Patient-controlled Sedation With Propofol Versus Combined Sedation During Bronchoscopy - a Randomized Controlled Trial
Phase: NA
Conditions: Sedation, Bronchoscopy
Sponsor: Lena Nilsson

                                                     BRONSE version 2 (2016-01-15) EudraCT 2015-005274-38 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patient-controlled sedation with propofol versus combined 
sedation during bronchoscopy – a randomized controlled trial 
 
EudraCT 2015-005274-38 
 
BRONSE 
2016-02-29 
version 3   
 
 
 
Sponsor: Lena Nilsson 
 
Investigational products:  
 Propofol (Propofol-®Lipuro 5/10/20 mg/ml, Propofol Sandoz 10/20 mg/ml, Diprivan® 
10/20 mg/ml, Propolipid 10/20 mg/ml, Recofol 10/20 mg/ml) 
 Midazolam (Midazolam Accord 1/5 mg/ml, Midazolam Actavis 1/5 mg/ml, 
Midazolam Hameln 1/5 mg/ml, Midazolam Panpharma 1/5 mg/ml, Dormicum® 5 
mg/ml) 
 Morphine-Scopolamine (Morfin-Skopolamin Meda (10+0.4) mg/ml) 
 Glycopyrronium bromide (Robinul® 0.2 mg/ml) 

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Table of contents 
 
List of abbreviations ................................................................................................ 6 
Contact ...................................................................................................................... 6 
Background information and rational ..................................................................... 7 
Objective ................................................................................................................... 8 
Study design ............................................................................................................. 9 
Selection of subjects .............................................................................................. 13 
Patient withdrawal criterias ............................................................................................ 14 
Premature termination of the study ............................................................................. 14 
Investigational medicinal product(s) .................................................................... 14 
Propofol (Propofol-®Lipuro 5/10/20 mg/ml, Propofol Sandoz 10/20 mg/ml, 
Diprivan® 10/20 mg/ml, Propolipid 10/20 mg/ml, Recofol 10/20 mg/ml) ............. 15 
Coadministration of other medicinal products .................................................... 16 
Registration of efficacy .......................................................................................... 17 
Post Anaesthetic Discharge Scoring System (PADSS) .................................................... 17 
Sense of coherence (SOC) ................................................................................................ 18 
Coping Strategies Questionnaire (CSQ-SWE) ................................................................. 18 
Hospital Anxiety and Depression Scale (HADS) ............................................................ 18 
Post-discharge Surgical Recovery Scale (S-PSR) ............................................................ 18 
Modified version of Quality of Recovery (QoR-23) ........................................................ 18 
Registration of safety ............................................................................................. 20 
Incident .................................................................................................................................. 20 
SUSAR-report ......................................................................................................................... 23 
Pregnancy .............................................................................................................................. 23 
Statistics.................................................................................................................. 23 
Quality control and quality assurance .................................................................. 24 
Monitoring ............................................................................................................... 24 
Source data ............................................................................................................................ 25 
Ethical considerations ........................................................................................... 25 
Procedure for recruiting and obtaining informed consent ................................. 25 
Handling and archiving data .................................................................................. 25 
Insurance ................................................................................................................. 26 
Finance .................................................................................................................... 26 
Reporting and publishing ...................................................................................... 26 
Substantial amendment of study and declaration of end of trial ....................... 27 
Discrepancies’ and violations ............................................................................... 27 
References .............................................................................................................. 28 
Appendix 1 – Observer's assessment of alertness/sedation (OAA/S) scale ............. 30 
Appendix 2 – Modified Post-discharge Surgical Recovery (S-PSR) scale ................ 31 
Appendix 3 –Post Anaesthetic Discharge Scoring System (PADSS) for Home 
readiness after Ambulatory Surgery ......................................................................... 34 
Appendix 4 – Modified Quality of Recovery (QoR-23) .............................................. 35 
Appendix 5 – Sense of coherence (SOC) ................................................................. 37 
Appendix 6 – Coping Strategies Questionnaire (CSQ-SWE).................................... 41 
Appendix 7 – Hospital Anxiety and Depression Scale (HADS) ................................. 43 
 

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List of abbreviations 
ACCP 
American College of Chest Physicians 
BAL 
Broncho-alveolar lavage 
BTS 
British Thoracic Society 
IC 
Informed consent 
IMP 
Investigational medicinal product 
OAA/S 
Observer’s Assessment of Alertness/sedation 
PCS 
Patient-controlled sedation 
 
Contact 
Primary investigator and sponsor 
Lena Nilsson, lena.nilsson@regionostergotland.se, 010-103 36 24 
 
 
Postal address for above are: 
Universitetssjukhuset i Linköping, 581 85 Linköping, Sweden 
 
External monitor 
Forum Östergötland, Linköpings universitet, 581 83 Linköping, Sweden, 010-103 35 55 

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Synopsis 
The study “Patient-controlled sedation with propofol versus combined sedation during 
bronchoscopy – a randomized controlled trial” (EudraCT number: 2015-005274-38, protocol 
number: “BRONSE”) is a phase IV single centre prospective randomized controlled trial with 
parallel groups. A total of 300 adult outpatients undergo diagnostic bronchoscopy during 
sedation and are randomized into three sedation arms (1:1:1); sedation with midazolam and 
morphine-scopolamine as premedication (clinical routine), sedation with propofol using PCS 
and morphine-scopolamine as premedication, and sedation with propofol using PCS and 
glycopyrronium bromide as premedication. The study is partially blinded, the bronchoscopist 
is blinded regarding given premedication for patients given PCS (two sedation arms). The 
hypothesis is that PCSincrease the amount of patients ready for discharge, and further that 
patients characteristics affect the amount of propofol administered. The endpoints are 
primarily the amount of patients ready for discharge within 2 hours and secondary assessment 
of patient characteristics using questionnaires, recovery and satisfaction as well as 
bronchoscopist evaluation and doses of administrated drugs. Finally safety variables are 
collected such as vital signs and interventions performed to maintain cardiovascular and 
respiratory stability. Study is planned to start during the first half of 2016 and end during the 
first half of 2017. 
 
 
Background information and rational 
Bronchoscopy is performed to investigate and diagnose patients with pulmonary disorders at 
the Pulmonary Clinic at Linköping University Hospital. The patient receives topical 
anaesthetic, analgesia and sedation during the bronchoscopic procedure according to the 
recommendations set by American College of Chest Physicians (ACCP) (Momen, M. W., et 
al. 2011) and British Thoracic Society (BTS) (Du Rand, I. A., et al. 2013) to achieve good 
patients’ satisfaction and procedure tolerance (Momen, M. W., et al. 2011). The standard of 
care at the clinic today for sedation is the use of benzodiazepine in combination with opioid. 
Clinical experience has shown that the combination affect the recovery time with a delay of 
discharge. The combination is frequently used for bronchoscopy but recent studies show a 
transition to use propofol as sedative agent. The pharmacokinetic properties for propofol are 
more favourable regarding onset of action and time for recovery (Stolz, D., et al. 2009), and 
equal level of patient satisfaction compared with benzodiazepine (Yoon, H. I., et al. 2011). 
Adding an opioid to propofol improve quality of sedation, tolerance to bronchoscopy, reduces 
coughing and usage of topical anaesthetic (Yoon, H. I., et al. 2011, Du Rand, I. A., et al. 
2013) but also increases the risk of respiratory depression (Yoon, H. I., et al. 2011) and may 
increase the risk of hypoxemia. 
 
The bronchoscopic procedure with sedation will be performed by a team consisting of: one 
bronchoscopist, who conducts the bronchoscopy; two pulmonary nurses who assist the 
bronchoscopist; one nurse anaesthetist administrating sedation drugs and monitoring the 
patient. During the procedure titration of the sedative agent with bolus doses is done. 
Differences between individuals need for sedation affect the depth of sedation and influence 
patient tolerance, cardiorespiratory functions and result in pro-longed post-procedural care. 
Patient Controlled Sedation (PCS) has been used to allow the patient to interact and self-
administrate an appropriate dose of sedation to tolerate the procedure (Hwang, J., et al. 2005). 
PCS using propofol as the only sedative agent may give optimal conditions for both the 
patient and the bronchoscopic team as well as shorten recovery time which makes an earlier 
discharge possible.  
 

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Except weight, type of procedure and combination with other drugs (Nilsson, A., et al. 2015), 
little is known about factors that can explain why different subjects administer different 
amounts of sedative drugs to themselves when using PCS. We aim to address this issue by 
exploring some patients’ characteristics using validated questionnaires. We will look at sense 
of coherence, coping strategies, anxiety and depression and investigate if there is a connection 
between these characteristics’ and dose requirement during PCS.     
 
 
Benefit-risk evaluation  
Bronchoscopy is undertaken as an outpatient procedure. As soon as the patient fulfils the 
discharge criteria he/she can leave the hospital. With the use of short acting drug (propofol) 
for procedural sedation time to discharge can be shortened compared to midazolam, but also 
time to return to stable vital signs. The latter means that the monitoring period after the 
procedure can be shortened. By a faster turnaround it is probable that more patients can be 
handled in the bronchoscopy unit during one day. The risk of having patients to stay in 
hospital overnight due to a slow recovery is also probably reduced.  
 
