POPULAR: POstanaesthesia PULmonary complications After use of muscle Relaxants in Europe

Transcription

1 POPULAR: POstanaesthesia PULmonary complications After use of muscle Relaxants in Europe INDEX I. General 1 II. Study Protocol 2 III. Ethical Approval 3 IV. Distribution 3 V. Investigator File 4 VI. In- and exclusion criteria 4 VII. Informed Consent 5 VIII. Data collection 5 IX. CRF specific questions 6 X. Electronic CRF 10 XI. Pre-Study survey 11 I. General: A European prospective multicentre observational study Frequently Asked Questions v4.0 (5-Dec-2014) 1. When is the period of recruitment planned? What is the approximate length of inclusion period? The recruitment period is from July 2014 to March The exact length of the inclusion period is two weeks. Each centre can choose its own 2 inclusion weeks within the time window of 9 months. Therefore, the last possible inclusion weeks will be from March 17 th, 2015 to March 31 st, Please inform the Study Management as soon as the definite inclusion weeks are decided. 2. Are there funds for the investigators to facilitate research? There is no budget for any payment to the Ethics Committee, translations, or print out of CRFs etc. The POPULAR study is an investigator initiated study. The ESA CTN grant provided to POPULAR study is solely used for building and supporting the electronic CRF (ecrf), statistical support and data cleaning. It is not possible to provide individual funding to participating centres. 3. What is the authorship policy in the POPULAR study? In the study publication, national coordinators, local coordinators and collaborators will be listed in the POPULAR study group list and will be assigned to the paper through PubMed. The number of authors listed per centre will be dependent of the number of patients included and followedup in the centre. Each participating centre will have at least one author listed in the collaborators list. For every set of 25 included patients, an additional collaborating authorship is offered. 4. Who is the Sponsor of the study? The study Sponsor is the Funder: the European Society of Anaesthesiology. 5. Do I need to be an ESA member to join the study? POPULAR is an ESA CTN study. Therefore, each centre must provide at least one (preferably more) colleague with an ESA membership. It is therefore required that either you, the Head of your department or a colleague is or will become an active ESA Member. 6. Is there a Certificate of indemnity provided by the sponsor? ESA does not provide a certificate of indemnity that covers research. This is an observational study where all study procedures are routine practice of each participating hospital. page 1 of 11

2 7. Who will get a participation certificate? In case your hospital collaborators will not be eligible for inclusion in the final collaborators list in the study publication, ESA and the study Steering Committee will provide them with an individual and personalised "ESA Clinical Trial Network POPULAR Study Participation Certificate" signed by the Chair of the ESA Research Committee and by the Chief Investigator of the Study. 8. Are there monitoring arrangements? This observational study will NOT be monitored by CRA/monitors onsite, etc. The data of the CRF will be encoded under the responsibility of the site local coordinator. The dataset will be checked and monitored by the Chief Investigator and the ESA Data Management. At the data cleaning stage queries will be sent from Data Management to the local Investigators for clarification if needed. 9. Do we have access to all collected study data? Yes, after the publication of the primary analysis of the study data, all participating centres will be granted access to the complete data-pool for secondary analysis. On request, the pooled dataset will be available for all members of the POPULAR collaboration for secondary analysis, after judgment and approval of scientific quality and validity of the proposed analysis by the Steering Committee. Before any submission of any version of a manuscript related to the POPULAR dataset, it must be approved by the Steering Committee. National data pool: Local Investigators can gain access to the national dataset, in consultation with the national coordinator. Local data pool: Local Investigators can gain direct access to their local dataset, for e.g., internal evaluation. The Local Coordinator can request this directly from the Data Management. After primary analysis,the ESA and the POPULAR Steering Committee will prepare a publication that will be available for the greater public.if you wish to present your own centre's data on a congress, there is no problem to ask for your local data pool, as described above. Basically, it is the same procedure for the national data, but, of course, there needs to be a consent about it between all participating centres and the national coordinator of one country. 