Postoperative Outcomes Within/Without an Enhanced Recovery After Surgery Protocol in Colorectal Surgery Across Europe
Conditions: Perioperative Care, Colorectal Surgery, Postoperative Complications
Sponsor: Grupo Español de Rehabilitación Multimodal

 
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Short Title 
EuroPOWER 
Sponsor 
RedGERm (Spain) 
GRACE (France 
Sponsor contact 
Prof José Manuel Ramírez-Rodríguez 
 
Chief Investigator 
Javier Ripollés-Melchor 
Coordinating centre       Infanta Leonor University Hospital 
Madrid, Spain 
   
 
 
 
Chief Investigator Agreement 
The clinical study as detailed within this research protocol (version 1.0, 04/2018), 
or any subsequent amendments will be conducted in accordance with the (Note 
for guidance on Good Clinical Practice, CPMP / ICH / 135/95) defined as an 
international standard of scientific and ethical quality aimed at designing, 
recording and writing reports on clinical trials involving human subjects. These 
standards publicly guarantee the protection of the rights, safety and well-being of 
the subjects participating in the study and ensure the integrity and credibility of 
the data obtained in a clinical trial; in accordance with the World Medical 
Association Declaration of Helsinki (1996) and the current and applicable 
regulatory requirements and any subsequent amendments of the appropriate 
regulations. 
 
Chief Investigator name: Javier Ripollés Melchor, José Manuel Ramírez-
Rodríguez 
 
Chief Investigator affiliation: Hospital Universitario Infanta Leonor, Madrid, 
Spain/ Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain 
 
Signature   

 
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STEERING COMMITTEE 
Ane Abad Motos 
Department of Anaesthesia and Surgical Critical Care 
Infanta Leonor University Hospital 
Madrid, Spain 
ane.abad@salud.madrid.org 
 
César Aldecoa 
Department of Anaesthesia and Surgical Critical Care 
Hospital Universitario Rio Hortega  
Valladolid, Spain 
caldecoaal@saludcastillayleon.es 
José Manuel Ramírez-Rodríguez 
Department of Surgery. Hospital Clínico 
Universitario Lozano Blesa. IACS. Zaragoza. 
Spain 
jramirez@unizar.es 
 
Maurizio Cecconi 
Department Anaesthesia and Intensive Care Units 
IRCCS Istituto Clinico Humanitas 
Milan, Italy 
maurizio.cecconi@hunimed.eu 
Marco Braga     
Department of Surgery, San Raffaele Hospital, 
Vita-Salute University, Milan, Italy, 
braga.marco@hsr.it  
Ib Jammer 
Department of  Anaesthesia and Intensive Care. 
Haukeland University Hospital 
Bergen, Norway 
ib.jammer@ihelse.net  
 
Samir Jaber 
Department of Anesthesiology and Intensive Care 
Centre Hospitalier Universitaire de Montpellier 
Montpellier, France 
s-jaber@chu-montpellier.fr   
Karem Slim 
Service de Chirurgie Digestive 
& Unité de Chirurgie Ambulatoire 
& Président de GRACE (Groupe francophone 
de Réhabilitation Améliorée après Chirurgie) 
CHU Estaing,Clermont-Ferrand, France 
kslim@chu-clermontferrand.fr 
Jean Joris 
Associate Chief, service of Anesthesia and Reanimation 
CHU de Lège, Université de Liège, Belgium 
jean.joris@chu.ulg.ac.be 
 
Rupert Pearse  
Intensive Care Medicine 
Queen Mary University London 
London, UK 
r.pearse@qmul.ac.uk 
Nader Francis 
Depatment of Surgery 
Yeovil District Hospital NHS Foundation Trust 
Nader.Francis@ydh.nhs.uk  
 
Javier Ripollés Melchor 
Department of Anaesthesia and Surgical Critical Care 
Infanta Leonor University Hospital 
Madrid, Spain 
ripo542@gmail.com 
 
Michael Sander 
Department of Anaesthesiology and Intensive Care 
Medicine, UKGM University Hospital Gießen, Justus-
Liebig-University Giessen, Giessen, Germany. 
michael.sander@chiru.med.uni-giessen.de 
Winfried Padber 
Klinik für Allgemein-, Viszeral-, 
Thorax-, Transplanations- und Kinderchirurgie 
Universitätsklinikum Gießen, UKGM GmbH 
Justus-Liebig-Universität Gießen 

 
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 wilfried.padberg@chiru.med.uni-giessen.de 
 
NATIONAL COORDINATOR LIST 
 
 
Austrian National Coordinator 
Ottokar Stundner 
Department of Anesthesiology, Perioperative 
Medicine and Intensive Care Medicine, 
Paracelsus Medical University, Salzburg, Austria 
otto.stundner@gmail.com 
 
 
  
Belgium National Coordinator 
 
Jean Joris 
Associate Chief, service of Anesthesia and 
Reanimation 
CHU de Lège, Université de Liège, Belgium 
jean.joris@chu.ulg.ac.be  
 
   
Czech R.  National Coordinator 
Tomas Vymazal 
Department of Anesthesiology and Intensive Care 
Motol University Hospital. Prague, Czech Republic 
Tomas.Vymazal@fnmotol.cz 
Petr Kocián 
Department of Surgery, 2nd 
Faculty of Medicine, Charles 
University and Motol University 
Hospital 
petr.kocian@fnmotol.cz  
 
 Eslovaquia National 
Coordinator 
Roman Zahorec 
Head of 2nd dpt Anesthesiology and Intensive 
Medicine. 
 Bratislava, Slovaquia 
roman.zahorec@ousa.sk  
 
 
  
France National Coordinator 
Samir Jaber 
Department of Anesthesiology and Intensive Care 
Centre Hospitalier Universitaire de Montpellier, 
Montpellier 
s-jaber@chu-montpellier.fr  
Karem Slim 
Service de Chirurgie Digestive 
& Unité de Chirurgie Ambulatoire 
& Président de GRACE (Groupe 
francophone de Réhabilitation 
Améliorée après Chirurgie) 
kslim@chu-clermontferrand.fr 
 
 
Germany National Coordinator 
Michael Sander 
Department of Anaesthesiology and Intensive 
Care Medicine, UKGM University Hospital 
Gießen, Justus-Liebig-University Giessen, 
Giessen, Germany. 
michael.sander@chiru.med.uni-giessen.de  
Winfried Padber 
Klinik für Allgemein-, Viszeral-, 
Thorax-, Transplanations- und 
Kinderchirurgie 
Universitätsklinikum Gießen, 
UKGM GmbH 
Justus-Liebig-Universität Gießen 
 Winfried.Padberg@chiru.med.uni-
giessen.de  
  
Greece National Coordinator 
Eirini Zarzava 
Department of Anaesthesia and Surgical Critical 
Care 
General Hospital "G.Papanikolaou " 
irzarzava@yahoo.gr  
 
Orestis Ioannidis 
Fourth Surgical Department, 
Medical School, Aristotle 
University of Thessaloniki, 
Thessaloniki, Greece. 
telonakos@hotmail.com  
 
Hungary National Coordinator 
János Fazakas 
Anesthesia and Intensive Care Unit 
Department of Transplantation and Surgery 
Semmelweis University. Budapest. Hungary 
jancsidora@gmail.com  
Daniel Wettstein 
Department of Transpalntion and 
Surgery 
Budapest 
Hungary 
wettsteindaniel@gmail.com  
 
  
Italian  National Coordinator 
Maurizio Cecconi 
Department Anaesthesia and Intensive Care Units 
IRCCS Istituto Clinico Humanitas 
Milan, Italy 
maurizio.cecconi@hunimed.eu  
 
Marco Braga     
Department of Surgery, San 
Raffaele Hospital, Vita-Salute 
University, Milan, Italy, 
braga.marco@hsr.it 

 
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Lhituania National Coordinator 
Jurate Gudaityte 
Anaesthesiology Department 
Lithuanian University of Health Sciences 
Kaunas.  Lithuania 
Jurate.Gudaityte@kaunoklinikos.lt  
Tadas Latkauskas 
Coloproctology Unit 
Department of Surgery 
Medical Academy 
Lithuanian University of Health 
Sciences 
 
Macedonian National 
Coordinator 
Filip Naumovski 
Department of Anesthesia, Reanimation and 
Intensive Care medicine 
University Hospital for TOARILUC 
Macedonia 
 
  
Netherlands  National 
Coordinator 
Markus W. Hollmann,  
Department of Anesthesiology 
Academic Medical Center Amsterdam (AMC), 
Netherlands 
E-mail%3Am.w.hollmann@amc.uva.nl  
 
 
 
Norwegian National 
Coordinator 
Ib Jammer 
Department of  Anaesthesia and Intensive Care 
Haukeland University Hospital, Bergen, Norway 
Department of Clinical Medicine 
University of Bergen, Norway 
ib.jammer@ihelse.net 
 
 
  
Poland National Coordinator 
 
Michał Pędziwiatr 
Centre for Research , Training 
and Innovation in Surgery 
(CERTAIN Surgery) , Krakow , 
Poland 
michal.pedziwiatr@uj.edu.pl  
 
  
Portugal   National Coordinator 
Humberto Machado 
Department of Anesthesiology and Intensive Care 
Centro Hospitalar do Porto, old Hospital Geral de 
Santo António 
hotelmacx@gmail.com  
Marisa Gomes Domingues dos 
Santos Saraiva 
Head of Colorectal Surgery, 
Coordinator of 
Rectal Cancer Reference Center, 
Centro Hospitalar do Porto (Porto 
Hospital Center)  
marisadsantos@gmail.com 
 
Romanian National Coordinator 
Gabriela Droc  
Associate Professor University of Medicine "Carol 
Davila" 
Anesthesia and Intensive Care Department (ATI 
1) 
Fundeni Clinical Institute 
Bucharest, Romania 
gabidroc@gmail.com  
 
  
Spain National Coordinator 
César Aldecoa  
Department of Anaesthesia and Surgical Critical 
Care, Hospital Universitario Río Hortega, 
Valladolid, Spain 
caldecoaal@saludcastillayleon.es  
 
José Manuel ramírez-Rodríguez 
Department of Surgery. Hospital 
Clínico Universitario Lozano 
Blesa. IACS. Zaragoza. Spain 
jramirez@unizar.es  
  
Sweeden National Coordinator 
Michelle Chew 
Department of Anesthesiology and Intensive Care 
Linköping University Hospital, Sweeden 
michelle.chew@liu.se  
 
 
  
 Switzerland  National 
Coordinator 
Samir Jaber 
Department of Anesthesiology and Intensive Care 
Centre Hospitalier Universitaire de Montpellier, 
Montpellier 
s-jaber@chu-montpellier.fr  
Karem Slim 
Service de Chirurgie Digestive 
& Unité de Chirurgie Ambulatoire 
& Président de GRACE (Groupe 
francophone de Réhabilitation 
Améliorée après Chirurgie) 
kslim@chu-clermontferrand.fr 