Another benefit is most probably the PCS technique itself. The level of sedation is in the hand 
of the patient himself, and in other studies this has shown to be something that patients put 
great value in. The PCS allows individually adjusted sedation levels, and the short acting 
properties of propofol facilitate deeper sedation during shorter specially difficult and 
demanding periods of the intervention. If insufficient sedation during the procedure occur, 
rescue medication (opioid) can be used to potentiate propofol and deepen the sedation as well 
as to give relief of any pain. If the level of sedation still is not acceptable for the patient or 
bronchoscopist additional propofol is administrated by the nurse anaesthetist. Replacing 
morphine-scopolamine with glycopyrronium (in sedation arm GP) may affect the pain relief. 
If the pain relief is insufficient the bronchoscopist may give additional topical anaesthetics 
and/or request additional rescue medication, as described above. 
 
The most severe risks connected to sedation, especially with deep sedation, are circulatory 
and respiratory events, but aspiration of gastric contents is also a risk. The same precautions 
as with general anaesthesia are undertaken. An anaesthesiologist will conduct a preprocedural 
assessment of the patient and is available for consultation via telephone and will be informed 
before sedation and bronchoscopy procedure begin. The anaesthesiologist is available within 
a few minutes if call is made to anaesthesiologist pager.. The patients’ vital signs are 
monitored by a nurse. In a recent meta-analysis of sedation during bronchoscopy it was 
concluded that the risk of hypoxia during the procedure was not increased during sedation 
compared to awake procedures (Hong, K., et al. 2015). Only patients planned for 
bronchoscopy as part of their clinical assessment are included in the study. We believe that 
the benefits of using the propofol PCS technique outweigh the risks with the trial. Possibly 
can the PCS technique in the future can be a routine method for outpatient bronchoscopy.  
 
 
Objective 
Our primary hypothesis is that the use of patient-controlled propofol sedation for outpatient 
bronchoscopy will increase the amount of patients ready for discharge after two hours, 
compared with sedation using midazolam and morphine. We further hypothesize that patient 
characteristics affect the amount of propofol self-administered by the patient during patient 
controlled sedation.    
 

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The primary endpoint is the amount of patients ready for discharge within 2 hours, according 
to the Post Anaesthetic Discharge Scoring System (PADSS) score, after outpatient 
bronchoscopy. 
 
Secondary endpoints; assessment of self-rated patient characteristics using questionaries’ 
(Sense of Coherence, Coping Strategies Questionnaire, Hospital Anxiety and Depression 
Scale) and recovery (Post-discharge Surgical Recovery Scale), patients’ satisfaction, 
bronchoscopist evaluation (perception of cough, bronchial secretion and acceptance of 
procedure), total dose given of topical anaesthetic, analgesia and sedation drugs. 
 
Safety variables; level of sedation, vital signs (arterial oxygen saturation, respiratory 
frequency, non-invasive blood pressure and heart rate) and interventions performed to 
maintain cardiovascular and respiratory stability.  
 
 
Study design 
Clinical trial, Phase IV; therapeutic use. The study is a prospective randomized controlled 
trial with parallel groups conducted in a clinical unit (single centre). It will be partly blinded; 
the bronchoscopist is blinded regarding given premedication for patients with PCS (two 
sedation arms). The study will be conducted at the Pulmonary Clinic, Linköping University 
hospital, according to the Helsinki Declaration principles. Screening will be performed during 
a planned pre-procedural visit some days to a couple of weeks before the bronchoscopy. The 
patient receives verbal and written information regarding the study from the pulmonary 
physician. After having had time to consider participation, the pulmonary physician checks 
inclusion and exclusion criteria’s and obtains an informed consent from the participants. It 
shall be noted that no study-related procedures will be done prior signed consent. The patient 
may cancel participation in the study at any time without having the medical care affected. 
Women of childbearing potential are tested with S-β-HCG pregnancy test, results are checked 
upon visit 2 before randomization. Self-rated patient assessment forms will be handed out for 
the patient to fill in at home between visit 1 and visit 2 as well as after visit 2. The patient will 
be informed to mail them back to the Pulmonary Clinic with attached prepaid envelope.  
 
 
At day for visit 2 (day of procedure) the patient shall be fasting from solid food for at least 6 
hours, and clear liquids two hours before the onset of sedation (according to the Swedish 
Society of Anaesthesiology and Intensive Care, 2013). Inclusion/exclusion criteria’s are 
rechecked (after results of the S-β-HCG test) and if patient is excluded from the study, 
treatment will be done according to routine. Each patient who fulfils participation in the study 
is allocated consecutively a sealed opaque randomization envelope containing instructions of 
which premedication and sedation shall be administrated before and during the procedure. 
Randomization is done in blocks with equal distribution between the three groups. An 
independent statistician produces a randomization list using the computer program STATA. 
Randomization is done by means of closed, numbered envelopes associated with 
randomization opened in consecutive order. The envelopes will be prepared by an 
independent individual, not involved in the study. The randomization number given for each 
patient shall be documented in their individual CRFs.  
 
 
There will be three sedation arms; premedication with subcutaneous morphine-scopolamine 
and sedation with midazolam (group MM) (todays standard of care), premedication with 

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subcutaneous morphine-scopolamine and sedation with PCS (propofol) (group MP), and 
premedication with intramuscular glycopyrronium bromide and sedation with PCS (propofol) 
(group GP). The research subject will be randomized 1:1:1 to one of the three sedation arms 
and conduct one bronchoscopy with sedation.  
 
If patient is randomized to sedation with PCS (group MP or GP) the nurse anaesthetist will 
give additional thorough information and instructions how to operate the PCS device before 
premedication is administrated and the bronchoscopy begins. 
 
The bronchoscopist is blinded regarding the premedication in the both PCS groups (group MP 
and GP) and therefore shall the premedication be filled in the same type of syringe and be 
marked only with study number, randomization number and route of administration by 
pulmonary nurse at clinic. Administration of premedication is done one hour before start of 
bronchoscopy by the same pulmonary nurse who prepared it. Time, route (subcutaneous or 
intramuscular) and name of pulmonary nurse who gave the premedication is documented in 
CRF.  During the procedure the type of sedation will be revealed for the bronchoscopist due 
to difficulties to conceal the technical equipment of the PCS. 
 
During the procedure the anaesthesiologist is available for consultation via telephone and will 
be informed before sedation and bronschoscopy procedure begins. Furthermore the 
anaesthesiologist is available within minutes if call is made to anaesthesiologist pager. Before 
bronchoscopy is initiated (one hour after premedication) the patient is encouraged to start 
using the PCS until the patient feel comfortable (Sedation scale OAA/S 4/3). At the same time 
local anaesthetic is administrated nasally and pharyngeally depending on type of 
bronchoscopy and during the procedure local anaesthetic is administrated with a spray-as-
you-go technique to anaesthetize vocal cords and trachea. During the procedure the 
bronchoscopist may request additional medication to achieve deeper sedation and/or pain 
relief due to a need that the patient has to be completely still during specially demanding and 
potentially dangerous parts of the procedure. If requested, the sedation is deepened with 
additional midazolam (if group MM) by nurse anaesthetist or by awaiting the PCS to deliver 
additional requests from the patient (if group MP or GP). If pain relief is needed additional 
topical anaesthetics is administrated by bronchoscopist and/or alfentanil (rescue medication) 
by nurse anaesthetist (all groups). The bronchoscopy takes approximately 1 hour. When the 
procedure is finished (bronchopscope is removed=time 0), the patient will monitored by nurse 
anaesthetist until sedation score OAA/S 5 and thereafter monitored by pulmonary nurse until 
home readiness score PADSS score ≥9 (approximately 1 to 4 hours) and thereafter discharged 
to home if outpatient else transferred to ward.  
 
The questionnaire S-PSR is filled out by the patient the in the evening the same day of 
discharge. The day after discharge the patient fills out the QoR-23 questionnaire. Both 
questionnaires’ are mailed back to the Pulmonary Clinic with attached prepaid envelope. 
 
Before, during and after the bronchoscopy the patient is continuously monitored regarding 
vital signs. Monitoring of vital signs during bronchoscopy until OAA/S 5 is reached after 
bronchoscopy will be done by nurse anaesthetist. Monitoring before bronchoscopy and when 
patient have achieved OAA/S 5 after bronchoscopy will be done by pulmonary nurse. Oxygen 
(2L, 0,5-1L for patients with chronic obstructive lung disease) is administrated by a nasal 
catheter during the procedure and if needed post-procedural. 
 

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The patients are planned to be discharged the same day as the procedure after post-procedural 
monitoring is completed and criterions for discharge (PADSS) is fulfilled. Patients who not 
fulfil the criteria for discharge will have a pro-longed monitoring and stay at the clinical ward 
until criteria are fulfilled. Any adverse events/serious adverse events that have happened 
during the visit shall be documented and reported (see further under Registration of safety). 
 
At home (or at ward, if pro-longed stay) the patient fills out the self-rated questionaries’ S-
PSR (day of procedure) and QoR-23 (day after procedure) which include adverse 
events/serious adverse events follow-up, which are sent by mail back to the Pulmonary Clinic. 
Participation in the study ends after this questionnaire and the study ends after last subject last 
questionnaire (day after bronchoscopy).  
 