10. What to do if our centre has many surgical procedures per week Every centre is offered the option to reduce their patient cohort by a specific procedure (see Study Protocol, 4.3 Type/Design of the Trial, p.11 and FAQ Question 13, Institutions with more than 50 patients per week.) 11. What does "Patient born outside the predetermined month(s) allocated for the specific study centre" actually mean? According to the workload of the post-anaesthesia visit and the medical chart round after discharge from the hospital/on Day 28, we assume that many hospitals will decide to reduce their recruitment rate (i.e. not 100% of the patients in the 2-week recruitment-period). To have a random selection of observed patients, we decided for a birthdate related method. The respective centre tells the ESA study organisation team the rate of observation it will be able to manage, e.g. 33% of all their patients. The study organisation team then determines the number and names of recruitment months. The hospital must then include all patients, who are born in these defined months. An example: Hospital will recruit 33% and tells us this rate. The ESA study organisations team randomly selects 33% of 12 months = 4 months, e.g. April, August, September, December and informs the centre about this decision. The centre includes all patients, who are operated in the 2-weeks period and are born in the predetermined months April, August, September, and December. See also detailed instructions in the website document section of POPULAR 12. In our hospital during the nightshifts, the ICU is a kind of PACU. A patient is there for 1-2hour (monitoring BP, HR, ECG, Sat.) and then goes back to ward. Should we fill it in CRF 02 or should skip to CRF 03? Use the CRF02 for the PACU treatment also in cases, for which the ICU serves as PACU. page 2 of 11

3 II. Study Protocol: 13. What is the meaning of the last paragraph of 4.2 Data Collection: Each centre will use (See study protocol, p11/28, 4.2 Data Collection) At the end of each centre's data collection, an "End of study Reporting Form" (Appendix 5) will be sent out. There you will be asked to give the absolute number of surgical procedures (screening population), the total number of included patients (study population) and the number of patients excluded to exclusion criteria (especially the birth month selection). The screening tracking form shall help you to get that information at your site. 14. You have designed a new form to report all patients not recruited. Are these patients who were eligible but not included or patients who didn t meet the inclusion requirements? See in Appendix 5 the 4 categories.eg. 1-Screened patients=total # of all patients who had an operation/ intervention of any kind of anaesthesia procedure during the 2-week time period (also patients not meeting the protocol inclusion criteria) III. Ethical Approval: 15. Do I need to get ethical approval for the study? It depends on the judgment of your local IRB (Institutional Review Board). If you need ethical approval, then you must obtain it before the study weeks. If your local IRB judges that you do not need ethical approval for the study, then a document from the IRB stating their decision is necessary. It is mandatory to submit the Study Protocol to your IRB for ethical judgment. Please discuss with your national coordinator (N.C.) before you apply for ethical approval locally. Some countries (like UK) have a single process valid for all centres. The N.C. will coordinate and ensure that all local necessary ethical and regulatory approvals are obtained before start of patient inclusion. If ethical judgment is organised nationally in your country, then the N.C. will coordinate this. The document of Ethical Judgment and/or Ethical Approval should be scanned and ed to the ESA Secretariat, together with the Approval Document Cover Sheet at popular@esahq.org at least 1 week before recruitment week in order to get your log-in to the ecrf. IV. Distribution: 16. Should each centre collect a minimum number of patients? All centres are expected to include and follow-up at least 10 patients. Preferably we aim for > 100 patients per centre, to be able to realise the calculated sample size. 17. In institutions with more than 50 patients per week, it is possible to make a selection through randomisation by month of birth. What is the maximum number of patients each centre can recruit? Somewhere in the text, a number between 10 to 200 is referred, but this is a real limit or is it only an expectation from previous experiences with other studies? For instance, if my hospital does 250 surgical interventions per week, we try to recruit all, or should we advance immediately to random selection? And if so, what should be my goal of total number of patients, so that I may choose the adequate recruitment rate? Each centre can recruit as many patients as they want during the 2 weeks recruitment period. A possible limitation for a high recruitment rate could be the postoperative workload. Accordingly, the decision must be done beforehand if a centre is able to handle the postoperative data collection in the targeted number of patients. Please refer to example above (see FAQ Question 13, Institutions with more than 50 patients per week ). page 3 of 11