 
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Turkish  National Coordinator 
Nüzhet Mert ŞENTÜRK 
Department Of Anaesthesiology, Istanbul 
University School Of Medicine, Istanbul, Turkey 
senturkm@istanbul.edu.tr 
 
 
 
Ukranian National Coordinator 
Sergiy Vorotyntsev 
Department of Anaesthesiology and Intensive 
Care, Zaporozhye State Medical University, 
Ukraine 
vorotyntsev_s@ukr.net 
 
  
UK  National Coordinator 
Rupert Pearse 
Intensive Care Medicine 
Queen Mary University London, London, UK 
r.pearse@qmul.ac.uk  
 
Nader Francis 
Depatment of Surgery 
Yeovil District Hospital NHS 
Foundation Trust 
Nader.Francis@ydh.nhs.uk  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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GLOSSARY OF TERMS AND ABBREVIATIONS 
 
AKI 
Acute kidney injury 
ARDS 
Acute respiratory distress syndrome 
ASA 
American Society of Anesthesiologists 
BMI 
Body mass index 
COPD 
Chronic obstructive pulmonary disease 
CRF 
Case Report Form 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EPCO 
European Perioperative Clinical Outcome 
ERAS 
Enhanced recovery after surgery 
ESA 
European Society of Anesthesiology 
ESICM 
European Society of Intensive Care Medicine 
IQR 
Interquartile range 
LOS 
Length of stay 
MAR 
Missing at random 
MCAR 
Missing completely at random 
MINS 
Miocardial injury after non-cardiac surgery 
PE 
Pulmonary embolism 
PONV 
Post-operative nausea and vomiting 
TSC 
Trial Steering Commitee 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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CONTENTS 
1. 
SUMMARY ................................................................................................................. 10 
2. 
INTRODUCTION ....................................................................................................... 12 
3. OBJECTIVE AND PURPOSE OF THE ASSAY ......................................................... 13 
3.1 Specific aims .............................................................................................................. 13 
4. STUDY DESIGN ........................................................................................................... 14 
4.1 Inclusion/Exclusion Criteria ........................................................................................ 14 
4.2. Outcome Measures ................................................................................................... 15 
4.3 Schedule of Assessment ............................................................................................. 16 
4.4 Methods against Bias ................................................................................................. 16 
4.5 Study data ................................................................................................................. 16 
4.5.1 Data collection ........................................................................................................ 17 
4.6 Audit organisation ..................................................................................................... 17 
4.7 End of Study Definition .............................................................................................. 18 
4.8 Ethics and informed consent ...................................................................................... 18 
4.9 Safety considerations ................................................................................................. 19 
4.10 Data handling and record keeping ............................................................................ 19 
4.11 Safety reporting ....................................................................................................... 21 
4.12 Monitoring and audit ............................................................................................... 21 
5. STATISTICAL ANALYSIS ................................................................................................. 21 
5.1 Objectives .................................................................................................................. 21 
5.2 Sample size calculation .............................................................................................. 22 
5.3 Initial descriptive analysis .......................................................................................... 23 
5.3.1 Participants ............................................................................................................. 23 
5.3.2 Baseline characteristics ........................................................................................ 23 
5.3.3 Primary analysis ..................................................................................................... 24 
5.3.4 Secondary analyses .............................................................................................. 26 
5.3.4.1 Postoperative mortality ............................................................................... 26 
5.3.4.2 All complications .......................................................................................... 27 
5.3.4.3 Postoperative hospital stay ........................................................................ 27 
5.3.5 Nation Specific analysis ........................................................................................ 27 
5.3.6 Handling of missing data ...................................................................................... 28 
5.3.6.1 Data missing from database ......................................................................... 28 
5.3.6.2 Sensitivity Analysis ...................................................................................... 28 
6. FUNDING AND INSURANCE ...................................................................................... 28 
7. DISSEMINATION OF RESEARCH FINDINGS .......................................................... 29 
8. EUROPOWER COMMITTEES .................................................................................... 29 
9. REFERENCES .............................................................................................................. 30 
APPENDIX I. DEFINITION OF POSTOPERATIVE COMPLICATIONS ....................... 32 
APPENDIX II. ERAS ITEMS ............................................................................................ 38 
APPENDIX III: FRAILTY. ROCKWOOD SCORE ........................................................... 41 
APPENDIX IV: PREHABILITATION VARIABLES DEFINITIONS FOR EUROPOWER
 
42 
APPENDIX V: CONFIDENTIAL PATIENT LOG SHEET ............................................... 45 

 
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APPENDIX VI: AUTHORSHIP POLICY .......................................................................... 46 
APPENDIX VII: WMA DECLARATION OF HELSINKI - ETHICAL PRINCIPLES FOR 
MEDICAL RESEARCH INVOLVING HUMAN SUBJECTS ........................................... 49 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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1. SUMMARY 
 
Short title 
EuroPOWER  
Methods 
30 days European Multicentre observational cohort 
study of postoperative complications following elective 
colorectal surgery within any compliance of an ERAS 
protocol (including patients with 0 compliance) in a 
participating hospital during the 30-day cohort period 
with a planned overnight stay. 
Research sites 
Hospitals across Europe with an elective colorrectal 
surgical service 
Objective 
To provide detailed data describing post-operative 
complications and associated mortality 
To provide detailed data describing adherence to 
ERAS protocol and its association to morbidity and 
length of stay. 
To provide detailed information on the influence of the 
volume of patients undergoing surgery on each center 
and postoperative complications censured at 30 days 
after surgery. 
Inclusion criteria 
All adult patients (aged ≥18 years) undergoing elective 
colorectal surgery during the 30-day study period. 
Statistical analysis 
Number of patients:  All eligible patients undergoing 
elective colorectal surgery during the study month in 
European participating hospitals.   
Univariate analysis will be used to test factors (patient, 
surgical, and ERAS related) associated with surgical 
complications, length of stay (LOS) and in-hospital 
death. Single and multi-level logistic regression models 
will be constructed to identify factors independently 
associated with these outcomes and to adjust for 
differences 
in 
confounding 
factors. 
A 
stepwise 
approach will be used to enter new terms. A single 
final analysis is planned at the end of the study. 

 
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Summary 
statistics 
with 
post 
hoc 
Bonferroni 
corrections will be used to assess possible dose–
response dependence in percentage of patients with 
postoperative complications and LOS. 
Proposed Start Date 
A 30 day period in 2019 
Proposed End Date 
2019 
Study Duration  
4 months 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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2. INTRODUCTION 
      
    Over 312 million major surgical procedures are performed globally each year(1) and 
despite advances in surgical and anaesthetic care, morbidity after abdominal surgery is 
still high. Colorectal surgery is associated with a high risk of morbidity and mortality in 
comparison to other general surgery subspecialties.  
 
 
Overall mortality rates following colorectal surgery range from 1 to 16.4%(2-4) with 
morbidity rates as high as 35%(2,3,5). The concept of fast-track surgery, also called 
enhanced recovery after surgery (ERAS) or multimodal surgery involves using various 
perioperative strategies to facilitate better conditions for surgery and recovery in an 
effort to achieve faster discharge from hospital and more rapid resumption of normal 
activities after surgery through reducing postoperative stress and improving clinical 
practice by incorporating evidence-based medicine into patient management. ERAS 
protocols have repeatedly been shown to reduce length of stay(6-8) without influencing 
complication or readmission rates(8,9).  
 
 
Although individual components may vary, most of the ERAS programs include 
avoidance of fasting, preoperative optimization of health, preoperative carbohydrate 
loading, avoidance of bowel preparation, goal-directed hemodynamic therapy, 
multimodal analgesia with avoidance of opiates, avoidance/early removal of tubes 
(nasogastric tube, Foley catheter, and drains), support of gastrointestinal function, and 
early convalescence(10).  
 
 
The development and widespread application of ERAS, in combination with 
laparoscopic surgery, represent a paradigm shift in perioperative care. Furthermore, 
the association between laparoscopic approach and ERAS perioperative management 
has recently proposed as the best option for patients undergoing segmental colectomy 
for colon cancer(9).  
 
      Our aim is to conduct a European 30-day cohort study of adults undergoing 
elective colorectal surgery within any compliance of an ERAS protocol (11-12) 
(including patients with 0 compliance) to provide detailed data describing post- 
operative predefined (13) complications and associated mortality.  
 
 

 
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3. OBJECTIVE AND PURPOSE OF THE ASSAY 
 
To assess the incidence of 30-day postoperative predefined complications following 
elective colorectal surgery within any compliance of an ERAS protocol (including 
patients with 0 compliance) in European centres. 
 
3.1 Specific aims 
  
Post-operative complications following major abdominal surgery are common. The 
inclusion of enhanced recovery protocols has shown that by applying a series of 
perioperative measures, postoperative complications can be reduced as well as 
hospital stay. Current knowledge is based on small, prospective single centre studies 
or retrospective databases. However, there are no long-term prospective data 
analysing compliance with these items and their relationship to postoperative 
complications. Compliance with these protocols is very variable across centres and 
countries; the decrease in postoperative complications seems to be directly related to 
the complete compliance of the protocols.  
 
To solve this problem we need concrete data in which these protocols are carried out 
with a high level of compliance and by the analysis of complications in a predefined 
way according to the European recommendations proposed by the ESA(10). 
Therefore, we propose a prospective observational study of one month of duration 
throughout Europe, analysing predefined postoperative complications within 30 days 
after surgery. The feasibility of this study is supported by the wide participation in 
observational studies carried out by the ESA, and by the wide participation in ongoing 
observational studies carried out by our research team. (NCT03012802).  Our 
hypothesis is that the number of patients who develop predefined postoperative 
complications within 30 days of surgery decreases as there is greater compliance with 
the predefined ERAS protocol items. The results of this study will allow to identify, on 
the one hand, the type of patients presenting postoperative complications and, on the 
other hand, to identify those items of the ERAS protocols that are independently 
associated with a reduction in postoperative complications and hospital stay, which will 
allow to focus the perioperative efforts in those items that actually improve the 
postoperative outcomes. 
 

 
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• 
Aim 1 will establish the number of patients developing predefined postoperative 
complications within 30 days of surgery in adult patients undergoing elective 
colorectal surgery with any compliance of an ERAS protocol (including patients with 
0 compliance). This will allow us to determine the actual impact of these protocols.  
 
 
• 
Aim 2 will allow us to know the type of predefined complication presented by the 
patients included in the ERAS protocols and in patients undergoing colorectal 
surgery; This will allow, on the one hand, to have a starting point for future clinical 
trials, and, on the other hand, to focus efforts to avoid these complications. 
 
 
• 
Aim 3 will allow us to identify those perioperative items of ERAS protocols that 
are actually associated with a decrease in postoperative complications. 
   
The proposed study will establish a real view of the number of patients presenting 
postoperative complications that will overcome the limitations of available retrospective 
studies and provide greater insight into the items of the protocols that are associated 
with decreased complications; on the other hand, our hypothesis is that the number of 
patients who develop predefined postoperative complications within 30 days of surgery 
decreases as there is greater compliance with the predefined ERAS protocol items. 
 
