Efficacy of virtual reality for pain relief in medical procedures: a systematic review and meta-analysis

Background Effective pain control is crucial to optimise the success of medical procedures. Immersive virtual reality (VR) technology could offer an effective non-invasive, non-pharmacological option to distract patients and reduce their experience of pain. We aimed to evaluate the efficacy of Immersive virtual reality (VR) technology in reducing patient’s pain perception during various medical procedures by conducting a systematic review and meta-analysis. Methods We searched MEDLINE, EMBASE, CENTRAL, CINAHL, and SIGLE until December 2022 for all randomised clinical trials (RCT) evaluating any type of VR in patients undergoing any medical procedure. We conducted a random effect meta-analysis summarising standardised mean differences (SMD) with 95% confidence intervals (CI). We evaluated heterogeneity using I 2 and explored it using subgroup and meta-regression analyses. Results In total, we included 92 RCTs (n = 7133 participants). There was a significant reduction in pain scores with VR across all medical procedures (n = 83, SMD − 0.78, 95% CI − 1.00 to − 0.57, I 2 = 93%, p = < 0.01). Subgroup analysis showed varied reduction in pain scores across trial designs [crossover (n = 13, SMD − 0.86, 95% CI − 1.23 to − 0.49, I 2 = 72%, p = < 0.01) vs parallel RCTs (n = 70, SMD − 0.77, 95% CI − 1.01 to − 0.52, I 2 = 90%, p = < 0.01)]; participant age groups [paediatric (n = 43, SMD − 0.91, 95% CI − 1.26 to − 0.56, I 2 = 87%, p = < 0.01) vs adults (n = 40, SMD − 0.66, 95% CI − 0.94 to − 0.39, I 2 = 89%, p = < 0.01)] or procedures [venepuncture (n = 32, SMD − 0.99, 95% CI − 1.52 to − 0.46, I 2 = 90%, p = < 0.01) vs childbirth (n = 7, SMD − 0.99, 95% CI − 1.59 to − 0.38, I 2 = 88%, p = < 0.01) vs minimally invasive medical procedures (n = 25, SMD − 0.51, 95% CI − 0.79 to − 0.23, I 2 = 85%, p = < 0.01) vs dressing changes in burn patients (n = 19, SMD − 0.8, 95% CI − 1.16 to − 0.45, I 2 = 87%, p = < 0.01)]. We explored heterogeneity using meta-regression which showed no significant impact of different covariates including crossover trials (p = 0.53), minimally invasive procedures (p = 0.37), and among paediatric participants (p = 0.27). Cumulative meta-analysis showed no change in overall effect estimates with the additional RCTs since 2018. Conclusions Immersive VR technology offers effective pain control across various medical procedures, albeit statistical heterogeneity. Further research is needed to inform the safe adoption of this technology across different medical disciplines. Supplementary Information The online version contains supplementary material available at 10.1186/s12916-024-03266-6.


