1292

Pediatric Anesthesia. 2022;32:1292–1304.wileyonlinelibrary.com/journal/pan

Received: 14 December 2021

Revised: 23 July 2022

Accepted: 16 August 2022

DOI: 10.1111/pan.14546

SYSTEMATIC REVIEW

Virtual reality in pediatrics, effects on pain and anxiety:

A systematic review and meta- analysis update

Floris Q. Tas* | Cynthia A. M. van Eijk* | Lonneke M. Staals | Jeroen S. Legerstee |

Bram Dierckx

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction

in any medium, provided the original work is properly cited and is not used for commercial purposes.

*The authors contributed equally to this project as co-first authors.

Child- and Youth psychiatry, Sophia

Children's Hospital – Erasmus MC,

Rotterdam, The Netherlands

Correspondence

Floris Q. Tas, Child- and Youth psychiatry,

Sophia Children's Hospital – Erasmus MC,

Wytemaweg 80 3015 CN Rotterdam, The

Netherlands.

Email: fqtas@icloud.com

Abstract

Introduction: Medical procedures are often accompanied by pain and anxiety in pedi-

atric patients. A relatively new technique to reduce pediatric pain and anxiety is virtual

reality. Virtual reality is both applied as a distraction tool and as an exposure tool to pre-

pare patients for medical procedures. Research into the application of virtual reality in

medical settings is rapidly evolving. This meta- analysis is an update of the meta- analysis

of Eijlers et al. investigating the effectiveness of virtual reality as an intervention tool on

pain and anxiety in pediatric patients undergoing medical procedures.

Methods: We searched the databases Embase, Medline, Web of Science Core

Collection, Cochrane Central Register of Controlled Trials and PsycINFO. For each

of these databases, different search strategies were developed. The search period

from the meta- analysis from Eijlers et al., reaching until April 2018, was extended to

December 2020. Pain and anxiety outcomes during medical procedures were com-

pared for virtual reality and standard care conditions for various medical procedures.

Results: The search yielded 1824 articles, of which 13 met our inclusion criteria.

Combined with 13 articles of Eijlers' review study, this resulted in 26 articles. Virtual

reality was applied as distraction (n = 23) during medical procedures or as exposure

(n = 4) before medical procedures. The effect of virtual reality distraction was mostly

studied in patients during venous access (n = 10). The overall weighted standardized

mean difference for virtual reality distraction was −0.67 (95% CI, −0.89 to −0.45;

p < .001) on patient- reported pain (based on 21 studies) and −0.74 (95% CI, −1.00

to −0.48; p < .001) on patient- reported anxiety (based on 10 studies). The effect of

virtual reality as an exposure tool on patient- reported anxiety was significant too

(standardized mean difference = −0.58; 95% CI, −1.15 to −0.01; p < .05).

Discussion: The current updated systematic review and meta- analysis indicates that

virtual reality is a useful tool to reduce pain and anxiety in pediatric patients under-

going a range of medical procedures as it significantly decreases pain and anxiety

outcomes when compared to care as usual.

Section Editor: Joseph Peter Cravero

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TAS et al.

1 | INTRODUCTION

Medical procedures often come with pain, which can result in a lot

of distress in children. This may then lead to preprocedural anxiety,

affecting 30% to 75% of children undergoing medical procedures.

2,3

In children, higher anxiety levels before and during medical pro-

cedures are associated with more peri- and post- procedural pain,

slower and more complicated recovery and lower success of seda-

tion.

4 – 8

Furthermore, inadequate relief of pain and distress may lead

to less pain tolerance and more pain responses in the long- term.

Psychological preparation of children for surgery has shown to be

related to improved postoperative recovery.

Hence, addressing

preprocedural anxiety is likely to not only increase patient comfort,

but may also improve recovery from medical procedures and lessen

pain.

Distraction is a commonly used technique to reduce anxiety and

pain during medical procedures.

10– 13

Especially listening to music

and relaxation- guided imagery seem effective ways of reducing

anxiety and pain.

12,13

Another way to deliver distraction is by using

Virtual Reality (VR), an advanced technology that allows us to create

realistic simulations of the world around us that can be explored and

interacted with freely.

In medicine, VR has proven to be useful,

1 5 – 1 8

for example, in reducing pain and anxiety,

19,20

especially when VR

is interactive compared with passive.

More interaction comes

with more immersion, which is linked to greater pain tolerance.

As children appear more sensitive to anxiety and pain,

VR might

be more effective in reducing anxiety and pain than in adults. Thus,

it is important to study the effects of VR interventions in children

independently, as Eijlers et al. did in their review.

Next to distraction, VR offers promise as a tool for exposure.

Exposure can be used to calm patients by informing them about the

medical procedure in advance.