4. STUDY DESIGN 
 
4.1 Inclusion/Exclusion Criteria  
 
Inclusion Criteria 
All adult patients (aged ≥18 years) undergoing primary elective colorectal surgery 
and by any approach (Includes surgery with laparoscopic, assisted laparoscopic 
approach or open approach) in a participating hospital during the 30-day cohort 
period with a planned overnight stay. 
 
Exclusion Criteria 
• 
Patients submitted for emergency surgery 
• 
Patients with complex cancer who required resection of organs other than 
bowel.  (i.e. kidney, gastric resection, ovarian) 

 
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• 
Patients treated with endoscopic techniques using the hybrid TaTME 
technique (Transanal Total Mesorectal Excision) 
• 
Bowel transit reconstruction surgery 
• 
Patients who refuse to participate 
 
4.2. Outcome Measures 
 
Primary outcome measure 
All predefined mild-moderate-severe postoperative complications within 30 days of 
surgery (See Appendix I).  
 
Secondary outcome measures 
• In-hospital all-cause mortality (censored at 30 days after surgery) 
• Compliance with ERAS items (within 30 days after surgery). See Appendix II for a 
description of ERAS items.  
• Duration of hospital stay (duration of primary hospital stay after surgery) 
 
 
 
Rationale 
Standards for definitions and use of outcome measures for clinical effectiveness 
research in perioperative medicine were published by the EPCO definitions: a 
statement from the ESA-ESICM joint taskforce on perioperative outcome measures in 
2015(10). We believe it is the best way to evaluate postoperative complications. The 
European Society of Anesthesiology recommends its use. In addition, these definitions 
of complications have already been used in large observational studies. Besides, 
Clavien-Dindo classification of surgical complications will be included.   
 
 
 
 
 
 
 
 

 
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4.3 Schedule of Assessment 
 
 
Pre-
assessment 
clinic 
Day of 
operation 
Post-
op 
day 
1 
Post-
op 
day 
2 
Post-
op 
day 
3 
Day of 
discharge 
4 
weeks 
90 
days 
Baseline 
CRF 
X 
X 
 
 
 
 
 
 
Treatment 
CRF 
 
X 
 
 
 
 
 
 
Discharge 
CRF 
 
 
 
 
 
X 
 
 
30 day 
CRF 
 
 
 
 
 
 
X 
 
90 day 
CRF 
 
 
 
 
 
 
 
X 
 
 
4.4 Methods against Bias 
 
To avoid the confusion generated by the application of the ERAS protocols or their 
particular items, compliance with these will be collected individually, as well as their 
overall compliance in each patient and centre (see Appendix II). 
 
4.5 Study data 
 
The study data collection will comply with the General Data Protection Regulation 
(GDPR) (Regulation (EU) 2016/679). Data will be collected on all eligible patients who 
undergo elective colorectal surgery within any compliance of an ERAS protocol during 
the study month. Only routine clinical data will be included and where this is 
unavailable the domain will be left blank e.g. patients who do not require blood tests. It 
is possible that national groups may supplement their core data set with a very limited 
number of additional variables if these can be accommodated within the case record 
form (CRF) and they comply with regulations applied to this study.  
 
The researchers must complete the CRF provided by the Promoter and send the data 
as indicated at the beginning of the study. The researcher's file must be conserved in a 
safe place, which contains all the relevant documentation of the study. The data of the 
patients collected CRFs during the trial, should be documented anonymously and 

 
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dissociated, linking to a code (patient trial identification number), so that only the 
researcher can associate such data with an identified or identifiable person. 
 
The researcher will keep the original clinical documents of each patient of the study, 
which consist of all medical and demographic information including laboratory data, 
electrocardiograms, etc., and a copy of the signed informed consent form, for at least 
25 years after completion or suspension of the study. 
 
By signing the protocol, the researcher agrees to follow the procedures for document 
preservation. 
 
 
 
4.5.1 Data collection 
 
Complications will be evaluated through the patient's medical records. 
Data will be collected in individual hospitals on a paper CRF for each patient recruited. 
Paper CRFs will be stored within a locked office in each centre. This will include 
identifiable patient data in order to allow follow-up of clinical outcomes. Data will then 
be pseudo-anonymised by generating a unique numeric code and transcribed by local 
investigators onto an internet based electronic CRF (eCRF). Each patient will only be 
identified on the electronic CRF by their numeric code. Thus the co-ordinating study 
team cannot trace data back to an individual patient without contact with the local 
team. A patient list will be used in each centre to match identifier codes in the database 
to individual patients in order to record clinical outcomes and supply any missing data 
points (See Appendix V).  
 
4.6 Audit organisation 
 
EuroPOWER will be led by the study management group who will be responsible for 
study administration, communication between project partners, data collation and 
data management. National coordinators will lead the project in each European 
country and: 
• Identify local coordinators in participating hospitals 
• Assist with translation of study paperwork as required 

 
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• Ensure distribution of study paperwork and other materials 
• Ensure necessary regulatory approvals are in place prior to the start date 
• Ensure good communication with the participating sites in his/her nation 
 
Local coordinators in individual institutions will have the following responsibilities: 
• Provide leadership for the study in their institution 
• Ensure all relevant regulatory approvals are in place for their institution 
• Ensure adequate training of all relevant staff prior to data collection 
• Supervise daily data collection and assist with problem solving 
• Act as guarantor for the integrity and quality of data collected 
• Ensure timely completion of eCRFs by supervising local data entry 
• Communicate with the relevant national co-ordinator  
 
 
4.7 End of Study Definition 
 
The end of the study is defined as the end of the 30-day follow-up for the last patient 
included. Data analysis shall follow this. 
 
4.8 Ethics and informed consent 
 
We anticipate that patient consent will not be required in EuroPOWER on the basis that 
the dataset will only include variables documented as part of routine clinical care and 
that identifiable patient data will not leave the hospital where each individual patient is 
treated. The need for informed consent will depend on each participating country. 
However, the Direction of EuroPOWER will provide informed consent for all 
participating countries.  Unless written informed patient consent is provided, only 
anonymised or coded data will be provided to the EuroPOWER.  
 
Informed consent will be provided through standard writing, in language easily 
understandable to the participant. The patient must write his name and that of the 
informant doctor in his own handwriting and, date and sign the informed consent, as 
well as receive a copy of the signed document. 
 

 
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If the subject cannot read or sign the documents, an oral presentation can be made or 
the signature of the authorized legal representative of the subject can be obtained, 
whenever a witness not involved in the study witnesses it and is mentioned in the same 
document and / or clinical history.  
 
It is expected that different countries have different regulatory requirements regarding 
patient consenting. Where required, the EuroPOWER study protocol will include 
country specific appendices to describe specific procedures regarding the use of 
identifiable patient data and the procedures involved and regulatory approvals 
required. Where individual patient consent is given for participation, it is recognised 
that this may provide the opportunity to link EuroPOWER data to national registry data 
on survival and other healthcare information. Plans for supplementary data collection in 
individual nations will also be detailed in a country specific appendix to this protocol. 
 
 
 
4.9 Safety considerations 
 
There are no safety considerations relating to the EuroPOWER. There is no risk of 
harm to either patients or investigators. 
 
4.10 Data handling and record keeping 
 
All identifiable data collected, processed and stored for the purposes of the project will 
remain confidential at all times and comply with Good Clinical Practice for research 
(GCP) guidelines; the principles of the Data Protection Act 1998 (UK), and The 
General Data Protection Regulation (GDPR) (Regulation (EU) 2016/679).  Data will 
only be handled by the 'direct care team'. This means only the normal doctors and 
nurses etc see the data.  
 
The data collection platform used will be Castor EDC https://www.castoredc.com/.  
Castor EDC complies with all applicable laws and regulations: Good Clinical Practice 
(GCP), 21 CFR Part 11, EU Annex 11, and the European Data Protection Directive. 
 

 
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Each centre will maintain a trial file including a protocol, local investigator delegation 
log, documentation of the relevant regulatory approvals and patient list. EuroPOWER 
data collection sheets will be stored securely in a locked cupboard and handled only by 
clinical staff familiar will handling personal data and with Good Clinical Practice for 
research. Data will be anonymised prior to transfer to the EuroPOWER Audit 
management group except where the patient has given written informed consent to 
allow transfer of identifiable data. Access to the data entry system will be protected by 
username and password, delivered during the registration process for individual local 
investigators. All electronic data transfer between participating centres and the 
coordinating centre will be encrypted using the SSL 3.0 protocol (HTTPS). Desktop 
and laptop security will be maintained through user names and passwords. All local 
investigators will be asked to undergo training in accordance with the Research 
Governance Framework. The study master files will be stored in an approved 
repository for 25 years following the end of the study.  
 
The data collection platform that will be used allows for a security system that: 
• Each user has their own individual account; sharing of passwords is not permitted 
and we enforce strong password choices when creating or changing passwords. 
• Customers log in through SSL/TLS1.2. 
• The authorisation to access data is determined per person per institute and is 
always maintained by the study administrator, thereby excluding the possibility of 
unauthorised access to data by other researchers or institutes. 
• The application code has been written in such a way that the risk of SQL injection 
and related attacks is kept at as low as possible. 
• Continuous Penetration Tests ensure that the application and infrastructure security 
is always state-of-the-art. 
•    The application servers are hosted at True; True has been certified by the Lloyd’s 
Register Quality Assurance (LRQA) according to the international information 
security norm ISO 27001:2013. True provides its services in accordance with the 
Dutch NEN7510 norm for information security in healthcare. 
•     The application servers are located at Overamstel, Amsterdam, The 
Netherlands. 
•     The data center is managed 24/7 and has round-the-clock physical security. 
•     Unauthorized access to the data center is not possible. 
•     The data center is protected by digital surveillance equipment 

 
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•     All data is stored on servers in the Netherlands, and backups are stored at 
another geographical location to ensure maximum security and continuity, in line with 
the EU Data Protection Directive. 
•     Castor EDC runs on fully managed virtual private servers. All servers are 
continually and pro-actively monitored, and in the event of any emerging problems or 
loss of availability action is immediately taken according to our standard operating 
procedures. 
•     Backups are made four times a day and are moved to another geographical 
location on a daily basis. 
•     Intrusion detection systems and other systems continuously check for errors and 
prevent hackers from accessing the system. 
•     The application runs on a protected server with only strictly necessary services 
and ports open to the outside world. 
•     A hardware firewall ensures that no unwanted connections can be made to any 
of the Castor servers. 
 
4.11 Safety reporting 
 
The trial involves negligible risks to patients and investigators. Adverse events will 
not be monitored or reported. 
 
4.12 Monitoring and audit 
 
The Data monitoring and ethics committee will routinely monitor data collection in 
individual hospitals or conduct source data verification. 
 