4 18. Multiple operations: How must we deal with patients who are operated on multiple times? The key is to decide whether the reoperation was expected (exclusion) or unexpected (carry on). Here is a FAQ that hopefully clarifies the issue. 3 scenarios: 1. If a patient is already scheduled for more operations within 7 days after inclusion, he has to be excluded. 2. If a patient is re-operated during the hospital stay (but not within 7 days after the inclusion operation ) or unexpectedly within 7 days after inclusion, the study is not stopped and follow-up has to be continued until discharge/day 28. The date of the first reoperation and the total number of reoperations has to be recorded (CRF04). If a complication appears after the second operation, it is also recorded in the CRF (in fact, the complication is also related to the first operation). 3. If the patient leaves the hospital and is re-operated later (one or several times), follow-up is finished on the day of the first discharge. 19. We have encountered a subject who had a cystoscopy and TURP under general anaesthetic, but had a bleed in Recovery, having to return straight to OR to surgically obtain haemostasis. Is this subject eligible? If this subject was eligible, what would be the time of admission to Recovery? 1st time (12:30) or second time (13:10)? Yes, this subject is still eligible, as the reoperation was unexpected. Of course, the timing is very tight, but anyhow, in this case, I would recommend to take the time of the first admission to the recovery room. 20. Should I include a patient that underwent on-pump cardiac surgery a few days ago (before start of inclusion weeks), but now undergoes a re-operation due to a complication? If the first surgery took place more than 7 days ago, you can include the patient. If he then needs a third unexpected operation within 7 days, he will stay in the study. If you already know that he will be operated again within 7 days, he has to be excluded. (see FAQ question #17) V. Investigator File: VI. 21. What is the Task Delegation Form? In the Task Delegation Form, you should log all investigators participating in the POPULAR study and specify the different tasks they perform. The Qualified Investigator (QI) is responsible for the different local investigators and is required to sign for each of them. The Qualified Investigator should be GCP-approved. 22. How long should I store the paper documents (Investigator File) at my site? Centres should keep all data stored for the length of the study and the time foreseen by local rules, but at least for a period of 10 years from the moment of the study completion. The Investigator File should include: protocol, IRB judgment, E.C. approval (if applicable), local investigator delegation log, local translation of informed consent form (if applicable), signed informed consent forms, etc. In- and exclusion criteria: 23. Should all patients submitted to general anaesthesia be included? Yes. To be more precisely, patients with general anaesthesia that have not received a NMBA are to be included, too. 24. In my country there are hospitals with a central operating theatre and a central PACU and with small peripheral operating rooms, usually of a single surgical specialty and with a small recovery unit. In some institutions it may be difficult to establish an internal organisation in order to allow recruiting patients in these peripheral locations. Is it reasonable in terms of study design to recruit patients only in a central operating theatre and not in another of the same hospital? Unfortunately not, because this will lead to a selection bias. The differences between the peripheral and the central ORs are of major interest. The task of the "peripheral" ORs would be to start the observation and collect the pre-, intra-operative and PACU data. For example, a study person must collect the paper CRFs and proceed with the visit and the discharge (medical chart) visit. Please have also a look at the Tip sheet for Local Coordinator (available on study website), where we share the first centres experience in the organisation of the data collection. page 4 of 11

5 25. Are daily care surgical patients included? Ambulatory patients and patients that are discharged within 12 hours post anaesthesia cannot be included (see Study Protocol, 2.3 Study Population, p.9) 26. Are patients with pulmonary disorders included in the study? Yes. Literally, every patient that gets general anaesthesia can be included, unless an exclusion criteria applies (see Study Protocol, 5.1 Inclusion criteria, p.15) 27. Should we include gynaecologic curettages, ventilated in mask anaesthesia? Yes, if it is a general anaesthesia and the patients need some sort of ventilation device (mask by the hand of the anaesthesiologist, endotracheal tube, tracheostomy, laryngeal mask, etc). In case of ventilation by laryngeal or face mask, the item 27 (CRF01) has to be answered No. The item 32 (CRF01) Extubation within 6 hours after the end of surgery has to be answered with yes. The time is the end of mask