A Randomised Control Trial to Compare Quality of Recovery Between Desflurane and Isoflurane Inhalational Anaesthesia in Patients Receiving General Anaesthesia for Ophthalmological Surgery at Dr. George Mukhari Academic Hospital
Phase: NA
Conditions: Quality of Recovery, Anesthesia Recovery Period
Sponsor: Sefako Makgatho Health Sciences University

 
 
 
A Randomised Control Trial to Compare Quality of Recovery 
between Desflurane and Isoflurane Inhalational Anaesthesia in 
Patients Receiving General Anaesthesia for Ophthalmological 
Surgery at a Tertiary Hospital 
(DIQoR Trial) 
ClinicalTrials.gov: NCT04188314 
 
 
 
Chief Researcher: 
Dr. Charlé Steyl, Registrar, Department of Anaesthesiology  
Student Number: 201710494 
 
Supervisor: 
Prof. Hyla Kluyts, Clinical Lead, Department of Anaesthesiology  
 
 
 
 
 
Issue Date:   
 
 
19 April 2021 
Protocol Amendment Number: 5 
Authors: 
 
 
 
C.S. 
 
 
 
 

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Table of Contents 
1 
ADMINISTRATIVE INFORMATION ............................................................................................................................... 2 
1.1 
TRIAL REGISTRATION ....................................................................................................................................................... 2 
1.2 
REVISION CHRONOLOGY ................................................................................................................................................... 3 
1.3 
ROLES AND RESPONSIBILITIES ............................................................................................................................................ 4 
1.4 
FUNDING....................................................................................................................................................................... 4 
1.5 
TIMELINE....................................................................................................................................................................... 5 
2 
INTRODUCTION .......................................................................................................................................................... 5 
2.1 
BACKGROUND ................................................................................................................................................................ 5 
2.2 
AIM AND OBJECTIVES ...................................................................................................................................................... 9 
3 
METHODOLOGY ....................................................................................................................................................... 10 
3.1 
TRIAL DESIGN ............................................................................................................................................................... 10 
3.2 
PARTICIPANTS, INTERVENTIONS AND OUTCOMES ................................................................................................................ 10 
3.3 
ASSIGNMENT OF INTERVENTIONS ..................................................................................................................................... 20 
3.4 
DATA COLLECTION ........................................................................................................................................................ 21 
3.5 
DATA MANAGEMENT .................................................................................................................................................... 22 
3.6 
DATA ANALYSIS & STATISTICAL METHODS ......................................................................................................................... 24 
3.7 
MONITORING ............................................................................................................................................................... 25 
3.8 
RELIABILITY AND VALIDITY .............................................................................................................................................. 25 
3.9 
BIAS ........................................................................................................................................................................... 26 
4 
ETHICS AND DISSEMINATION ................................................................................................................................... 27 
5 
REFERENCES ............................................................................................................................................................. 28 
6 
APPENDICES ............................................................................................................................................................. 30 
6.1 
SPIRIT STATEMENT CHECKLIST........................................................................................................................................ 30 
6.2 
FEASIBILITY QUESTIONNAIRE TO TREATING ANAESTHETISTS ................................................................................................... 33 
6.3 
PATIENT INFORMATION LEAFLET ...................................................................................................................................... 34 
6.4 
CONSENT FORM ........................................................................................................................................................... 35 
6.5 
STANDARDISED ANAESTHESIA PROTOCOL FOR TREATING ANAESTHETISTS – VERSION 1 .............................................................. 36 
6.6 
STANDARDISED ANAESTHESIA PROTOCOL FOR TREATING ANAESTHETISTS – VERSION 2 (FINAL) ................................................... 37 
6.7 
CASE REPORT FORM: DATA COLLECTION ........................................................................................................................... 38 
6.8 
CASE REPORT FORM: QOR-15 ENGLISH............................................................................................................................ 39 
 
 

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1 Administrative Information 
1.1 Trial Registration 
1.1.1 
Registry 
Registered in ClinicalTrials.gov with reference number: NCT04188314. 
Submitted protocol to National Health Research Database (NHRD) – awaiting feedback. 
1.1.2 
WHO Data Set 
Data category 
Information 
Primary registry and trial identifying number 
ClinicalTrials.gov: 
NCT04188314 
Date of registration in primary registry 
4 December 2019 
Secondary identifying numbers 
SAHPRA Phase IV Notification: N20210205 
Source(s) of monetary or material support 
JPRF Research Fund 
Primary sponsor 
JPRF Research Fund 
Secondary sponsor(s) 
Abbvie Scholarship 
Contact for public queries 
C. Steyl: csteyl1@gmail.com 
Contact for scientific queries 
C. Steyl: csteyl1@gmail.com 
Public title 
Comparing Quality of Recovery Between Desflurane & 
Isoflurane in Eye Surgery Patients at Dr George Mukhari 
Academic Hospital (DIQoR Trial) 
Scientific title 
A Randomised Control Trial to Compare Quality of 
Recovery between Desflurane and Isoflurane Inhalational 
Anaesthesia in Patients Receiving General Anaesthesia 
for Ophthalmological Surgery at Dr. George Mukhari 
Academic Hospital (DIQoR Trial) 
Countries of recruitment 
South Africa 
Health condition(s) or problem(s) studied 
Quality of Recovery after General Anaesthesia 
Intervention(s) 
Control drug: Isoflurane 
Intervention drug: Desflurane 
Key inclusion and exclusion criteria 
Ages eligible for study: 18-80 years 
Sexes eligible for study: both 
Accepts healthy volunteers: no 
Inclusion criteria: adult patients (18-80 years), patients 
presenting for ophthalmological surgery under general 
anaesthesia, ASA I and II, able to communicate in English, 
Setswana or Afrikaans. 

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Data category 
Information 
Exclusion criteria: ASA III and above, contra-indications to 
Laryngeal Mask Airway use during general anaesthesia, 
severe medical or surgical conditions who are expected to 
have prolonged admissions or ICU admissions, 
uncontrolled psychiatric conditions, known allergy or 
adverse reaction to volatile anaesthetics, known or 
suspected susceptibility to Malignant Hyperthermia, 
incomplete records, patients who are not treated according 
to the prescribed treatment protocol. 
Study type 
Interventional 
Allocation: randomised 
Masking: double blind (patient and observer) 
Date of first enrolment 
February 2020 
Target sample size 
180 
Recruitment status 
Recruiting 
Primary outcome(s) 
To evaluate whether there is a difference between post-
operative quality of recovery in patients who received 
desflurane and in patients who received isoflurane for 
maintenance of anaesthesia, using the QoR-15 score, a 
patient-rated outcome measure. 
Key secondary outcomes 
• 
To compare the consumption and relative cost of 
using isoflurane vs desflurane with a minimal or basal 
flow anaesthetic technique. 
• 
To evaluate the difference in time spent in the recovery 
room between the two patient groups will also be 
compared. 
 
1.2  Revision Chronology 
Date 
Protocol Amendment 
Number 
Description 
1 Nov 2018 
1 
Original 
8 April 2019 
2 
Amendments after first review by SMU School Research 
Committee, formatted according to SPIRIT Statement 2013. 
Change in title and development of acronym. 
14 Feb 2020 
3 
Updated Standard Anaesthesia Treatment Protocol, Updated 
Case Report Form: Data Collection, Included results from 

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Feasibility Questionnaire and Pilot Study. Included details of 
registration with ClinicalTrials.gov. 
10 Oct 2020 
4 
Updated title: Removed “Dr George Mukhari Academic 
Hospital”, replaced with “a Tertiary Hospital”. 
This was requested by the SMU Research Ethics Committee 
to make the research more generalizable. 
19 April 2021 
5 
Added SAHRA reference number for notification of Phase IV 
trial. 
Adjusted time-line, which has been affected severely by the 
COVID-19 pandemic. 
 