 
 
5. STATISTICAL ANALYSIS  
 
5.1 Objectives 
 
 
The primary objective of the study is to measure the incidence of predefined 
postoperative complications within 30 days following elective colorectal surgery with 

 
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any compliance of an ERAS protocol (including patients with 0 compliance), including 
complications that occurred before hospital discharge and those that happened after 
discharge and required ambulatory or in-hospital care. The complications that will be 
analysed in this study are: infections, cardiovascular complications and other 
complications such as bleeding and acute kidney injury (please refer to EPCO 
definitions)(13). The secondary objectives of this study include measuring the 30-day 
mortality and LOS associated with these complications and describing the incidence of 
complications for different adherence to the ERAS protocol. EuroPOWER will address 
the need to describe the frequency, severity and nature of complications following 
surgery and the associated short-term mortality. 
 
Primary outcome measure 
All predefined postoperative complications within 30 days after surgery, including 
complications that occurred before hospital discharge and those that happened after 
discharge and required in-hospital care. Complications will be evaluated through the 
patient's medical records.  Postoperative complications are defined according 
standards for definitions and use of outcome measures for clinical effectiveness 
research in perioperative medicine (EPCO)(13). 
 
Secondary outcome measures 
• 
In-hospital all-cause mortality (censored at 30 days following surgery) 
• 
Compliance with ERAS items (within 30 days following surgery). See Appendix II 
for a description of ERAS items. Compliance of an individual component will be 
presented as a binary relationship yes / no. While overall compliance will be 
reported as a percentage: number of interventions fulfilled/total number of 
perioperative interventions evaluated. 
• 
Duration of hospital stay (duration of primary hospital stay after surgery) 
 
 
5.2 Sample size calculation 
 
Our plan is to recruit as many centres as possible on an international basis and ask 
them to include all eligible patients in the study. Only centres including 10 valid patients 
will be included in the data analysis. We do not have a specific sample size and 
statistical models will be adapted to the event rate provided by the sample recruited. 

 
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5.3 Initial descriptive analysis 
 
5.3.1 Participants 
 
All participating hospitals have been asked to keep a log of the data that is collected. 
Data included in the study, missing data and completeness of follow up will be 
illustrated using a STROBE flow diagram. The inclusion criteria are all adult patients 
(age≥18 years) undergoing elective colorectal surgery within any compliance of an 
ERAS protocol (including patients with 0 compliance) in a participating hospital during 
the 30-day study period. Patients undergoing emergency surgery are excluded. Only 
hospitals returning valid data describing 10 or more patients will be included in the 
study. All eligible patients’ data should be uploaded to the online e-CRF. A thorough 
data cleaning procedure will be implemented as follows: 
• 
A robust e-CRF is designed to ensure data entry errors are minimised. The e-CRF 
provides a warning message and asks the user to confirm the value of any data 
entered which lie outside the pre-determined validity range. 
• 
Checking for outliers. If there are extreme outliers, the data points will be excluded 
from the analysis. A secondary analysis will be conducted with all data included to 
gauge the difference in results. 
• 
Duplicates will be checked for and removed using the software package SPSS 
Statistics 22. 
• 
Handling of missing data is outlined in section 6.0. 
 
5.3.2 Baseline characteristics 
 
To give a broader understanding of the patients enrolled in the study, baseline 
characteristics of all the patients will be presented. Numbers (%) or means (SD) and 
medians (IQR) will be given for each group as appropriate. 
 
• 
Demographic: 
Age, 
sex, 
smoking 
status 
and 
American 
Society 
of 
Anesthesiologists (ASA) Physical Status grade, weight, height, preoperative 
transfusion.  

 
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• 
Nutrition related: body mass index, unplanned weight loss> 10% in the past 6 
months, Albumin <3; preoperative (oral) nutritional supplements, preoperative oral 
carbohydrate load (Type and amount). 
• 
Frailty related (see Appendix III) 
• 
Prehabilitation related (see Appendix IV) 
• 
Anaemia related: preoperative anaemia treatment, preoperative iron treatment 
(dose, route).  
• 
Surgery related: Surgical procedure, surgical approach, cancer surgery, conversion 
to open (defined as: the inability to complete the dissection laparoscopically, 
including the vascular ligation, and usually, but not always, requiring an incision 
larger than that required to remove the specimen), duration of surgery, drains, 
stomas, fluids administered (types and amount), intraoperative diuresis, 
anaesthesia (epidural, spinal, wall block) 
• 
Comorbidities: Presence of Hypertension, Diabetes Mellitus, Coronary Artery 
Disease, Heart failure (ejection fraction), Cirrhosis (portal Hypertension), 
Metastasis cancer, Stroke or Transient Ischaemic Attack, COPD/Asthma, Chronic 
kidney disease 
• 
Preoperative blood test results: haemoglobin, albumin, and creatinine. 
• 
Postoperative 
variables: 
haemoglobin, 
creatinine, 
Postoperative 
(oral 
or 
intravenous) nutritional supplements, postoperative transfusion, gum chewing after 
surgery, Intravenous fluids discontinued in the early postoperative period after 
recovery room discharge; time to mobilization, time to oral intake, postoperative 
anaemia treatment, postoperative iron treatment (dose, route), re intervention, 
readmission.  
 
 
 
 
5.3.3 Primary analysis 
 
The primary outcome measure of this study is the percentage of patients with 
predefined postoperative complications within 30 days after surgery. LOS, the number 
of deaths and the overall of complications within 30 days after surgery will be reported. 
The primary effect estimate will be the odds ratio of 30-day, percentage of patients with 

 
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postoperative complications, reported with 95% confidence intervals and p-value. The 
significance level will be set at p<0.05. 
  
A multivariable logistic regression analysis will be used to develop a generic model in 
which all biologically plausible predictor variables will be entered. With the expected 
large sample size, a large number of predictors can be included in the model without 
over fitting, thus predictors will be selected based on clinical suitability and assessment 
of correlated variables. The model will be adjusted for the following covariates: age, 
sex, smoking status, surgical procedure category, ASA grade, presence of co-
morbidities, anaesthetic technique, laparoscopic surgery, cancer surgery, baseline 
blood test results (namely haemoglobin, albumin and creatinine) and those described 
in point 5.3.2. For the purpose of this analysis will be grouped with upper 
gastrointestinal surgery and lower gastrointestinal surgery. All predictors will be 
entered into the model using forced simultaneous entry. To assess the reliability of our 
models, bootstrapping will be undertaken. To account for variations within countries, 
hospitals and patient groups and their influence on outcome, a three-level hierarchical 
generalised linear mixed model will be used. Patients will be entered in the first level, 
hospitals in the second level and countries in the third level. This model will take into 
account the differences between countries and hospitals (e.g. among countries and 
hospitals) in relation to differences within those levels (e.g. among patients within 
hospitals). If this model fails to converge, a two level hierarchical model will be 
constructed with patients in the first level and countries in the second level. The results 
of the regression models will be reported with adjusted odds ratios, 95% confidence 
intervals and associated p-values. Unadjusted odds ratios will also be presented for 
comparison. To characterise the differences across hospitals, median odds ratio will 
also be reported for 30 days complications and mortality. 
 
Residuals will be examined to ensure the assumptions for regression analyses are 
met. Goodness-of- fit for the models will be performed using the Hosmer-Lemeshow 
test. For multivariable regression analysis, multi-collinearity (correlations among 
predictor variables) is expected. Multi-collinearity will be assessed using the Variance 
Inflation Factor (VIF). This measures the extent to which the variance of the model 
coefficient will be inflated (due to correlation of the variable with the other predictor 
variables) if that variable is included in the model. A VIF>10 will be considered to be 
collinear and will be excluded from the analysis. 
 

 
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Overall compliance will be calculated as the average of all pre- and intraoperative 
ERAS adapted elements, as specified in the ERAS society colon and rectal guidelines 
ERAS patients’ guideline compliance will be categorised into quartiles. The sample will 
be divided into four quartiles in dependence on the median and the intercuartilic range 
of the registered ERP compliance. Summary statistics with post hoc Bonferroni 
corrections will be used to assess possible dose–response dependence in a 
percentage of patients with postoperative complications and LOS.  
 
The data set will be analyzed using the percentage of patients with postoperative 
complications and LOS the main and secondary outcome variables. The influence of 
the following factors will be assessed: sex, age, ASA status, BMI, nutrition, frailty and 
prehabilitation variables (when recorded) preoperative haemoglobin, comorbidity, 
including hypertension, diabetes mellitus, coronary arterial disease, chronic obstructive 
pulmonary disease, and chronic renal disease; surgical approach (open, laparoscopic), 
duration of surgery, intraoperative fluid administration; and individual components of 
the ERAS protocol. Univariate analysis will be initially undertaken to assess the 
relationship between each factor and the outcome variables. Comparisons will be 
made using the χ2 test for all categorical variables and the t test and Kruskall-Wallis 
test will be used to evaluate differences between continuous normally and non-
normally distributed variables, respectively. Owing to its non-normal distribution, LOS 
was analyzed by log-normal transformation and independent t tests with back 
exponentiation. Multivariate analysis, using binary logistic regression for development 
of complications and linear regression of log transformed length of LOS, will be then 
performed for all variables in the univariate analysis with a significant or near-
significant difference (P < 0.1). P < 0.05 will be considered statistically significant. 
Differences in LOS between the ERAS compliance groups will be also analyzed using 
Kaplan–Meier curves and log-rank tests as LOS was censored if the patient will 
decease. 
 
5.3.4 Secondary analyses 
 
5.3.4.1 Postoperative mortality 
 
The number and percentage of deaths within 30 days of surgery will be reported for 
each surgical category A logistic regression model with mortality as an outcome will be 
developed. The variable selection procedure will follow that of the primary analysis. 

 
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The results will be reported as odds ratios with 95% confidence intervals and 
associated p-values. 
 
5.3.4.2 All complications 
 
The 30-day in-hospital complications that will be recorded in the e-CRF are: infectious 
complications, cardiovascular complications and other types of complications. Each 
complication will be graded as mild, moderate or severe. The overall incidence of each 
type and severity of complication and associated mortality rate will be reported. 
Association between hospital mortality, complications and mortality after major 
complications will be analysed according to the method previously described by 
Ghaferi and colleagues. For this analysis, hospitals will be ranked anonymously 
according to their risk adjusted mortality rate and divided into five quintiles. For 
hospitals in each quintile, the incidence of overall and major complications and the rate 
of death among patients with major complications will be compared and reported.  
 
5.3.4.3 Postoperative hospital stay  
 
The median hospital length of stay (LOS) following the start of surgery, overall, by 
survival status and by complication status will be reported. Post-operative LOS is the 
duration in days from the date of the end of surgery to the date of discharge from 
hospital.  
 
5.3.5 Nation Specific analysis 
 
Data will be collected all countries. The number of participating sites and total number 
of patients for each country will be reported. Number and percentage of patients 
experiencing mortality and surgical complications within 30 days of surgery will be 
reported for each region. This will help to provide an understanding of post-surgical 
care in different European countries. Post-operative complications and mortality will be 
documented for each region, but will not be published since the multivariable 
regression used in the primary analysis will adjust for country-level differences. 
 