ventilation or the removal of the laryngeal mask. 28. Joint replacements with Regional Block and sedation and supplemental O2, I interpret as not being included, is that correct? Should the following be included? Joint replacement with regional block plus sedation and 1. planned nasopharyngeal airway insertion at start of case? 2 unplanned nasopharyngeal airway insertion? (i.e. in middle of case) Please include the patient whenever he stops breathing at some moment and needs external ventilation. This can be performed mechanically via an endotracheal tube or a laryngeal mask or even by hand and face mask by an anaesthesiologist. The wording "intubation" and "extubation" stands as equivalent for any kind of beginning or ending of external ventilation. As I understand that your setting is in the OR, it does not matter, if the need of airway management is planned or unplanned. If the patient needs any kind of ventilation in the OR, he can be included. Even if the duration of ventilation is very short. VII. Informed Consent: 29. Is it necessary to obtain patient informed consent? This depends on your local ethical rules. The study must be judged by your local institutional review board. We have designed the study to be purely observational, only collecting data which are recorded in the medical charts. We hope that this will facilitate assignment of a waiver for the Informed Consent by the IRB. However, if locally required, patient informed consent must be obtained before the patient participates in the study. 30. Can I obtain the patient informed consent on the day of surgery? As long as your local IRB and national legislation approve, you can obtain patient informed consent on the day of the procedure. 31. As the majority of patients eligible for this trial in our hospital will be inpatients entering the hospital the day before their surgery, we will include (i.e. let them sign informed consent) this patients. Is this a problem? No it is not a problem. If your recruitment week is from Monday 29 September 2014 from 7.00 AM to Monday 13 October 2014 at 6.59 AM, the Consent can be signed up the day(s) before. We consider the recruitment period from your site includes all operations with anaesthesia induction as of 29 September AM to operation with anaesthesia induction on 13 October 2014 at Therefore the Informed consent could be signed in this case on 28 September VIII. Data collection: 32. Which different CRF exist for data collection? CRF01 Pre- and intraoperative Data CRF02 Post-operative Care Unit or Recovery Room CRF03 Postanaesthesia Visit (Day1, 2 or 3) CRF04 Follow-up Visit (Discharge or Day 28) page 5 of 11

6 IX. CRF specific questions: 33. In my hospital, we do not have PACU/Recovery room and all patients from OR go directly on wards or in ICU and we haven't TOF monitoring precisely any neuromuscular monitoring. Is it a problem to participate in this study? POPULAR is an observational study. We are interested in your clinical reality as it is. Nobody knows which practice has fewer complications. Please fill in CRF01 for every case that fulfils the study inclusion criteria and then follow the instructions at the end "Discharge from OR": If patient is transferred to PACU/Recovery room, please complete CRF02 If patient goes to ICU/ward, please complete CRF03 If patient is discharged from hospital to home or dies, please cease data collection here If patient remains intubated >= 6 hours or has tracheotomy intraoperatively, please cease data collection here. 34. What are the mandatory postoperative visits or examinations? For example, should we perform arterial blood sample and chest X-ray systematically in order to diagnose a respiratory event? You ought to visit the patient on postoperative day 1, 2 or 3 in order to collect the data of this day. Postoperative pulmonary complications (POPC) are a result of clinical diagnosis from physicians and nurses regularly working on the specific ward. The study staff should only document this information. As you visit the patient, it is however, expected that the alertness by the staff will be increased. In consequence they may do something in addition. Again: Please document what they do and what they measure or detect, but do not interfere with their decisions. The items of a diagnosis of POPC on the CRF must be marked if you can find any congruent result but not more. Do not provoke any additional examination in terms of the study. If there is no clinical need to make an X-ray, you don t have to do it. The X-ray diagnoses of the CRF, e.g. atelectasis become No in this case. But if your question regarding the patients condition provokes the responsible physician to indicate an additional examination, it is ok and you must document the respective results. 35. Does Chest X-ray have to be interpreted by a radiologist? We accept any physician's diagnosis based on X-rays. 36. What should I record if a patient dies after hospital discharge? We are not collecting any data after hospital discharge. If a patient is discharged from the hospital, follow-up ends. Please record the date of the event that came first (e.g. in this case: date of discharge). 