fi/web/kh/suositukset/suositus?id=hoi17010 [2016, 02/29].

Kim, F., Nichol, G., Maynard, C., Hallstrom, A., Kudenchuk, P.J., Rea, T., Copass, M.K., Carlbom, D., Deem, S., Longstreth, W.T.,Jr, Olsufka, M. & Cobb, L.A. 2014, "Effect of prehospital induction of mild hypothermia on survival and neurological status among adults with cardiac arrest: a randomized clinical trial", JAMA : the journal of the American Medical Association, vol. 311, no. 1, pp. 45-52.

King County Government Health Services 2015, , Emergency Medical Dispatch (EMD) Program [Homepage of King County], [Online]. Available: www.kingcounty.gov/healthservices/health/ems/community/emdprogram.aspx.

Kirves, H., Skrifvars, M.B., Vahakuopus, M., Ekstrom, K., Martikainen, M. & Castren, M. 2007, "Adherence to resuscitation guidelines during prehospital care of cardiac arrest patients", European journal of emergency medicine : official journal of the European Society for Emergency Medicine, vol. 14, no. 2, pp. 75-81.

KOUWENHOVEN, W.B., JUDE, J.R. & KNICKERBOCKER, G.G. 1960, "Closed-chest cardiac massage", Jama, vol. 173, pp. 1064-1067.

Kuisma, M. & Alaspää, A. 1997, "Out-of-hospital cardiac arrests of non-cardiac origin. Epidemiology and outcome", European heart journal, vol. 18, no. 7, pp. 1122-1128.

Kuisma, M., Boyd, J., Väyrynen, T., Repo, J., Nousila-Wiik, M. & Holmstrom, P. 2005, "Emergency call processing and survival from out-of-hospital ventricular fibrillation", Resuscitation, vol. 67, no. 1, pp. 89-93.

Kuisma, M. & Määttä, T. 1996, "Out-of-hospital cardiac arrests in Helsinki: Utstein style reporting", Heart (British Cardiac Society), vol. 76, no. 1, pp. 18-23.

Kurola, J., Harve, H., Kettunen, T., Laakso, J.P., Gorski, J., Paakkonen, H. & Silfvast, T. 2004, "Airway management in cardiac arrest--comparison of the laryngeal tube, tracheal intubation and bag-valve mask ventilation in emergency medical training", Resuscitation, vol. 61, no. 2, pp. 149-153.

60

Langhelle, A., Lossius, H.M., Silfvast, T., Bjornsson, H.M., Lippert, F.K., Ersson, A. & Soreide, E. 2004, "International EMS Systems: the Nordic countries", Resuscitation, vol. 61, no. 1, pp. 9-21.

Laver, S., Farrow, C., Turner, D. & Nolan, J. 2004, "Mode of death after admission to an intensive care unit following cardiac arrest", Intensive care medicine, vol. 30, no. 11, pp. 2126-2128.

Lerner, E.B., Rea, T.D., Bobrow, B.J., Acker, J.E.,3rd, Berg, R.A., Brooks, S.C., Cone, D.C., Gay, M., Gent, L.M., Mears, G., Nadkarni, V.M., O'Connor, R.E., Potts, J., Sayre, M.R., Swor, R.A., Travers, A.H., American Heart Association Emergency Cardiovascular Care Committee & Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation 2012, "Emergency medical service dispatch cardiopulmonary resuscitation prearrival instructions to improve survival from out-of-hospital cardiac arrest: a scientific statement from the American Heart Association", Circulation, vol. 125, no. 4, pp. 648-655.

Lindner, T.W., Soreide, E., Nilsen, O.B., Torunn, M.W. & Lossius, H.M. 2011, "Good outcome in every fourth resuscitation attempt is achievable-An Utstein template report from the Stavanger region", Resuscitation, vol. 82, no. 12, pp. 1508-1513.

Lund-Kordahl, I., Olasveengen, T.M., Lorem, T., Samdal, M., Wik, L. & Sunde, K. 2010, "Improving outcome after out-of-hospital cardiac arrest by strengthening weak links of the local Chain of Survival; quality of advanced life support and post-resuscitation care", Resuscitation, vol. 81, no. 4, pp. 422-426.

Marwick, C. 1995, "Pathologists request autopsy revival", Jama, vol. 273, no. 24, pp. 1889, 1891.

