Study design
This study is a prospective, randomized controlled trial with two parallel groups. After randomization, participants will receive either (1) standard care after surgery (control group) or (2) VR based intervention along with standard care for testing the superiority of the intervention delivered through VR environments for reducing postoperative pain.
The study protocol followed the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) (44) instructions and received the ethical approval from the Babes-Bolyai University committee as from the committee of Municipal Hospital of Cluj-Napoca and is retrospectively registered on ClinicalTrials.gov (NCT03776344).
Study sample size
Using G*Power 3.1.9.2 (45), we estimated a minimum of 54 participants (27 in each group) needed to detect an effect size of 0.80, with α = 0.05 and power = 0.80. The expected effect size of 0.80 was based on the results of an under-review meta-analysis conducted in our lab, which assess the effectiveness of VR interventions for hospitalized patients to decrease pain intensity in studies with parallel design. However, we expect to have some incomplete or unusable data, especially on the physiological measure, therefore, we aim to recruit 30 participants in each group.
Participants
All the participants are recruited from one community hospital from Romania. Starting October 2018, each patient admitted to the hospital for surgery is screened for eligibility criteria to this trial.
Inclusion/exclusion criteria
The below criteria should be cumulative met in order that a participant be included in the trial.
Inclusion criteria:
- Adults aged 18–65 years, after surgery of varicose veins, hernia repair or gallbladder surgery.
- Patient in the acute care units, 1–3 days following surgery.
- Willing and able to provide informed consent and participate in the study visit and study follow-up questionnaire.
Presence of any criteria listed below will conduct at the exclusion of the participant from the trial.
Exclusion criteria:
- Age below 18 and under 65 years.
- Patients with neoplastic pathologies.
- Patients with a history of motion sickness.
- Patients with visual impairment.
- Patients with severe/profound cognitive impairments measured with Six-item Cognitive Impairment Test (6CIT).
- Use of strong opioids (i.e., morphine)
- Other reasons for exclusion (e.g., Non-Romanian speaking patients, patients with severe psychological problems)
Randomization and blinding
Randomization is conducted within the type of surgery using a random number generator, with an equal number of participants in the control and experimental group. The allocation sequence is stored on a secured computer until the participants are assigned to one of the interventions. An independent researcher conducted the randomization sequence, and every patient is treated in a separate room. Collecting all the data on separate room for every participant ensure the blindness of medical personnel and participants through the entire procedure. In the case that a participant explicitly requests to end the study procedure for any reasons, the procedure will be stopped and counted as a dropout. Those patients, who ask to end the procedure earlier will be asked to respond at a short interview to quantify the reasons.
Recruitment procedure and interventions
The process of recruitment and data collection is presented in Figure 1. The day following the surgical procedure, all patients from the acute care unit who meet the primary criteria for inclusion (i.e., age, type of surgery, type of opioids used, free of visual impairments, able to fluently speak in Romanian and without recorded psychological problems) are invited to participate. Information regarding duration, procedure, implications, and conditions for withdrawing are presented and explained. Those who are interested and sign the informed consent are invited in a separate room where they complete the Six-item Cognitive Impairment Test for assessing the eligibility regarding executive functions. Subsequently, patients are randomly allocated to one of the two groups:
(a) Treatment group: VR based intervention
Patients allocated to the VR based intervention will follow the standard protocol after surgery as prescribed by the current medical personnel and are exposed for 15 minutes to an interactive virtual environment (i.e., Nature Treks© VR). This application is a commercially available app from the Oculus store, promoting relaxation through fifteen highly immersive environments. Each environment recreates a different natural scene (e.g., a tropical beach, savannas at sunset, snowy forests) which can be explored by the patients through a controller. Concomitant with the activities (e.g., walking on the beach, climbing the mountains) environmental effects are changing smoothly to create a vivid experience. Additionally, in some environments (i.e., deep blue and black beginning), patients can freely explore the scenes in 360 degrees for enhancing the feeling of presence and immersion.
As previous studies testing the efficacy of the analgesic effect of VR (41) showed that better immersion is associated with lower scores for pain intensity, the device used is an Oculus Rift®. This device is the premium device from Oculus, equipped with a highly immersive headset, one controller, and integrated headphones.
During the VR exposure, the fluctuations of skin conductance are measured for all patients. Before and after the intervention, pain intensity, relaxation, and VR adverse effects are recorded. Additionally, the catastrophizing level, anxiety, and depression related to health and presence in the VR environment are measured.
(b) Control group: standard as usual intervention
Patients allocated to the standard as usual group follows the treatment after surgery as prescribed by current medical personnel. They are also following the same protocol as the patients in the intervention group regarding psychological and physiological measures but are not exposed to the VR environments.
Data collection procedure
Figure 2 offers an overview of the process of the data collection process and measures. The level of pain intensity and relaxation is collected before and after the intervention. The amount of analgesic used will be extracted from the medical records. Excepting the fluctuations of skin conductance, all measures are collected through an online platform. All psychological and physiological measures will be collected by a previously trained researcher. In order to ensure an accurate baseline for the physiological measure as to control for the individual differences in skin conductance (SC), the signal of SC for each participant will be taken before the study procedure start for five minutes. During this time, participants will have no other instructions, and the communication will be maintained at the minimum level.
Patient and Public Involvement
The aim and the design of this protocol were based on the previous studies using VR technology without including the patient’s preferences or experience. However, the qualitative and quantitative participant feedback from other studies in similar contexts using VR was reviewed and considered. Participants will not be directly involved in the recruitment or data collection process. At the end of the data collection process, each patient receives a debriefing regarding study objectives and a summary of the psychological results. In the case that they will have high anxiety or depression scores (assesses through Hospital Anxiety and Depression Scale), the option to meet the hospital psychologist will be presented. After the statistical analysis is completed, all patients will receive an email communicating that if they want can ask for a summary result of the entire study.