37. CRF01 V Surgical details, 21. Surgical procedure. We do psaeudomyxoma surgery at my site. This involves an extensive laparotomy with both upper and lower abdominal surgery. Which box should I tick upper abdominal open or lower abdominal open. In this case, we would recommend to choose upper abdominal open. Background: Upper abdominal surgery is known to have a greater impact on POPC. A "missclassification" of the type of surgery in this direction seems less problematic. 38. CRF01 IV Anaesthetic details during surgery, 26. Anaesthesia is maintained both with volatile inhalational anaesthetic and a continouous intravenous infusion at the same time. Should we choose the "volatile maintenance" option? Yes, please choose "volatile" in this case, because it is the application of inhalational anaesthetic that has an effect on neuromuscular monitoring. page 6 of 11

7 39. CRF01, IV Anaesthetic details during surgery, If only a single on-off dose of muscle relaxant is given at the beginning of the case, does this count as the first and the last or do we leave section blank as no second/last dose is given? If a patient receives only one dose of NMBA, the first dose is indeed the last dose. Please enter the parameters (time, date, dose) in both (!) fields. It seems a repetition, but then we'll exactly know that there was only dose. Otherwise we might suppose that another last dose was simply forgotten to be entered. 40. CRF01, IV Anaesthetic details during surgery, Intraoperatively we administer a NMBA first as bolus(es), then continue with a continuous intravenous infusion for the remainder of the surgical procedure. In this situation, how do we establish the "Last dose of NMBA" and the "Time of last dose of NMBA"? For the "Time of last dose of NMBA" please enter the end of your continuous IV - infusion. The "last dose" is indeed a problem, but we discussed it and propose following: In the ecrf, please do not enter anything for the last dose. This will create a "Discrepancy note" that will be saved. In the work-up of your dates in the ecrf, we will ask you about the discrepancy notes. Then please answer in these cases, that you performed a continuous infusion. We will register it then. 41. CRF01, VI Anaesthetic details during surgery, 28. Muscle relaxant infusions are common at my site for prolonged surgery. How do I record this on the CRF especially question 28.13? This is a special situation which we decided to address as follows: Please give time and date of the first dose (Q28) and the total dose. Then give date and time for the last dose that means the stop of the infusion. Leave the dose blank (Q28.13) and save it. That will create a discrepancy note. During the data cleaning, we will work-up all the discrepancy notes with the centres. Here, please explain the fact of the NMBA infusion, then we can take your proceeding into account. 42. CRF01- V-21 Surgical procedures. How should an ERCP be classified as "upper abdominal closed" or "other procedure"? Upper abdominal closed 43. CRF I VII 32 Does "Extubation within 6 hours after of end surgery?" also apply for the use of a laryngeal mask? Yes, please enter the time for the end of any kind of ventilation (extubation, removal of a laryngeal mask, end of mask ventilation) and proceed entering data (CRF02, CRF03 and CRF04, if applicable). 44. CRF02; 1. It is possible to arrive to the PACU before the trachea is extubated? Yes, it is. You can give an extubation location under number CRF01 VII If the patient is extubated in the PACU within 6 hours postoperatively, you simply go on with CRF02. Of course, I see that one has to jump (especially mentally) between the CRFs in that case, because it is not chronological. But I guess, we should stick to the most frequent patient flow: first, extubation in the OR and second, admission to the PACU. 45. CRF01, VIII Discharge from OR, 33. Postoperatively all our patients are transferred to an area which functions both as PACU / recovery room, and as an ICU, and additionally as a preoperative preparation area. In this situation, in which our unit = preop=pacu=recovery room=icu, there are several problems. We understand that at your hospital you have one unit that is run as PACU und ICU. I would like you to think about the patients' situation postoperatively. If a patient only needed standard postoperative monitoring and care and was discharged to normal ward within a few hours, I would give the label "PACU" and follow the path to CRF02. If your patient was instable and needed prolonged ICU treatment at once, I would label this ICU and skip CRF02. There is also the possibility that the patient is in the PACU for a while (CRF02), then it becomes clear that he is too critical and needs ICU care. In this case, I would finish CRF02 and follow the path "goes to ward/icu". CRF03 can be performed on normal ward or ICU. page 7 of 11