McMullan, J., Gerecht, R., Bonomo, J., Robb, R., McNally, B., Donnelly, J., Wang, H.E. & CARES Surveillance Group 2014, "Airway management and out-of-hospital cardiac arrest outcome in the CARES registry", Resuscitation, vol. 85, no. 5, pp. 617-622.

McSwain, N.E.,Jr 2005, "Prehospital care from Napoleon to Mars: the surgeon's role", Journal of the American College of Surgeons, vol. 200, no. 4, pp. 487-504.

Meaney, P.A., Bobrow, B.J., Mancini, M.E., Christenson, J., de Caen, A.R., Bhanji, F., Abella, B.S., Kleinman, M.E., Edelson, D.P., Berg, R.A., Aufderheide, T.P., Menon, V., Leary, M. & CPR Quality Summit Investigators, the American Heart Association Emergency Cardiovascular Care Committee, and the Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation 2013, "Cardiopulmonary resuscitation quality: [corrected] improving cardiac resuscitation outcomes both inside and outside the hospital: a consensus statement from the American Heart Association", Circulation, vol. 128, no. 4, pp. 417-435.

Mikkelsen, S., Kruger, A.J., Zwisler, S.T. & Brochner, A.C. 2015, "Outcome following physician supervised prehospital resuscitation: a retrospective study", BMJ open, vol. 5, no. 1, pp. e006167-2014-006167.

Monsieurs, K.G., Nolan, J.P., Bossaert, L.L., Greif, R., Maconochie, I.K., Nikolaou, N.I., Perkins, G.D., Soar, J., Truhlar, A., Wyllie, J., Zideman, D.A. & ERC Guidelines 2015 Writing Group 2015, "European Resuscitation Council Guidelines for Resuscitation 2015: Section 1. Executive summary", Resuscitation, vol. 95, pp. 1-80.

Morrison, L.J., Visentin, L.M., Kiss, A., Theriault, R., Eby, D., Vermeulen, M., Sherbino, J., Verbeek, P.R. & TOR Investigators 2006, "Validation of a rule for termination of

61

resuscitation in out-of-hospital cardiac arrest", The New England journal of medicine, vol. 355, no. 5, pp. 478-487.

Mort, T.C. 2004, "Emergency tracheal intubation: complications associated with repeated laryngoscopic attempts", Anesthesia and Analgesia, vol. 99, no. 2, pp. 607-13, table of contents.

Murray, C.J. & Lopez, A.D. 1997, "Mortality by cause for eight regions of the world: Global Burden of Disease Study", Lancet (London, England), vol. 349, no. 9061, pp. 1269-1276.

Newton, J.N., Briggs, A.D., Murray, C.J., Dicker, D., Foreman, K.J., Wang, H., Naghavi, M., Forouzanfar, M.H., Ohno, S.L., Barber, R.M., Vos, T., Stanaway, J.D., Schmidt, J.C., Hughes, A.J., Fay, D.F., Ecob, R., Gresser, C., McKee, M., Rutter, H., Abubakar, I., Ali, R., Anderson, H.R., Banerjee, A., Bennett, D.A., Bernabe, E., Bhui, K.S., Biryukov, S.M., Bourne, R.R., Brayne, C.E., Bruce, N.G., Brugha, T.S., Burch, M., Capewell, S., Casey, D., Chowdhury, R., Coates, M.M., Cooper, C., Critchley, J.A., Dargan, P.I., Dherani, M.K., Elliott, P., Ezzati, M., Fenton, K.A., Fraser, M.S., Furst, T., Greaves, F., Green, M.A., Gunnell, D.J., Hannigan, B.M., Hay, R.J., Hay, S.I., Hemingway, H., Larson, H.J., Looker, K.J., Lunevicius, R., Lyons, R.A., Marcenes, W., Mason-Jones, A.J., Matthews, F.E., Moller, H., Murdoch, M.E., Newton, C.R., Pearce, N., Piel, F.B., Pope, D., Rahimi, K., Rodriguez, A., Scarborough, P., Schumacher, A.E., Shiue, I., Smeeth, L., Tedstone, A., Valabhji, J., Williams, H.C., Wolfe, C.D., Woolf, A.D. & Davis, A.C. 2015, "Changes in health in England, with analysis by English regions and areas of deprivation, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013", Lancet (London, England), .