1.3 Roles and Responsibilities 
CS conceived of the study and wrote the protocol. HK acted as supervisor and guided the process. 
CS will be responsible for obtaining funding through research grants. 
CS will be responsible for the overall conducting of the trial: including recruitment, training and liaising with treating 
anaesthetists and the research assistant, data collection and analysis and writing up the trial for publication. 
1.4 Funding 
• 
Expenses = R 51 037: 
o 
Statistician fee (including: data plan, data analysis and randomisation service): R 5 000 
o 
Desflurane (6 bottles): R 9 537 (incl. VAT) 
o 
Translation costs: R 3 500 
o 
Printing costs: R 3 000 
o 
Research assistant: a research assistant will be paid R100 per hour to visit the patient post-
operatively in order to complete the QoR, as well as to read the data into REDCap. 
▪ 
Estimated 2 hours per day, 25 days per month, for 6 months = R30 000 
• 
Income: 
o 
Abbvie Scholarship: R 10 000 
▪ 
The chief researcher is a current recipient of the Abbvie Scholarship. 
o 
JPRF application: R50 000 

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▪ 
The chief researcher was successful in the application for funding from the SASA Jan 
Pretorius Research Fund. (Grants are made to deserving members of SASA for clearly 
defined research projects, which are acceptable to SASA and fall within the scope of 
Anaesthesia.) 
 
1.5 Timeline 
8 November 2018 
Submission to School Research Committee 
April 2019 
Submission of revised protocol to School Research Committee 
July 2019 
Submission to SMU Research Ethics Committee 
October 2019 
Approval obtained from SMUREC: SMUREC/M/240/2019:PG 
December 2019 
Trial registered with ClinicalTrials.gov: NCT04188314 
January- February 2020 
Pilot Study (10 patients) 
Early February 2020 
Review results of pilot study 
February 2020 
Start data collection 
March 2020 
Covid-19 Pandemic starts 
October 2020 
Data collection resumes 
July 2021 
End data collection 
August 2021 
Analyse data 
September 2021 
Write dissertation and article for publication 
October 2021 
Submit dissertation for evaluation 
 
2 Introduction 
2.1 Background 
2.1.1 
Study Problem and Research Question 
Recovery after surgery and anaesthesia has traditionally been assessed with objective measures including time 
to awakening, time to regaining airway reflexes, duration of stay in the recovery room and/or hospital, and 
incidence of adverse events like pain and post-operative nausea and vomiting. Increasingly, the patient’s 
experience of their post-operative recovery is being recognised as an important outcome after surgery. The 15-
Item Quality of Recovery score (QoR-15) has been validated to give a patient-centred global measure of overall 
health status after surgery and anaesthesia (1,2). This score has recently been translated and validated in isiZulu 
(3). 

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Desflurane is the newest anaesthetic vapour to market, with many benefits from the anaesthetist’s perspective: 
faster time to awakening, faster time to regaining airway reflexes, and a clearer sensorium post-operatively. 
However, there is a paucity of data evaluating whether this translates to better quality of recovery for the patient. 
Desflurane is more expensive than other volatiles; for economic use, it is recommended to use Desflurane with a 
low flow (up to 2L) anaesthetic technique.  
Isoflurane is the most commonly used volatile anaesthetic agent at Dr. George Mukhari Academic Hospital. 
Concerns about the increased cost of desflurane compared to isoflurane limits the use of this novel agent in the 
public sector in South Africa. Following an extensive literature review, no studies could be found comparing quality 
of recovery between desflurane and isoflurane using a validated quality of recovery tool like the QoR-15.  
The research question in this study is whether there is a clinically significant difference in post-operative quality 
of recovery (using the QoR-15 score) between desflurane and isoflurane inhalational anaesthesia in adult patients 
presenting for elective ophthalmological surgery under general anaesthesia. 
This study will therefore compare quality of recovery between desflurane and isoflurane inhalational anaesthesia. 
Furthermore, the study will evaluate the relative cost of using either volatile with a minimal or basal flow anaesthetic 
technique. 
2.1.2 
Literature Review 
The ideal volatile anaesthetic should be potent, with a low solubility in blood and tissues, which should promote 
fast onset and offset of the drug effect. It should provide safe, effective and reliable anaesthesia with minimal side-
effects. The agent must be able to resist physical and metabolic degradation, and it should not pose a threat to 
the environment (4). Preferably, it should also be cost-effective and simple to use. One aspect that is often 
overlooked in the description of the “ideal anaesthetic agent”, is the quality of recovery from the patient’s point-of-
view. 
Isoflurane is the most commonly used inhaled anaesthetic agent at Dr. George Mukhari Academic Hospital. 
Desflurane has recently become available. Both agents are indicated for maintenance of anaesthesia. Neither 
agent is indicated for induction of anaesthesia, as they are pungent and irritating to the airways. 
The side-effect profiles of the two vapours are similar. Both agents may cause respiratory irritation (coughing, 
bronchospasm, laryngospasm) and respiratory depression. Both agents may cause myocardial depression and 
hypotension in a dose-dependent fashion. Desflurane may cause a transient, indirect stimulation of the 
sympathetic nervous system which may arise from stimulation of rapidly adapting upper airway receptors. 
Isoflurane may also cause emergence reactions, cardiac arrythmias, involuntary muscle movements and 

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hiccupping. Both agents may cause post-operative shivering, nausea and vomiting, as well as leucocytosis (even 
in the absence of surgical stress). Both agents may interact with carbon dioxide adsorbents to form carbon 
monoxide, especially when the adsorbent dries out; carbon monoxide inhalation may lead to formation of 
carboxyhaemoglobin in exposed patients (5–7).  
Both Isoflurane and Desflurane are contra-indicated in patients who may be susceptible to Malignant Hyperthermia 
or to auto-immune hepatitis. Isoflurane should be avoided in patients with cerebral space occupying lesions or 
raised intracranial pressure. Both agents will be contra-indicated when general anaesthesia is contra-indicated. 
“Recovery” and “Quality of Recovery” are complex, abstract concepts, lacking in universally accepted definitions. 
In basic terms, “Recovery” can be seen as a return to the patient’s pre‐operative state, or indeed, to an improved 
state. This is dependent on patient, surgical and anaesthetic factors. “Quality of Recovery” is a patient-centred 
concept, and several valid and reliable instruments have been developed that take into account physical and 
mental well-being factors that impact on the patient’s experience of their recovery (8).  
Quality of recovery should be distinguished from patient satisfaction. Whether quality of recovery has an impact 
on patient satisfaction is unclear (9). Patient expectations, cultural and social background and cognitive factors all 
impact on patient satisfaction. Tools evaluating patient satisfaction emphasise the following: information provided 
to the patient, physical comfort, involvement in care, emotional support and privacy (8).  
Recovery after inhaled anaesthesia has mostly been evaluated by parameters related to speed of emergence from 
anaesthesia, for example: time to open eyes, time to respond to command, time to remove LMA, and time to state 
date of birth. For all of these parameters, the time to effect is significantly shorter for desflurane compared to 
sevoflurane, isoflurane and propofol (4,10,11). 
Some studies have evaluated later end-points of recovery including level of activity and side-effects on the day 
after surgery. Mahmoud et al (12) evaluated female patients who underwent laparoscopic gynaecological day-
case surgery with either sevoflurane or desflurane for maintenance of anaesthesia; they found that the patients 
who received desflurane had greater return to normal activity the day after surgery compared to the sevoflurane 
group. This was done using a semi-structured telephonic questionnaire. White et al (13) found no difference in 
later end-points of recovery between sevoflurane and desflurane in patients undergoing superficial surgical 
procedures. This was assessed with a telephonic interview the day after surgery. This trial also included a basic 
assessment of patient satisfaction with their anaesthetic experience on a 3-point rating scale: 0 = dissatisfied, 1 = 
satisfied and 2 = highly satisfied. There was no difference in satisfaction between the two groups.  