Background
Pain is the commonest symptom encountered in clinical practice often manifesting as an unavoidable consequence of medical procedures.Effective pain management is crucial to optimise medical procedures, boost patients' satisfaction [1][2][3], reduce their anxiety, reduce hospital stay and minimise long-term analgesic dependence [4][5][6].The use of immersive virtual reality (VR) technology has emerged as a potential tool to distract patients and to modify their perception of pain.Its adoption in clinical practice remains limited.
The search for effective, safe, and cheap analgesic treatment options is a priority accelerated in part by the emerging opiates epidemic in several countries associated with dependence risk and narrow safety profile [7,8].VR technology seems to offer a credible option for effective acute pain relief either as an alternative or as a combined treatment as part of a multi-modal pain relief strategy [9].
The term 'virtual reality' was coined by Jaron Lanier, a writer, musician, visual artist, and computer scientist, who first used it in 1986.The first application of VR in healthcare dates back to the beginning of the 1990s.It stemmed from the need to visualize complex medical data, especially when planning surgical treatment [10].Since then, the use of VR technology in medicine proliferated into several domains including surgical training, neuropsychiatry, acute and chronic pain management, and rehabilitation [10,11].
VR devices are designed to alter one's perception of presence in an alternate reality and augment their immersion, and interactivity [12].Today, several cheap and user-friendly devices offer an immersive environment largely delivered via high-resolution head-mounted displays (HMDs) with built-in sound capabilities [13].In clinical practice, immersive VR experience aims to distract patients during medical procedures, suppressing their appreciation of immediate physical surroundings, allowing them to escape into an alternative reality away from the painful stimuli [14][15][16].Early VR equipment had several technological barriers that limited their use in everyday practice, including high cost, relatively large size, complex operating interface, and user unfamiliarity [17].Recent advances in audio-visual technology, driven by the wide use of smartphones, have enabled the development of affordable and user-friendly equipment [18].Coupled with bespoke medical software, these new VR devices offer patients a versatile immersive visual and auditory experience that could be adopted across different clinical settings [11,19].
Several meta-analyses have evaluated the efficacy of VR showing a beneficial effect with its use.Georgescu et al. [20] performed a meta-analysis for randomised trials that evaluated VR until 2018 (n = 27 RCTs, 1452 patients) showing a beneficial effect for pain reduction following medical procedure although the findings were limited by high heterogeneity and high trial risk of bias [20].Scapin et al. [21] performed a systematic review including [22] randomised trials on the use of VR in burn patients.The findings were also supportive of the role of VR as an effective complementary drug strategy for pain relief in burn patients [21].However, these reviews were either limited to specific clinical situations, suffered from high heterogeneity, or lacked detailed subgroup analyses to explore the reasons for heterogeneity [21].
In the year 2022, there have been 24 new randomised clinical trials (RCT)  published evaluating VR technology highlighting the increased interest in this technology and offering further insight into its applicability across different medical disciplines.Still, the translation of this evidence has remained poor with respect to implementation of VR technology at scale and with variation in practice where medical specialities have taken steps towards adoption.Appreciation of the role of VR for pain relief can be aided by updated evidence synthesis [46].
In this systematic review, we conducted a comprehensive assessment of the evidence on VR efficacy as a noninvasive and non-pharmacological pain management method in patients undergoing different medical procedures.We performed an overall evidence synthesis pooling data from all relevant RCTs in addition to bespoke subgroup and meta-regression analyses to help interpret the evidence [17,47].

Methods
We conducted this systematic review using a prospectively registered protocol (CRD 42020195919) [48] and reported in accordance with PRISMA guidelines [49].

Literature search
We searched major electronic databases (MEDLINE, EMBASE, Cochrance CENTRAL, CINAHL, and SIGLE) for randomised trials that evaluated the efficacy of immersive VR technology equipment for pain relief from inception until December 2022.We developed a comprehensive and inclusive search strategy using MeSH search terms and combined them using the Boolean ' AND' and 'OR' (Additional File 1: Appendix S1).We applied this search strategy to individual databases after amending it to the specification of each database.We then deduplicated the results and produced a final long list of citations.We manually searched the bibliographies of relevant studies to identify any additional trials not captured by our electronic database search.We also conducted supplementary searches in Google Scholar and Trip database to identify additional studies of relevance [50].We did not apply any search filters or language restrictions.Relevant citations in non-English were obtained and translated for assessment against our inclusion criteria.

Study selection
Five independent reviewers (JJT, DP, SH and RP, AK) completed the study screening and inclusion process in two stages.First, titles and abstracts were screened to identify potentially relevant studies following which, the full text of relevant articles were reviewed against our inclusion criteria.We included all randomised trials of any design that evaluated the efficacy of any immersive VR technology equipment for pain relief during any medical procedure, including labour and childbirth.We initially planned this review to include only adult participants and later extended this to include paediatric participants to provide a more comprehensive evidence synthesis.We excluded non-randomised studies, review articles, and animal studies.We also excluded studies that assessed distraction techniques only (e.g. a display screen with no immersive capabilities), studies in dental procedures, and those that did not assess pain using a standardised measurement tool or reported on pain scores more than an hour after the procedure.Discrepancies and disagreements between reviewers were discussed and resolved in consensus with two additional reviewers (MPR and BHA).

Data extraction
Three reviewers (JJT, DP, SH, AK) extracted data in duplicate using a piloted electronic data extraction tool.We collected data on study design (crossover vs parallel), intervention settings, population characteristics, inclusion and exclusion criteria, type of VR technology and equipment used, nature of the medical procedure or intervention, loss to follow-up, and dropouts.Our primary outcome was pain scores measured immediately after or within an hour of the procedure.We also collected data on anxiety scores where relevant.In trials including paediatric patients, we included the parents' reported pain scores.