Nichol, G., Thomas, E., Callaway, C.W., Hedges, J., Powell, J.L., Aufderheide, T.P., Rea, T., Lowe, R., Brown, T., Dreyer, J., Davis, D., Idris, A., Stiell, I. & Resuscitation Outcomes Consortium Investigators 2008, "Regional variation in out-of-hospital cardiac arrest incidence and outcome", JAMA : the journal of the American Medical Association, vol. 300, no. 12, pp. 1423-1431.

Nielsen, N., Wetterslev, J., Cronberg, T., Erlinge, D., Gasche, Y., Hassager, C., Horn, J., Hovdenes, J., Kjaergaard, J., Kuiper, M., Pellis, T., Stammet, P., Wanscher, M., Wise, M.P., Aneman, A., Al-Subaie, N., Boesgaard, S., Bro-Jeppesen, J., Brunetti, I., Bugge, J.F., Hingston, C.D., Juffermans, N.P., Koopmans, M., Kober, L., Langorgen, J., Lilja, G., Moller, J.E., Rundgren, M., Rylander, C., Smid, O., Werer, C., Winkel, P., Friberg, H. & TTM Trial Investigators 2013, "Targeted temperature management at 33 degrees C versus 36 degrees C after cardiac arrest", The New England journal of medicine, vol. 369, no. 23, pp. 2197-2206.

Nishiyama, C., Brown, S.P., May, S., Iwami, T., Koster, R.W., Beesems, S.G., Kuisma, M., Salo, A., Jacobs, I., Finn, J., Sterz, F., Nurnberger, A., Smith, K., Morrison, L., Olasveengen, T.M., Callaway, C.W., Shin, S.D., Grasner, J.T., Daya, M., Ma, M.H., Herlitz, J., Stromsoe, A., Aufderheide, T.P., Masterson, S., Wang, H., Christenson, J., Stiell, I., Davis, D., Huszti, E. & Nichol, G. 2014, "Apples to apples or apples to oranges? International variation in reporting of process and outcome of care for out-of-hospital cardiac arrest", Resuscitation, vol. 85, no. 11, pp. 1599-1609.

Nolan, J.P., Hazinski, M.F., Aickin, R., Bhanji, F., Billi, J.E., Callaway, C.W., Castren, M., de Caen, A.R., Ferrer, J.M., Finn, J.C., Gent, L.M., Griffin, R.E., Iverson, S., Lang, E., Lim, S.H., Maconochie, I.K., Montgomery, W.H., Morley, P.T., Nadkarni, V.M., Neumar,

62

R.W., Nikolaou, N.I., Perkins, G.D., Perlman, J.M., Singletary, E.M., Soar, J., Travers, A.H., Welsford, M., Wyllie, J. & Zideman, D.A. 2015, "Part 1: Executive summary: 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations", Resuscitation, vol. 95, pp. e1-e31.

Nolan, J.P., Neumar, R.W., Adrie, C., Aibiki, M., Berg, R.A., Bottiger, B.W., Callaway, C., Clark, R.S., Geocadin, R.G., Jauch, E.C., Kern, K.B., Laurent, I., Longstreth, W.T., Merchant, R.M., Morley, P., Morrison, L.J., Nadkarni, V., Peberdy, M.A., Rivers, E.P., Rodriguez-Nunez, A., Sellke, F.W., Spaulding, C., Sunde, K. & Hoek, T.V. 2008, "Post-cardiac arrest syndrome: epidemiology, pathophysiology, treatment, and prognostication. A Scientific Statement from the International Liaison Committee on Resuscitation; the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; the Council on Stroke", Resuscitation, vol. 79, no. 3, pp. 350-379.

Nolan, J.P. & Soar, J. 2008, "Airway techniques and ventilation strategies", Current opinion in critical care, vol. 14, no. 3, pp. 279-286.

Nolan, J.P., Soar, J., Cariou, A., Cronberg, T., Moulaert, V.R., Deakin, C.D., Bottiger, B.W., Friberg, H., Sunde, K. & Sandroni, C. 2015, "European Resuscitation Council and European Society of Intensive Care Medicine Guidelines for Post-resuscitation Care 2015: Section 5 of the European Resuscitation Council Guidelines for Resuscitation 2015", Resuscitation, vol. 95, pp. 202-222.