VR as exposure is well- established

within general psychology,

1 5 – 1 8 , 2 4

and thus, VR may be even more

suited as a tool of exposure compared with distraction.

The aim of this paper was to provide an update of the meta-

analysis of Eijlers et al., building on the studies that have been pub-

lished since April 2018. We will further investigate the effectiveness

of VR as an intervention tool on pain and anxiety in pediatric patients

undergoing medical procedures both as a way of distraction and as

a way of exposure. This update is needed, as the number of stud-

ies using VR interventions has grown exponentially. VR equipment

has become more accessible for day- to- day use in clinical settings.

Mainly because nowadays, a lot of cheap VR glasses that can be used

with mobile phones are broadly available. Based on the earlier study

of Eijlers et al., we expect VR distraction to be a useful technique

to reduce pain and anxiety in children during medical procedures.

Furthermore, due to the growing interest in the field of VR inter-

ventions, we expect an increase in the number of studies targeted

towards VR exposure. This would allow the current study to get an

insight into the effects of VR exposure on anxiety and pain in pedi-

atric medical procedures, which was not possible for Eijlers et al. due

to the limited amount of exposure studies they found.

2 | METHODS

2.1 | Selection criteria

Corresponding with Eijlers' meta- analysis,

the following inclusion

and exclusion criteria were used. Studies investigating the effect of

VR on pain and/or anxiety in patients ≤21 years of age undergoing

medical procedures were included. Since various interpretations and

definitions of VR exist, we defined VR as a technology that allows for

the creation of immersive and interactive environments and is pro-

jected in front of the user's eyes via a head- mounted display. Studies

were selected for inclusion if they had at least the following data

available: a mean/median score for pain or anxiety during the pro-

cedure, as well as a measure of dispersion, for both the intervention

and standard care groups.

Exclusion criteria consisted of the application of VR in nonso-

matic patients, no possibility of interaction between the user and

the virtual reality environment, and the absence of distinction be-

tween pediatric and adult patients. In contrast to our earlier meta-

analysis,

studies that consisted of noninteractive movies displayed

on VR glasses were excluded. This way, only studies with highest

immersion were included, due to the interactive component that

makes the entire experience more immersive. Additionally, the fol-

lowing study types were excluded: reviews, meta- analyses, single-

case studies, dissertations, conference papers, and abstract only

papers.

2.2 | Search strategy

We used the same search terms as Eijlers et al.,

namely “VR” and

“children” or “adolescents”. The databases Embase, Medline, Web of

Science Core Collection, Cochrane Central Register of Controlled

Trials and PsycINFO were used. For each of these databases, differ-

ent search strategies were developed. The initial search period from

the previous review

that reached until April 2018 was extended to

December 2020.

2.3 | Assessment of study quality

Two authors (F.Q.T. and C.A.M.v.E.) independently examined the

quality of the included studies using the Delphi List (see Table 1).

This criteria list consists of nine items which can be scored as “Yes,”

KEYWORDS

anesthesia < Audit, child < Age, pain < Complications, research

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TAS et al.

“No,” or “Don't know.” Only items valued “yes” were given a score

of 1 point.

2.4 | Synthesis of results

Mean scores and SDs for pain and anxiety during the procedure in

the VR intervention and standard care conditions were either ex-

tracted from articles or estimated using median scores and inter-

quartile ranges.

These data were analyzed with Comprehensive

Meta- analysis software version 2

by three authors (F.Q.T.,

C.A.M.v.E., and B.D.). Self- reported pain and anxiety were consid-

ered as primary outcome. Assessment instruments for pain and anxi-

ety were categorized as visual scales or questionnaires. In addition,

anxiety and pain scores from children undergoing the medical proce-

dure, as reported by caregivers and/or professionals, were included

as a secondary outcome if reported by the study. The nature of the

VR intervention was the same for all reporters. Study design was

divided in parallel or crossover design. When data on different as-

pects of pain were available, (e.g., sensory, affective, and cognitive)

the sensory component was used in our analysis.

The outcomes of pain and anxiety were analyzed separately.

Effect sizes were computed as standardized mean difference (SMD)

by calculating the mean difference on pain or anxiety outcomes be-

tween VR and standard care conditions during the procedure and

dividing the result by the pooled SD.

A generally accepted rule of

thumb is that a Cohen's d of 0.2 represents a small effect size, 0.5 a

medium effect size, and 0.8 a large effect size.

Meta- analyses for both pain and anxiety were conducted to

compare overall effect sizes of VR distraction to control conditions.

Studies using VR distraction and VR exposure therapy were ana-

lyzed separately.

A random- effects model was used, because of the expected het-

erogeneity of the included studies due to the broad range of med-

ical procedures. Sensitivity analyses were performed by removing

studies with low methodological quality (i.e., a quality score of 0– 2)

from both meta- analyses. Additionally, separate sensitivity analyses

were run for type of medical procedure and type of informant on VR

distraction effectivity. In these analyses, low- quality studies were

excluded as well.