Roles in study 
 
Visit 1 
Pre-procedural visit 
Visit 2 
Day for procedure 
 
Pre-procedural 
Per-procedural 
Post-procedural 
Pulmonary 
physician 
/bronchoscopist 
Screening 
Inclusion /exclusion 
criteria  
Informed consent 
Check result of S-β-
HCG test 
Inclusion /exclusion 
criteria  
 
Bronchoscopy 
 
Pulmonary nurse 
 
Randomization 
Premedication  
Monitoring 
Assist 
bronchoscopist 
Monitoring (after 
OAA/S 5) 
Nurse anaesthetist 
 
 
Monitoring 
Sedation 
Monitoring (until 
OAA/S 5) 
Anaesthesiologist 
Preprocedural 
assessment 
Be available for consultation and immediate assistance 
 
 
Primary investigator may at any time withdraw a patient if the patient does not follow the 
procedures in the study protocol. Participation in the study is completely voluntary and the 
research subject may at any time terminate his/her participation in the study without having to 
explain why and without incurring any consequences for continued care. Upon termination of 
participation, treatment continues according to praxis on the clinic. Already collected data 
may be analysed if the patient does not oppose this.  
 
 
Visit 1 
Pre-procedural 
Visit 2 
Day for 
Follow-up 
Day after 

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visit 
procedure 
procedure 
Screening 
- 
Inclusion criteria 
- 
Exclusion criteria 
X 
X5 
 
Informed consent 
X 
 
 
Medical history 
- 
Relevant medical 
history and 
medication that 
affect the patient's 
cardiorespiratory 
stability and / or 
treatment of pain / 
anxiety1 
X 
 
 
Self-rated patient 
questionnaires (handed out) 
X 
(SOC, CSQ-
SWE, HADS) 
X 
(S-PSR2) 
X 
(QoR-233) 
Randomization 
- 
Premedication 
- 
Type of sedation 
during procedure 
 
X 
 
Procedure 
- 
Bronchoscopy 
- 
Sedation 
- 
Monitoring 
 
X 
 
Post-procedural monitoring 
 
X 
 
Adverse events and serious 
adverse events follow-up4 
 
X 
X4 
 

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1 Relevant data is medical history and medication that affect the patient's cardiorespiratory 
stability and / or treatment of pain / anxiety  
2 Filled out by the patient in the evening of discharge  
3 Filled out by the patient the day after discharge  
4 Documented by patient in QoR-23 questionnaire 
5 Inclusion/exclusion criteria’s are rechecked after S-β-HCG test 
 
 
 
The study is planned to start during the first half of 2016 and last visit at the clinic is planned 
to be during the first half of 2017. 
 
Selection of subjects  
 
Inclusion criteria 
- 
Adult patient (≥18 years)  
- 
Planned bronchoscopic procedure with sedation in an outpatient setting   
- 
The patient have after receiving information about the study given his/her signed 
informed consent to participate. 
- 
Women of childbearing potential only if use of an effective contraceptive. 
 
Exclusion criteria 
- 
Positive pregnancy test S-β-HCG. 
- 
Known/suspected allergy or contraindication* to any medication within the study. 
- 
Functional disability in both hands which affect the possibility to operate the PCS 
device.   
- 
Cognitive impairment, unwillingness or language difficulties resulting in difficulty to 
understand the meaning of participation in the study or to operate the PCS device.  
 
*Contraindications (exclusion of patient is made for each substance): 
 
Propofol 
- 
Hypersensitivity to propofol, peanut, soya or any of the excipients. 
 
Midazolam 
- 
Hypersensitivity to midazolam, benzodiazepines or to any of the excipients. 
- 
Severe respiratory failure or acute respiratory depression. 
 
Morphine-Scopolamine  
- 
Secretion stagnation, respiratory depression. Anxiety during alcohol or hypnotic 
effect. 
 
- 
Glycopyrronium bromide Hypersensitivity to glycopyrronium bromide or to any of the 
excipients. 
 
Lidocaine and Lidocaine-naphazoline 
- 
Hypersensitivity to the active substance, local anaesthetics of the amide type or to any 
excipients. 
- 
Hypersensitivity of the methyl and / or propyl (methyl / propyl paraben), or the 
metabolite para-aminobenzoic acid (PABA). 

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- 
Pharmaceutical formulations of lidocaine containing parabens should be avoided in 
patients who are allergic to ester local anaesthetics or its metabolite PABA. 
 
Alfentanil  
- 
Hypersensitivity to the active substance or to any of the excipients listed. 
 
Naloxone 
- 
Hypersensitivity to the active substance or to any of the excipients listed. 
 
Flumazenil 
- 
Hypersensitivity to the active substance or to any of the excipients listed. 
 
Patient withdrawal criterias 
Patient is withdrawn from study by primary investigator if any of the following criteria are 
fulfilled: 
- 
patient withdrawal of informed consent 
- 
if patient safety is jeopardized  
- 
if the procedure is not possible to perform in accordance with the protocol due to 
insufficient sedation, insufficient pain relief or other circumstances. 
- 
if protocol is violated 
 
Premature termination of the study 
The sponsor/primary investigator may terminate the study if: 
- the study reveals indications that either of groups has significant anomalous outcomes in 
relation to the other treatments 
- safety for the patients within the study may be affected 
- insufficient number of patients can be included in the study 
- study drugs according to the protocol cannot be delivered   
 
In case of termination of study by the sponsor, MPA and EPN will be promptly informed and 
receive a detailed written explanation of the reasons for termination. 
 
Investigational medicinal product(s) 
 
Patient-controlled sedation 
The software used in the PCS device (T34L PCA, CME Ltd. Lichtenstein, Germany) used for 
the procedure has no lockout period or background infusions and size for bolus dose of 
propofol is set in advance. Administration of the drug is controlled by the patient by using the 
delivery button that may self-administrate the drug when there is a need for sedation. 
Repeated administration will increase concentration of the drug which will affect the patient 
consciousness and level of sedation which results in lower frequencies or none requested 
bolus doses. When concentration decreases the patient may start to interact with the PCS 
again and if needed continue the administration. Due to potential discomfort during the 
initiation of the intervention the patient usually begins using the PCS before the intervention 
starts. The nurse anaesthetist should during the whole procedure encourage the patient to use 
the PCS whenever there is need to decrease discomfort.  

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Propofol (Propofol-®Lipuro 5/10/20 mg/ml, Propofol Sandoz 10/20 mg/ml, Diprivan® 
10/20 mg/ml, Propolipid 10/20 mg/ml, Recofol 10/20 mg/ml) 
Propofol is a sedative-hypnotic agent used for induction or maintaining anaesthesia or 
sedation during surgery, diagnostics, or procedures. It produces sedation/hypnosis rapidly 
(usually within 40 seconds from the start of an injection) and smoothly with minimal 
excitation; decreases intraocular pressure (IOP) and systemic vascular resistance; rarely is 
associated with malignant hyperthermia and histamine release; suppresses cardiac output and 
respiratory drive. For intravenous sedation in diagnostic and surgical procedures: Initially, 6-9 
mg/kg/h by infusion given for 3-5 minutes or an alternative dose of 0.5-1 mg/kg by slow 
injection over 1-5 minutes. Sedation is maintained with 1.5-4.5 mg/kg/h infusion. 
The agent is supplied locally from the locked storage (room temperature) at the department of 
anaesthesia and surgery. An accountability list will ensure the possibility to trace the agent 
from delivery on the department to administration. Due to use of agent from the local storage 
no additional labelling of the agent is needed. The agent will be administrated intravenously 
using a peripheral venous catheter. Based on former experience and knowledge from similar 
procedures with PCS and the estimated time for the procedure, totally 420 mg propofol 10 
mg/ml (=42 ml) is prepared in a 50 ml syringe compatible with the PCS device. The PCS 
software is set to make it possible to deliver 5 mg propofol (0,5 ml) for each request with a 
infusion rate of 300 ml/h (6 requests/min or 3 ml/min or 30 mg/min). Dose level is based on 
previous experiences from procedures with PCS. The agent will only be supplied during the 
procedure and the patient will be monitored bedside by nurse anaesthetist. 
 
Midazolam (Midazolam Accord 1/5 mg/ml, Midazolam Actavis 1/5 mg/ml, Midazolam 
Hameln 1/5 mg/ml, Midazolam Panpharma 1/5 mg/ml, Dormicum® 5 mg/ml) 
Midazolam is a short acting potent sedating drug used for instance before and during 
diagnostic interventions together with or without local anaesthetics. It can also be used as pre 
medication before anaesthesia, to provide anaesthesia or for sedation in connection with 
intensive care. The drug will be given intravenously. An initial dose of 1.5 mg will be given 
and additional doses titrated and adjusted to the patient’s age and physical status. A maximum 
of 3.75 mg will be given during a procedure.  
The agent is supplied locally from the locked storage (room temperature) at the department of 
anaesthesia and surgery. An accountability list will ensure the possibility to trace the agent 
from delivery on the department to administration. Due to use of agent from the local storage 
no additional labelling of the agent is needed. The agent will be administrated intravenously 
using a peripheral venous catheter.  
 