Nolan, J.P., Soar, J., Zideman, D.A., Biarent, D., Bossaert, L.L., Deakin, C., Koster, R.W., Wyllie, J., Bottiger, B. & ERC Guidelines Writing Group 2010, "European Resuscitation Council Guidelines for Resuscitation 2010 Section 1. Executive summary", Resuscitation, vol. 81, no. 10, pp. 1219-1276.

Nordberg, P., Hollenberg, J., Herlitz, J., Rosenqvist, M. & Svensson, L. 2009, "Aspects on the increase in bystander CPR in Sweden and its association with outcome", Resuscitation, vol. 80, no. 3, pp. 329-333.

Nurmi, J., Pettilä, V., Biber, B., Kuisma, M., Komulainen, R. & Castren, M. 2006, "Effect of protocol compliance to cardiac arrest identification by emergency medical dispatchers", Resuscitation, vol. 70, no. 3, pp. 463-469.

Nyström, S., 2005, Stadin tabis sata vuotta : Helsingin pelastuslaitoksen ensihoito- ja sairaankuljetustoiminta 1905-2005, Helsingin pelastuslaitos, [Helsinki].

Oksanen, T., 2015, Sydänpysähdyksestä elvytetyn potilaan tehohoito, Suomen Ensihoidon Tiedotus, Espoo.

Olasveengen, T.M., Lund-Kordahl, I., Steen, P.A. & Sunde, K. 2009, "Out-of hospital advanced life support with or without a physician: effects on quality of CPR and outcome", Resuscitation, vol. 80, no. 11, pp. 1248-1252.

Ong, M.E., Shin, S.D., De Souza, N.N., Tanaka, H., Nishiuchi, T., Song, K.J., Ko, P.C., Leong, B.S., Khunkhlai, N., Naroo, G.Y., Sarah, A.K., Ng, Y.Y., Li, W.Y., Ma, M.H. & PAROS Clinical Research Network 2015, "Outcomes for out-of-hospital cardiac arrests across 7 countries in Asia: The Pan Asian Resuscitation Outcomes Study (PAROS)", Resuscitation, vol. 96, pp. 100-108.

63

Ong, M.E., Shin, S.D., Tanaka, H., Ma, M.H., Khruekarnchana, P., Hisamuddin, N., Atilla, R., Middleton, P., Kajino, K., Leong, B.S. & Khan, M.N. 2011, "Pan-Asian Resuscitation Outcomes Study (PAROS): rationale, methodology, and implementation", Academic emergency medicine: official journal of the Society for Academic Emergency Medicine, vol. 18, no. 8, pp. 890-897.

Pantridge, J.F. & Geddes, J.S. 1967, "A mobile intensive-care unit in the management of myocardial infarction", Lancet (London, England), vol. 2, no. 7510, pp. 271-273.

Paradis, N.A., Martin, G.B., Goetting, M.G., Rosenberg, J.M., Rivers, E.P., Appleton, T.J. & Nowak, R.M. 1989, "Simultaneous aortic, jugular bulb, and right atrial pressures during cardiopulmonary resuscitation in humans. Insights into mechanisms", Circulation, vol. 80, no. 2, pp. 361-368.

Pell, J.P., Sirel, J.M., Marsden, A.K., Ford, I., Walker, N.L. & Cobbe, S.M. 2003, "Presentation, management, and outcome of out of hospital cardiopulmonary arrest: comparison by underlying aetiology", Heart (British Cardiac Society), vol. 89, no. 8, pp. 839-842.

Perkins, G.D., Jacobs, I.G., Nadkarni, V.M., Berg, R.A., Bhanji, F., Biarent, D., Bossaert, L.L., Brett, S.J., Chamberlain, D., de Caen, A.R., Deakin, C.D., Finn, J.C., Grasner, J.T., Hazinski, M.F., Iwami, T., Koster, R.W., Lim, S.H., Ma, M.H., McNally, B.F., Morley, P.T., Morrison, L.J., Monsieurs, K.G., Montgomery, W., Nichol, G., Okada, K., Ong, M.E., Travers, A.H., Nolan, J.P. & Utstein Collaborators 2015, "Cardiac Arrest and Cardiopulmonary Resuscitation Outcome Reports: Update of the Utstein Resuscitation Registry Templates for Out-of-Hospital Cardiac Arrest: A Statement for Healthcare Professionals From a Task Force of the International Liaison Committee on Resuscitation (American Heart Association, European Resuscitation Council, Australian and New Zealand Council on Resuscitation, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Southern Africa, Resuscitation Council of Asia); and the American Heart Association Emergency Cardiovascular Care Committee and the Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation", Resuscitation, vol. 96, pp. 328-340.