8 46. CRF01, VIII Discharge from OR, 33. If a patient is admitted into our unit for preoperative preparation, when going to surgery he will be "coming from an ICU", even if the patient is not in critical condition. "Patient coming from an ICU" is officially one of the exclusion criteria, but many of our patients are perfectly stable, coming in for elective surgery. Should these patients be excluded or not? The exclusion criteria refers to patients that are critically ill and already need intensive care. This should not be the case for patients coming in from home for elective surgery. Also emergency cases like fractures or patients with acute abdomen that need immediate operations, but had not been to admitted to ICU, shall be included. 47. CRF01, VIII Discharge from OR, 33. After cardiac surgery, most of our patients remain intubated for more than 6 hours (this is standard procedure even for good postoperative outcomes). How do we proceed? Do we stop the data collection or should we continue? For these patients, please fill in CRF01 and choose option "is transferred to recovery room/pacu/icu and remains intubated". If a patient remains intubated more than 6 hours postoperatively, please stop data collection and only enter CRF01 in the ecrf. 48. CRF01, VIII Discharge from OR, 33. Many of our elective patients for pseudomyxoma go straight to ITU intubated planned. How do I indicate this is planned and not due to a problem? Please choose "is transferred to ICU/PACU/ Recovery Room and remains intubated" (Q33) for Discharge from the OR and follow the instructions at the bottom of CRF01 (applies for every patient that you include): - If patient is transferred to PACU/Recovery room, please complete CRF02. - If patient goes to ICU/ward, please complete CRF03 - If patient is discharged from hospital to home or dies, please cease data collection here - If patient remains intubated >= 6 hours or has tracheotomy intraoperatively, please cease data collection here 49. CRF01, VIII Discharge from OR, 33. Many of our liver resection patients go to recovery (PACU) extubated but have a planned stay in recovery (PACU) of 24 hours where they receive level 2 ITU care. They are basically being looked after in a high dependency/icu environment but physically in the PACU (a special side bay). How should I record this? In Munich, we have a similar situation, where some patients stay overnight in the PACU. We decided to stick to the label PACU, and filled-in CRF02 for these prolonged stays. This will give a long time in the PACU (organisational issue), but not a change in the surveillance of pulmonary function and the possible appearance of POPC. 50. CRF02 II PACU/Recovery room, 9. Patients are often transferred to the PACU from theatre with an LMA in situ and on oxygen. This is then removed by the recovery staff. Does that mean we have to tick every patient (Q9) as needing airway management in recovery even though it is just an extension of the anaesthetic and not a complication? Or do we only look at those patients who needed a new airway intervention once in recovery? No, this is indeed no complication and no airway intervention. Please remark that the time of extubation (Q32) also applies for the removal of a LMA. When it is removed in the PACU, please note date, time and PACU for the location. 51. CRF 02; 4-5. It is possible to enter both mild and severe hypoxemia at the same time. Of course, mild and severe hypoxaemia cannot occur at the same time, but consecutively. After all, the stay at the PACU is a time period where different things can happen and be observed. For example, one patient starts with mild hypoxaemia, than deteriorates to severe hypoxaemia and ends up with reintubation. As we did not give a timeline (time and date) for the appearance of the events in the PACU, we prefer to leave it as it is now. An error message is not necessary. 52. Postoperative complications reviewed at personal postanaesthesia visit. Do I understand that there is no visit to the patient and only the patient s data should be reviewed? The Postanaesthesia visit on Day 1, 2 or 3 is mandatory and PERSONAL (CRF03). That means it should be a face-to-face contact. We decided to do this, because we doubted the quality (and competence) to note POPC by the normal ward staff. The follow-up visit (CRF04) is only on papers. page 8 of 11

9 53. When a patient has two operations, but the second is after 7 days (so the patient is not excluded). Do we carry on CRF (CRF 04) like there was no second operation or do we stop on CRF 03 and start another (new) CRF? If a patient is re-operated during the hospital stay (but not within 7 days after the inclusion operation ), the study is not stopped and follow-up has to be continued until discharge/day 28 in the same CRF. If a complication appears after the second operation, it is also recorded (in fact, the complication is also related to the first operation). 