Finally, a meta- regression analysis was performed with mean age

of the patients as predictor and a random- effects model (with meth-

ods of moments) to investigate if young children respond differently

to VR distraction interventions than older children. Heterogeneity

was assessed using the I

statistic, with values ≥75% indicating sub-

stantial heterogeneity.

Publication bias was assessed with funnel

plot asymmetry and Egger's regression tests.

3 | RESULTS

3.1 | Data extraction

In Eijlers' search, 17 articles were selected based on full text.

We in-

cluded 13 of these articles, due to the exclusion of studies without in-

teractive VR. The current search resulted in 1824 articles. Two authors

(F.T. and C.E.) screened the titles and abstracts of these articles inde-

pendently, applying the inclusion and exclusion criteria. Discrepancies

(1.8%) were discussed until consensus was reached. The authors se-

lected 74 articles based on title and abstract. The full text of these

74 articles was read by the two authors independently. Discrepancies

(18%) were discussed until consensus was reached. We excluded 61

of the 74 studies. Most of these studies were excluded because they

did not use interactive VR. Another important reason for exclusion

was a research population of only adults. The resulting 13 articles to-

gether with the 13 previous articles were used for final analysis. One

study

comprised two RCT's, which are included as separate studies.

This resulted in an inclusion of 27 studies. The outcome of our search

strategy is summarized in the flow diagram shown in Figure 1.

3.2 | Study characteristics

Main characteristics and relevant results of all included studies

can be found in Table 2. The 27 studies were organized based on

the type of medical procedure. VR was used as a way of distrac-

tion in 23, and exposure in 4 of the included studies. Types of

medical procedures using VR distraction included venous access

TABLE 1 Delphi list for quality assessment of randomized

controlled trials

Criteria Evaluation

1 Was a method of randomization

performed?

Yes (1)/No (0)/Don't

know (0)

2 Was the treatment allocation concealed? Yes (1)/No (0)/Don't

know (0)

3 Were the groups similar at baseline

regarding the most important

prognostic indicators?

Yes (1)/No (0)/Don't

know (0)

4 Were eligibility criteria specified? Yes (1)/No (0)/Don't

know (0)

5 Was the outcome assessor blinded?

Yes (1)/No (0)/Don't

know (0)

6 Was the care provider blinded?

Yes (1)/No (0)/Don't

know (0)

7 Was the patient blinded?

Yes (1)/No (0)/Don't

know (0)

8 Were point estimates and measures of

variability presented for the primary

outcome measures?

Yes (1)/No (0)/Don't

know (0)

9 Did the analysis include an intention- to-

treat analysis?

Yes (1)/No (0)/Don't

know (0)

Depending on the moment of VR use, the application of criteria 5

and 6 differed. When VR was applied before the medical procedure,

the maximum possible score was 8. When VR was applied during the

medical procedure, the maximum possible score was 6.

Criteria item 7 was not applicable in this study context.

1295

TAS et al.

(n = 10),

2 9 – 3 7

oncological care (n = 3),

3 8 – 4 0

burn care (n = 7),

4 1 – 4 7

endoscopy (n = 1),

dental care (n = 1),

or before surgery

(n = 1).

Types of medical procedures using VR exposure included

radiography (n = 1)

or before surgery (n = 3).

All studies were

conducted between 1999 and 2020. The number of participants

varied between 5 and 201, with a median of 56. Furthermore, all

studies used validated visual scales or questionnaires to meas-

ure anxiety or pain. To be able to compare the study results with

each other, we calculated effect size scores with corresponding

p- values for all studies by using available mean scores and stand-

ard deviations from the groups in each study. As effect sizes were

calculated the same way, regardless of the questionnaire or scale

used, we could compare these effect sizes directly to each other

in the software package that was used.

Most studies were randomized controlled trials (RCT) (n = 23),

of which 17 used a parallel design and six used a crossover design.

The remaining four studies were quasi- experimental, of which

three were not randomized and one used an interrupted time

series design with removed treatment. All studies compared an

intervention group (VR) to care- as- usual (CAU), although care- as-

usual was often not well defined. Studies used nonVR distraction

like playing games, while other studies did not use any form of

distraction. Parental presence was not clear in all studies, as well

as if and which pharmacological analgesia was being used. Four

RCT's added a nonVR intervention group, such as distraction by a

computer game or television.

The ages of participants in the 26 studies varied between 4 and

21 years. One study did not indicate an age range and only provided

a mean age (M = 6.54). Studies were heterogeneous regarding VR

software and hardware.

3.3 | Study quality assessment

Criteria 5 and 6 of the Delphi List, blinding of the outcome asses-

sor and caregiver, were only applicable to four studies.