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Studies comparing desflurane and isoflurane have been done, most also focussing on parameters relating to 
emergence from anaesthesia, as stated above. Emergence has been found to be faster for patients receiving 
desflurane; a finding that holds true for obese and elderly patients (4). Many of the early studies aimed for alveolar 
concentrations in excess of 1x the minimum alveolar concentration (MAC) of the volatile agents, which may explain 
the greater incidence of adverse reactions seen with desflurane. Jakobsson et al (14) compared desflurane and 
isoflurane anaesthesia in patients undergoing laparoscopic gynaecological surgery. Their study confirmed shorter 
time to emergence with desflurane, including time to extubation and return of cognitive function, and similar rates 
of post-operative nausea and vomiting and pain. Patients were asked to rate the quality of anaesthesia as “good 
– better than expected” or “bad – worse than expected”. There was no significant difference between the two 
groups.  
A systematic review published in 2004 comparing the recovery profiles after ambulatory anaesthesia with propofol, 
isoflurane, sevoflurane and desflurane, included 4 studies comparing desflurane and isoflurane. Unfortunately, 
none of the studies included in the review reported on later end-points of recovery or quality of recovery (15). 
Few studies comparing volatile anaesthetic agents used validated quality of recovery tools. One study, reported 
in German in 2011, used the QoR-40 at 24 hours to evaluate differences between anaesthesia with desflurane 
and sevoflurane. Though parameters for early postanaesthetic recovery were superior in the patients receiving 
desflurane, there was no difference in the QoR-40 after 24 hours (16). A recently published randomised controlled 
trial primarily evaluating the effects of desflurane, sevoflurane and propofol on emergence times and airway 
reactions, evaluated patient responses to the Post-operative Quality of Recovery Score (PQRS) as a secondary 
outcome, and found no difference in quality of recovery between the groups (11). 
Numerous tools have been developed in recent years to evaluate the quality of recovery from the patient’s 
perspective (8). Multi-dimensional scales like the 24h Functional Ability Questionnaire (24h-FAQ), Postoperative 
Recovery Profile, Postoperative Quality of Recovery Scale (PQRS), Functional Recovery Index (FRI), and the 40-
Item and 15-Item Quality of Recovery Scores (QoR-40 and QoR-15) have demonstrated comprehensive 
postoperative outcome results. The recent systematic review by the StEP-COMPAC group (Standardized 
Endpoints for Perioperative Medicine, Core Outcomes Measures in Perioperative and Anaesthetic Care) 
recommended one or more of six defined end-points be used in clinical trials assessing patient comfort after 
surgery (17). The QoR-15 is included in this list of six end-points: pain intensity at 24 h postoperatively, nausea 
and vomiting, one of two quality-of-recovery (QoR) scales (QoR score or QoR-15), time to gastrointestinal 
recovery, time to mobilisation, and sleep quality. The systematic review by Kleif et al (2) also recommends that 
the QoR-15 be used as a standard measure of quality of recovery in clinical trials in surgery and anaesthesia. 

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Previously, the QoR-40 was recommended as a global measure to assess the patient’s experience of their overall 
health status after surgery and anaesthesia, but it takes around 10 minutes to complete. The QoR-15 was 
developed as an abbreviated version of the QoR-40, that would be more feasible in research and clinical practice; 
this questionnaire can be completed in less than 3 minutes (1).  
The QoR-15 is a 15-item post-operative score evaluating both physical and mental well-being by assessing five 
dimensions: emotional state, physical comfort, psychological support, physical independence and pain. Each of 
the 15 items are scored by the patient from 0 (worst score) to 10 (best score), giving a lowest possible score of 0, 
and a highest possible score of 150. This continuous composite score allows comparisons between intervention 
groups. The minimal clinically important difference (MCID) and patient acceptable symptom state score for the 
QoR-15 score has been determined: the MCID is 8 and the acceptable symptom state score is 118 (18). The QoR-
15 has good scaling properties, and during development and testing the scores followed a normal distribution (1). 
The QoR-15 has undergone extensive validation and psychometric evaluation. The English and translated 
versions have been found to have good validity and reliability in assessing quality of recovery (2). During 
development and testing, the QoR-15 was able to discriminate between men and women. This is important as it 
has previously been shown that women generally have a worse post-operative experience. The QoR-15 
furthermore showed a negative correlation with duration of surgery, duration of time spent in the post-anaesthesia 
care unit, and duration of hospital stay (1).   
During an extensive review of the literature, no studies could be found comparing quality of recovery between 
desflurane and isoflurane using a validated quality of recovery tool like the QoR-15. Isoflurane is the most 
commonly used volatile anaesthetic agent at Dr. George Mukhari Academic Hospital. Desflurane is being 
introduced into our practice, and it remains to be seen if it holds benefits with regards to patient-rated quality of 
recovery.  
2.2 Aim and Objectives 
2.2.1 
Aim 
This study will compare quality of recovery between desflurane and isoflurane inhalational anaesthesia.  
2.2.2 
Primary Objective and Hypothesis 
The primary objective of the study is to evaluate whether there is a difference between post-operative quality of 
recovery in patients who received desflurane and in patients who received isoflurane for maintenance of 
anaesthesia, using the QoR-15 score, a patient-rated outcome measure. 

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Isoflurane is the standard drug used in our setting for maintenance of anaesthesia and will therefore be used as 
the drug for the control group. Desflurane will be used as the interventional drug. 
The minimal clinically important difference for the post-operative QoR-15 has been found to be 8. In other words, 
an intervention that changes the mean post-operative score by 8, can be interpreted to signify a clinically important 
improvement or deterioration. 
The null hypothesis for this study is that there is no statistically significant difference in mean post-operative QoR-
15 scores of patients receiving isoflurane and desflurane for maintenance of anaesthesia. The alternative 
hypothesis is that there is a statistically significant difference in mean post-operative QoR-15 scores between 
patients receiving isoflurane and desflurane. 
2.2.3 
Secondary Objectives 
A secondary objective will be to compare the consumption and relative cost of using isoflurane vs desflurane with 
a minimal (0.25-0.5 ml/min) or basal (0.2-0.25 ml/min) flow anaesthetic technique. This will be done by comparing 
the amount of vapour used in millilitre per hour between desflurane and isoflurane during minimal or basal flow 
anaesthesia. The relative cost of the vapour used will be estimated, based on the current government purchase 
price of isoflurane and desflurane.  
Furthermore, the difference in time spent in recovery between the two patient groups will also be compared. 
3 Methodology 
3.1 Trial Design 
This study will be conducted as a randomised, controlled, patient and observer blinded, single-centre trial with two 
parallel groups and a primary end-point of 15-point Quality of Recovery Score on day 1 after surgery. 
Randomization will be performed as block randomization with a 1:1 allocation. 
3.2 Participants, Interventions and Outcomes 
3.2.1 
Study Setting 
The study will be conducted in the theatre complex at Dr. George Mukhari Academic Hospital, a tertiary training 
centre affiliated with Sefako Makgatho Health Sciences University. Specifically, the study will be conducted in the 
ophthalmological theatre, on patients undergoing ophthalmological surgery under general anaesthetic. 
The decision to use patients for ophthalmological surgery is based on the consideration that the procedures last 
an average of 1 hour, the patients are usually systemically well, the anaesthetic technique can be standardised 
for all patients, the surgery itself is unlikely to lead to poor quality of recovery and the patients are unlikely to require 
high doses of opioids for analgesia. Review of the theatre records for the ophthalmology theatre revealed that 166 