Pozner, C.N., Zane, R., Nelson, S.J. & Levine, M. 2004, "International EMS systems: The United States: past, present, and future", Resuscitation, vol. 60, no. 3, pp. 239-244.

Rea, T.D., Eisenberg, M.S., Culley, L.L. & Becker, L. 2001, "Dispatcher-assisted cardiopulmonary resuscitation and survival in cardiac arrest", Circulation, vol. 104, no. 21, pp. 2513-2516.

Reinikainen, M., Oksanen, T., Leppänen, P., Torppa, T., Niskanen, M., Kurola, J. & Finnish Intensive Care Consortium 2012, "Mortality in out-of-hospital cardiac arrest patients has decreased in the era of therapeutic hypothermia", Acta Anaesthesiologica Scandinavica, vol. 56, no. 1, pp. 110-115.

Remba, S.J., Varon, J., Rivera, A. & Sternbach, G.L. 2010, "Dominique-Jean Larrey: the effects of therapeutic hypothermia and the first ambulance", Resuscitation, vol. 81, no. 3, pp. 268-271.

Ringh, M., Rosenqvist, M., Hollenberg, J., Jonsson, M., Fredman, D., Nordberg, P., Jarnbert-Pettersson, H., Hasselqvist-Ax, I., Riva, G. & Svensson, L. 2015, "Mobile-phone dispatch of laypersons for CPR in out-of-hospital cardiac arrest", The New England journal of medicine, vol. 372, no. 24, pp. 2316-2325.

64

Roudsari, B.S., Nathens, A.B., Arreola-Risa, C., Cameron, P., Civil, I., Grigoriou, G., Gruen, R.L., Koepsell, T.D., Lecky, F.E., Lefering, R.L., Liberman, M., Mock, C.N., Oestern, H.J., Petridou, E., Schildhauer, T.A., Waydhas, C., Zargar, M. & Rivara, F.P. 2007, "Emergency Medical Service (EMS) systems in developed and developing countries", Injury, vol. 38, no. 9, pp. 1001-1013.

Saarinen, S., Kämäräinen, A., Silfvast, T., Yli-Hankala, A. & Virkkunen, I. 2012, "Pulseless electrical activity and successful out-of-hospital resuscitation - long-term survival and quality of life: an observational cohort study", Scandinavian journal of trauma, resuscitation and emergency medicine, vol. 20, pp. 74-7241-20-74.

SAFAR, P., ESCARRAGA, L.A. & CHANG, F. 1959, "Upper airway obstruction in the unconscious patient", Journal of applied physiology, vol. 14, pp. 760-764.

Sainio, M., Hoppu, S., Huhtala, H., Eilevstjonn, J., Olkkola, K.T. & Tenhunen, J. 2015, "Simultaneous beat-to-beat assessment of arterial blood pressure and quality of cardiopulmonary resuscitation in out-of-hospital and in-hospital settings", Resuscitation, vol. 96, pp. 163-169.

Sandroni, C., Cariou, A., Cavallaro, F., Cronberg, T., Friberg, H., Hoedemaekers, C., Horn, J., Nolan, J.P., Rossetti, A.O. & Soar, J. 2014, "Prognostication in comatose survivors of cardiac arrest: an advisory statement from the European Resuscitation Council and the European Society of Intensive Care Medicine", Resuscitation, vol. 85, no. 12, pp. 1779-1789.

Sanghavi, P., Jena, A.B., Newhouse, J.P. & Zaslavsky, A.M. 2015, "Outcomes after out-of-hospital cardiac arrest treated by basic vs advanced life support", JAMA internal medicine, vol. 175, no. 2, pp. 196-204.

Sasson, C., Rogers, M.A., Dahl, J. & Kellermann, A.L. 2010, "Predictors of survival from out-of-hospital cardiac arrest: a systematic review and meta-analysis", Circulation.Cardiovascular quality and outcomes, vol. 3, no. 1, pp. 63-81.

