Comparing Quality of Recovery Between Desflurane & Isoflurane in Eye Surgery Patients at Dr George Mukhari Acad Hospital
Condition: Quality of Recovery; Anesthesia Recovery Period
Study type: Interventional

Summary: 
      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. This score has recently been translated and validated in isiZulu.

      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 basal flow anaesthetic technique.
    

Detailed description: 
      Aims & Objectives:

      The aim of this study is to compare quality of recovery between desflurane and isoflurane
      inhalational anaesthesia. 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.

      Isoflurane is the standard drug used at Dr. George Mukhari Academic Hospital theatre complex
      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.

      A secondary objective will be to compare the consumption and relative cost of using
      isoflurane vs desflurane with a minimal or basal flow anaesthetic technique. This will be
      done by comparing the amount of vapour used in millilitre per hour between desflurane and
      isoflurane during 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.

      Methods:

      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.

      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.

      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.

      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:

             1. Explain the objectives of the study to the patient.

             2. Hand the patient a patient information leaflet and discuss any questions the
                patient may have.

             3. 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

      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.

      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.

      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.

      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. As far as 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 the patinet, 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
      above.

      As follow-up will be done before discharge, retention of patients to follow-up should not
      present any difficulties.

      Data Management:

      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 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.

      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.

      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. Anaesthetic workstation stored history

        4. Theatre record book

      Missing data on vapour start/end times:

        1. Blue anaesthesia report card

        2. Anaesthetic workstation stored history

      Missing data on millilitres vapour used:

      1. Anaesthetic workstation stored history

      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.

      Statistical Analysis:

      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.
    

Intervention name(s): Desflurane; Isoflurane
Intervention type(s): Drug; Drug
Intervention description(s): The intervention group will receive desflurane for maintenance of anaesthesia, and the quality of recovery score will be compared post-operatively with the control group who received isoflurane.; The control group will receive Isoflurane for maintenance of anesthesia. The quality of recovery score will be compared post-operatively with patients in the intervention group who received desflurane.
Other intervention name(s): Suprane; Forane
Intervention MeSH terms: Desflurane; Isoflurane
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: 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.
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Supportive Care
Keywords: Anesthesia: General; Outcome; Quality of Recovery Score; Anesthetics: Volatile; Desflurane; Isoflurane