Virtual Reality as a distraction therapy during cystoscopy: a clinical trial

ABSTRACT Objectives: to investigate whether virtual reality (VR) experience is associated with decreased pain sensation among patients who undergo rigid cystoscopy under local anesthesia. Methods: we performed a prospective, randomized, controlled study of 159 patients who were aleatorily enrolled into two groups: VR and control. VR experience intervention consisted of using a headset with a smartphone adapted to a virtual reality glasses where an app-video was played during the procedure. Main outcomes analyzed were pain, discomfort, heart rate variability, difficulty and duration of the cystoscopy. Statistical analyses were performed using a Student’s t test, Mann-Whitney test and Chi-square test. A P<0.05 was considered to be statistically significant. Results: among 159 patients studied (VR group=80 patients; control group=79 patients), the mean age was 63,6 years and 107 (67,3%) were male. There was no statistically significant difference in baseline characteristics between the 2 groups. VR was significantly associated to decreased heart rate variability (6,29 vs 11,09 bpm, P<0,001) and lower duration of the procedure (5,33 vs 8,65 min, P<0,001). Also, when cystoscopies due to double-J extraction were excluded, VR experience was associated with reduced pain on the visual analog score of pain (3,26 vs 4,33 cm, P=0,023). Conclusions: the use of VR as a distraction therapy while performing outpatient cystoscopies is safe, has no side effects, is associated with less pain and discomfort, and reduces length of procedure.

has showed good results in alleviating pain in special populations, as pediatric oncology patients, burned victims, children undergoing procedures [6][7][8] .
Virtual Reality (VR) is a type of cognitive distraction that creates a visual and auditory immersion, lowering the noise and connection with the external environment 4 .VR systems consists of a hardware (headset, glasses, gloves, computers or mobile devices) and a software that provides a multi-context intervention environment 9 .It is an immersive and interactive experience, integrating multiple sensory levels and capturing a greater degree of attention 10 .
Though VR is a technique still unknown by several medical doctors, it has been successfully used to minimize procedural pain in various situations as changing burn dressings, venipuncture, dental procedures, lipoma resections and minor surgeries [11][12][13] .
Based on the hypothesis that the use of distractions might reduce discomfort and anxiety during medical procedures, we sought to analyze whether the use of VR during rigid cystoscopy is correlated to decreased pain when compared to patients not using this technology.

Study sample
We performed a prospective randomized clinical trial that included patients who underwent elective rigid cystoscopy under local anesthesia between April 2019 to September 2019.Were excluded from the study patients younger than 18 years old, with cognitive or sensorial limitations (such as dementia or blind patients), and patients who refused to participate, or who underwent an aggregate procedure (such as urethral dilatation or meatotomy).The cystoscopies were subdivided according to their indications: diagnostic (hematuria; lower urinary tract symptoms); follow-up (after or during non-muscle-invasive bladder cancer therapy); or for double-J stent extraction.
The sample size was calculated based on an alpha error of 5% and a beta error of 20% (with a power of the study of 80%), with an average pain of 4,4 (on a scale from 0 to 10) and a standard deviation of 214.The

Procedure technique
Cystoscopy with a rigid cystoscope was performed two minutes after intraurethral injection of 20ml of 2% lidocaine gel.The procedure was executed by one of a team of three medical residents in Urology.
Decision to perform bladder biopsy was assessed during the procedure.As an objective parameter of pain, heart rate (HR) was monitored during cystoscopy and registered as variation over the basal HR on the peak.The duration of procedure was timed at the moment the cystoscope was introduced into the urethra and ended with its removal.
VR experience: the patient was instructed about VR before the procedure at the time of consent.We used a Samsung ® A5 mobile phone adapted to Trust Urban ® Exos 3D virtual reality glasses and a headset.The patient placed the glasses on his face and positioned himself for the cystoscopy.On the screen, an app-video was playing simulating a ride on rails (screenshot at Figure 2) while study was designed to detect a 20% difference between groups.Thus, the calculated sample was 156 patients (78 in each group).
A Visual Analog Scale (VAS) was applied to each patient to assess pain and anxiety status (Figure 1).Difference between groups regarding VAS was analyzed in centimeters (cm).After the procedure was done, the glasses were removed and the scales applied.

Statistical Analysis
After the procedure, visual analog scales to evaluate pain and discomfort was applied (Figure 1).Side effects were also reported at this moment.After cystoscopy, the surgeon (a medical resident in Urology) described the difficulty level to perform the exam, on a scale of 0 to 10.
Main outcomes analyzed were: pain (on a VAS scale of 0 to 10), discomfort (on a VAS scale of 0 to 10), heart rate variation (on bpm), difficulty (on a VAS scale of 0 to 10), and duration (on minutes).Difference among scale rates were measured in centimeters (cm).
Quantitative variables were analyzed using Student's t-test for variables with normal distribution and Mann-Whitney for non-normal distribution.Categorical variables were analyzed using Chi-square test.The level of statistical significance was considered as p<0.05.