Schalk, R., Byhahn, C., Fausel, F., Egner, A., Oberndorfer, D., Walcher, F. & Latasch, L. 2010, "Out-of-hospital airway management by paramedics and emergency physicians using laryngeal tubes", Resuscitation, vol. 81, no. 3, pp. 323-326.

Silfvast, T. 1991, "Cause of death in unsuccessful prehospital resuscitation", Journal of internal medicine, vol. 229, no. 4, pp. 331-335.

Silfvast, T. 1990, "Prehospital resuscitation in Helsinki, Finland", The American Journal of Emergency Medicine, vol. 8, no. 4, pp. 359-364.

Silfvast, T. 2009, Ensihoito-opas, 4. uud. p. edn, Duodecim, Helsinki. Soar, J. & Nolan, J.P. 2013, "Airway management in cardiopulmonary resuscitation",

Current opinion in critical care, vol. 19, no. 3, pp. 181-187. Soar, J., Nolan, J.P., Bottiger, B.W., Perkins, G.D., Lott, C., Carli, P., Pellis, T., Sandroni, C.,

Skrifvars, M.B., Smith, G.B., Sunde, K., Deakin, C.D. & Adult advanced life support section Collaborators 2015, "European Resuscitation Council Guidelines for Resuscitation 2015: Section 3. Adult advanced life support", Resuscitation, vol. 95, pp. 100-147.

Soar, J., Perkins, G.D., Abbas, G., Alfonzo, A., Barelli, A., Bierens, J.J., Brugger, H., Deakin, C.D., Dunning, J., Georgiou, M., Handley, A.J., Lockey, D.J., Paal, P., Sandroni, C., Thies, K.C., Zideman, D.A. & Nolan, J.P. 2010, "European Resuscitation Council Guidelines for Resuscitation 2010 Section 8. Cardiac arrest in special circumstances:

65

Electrolyte abnormalities, poisoning, drowning, accidental hypothermia, hyperthermia, asthma, anaphylaxis, cardiac surgery, trauma, pregnancy, electrocution", Resuscitation, vol. 81, no. 10, pp. 1400-1433.

Sollid, S.J., Lockey, D., Lossius, H.M. & Pre-hospital advanced airway management expert group 2009, "A consensus-based template for uniform reporting of data from pre-hospital advanced airway management", Scandinavian journal of trauma, resuscitation and emergency medicine, vol. 17, pp. 58-7241-17-58.

Song, K.J., Shin, S.D., Park, C.B., Kim, J.Y., Kim, D.K., Kim, C.H., Ha, S.Y., Eng Hock Ong, M., Bobrow, B.J. & McNally, B. 2013, "Dispatcher-assisted bystander cardiopulmonary resuscitation in a metropolitan city: A before-after population-based study", Resuscitation, vol 85, no. 1, pp.34-41.

Stewart, R.D., Paris, P.M., Winter, P.M., Pelton, G.H. & Cannon, G.M. 1984, "Field endotracheal intubation by paramedical personnel. Success rates and complications", Chest, vol. 85, no. 3, pp. 341-345.

Stiell, I.G., Brown, S.P., Christenson, J., Cheskes, S., Nichol, G., Powell, J., Bigham, B., Morrison, L.J., Larsen, J., Hess, E., Vaillancourt, C., Davis, D.P., Callaway, C.W. & Resuscitation Outcomes Consortium (ROC) Investigators 2012, "What is the role of chest compression depth during out-of-hospital cardiac arrest resuscitation?", Critical Care Medicine, vol. 40, no. 4, pp. 1192-1198.

Stone, B.J., Chantler, P.J. & Baskett, P.J. 1998, "The incidence of regurgitation during cardiopulmonary resuscitation: a comparison between the bag valve mask and laryngeal mask airway", Resuscitation, vol. 38, no. 1, pp. 3-6.

Suffoletto, B.P., Salcido, D.D., Menegazzi, J.J. & National Association of Emergency Medical Services Physicians 2008, "Use of prehospital-induced hypothermia after out-of-hospital cardiac arrest: a survey of the National Association of Emergency Medical Services Physicians", Prehospital emergency care : official journal of the National Association of EMS Physicians and the National Association of State EMS Directors, vol. 12, no. 1, pp. 52-56.