Morphine-Scopolamine (Morfin-Skopolamin Meda (10+0.4) mg/ml) 
Morphine-Scopolamine is used to reduce pain and receive an anticholinergic effect before 
invasive interventions. The agent will be given as a subcutaneous injection of 0.5-1.0 ml 
depending on the age of the patient.   
The agent is supplied locally from the locked storage (room temperature) at the clinic. An 
accountability list will ensure the possibility to trace the agent from delivery on the clinic to 
administration. The agent will be labelled with patient id and randomisation number by 
designated pulmonary nurse who will not attend during the procedure. One hour before 
procedure start is administrated subcutaneously. Dose level is based on previous experiences 
for reduction of pain and secretion on patients during bronchoscopy.  
 
Glycopyrronium bromide (Robinul® 0.2 mg/ml) 

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Glycopyrronium bromide is an anticholinergic agent used to reduce secretions in the mouth, 
throat, airway, and stomach before surgery. It blocks the activity of acetylcholine in the body, 
which decreases secretions and decreases side effects caused by medicines that may increase 
the action of acetylcholine in the body. Glycopyrronium bromide decreases acid secretion in 
the stomach. Hence it can be used for treating ulcers in the stomach and small intestine, in 
combination with other medications. In anaesthesia, glycopyrronium bromide injection serves 
as a preoperative antimuscarinic drug that reduces salivary, tracheobronchial, and pharyngeal 
secretions, as well as decreases the acidity of gastric secretions blocks cardiac vagal inhibitory 
reflexes during intubation.  
The agent is supplied locally from the locked storage (room temperature) at the clinic. An 
accountability list will ensure the possibility to trace the agent from delivery on clinic to 
administration. The agent will be labelled with patient id and randomisation number by 
designated pulmonary nurse who will not attend during the procedure. One hour before 
procedure start 0.2 mg (=1 ml) glycopyrronium bromide is administrated intramuscular. Dose 
level is based on previous experiences for reduction of secretion on patients during sedation 
or anaesthesia. The agent will be supplied before procedure and the patient will be monitored 
bedside by a nurse anaesthetist. 
 
 
Coadministration of other medicinal products 
 
Lidocaine (Lidokain FarmaPlus 10mg/ml, Xylocain® 10 mg/ml) and Lidocaine-
naphazoline (Lidokainhydroklorid-nafazolin 34 mg/ml + 0,17 mg/ml)  
Lidocaine is a local anaesthetic of the amide group. The dosage will be adjusted according to 
the response of the patient and the site of administration. The lowest concentration and 
smallest dose producing the required effect should be given. The maximum dose for healthy 
adults should not exceed 200 mg. The agent is supplied locally from the locked storage (room 
temperature) at the clinic. The agent will be supplied before bronchoscopy starts and the 
patient and repeated if needed during the procedure.  
 
 
Rescue medication 
 
Alfentanil (Rapifen® 0.5mg/ml) 
Alfentanil is a narcotic analgesic, in general, as well as adjuvant to regional anaesthesia and 
for both short (bolus injections) and long (bolus, supplemented by increments or by infusion) 
surgical procedures. Because of its rapid and short-lasting action, alfentanil is particularly 
suited as a narcotic analgesic for short procedures and outpatient surgery, but also as an 
analgesic supplement for procedures of medium and long duration, since periods of very 
painful stimuli can easily be overcome by small increments of alfentanil or by adapting its 
infusion rate.  
The agent is supplied locally from the locked storage (room temperature) at the clinic. An 
accountability list will ensure the possibility to trace the agent from delivery on the clinic, by 
the local pharmacy, to administration. The agent will only be used as rescue medication if 
sedation with PCS is insufficient and will be labelled according to local regulations (not 
blinded). Intermittent bolus doses of 0.125 mg (=0.25 ml) alfentanil is administrated 
intravenously using a peripheral venous catheter. Dose level is based on previous experiences 
from procedures were additional analgesic is needed. The agent will only be supplied during 
procedure and the patient will be monitored bedside by nurse anaesthetist. 
 

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Naloxone (Naloxon B. Braun 0,4 mg/ml, Naloxon Hameln 0,4 mg/ml, Nexodal 0,4 mg/ml) 
Naloxone is indicated for the treatment of respiratory depression induced by natural and 
synthetic opioids. It may also be used for the diagnosis of suspected acute opioid overdosage. 
The agent is supplied locally from the locked storage (room temperature) at the clinic. An 
accountability list will ensure the possibility to trace the agent from delivery on the clinic, by 
the local pharmacy, to administration. The agent will only be used as rescue medication if 
suspected acute opioid over dosage occur and will be labelled according to local regulations 
(not blinded).  The dose should be titrated for each patient in order to obtain respiratory 
response while maintaining analgesia. An intravenous dose of 1.5 - 3.0 micrograms/kg body 
weight is usually sufficient, but a full two minutes should be allowed between each 100 
microgram increment of naloxone administered. 
 
Flumazenil (Lanexat® 0,1 mg/ml) 
Flumazenil is used to reverse the effects of benzodiazepines. By reversing the effects of 
benzodiazepines, it allows the patient to become conscious so that they can breathe unaided. 
An accountability list will ensure the possibility to trace the agent from delivery on the clinic, 
by the local pharmacy, to administration. The agent will only be used as rescue medication if 
suspected acute benzodiazepine over dosage occur and will be labelled according to local 
regulations (not blinded). The starting dose for adults is 0.2mg administered intravenously 
over 15 seconds. If the required level of consciousness is not obtained within 60 seconds, a 
further dose of 0.1mg can be injected and repeated at 60-seconds intervals to a maximum of 
1mg during anaesthesia. 
 
The study has no restrictions regarding concomitant medication used by the patient.  
 
 
Registration of efficacy 
 
Primary endpoint 
 
Discharge assessment 
Post Anaesthetic Discharge Scoring System (PADSS) 
The PADSS is used to clinically assess if the patient is ready to be discharged after 
anaesthesia/sedation and consist of five criteria: vital signs, ambulation, nausea and/or 
vomiting, pain and surgical bleeding (see further appendix 3). Each criterion is given a 
score ranging from 0 to 2. Only patients who achieve a total score of 9 or more are 
considered ready for discharge. A measurement of the PADSS score is done by pulmonary 
nurse every 15 min after bronchoscopy is finished (time =0 is when bronchoscope is 
removed) for 2 hours and thereafter every hour until two consecutive PADSS scores ≥ 9. 
When this is reached the patient may be discharged. It takes less than 1 minute to complete 
the assessment. 
 
Secondary endpoints 
 
Assessment of self-rated patient questionaries’ 

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Sense of coherence (SOC) 
The SOC is a theoretical formulation that provides a central explanation for the role of 
stress in human functioning. It is a self-rating scale and consists of 29 items (see further 
appendix 5). Scores are set by the patient for each question from 1 to 7 and codification of 
the items follows giving scores on a sub-scale level as well as a total score. The 
questionnaire used in the study is in Swedish language and will be handed out after 
informed consent is given and filled out by the patient between visit 1 and visit 2. It takes 
approximately 5 minutes to complete the questionnaire. The questionnaire will be mailed 
by the patient in a prepaid envelope to the Pulmonary Clinic. 
Coping Strategies Questionnaire (CSQ-SWE) 
The CSQ-SWE is the Swedish version of “The coping strategy questionnaire” and is a 50-
items self-rated questionnaire used to assess cognitive and behavioural strategies to cope 
with pain (see further appendix 6). Each coping strategy subscale consists of six items 
measured with a numerical rating scale ranging from 0 (“never do that”) to 6 (“always do 
that”). Subscale scores and total score is calculated. The questionnaire will be handed out 
after informed consent is given and filled out by the patient between visit 1 and visit 2. It 
takes approximately 5 minutes to complete the questionnaire. The questionnaire will be 
mailed by the patient in a prepaid envelope to the Pulmonary Clinic. 
Hospital Anxiety and Depression Scale (HADS) 
HADS is used to assess patents’ experience of anxiety and depression. It is a 14-item self-
rating scale and consists of seven questions for the subscales anxiety and depression (see 
further appendix 7). Each item is scored 0-3 and a total score for each subscale is 
calculated. The questionnaire used in the study is in Swedish language and will be handed 
out after informed consent is given and filled out by the patient between visit 1 and visit 2. 
It takes approximately 2 minutes to complete the questionnaire. The questionnaire will be 
mailed by the patient in a prepaid envelope to the Pulmonary Clinic. 
 
Post-discharge Surgical Recovery Scale (S-PSR) 
The modified Swedish version S-PSR is based on the “Post-discharge Surgical Recovery 
Scale” and is a 14-item questionnaire to assess the recovery post-discharge regarding the 
patients’ health status and activity (see further appendix 2). Each item is rated using a 
semantic differential scale and the total sum is multiplied by 100. The possible range is 10-
100, with higher score indicating a more favourable postoperative recovery. The 
assessment is done by the patient at home (or at ward if pro-longed hospital stay is 
necessary) in the evening on the day of bronchoscopy. It takes approximately 2 minutes to 
complete the questionnaire. The questionnaire will be mailed by the patient in a prepaid 
envelope to the Pulmonary Clinic. 
Modified version of Quality of Recovery (QoR-23) 
The questionnaire “Quality of Recovery” (QoR-23) is a 23 item questionnaire to assess 
recovery after day surgery regarding the patients’ emotional state, physical comfort and 
physical independence (see further appendix 4). Each item is rated on a five-point scale (1-
5) and the scores are summed. A higher score indicate a better quality of recovery. The 
assessment is done by the patient at home (or at ward if pro-longed hospital stay is 
necessary) in the morning the day after bronchoscopy. It takes less than 1 minute to 

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complete the assessment. The questionnaire will be mailed by the patient in a prepaid 
envelope to the Pulmonary Clinic. 
 