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patients between the ages of 18-87 years underwent general anaesthesia in the 6 months between 1 March – 31 
August 2018. Mean age was 42 years, with 150 patients in the age range 18-65 years. Mean duration of surgery 
was 74 minutes (range: 20-180 minutes), with 141 cases lasting 40-120 minutes. 
3.2.2 
Eligibility Criteria 
Inclusion Criteria: 
• 
Adult patients between the ages of 18-80 years of age. 
• 
Patients presenting for ophthalmological surgery under general anaesthesia. 
• 
ASA I and II. 
• 
Able to communicate in English, Setswana or Afrikaans. 
Exclusion Criteria: 
• 
Patients outside the specified age range. 
• 
ASA III and above. 
• 
Patients with contra-indications to Laryngeal Mask Airway use during general anaesthesia. 
• 
Patients with severe medical or surgical conditions, who are expected to have prolonged admissions or 
ICU admissions. 
• 
Patients with uncontrolled psychiatric conditions like depression, schizophrenia, mania, dementia. 
• 
Patients with known allergy or adverse reaction to volatile anaesthetics. 
• 
Patients with known or suspected susceptibility to Malignant Hyperthermia. 
• 
Patients with incomplete records (Data Collection Form and QoR-15). 
3.2.3 
Interventions 
The control group will receive isoflurane for maintenance of anaesthesia. The intervention group will receive 
desflurane for maintenance of anaesthesia. 
Standard protocols for induction and maintenance of anaesthesia will be followed, as discussed with Prof. F. 
Puehringer, an international expert in the field of desflurane use. A detailed leaflet describing the protocol has 
been developed (see Appendix 6.5), which will be handed to the treating anaesthetist on the day of surgery. 
• 
Confirm anaesthetic workstation has passed the machine check, and record any machine leak, if present. 
• 
Intravenous Induction of Anaesthesia: 
o 
Fentanyl 1.5-3 mcg/kg pre-induction to reduce airway responses during manipulation. Lower 
doses to be used for short procedures and larger dose for longer procedures. 
o 
Lignocaine 40 mg pre-induction to minimize Propofol-induced injection pain. 

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o 
Propofol 2-2.5 mg/kg until induction of anaesthesia. 
o 
Dexamethasone 8mg after induction of anaesthesia to prevent post-operative nausea and 
vomiting and to decrease opioid requirements. 
o 
Mask ventilation with 6 l/min 100% oxygen until airway is placed. 
o 
Airway management will be with a Laryngeal Mask Airway (LMA), size selected according to 
patient weight. 
• 
Use of Muscle Relaxants During Procedure: 
o 
If required, a small dose of muscle relaxant may be administered to facilitate immobility during the 
procedure. 
o 
For Rocuronium, a dose of up to 0.15mg/kg may be used (about 10-15mg for most adults). This 
dose is a quarter of the normal intubating dose for Rocuronium. 
o 
For Cisatracurium, a dose of up to 0,05mg/kg may be used (about 2.5 – 4mg for most adults). 
This dose if a quarter of the normal intubating dose for Cisatracurium. 
o 
Top-up doses may be given every 30-40 minutes, if required; dosing should be the same as the 
initial dose. 
• 
Maintenance of Anaesthesia: 
o 
Isoflurane: 
▪ 
After the airway is secured, fresh gas flow is reduced to 2 l/min and the Isoflurane 
vaporiser is opened and adjusted to attain 1MAC. 
▪ 
Once 1MAC is attained, the fresh gas flow will be reduced to 0.2-0.5 l/min and the 
vaporiser will be adjusted to maintain 1MAC. The aim will be to reduce the fresh gas flow 
as low as possible, taking into consideration the amount of machine and/or circuit leak. 
▪ 
If basal flow (0.2L/min) is reached, FiO2 will be set to 100% to meet the patient’s oxygen 
demand. 
▪ 
Should the bag on the anaesthetic machine collapse during minimal or basal flow 
anaesthesia (e.g. because of a poor seal from the LMA, or due to circuit leak) the following 
steps should be taken: increase the fresh gas flow to 2 L/min and adjust the vaporiser 
concentration to maintain 1MAC, allow the bellows to fill and then return to the previous 
concentration and fresh gas flow settings. 
o 
Desflurane: 

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▪ 
After the airway is secured, fresh gas flow is reduced to 2 l/min and the desflurane 
vaporiser is opened to 12%. This is maintained until 1MAC is reached, usually about 3-5 
minutes. 
▪ 
The fresh gas flow will then be turned down to 0.2-0.5 l/min and the vaporiser adjusted to 
maintain 1MAC. The aim will be to reduce the fresh gas flow as low as possible, taking 
into consideration the amount of machine and/or circuit leak. 
▪ 
If basal flow (0.2L/min) is reached, FiO2 will be set to 100% to meet the patient’s oxygen 
demand. 
▪ 
Should the bag on the anaesthetic machine collapse during minimal or basal flow 
anaesthesia (e.g. because of a poor seal from the LMA, or due to circuit leak) the following 
steps should be taken: turn the vaporiser concentration to 12% and the fresh gas flow to 
2 L/min, allow the bellows to fill and then return to the previous concentration and fresh 
gas flow settings. 
o 
The use of minimal or basal fresh gas flow is intentional, to minimise the amount of anaesthetic 
vapour used. When basal flow is used, 100% oxygen is required to meet patient’s oxygen demand. 
• 
Managing Potential Problems: 
o 
Should the ophthalmologist complain that the patient is in too light a plane of anaesthesia, the 
patient may be deepened with a bolus of Propofol 0.5-1 mg/kg. 
o 
For intra-operative analgesia (for example if patient develops tachycardia or hypertension), 
administer 50mcg Fentanyl boluses intravenously. 
o 
When post-operative analgesia is required, administer 50-100mg of Tramadol intravenously as a 
bolus 20 minutes before the end of the procedure. 
o 
For post-operative nausea or vomiting (only if required), administer 4mg of Ondansetron 
intravenously as a bolus, followed by 10mg of Metoclopramide after 30 minutes (only if further 
treatment is required). 
• 
End of Procedure: 
o 
If a small dose of muscle relaxant was used, the effects should be reversed with Neostigmine 
0.04mg/kg (2-3mg for most adults) 10-20 minutes before the end of the procedure. Glycopyrrolate 
or Atropine may be added to prevent bradycardia and gastro-intestinal side-effects. 
o 
The vaporisers will be closed, and fresh gas flow will be increased to 6 l/min in order to wash out 
the volatile anaesthetic. 
• 
Recovery and Discharge 