Assessment of risk of bias
We assessed the risk of bias in included trials in duplicate (JJT, RP, AK, DP, MPR, SH) using the Cochrane Risk of Bias assessment tool 2.0 [51].We assessed studies in five domains: participant randomisation and sequence generation, allocation concealment, outcome assessment, completeness of outcome data, and selective outcome reporting.Due to the nature of the intervention, we did not penalise unblinded trials.Studies with a crossover design were assessed using a modified version of an established tool [52].We assessed the risk of bias in these studies for appropriate crossover design, randomisation and order of receiving the treatment, risk of carry-over effect, data collection, allocation concealment, outcome detection, data completeness, and selective outcome reporting.

Data synthesis
We pooled data using a meta-analysis with a random effect and adjusted using restricted maximum likelihood (REML) [53].We reported on the difference in pain scores measured using standardised mean difference (SMD) with 95% confidence intervals (CI).We assessed any detected heterogeneity using the I 2 statistics.The I 2 index is an approach to quantify heterogeneity in metaanalyses.I 2 provides an estimate of the percentage of variability in results across studies that is due to real differences and not due to chance.The I 2 index measures the extent of heterogeneity by dividing the result of Cochran's Q test and its degrees of freedom by the Q-value itself.An I 2 of less than 25% is usually viewed as low heterogeneity, between 25 and 50% as moderate, and over 50% as high heterogeneity.
We planned subgroup analyses to investigate potential effect modifiers (patient age group (paediatric patients defined as < 16 years old) vs adults), type of medical intervention (venepuncture-related procedures, minimally invasive medical procedures (defined as any medical procedure conducted in office setting without the need for general anaesthesia), dressing changes in burn patients, and childbirth), trial design (parallel group vs crossover trials), the trial quality as assessed using the risk of bias tool), the type of VR technology (interactive: arbitrarily defined when VR software is asking the participant to take part in specific activities compared to a passive VR experience), the VR delivery settings (inpatient vs outpatient vs emergency department) and assessed their impact on the effect estimates using a meta-regression [54].We explored potential sources of heterogeneity using a leave-one-out analysis and a sensitivity analysis excluding potential outliers.We also investigated the risk of publication bias using Egger's test, a funnel plot, and Galbraith plot to identify potential outliers [55].Where publication bias was detected, we explore potential impact using the trim and fill method [56] to estimate and adjust for the number and outcomes of missing studies in the meta-analysis.We conducted a cumulative meta-analysis for selected outcomes to evaluate temporal trends and changes in effect estimate over time as new trials emerged [57].Statistical analyses were conducted in STATA V17 (StataCorp, TX) and Open Meta-analyst software (Brown University; Providence, RI, USA).

Patient and public involvement
No input was sought from lay service consumers in the design, conduct, and reporting of this systematic review.

Results
We identified 51,140 potentially relevant citations, of which we assessed 132 studies against our inclusion criteria and included 90 articles reporting on 92 unique RCTs in our meta-analysis (7133 participants) (Fig. 1) (Additional File 1: Appendix S2. (40 studies were excluded ).No relevant citations were identified in non-English.The majority of included RCTs had a two-group parallel design (77/92, 84%), including a threearm RCT [100], and less than one fifth had a crossover design (15/92, 16%).

Risk of bias
For parallel-group RCTs, the overall quality of the included studies was moderate with the majority of studies showing low or moderate risk of bias for selective reporting (73/77, 95%), outcome assessment (72/77, 94%),

Interactive
Xie 2022 [24] 3D SpaceMax software The real scene shooting in the delivery room is added to the system to bring the 3D interactive virtual scene to life, including characters, sites, objects, environments, time and voices

Non-interactive
Yildirim 2023 [23] Immersive experiments with VR glasses (Oculus Rift VR and Samsung Galaxy S7 mobile phone and headset) 3 virtual environments (i.e.roller coaster, mine craft, ocean rift)
We assessed publication bias using Egger's test, which was significant (p = 0.11).We visually inspected the variance in effect estimates for potential small study effect using a funnel plot (Additional File 1: Figure S3) and a Galbraith plot (Additional File 1: Figure S3) which identified several outliers although the overall precision in the effect estimate was high.We explored the potential impact of publication bias using the trim and fill method which did not identify any missing studies (Hedge's g 0.00, 95%CI − 0.051 to 0.051) (Additional File 1: Figure S3).
We conducted a leave-one-out analysis, which identified five studies as potential outliers [101,126,131,134,153,154]. We then conducted a sensitivity analysis excluding these trials, which led to a small reduction in the overall effect estimate (SMD − 0.58, 95% CI − 0.71 to − 0.45), but did not resolve the observed heterogeneity (I 2 = 82%).