Patients’ satisfaction 
After patient has recovered according to the protocol and before discharge, the patient 
assesses their overall satisfaction with the procedure using the Likert-type scale (1. Very 
dissatisfied, 2. Dissatisfied, 3. Neither satisfied nor dissatisfied, 4. Satisfied, 5. Very 
satisfied). The patient may comment any cause which made the satisfaction score high or low 
and if the patient would like to receive the same method of sedation during a future 
bronchoscopy. 
 
Bronchoscopist evaluation  
After completion of the procedure the bronchoscopist assess their perception of cough, 
bronchial secretion respectively circumstances for a smooth performance of the bronchoscopy 
of procedure using the Likert-type scale (1. Very dissatisfied, 2. Dissatisfied, 3. Neither 
satisfied nor dissatisfied, 4. Satisfied, 5. Very satisfied).  
 
Requested/given bolus doses from PCS 
Each time the patient is requesting a bolus dose of propofol from the PCS it will deliver a pre-
set dose. If an additional dose is requested before the first dose has been completely delivered 
(due to multiple requests) an additional dose will not be delivered. All requests, delivered or 
not delivered, will be recorded in the PCS software and transferred to the CRF. 
 
Total dose given of topical anaesthetic, analgesia and sedation  
The total dose of given medication of topical anaesthetic, analgesia and sedation will be 
registered for each patient. For patients using the PCS requested respectively given bolus 
doses of propofol will be registered. 
 
Procedure safety variables  
Vital signs 
Vital signs (arterial oxygen saturation, respiratory frequency, non-invasive blood pressure and 
heart rate) will be recorded every five minutes as well as any interventions performed to 
maintain cardiovascular and respiratory stability.  
 
Level of sedation 
Level of sedation is assessed by the nurse anaesthetist using The Observer’s Assessment of 
Alertness/Sedation (OAA/S) scale (Chernik, D., et al. 1990) by specifying sedation level 
score between “Does not respond to mild prodding or shaking” (score 1) to “Responds readily 
to name spoken in normal tone” (score 5) (see further appendix 1).  
 
Level of sedation is measured by the nurse anaesthetist in 5 minutes intervals until procedure 
completion. 
 
Interventions 
When the pre-defined safety limits (see below) are breached during the procedures 
appropriate interventions has to be undertaken by the nurse anaesthetist and registered. 
 
Pre-defined safety limits and interventions 
Symptom 
Definition 
Intervention 

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Respiratory depression 
Respiratory rate < 8 breaths/min 
according to surveillance monitor 
OR 
visual count by nurse anaesthetist 
Encourage patient to breath 
Low oxygen saturation 
Oxygen saturation < 90% 
Increase oxygen flow 
Obstructed airway 
Obstructive apnea 
Apply chin lift 
Apnea 
Apnea according to surveillance 
monitor AND oxygen saturation < 
90% 
OR 
apnea > 30s detected visually by 
nurse anaesthetist AND oxygen 
saturation < 90% 
Assisted ventilation with 
mask and addition of at 
least 50% O2 
Bradycardia 
Heart rate < 40 beats/min 
Give atropine 0,5 mg 
Hypotension 
Non-invasive systolic blood pressure 
< 90 mmHg 
Give ephedrine 5 mg 
 
 
Registration of safety 
Safety variables regarding the level of sedation and vital signs are described above. A nurse 
anaesthetist is present during the whole procedure until sedation level OAA/S 5 is reached, 
thereafter and before procedure a pulmonary nurse is present. Bronchoscopist and 
anaesthesiologist are available via telephone and/or pager and can be present within a few 
minutes.  
All of the drugs are administered by routes and given in doses in accordance with approval 
from the Swedish Medical Products Agency. The personnel involved in the procedure are all 
familiar with the use of the drugs being studied.   
 
Incident 
The definition of an incident is any untoward event or unintended response to the study drug, 
irrespective of dose. Incidents should be reported whether they are related to the procedure or 
not, even a slight cold, a sprained foot etc. Exceptions that will not be reported as an incident 
is the most common adverse reactions reported in FASS from each study agent (see table 
below) or events considered to be part of the normal post-procedural process such as local 
pain from upper airway, hoarseness, fever, cough etc.  
 
Propofol 
Body system 
Adverse reaction 
Central and peripheral nervous system 
Headache when awakening 
Heart 
Bradycardia 
Vascular 
Hypotension 
Respiratory, thoracic and mediastinal 
Transient apnea during induction 
Gastrointestinal 
Nausea and vomiting during awakening 
General symptoms from site of administration 
Local pain at induction 
 
Midazolam 
Body system 
Adverse reaction 

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Psychiatric 
Agitation, excitation, anger 
Central and peripheral nervous system 
Unconscious movements, hyperactivity 
Heart 
Bradycardia 
Vascular 
Hypotension 
Respiratory, thoracic and mediastinal 
Respiratory depression, apnea 
Gastrointestinal 
Nausea and vomiting  
General symptoms from site of administration 
Local pain at induction 
 
Morphine-Scopolamine 
 
Body system 
Adverse reaction 
Psychiatric 
Euphoria, confusion, hallucination 
Central and peripheral nervous system 
Dysphoria, disorientation, dizziness, 
respiratory depression 
Eye 
Difficult accommodation, meiosis 
Heart 
Tachycardia, hypertension 
Vascular 
Hypotension 
Respiratory, thoracic and mediastinal 
Bronchoconstriction 
Gastrointestinal 
Nausea and vomiting, dry mouth  
General symptoms from site of administration 
Urticaria, itching 
 
Glycopyrronium bromide 
Body system 
Adverse reaction 
Central and peripheral nervous system 
Drowsiness 
Eyes 
Visual disturbances 
Heart 
Tachycardia, palpitations, ventricular 
arrhythmia 
Gastrointestinal 
Dry mouth 
 
Lidocaine and Lidocaine-naphazoline 
Body system 
Adverse reaction 
Vascular  
Hypotension, hypertension 
Central and peripheral nervous system 
Dizziness, paresthesia 
Heart 
Bradycardia 
Gastrointestinal 
Nausea and vomiting 
 
Alfentanil 
Body system 
Adverse reaction 
General 
Chills, pain at the injection site, fatigue 
Circulatory 
Bradycardia, tachycardia, hypotension, 
hypertension, decreased blood pressure, 
high blood pressure 
Airways 
Apnea 
Musculoskeletal 
Muscle rigidty 
Central and peripheral nervous system 
Drowsiness 

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Neurological 
Movement disorder, dizziness, sedation, 
dyskinesia 
Psychiatric 
Euphoric mood 
Eyes 
Visual disturbances 
 
Naloxone  
Body system 
Adverse reaction 
Central and peripheral nervous system 
Dizziness, headache 
Vascular 
Hypotension, hypertension 
Heart 
Tachycardia 
Gastrointestinal 
Nausea and vomiting 
 
Flumazenil  
Body system 
Adverse reaction 
Central and peripheral nervous system 
Dizziness, headache, agitation, tremor 
Eyes 
Diplopia, strabismus, increased amount of 
tear fluid. 
Vascular 
Hypotension, orthostatic hypotension 
Gastrointestinal 
Nausea and vomiting 
Skin 
Sweating 
General 
Fatigue, pain at the injection site 
 
All incidents that investigator, identifies as incident will be documented in the medical record 
and incident report until day after procedure due to short exposure to IMP and short half-life 
of IMP. 
 
In the incident report the following grading is used to rate the severity of an incidence: 
 Mild = aware of the symptoms but they are tolerable 
 Moderate = symptoms partially affect daily activities 
 Severe = symptoms significantly affect daily activities 
 
The investigator assesses the relationship between the incidence and the study drug, as 
defined: 
 Likely = good reasons and sufficient documentation to suspect causality 
 Possible = causality cannot be dismissed 
 Unlikely = Another reason is more likely 
 Not evaluable = causality cannot be confirmed 
 
Serious adverse events 
Investigator of the study will determine if the incidence is a SAE or not. Criteria for being a 
SAE: 
 Death 
 Life-threatening condition 
 Conditions that require hospitalization or prolongs time at hospital 
 Conditions which cause a lasting or significant disability or incapacity 
 Congenital malformation or congenital defect 

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 Other serious medical event according to investigator 
 
The investigator shall report all SAE to the sponsor within 24 hours. The sponsor will decide 
whether the SAE is considered as a SUSAR, which promptly shall be reported to the Medical 
Products Agency and the Ethics Review Board. 
 
