DOI: https://doi.org/10.21203/rs.2.12519/v1
As defined by the International Association for the Study of Pain (IASP), pain is an unpleasant sensory and an emotional experience associated with actual or potential tissue damage or described in terms of such damage. Although pain is not equally distributed across the globe, pain affects all populations against age, salary, or geopolitics factors (1). Acute pain symptoms are estimated to be present in 1 of 5 adults, while 1 of 10 adults suffers from chronic pain (2). Surgeries are considered one of the most prevalent causes of acute and chronic pain with a percent of acute postoperative pain bigger than 85% and pain severity rated as moderate, severe or extreme being reported in 75% of those cases (3).
Though in the last year’s pain management gained a lot of interest in both research and practice areas with some essential developments in the management of chronic pain, the management of postoperative pain remains a tremendous challenge with high costs for patients and health care providers (3). Specifically, poorly or ineffective management of postoperative pain was associated with prolonged hospitalization (4), alveolar ventilation, tachycardia, insomnia, flawed wound healing (5) as well as with an increased risk of chronic post-surgery pain (CPSP) (6). Described as the pain which persists beyond the expected recovery time after a surgical procedure (7), CPSP is reported in 10% to 70% of cases depending on the type of surgery (6,8,9), biological and psychological factors (10). Although evidence-based treatments, including pharmacological and psychological, are promoted by the clinical practice guidelines of postoperative management (10), often the non-pharmacological interventions are seldom implemented (12). The consequences of treating pain mainly through pharmacological options are the array of side effects derived from opioids consumptions such as vomiting, nausea, respiratory depression and physical dependence (13,14) which increase the costs of pain care and places pain medicine in a peerless crisis (15).
As a tailored component of non-pharmacological strategies for postoperative care, interventions based on Cognitive Behavioral Therapy (CBT) prove their efficacy in decreasing pain and distress in different surgical settings, such as lumbar spinal fusion (16,17), abdominal surgery (18), cardiac surgery (19) or orthopedic surgeries (20). Results of a recent meta-analysis (21) which are estimating the efficacy of psychological interventions on postoperative pain management after orthopedic surgery showed a small to medium effect size (g = 0.26) of these interventions in decreasing pain intensity, a medium effect in improving recovery (g = 0.38) and no significant improvements on the frequency of the analgesic used. These results were also evidenced in primary studies estimating the efficacy of psychological interventions (22–25). However, these interventions were associated with several threats regarding their applicability on a large scale. One of the biggest challenges being to synchronize the hospitalization time and patients’ availability as some of these interventions are designed to be conducted in pre-surgical settings. Moreover, other interventions were designed to be conducted in several sessions in order to be effective where again, time is often an impediment. As a consequence of these mismatches between intervention protocols and available time are the low rates of CBT interventions implemented in hospital settings. One potential approach for increasing the applicability and for enhancing the effectiveness of these interventions, respectively for improving the postoperative management could be to deliver the psychological content through technology, such as virtual reality (VR). These interventions already proved their effectiveness in other hospital settings, such as burn units (26–28) or cancer units (29–32).