51– 5 4

These

studies used VR as an exposure intervention before the medical pro-

cedure. The other studies used VR as distraction during the proce-

dure, and therefore, the outcome assessor and caregiver could not

be blinded. This resulted in a maximum possible score of 6 instead

of 8 for these studies.

As shown in Table 2, the quality scores (see Table 2) varied between

1 and 8 points, with an average score of 4.5 (SD = 1.7). Discrepancies

in study quality scores (16%) were discussed until consensus was

reached. Most studies had a high quality (n = 14) (i.e., a maximum

score, or 1 point below the maximum score). Eight studies had moder-

ate quality, and four studies poor quality (i.e., a score of 0– 2).

Elaborate explanation of the quality assessment of the studies

used by Eijlers et al.

are described in their article.

Of the new included studies, three studies performed

intention- to- treat analysis (23%). In five studies, there were no

dropouts, and therefore, no intention- to- treat analysis was per-

formed (38%). These five studies were scored as 1 on the question

if intention- to- treat analysis was performed. A method of ran-

domization was performed in 92% (n = 12) studies, 69% (n = 9) of

the studies guaranteed a concealed treatment allocation. In 85%

FIGURE 1 Flow diagram showing

different stages of study selection

Records idenﬁed through database

searching aer removal of duplicates

(n = 1824)

Screenin

Included

Eligibility

noitacifitnedI

Records screened

(n = 1824)

Records excluded

(n =1750)

Full-text arcles assessed

for eligibility

(

n =74

)

Full-text arcles excluded

(n =61)

Only adults (n = 15)

No full text arcle (n = 11)

Not interacve VR (n = 19)

Without outcome of interest (n = 3)

Not RCT (n = 5)

No HMD (n = 2)

Not English (n= 1)

No medical procedure (n = 1)

Included in prior research (n = 2)

Non-comparable outcomes (n=2)

Studies included

(

n =13

)

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TAS et al.

TABLE 2 Study characteristics and results of included studies that investigate the effect of virtual reality on pain and anxiety in pediatric patients undergoing medical procedures (n = 27)

Medical

procedure Author (Year)

Participants

Moment of VR VR equipment Treatment conditions Study design Key findings

Quality

score

n Age

Venous access Chan et al.

(2019)

123 4– 11 y During intravenous

cannulation

Google Daydream Emergency department:

VR distraction

CAU

RCT crossover VR is effective in decreasing pain

and anxiety during intravenous

cannulation

129 4– 11 y During venipuncture Outpatient laboratory:

VR distraction

CAU

VR is effective in decreasing pain and

anxiety during venipuncture

Dumoulin et al.

(2019)

35 8– 17 y During intravenous

placement

eMagin z800 HMD VR distraction

NonVR distraction

(television)

CAU

RCT parallel VR is effective in decreasing fear of pain

compared to TV and CAU, but this

effect was not found for decreasing

pain

Atzori, Hoffman

et al. (2018)

15 7– 17 y During venipuncture HMZ T- 2 VR distraction

CAU

Within subjects

(not

randomized)

During VR, patients reported significant

reductions in worst pain compared

to CAU

Aydin et al.

(2019)

120 9– 12 y During venipuncture Sanal Gözlük VR VR distraction CAU RCT parallel Pain levels reported by children were

significantly lower in the VR group

compared to control group

Piskorz et al.

(2020)

57 7– 17 y During blood draw Samsung Gear VR VR distraction (active

VR) VR distraction

(passive VR) CAU

RCT parallel Both active and passive VR groups

reported less pain and stress than

the control group. When comparing

active and passive VR, no significant

differences were found, although

there was a difference in perceived

pain and stress

Walther- Larsen

et al. (2019)

64 7– 16 y During venous cannulation

before planned

intravenous anesthesia

induction

Samsung Gear VR with

Samsung Galaxy S6

VR distraction CAU RCT parallel There were no significant differences in

pain scores between VR distraction

and standard care

Gold et al.

(2006)

20 8– 12 y During IV placement for

magnetic resonance

imaging or computed

tomography scan

5DT HMD 800 with

InterSens InertiaCube2

tracker

VR distraction CAU RCT parallel Less self- reported pain (FPS- r) in VR than

CAU during procedure

No differences in self- reported pain

measured with faces during procedure

No differences in self- reported, parent- ,

or nurse- observed pain (VAS) during

procedure

Piskorz and Czub

(2018)

38 7– 17 y During blood draw Oculus Rift DK2 VR distraction CAU Between

subjects

design (not

randomized)

Less self- reported pain (VAS) and anxiety

(VAS) than CAU during procedure

Gold and Mahrer

(2018)

143 10– 21 y During blood draw Samsung Galaxy S6 +

1. Google Pixel Merge VR

( 1 0 – 1 2 )

2. Samsung Gear VR (13– 21)

VR distraction CAU

(television)

RCT parallel Less self- reported and parent- observed

pain (VAS) and anxiety (VAS) in VR

than CAU during procedure

(Continued)

1297

TAS et al.