Sunde, G.A., Brattebo, G., Odegarden, T., Kjernlie, D.F., Rodne, E. & Heltne, J.K. 2012, "Laryngeal tube use in out-of-hospital cardiac arrest by paramedics in Norway", Scandinavian journal of trauma, resuscitation and emergency medicine, vol. 20, pp. 84-7241-20-84.

Sunde, K., Pytte, M., Jacobsen, D., Mangschau, A., Jensen, L.P., Smedsrud, C., Draegni, T. & Steen, P.A. 2007, "Implementation of a standardised treatment protocol for post resuscitation care after out-of-hospital cardiac arrest", Resuscitation, vol. 73, no. 1, pp. 29-39.

Suomalaisen Lääkäriseuran Duodecimin, Suomen Elvytysneuvoston, Suomen Anestesiologiyhdistyksen & Suomen Punaisen Ristin Asettama Työryhmä 2011, "Update on current care guidelines: resuscitation", Duodecim; lääketieteellinen aikakauskirja, vol. 127, no. 10, pp. 1061-1063.

Syväoja, S., Castren, M., Mäntylä, P., Rissanen, T.T., Kivelä, A., Uusaro, A. & Jäntti, H. 2014, "The feasibility of recognizing the heart rhythm with an automated external defibrillator from an area the size of a mobile phone", European journal of emergency medicine, vol. 23, no. 2, pp. 102-107.

66

Tanabe, S., Ogawa, T., Akahane, M., Koike, S., Horiguchi, H., Yasunaga, H., Mizoguchi, T., Hatanaka, T., Yokota, H. & Imamura, T. 2013, "Comparison of neurological outcome between tracheal intubation and supraglottic airway device insertion of out-of-hospital cardiac arrest patients: a nationwide, population-based, observational study", The Journal of emergency medicine, vol. 44, no. 2, pp. 389-397.

Tilastokeskus 2014a, Tilastokeskus: Kuolemansyyt 2013. Available: http://www.stat.fi/til/ksyyt/2013/ksyyt_2013_2014-12-30_laa_001_fi.html.

Tilastokeskus 2014b, 21/03/2014-last update, Väestörakenne. Available: http://tilastokeskus.fi/til/vaerak/2013/vaerak_2013_2014-03-21_tau_001_fi.html.

Tilastollinen kuntaryhmitys , Tilastollinen kuntaryhmitys. Available: http://www.stat.fi/meta/luokitukset/kunta/001-2012/luokitusavain_kuntar.html.

Timmermann, A., Russo, S.G. & Hollmann, M.W. 2008, "Paramedic versus emergency physician emergency medical service: role of the anaesthesiologist and the European versus the Anglo-American concept", Current opinion in anaesthesiology, vol. 21, no. 2, pp. 222-227.

Truhlar, A., Deakin, C.D., Soar, J., Khalifa, G.E., Alfonzo, A., Bierens, J.J., Brattebo, G., Brugger, H., Dunning, J., Hunyadi-Anticevic, S., Koster, R.W., Lockey, D.J., Lott, C., Paal, P., Perkins, G.D., Sandroni, C., Thies, K.C., Zideman, D.A., Nolan, J.P. & Cardiac arrest in special circumstances section Collaborators 2015, "European Resuscitation Council Guidelines for Resuscitation 2015: Section 4. Cardiac arrest in special circumstances", Resuscitation, vol. 95, pp. 148-201.

Vaillancourt, C., Charette, M.L., Bohm, K., Dunford, J. & Castren, M. 2011, "In out-of-hospital cardiac arrest patients, does the description of any specific symptoms to the emergency medical dispatcher improve the accuracy of the diagnosis of cardiac arrest: a systematic review of the literature", Resuscitation, vol. 82, no. 12, pp. 1483-1489.

Valenzuela, T.D., Roe, D.J., Nichol, G., Clark, L.L., Spaite, D.W. & Hardman, R.G. 2000, "Outcomes of rapid defibrillation by security officers after cardiac arrest in casinos", The New England journal of medicine, vol. 343, no. 17, pp. 1206-1209.

Väyrynen, T., Boyd, J., Sorsa, M., Määttä, T. & Kuisma, M. 2011, "Long-term changes in the incidence of out-of-hospital ventricular fibrillation", Resuscitation, vol 82, no. 7, pp. 825-9.