VR uses a combination of technologies (i.e., head-mounted display-HMD, vibrotactile gloves, individualized sounds, and gesture-sensing joysticks) to create an immersive (33) and multi-sensorial experience (34). Immersion in the virtual world is believed to facilitates the shifting of attention away from the painful stimuli or the experience of pain, to more engaging or enjoyable stimuli, developing effective distraction strategies and reshaping the pain perception (35,36). A recent meta-analysis (37) estimating the efficacy of VR interventions for acute pain management in clinical settings found a medium effect size of these interventions (g = 0.49) being a reassuring result in using VR in acute procedural pain management. Even though VR technology could be effectively exported in medical care settings (37) as a potentially cost-effective tool (38) in postoperative pain management, is rarely implemented and only a few studies examined his efficacy. In one study conducted by Mosso-Vazquez and colleagues (39) found that 30 minutes of VR exposure can reduce pain intensity after cardiac surgery. Analyzes have shown similar results when using self-report or physiological pain measurements (i.e., breathing rate, arterial pressure, and heart rate). However, this study is an uncontrolled study leading to possible overestimation of the VR efficacy. One subsequent study of Mosso-Vazquez and colleagues (40) compared two different VR devices (i.e., HMD and mobile VR) for pain outcomes during ambulatory surgery. Results revealed that both technologies decreased pain intensity, with better outcomes for VR environments delivered through HMD. This result is consistent with other results proving that high-quality VR environments create a better distractor from pain (41) although the estimates were not in postoperative settings. Despite these positive, clinically significant results which are highlighting the potential usefulness of VR in the postoperative pain management, to date, as far as we know, none of the studies tested the effectiveness of VR for postoperative pain following surgery under general anesthesia in a randomized clinical trial. Moreover, the VR contents used in previous studies was intended only to distract patients from pain. Using environments that promote distraction stimuli, but also relaxation stimuli can be particularly useful because a relaxed state of mind was associated with a reduced demand of tissues oxygen and a reduced level of lactic acid, both being harbingers of a decreased level of pain (42). In addition, relaxation was associated with an increased level of endorphins, lower levels of anxiety and skeletal muscle tension. Consequently, we propose a confirmative, randomized controlled trial design, which follows the CONSORT (43) reporting guidelines to assess the effectiveness of VR environments for post-surgical pain intensity.
The aim of this study is to assess whether exposure to VR environments is associated with decreased levels of pain after surgery. We hypothesize that VR based intervention will have a better result in decreasing pain when it is used as a complementary treatment of standard care. Additionally, we will assess the safety of VR based intervention in patients after surgery.
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).
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.
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.
The below criteria should be cumulative met in order that a participant be included in the trial.
Presence of any criteria listed below will conduct at the exclusion of the participant from the trial.
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.
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:
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.
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.
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.
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.
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.
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).
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.
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.
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.
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.
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.
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.
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 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.
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.
Treating pain after surgery with a minimum level of side effects is the ultimate challenge in pain medicine. The guidelines strongly recommend additional interventions along with the standard pharmacological treatments for postoperative pain management (10). Besides, limited medical personnel resources and short periods of hospitalization are widely known problems of the postoperative management, highlighting the need of additional interventions that are requiring very little set-up time to co-occur with the standard pharmacological treatment. Addressing this, VR interventions can be used as a non-pharmacological tool for reducing pain after surgery. The present protocol offers a detailed description of a randomized and controlled clinical trial to determine the effectiveness of VR environments in reducing pain intensity in surgical patients. The results of the further RCT either will offer support for pain interventions to be implemented on a large scale or will provide scientific support in discussing treatment options for individual patients.
During data collection, all the data will be safely stored at the Municipal Hospital. After the implementation phase is completed, all the data will be transferred in a secured PC at the International Institute of Psychotherapy, accessible only by the principal investigator (RG) and the corresponding author (AD).
Following the recommendations of the Consolidated Standards of Reporting Trials (CONSORT) (43) statement for reporting RCTs, results will be submitted to peer-reviewed journals and presented as oral or poster presentation at international scientific conferences. Additionally, we will make available all the results to patients if required. After the results are published in a peer-review journal, all the materials used will be made public at request.
Recruitment start date: 10.10.2018; Predicted recruitment end date: 30.09.2019
The trial has been reviewed and given a favorable opinion by the Babeș-Bolyai Committee (ref. number 7150/03/05/2018). In order to be included in the study, every participant should complete and sign the study consent form. The supplementary information contains the consent form.
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The authors declare that they have no competing interests. All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/coi_disclosure.pdf (available upon request from the corresponding author) and have nothing to disclose.
The present study has no funding. The work of Anca Dobrean was supported by a grant from the Romanian Ministry of Research and Innovation, CNCS—UEFISCDI (project number PN-III-P4-ID-PCE–2016–0861). The funder had no role in the conceptualization, writing, and the decision to approve publication.
Conceptualization (RG,AD); Writing - original draft (RG); Writing - reviews & editing (AD, HS, AS). All the authors have reviewed the present version of the manuscript and approved it for submission. No conflicts of interest have been disclosed for any of the authors.
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