Medical

procedure Author (Year)

Participants

Moment of VR VR equipment Treatment conditions Study design Key findings

Quality

score

n Age

Preoperative Eijlers et al.

(2019)

201 4– 12 y Before the induction of

anesthesia

HTC Vive VR exposure CAU RCT parallel VR did not influence self- reported

anxiety (VAS) and pain (FPS- r)

pre- and postprocedural. Observed

preprocedural anxiety (m- YPAS) and

observed postprocedural pain (FLACC

& PPPM) did not differ between VR

and CAU as well

Jung et al.

(2020)

71 5 – 12 y During induction of

anesthesia before

surgery

Samsung Gear VR VR distraction CAU RCT parallel VR led to significant reduction in observed

anxiety levels (m- YPAS) compared to

standard care

Ryu et al. (2018)

69 4 – 10 y Before the induction of

anesthesia

Oculus Rift VR exposure CAU

(conventional

education)

RCT parallel Researcher- observed preoperative

anxiety (m- YPAS) was significantly

lower in the VR group compared to

the standard care group

Ryu et al. (2017)

69 4 – 10 y Before entering the

operating theater

Samsung Galaxy

S6 + Samsung Gear VR

VR exposure CAU (face-

to- face information)

RCT parallel Less researcher- observed preoperative

anxiety (m- YPAS) in VR than in CAU

Oncological

care

Schneider and

Workman

(1999)

11 10– 17 y During chemotherapy Virtual IO VR distraction CAU Interrupted

time

series with

removed

treatment

No differences in self- reported state

anxiety (state– trait anxiety inventory

for children- 1) during procedure

Gershon et al.

(2004)

59 7– 19 y During port access for

chemotherapy

Unknown VR distraction NonVR

distraction CAU

(personal computer

game)

RCT parallel Less nurse- observed pain (VAS) in VR

and nonVR distraction than CAU

during procedure No differences in

researcher- observed pain (CHEOPS),

self- reported or parent- observed pain

or anxiety (VAS) during procedure

Wolitzky et al.

(2005)

20 7– 14 y During port access for

chemotherapy

Unknown VR distraction CAU RCT parallel Less researcher- observed pain (CHEOPS)

in VR than CAU during procedure No

differences in self- reported, parent-

observed, or nurse- observed pain or

anxiety (VAS) during procedure

Burn care Das et al. (2005)

5– 16 y During burn dressing

change

IO i- glasses VR distraction CAU RCT crossover Less self- reported pain (faces scale) during

procedure in VR than CAU

Chan et al.

(2007)

8 M = 6.54 During burn dressing

change

i- glasses VR distraction CAU RCT crossover No differences in self- reported pain (FPS-

r) during and after procedure

Schmitt et al.

(2011)

54 6– 19 y During postburn physical

therapy

nVisor SX

V R - 1 2 8 0

ProView XL50 ProView SR80

VR distraction CAU RCT crossover Less self- reported cognitive, affective, and

sensory pain (GRS) in VR than CAU

during procedure

Kipping et al.

(2012)

41 11– 17 y During burn dressing

change

eMagin, Z800 3DVisor VR distraction CAU

(television, stories, or

music)

RCT parallel Less observed pain (FLACC) during

procedure in VR than CAU. No

differences in self- reported or parent-

observed pain (VAS) during procedure.

TABLE 2 (Continued)

1298

TAS et al.

Medical

procedure Author (Year)

Participants

Moment of VR VR equipment Treatment conditions Study design Key findings

Quality

score

n Age

Jeffs et al.

(2014)

28 10– 17 y During burn treatment Kaiser Optical SR80a on

tripod

VR distraction NonVR

distraction

(television)

CAU

RCT parallel Less self- reported pain (APPT- WRGS)

during procedure in VR than in nonVR

distraction but not less than CAU

Hua et al.

(2015)

56 4– 16 y During burn dressing

change

eMagin Z800 3DVisor VR distraction CAU

(toys, television,

books)

RCT parallel Less self- reported pain (faces), during, less

parent- observed pain (VAS) before,

during and after, and less researcher-

observed pain (FLACC) during and

after procedure in VR than CAU

Hoffman et al.