54. What is a definition of PACU, because some of our patients go on ward (one department is in another place in the building with their operating rooms and these patients go directly to ward) or ICU (during the night shifts it works as PACU) but in both cases they are monitored- ECG, BP, Sat (also on ward). Should we fill CRF 02 there? Unstable patients stay in ICU longer or till morning how long can we take it as a PACU (normally patients stay in PACU 1-1.5h) (for example, if patient during a night shift goes to ICU (as an alternative PACU ) and stay there for 4 hours (more than usual on PACU ) and then go to ward, should we fill CRF 02 or skip to CRF03? PACU means that there is at least one trained person (nurse/anaesthetist) permanently in the room to take care for postanaesthesia patients. Monitoring is usually available in a PACU but monitoring in a room does not qualify as PACU itself. Rooms on normal wards with monitoring, e.g. but without qualified anaesthesia staff, are no PACU. Even more important, absence of monitoring (as problematic it may be) does not disqualify as PACU by definition. I hope that these reflexions help you to decide whether to declare it a PACU or an ICU situation or a simple ward. In our hospital, we run an overnight PACU where patients can stay until the next morning. Those cases need prolonged postoperative monitoring and observation, but not a real ICU treatment. We filled in CRF02 for all of them. 55. In CRF 03 there is written that we should record information between discharge from PACU and day of visit. Question is if patient have Saturation 89% in PACU but responding on mask oxygen. If we should write down immediately to CRF 03 that there was Respiratory failure (I presume that he will have decreased saturation also at ward). Please stick to the findings at your CRF03 visit to the patient. If the patients need oxygen at the ward, it should normally be noted in the records on the ward. 56. In CRF 03 if there is information from nurses that patient have no subjective problem, should I give answer NO to every Question? How can I detect Atelectasis or pulmonary infiltrates without X- ray? Or it is like- if somebody has no subjective problem I can record NO as an answer? For CRF03, the clinical impression counts. If there is nothing suspicious for a POPC, there is no need to make an X-ray. If there is no X-ray, it gets a "No" for all the radiologic diagnoses. But if you feel that there is a problem that the ward staff has not detected, you might like to initiate an x-ray. If this ends in a chest x-ray, of course, you will have a look at it and eventually get a diagnosis of atelectasis, for example. 57. In case I go to visit patient in Day 1 after surgery and patient is discharged on Day 2 should I fill also CRF 04? If I decided to record just Day 3, will I record just CRF 02? If you record CRF03 on Day 1 and the patient is discharged on Day 3, then please record CRF04. If you record CRF03 onday 2 and the patient leaves hospital on the same day, you can choose "goes home" and cease data collection. See also the instructions at the end of CRF03: If patient goes to ICU/ ward, or stays on ward please complete CRF04 If patient is discharged from hospital to home or dies, please stop data entry. 58. Postoperatively, most of our patients remain in our PACU/ICU for 2 days or more, after which they are discharged to the cardiac surgery ward. Could we perform the Postanaesthesia Visit on days 1 or 2 postop while the patient is still in our unit (PACU/ICU)? Waiting until discharge to the ward would present a disadvantage because less data is collected there, that could help us diagnose early pulmonary complications. It is absolutely correct to perform the postanaesthesia visit on the ICU, as long it is on postoperative day 1, 2 or 3. page 9 of 11

10 59. The post anaesthesia visit. Do we examine all patients or just do an end of bed assessment after a notes/bloods/obs chart review and examine if necessary? In principle, it is up to you how you will proceed in order to detect POPC. You can use whatever is generally available (at your site) and seems appropriate to help you to diagnose POPC. Those possible tools include hands, ears, eyes and nose of an examiner as well. 60. If patient goes from orthopaedic surgery to rehabilitation department, which one is the discharge day? The day he goes to rehabilitation or when he leaves the hospital? Discharge from the orthopaedic department is the discharge day (even when the rehabilitation department is in the same hospital). 61. When a patient goes home at the end of CRF03, I cannot fill in CRF04. Must I inactivate CRF04? If yes, how must I do that? Please note that data collection ends here (CR03) and you have to choose the option "goes home. Please cease data collection and don t schedule a CRF04 in the electronic data entry. 62. Forecast date of discharge (on the first page of the CRF) refers to discharge from hospital or discharge from our unit (PACU/ICU)? The forecast date of discharge refers to the discharge from the hospital. This shall help you to organise the data collection for CRF04 that is only based on the medical charts. In our hospitals, we tried to go to the wards on the date of discharged, because it was easier to find the records. It is not an obligation to do so, but we found it better in order to avoid a lot of searching for the medical records. X. Electronic CRF: Check the ecrf Guidance, soon available at the ESA website, for more details 63. Is the national coordinator responsible for encoding the ecrf s from the sites in his country? No. Each individual local coordinator is responsible for ecrf encoding in their institution. 