Annual safety report 
Annually, while the study is ongoing, the sponsor reports a safety report to the Medical 
Products Agency (MPA) and Ethics Review Board (ERB). The report defines the time period 
reported and summarizes number of patients that have completed/discontinued/withdrawn, all 
SAEs, all SUSARs, changes in the study drugs safety information (Summary of Product 
Characteristics (SmPC)) as well as a summary regarding the safety of the patients within the 
study concerning the risk-benefit since the study was approved.  
 
SUSAR-report 
A SUSAR is a suspected serious unforeseen incident, undesirable severe reaction to a study 
drug (which has not been previously reported). 
 
A SUSAR that is fatal or life-threatening shall be reported as soon as possible and no later 
than 7 days after it has become known to the sponsor. Relevant follow-up information will be 
forwarded within another 8 days. Other SUSARs shall be reported as soon as possible and no 
later than 15 days after they come to the sponsor's knowledge. The sponsor shall inform all 
investigators participating in the study about the SUSAR. 
Report regarding SUSARs to the MPA will be done using the CIOMS form which will be 
scanned and snet electronically via email to mpa@registrator.se by sponsor. 
 
Pregnancy 
Women of childbearing potential will be asked about pregnancy. Pregnant women and 
women with positive S-β-HCG will be excluded in the study. All sedation arms include drugs, 
midazolam or propofol, classified as “Category C” during pregnancy. The accumulated doses 
of propofol or midazolam given as sedation during bronchoscopy is low. To the best of our 
knowledge the risk of unknown pregnancy is low and the fetal risks are very low. Inclusion of 
women of childbearing potential requires use of a effective contraceptive which shall be 
maintained from day of informed consent until day after procedure. Women who are 
breastfeeding suspend breastfeeding during 24 hours after bronchoscopy.        
 
Statistics 
A total of 300 patients (100 patients in each group) with a power of 80% and we estimate to 
generate a statistical significant level of less than 0,05 for the primary endpoint. Interim 
analysis will be performed after 150 patients. We use the method according to Pocock, where 
the significance limit is p=0.0294 at the interim analysis and 0.0294 at the main analysis.  
The primary endpoint, discharge within two hours, will be analysed using a Chi2 test. 
Secondary endpoints, the questionnaires (SOC, CSQ-SWE, HADS, S-PSR, QoR-23), patient 
satisfaction and bronchoscopists evaluation, both on a Likert type scale will be analysed with 
Mann-Whitney U-test.  
Number of requests and total dose of propofol will be analysed with Student´s t-test.  
All analyses above will be done with planned comparison, first we compare group MM with 
the combined MP+GP group, and thereafter the groups MP and GP will be compared.  

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The number of dose request from the PCS device and total dose of propofol/alfentanil/topical 
anaesthetics, respectively, will only be compared between groups GP and MP. To investigate 
if the total administered dose of propofol is associated with patient characteristics according 
to questionnaires (SOC, CSQ-SWE, HADS) we will use Pearson correlation analysis and 
linear regression with total dose as dependent variable to be able to analyse several 
questionnaires simultaneously. 
Safety variables, vital parameters, level of sedation and number of interventions will be 
analysed with Students t-test or Mann-Whitney U-test. 
 
Quality control and quality assurance 
Department of Anesthesiology and surgical clinic, University hospital of Linköping is the 
coordinating center for the study with Lena Nilsson as sponsor and primary investigator. 
The study team consists of the study actively participating researchers (doctors and nurses). 
Concerned staff at the pulmonary clinic will be informed in detail about the study by the 
research team before the study start, and the research team will have regular contact with the 
staff during the study period. Once the study is completed results of the study are presented to 
all personnel involved. 
 
The sponsor is responsible for implementing and maintaining quality assurance and quality 
control systems with written standard operating procedures to ensure that trials are conducted 
and data are generated, documented and reported in compliance with the protocol, ICH GCP, 
and Helsinki Declaration (2013). 
 
Monitoring 
The study will be monitored according to an agreement between sponsor/principal 
investigator and the independent monitor Forum Östergötland (University Hospital, SE-581 
85 Linköping). 
 
The investigator is obligated to give direct access to medical record for monitors, inspectors 
from the Medical Product Agency and any possible evaluator from the ethics committee. 
 
The monitor will ensure that informed consent are obtained according to regulations, 
compliance with the study protocol, to correct the data collected for the study developed CRF 
and that adverse events reported according to LVFS 2011: 19. It is not planned for external 
control (audit) of the study. The study will be registered in accordance with "The International 
Committee of Medical Journal Editors (ICMJE) Initiative" to "Clinical Trials.gov" upon 
approval by the MPA and EPN. 
 
At the initial meeting the monitor will review study protocol, clinical research form (CRF), 
study binder including all essential documents, the facility and equipment used within the 
study. Afterwards a written report is sent to the sponsor. 
 
The first monitoring visit will take place when the first 2-5 patients are enrolled in the study. 
At each visit the monitor checks inclusion/exclusion criteria, signed consents, that source data 
conform to the information specified for the study efficacy/safety variables and SAEs but also 
other documents of importance. The monitor checks with the sponsor if significant changes 
have been made in study related documents and that permission for the changes have been 
obtained as well as that changes are traceable. A report will be sent by the monitor to the 
sponsor after each conducted visit. 
 

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Further visits during the study will be done according to the agreement. 
 
The last monitoring visit at the clinic will be when the last participant has completed his last 
visit. The monitor verifies that study binder with essential documents including CRF is 
complete and ready for archiving. A written report of the visit is written by the monitor and 
sent to the sponsor. 
 
Source data 
Source data is defined as any information in original records and certified copies of original 
records of clinical findings, observations or other activities necessary for reconstruction and 
evaluation for the study (e.g. CRFs, medical records). For this study, a separate Source Data 
Identification List will be written defining the source data for this study. 
 
Ethical considerations 
 
The patients are supervised by experienced personnel during and after the procedure. The 
anaesthetic nurses and anaesthesiologist are trained to handle possible emergency situations 
that might occur in connection with sedation and recovery. Respiration and circulation is 
monitored continuously in accordance with clinical routine, and does not cause any 
discomfort or pain to the patient.  
 
The study does not require any extra hospital visits for the patient. The questionnaires might 
by some be regarded as integrity violating. We stress that answering is voluntary and that all 
questions need not to be answered. Our experience is that patients in a phase of stress and 
sorrow after serious information about illness, often find it of value to express their thoughts 
and feelings.   
 
Procedure for recruiting and obtaining informed consent 
 
During the first visit (pre-procedural visit) at the clinic recruitment to the study will be done. 
The patient is given verbal and written information about the study objectives, purpose and 
approach and will be given the opportunity to ask questions to the investigator. Participation 
is entirely voluntary. If the patient accepts study participation it results in a signed informed 
consent by the patient and investigator. The information and subsequent consent informs the 
patient that an independent monitor and medical regulatory authorities are allowed to compare 
data from the medical record with CRF.  
 
 
Handling and archiving data 
Patients, who are selected to undergo bronchoscopy during the time for the study will be 
recorded in a screening log. Reason for exclusion shall be documented in the log. Patients’ 
that fulfil the criteria for inclusion and have no exclusion criteria will be registered in a patient 
identification list with their personal identification number, full name and the assigned study 
number (consecutively). Information regarding the participation, including where the code list 
is stored (if necessary to break the code), will be recorded by the investigator in the patients’ 
medical journal. The patient will receive a study number which can be tracked through the 
patient identification list. The patient identification list will be kept with the signed consent in 
a locked room at the clinic. Patients will not be given a "Study ID card" due to the drugs short 

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half-life. The envelopes for randomization are stored in a locked drug room at the clinic only 
accessible for pulmonary nurses at the clinic. 
 
For this study, a study binder will be established that contains study protocol, patient 
information, informed consent from patients, patient registration form, form for the 
registration of adverse events (AE), form for recording serious adverse events (SAE), patient 
questionnaires’ used in the study, screening and patient identification list, data source list, 
delegation list, application and approval of the study from the regional Ethics Committee in 
Linköping and Medical Proiduct Agency, and any amendments. 
 
Codelist will be stored in locked room at the clinic. Relevant data from the patients’ medical 
history is recorded in CRF. Relevant data is medical history and medication that affect the 
patient's cardiorespiratory stability and / or treatment of pain / anxiety. Other data collected 
will be written in the CRF at each visit. Data from PCS will manually be transferred from 
device to CRF. A delegation list will be established which identify all individuals involved 
and the primary investigator delegated tasks.  
The CRF will be recorded both by pulmonary nurse, nurse anaesthetic, anaesthesiologist and 
pulmonary physician/bronchoscopist who individually will all have the right to make 
corrections of their individual records in the CRF. Deviations from the study protocol will be 
treated individually. Data will be analysed according to intention-to-treat (ITT). Deviations 
from the study protocol will be treated individually. Data will be analysed according to 
intention-to-treat (ITT). Data will be coded and entered into a computer database. The 
handling of data, including data quality control, will comply with regulatory guidelines (e.g., 
International Conference on Harmonization Good Clinical Practice [ICH GCP]).  
 
 
All study-related data will be stored in rooms with limited access. Medical records will be 
archived in the County Archives under current regulations for archiving of patient medical 
records. The study documents are stored according to RA-FS 1999: 1 and rules for 
conservation and thinning of research documents at Linköping University of at least 10 years. 
Thereafter the documents will be destroyed. Privacy applies according to Hälso- och 
sjukvårdslagen for persons who take part of the medical record and study documents 
concerning patients in the study.  
 