 
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5.3.6 Handling of missing data 
 
5.3.6.1 Data missing from database 
 
A thorough approach will be undertaken by investigators to ensure completeness of 
data collection and data uploading. However, if data are still missing, then the following 
data handling technique will be used. If data are missing completely at random 
(MCAR), then case-wise deletion will be used to exclude the subjects from the 
analysis. Little’s test will be used to investigate the patterns of the missing data.15 It 
tests whether data is MCAR or missing at random (MAR). If ≤5% of data is missing at 
random, then a complete case analysis will be conducted by excluding patients with 
missing data. If ≥5% of data is missing at random, then multiple imputation will be  
used. Multiple   imputation substitutes a predicted value on the basis of other variables 
that are available for each subject. If data for any particular site are completely missing, 
then the site will be excluded from the analysis. 
 
5.3.6.2 Sensitivity Analysis 
 
A sensitivity approach will be taken if some data seem unrealistic. The primary analysis 
will be repeated excluding these patients. If relevant outcome data are missing, such 
as complications, the primary analysis will be repeated once, assuming that all patients 
with missing outcome data had no complications. The analysis will then be repeated 
again with the opposite outcome. This will provide an understanding of how the 
findings may be affected if the data were complete.  
 
 
6. FUNDING AND INSURANCE 
 
The EuroPOWER will be funded by RedGERM (Spain). 
No commercial funding for conducting this study is expected. 
 
 

 
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7. DISSEMINATION OF RESEARCH FINDINGS 
 
Results from this study will be presented in a peer-reviewed journal. Authorship will 
follow international guidelines (See Appendix IV). 
 
8. EUROPOWER COMMITTEES 
 
Trial management group 
Day-to-day trial management will be coordinated by a trial management group 
consisting of the Chief investigator, his/her support staff and members of the 
RedGERM. 
 
Trial Steering Committee 
The trial Steering Committee will oversee the trial and will consist of several 
independent clinicians and trialists, lay representation, co-investigators, and an 
independent Chair. Meetings will be held at regular intervals determined by need but 
not less than once a year. The TSC will take responsibility for: 
• 
Approving the final trial protocol 
• 
Major decisions such as need to change the protocol for any reason 
• 
Monitoring and supervising the progress of the trial 
• 
Reviewing relevant information from other sources 
• 
Considering recommendations from the DMEC  
• 
Informing and advising on all aspects of the trial 
 
Data monitoring and ethics committee 
The Data Monitoring and Ethics Committee (DMEC) is independent of the trial team 
and comprises of two clinicians with experience in undertaking clinical trials and a 
statistician. The committee will agree conduct and remit, which will include the early 
termination process. During the period of recruitment into the trial the DMEC will 
monitor safety data and routinely meet to assess safety analyses. The trial will be 
terminated early if there is evidence of harm in the intervention group or if recruitment 
is futile. The DMEC functions primarily as a check for safety by reviewing adverse 
events. 
 
 

 
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9. REFERENCES 
 
1. Weiser TG, Haynes AB, Molina G, Lipsitz SR, Esquivel MM, Uribe-Leitz T et al 
Estimate of the global volume of surgery in 2012: an assessment supporting 
improved health outcomes. Lancet. 2015, 27;385 Suppl 2:S11 
 
2. Alves A, Panis Y, Mathieu P, Mantion G, Kwiatkowski F, Slim K; Association 
Française de Chirurgie. Postoperative mortality and morbidity in French patients 
undergoing colorectal surgery: results of a prospective multicenter study. Arch 
Surg. 2005;140:278-83 
3. Longo WE, Virgo KS, Johnson FE, Oprian CA, Vernava AM, Wade TP, et al.. 
Risk factors for morbidity and mortality after colectomy for colon cancer. Dis 
Colon Rectum. 2000;43:83-91. 
4. Tevis SE, Carchman EH, Foley EF, Harms BA, Heise CP, Kennedy GD. 
Postoperative Ileus--More than Just Prolonged Length of Stay? J Gastrointest 
Surg. 2015;19:1684-90 
5. de Silva S, Ma C, Proulx MC, Crespin M, Kaplan BS, Hubbard J, et al. 
Postoperative complications and mortality following colectomy for ulcerative 
colitis. Clin Gastroenterol Hepatol. 2011;9:972-80 
6. King PM, Blazeby JM, Ewings P, Franks PJ, Longman RJ, Kendrick AH, et al. 
Randomized clinical trial comparing laparoscopic and open surgery for 
colorectal cancer within an enhanced recovery programme. Br J Surg. 
2006;93:300-8. 
7. Lovely JK, Maxson PM, Jacob AK, Cima RR, Horlocker TT, Hebl JRet añ. 
Case-matched series of enhanced versus standard recovery pathway in 
minimally invasive colorectal surgery. Br J Surg. 2012 ;99:120-6. 
8. Keane C, Savage S, McFarlane K, Seigne R, Robertson G, Eglinton T. 
Enhanced recovery after surgery versus conventional care in colonic and rectal 
surgery. ANZ J Surg. 2012;82:697-703. 
9. Wind J, Hofland J, Preckel B, Hollmann MW, Bossuyt PM, Gouma DJ et al. 
Perioperative strategy in colonic surgery; LAparoscopy and/or FAst track 
multimodal management versus standard care (LAFA trial). BMC Surg. 2006 
29;6:16. 
10. Scott MJ, Baldini G, Fearon KC, Feldheiser A, Feldman LS, Gan TJ. Enhanced 
Recovery After Surgery (ERAS) for gastrointestinal surgery, part 1: 
pathophysiological considerations. Acta Anaesthesiol Scand. 2015;59:1212-31 

 
REDGERM/SPARN EuroPOWER 
Postoperative Outcomes within/without an Enhanced Recovery After Surgery protocol in Colorectal Surgery V1 July 2018  
Page 31 of 56 
 
11. Gustafsson UO, Scott MJ, Schwenk W, Demartines N, Roulin D, Francis N, et 
al. Guidelines for perioperative care in elective colonic surgery: Enhanced 
Recovery After Surgery (ERAS(®)) Society recommendations. World J Surg 
2013;37:259–284. 
12. Alfonsi P, Slim K, Chauvin M, Mariani P, Faucheron JL, Fletcher D, et al. 
French guidelines for enhanced recovery after elective colorectal surgery. J 
Visc Surg 2014;151:65–79. 
13. Jammer I, Wickboldt N, Sander M, Smith A, Schultz MJ, Pelosi P, Leva B, 
Rhodes A, Hoeft A, Walder B, Chew MS, Pearse RM; European Society of 
Anaesthesiology (ESA) and the European Society of Intensive Care Medicine 
(ESICM); European Society of Anaesthesiology; European Society of Intensive 
Care Medicine. Standards for definitions and use of outcome measures for 
clinical 
effectiveness 
research 
in 
perioperative 
medicine: 
European 
Perioperative Clinical Outcome (EPCO) definitions: a statement from the ESA-
ESICM joint taskforce on perioperative outcome measures. Eur J Anaesthesiol. 
2015;32:88-105. 
14. Levett DZH, Jack S, Swart M, Carlisle J, Wilson J, Snowden C, Riley M, 
Danjoux G, Ward SA, Older P, Grocott MPW; Perioperative Exercise Testing 
and Training Society (POETTS). Perioperative cardiopulmonary exercise 
testing (CPET): consensus clinical guidelines on indications, organization, 
conduct, and physiological interpretation. Br J Anaesth. 2018 Mar;120(3):484-
500 
15. Levett DZH, Grocott MPW. Cardiopulmonary exercise testing, prehabilitation, 
and Enhanced Recovery After Surgery (ERAS). Canadian Journal of 
Anaesthesia. 2015;62:131-142. doi:10.1007/s12630-014-0307-6. 
 
 
 
 
 
 
 
 
 
 

 
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APPENDIX I. DEFINITION OF POSTOPERATIVE COMPLICATIONS  
 
Pre-defined 
mild-moderate-severe 
postoperative 
complications. 
This 
includes 
complications that occurred before hospital discharge and those that happened after 
discharge and required ambulatory or in-hospital care. Postoperative complications are 
defined according standards for definitions and use of outcome measures for clinical 
effectiveness research in perioperative medicine (EPCO)(13). 
 
• 
Acute Kidney Injury8 
Severity grading: 
- 
Mild: Serum creatinine Increase of 1.5-1.9 times baseline value within 7 days or 
≥0.3mg/dL (30 µmol/L) within 48 hours. Urine output ≤0.5ml/kg/h for 6-12 hours 
- 
Moderate: Serum creatinine Increase of 2.0-2.9 times baseline value within 7 
days. Urine output ≤0.5 ml/kg/h for 12 hours. 
- 
Severe : Serum creatinine Increase of 3.0 times baseline within 7 days or 
increase in serum creatinine  to  ≥4.0  mg/dL  (≥350 µmol/L) with an acute rise 
of >0.5 mg/dL (>50 µmol/L) or initiation of renal replacement therapy. Urine 
output ≤0.3 ml/kg/h for 24 hours or Anuria for 12 hours. 
 
• 
Acute Respiratory Distress Syndrome (ARDS) 
Respiratory failure, or new or worsening respiratory symptoms, commencing within one 
week of surgery; and a chest radiograph or computed tomography scan which 
demonstrates bilateral opacities not fully explained by effusions, lobar/lung collapse, or 
nodules; and respiratory failure not fully explained by cardiac failure or fluid overload. 
Need objective assessment (e.g. echocardiography) to exclude hydrostatic oedema if 
no risk factor present. 
Severity grading: 
- 
Mild: PaO2:FiO2  between 200 and 300 mmHg with PEEP or CPAP ≥5 cmH2O 
- 
Moderate: PaO2:FiO2  between 100 and 200 mmHg with PEEP ≥5 cmH2O 
- 
Severe: PaO2:FiO2  ≤100 mmHg with PEEP ≥5 cmH2O 
 
• 
Anastomotic leak 
Leak of luminal contents from a surgical connection between two hollow viscera. The 
luminal contents may emerge either through the wound or at the drain site, or they may 
collect near the anastomosis, causing fever, abscess, septicaemia, metabolic 
disturbance and/or multiple-organ failure. The escape of luminal contents from the site 

 
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of the anastomosis into an adjacent localised area, detected by imaging, in the 
absence of clinical symptoms and signs should be recorded as a sub-clinical leak. 
 
Severity grading* (This severity rating is valid for all complications that are marked with 
an asterisk) 
- 
Mild: Results in only temporary harm and would not usually require specific 
clinical treatment. 
- 
Moderate: More serious complication but one which does not usually result in 
permanent harm or functional limitation. Usually requires clinical treatment. 
- 
Severe: Results in significant prolongation of hospital stay and/or permanent 
functional limitation or death. Almost always requires clinical treatment. 
 
• 
Arrhythmia* 
Electrocardiograph (ECG) evidence of cardiac rhythm disturbance. 
 
• 
Cardiac arrest 
The cessation of cardiac mechanical activity, as confirmed by the absence of signs of 
circulation. ECG changes may corroborate the incidence of cardiac arrest. 
Severity grading: None 
 
• 
Pulmonary oedema* 
Evidence of fluid accumulation in the alveoli due to poor cardiac function. 
 