(2019)

96 6– 17 y During burn treatment MX90 VR Goggle VR distraction CAU RCT crossover VR distraction leads to less self- reported

pain (GRS) in children during burn

wound care

Endoscopy Liu et al. (2020)

53 7– 17 y During nasal endoscopy Oculus Go VR distraction CAU RCT parallel Self- reported pain (FACES) and self-

reported anxiety (SUDS) levels, as well

as observed (caregiver) anxiety levels

in the VR group, were significantly

lower

Dental care Atzori, Lauro

et al. (2018)

5 7– 17 y During dental filling or

tooth extraction

Oculus Rift VR distraction CAU Within subjects

crossover

design (not

randomized)

Self- reported (worst) pain (GRS)

were significantly lower in the VR

intervention group

Radiography Han et al. (2019)

99 4– 8 y Before chest radiography Oculus Go VR exposure CAU RCT parallel Observed anxiety levels (OSBD)

were significantly lower in the VR

intervention group

Note: Manufacturer information for the equipment noted in the table: i- glasses 920HR (Ilixco, Inc, Menlo Park, CA); i- glasses (i- O Display Systems, LLC, Sacramento, CA); nVisor SX (NVIS, Inc, Reston, VA);

VR- 1280 (Virtual Research Systems, Inc, Aptos, CA); ProView XL50 (Kaiser Electro- Optics, Inc, Carlsbad, CA); ProView SR80 (Kaiser Electro- Optics, Inc, Carlsbad, CA); eMagin Z800 3DVisor (eMagin

Corporation, Hopewell Junction, NY); Kaiser Optical SR80a (on tripod; Kaiser Optical Systems, Inc, Ann Arbor, MI); 5DT HMD 800 (5DT, Inc, Irvine, CA); Oculus Rift DK2 (Facebook Technologies, LLC,

Menlo Park, CA); Samsung Galaxy S5 (Samsung Electronics Co, Ltd, Suwon, South Korea); Samsung Gear VR (Facebook Technologies, LLC, Menlo Park, CA); Google Pixel (HTC Corporation, New Taipei

City, Taiwan); Merge VR (Merge Labs, Inc, San Antonio, TX); Samsung Galaxy S6 (Samsung Electronics Co, Ltd, Suwon, South Korea).

Abbreviations: APPT- WRGS, adolescent pediatric pain tool - word graphic rating scale; CAU, care as usual; CHEOPS, Children's Hospital of Eastern Ontario pain scale; FLACC, face, legs, activity, cry,

consolability; FPS- r, faces pain scale- revised; GRS, graphic rating scale; IV, intravenous; M, mean; m- YPAS, modified Yale preoperative anxiety scale; OSBD, observational scale of behavioral distress; RCT,

randomized controlled trial; VAS, visual analog scale; VR, virtual reality.

Maximum possible score for four studies is 8.

51– 5 4

Maximum possible score for all other studies is 6.

Seven subjects were unique and could participate more than once.

TABLE 2 (Continued)

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TAS et al.

(n = 11) of the studies, groups were similar at baseline regarding

the most important prognostic indicators. For the remaining two

studies, the article did not provide enough information about

baseline characteristics to determine whether the groups were

similar at baseline. For only one study (8%), inclusion and exclusion

criteria were not described precisely enough.

3.4 | Virtual reality distraction and

pain management

Figure 2 shows the effect sizes of VR distraction for patient-

reported pain (21 studies). Negative effect sizes represent

less pain in the VR distraction group. Across all studies, using a

random- effects model, the weighted effect size of VR distrac-

tion on pediatric self- reported pain during a medical procedure

was statistically significant (SMD = −0.67; 95% CI, −0.89 to

−0.446; p < .001). A SMD of 0.67 represents a medium effect size.

Heterogeneity of study effects was considerable (I

= 67.9%). A

sensitivity analysis was performed by excluding studies with low

methodological quality. This resulted in exclusion of three stud-

ies.

35,42,55

This analysis also indicated a statistically significant ef-

fect with a medium effect size (SMD = −0.60; 95% CI, −0.82 to

−0.37; p < .001). Heterogeneity did not substantially differ com-

pared with the main analysis (I

= 68.4%). In addition, the current

dataset and the adapted (i.e., studies that were removed in the

current study, but included in the original study) dataset from

Eijlers et al.

was analyzed separately. This analysis indicated a

significant effect for both the current dataset (SMD = −0.78; 95%

CI, −1.12 to −0.44; p < .001), as well as the adapted dataset from

the earlier review (SMD = −0.55; 95% CI, −0.84 to −0.28; p < .001),

suggesting a greater effect size in the current dataset.

Sensitivity analyses were carried out on pain for each type of

medical procedure when data from more than 1 study were available.

Statistically significant effects were found for burn care (SMD = −0.85;

95% CI, −1.15 to −0.56; p < .001; I

= 39.2%) and venous access

(SMD = −0.521; 95% CI, −0.84 to −0.20; p < .01; I

= 75.7%).

A random- effects model (with methods of moments) was used

for the meta- regression analysis with age as a predictor. The results

did not suggest that VR distraction interventions for pain reduction

were more efficacious for younger than for older children (p = .25).