Insurance 
Patients are insured by Läkemedelsförsäkringen and Patientförsäkringen. 
 
Finance 
The study is funded by grants from regional funds. The application is made by the 
Department of Anesthesiology and surgical clinic, University hospital of Linköping. The 
study has no sponsorship from industry. 
 
Reporting and publishing 
Study results will be summarized and submitted to the MPA within one year after end of 
study. Presentation of the results is planned in regional, national and international contexts, 
and the results will be sent for publication in an internationally recognized journal. 
 

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Substantial amendment of study and declaration of end of trial 
Requests for a substantial amendment in the study protocol will be sent by sponsor to the 
MPA and Ethics Committee. When the study is closed an End-of-trial (EOT) report will be 
sent by sponsor to the MPA. 
 
Discrepancies’ and violations 
If discrepancies or violations are made that affect, or with high probability could affect the 
patients’ safety or the study's scientific value, sponsor will report immediately to the MPA.  
 
 
 

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References 
 
Chernik, D. A., et al. (1990). "Validity and reliability of the Observer's Assessment of 
Alertness/Sedation Scale: study with intravenous midazolam." J Clin Psychopharmacol 10(4): 
244-251. 
 
Du Rand, I. A., et al. (2013). "British Thoracic Society guideline for diagnostic flexible 
bronchoscopy in adults: accredited by NICE." Thorax 68(8):786-787.  
 
Hong, K., et al. (2015). “Safety and Efficacy of the Moderate Sedation During Flexible 
Bronchoscopic Procedure: A Systematic Review and Meta-Analysis of Randomized 
Controlled Trials.” Medicine (Baltimore) 94(40): e1459 
 
Hwang, J., et al. (2005). "Comparison of alfetanil and ketamine in combination with propofol 
for patient-controlled sedation during fiberoptic bronchoscopy." Acta Anaesthesiol Scand 
49(9): 1334-1338. 
 
Momen, M. W., et al. (2011). “American College of Chest Physicians Consensus Statement 
on the Use of Topical Anesthesia, Analgesia, and Sedation During Flexible Bronchoscopy in 
Adult PatientsChest 140(5):1342-1350.  
 
Nilsson, A., et al. (2015). "Should Propofol and Alfentanil Be Combined in Patient-
Controlled Sedation? A Randomised Controlled Trial Using Pharmacokinetic Simulation." 
Open Journal of Anesthesiology 5: 122-129. 
 
Stolz, D., et al. (2009). "Propofol versus combined sedation in flexible bronchoscopy: a 
randomised non-inferiority trial." Eur Respir J 34(5): 1024-1030. 
 
Yoon, H. I., et al. (2011). "Comparison of propofol and the combination of propofol and 
alfentanil during bronchoscopy: a randomized study." Acta Anaesthesiol Scand 55(1): 104-
109. 
 
 
 

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Agreement 
I have read the protocol and will conduct the study according to the protocol, Good Clinical 
Practice and applicable regulations. 
I will inform the employees who will be involved in the study and will assure me that they 
have sufficient knowledge to carry out the study.  
 
 
Primary investigator and sponsor signature                                              Date 
 
Printed name 
 
 
 
 
 

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Appendix 1 – Observer's assessment of alertness/sedation 
(OAA/S) scale 
 
Observation  
Score level  
Responds readily to name spoken in normal tone 
5 
Lethargic response to name spoken in normal tone 
4 
Responds only after name is called loudly and/or repeatedly 
3 
Responds only after mild prodding or shaking 
2 
Does not respond to mild prodding or shaking 
1 
 
 
 
 
  
 
 

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Appendix 2 – Modified Post-discharge Surgical Recovery (S-PSR) scale 
 
Enkäten fylls i samma dag på kvällen (kl 20) som Du genomförde undersökningen 
 
Samtliga uppgifter kommer att behandlas konfidentiellt och vad du svarat kommer inte att 
kunna identifieras i resultatredovisningen. 
 
 
 
Dagens datum är: 
 
 
Tid du denna enkät fylls i? Klockan______ 
 
 
Vilket datum gjorde Du undersökningen? Den 
 
 
När ankom du till sjukhuset? Klockan 
___ 
 
När fick du åka hem? Datum 
 
Klockan 
 
 
 
 
 
 
 
 
 
 
 
 
Nedanstående fråga handlar om hur du upplever din hälsa. Ringa in den siffra som bäst 
överensstämmer med hur du upplever din hälsa just nu, där 1 står för ”mycket dålig” och 10 
för ”mycket god”. 
 
Just nu upplever jag att min hälsa är: 
 
Mycket dålig  
1 
2 
3 
4 
5 
6 
7 
8 
9 
10  
Mycket god  
 
 
Om du graderar din hälsa med 5 eller lägre vilka hälsoproblem/svårigheter har du idag? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
V.g vänd på bladet 

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Följande påståenden handlar om hur du känner dig just nu. Varje påstående består av två 
ändpunkter med en gradering däremellan. Ringa in den siffra som bäst motsvarar hur du 
känner dig. 
 
Just nu känner jag mig: 
 
pigg 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 slö 
 
smärtfri 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 mycket smärtpåverkad 
 
mycket trött 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 full av energi 
 
inte alls kapabel att göra 
det som jag brukar göra 
 
1 
 
2 
 
3 
 
4 
 
5 
 
6 
 
7 
 
8 
 
9 
 
10 
 
helt kapabel att göra 
det som jag brukar 
göra 
 
ha ett stort behov av vila 
på dagtid 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 inte alls i behov av vila 
på dagtid 
 
inte alls lika rörlig som 
vanligt 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 precis lika rörlig som 
vanligt 
 
i behov av att bara vara 
hemma i bostaden 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 helt redo för att lämna 
bostaden 
 
har kraft/ork att fysiskt 
anstränga mig 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 helt utan kraft/ork att 
fysiskt anstränga mig 
 
bättre än jag trodde att jag 
skulle göra 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 sämre än jag trodde att 
jag skulle göra 
 
 
 
 
 
V.g vänd på bladet. 

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Just nu känner jag mig: 
inte alls återhämtad efter 
undersökningen 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 helt återhämtad efter 
undersökningen 
 
helt tillbaka till min 
vanliga livsföring  
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 inte alls tillbaka till 
min vanliga livsföring 
 
helt tillbaka till mitt 
vanliga själsliga tillstånd 
 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 inte alls tillbaka till 
mitt vanliga själsliga 
tillstånd 
 
 
 
 
 
 

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Appendix 3 –Post Anaesthetic Discharge Scoring System (PADSS) 
for Home readiness after Ambulatory Surgery 
 
 
 

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Appendix 4 – Modified Quality of Recovery (QoR-23) 
 
Kryssa i det som stämmer bäst överensstämmer med hur du mått de 
senaste 24 timmarna.  
 
Under de senaste 24 timmarna har jag; 
 
 
Instämmer inte alls 
 
Instämmer helt  
1 
2 
3 
4 
5 
1. Kunnat andas lätt 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2. Sovit gott 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3. Kunnat njuta av maten 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4. Känt mig utvilad 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
5. Haft en känsla av allmänt 
välbefinnande 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6. Haft kontroll över min 
situation 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
7. Känt mig avslappnad 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8. Haft en röst som varit som 
vanligt 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
9. Kunnat borsta tänderna  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
10. Kunnat sköta om mitt eget 
utseende 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
11. Kunnat skriva som vanligt 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
12. Kunnat återgå till arbetet 
eller sköta om vanliga bestyr 
i hemmet 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Har du upplevt något av följande  
under de senaste 24 timmarna? 
 
Inte alls 
 
 
 
Hela tiden 
 
5 
4 
3 
2 
1 
13. Illamående 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
14. Kräkningar 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
15. Rastlöshet 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
16. Skakningar eller ryckningar 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
17. Frusenhet 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
18. Yrsel 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
19. Oro 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
20. Nedstämdhet 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
21. Ensamhet 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
22. Insomningssvårigheter 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
23. Mardrömmar 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Sedan du kom hem efter proceduren har du haft några besvär som du inte hade innan? 
 
Nej  
Ja     
Om ja, vilket besvär har du haft? 
 
 
 
 
 
 
 
 
 
_______________ 
 
 
Om ja, har du behövt kontakta sjukvården?  
 
 
 
 
 
 
 
 
_______________ 
 
 
 

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Appendix 5 – Sense of coherence (SOC) 
 
Här är några frågor som berör skilda områden i livet. Varje fråga har 7 möjliga svar. Var 
snäll och markera den siffra som bäst passar in på ditt svar. Siffran 1 eller 7 är svarens 
yttervärden. Om du instämmer i det som står under 1, så ringa in 1:an; om du instämmer i 
det som står under 7, så ringa in 7:an. Om du känner annorlunda, ringa in den siffra som bäst 
överensstämmer med din känsla. Ge endast ett svar på varje fråga. 
 