• 
Gastro-intestinal bleeding* 
Unambiguous clinical or endoscopic evidence of blood in the gastro-intestinal tract. 
Upper gastrointestinal bleeding is that originates from the oesophagus, stomach and 
duodenum. Lower gastro-intestinal bleeding originates from the small bowel and colon. 
 
• 
Bloodstream infection* 
An infection which is not related to infection at another site and which meets either of 
the following criteria: 
 
1)Patient has a recognised pathogen cultured from blood cultures which is not 
related to an infection at another site 
2)Patient has at least one of the following signs or symptoms: fever (>38°C), 
chills, or hypotension and at least one of the following: 

 
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a) Common skin contaminant cultured from two or more blood cultures 
drawn on separate occasions 
b) Common skin contaminant cultured from at least one blood culture 
from a patient with an intravascular line, and a physician starts 
antimicrobial therapy 
c) Positive blood antigen test 
 
• 
Myocardial infarction* 
Increase in serum cardiac biomarker values (preferably cardiac troponin) with at least 
one value above the 99th percentile upper reference limit and at least one of the 
following criteria: 
- 
Symptoms of ischaemia 
- 
New or presumed new ST-segment or T-wave ECG changes or new left bundle 
branch block 
- 
Development of pathological Q-waves on ECG 
- 
Radiological or echocardiographic evidence of new loss of viable myocardium 
or new regional wall motion abnormality 
- 
Identification of an intra-coronary thrombus at angiography or autopsy 
• 
Pneumonia* 
Chest radiographs with new or progressive and persistent infiltrates, or consolidation, 
or cavitation, and at least one of the following: 
a)Fever (>38°C) with no other recognized cause 
b)Leucopaenia (<4,000 white blood cells/mm3) or leucocytosis (>12,000 white 
blood cells/mm3) 
c)For adults >70 years old, altered mental status with no other recognised 
cause 
…and at least two of the following: 
- 
New onset of purulent sputum or change in character of sputum, or increased 
respiratory secretions, or increased suctioning requirements 
- 
New onset or worsening cough, or dyspnoea, or tachypnoea 
- 
Râles or bronchial breath sounds 
- 
Worsening gas exchange (hypoxia, increased oxygen or ventilator demand) 
 
• 
Post-operative haemorrhage* 
Blood loss occurring within 72 hours after the end of surgery which would normally 
result in transfusion of blood. Gastro-intestinal bleeding is defined above. 

 
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• 
Pulmonary embolism (PE)* 
A new blood clot or thrombus within the pulmonary arterial system. 
Guidance: Appropriate diagnostic tests include scintigraphy and CT angiography. 
Plasma D- dimer measurement is not recommended as a diagnostic test in the first 
three weeks following surgery. 
 
• 
Stroke* 
Embolic, thrombotic, or haemorrhagic cerebral event with persistent residual motor, 
sensory, or cognitive dysfunction (e.g. hemiplegia, hemiparesis, aphasia, sensory 
deficit, impaired memory). 
 
 
• 
Surgical site infection (superficial)* 
Infection involving only superficial surgical incision which meets the following criteria: 
1)Infection occurs within 30 days after surgery and 
2)Involves only skin and sub-cutaneous tissues of the incision and 
3)The patient has at least one of the following: 
a) Purulent drainage from the superficial incision 
b) Organisms isolated from an aseptically obtained culture of fluid or 
tissue from the superficial incision and at least one of the following signs 
or symptoms of infection: pain or tenderness, localized swelling, 
redness, or heat, or superficial incision is deliberately opened by 
surgeon and is culture positive or not cultured. A culture- negative 
finding does not meet this criterion. 
c) Diagnosis of a incisional surgical site infection by a surgeon or 
attending physician 
 
 
• 
Surgical site infection (deep)* 
An infection which involves both superficial and deep parts of surgical incision and 
meets the following criteria: 
1) Infection occurs within 30 days after surgery if no surgical implant is left in 
place or one year if an implant is in place and 
2) The infection appears to be related to the surgical procedure and involves 
deep soft tissues of the incision (e.g. fascial and muscle layers) and 

 
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3) The patient has at least one of the following: 
a) Purulent drainage from the deep incision but not from the organ/space 
component of the surgical site 
b) A deep incision spontaneously dehisces or is deliberately opened by 
a surgeon and is culture-positive or no cultures were taken whilst the 
patient has at least one of the following signs or symptoms of infection: 
fever (>38°C) or localized pain or tenderness. A culture-negative finding 
does not meet this criterion. 
c) An abscess or other evidence of infection involving the deep incision 
is found on direct examination, during surgery, or by histopathologic or 
radiologic examination 
d) Diagnosis of a deep incisional surgical site infection by a surgeon or 
attending physician 
 
• 
Surgical site infection (organ/space)* 
An infection which involves any part of the body excluding the fascia or muscle layers 
and meets the following criteria: 
1) Infection occurs within 30 days after surgery and 
2) The infection appears to be related to the surgical procedure and involves 
any part of the body, excluding the skin incision, fascia, or muscle layers, that is 
opened or manipulated during the operative procedure and 
3) The patient has at least one of the following: 
a) Purulent drainage from a drain that is placed through a stab wound 
into the organ/space 
b) Organisms isolated from an aseptically obtained culture of fluid or 
tissue in the organ/ space 
c) An abscess or other evidence of infection involving the organ/space 
that is found on direct examination, during reoperation, or by 
histopathologic or radiologic examination 
d) Diagnosis of an organ/space surgical site infection by a surgeon or 
attending physician 
 
• 
Urinary tract infection* 
An infection associated with at least one of the following signs or symptoms which 
should be identified within a 24 hour period: Fever (>38 °C), urgency, frequency, 
dysuria, suprapubic tenderness, costovertebral angle pain or tenderness with no other 

 
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recognised cause and a positive urine culture of ≥105 colony forming units/mL with no 
more than two species of microorganisms 
 
• 
Paralytic ileus* 
Failure to tolerate solid food or defecate for three or more days after surgery. 
 
• 
Delirium 
Delirium may be identified using the Intensive Care Delirium Screening Checklist. 
Patients are first evaluated for an altered level of consciousness. Those with a 
response to mild or moderate stimulation, an exaggerated response to stimulation or 
normal wakefulness are evaluated fully. Patients receive one point for each of the 
following 
criteria: 
inattention, 
disorientation, 
hallucination-delusion-psychosis, 
psychomotor agitation or retardation, inappropriate speech or mood, sleep/wake cycle 
disturbance or symptom fluctuation. Severity grading: Integrated into definition 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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APPENDIX II. ERAS ITEMS  
 
1. Data on prior income, education and counselling(11-12) 
It will be considered a completed item if dedicated advice and preoperative information 
by a surgeon or an anesthetist about the process is given to the patient.  
 
2. Preoperative Optimization 
It will be considered a completed item if the smoker patient stops smoking 4 weeks 
before the intervention; and/or the alcohol abuser patient ceases the consumption of 
alcohol 4 weeks before surgery. In those cases in which patients do not smoke or drink 
alcohol, this component will not be taken into account. 
 
3. Mechanical Bowel Preparation  
It will be considered a completed  if no mechanical bowel preparation is used.  
The administration of oral antibiotics will also be considered in cases where 
mechanical bowel preparation is performed. 
 
4. Preoperative fasting 
It will be considered a completed item if preoperative fasting is limited to two hours for 
clear liquids (water, coffee, juice without pulp); and 6 hours for solids.  
 
5. Preoperative Administration of carbohydrate drinks 
It will be considered a completed component if a carbohydrate drink is administered 
preoperatively (400 cc of 12.5% maltrodextrinae carbohydrate drink 2-3 hours before 
surgery). 
 
6. Avoid sedative drugs before intervention 
It will be considered a completed item if medium or long-acting sedatives are not 
administered. The administration of short-acting or ultra-short-acting sedatives to 
perform loco-regional anaesthesia or spinal or epidural anaesthesia is permitted. The 
following are considered as short-acting or ultrashort-acting sedatives: Lorazepam, 
Midazolam, Methohexital, Dexmedetomidine, Ketamine. 
 
7. Thromboprophylaxis 
It will be considered a completed item if patients receive compression stockings, 
intermittent pneumatic compression stockings, and receive antithrombotic prophylaxis 

 
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with low molecular weight heparin in the postoperative period, which should be 
extended to 28 days after surgery. 
 
 8. Antibiotic prophylaxis 
It will be considered a completed item if routine prophylaxis with intravenous antibiotics 
is given 30 to 60 minutes before starting surgery. Additional doses should be 
administered for prolonged procedures in accordance with the half-life of the drug 
used. The antibiotic is not docketed. 
 
9. Prevention of postoperative nausea and vomiting (PONV) 
It will be considered a completed item if patients receive PONV prophylaxis according 
to their risk based on a multimodal approach.  
 
10. Laparoscopy or minimal incisions 
It will be considered a completed item if laparoscopy is performed. Although this item 
will be regarded as positive in cases where despite open approach, small incisions are 
used. 
 
11. Nasogastric intubation 
It will be considered a completed item if nasogastric intubation is not used, neither 
intraoperatively nor postoperatively. 
 
12. Prevention of intraoperative hypothermia 
It will be considered a completed item if fluid heaters and / or thermal blanket during 
surgery are used. 
 
13. Perioperative management of fluids. 
It will be considered a completed item if restrictive fluid therapy (defined as 
maintenance fluid therapy <2 ml / kg / h) along with goal-directed hemodynamic 
therapy that includes stroke volume, stroke volume variation or cardiac output as a 
goal are used.  
 
14. Drains 
It will be considered a completed item if drains in abdominal cavity are avoided (pelvic 
drain is permitted in rectal surgery with low anastomosis). 
 

 
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15. Urinary catheter 
It will be considered a completed item if the urinary catheterisation is removed 24-48 
hours after surgery. 
 
16. Prevention of Postoperative ileus 
It will be considered a completed item if intraoperative fluid balance is less than 
2000cc. The intraoperative balance will be calculated according to: Total intraoperative 
fluid administered (Crystalloid + colloid + blood products) - (estimated blood loss - 
diuresis - insensitive losses). Insensitive losses will be considered as 1.5 ml / kg / h in 
all cases. This calculation, and the fulfilment of this point, will be carried out based on 
eCRF variables (weight, total intraoperative fluid administered, diuresis, estimated 
blood loss). 
 
17. Postoperative Nutrition 
It will be considered a completed item if patients with preoperative malnutrition (defined 
as weight loss> 10% in 6 months or BMI <18) receive nutritional supplementation. The 
fulfilment of this point, will be carried out based on eCRD variables. In those cases in 
which there were no preoperative nutritional alterations, this component will not be 
evaluated 
 
18. Postoperative glycaemic control 
It will be considered a completed item if that patients receive glycaemic control within 
24 hours from the end of surgery, with a blood glucose target of <180mg / dl. 
 
20. Early mobilization 
It will be considered a completed item when the patient moves at least into an armchair 
in the first 12 hours after surgery  (alone or helped by others). 
 
21. Early Oral Intake 
It will be considered a completed item if there is oral intake in the first 6 hours after 
surgery. 
 