Outcomes
The present study assesses the efficacy of a Nature Track© VR to decrease pain intensity in surgical patients. Pain ratings will be measured before and after the intervention. Secondary outcomes will measure the effects of the application on relaxation and time spent thinking about pain. Also, to allow for an in-depth investigation on the effect of VR environments, the primary outcome will be complemented with measures of the adverse effects, level of immersion, and level of presence in the VR.
Measures
Primary measures
Pain
The pain intensity will be measured using the Numerical Rating Scale (NRS) by asking participants to report their intensity before and after the intervention. To help patients to discriminate between different pain levels, will ask them to report the mean level of pain intensity in the last 24 hours, the peak of intensity in the same period and the intensity right before the intervention. We chose NRS for this study rather than other measures more extensively used, such as Visual Analog Scales (VAS), due to the consensus of the better psychometric properties (46–49). In addition, we will measure the fluctuations of the SC, as a physiological indicator. Similarly, the fluctuations of the SC were chosen following the literature recommendations of assessing the postoperative pain with physiological markers (50–52).
Secondary measures
Relaxation
As the level of relaxation could affect the perception of the pain intensity, the state of relaxation will be measured using the NRS before and after the intervention. We chose to measure through an NRS rather than other scale designed to measure relaxation due to his factual effect and similarities with the pain intensity measures.
Time spent thinking about pain
Another factor which can contribute to an increased perception of pain intensity is the time spent thinking about pain (53). Consequently, we will ask patients to report after the interventions, on NRS, the amount of time they spent thinking about their pain during the intervention.
Adverse effects
Potential adverse effects will be evaluated using the Simulator Sickness Questionnaire (SSQ). Because some of the unintended effects of VR could also be effects of the opioid’s consumptions (e.g., headaches, nausea), we will ask participants to complete the scale twice, before and after the interventions. The SSQ was previously validated and proved robust psychometrics properties (54,55) being the most widely measure of cyber-sickness. The patients will be instructed to answer on a 4-point Likert scale, corresponding to not at all, slight, moderate and strong sensations regarding the occurrence of possible side effects such as general discomfort, fatigue, headache, and dizziness.
Treatment satisfaction
Engagement, interaction with the VR system, and expectancy for recovery will be measured through the Suitability Evaluation Questionnaire (SEQ). Derived from the User Satisfaction Evaluation Questionnaire, SEQ proved good psychometrics properties (56). This is a six items questionnaire, and patients will be instructed to answer on a scale from 1 (not at all) to 5 (very much). In the end, once the SEQ completed, the patients will be instructed to answer an additional question (i.e., Are you willing to use VR systems in the future?) with dichotomous response developed by the authors for assessing the willingness for further sessions with VR system.
Covariates and measures for baseline imbalances
Opioids used
The amount of analgesic used will be extracted from the medical records and will be used as a covariate in the estimation of the intervention effect. The usage of opioids will be coded as present and absent. The mean drug metabolism time will be calculated in order to determine if an opioid agent is active, coding one when the opioid agent is active and zero when is out of his acting range.
Pain catastrophizing
Level of catastrophizing will be measured through the Pain Catastrophizing Scale (PCS). This scale is a self-report measure with 13 items structured in three subscales, namely rumination, magnification, and helplessness, and proved good psychometrics properties (57). Patients will be instructed to answer on a scale from 0 (“not at all”) to 4 (“all the time”) if they practice the behaviors expressed by the items.
Assessment of mood
Anxiety and depression levels will be assessed through the Hospital Anxiety and Depression Scale (HADS). This scale is a self-report measure with 14 items, with half of the items measuring anxiety symptoms (e.g., items targeting tension, panic attacks) and the other half measuring depression symptoms (e.g., items targeting anhedonia or inability to enjoy things or experiences). Responses are recorded on a scale from 0 to 3, and each item has a different response in accordance with the item content.
Cognitive abilities
Cognitive abilities were measured though the Six-item Cognitive Impairment Test (6CIT), a screening tool for measuring the global cognitive status. The items of the 6CIT cover six questions; one assessing the memory (remembering a 5-item name and address), two items including calculation (reciting numbers backward from 20 to 1 and months of the year backward) and three items assessing orientation (year, month, and time of day). The cutoff of seven from the total score was used for excluding patients with low cognitive abilities.
Statistical analysis
All analysis will be conducted in accordance with the intent to treat principle (58). For assessing if our data adhere to the normal distribution, the Shapiro-Wilk test will be employed. Depending on the form of our distribution, the parametric variables will be presented as mean and standard deviation (SD) and the non-parametric variables as median and inter-quartile ranges (IQR). Simple t-test and Chi-Square test will be employed for exploring the baseline imbalances from the two groups regarding age, type of surgery, experiences with surgery, the number of opioids used, level of pain catastrophizing, and levels of anxiety and depression. In order to assess the efficacy of the VR intervention for reducing pain intensity as compared with standard care intervention, we will employ repeated measure analysis of variance (RM-ANOVA). Analgesic consumptions will be used as covariate measure if t-test will show significant differences. In order to estimate the effect size of the intervention, we will use the Cohen’s d coefficient (small effect size d =.20, medium effect size d =.50, large effect size d =.80) (59) which will be calculated based in the mean and SD of both groups. In the case that the primary outcome will not be normally distributed, a log-transformation will be employed by extracting for each subject a coefficient of variance (CV) (SD/mean). The categorical measures of the secondary outcomes will be analyzed using the Chi-Square test, Fisher’s exact test or Mann-Whitney U test as appropriate. For all analysis, a value of p below or equal with.05 will be considered.