Anxiety
Thirty-one trials reported on changes in anxiety between the VR group and routine care, mainly involving minor medical procedures and venepuncture procedures [101,111,117,120,127,128,142].The overall effect estimate showed a significant reduction in anxiety scores with the use of VR across all populations, although heterogeneity was high (n = 31, SMD − 0.82, 95% CI − 1.09 to − 0.54, I 2 = 91%, p = < 0.01) (Additional File 1: Figure S4).The cumulative meta-analysis showed more precise effect estimates with the addition of newer trials over the last 2 years, although the confidence interval remained relatively wide (Additional File 1: Figure S4).

Summary of main findings
Our review summarised evidence sought from different medical disciplines evaluating the efficacy of VR technology.Despite heterogeneity, the reduction in pain perception was consistent across different clinical settings, medical procedures, and patient characteristics.We identified a relatively high number of relevant trials, particularly within the last 5 years.This was associated with a gradual development in the VR equipment used moving from larger head mount display screens to lighter and cheaper smartphones interfaces [100-103, 105-107, 115, 116, 118-122, 125-128, 130, 133, 155, 159, 160, 164].The reduction in pain scores was observed across all evaluated medical procedures, participant age groups and trial designs, which increased the generalisability of our findings.

Implications for clinical practice
The rapid progress in immersive VR technology has facilitated its evaluation within different clinical settings driven by smaller, cheaper, and more user-friendly VR equipment.VR immersion was defined as according to this point of view VR is described as 'an advanced form of human-computer interface that allows the user to interact with and become immersed in a computer-generated environment in a naturalistic fashion' [169].
As this technology becomes more widespread within the general population, its use within the health sector will gradually become mainstream with higher user acceptability and satisfaction [170].Unlike other disciplines, e.g.engineering [171] and education [172], where VR use has grown organically, introducing it into healthcare requires deliberate implementation steps to ensure feasibility and patients' safety [173].Considering the beneficial effect observed in our meta-analysis, we argue that health policy makers should incorporate the use of VR within their pain management guidelines to enable its safe adoption [174].This is particularly relevant for certain patient groups, such as in paediatric phlebotomy [175].

Implications for future research
Our review is focused on evaluating VR technology in acute pain relief settings, largely using non-standardised software.Such versatile and easy-to-use technology has the potential to help chronic pain patients within the community enabled by virtual reality meditation and mindfulness techniques [176].Similarly, developing procedure or condition-specific software could also help to maximise its analgesic effect as shown by some early experimental studies [177].Lastly, clinical implementation pathways should consider the ideal format, frequency, and timing of using VR for medical procedures as per local feasibility.
Previous systematic reviews [20,[178][179][180] called for larger trials to address the perceived heterogeneity.Our trim and fill analysis suggests that larger trials are unlikely to nullify the depicted cumulative beneficial effect across the trials included in our analysis, thus offering low added value.
The majority of the included trials in our review focused on acute pain control following medical intervention.VR could be a game-changer to convert several inpatient procedures to outpatient settings, thus driving down cost, hospital stay, and in-hospital complications [120].
The reduction in pain management cost alone could offer a substantial advantage to reduce the length of hospital stay and associated costs, which was estimated at around $5.4 per patient (95% CI − 11 to 156) with VR use compared to routine care [181].In this case, VR will prove dominant without the need for a formal cost-effectiveness study.
Most of the included trials used varied pain scales with no clear justifications, which may have led to higher heterogeneity at evidence synthesis.Adopting available standardised and validated outcome measurement tools would enable precise evidence synthesis and help to eliminate across trial heterogeneity.Leveraging the advances in VR user interfaces could enable interactive and contemporary built-in outcomes assessment, thus eliminating assessment bias in future studies.