22. Strategies to spare opioid consumption 
It will be considered a completed item if more than two drugs and/or analgesic 
strategies are used to spare opioid consumption. 
 

 
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APPENDIX III: FRAILTY. ROCKWOOD SCORE 
 
 
 
 
 
 
 
 
 
 

 
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APPENDIX IV: PREHABILITATION VARIABLES DEFINITIONS FOR EUROPOWER 
 
Cardiopulmonary exercise testing (CPET)14, 15 
 Provides a global assessment of the integrated response of the pulmonary, cardio- 
vascular, metabolic, and haematological systems. Key is the integration of respired gas 
analysis (O2 and CO2 concentrations) with ventilatory flow measurements, thereby 
enabling calculation of O2 uptake (V_ O2) and CO2 output (V_ CO2), typically on a 
breath-by-breath basis, under conditions of progressively increasing physiological 
stress imposed by a defined profile of external work rate (WR). 
 
 
Cardiopulmonary exercise testing variables registered in EuroPOWER 
 
 
 
 
 
 
 
 
V_ O2peak  
V_ O2peak is a metabolic rate defined as the highest oxygen uptake (V_ O2) attained 
on a rapid incremental test at end-exercise. 
As such, it is reflective of the patient’s ‘best effort’ but it may not reflect what was 
potentially achievable for that patient (i.e. it is not necessarily a physiologically maximal 
end-point). The highest V_ O2 that could be attained by a patient is defined as  the  
maximum V_ O2 
‘the oxygen uptake during an exercise intensity at which actual 
oxygen uptake reaches a maximum beyond which no increase in effort can raise it’ (a 
physiological  end  point). It is a metabolic rate defined as the highest V_ O2 attained 
on a  rapid  incremental  test  at  end-exercise. 
 
Anaerobic Threshold (AT) 
The AT provides an index of submaximal, sustainable exercise capacity, and if present 
cannot be volitionally influenced by the patient. Importantly, it predicts postoperative 
complications and mortality in a wide range of surgical populations with more precision 
than other CPET variables. The AT is a metabolic rate defined as the V_ O2 above 
which arterial [lactate] first begins to increase systematically during incremental 
exercise. 

 
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The AT is a metabolic rate expressed in ml kg1 min1 or ml min1. It is defined as the V_ 
O2 above which arterial (lactate) first begins to increase systematically during 
incremental exercise reflecting increased glycolysis 
 
Functional Walk Tests 
Simple walk tests utilize an activity that patients are familiar with, are inexpensive, 
require little equipment and are easy to administer. They can be used to assess 
functional capacity and provide an alternative when the more comprehensive gold 
standard CPET is not available. The most widely employed and investigated of these 
are the 6-minute walk test (6MWT) and the incremental shuttle walk test (ISWT). 
 
6MWT  
Measures how far subjects can walk along a flat corridor, turning around cones at each 
end, at normal pace, in 6 minutes. Median distances are 500–600 m in healthy 
subjects. Units: metres 
 
Prehabilitation 
A group of interventions, integrated into the clinical pathway before a surgical 
procedure and aimed at both reducing imminent patient risk and promoting lasting 
beneficial effects on perioperative recovery and outcome. 
 
Exercise programmes for surgery 
When prescribing any exercise training programme, consideration should be given to 
the frequency, intensity, time, type, volume and progression (FITT-VP) principles. 
 
• 
Frequency 
Describes how many times per day, per week or per month exercise training takes 
place. For the EuroPOWER study: How many times/week. 
 
• 
Intensity 
Describes, in relative or absolute terms, the effort associated with the exercise. 
“Moderate intensity” is used to describe exercise performed at either 46 to <64 % of 
VO2max, 64 to <76 % HRmax, or 12 to 13 on Borg’s 6 to 20 RPE scale. 
“Vigorous intensity” defines exercise completed at 64 to <91 % of VO2max, 76 to <96 
% of HRmax, or an RPE of 14 to 17. 

 
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“Maximal” exercise performed at ≥91 % of VO2max, ≥96 % of HRmax, or at an RPE 
≥18. In the EuroPOWER study High Intensity trainining is considered as a maximal 
exercise. 
 
• 
Time 
Describes the duration of the exercise session, in terms of hours. 
 
• 
Type 
Refers to the mode of exercise being undertaken (e.g. walking, running, cycling, 
dancing and resistance training). 
 
• 
Volume 
Is the product of the frequency, intensity and time principles of exercise and therefore 
describes the total amount of exercise performed. 
(Self calculated in EuroPOWER CRF) 
 
Anxiety reduction  
Defined as: patients scheduled for a visit with a trained psychologist focusing on 
providing anxiety reduction techniques such as relaxation exercises and breathing 
exercises.  
 
Abbreviations 
 
6MWT: 6-minute walk test  
CPET:   cardiopulmonary exercise test 
ISWT: incremental shuttle walk test 
FITT-VP:  frequency, intensity, time, type, volume and progression 
HIT:   high-intensity interval training 
HRmax:   maximal heart rate 
RPE:  ratings of perceived exertion 
VO2max:  maximal oxygen uptake 
 

 
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APPENDIX V: CONFIDENTIAL PATIENT LOG SHEET 
 
 
 
 
 
CONFIDENTIAL Patient log sheet 
Study 
EuroPOWER 
Local Principal Investigator’s Name : 
Centre / Institution Name : 
Centre Number : 
Patient study 
subject ID 
Patient Name 
Patient Date of 
Discharge 
30 days Follow-up  
 
Planned date 
Actual date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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APPENDIX VI: AUTHORSHIP POLICY 
This publication charter is based on recommendations of the International Committee 
of Medical Editors (http://www.icmje.org/icmje-recommendations.pdf). 
 
1.  Group Authorship  
The principal EuroPOWER paper will be published on behalf of all contributors. The 
author will be listed as ‘The EuroPOWER Study Group’ and a footnote will carry the 
names and affiliations of contributors. Individual contributors will be included in this list 
if they registered as local investigators on the EuroPOWER data entry website and 
have a certificate of participation, or they are a member of the core study management 
team. Where an author takes responsibility for preparing a manuscript on behalf of the 
study group, this would be listed as ‘John Smith and the EuroPOWER Study Group’. 
Where an author takes responsibility for preparing the manuscript and for the content 
of the paper, the study group would be acknowledged and the author listed as ‘John 
Smith for the EuroPOWER Study Group.’ 
 
2. Individual Authorship  
Reports of sub-studies using EuroPOWER data may qualify for individual authorship. A 
contributor claiming authorship should meet the following criteria: 
• 
Substantial contribution to the work: conception or design or data collection or 
  
analysis or data interpretation AND 
• 
Contributed to drafting or revising the manuscript AND 
• 
Approved the final version of the manuscript AND 
• 
Agreement to be accountable for all aspects of the work and agree that all 
questions regarding accuracy and integrity of the data are investigated and 
resolved. 
 
Authors should be listed on any secondary study analysis plans that are submitted for 
review by the steering committee. 
 
3. Acknowledgements 
The trial funders must be acknowledged in all publications. 
 

 
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4. Arbitration  
In the event of a dispute, the steering committee will make a ruling. In the event 
disagreement within the steering committee, the Chief Investigator will be the final 
arbiter.  
 
5. Standard Operating Procedure – publications  
Any investigator wishing to publish any data derived from EuroPOWER, including 
national or local data should follow the following procedure. 
 
6. Secondary study proposal  
The EuroPOWER trial steering committee encourages high quality secondary analyses 
of the trial data and supports the wider principle of data sharing. EuroPOWER 
investigators will be given priority to lead secondary analyses. Participation and 
authorship opportunities will be based on contribution to the primary study. No 
publications are allowed before the primary publication, however, if the primary 
manuscript has not been accepted for publication within twelve months following the 
completion or termination of the clinical trial at all sites, a co-ordinating investigator 
may publish clinical methods and data from their own site. Where necessary, a prior 
written agreement will set out the terms of such collaborations. Investigators should 
submit a secondary study proposal for review by the steering committee. The steering 
committee will consider the scientific validity and the possible effect on the anonymity 
of participating centres prior to approval of secondary study proposals. ‘Cleaned’ data 
from the international dataset will only be released after the statistical analysis plan for 
the secondary study has been approved. Any data sharing requests/proposals must be 
approved by the Data Sharing Committee at the coordinating centre and will require a 
Data Sharing Agreement. Any analysis incorporating EuroPOWER data from one or 
more study sites will be considered a secondary analysis and subject to these rules 
 
7. Confidentiality and anonymity  
The identity of study participants must be protected. Before data is released, patient- 
identifying information will be removed. However, it remains the responsibility of the 
authors to ensure that individual patients cannot be identified as a result of publication. 
  
8. Responsibilities of the lead author 

 
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• Writing the statistical analysis plan and submitting this to the steering committee for 
peer review 
• Co-ordinating the data analysis 
• Co-ordinating the writing of the paper 
• Circulating drafts 
• Ensuring that all authors listed meet the authorship criteria 
• Ensuring quality assurance of the data and analysis 
• Submitting the manuscript for internal peer review by the EuroPOWER trial steering 
committee 
• Informing the EuroPOWER study group when the paper has been submitted to a 
journal and when it has been approved for publication. 
 
9. Internal peer-review  
Publications using data derived from EuroPOWER have the potential to impact the 
reputation of the study. Before any manuscript is submitted to a journal it must be 
reviewed and approved by the trial steering committee or nominated deputies. This 
process will occur in a timely manner. If a manuscript is rejected, constructive feedback 
will be given to help the authors improve the paper. 
 
10. Funders Peer Review  
The trial funders must be afforded the opportunity to review any proposed publication 
in accordance with the relevant contracts. 
 
11. Publications without approval  
The EuroPOWER Study Group is supportive of access to EuroPOWER data by local 
contributors. The EuroPOWER trial steering committee is responsible for protecting the 
reputation of the EuroPOWER Study Group and ensuring that publications derived 
from EuroPOWER are of high quality, accurate and representative of the data 
collected. If data derived from EuroPOWER is published without internal peer-review 
and approval outlined above, the EuroPOWER trial steering committee reserves the 
right to contact the publisher to report a breach of the publication charter. We expect 
that this would result in either the retraction of the paper or refusal to publish the work. 
 

 
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Submission of a secondary study proposal 
Secondary study proposals and data sharing requests should be submitted to the data 
management team  
 
12. References  
Defining the role of authors and contributors. International Committee of Medical 
Journal Editors. 
http://www.icmje.org/recommendations/browse/roles-and-responsibilities/defining- the-
role-of-authors-and-contributors.htm 
 
 
APPENDIX VII: WMA DECLARATION OF HELSINKI - ETHICAL PRINCIPLES FOR 
MEDICAL RESEARCH INVOLVING HUMAN SUBJECTS  
 
Preamble  
1. The World Medical Association (WMA) has developed the Declaration of Helsinki as 
a statement of ethical principles for medical research involving human subjects, 
including research on identifiable human material and data.  
The Declaration is intended to be read as a whole and each of its constituent 
paragraphs should be applied with consideration of all other relevant paragraphs.  
2. Consistent with the mandate of the WMA, the Declaration is addressed primarily to 
physicians. The WMA encourages others who are involved in medical research 
involving human subjects to adopt these principles.  
General Principles  
3. The Declaration of Geneva of the WMA binds the physician with the words, “The 
health of my patient will be my first consideration,” and the International Code of 
Medical Ethics declares that, “A physician shall act in the patient's best interest when 
providing medical care.”  