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o 
The patient will be taken to the recovery room when they are able to protect their airway, as per 
normal practice. 
o 
Discharge from the recovery room to the ward will be according to the standard procedures in the 
post-anaesthesia recovery room. Patients should score at least 9 on the modified Aldrete score, 
with the patient awake and alert with stable vital signs, not experiencing any acute side effects 
(e.g., nausea or vomiting) or moderate-to-severe pain. 
3.2.4 
Materials, Apparatus and Instruments 
Basic Materials and Apparatus: 
• 
Patients will be induced in the ophthalmology theatre; anaesthesia will be maintained with the Datex-
Ohmeda Aisys CS2 anaesthetic workstation. 
• 
Isoflurane is freely available, and the standard anaesthetic vapour that is used in our setting. 
• 
Desflurane will be purchased for use in the study. 
• 
Vaporisers for both isoflurane and desflurane are available in our theatre complex. 
• 
Nitrous Oxide will not be used as part of the fresh gas mixture, because it is not always available in our 
setting. 
• 
Standard monitors will be used during anaesthesia: non-invasive blood pressure monitoring, pulse 
oximetry, 3-lead electrocardiogram, capnography and gas analysis. 
Instruments: 
Quality of Recovery will be measured with the 15-Item Quality of Recovery score (QoR-15): 
• 
The English version can be used for English-speaking patients. There is no copyright on the form 
(confirmed by the author, Prof. P.S. Myles via email). 
• 
The form will be translated into Afrikaans and Setswana. 
o 
Forward translation has been done in advance by an accredited medical translator at Zwelinhle 
Translation Services. 
o 
Back translation of both translations has been done by a separate panel of health care 
professionals, who were blinded to the original English version. Three Setswana home language 
speakers did the back-translation for the Setswana version, and three Afrikaans home language 
speakers did the back-translation for the Afrikaans version. 
o 
The final versions have been corrected and adapted by all panel members. 
o 
See Appendices 6.9 and 6.10 for the translated versions. 

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• 
The QoR-15 is a validated and reliable tool for measuring quality of recovery. The patient is asked to rate 
their experience of 15 items from 0 (worst score) to 10 (best score). 
• 
Where possible, the QoR-15 form will be handed to the patient to complete by themselves. However, in 
cases where patients are visually impaired, the items on the questionnaire will be read to them, and their 
responses recorded. 
3.2.5 
Feasibility 
Consensus on the acceptability feasibility of the treatment protocol has been obtained from peers and 
colleagues in the Department of Anaesthesia by circulating the proposed standardised treatment protocol (see 
Appendix 6.5) and asking for feedback. 
Eleven feasibility questionnaires were completed (See Appendix 6.2 for template of the questionnaire). All 11 
respondents indicated that they thought the protocol to be practical and easy to follow. All 11 respondents indicated 
that they would be comfortable giving anaesthesia according to the treatment protocol. Five respondents have 
never used Desflurane before in clinical practice; of these 3 respondents were subsequently taught how to use 
Desflurane during a training workshop, the other 2 respondents were instructed on the use of Desflurane by the 
Chief Researcher during clinical cases. 
Most of the concerns recorded on the forms related to the use of basal fresh gas flow. One responded commented 
that the technique is labour-intensive and user-dependent. The same respondent was concerned about flushing 
the circuit with oxygen only when the bellows collapse, as this may lead to a drop in MAC, which may cause the 
patient to be in too light a plane of anaesthesia. One respondent was concerned about using basal flow with a 
Laryngeal Mask Airway, as there may be a leak if the airway does not seal properly. Another respondent was 
concerned about using basal fresh gas flow with the Drager Perseus anaesthetic workstation, as the bag tends to 
collapse when fresh gas flows below 0.6 l/min are used. One consultant anaesthetist was concerned about 
potential for carbon dioxide retention with basal flow anaesthesia and exhausted carbon dioxide absorber. These 
concerns are addressed in the changes to the treatment protocol – see below. One respondent was concerned 
about laryngospasm and bronchospasm – this is rarely a problem when Desflurane is used according to the 
recommended protocol with a maximum fresh gas flow of 2L and maximum vaporiser concentration of 12%. 
Practicality feasibility of the standardised anaesthesia treatment protocol has been tested in a pilot of ten cases. 
Initially four cases were selected for the pilot study, but after these cases changes were made to the standardised 
treatment protocol, and a further six cases were piloted to ensure all concerns and issues had been addressed in 
the amended treatment protocol. Two of the further six cases received Sevoflurane instead of Isoflurane or 

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Desflurane; one case due to the treating anaesthetist not receiving the message about the study in time, the other 
case due to the patient requesting a gas induction. An additional two pilot cases were done, bringing the total 
number of pilot cases to 12. The cases for the pilot were not randomised and will not be included in the final study 
data. Isoflurane was used for three pilot cases and desflurane was used for seven pilot cases (the two sevoflurane 
cases were not counted). It was decided to increase the number of Desflurane pilot cases to ensure the treating 
anaesthetists had enough exposure to using the newer agent before starting the actual trial.  
For the first four pilot cases the Chief Researcher went to assess the patients pre- and post-operatively. Two of 
the patients had already been discharged by the time the Chief Researcher went to their wards. This confirmed 
the need for a research assistant to see the patients post-operatively before discharge. It was also not possible 
for the Chief Researcher to be blinded to the anaesthetic agent used, as she assisted the treating anaesthetists 
during induction. In one of the pilot cases, the patient developed laryngospasm when Desflurane was started after 
placement of the airway; the likely reason was that low doses of fentanyl and propofol were given during induction. 
In another case, 3mcg/kg of fentanyl was given at induction, and then the surgeons decided after the examination 
under anaesthesia that the patient was not for further intervention – it took time for the respiratory depression from 
fentanyl to wear off. During one of the pilot cases, the consultant anaesthetist in the ophthalmological theatre 
recommended a small dose of muscle relaxant to assist with patient immobility during delicate surgery. 
Having evaluated the acceptability and practicality feasibility, the following changes were made to the standard 
treatment protocol (See appendix 6.6 for the full updated version): 
• 
Treating anaesthetist to test the machine daily, as per standard practice, with a clean circuit. Carbon 
dioxide absorber should be checked daily and replaced when needed. The treating anaesthetist will record 
the machine leak as determined during the machine check. 
• 
Allow fresh gas flow of 0.2-0.5 l/min, aiming to reduce the fresh gas flow as low as possible, taking into 
consideration the machine leak. This change allows the treating anaesthetist to adjust the fresh gas flow 
according to the amount of leak in the circuit. All responding anaesthetists felt more comfortable with this 
adjustment to the protocol. 
• 
Steps to take when the bellows collapse: increase the fresh gas flow to 2 l/min and increase the 
concentration on the vaporiser to maintain 1MAC (maximum 12% for Desflurane). This will prevent a 
decrease in the MAC from flushing the circuit with oxygen only. 
• 
In some cases, a small dose of muscle relaxant may be used to facilitate immobility during the procedure. 
The dose of muscle relaxant will be limited to 25% of the intubating dose, and reversal with neostigmine 
(plus glycopyrrolate or atropine) is mandatory. Glycopyrrolate is preferred, but it is currently out of stock. 