1.   När du talar med människor, har du då en känsla av att de inte förstår dig?  
1            2            3            4            5            6            7 
har aldrig                                                                                          har alltid 
den känslan                                                                                       den känslan 
 
2.  När du har varit tvungen att göra någonting som krävde samarbete med andra, hade du 
då en känsla av att det  
1            2            3            4            5            6            7 
kommer säkert                                                                                  kommer säkert 
inte att bli gjort                                                                                 att bli gjort 
 
3.   Tänk på de människor du kommer i kontakt med dagligen, bortsett från dem som står 
dig närmast. Hur väl känner du de flesta av dem?  
1            2            3            4            5            6            7 
tycker att                                                                                            känner dem 
de är främlingar                                                                                 mycket väl 
 
4.   Har du en känsla av att du inte riktigt bryr dig om vad som händer runt omkring dig?  
1            2            3            4            5            6            7 
mycket sällan                                                                                     mycket ofta 
eller aldrig 
 
5. Har det hänt att du blev överraskad av beteendet hos personer som du trodde du 
kände väl?  
1            2            3            4            5            6            7 
har aldrig                                                                                            har ofta 
hänt                                                                                                     hänt 
 
6.    Har det hänt att människor som du litade på har gjort dig besviken?  
1            2            3            4            5            6            7 
har aldrig                                                                                            har ofta 
hänt                                                                                                     hänt 
 
7.    Livet är:   
1            2            3            4            5            6            7 
alltigenom                                                                                          fullständigt 
intressant                                                                                            enahanda 
 
8.     Hittills har ditt liv:  
1 
2 
3 
4 
5 
6 
7 
helt saknat 
genomgående haft 
mål och mening                                                                                  haft mål och mening 
 

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1 
2 
3 
4 
5 
6 
7 
mycket ofta 
mycket sällan/aldrig 
1 
2 
3 
4 
5 
6 
7 
mycket ofta 
mycket sällan/aldrig 
9.     Känner du dig orättvist behandlad?  
 
 
 
 
 
 
 
 
 
 
 
11.     De flesta saker du gör i framtiden kommer troligtvis att vara:   
1            2            3            4            5            6            7 
helt                                                                                                   fullkomligt 
fascinerande                                                                                    urtråkiga 
 
12. 
Har du en känsla av att du befinner dig i en obekant situation och inte vet vad du skall 
göra?  
  
 
 
13.      Vilket påstående beskriver bäst hur du ser på livet?  
1            2            3            4            5            6            7 
det går alltid                                                                                   det finns ingen lösning på 
att finna en                                                                                     livets svårigheter 
lösning på 
livets 
svårigheter 
 
14.       När du tänker på ditt liv, händer det mycket ofta att du:  
1            2 
3 
4 
5 
6 
7 
känner hur 
frågar dig själv varför du 
härligt det är 
överhuvudtaget finns till 
att leva 
 
15.       När du ställs inför ett svårt problem är lösningen:  
1            2            3            4            5            6            7 
alltid förvirrande                                                                           fullständigt solklart 
och svår att finna 
 
16. 
Är dina dagliga sysslor en källa till:  
1            2            3            4            5 
glädje och djup 
tillfredsställelse 
6 
7 
smärta och leda 
17.       I framtiden kommer ditt liv förmodligen att vara:  
1            2            3            4            5            6            7 
fullt av för-                                                                                    helt förutsägbart och utan 
ändringar utan                                                                               överraskande förändringar 
att du vet vad som 
händer härnäst 
 
 
10. De senaste tio åren har ditt liv varit:  
1            2            3            4            5 
6 
7 
fullt av för- 
helt förutsägbart 
ändringar utan 
utan överraskande 
att du visste vad 
förändringar 
som skulle hända 
härnäst 

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18. 
När något otrevligt hände tidigare brukade du:  
1            2            3            4            5            6 
älta det om 
och om igen 
7 
säga ”Det var det” och sedan 
gå vidare 
 
19. 
Har du mycket motstridiga känslor och tankar?  
1            2            3            4            5            6 
mycket 
ofta 
7 
mycket sällan/aldrig 
 
20.       När du gör något som får dig att känna dig väl till mods:  
1            2 
3 
4 
5 
6 
7 
kommer du 
kommer det säkert att 
säkert att fortsätta 
hända något som förstör 
att känna dig väl 
den goda känslan 
till mods 
 
21.       Händer det att du har känslor inom dig som du helst inte vill känna?  
1            2            3            4            5            6            7 
mycket                                                                                           mycket sällan/aldrig 
ofta 
 
22.       Du är inställd på att ditt personliga liv i framtiden kommer att vara:  
1            2            3            4            5            6            7 
helt utan                                                                                         fyllt av mål och mening 
mål och mening 
 
23. 
Tror du att det i framtiden alltid kommer att finnas människor som du kan räkna 
med?  
1            2            3            4            5            6            7 
det är du                                                                                         det tvivlar du på 
säker på 
 
24. 
Händer det att du har en känsla av att du inte exakt vet vad som håller på att 
hända?  
1            2            3            4            5            6            7 
mycket                                                                                           mycket sällan/aldrig 
ofta 
 
25.       Även en människa med stark självkänsla kan ibland känna sig som en ”olycksfågel”. 
Hur ofta har du känt det så?  
1 
2 
3 
4 
5 
6 
7 
aldrig 
mycket ofta 
 
26. 
När något har hänt, har du vanligtvis funnit att:  
1            2            3            4            5            6 
du över- eller 
undervärderade 
dess betydelse 
7 
du såg saken i dess rätta 
perspektiv 
 
 
 
 
 
 
 

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27. 
När du tänker på svårigheter som du troligtvis kommer att möta inom viktiga 
områden av ditt liv, har du då en känsla av att:  
1            2            3            4            5            6            7 
du alltid                                                                                         du inte kommer att lyckas 
kommer att                                                                                    övervinna svårigheterna 
lyckas övervinna 
svårigheterna 
 
28. 
Hur ofta känner du att det inte är någon mening med de saker du gör i ditt dagliga 
liv?  
1            2            3            4            5            6            7 
mycket                                                                                           mycket sällan/aldrig 
ofta 
 
29.       Hur ofta har du känslor som du inte är säker på att du kan kontrollera?  
1            2            3            4            5            6            7 
mycket                                                                                           mycket sällan/aldrig 
ofta 
  
 
 
 
 
 
 
 

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Appendix 6 – Coping Strategies Questionnaire (CSQ-SWE) 
 
 

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Appendix 7 – Hospital Anxiety and Depression Scale (HADS) 
Läs varje påstående nedan och sätt ett kryss i rutan till vänster om det svar, som kommer 
närmast hur du känner dig under den senaste veckan. Fundera inte alltför länge. Det första 
svar som dyker upp är antagligen riktigare än ett svar som du funderat på länge. 
Svara på alla frågorna, kryssa bara i en ruta för varje påstående! 
 
1. 
Jag känner mig spänd eller ”uppskruvad” 
 
 För det mesta 
 
 Ofta 
 
 Då och då 
 
 Inte alls 
 
2.  Jag uppskattar fortfarande samma  
      saker som förut. 
 
 Precis lika mycket 
 
 Inte riktigt lika mycket 
 
 Bara lite 
 
 Nästan inte alls 
 
3. Jag känner mig rädd, som om något  
     förfärligt håller på att hända. 
 
 För det mesta 
 
 Ofta 
 
 Då och då 
 
 Inte alls 
 
4. Jag kan skratta och se saker från den  
     humoristiska sidan. 
 
 Lika mycket som jag alltid kunnat 
 
 Inte riktigt lika mycket som förut 
 
 Absolut inte så mycket som förut 
 
 Inte alls 
 
5. Oroande tankar kommer för mig. 
 
 Mycket ofta 
 
 Ofta 
 
 Då och då  
 
 Någon enstaka gång 
 
6. Jag känner mig glad.  
 
 Inte alls 
 
 Inte så ofta 
 
 Ibland 
 
 För det mesta  
 
7. Jag kan sitta i lugn och ro 
      och känna mig avspänd. 
 
 Absolut 
 
 Oftast 
 
 Inte ofta 
 
 Inte alls 
 
 
8. Jag känner mig som om allting går trögt. 
 
 Nästan jämt 
 
 Ofta 
 
 Ibland 
 
 Inte alls 
 
9. Jag känner mig rädd, som om jag har 
    ”fjärilar i magen”. 
 
 Inte alls 
 
 Någon gång 
 
 Rätt ofta 
 
 Mycket ofta 
 
10. Jag har tappat intresset för mitt  
      utseende. 
 
 Helt och hållet 
 
 Ganska mycket 
 
 Lite grand 
 
 Inte alls 
 
11. Jag känner mig rastlös, som om jag  
        måste vara på språng. 
 
 Väldigt mycket 
 
 En hel del 
 
 Inte så mycket 
 
 Inte alls 
 
12. Jag ser fram emot saker och ting med 
       glädje. 
 
 Lika mycket som förut 
 
 Något mindre än tidigare 
 
 Klart mindre än tidigare 
 
 Nästan inte alls 
 
13. Jag får plötsliga panikkänslor. 
 
 Mycket ofta 
 
 Ganska ofta 
 
 Inte så ofta 
 
 Inte alls  
 
14. Jag kan njuta av en bra bok, eller ett 
       bra radio- eller TV – program. 
 
 Ofta 
 
 Ibland 
 
 Inte så ofta 
 
 Mycket sällan 

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