 
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4. It is the duty of the physician to promote and safeguard the health, well-being and 
rights of patients, including those who are involved in medical research. The 
physician's knowledge and conscience are dedicated to the fulfilment of this duty.  
5. Medical progress is based on research that ultimately must include studies involving 
human subjects.  
6. The primary purpose of medical research involving human subjects is to understand 
the causes, development and effects of diseases and improve preventive, diagnostic 
and therapeutic interventions (methods, procedures and treatments). Even the best 
proven interventions must be evaluated continually through research for their safety, 
effectiveness, efficiency, accessibility and quality.  
7. Medical research is subject to ethical standards that promote and ensure respect for 
all human subjects and protect their health and rights.  
8. While the primary purpose of medical research is to generate new knowledge, this 
goal can never take precedence over the rights and interests of individual research 
subjects.  
9. It is the duty of physicians who are involved in medical research to protect the life, 
health, dignity, integrity, right to self-determination, privacy, and confidentiality of 
personal information of research subjects. The responsibility for the protection of 
research subjects must always rest with the physician or other health care 
professionals and never with the research subjects, even though they have given 
consent.  
10. Physicians must consider the ethical, legal and regulatory norms and standards for 
research involving human subjects in their own countries as well as applicable 
international norms and standards. No national or international ethical, legal or 
regulatory requirement should reduce or eliminate any of the protections for research 
subjects set forth in this Declaration.  
11. Medical research should be conducted in a manner that minimises possible harm 
to the environment.  
12. Medical research involving human subjects must be conducted only by  individuals 
with the appropriate ethics and scientific education, training and individuals with the 

 
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appropriate ethics and scientific education, training and qualifications. Research on 
patients or healthy volunteers requires the supervision of a competent and 
appropriately qualified physician or other health care professional.  
13. Groups that are underrepresented in medical research should be provided 
appropriate access to participation in research.  
14. Physicians who combine medical research with medical care should involve their 
patients in research only to the extent that this is justified by its potential preventive, 
diagnostic or therapeutic value and if the physician has good reason to believe that 
participation in the research study will not adversely affect the health of the patients 
who serve as research subjects.  
15. Appropriate compensation and treatment for subjects who are harmed as a result 
of participating in research must be ensured.  
Risks, Burdens and Benefits  
16. In medical practice and in medical research, most interventions involve risks and 
burdens.  
Medical research involving human subjects may only be conducted if the importance of 
the objective outweighs the risks and burdens to the research subjects.  
17. All medical research involving human subjects must be preceded by careful 
assessment of predictable risks and burdens to the individuals and groups involved in 
the research in comparison with foreseeable benefits to them and to other individuals 
or groups affected by the condition under investigation.  
Measures to minimise the risks must be implemented. The risks must be continuously 
monitored, assessed and documented by the researcher.  
18. Physicians may not be involved in a research study involving human subjects 
unless they are confident that the risks have been adequately assessed and can be 
satisfactorily managed.  
When the risks are found to outweigh the potential benefits or when there is conclusive 
proof of definitive outcomes, physicians must assess whether to continue, modify or 
immediately stop the study.  

 
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Vulnerable Groups and Individuals  
19. Some groups and individuals are particularly vulnerable and may have an 
increased likelihood of being wronged or of incurring additional harm.  
All vulnerable groups and individuals should receive specifically considered protection.  
20. Medical research with a vulnerable group is only justified if the research is 
responsive to the health needs or priorities of this group and the research cannot be 
carried out in a non-vulnerable group. In addition, this group should stand to benefit 
from the knowledge, practices or interventions that result from the research.  
Scientific Requirements and Research Protocols  
21. Medical research involving human subjects must conform to generally accepted 
scientific principles, be based on a thorough knowledge of the scientific literature, other 
relevant sources of information, and adequate laboratory and, as appropriate, animal 
experimentation. The welfare of animals used for research must be respected.  
22. The design and performance of each research study involving human subjects 
must be clearly described and justified in a research protocol.  
The protocol should contain a statement of the ethical considerations involved and 
should indicate how the principles in this Declaration have been addressed. The 
protocol should include information regarding funding, sponsors, institutional 
affiliations, potential conflicts of interest, incentives for subjects and information 
regarding provisions for treating and/or compensating subjects who are harmed as a 
consequence of participation in the research study.  
In clinical trials, the protocol must also describe appropriate arrangements for post-trial 
provisions.  
Research Ethics Committees  
23. The research protocol must be submitted for consideration, comment, guidance 
and approval to the concerned research ethics committee before the study begins. This 
committee must be transparent in its functioning, must be independent of the 
researcher, the sponsor and any other undue influence and must be duly qualified. It 
must take into consideration the laws and regulations of the country or countries in 

 
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which the research is to be performed as well as applicable international norms and 
standards but these must not be allowed to reduce or eliminate any of the  standards 
but these must not be allowed to reduce or eliminate any of the protections for 
research subjects set forth in this Declaration.  
The committee must have the right to monitor ongoing studies. The researcher must 
provide monitoring information to the committee, especially information about any 
serious adverse events. No amendment to the protocol may be made without 
consideration and approval by the committee. After the end of the study, the 
researchers must submit a final report to the committee containing a summary of the 
study’s findings and conclusions.  
Privacy and Confidentiality  
24. Every precaution must be taken to protect the privacy of research subjects and the 
confidentiality of their personal information.  
Informed Consent  
25. Participation by individuals capable of giving informed consent as subjects in 
medical research must be voluntary. Although it may be appropriate to consult family 
members or community leaders, no individual capable of giving informed consent may 
be enrolled in a research study unless he or she freely agrees.  
26. In medical research involving human subjects capable of giving informed consent, 
each potential subject must be adequately informed of the aims, methods, sources of 
funding, any possible conflicts of interest, institutional affiliations of the researcher, the 
anticipated benefits and potential risks of the study and the discomfort it may entail, 
post-study provisions and any other relevant aspects of the study. The potential subject 
must be informed of the right to refuse to participate in the study or to withdraw consent 
to participate at any time without reprisal. Special attention should be given to the 
specific information needs of individual potential subjects as well as to the methods 
used to deliver the information.  
After ensuring that the potential subject has understood the information, the physician 
or another appropriately qualified individual must then seek the potential subject’s 
freely-given informed consent, preferably in writing. If the consent cannot be expressed 
in writing, the non-written consent must be formally documented and witnessed.  

 
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All medical research subjects should be given the option of being informed about the 
general outcome and results of the study.  
27. When seeking informed consent for participation in a research study the physician 
must be particularly cautious if the potential subject is in a dependent relationship with 
the physician or may consent under duress. In such situations the informed consent 
must be sought by an appropriately qualified individual who is completely independent 
of this relationship.  
28. For a potential research subject who is incapable of giving informed consent, the 
physician must seek informed consent from the legally authorised representative. 
These individuals must not be included in a research study that has no likelihood of 
benefit for them unless it is intended to promote the health of the group represented by 
the potential subject, the research cannot instead be performed with persons capable 
of providing informed consent, and the research entails only minimal risk and minimal 
burden.  
29. When a potential research subject who is deemed incapable of giving informed 
consent is able to give assent to decisions about participation in research, the 
physician must seek that assent in addition to the consent of the legally authorised 
representative. The potential subject’s dissent should be respected.  
30. Research involving subjects who are physically or mentally incapable of giving 
consent, for example, unconscious patients, may be done only if the physical or mental 
condition that prevents giving informed consent is a necessary characteristic of the 
research group. In such circumstances the physician must seek informed consent from 
the legally authorised representative. If no such representative is available and if the 
research cannot be delayed, the study may proceed without informed consent provided 
that the specific reasons for involving subjects with a condition that renders them 
unable to give informed consent have been stated in the research protocol and the 
study has been approved by a research ethics committee. Consent to remain in the 
research must be obtained as soon as possible from the subject or a legally authorised 
representative.  
31. The physician must fully inform the patient which aspects of their care are related 
to the research. The refusal of a patient to participate in a study or the patient’s 

 
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decision to withdraw from the study must never adversely affect the patient- physician 
relationship.  
32. For medical research using identifiable human material or data, such as research 
on material or data contained in biobanks or similar repositories, physicians must seek 
informed consent for its collection, storage and/or reuse. There may be exceptional 
situations where consent would be impossible or impracticable to obtain for such 
research. In such situations the research may be done only after for such research. In 
such situations the research may be done only after consideration and approval of a 
research ethics committee.  
Use of Placebo  
33. The benefits, risks, burdens and effectiveness of a new intervention must be tested 
against those of the best proven intervention(s), except in the following circumstances:  
Where no proven intervention exists, the use of placebo, or no intervention, is 
acceptable; or  
Where for compelling and scientifically sound methodological reasons the use of any 
intervention less effective than the best proven one, the use of placebo, or no 
intervention is necessary to determine the efficacy or safety of an intervention and the 
patients who receive any intervention less effective than the best proven one, placebo, 
or no intervention will not be subject to additional risks of serious or irreversible harm 
as a result of not receiving the best proven intervention.  
Extreme care must be taken to avoid abuse of this option.  
Post-Trial Provisions  
34. In advance of a clinical trial, sponsors, researchers and host country governments 
should make provisions for post-trial access for all participants who still need an 
intervention identified as beneficial in the trial. This information must also be disclosed 
to participants during the informed consent process.  
Research Registration and Publication and Dissemination of Results  
35. Every research study involving human subjects must be registered in a publicly 
accessible database before recruitment of the first subject.  

 
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36. Researchers, authors, sponsors, editors and publishers all have ethical obligations 
with regard to the publication and dissemination of the results of research. 
Researchers have a duty to make publicly available the results of their research on 
human subjects and are accountable for the completeness and accuracy of their 
reports. All parties should adhere to accepted guidelines for ethical reporting. Negative 
and inconclusive as well as positive results must be published or otherwise made  
publicly available. Sources of funding, institutional affiliations and conflicts of interest 
publicly available. Sources of funding, institutional affiliations and conflicts of interest 
must be declared in the publication. Reports of research not in accordance with the 
principles of this Declaration should not be accepted for publication.  
Unproven Interventions in Clinical Practice  
37. In the treatment of an individual patient, where proven interventions do not exist or 
other known interventions have been ineffective, the physician, after seeking expert 
advice, with informed consent from the patient or a legally authorised representative, 
may use an unproven intervention if in the physician's judgement it offers hope of 
saving life, re-establishing health or alleviating suffering. This intervention should 
subsequently be made the object of research, designed to evaluate its safety and 
efficacy. In all cases, new information must be recorded and, where appropriate, made 
publicly available.