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This small dose of muscle relaxant should not affect the patient’s post-operative quality of recovery, 
especially if it is reversed. 
• 
Dose of Fentanyl changed to 1.5-3mcg/kg, to allow for smaller doses to be given for short procedures 
lasting 30 minutes or less. 
• 
In cases where post-operative pain is expected, the treating anaesthetist may administer 50-100mg 
Tramadol 20 minutes before the end of the procedure, rather than waiting until the patient was in the 
recovery room. 
• 
The anaesthetic workstation in the ophthalmology theatre has been changed to a Datex-Ohmeda CS2, 
which gives a clear indication of the amount of circuit leak after the machine check, and experience has 
shown that it has a smaller baseline leak than the Drager Perseus workstation. 
The changes made to the standardised anaesthesia treatment protocol makes it more practical and pragmatic, 
and it will improve adherence to the study protocol. This will prevent exclusion of cases which were not treated 
according to the study protocol. 
3.2.6 
Outcomes 
Primary outcome measures: 
• 
Quality of recovery will be assessed in all participants with the QoR-15 score.  
o 
A baseline QoR-15 will be measured pre-operatively, and a repeat measurement will be done on 
day 1 post-operatively before discharge. 
o 
For each patient, the pre- and post-operative QoR-15 scores will be recorded, as well as the 
difference between the two measurements. The mean and median differences between the pre- 
and post-operative QoR-15 scores of the control group and the intervention group will be 
compared and tested for significance. 
o 
The mean and median post-operative QoR-15 scores of the control group and the intervention 
group will be compared and tested for significance. 
Secondary outcome measures: 
• 
To evaluate the consumption and cost of isoflurane and desflurane with a minimal or basal anaesthetic 
technique: 
o 
The vapour use per case in millilitres will be recorded from the anaesthetic machine. 
o 
The purchase price for isoflurane and desflurane will be obtained from the pharmacy. 
o 
The mean and median consumption of vapour between the two groups will be compared. 
o 
The mean and median cost of isoflurane and desflurane will be compared. 

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• 
To evaluate time in recovery: 
o 
The time the patient enters and leaves the recovery room will be recorded, as well as the total 
time the patient spends in the recovery room. 
o 
The mean and median time spent in recovery will be compared between the two groups. 
3.2.7 
Participant Timeline and Flow-Diagram 
 

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3.2.8 
Sample Size 
Sample size calculation is based on estimation of the difference in mean post-operative Quality of Recovery (QoR) 
scores, after anaesthesia with desflurane or isoflurane. With a sample size of 85 in each group, a two-sided two-
sample t-test at the 5% significance level, will have 80% power to detect a difference of 8 between the mean post-
operative QoR scores with desflurane and isoflurane, assuming a standard deviation of 18.5, Sample size 
calculation was done on nQuery Advanced (Statistical Solutions Ltd, Cork, Ireland), Release 8.0. 
A sample of 170, randomised in a 1:1 ratio to treatment with desflurane and isoflurane (85 per group) is proposed 
for this study. 
3.2.9 
Recruitment 
Recruitment will be done by the Chief Investigator. The following steps will be followed: 
1. Review the theatre booking list for theatre 11 the day before surgery. 
2. Identify adult patients between the ages of 18 and 80 on the list, scheduled for general anaesthesia. 
3. Review the patients in the ward: 
a. Screen for any exclusion criteria. 
4. Once confirmed that there are no exclusion criteria: 
a. Explain the objectives of the study to the patient. 
b. Hand the patient a patient information leaflet and discuss any questions the patient may have. 
c. Take informed consent if the patient agrees to participate in the study. 
5. Record the patient’s name on a sequentially numbered list. This will be the only document to contain any 
personal information of the patient. It will be stored securely by the Chief Researcher. The number on the 
list will be the patient’s study number and this number will be recorded on all study documents. 
3.3 Assignment of Interventions 
3.3.1 
Allocation and Randomisation 
Patients will be randomly allocated to either the control or the intervention group by computer randomisation. 
Randomisation and allocation will be managed remotely by the statistician, who will not be involved in patient care, 
and who will only gain access to study data after completion of data collection. 
Block randomisation will be done to ensure that an equal number of patients are assigned to each treatment arm. 
Random block sizes will be used and the chief investigator, research assistant and treating anaesthetists will be 
blind to the size of each block. 

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Sequentially numbered, sealed, opaque envelopes will be prepared by the statistician. This will include a piece of 
paper indicating the group the patient has been randomised to. The sealed envelope will be handed to the treating 
anaesthetist on the day of surgery by the Chief Researcher. The Chief Researcher will be responsible for 
enrolment and assignment of participants. 
3.3.2 
Blinding 
The patient will be blinded to the group they have been randomised to, as the vapour will only be started after 
induction of anaesthesia. The research assistant administering the post-operative QoR-15 will be blinded to the 
intervention. 
The treating anaesthetist, the Chief Researcher and theatre staff will not be blinded to the intervention, as this 
would not be practical. All treating anaesthetists and theatre staff will be strongly inculcated not to disclose the 
allocation status of the participant at any time prior or after the general anaesthetic.  
The piece of paper indicating the group will be attached to the Case Report Form. The Case Report Form will be 
collected by the Chief Researcher and will not be in the patient’s file where it may unblind the patient or research 
assistant. 
There are no circumstances under which unblinding will be permissible.  
3.4 Data Collection 
3.4.1 
Source Documents 
The following documents will be used as original source documents from which patient information will be 
gathered: 
• 
Patient file: history, vital signs, comorbidities, previous anaesthesia and complications. 
• 
Theatre booking list: patient age, type of anaesthesia. 
• 
Blue anaesthetic report card: complete record of the anaesthesia care to the patient. 
• 
Theatre record book: anaesthesia times, basic record of medications given. 
• 
Nursing theatre record: anaesthesia times, recovery times, basic record of medications given. 
• 
Stored history on the Datex-Ohmeda Aisys CS2 workstation in theatre 11: vapour consumption, 
anaesthesia times. 
3.4.2 
Study Documents 
The following documents will be used as study documents to record relevant information: 
• 
Case Report Forms (CRF) 
o 
CRF: Data Collection 

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o 
CRF: Pre-operative QoR-15 form 
o 
CRF: Post-operative QoR-15 form 
• 
Consent Form 
• 
Patient Information Leaflet 
• 
Standardised Anaesthesia Protocol  
The templates for all the above documents are added to this protocol as Appendices. 
3.4.3 
Data Collection Procedures 
Patients will be assessed by the chief researcher pre-operatively on the day before surgery. The demographic 
information on the Data Collection Form (Section A) will be completed. Information will be obtained from the 
patient’s file, as well as from an interview with the patient. The chief researcher will accurately measure the 
patient’s weight and height with the available scales and measuring devices in the wards. 
Patients will then be asked to complete the QoR-15 in the language of their choice, as a measure of health status 
over the previous 24 hours. Where possible, the QoR-15 form will be handed to the patient to complete by 
themselves. However, in cases where patients are visually impaired, the items on the questionnaire will be read 
to them, and their responses recorded. 
The following day, the treating anaesthetist will complete the information about the procedure in Section B of the 
Data Collection Form: anaesthetic time, amount of vapour used, additional medication administered, recovery 
time, any adverse events (bronchospasm, laryngospasm, post-operative nausea and vomiting and/or other), and 
whether the prescribed anaesthetic protocol was followed. 
Post-operatively, a blinded observer (research assistant) will review the patient on the day following their surgery, 
prior to discharge. The patients will complete the QoR-15 again. 
As follow-up will be done before discharge, retention of patients to follow-up should not present any difficulties. 
3.5 Data Management 
3.5.1 
Database Entry 
All study documents will be printed. All data will be recorded by hand on paper forms. After recruitment, the Chief 
Researcher will record the sequential study number on all documents relating to a particular patient. 
The data will be captured electronically on the REDCap database by the research assistant (19). REDCap 
(Research Electronic Data Capture) is a secure, web-based application designed to support data capture for 
research studies, providing 1) an intuitive interface for validated data entry; 2) audit trails for tracking data 