Strengths and limitations
The main strength of our review stems from our comprehensive approach to evaluating the efficacy of VR technology across different medical disciplines in contrast to previous reviews that focused on particular patient demographics or medical conditions [21].We undertook a prospective registration, employed an exhaustive search strategy, and evaluated the sources of bias.We followed an established methodology to explore potential sources of heterogeneity and evaluated the risk of publication bias.
Our findings suffered some limitations, most notably the heterogeneity of effects among included trials.We explored this heterogeneity in a meta-regression which suggested a higher effect in minor procedures and in trials involving children.However, the observed beneficial effect pertaining across all evaluated subgroups with relatively narrow confidence intervals supports the overall benefit of VR technology for pain control.We explored this heterogeneity using a cumulative meta-analysis which confirmed that future trials are unlikely to change the certainty in the beneficial effect of VR in reducing pain following medical procedures.The prediction intervals also suggest that most population would see a benefit from using VR although a small portion might not observe this benefit (Additional File 1: Figure S7).
A potential source of heterogeneity could stem from the assumed variation in the reported common comparator (routine care).Several analgesic agents, doses, and frequencies could have been used in the control group across included studies which we were unable to adjust for in our analysis.
Several factors could drive this heterogeneity, including variations in the common comparator, background, type of software (e.g.interactive vs static), hardware fidelity, procedure and exposure duration, patient morbidity and pain tolerance, and measurement assessment tools.Exploring these effect modifiers is only possible using individual patient data.However, such analysis might fail to add significant value especially when evaluating a subjective outcome such as pain, even within the context of an individual patient data meta-analysis [182].
Most of the included studies had a small sample size, with some evident outliers identified on the funnel plot.To address the risk of publication bias, we conducted a cumulative and one-out trial analysis, excluding obvious outliers, which helped us to refine the effect estimates.While some of the included crossover RCTs suffered from risk of bias [124,125,131], our subgroup analysis supported the overall beneficial effect of VR across both crossover and parallel-group RCTs.Majority of the included crossover trials only reported on the effect estimates after the final crossover step which limited our ability to adjust for the potential risk of bias when pooling data from such trials.We explored the limitation of evidence sought from crossover trials using a subgroup analysis which demonstrated a wider confidence intervals compared to evidence from parallel-group trials.However, evidence of reduction in pain scores remained significant (Additional File 1: Figure S2).
Lastly, we were unable to report on the planned secondary outcomes in our protocol due to limitations in reporting across the included trials.

Conclusions
Immersive VR technology offers effective pain control across various medical procedures, albeit statistical heterogeneity, albeit statistical heterogeneity.Further research is needed to inform the safe adoption of this technology across different medical disciplines.

Fig. 2
Fig. 2 Meta-analysis on the effectiveness of VR technology for pain control compared to routine care across different medical procedures

Fig. 3
Fig.3Cumulative meta-analysis on the effectiveness of VR technology for pain control compared to routine care across different medical procedures

Table 1
Description of the VR equipment and software used in randomised trials evaluating the effectiveness of virtual reality for pain control in medical procedures

VR equipment VR software Interactive or non- interactive Akin
[132]132]VR Box 3D virtual reality glass Video images recorded on the phone of the pregnant woman by looking at the baby's face with the help of a 3D/4D probe Non-interactive Atzori 2018 [107] VR helmet (HMZ T-2 3D viewer Sony) with 45° diagonal field of view supported by laptop, latex-free earphones Interactive game (Snow World) Interactive Atzori 2022 [45] VR helmet, the Personal 3D Viewer Sony: HMZ T-2, supported by a laptop Interactive game (Snow World) Interactive Aydin and Ozyazicioglu 2019 [133] VR headset Non-interactive 3D video stimulating a submarine journey to discover things in the virtual aquarium Non-interactive Basak 2021 [134] 3-D audio-visual presentation was watched using VR glasses Submarine view video Non-interactive Boonreunya 2022 [44] VR headset Olympus GIF-HQ190.The content on the VR screen showed nature scenarios in relaxing mode Commercially available VR program and specific content about nature scenarios and sightseeing in relaxing mode Non-interactive Bosso 2023 [43] Oculus GO headset with sound played through headphones with active noise reduction Zen garden developed by Healthy Mind Non-interactive Bozdoğan Yesilot 2022 [135] VR headset (not specified) Relaxing video Non-interactive Brunn 2022 [41] Oculus Go headset with guided meditation VR App Nokia Spot 1 environment and 10-min guided Zen meditation Interactive Karaveli-Cakir 2021 [136] Android mobile phone placed in Cardboard Super Flex Goggles 'A walk on the beach' Non-interactive Canares 2021 [137] Commercially available VR headset with game Not specified Not specified Carrougher 2009 [108] VR helmet with head-position tracking and audio feedback Interactive game (Snow World) Interactive Carus 2022 [40] Oculus Quest All-in-one VR Gaming Headset (128 GB) VR system Several virtual environments, including orange sunset, green meadows, black beginning, red savannah, blue deep, blue moon, blue ocean, white winter, and red fall