Finally, analyses were carried out for caregivers and profes-

sionals as observers of pediatric pain. Statistically significant re-

sults were found based on both types of informants (caregivers:

SMD = −0.47; 95% CI −0.72 to −0.22; p < .001; I

= 0.00%, profes-

sionals: SMD = −0.93; 95% CI, −1.31 to −4.78; p < .001).

3.5 | Virtual reality distraction and

anxiety management

Figure 3 shows the effect sizes of VR distraction for patient- reported

anxiety (10 studies). Negative effect sizes represent less anxiety in

the VR distraction group. Using the random- effects model, a statis-

tically significant effect with a medium effect size was found for VR

distraction on patient- reported anxiety (SMD = −0.74; 95% CI, −1.00

to −0.48; p < .001). Heterogeneity of the study effects was moderate

= 59.3%). A sensitivity analysis was performed by excluding studies

FIGURE 2 Random- effects meta- analysis for the effect of VR on patient- reported pain during a medical procedure compared with CAU

1300

TAS et al.

with low methodological quality. This resulted in exclusion of two

studies.

38,55

This analysis also indicated a statistically significant effect

of VR distraction on self- reported anxiety, with a medium effect size

(SMD = −0.72; 95% CI, −1.00 to −0.43; p < .001). Heterogeneity did

not substantially differ compared with the main analysis (I

= 62.7%).

Sensitivity analyses were carried out on patient- reported anxiety

for each type of medical procedure, when data from >1 study were

available. Statistically significant effects were found for venous ac-

cess (SMD = −0.63; 95% CI, −0.98 to −0.28; p < .001; I

= 68.2%)

and oncological procedures (SMD = −0.53; 95% CI, −0.96 to −0.101;

p < .05, I

= 0.0%).

A random- effects model (with methods of moments) was used for

the meta- regression analysis with age as a predictor. The results did

not suggest that VR interventions for patient- reported anxiety reduc-

tion were more efficacious for younger than for older children (p = .18).

Analyses were also carried out for caregivers as observers

of pediatric anxiety. Statistically significant results were found

(SMD = −0.59; 95% CI −1.02 to −0.15; p < .01; I

= 0.00%).

Finally, the current dataset and the adapted dataset from Eijlers

et al.

were analyzed separately. This analysis indicated a significant

effect for both the current dataset (SMD = −0.90; 95% CI −1.26 to

−0.54; p < .001) as well as the adapted dataset from the earlier re-

view (SMD = −0.45; 95% CI −0.69 to −0.20; p < .001), suggesting a

greater effect size in the current dataset.

3.6 | VR exposure

Figure 4 shows the effect sizes of VR exposure for patient-

reported anxiety. Using the random- effects model, a statistically

significant effect size was found for VR exposure on anxiety

(SMD = −0.58; 95% CI, −1.15 to −0.01; p < .05). A SMD of 0.58

represents a medium effect size. Heterogeneity of the study ef-

fects was high (I

= 87.1%).

Only one VR exposure study investigated the outcome “pain.”

Therefore, we could not perform meta- regression analysis on this

outcome.

3.7 | Publication bias and heterogeneity

Egger regression asymmetry tests did not indicate the presence of a

statistically significant publication bias for pain (p = .300) or anxiety

(p = .555) in the VR distraction studies. We did not perform Egger

regression asymmetry analysis on the exposure studies, because of

the small number of studies.

4 | DISCUSSION

As the scientific field of VR research to diminish pain and anxiety

during pediatric medical procedures is rapidly evolving, the current

paper provides an update of the first systematic review and meta-

analysis from Eijlers et al.

The current meta- analysis showed that

VR is a useful distraction tool for significantly reducing self- reported

pain and anxiety, as well as a useful exposure tool during various

medical procedures.

Meta- regression analyses showed that VR interventions were

not more efficacious for younger than for older children, contradic-

tory to the findings by Eijlers et al.

However, as Eijlers et al. already

FIGURE 3 Random- effects meta- analysis for the effect of VR on patient- reported anxiety during a medical procedure compared with CAU

1301

TAS et al.

noted, these results might not represent true relations due to eco-

logical fallacy.

Regarding VR as a distraction technique, VR was found to sig-

nificantly reduce pain and anxiety more compared with CAU. It

should however be noted, that comparing VR to other distraction

techniques is difficult due to CAU not always being (clearly) defined.

Compared to Eijlers' weighted effect sizes for anxiety (SMD = 1.32)

and pain (SMD = 1.30), our weighted effect sizes are lower for both

anxiety (SMD = −0.74) and pain (SMD = −0.67). This could be the re-

sult of the additional studies the current meta- analysis included, but

this could also be due to two studies that the current meta- analysis

excluded that were both included in the original meta- analysis. Our

effect sizes are closer to the weighted effect size of 0.61 from an-

other meta- analysis that looked at other distraction techniques like

games and music

and −0.64 found by a more recent meta- analysis

into the effect of distraction on self- reported pain.