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manipulation and export procedures; 3) automated export procedures for seamless data downloads to common 
statistical packages; and 4) procedures for importing data from external sources. 
Data from each patient will be captured on REDCap sequentially so that the study number correlates with the 
database entry number. 
3.5.2 
Data Storage 
Study documents will be stored securely by the Chief Researcher. Documents will be kept in a dedicated lever-
arch file and will be arranged sequentially according to study number. All study documents relating to a single 
patient will be stored together. 
3.5.3 
Data Inspection 
In case of incomplete data in Section B of the Data Collection Form, the chief researcher will review the following 
source documents in the order listed to obtain the information: 
Missing data on medication given intra-operatively: 
1. Blue anaesthesia report card 
2. Nursing theatre record 
3. Theatre record book 
Missing data on medication given post-operatively: 
1. Blue anaesthesia report card 
2. Nursing theatre record 
Missing data on anaesthesia start/end times: 
1. Blue anaesthesia report card 
2. Nursing theatre record 
3. Datex-Ohmeda Aisys CS2 stored 
history 
4. Theatre record book 
Missing data on vapour start/end times: 
1. Blue anaesthesia report card 
2. Datex-Ohmeda Aisys CS2 stored 
history 
Missing data on millilitres vapour used: 
1. Datex-Ohmeda Aisys CS2 stored 
history 
 
Patients will complete the QoR-15 forms pre-operatively and post-operatively. The Chief Researcher (pre-
operatively) and the research assistant (post-operatively) will review the QoR-15 forms for completeness before 
leaving the patient’s bedside. If the patient omitted any responses, they will be asked to review and complete the 
form. 

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3.6 Data Analysis & Statistical Methods 
Demographic and clinical characteristics of patients will be summarised descriptively. Continuous variables (e.g. 
age or weight) will be summarised by mean, standard deviation, median, interquartile range, minimum and 
maximum values. Categorical variables (e.g. ethnicity or ASA status), will be summarised by frequency count and 
percentage calculations. 
QoR scores will be considered as a continuous variable and will be summarised as above per treatment group 
(desflurane and isoflurane). 
The null hypothesis for this study is that there is no statistically significant difference in mean post-operative QoR-
15 scores of patients receiving isoflurane and desflurane for maintenance of anaesthesia. The alternative 
hypothesis is that there is a statistically significant difference in mean post-operative QoR-15 scores between 
patients receiving isoflurane and desflurane. 
Based on the available literature, it is assumed that the quality of recovery scores will follow a normal distribution. 
The data will be inspected for normality prior to analysis. 
For the primary objective, the mean and median difference in post-operative QoR-15 scores between the two 
groups will be tested for significance by the two-sided two-sample t-test and the nonparametric Wilcoxon rank sum 
test respectively. The mean and median difference between the pre-operative and post-operative QoR-15 scores 
for the two groups will also be tested for significance by the two-sided two-sample t-test and the nonparametric 
Wilcoxon rank sum test respectively. 
For the secondary objectives, mean and median difference in consumption of vapour and time spent in recovery 
will be tested for significance by the t-test and Wilcoxon test as above.  
Analysis, or comparisons, of subgroups of patients may be performed if it would be of clinical interest; for example, 
if there appears to be a significant difference in QoR scores between male and female patients. 
Results will be presented in tables and graphs or verbatim, as applicable. 
All statistical analyses will be performed on SAS (SAS institute Inc, Carey, NC, USA), Release 9.4 or higher, 
running under Microsoft Windows for a personal computer. Statistical tests will be two-sided and p values ≤0.05 
(5%) will be considered significant. 

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3.7 Monitoring  
3.7.1 
Data Quality Monitoring 
The Chief Researcher will periodically monitor the completed study documents and the database entries. If any 
problems are found with completion of study documents, training sessions will be arranged in the Department of 
Anaesthesia.  
3.7.2 
Interim Analysis 
Interim analysis will not be done. 
3.7.3 
Harms 
Adverse events will be recorded on the Data Collection Form. The form makes provision for expected adverse 
events (bronchospasm, laryngospasm, nausea & vomiting and/or other), as well as for unexpected adverse 
events. Treating anaesthetists will be instructed to report all adverse events to the Chief Researcher as soon as 
possible. 
Both the control and interventional drugs have been extensively studied and used safely in clinical practice. A brief 
description of their side-effect profiles, which are very similar, can be found in the literature review. It is therefore 
not foreseen that many unexpected adverse events will occur. The purpose of the study is not to determine 
frequency or severity of adverse events, but it is acknowledged that adverse events may occur, and therefore 
monitoring is important. 
Patients with known or suspected susceptibility to Malignant Hyperthermia are excluded from participation in the 
trial. In the unlikely event that a patient presents with signs and symptoms suggestive of Malignant Hyperthermia, 
treating anaesthetists will be instructed to stop all volatile agents and to follow departmental emergency 
management protocols. 
3.8 Reliability and Validity  
• 
Validity: 
o 
Internal validity should be assured on the basis that the anaesthetic techniques will be unchanged 
between the two groups, except for the anaesthetic vapour. Maintaining the end-tidal vapour 
concentration at 1MAC for both drugs will prevent disproportionate effects of one drug over the 
other. The patient population should be homogenous, as only ASA I and II patients presenting for 
ophthalmological surgery will be included in the study.  
o 
The chief researcher will counsel each treating anaesthetist prior to them starting a study case to 
ensure that they follow the required standardised anaesthesia protocol. This will reduce the 

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chance of protocol violations occurring. Any deviations from the standardised protocol will be 
recorded on the Data Collection Form and will be assessed by the chief researcher. 
o 
Construct and content validity are assured on the basis that the QoR-15 has been extensively 
validated in many different languages and for many different surgery types. 
o 
Data on the Case Report Forms will be inspected for completeness as per section 4.3.5. 
Incomplete cases will be excluded from analysis. 
• 
Reliability: 
o 
The QoR-15 is a reliable tool to use. During development of the tool, the internal consistency was 
measured using Cronbach α and split-half reliability, both of which had satisfactory results. 
o 
Reproducibility of the QoR-15 was excellent, and exceeded that reported for the QoR-40, 
indicating that the QoR-15 score can be interpreted with confidence. 
3.9 Bias 
Randomisation bias will be avoided by using computer randomisation of patients to either the desflurane or 
isoflurane groups. The randomisation process will be managed by the statistician who is not involved in patient 
care. Block randomisation will be done to ensure that an equal number of patients are assigned to each treatment 
arm. 
Selection bias will be reduced by using random block sizes and keeping the chief investigator, research assistant 
and treating anaesthetists blind to the size of each block. 
Response or recall bias is possible with the use of a self-reporting questionnaire. To minimise this, the QoR-15 
questionnaire will be administered on Day 1 post-operatively, prior to discharge, which will prevent poor memory 
recall. Blinding of patients will also help to minimise recall bias. Furthermore, the use of a validated scoring tool 
that uses clear statements and easy-to-understand scoring, like the QoR-15, should also minimise recall bias. 
Observer bias will be limited by the observer who will administer the post-operative questionnaire being blinded to 
the treatment groups. 
The QoR-15 has a score range of 0-150, and it was found not to be limited in its capacity to discriminate patients 
at the extremes of poor and good recovery. A floor or ceiling effect would therefore be unlikely. 
 