RESULTS
A total of 175 cystoscopies were performed.
Among 159 patients enrolled, 80 patients were randomized to VR group and 79 patients to control group.There was no significant difference between the groups regarding age, BMI, pre-procedure anxiety, pre-procedure heart rate, gender, ethnicity, number of previous procedures, biopsy and type of procedure (Table 1).
VR use was significantly associated to lower heart rate (p<0,001) and duration of the procedure (p<0,001) (Table 2).Surgeons reported lower difficulty during cystoscopies when patients were on VR experience when compared to controls (p=0,002) (Table 2).Subgroups analysis demonstrated that male patients were those who had more benefits on VR use (Table 3).

Goergen
Virtual Reality as a distraction therapy during cystoscopy: a clinical trial When double-J extraction (n=31/19,5%) was removed from the sample, VR group described lower pain when compared to controls with significance (p=0.023)(Table 4).None of the patients related any side effect associated with the VR experience.

DISCUSSION
Although several patients undergoing cystoscopy frequently complain about pain and discomfort during the procedure, there are several forms of distraction such as using a second screen for the patient, music, stress ball, or oral explanation to reduce pain 3,[15][16][17][18][19][20]   found that patients listening to music and with realtime visualization of the procedures during cystoscopies reported significantly lower pain when compared to controls.The authors also showed that in the intervention group post-procedural pulse rate was diminished in comparison to pre-cystoscopy (p<0.001) 17 .This is in line with our analysis, we found that patients who underwent to cystoscopies for causes other than double-J extraction had significantly lower increment in heart rate and diminished pain.In another study, Walker et al. randomized 45 patients before cystoscopy into two groups, with the VR immersion as intervention, failing in demonstrate any difference in pain improvement between the groups 14 .However, it was a small study and patients underwent to flexible cystoscopy, that is associated to lower pain than rigid cystoscopy 3 .
Moreover, baseline characteristics that might influence in results, as gender and first-time procedure, were not assessed.
The relationship of non-pharmacological distraction therapies and pain reduction throughout medical procedures is an interesting question still under investigation.It has been acknowledged that pain perception is closely related to mind attention 10 .
Melzack and Wall postulated that pain is perceived by the central nervous system as long as a painful stimulus travels through the body after passing certain nerve gates.This means that sensory pathways play a major role in pain awareness 25 .So, its plausible to think that VR immersion experience (that saturates several sensorial stimuli, like visual and auditory) may be an important tool to attenuate pain perception.Furthermore, pain sensation is also correlated to previous experiences and emotional status making painful threshold a very personal experience.
The pain can be modulated by cognitive factors, like attention and distraction.Generally, the attention has to be actively directed to non-painful stimuli to avoid that painful stimuli prevail.Also, other painful stimulus can reduce de pain of previous painful stimuli 26 .
We found that VR during cystoscopy is associated with lower pain in subgroup analysis, reduced length of procedure, diminished heart rate variability and less difficulty to perform cystoscopy.The clinical implications of our findings are multiple.In our country most part of cystoscopies are outpatient basis procedures and VR implementation might be a routine because it is costless and with neglectable side effects.In addition, it might reduce the use of analgesics and narcotics during other medical interventions making it a not so an unpleasant experience.Furthermore, VR environment is a multiple distraction method and appears to be as effective as using multiple distraction approaches.
Another important issue is that patient on VR seems to be less restless and more relaxed during the procedure, making it easier and faster for urologist to perform the cystoscopy.Consequently, these suggests that VR is an interesting intervention to be used in medicine.
Our study has several strengths, as a randomized controlled trial with a sizable sample.
However, there are some limitations.Therefore, the use of VR as a distraction therapy was correlated with a reduction on the physiological response of pain (heart rate variability), as well as a lower distress during the cystoscopy, reducing the difficulty level and the time required to complete the procedure.

CONCLUSION
Our study demonstrates that the use of VR as distraction therapy while performing outpatient cystoscopies is safe, has no side effects and reduces Goergen Virtual Reality as a distraction therapy during cystoscopy: a clinical trial objective parameters of pain and discomfort, as well as facilitates the procedure and reduces its duration.
The benefits of VR on reducing pain were significant in patients who underwent cystoscopy (excluding procedures for double-J extraction).However, given the fact that there are several new types of immersive technology of VR distraction, further studies are needed to analyze the feasibility of the method with more complex systems, as well as comparing it to other forms of distraction during the procedure.

Figure 1 .
Figure 1.Screenshot of the app.
First, mean age of our patients is over 60s and most of them are not familiarized with VR technology.Second, cystoscopies for double-J extraction were not excluded, and although this might influence in lowered length of procedure it also correlated to lower pain perception because it is faster than other cystoscopies as demonstrated on subgroup analysis.Third, there are other VR immersion technologies with different softwares and hardwares that might be compared in intervention group, because previous experiences occasionally may influence in painful threshold.Relaxing videos on VR immersive and interactive environment are probably more effective to attenuate pain than action videos.Fourth, all procedures were performed by medical residents in Urology who were in training and under learning curve.
had enough information to keep him distracted, but without sudden changes that could scare him and raise his heart rate.Despite the use of headphones, hearing communication was still maintained with the patient.

Table 3 -
Outcomes subdivided by gender.

Table 4 -
Outcomes without the double-J removals.Some studies have reported the use of distraction techniques during cystoscopies to alleviate pain with mixed results.For example, Gupta et al.