Väyrynen, T., Kuisma, M., Määttä, T. & Boyd, J. 2008, "Who survives from out-of-hospital pulseless electrical activity?", Resuscitation, vol. 76, no. 2, pp. 207-213.

Virkkunen, I., Paasio, L., Ryynänen, S., Vuori, A., Sajantila, A., Yli-Hankala, A. & Silfvast, T. 2008, "Pulseless electrical activity and unsuccessful out-of-hospital resuscitation: what is the cause of death?", Resuscitation, vol. 77, no. 2, pp. 207-210.

Warren, S.A., Prince, D.K., Huszti, E., Rea, T.D., Fitzpatrick, A.L., Andrusiek, D.L., Darling, S., Morrison, L.J., Vilke, G.M., Nichol, G. & ROC Investigators 2015, "Volume versus outcome: More emergency medical services personnel on-scene and increased survival after out-of-hospital cardiac arrest", Resuscitation, vol. 94, pp. 40-48.

Weaver, W.D., Cobb, L.A., Hallstrom, A.P., Copass, M.K., Ray, R., Emery, M. & Fahrenbruch, C. 1986, "Considerations for improving survival from out-of-hospital cardiac arrest", Annals of Emergency Medicine, vol. 15, no. 10, pp. 1181-1186.

WHO Scientific Group 1985, "Sudden cardiac death. Report of a WHO Scientific Group.", World Health Organization technical report series, vol. 726, pp. 5-25.

67

Wik, L., Kramer-Johansen, J., Myklebust, H., Sorebo, H., Svensson, L., Fellows, B. & Steen, P.A. 2005, "Quality of cardiopulmonary resuscitation during out-of-hospital cardiac arrest", Jama, vol. 293, no. 3, pp. 299-304.

Wnent, J., Masterson, S., Grasner, J.T., Bottiger, B.W., Herlitz, J., Koster, R.W., Rosell Ortiz, F., Tjelmeland, I., Maurer, H. & Bossaert, L. 2015, "EuReCa ONE - 27 Nations, ONE Europe, ONE Registry: a prospective observational analysis over one month in 27 resuscitation registries in Europe - the EuReCa ONE study protocol", Scandinavian journal of trauma, resuscitation and emergency medicine, vol. 23, pp. 7-015-0093-3.

Wong, K.C. 1983, "Physiology and pharmacology of hypothermia", The Western journal of medicine, vol. 138, no. 2, pp. 227-232.

Zeiner, A., Holzer, M., Sterz, F., Behringer, W., Schorkhuber, W., Mullner, M., Frass, M., Siostrzonek, P., Ratheiser, K., Kaff, A. & Laggner, A.N. 2000, "Mild resuscitative hypothermia to improve neurological outcome after cardiac arrest. A clinical feasibility trial. Hypothermia After Cardiac Arrest (HACA) Study Group", Stroke; a journal of cerebral circulation, vol. 31, no. 1, pp. 86-94.

Zipes, D.P., Camm, A.J., Borggrefe, M., Buxton, A.E., Chaitman, B., Fromer, M., Gregoratos, G., Klein, G., Moss, A.J., Myerburg, R.J., Priori, S.G., Quinones, M.A., Roden, D.M., Silka, M.J., Tracy, C., Priori, S.G., Blanc, J.J., Budaj, A., Camm, A.J., Dean, V., Deckers, J.W., Despres, C., Dickstein, K., Lekakis, J., McGregor, K., Metra, M., Morais, J., Osterspey, A., Tamargo, J.L., Zamorano, J.L., Smith, S.C.,Jr, Jacobs, A.K., Adams, C.D., Antman, E.M., Anderson, J.L., Hunt, S.A., Halperin, J.L., Nishimura, R., Ornato, J.P., Page, R.L., Riegel, B., American College of Cardiology, American Heart Association Task Force, European Society of Cardiology Committee for Practice Guidelines, European Heart Rhythm Association & Heart Rhythm Society 2006, "ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death) developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society", Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology, vol. 8, no. 9, pp. 746-837.

ZOLL, P.M., LINENTHAL, A.J., GIBSON, W., PAUL, M.H. & NORMAN, L.R. 1956, "Termination of ventricular fibrillation in man by externally applied electric countershock", The New England journal of medicine, vol. 254, no. 16, pp. 727-732.

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OUT-OF-HOSPITAL CARDIAC ARREST IN FINLAND

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