 

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4 Ethics and Dissemination 
Informed consent will be taken from all participants by the Chief Researcher. Consent forms will be available in 
English, Afrikaans and Setswana. Only adult patients who can consent to participation will be included in the study. 
A patient information leaflet explaining the objectives of the study in layman’s terms has been developed (see 
Appendix 6.3). This leaflet has been translated into Setswana and Afrikaans. A copy of the patient information 
leaflet will be given to each patient. 
The only document to contain the patient’s name will be the sequentially numbered list that will be completed at 
recruitment. This list will be stored securely by the Chief Researcher. All data will be de-identified: no personal 
patient information (for example name, date of birth and file number) will be recorded on any study documents 
(Data Collection Form and QoR-15 forms). Study documents will be numbered sequentially (Data Collection Form 
and QoR-15 forms for each patient will have the same number). Paper records will be read into the REDCap 
System in sequence to ensure the study numbers and the electronic record numbers correspond. All paper 
documents will be stored securely by the Chief Researcher.  
Patients will receive the same standard anaesthesia care, irrespective of which group they are randomised to. 
Desflurane is registered at the MCC for the maintenance of anaesthesia. Desflurane is freely available in South 
Africa and will be used for the registered indication in this study. 
Permission to perform the study at Dr. George Mukhari Academic Hospital has been obtained from the hospital 
superintendent. Approval has obtained from the SMU Research Committee, as well as from the SMU Research 
Ethics Committee. The SMUREC Ethics Reference Number for the study is: SMUREC/M/240/2019:PG. The trial 
has been submitted for registration with the National Health Research Database (NHRD). A Notification of Phase 
IV trial was submitted to the South African Health Products Regulatory Authority, with reference number 
N20210205.  The trial has been registered on ClinicalTrials.gov, with reference number NCT04188314.  
Any important changes to the protocol after approval (e.g. changes to eligibility criteria, outcomes or analyses) will 
be communicated to the SMU Research Committee and the SMU Research Ethics Committee. 
The results of the trial will be written up by the Chief Researcher for publication in a peer-reviewed academic 
journal. All supporting documents and de-identified data will be appended as supplements to the main publication. 
The results will also be presented at the annual SMU Research Day, and at the annual SASA conference, if 
selected for presentation. 
The Chief Researcher holds current certification in Good Clinical Practice. There are no financial or competing 
interests for the Chief Researcher. There is no industry involvement in this trial. 

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5 References 
1.  
Stark PA, Myles PS, Burke JA. Development and Psychometric Evaluation of a Postoperative Quality of 
Recovery Score. The QoR-15. Anesthesiology. 2013;118(6):1332–40.  
2.  
Kleif J, Waage J, Christensen KB, € Ogenur IG. Systematic review of the QoR-15 score, a patient- reported 
outcome measure measuring quality of recovery after surgery and anaesthesia. Br J Anaesth . 2018 [cited 
2018 Sep 10];120(1):28–36. 
3.  
Sikhakhane S, Kusel B, Rodseth R. Development and validation of the isiZulu quality of recovery score. 
South Afr J Anaesth Analg. 2018;24(3):65–9.  
4.  
Jakobsson J. Desflurane: A clinical update of a third-generation inhaled anaesthetic. Acta Anaesthesiol 
Scand. 2012;56(4):420–32.  
5.  
Kapoor MC, Vakamudi M. Desflurane - revisited. J Anaesthesiol Clin Pharmacol. 2012 Jan;28(1):92–100.  
6.  
Baxter. Suprane Product Insert. 2012.  
7.  
Safeline Pharmaceuticals. Isoflurane Product Insert. 2014.  
8.  
Bowyer A, Jakobsson J, Ljungqvist O, Royse C. A review of the scope and measurement of postoperative 
quality of recovery. Anaesthesia. 2014 Nov 1;69(11):1266–78.  
9.  
Berning V, Laupheimer M, Nübling M, Heidegger T. Influence of quality of recovery on patient satisfaction 
with anaesthesia and surgery: a prospective observational cohort study. Anaesthesia. 2017 Sep 
1;72(9):1088–96.  
10.  
Stevanovic A, Rossaint R, Fritz HG, Froeba G, Heine J, Puehringer FK, et al. Airway reactions and 
emergence times in general laryngeal mask airway anaesthesia A meta-analysis. Eur J Anaesthesiol. 2015 
[cited 2018 Sep 16];32:106–16.  
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Kowark A, Rossaint R, Pühringer F, Keszei AP, Fritz H, Fröba G, et al. Emergence times and airway 
reactions during general anaesthesia with remifentanil and a laryngeal mask airway: A multicentre 
randomised controlled trial. Eur J Anaesthesiol. 2018 Aug;35(8):588–97.  
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Mahmoud NA, Rose DJA, Laurence AS. Desflurane or sevoflurane for gynaecological day-case 
anaesthesia with spontaneous respiration? Anaesthesia. 2001;56(2):171–4.  
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White PF, Tang J, Wender RH, Yumul R, Stokes OJ, Sloninsky A, et al. Desflurane versus sevoflurane for 
maintenance of outpatient anesthesia: The effect on early versus late recovery and perioperative coughing. 
Anesth Analg. 2009;109(2):387–93.  
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Jakobsson J, Rane K, Ryberg G. Anaesthesia during laparoscopic gynaecological surgery: a comparison 
between desflurane and isoflurane. Eur J Anaesthesiol. 1997 Mar;14(2):148–52.  
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Gupta A, Stierer T, Zuckerman R, Sakima N, Parker SD, Fleisher LA. Comparison of Recovery Profile after 
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Anesth Analg. 2004;98(3):632–41.  
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Eberhart LHJ, Gerlach H, Knaber R, Koch T, Morin AM, Röhr F, et al. [Implementation of new standards in 
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Myles PS, Boney O, Botti M, Cyna AM, Gan TJ, Jensen MP, et al. Systematic review and consensus 
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Myles PS, Myles DB, Galagher W, Chew C, MacDonald N, Dennis A. Minimal Clinically Important 
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6 Appendices 
6.1 SPIRIT Statement Checklist 
 

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6.2 Feasibility Questionnaire to Treating Anaesthetists 
 

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6.3 Patient Information Leaflet 
 

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6.4 Consent Form 
 
 

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6.5 Standardised Anaesthesia Protocol for Treating Anaesthetists – Version 1 
 

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6.6 Standardised Anaesthesia Protocol for Treating Anaesthetists – Version 2 (Final) 
 

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6.7 Case Report Form: Data Collection 
 

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6.8 Case Report Form: QoR-15 English