64. How do I get an inlog/access to the OpenClinica website? When EC approval is received by the ESA Secretariat, each local coordinator receives a personalised inlog for the ecrf by the ESA before the start of the study. By default, only local investigator will be granted access to electronic data entry. We can include up to three ecrf profiles per hospital. If you would like to add a maximum of 2 additional collaborators then you must send the family name, first name and addresses of the additional users for your site to popular@esahq.org. 65. ecrf 01: It is possible to enter an invalid code (e.g. ACB ) at the patients first page where code and sex is entered. Make sure you fill in ecrf 01 item 2 with correct study subject number. The patient code (study subject ID) on the first page can only be changed by ESA OpenClinica Support team. 66. ecrf01 - VII Emergence from anaesthesia, 32.2: With the cases who breathe spontaneously under a GA through the whole case with a LMA in situ, these cases are never 'extubated' as they have never been intubated. Therefore it is not possible to answer p 32 for these. Does the 'time of extubation refer to the time of removal of LMA? Or should these cases be excluded For patients with a LMA, you make a "No" for the question "Has the patient been intubated? (This question refers strictly to endotracheal intubation.) The "Time of Extubation" applies for the removal of the LMA, too. Answering in this combination signals that the patient needed airway management (for his general anaesthesia), but was not intubated with an endotracheal tube. 67. ecrf It is possible to enter a different sex compared to the first time screen when subj # was created? Make sure you fill in ecrf 01 item 4 with correct sex. The sex on the first page can only be changed by ESA OpenClinica Support team. page 10 of 11

11 XI. 68. Who can I turn to, if I have troubles using OpenClinica? Elaborate ecrf Guidance are available on the ESA website: If you cannot find the answer to your questions in het Guidance, please contact the ESA Secretariat at: openclinicasupport@esahq.org 69. When can I start encoding data in the ecrf? As soon as EC approval is received and sent to ESA Secretariat; it is possible to start encoding from the first day of patient inclusion. For example, you can start the data-entry for the Intra-Operative data, save and return to enter the follow-up data at a later stage. Please start your data-entry quickly, as many data needs to be encoded. 70. What to do if the value that I want to record exceeds the pre-set ranges? If you have such an extreme value that it exceeds the ranges, please do record it on the paper CRF (providing it is not a measurement error). When entering the value in the ecrf, please leave a discrepancy note by clicking on the little flag. You can declare that this is the correct value, even though it exceeds the ranges. The value will then be included in the data-analysis. 71. When I want to record 423, 5 mg as drug dose, the system gives an error message when I enter decimals. Please only use whole numbers for entering. In this case enter 423 mg or 424 mg. 72. By mistake I scheduled CRF04 for two patients who had gone home on the day of CRF03. Is there a possibility to delete this? If you have scheduled a CRF04 by error, follow the steps to mark the status skipped : 1. First navigate to Subject Matrix 2. Enter the study subject ID 3. In the Actions column, click on the magnifier 4. Another window opens: View Subject 5. Select the Edit icon of the CRF you have added by error 6. Another window opens: Update Study Event 7. Select stopped from the Status drop down list 8. Click on Submit changes button 9. Select skipped 10. Click on Submit changes button Pre-Study survey: 73. How many cases are done in a year in your hospital? Total number of patients operated on (screening population), but not necessarily candidates for the trial. 74. What percentage of patients having a general anaesthesia do you have within a 2-week period in your hospital? Percentage: Number of all the patients being operated under general anaesthesia in relation to all operated patients. Example: 800 patients out of 1000 operated patients had general anaesthesia. That makes 80%. 75. The pre-study questionnaire asked about methods of detecting pulmonary complications at our institution. Does this refer to the methods used by the Research team or methods used generally by clinicians in the hospital? This applies for the research team. (There might be interesting differences between the study centres that will lead to different detection rate for POPC.) Remember the POPULAR FAQ s will be updated on a regular basis. Please check the ESA website to make sure you have the latest version of the study documents. page 11 of 11