Anxiety levels reported by professionals show a larger effect

size than patient- reported anxiety and anxiety reported by parents

resulted in a smaller effect size than patient- reported anxiety. A

possible explanation for this finding could be the difficulty of esti-

mating children's emotions while they are wearing VR glasses. The

lack of visibility of facial expression could make it harder to correctly

score patients pain or anxiety, and therefore, not correspond with

patients' self- reported pain or anxiety. In future research, this prob-

lem could be addressed by using different measurements to score

patients pain or anxiety. Possible parameters could be heart rate,

temperature or EDA (electrodermal activity). Next to that, profes-

sionals reporting the patients' anxiety see both children with and

without VR intervention by which they could subconsciously be

influenced in their observations. Interestingly, the current dataset

without the data from Eijlers et al.

showed a greater effect size

compared with the data from Eijlers et al.

This could be the result

of huge advancements within VR which has made VR more acces-

sible to all kinds of users. Simulations are more lifelike, and VR can

be used with simple, cheap glasses nowadays. Furthermore, quality

scores of studies that were published after the review from Eijlers

et al.

are higher (see Table 2), suggesting that the quality of studies

has been improved much in the recent years.

Regarding VR as an exposure technique, analysis of four stud-

ies showed VR to significantly reduce anxiety more compared with

CAU, although it should be noted that the number of studies investi-

gating exposure is rather small. The effect of VR exposure on pain in

children during procedures could not be analyzed, as there were too

few studies to include in analysis. Hence, more studies investigating

exposure are needed.

As pointed out by Eijlers et al., immersion is an important area of

focus.

Regarding immersion, heterogeneity of studies in the cur-

rent review was lower than in Eijlers et al., since we were stricter in

excluding studies without active VR. By doing this, we ensured that

only studies were included where immersion was highest, due to the

interactive component that makes the entire experience more im-

mersive. As shown by Gutierrez- Maldonado et al., interactive VR is

more effective in reducing pain than passive VR.

Nevertheless, im-

mersion is a complex construct and the amount of immersion might

vary greatly between studies, as some studies allowed full interac-

tion, while other studies only allowed partial interaction like moving

the head. Of course, not all medical procedures allow for an inter-

active component, as you cannot always move your body. Hence,

future research could focus more on the exact role of immersion and

how immersion can be improved— perhaps even when movement is

not possible.

4.1 | Implications

VR distraction has a statistically significant effect on pediatric pain

and anxiety during medical procedures. As it is easy- to- use in clini-

cal practice, provides endless opportunities and can be personal-

ized in almost every way to comfort the patient as much as possible,

VR can be used as a way of distraction. In addition, VR exposure

has a significant effect on pediatric anxiety during medical proce-

dures, and thus, it seems that exposure also is a useful technique to

FIGURE 4 Random- effects meta- analysis for the effect of VR exposure on patient- reported anxiety during a medical procedure

compared with CAU

1302

TAS et al.

reduce anxiety. This is an important finding, because preprocedural

anxiety occurs frequently

and is linked to postprocedural pain.

4,6

Furthermore, patients are often unable to move during medical pro-

cedures, and cannot use electronic devices during MRI scanning,

which highlights the importance of a VR intervention that can be ap-

plied before the procedure (i.e., exposure procedures) and perhaps

even be used at home.

4.2 | Limitations

The current review has several limitations that should be considered

when interpreting the results. First, the number of studies using VR

as a way of exposure are still low, and thus, more research into ex-

posure is needed before accurate conclusions can be drawn from

the results. Second, quality assessment scores of the included stud-

ies varied. While randomization and concealed treatment allocation

were applied in most studies, intention- to- treat analyses were miss-

ing in most studies. Additionally, barely any of the studies included

possible moderating factors of VR effectivity. Third, heterogeneity

was mostly between 60% and 70%, which can be seen as substan-

tial heterogeneity. Excluding low quality studies did not appear to

be responsible for these values. The difference between medical

procedures seems to be more important. Heterogeneity values for

medical procedures that are more specific for one type of care, as

is the case with oncological care and burn care, were low. On the

contrary, more general procedures that can differ a lot in circum-

stances, such as venous access, showed substantial heterogeneity.

Due to this difference in effect sizes, generalizing the effects of VR

should be done carefully, because what appears to work in one pro-

cedure, might have different results in another procedure. Of special

interest is the high heterogeneity that was found for VR exposure

studies on anxiety (I

= 87.1%). Three of the four included exposure

studies used VR as a preoperative exposure technique. High hetero-

geneity is understandable as “preoperative” does not imply which

type of surgery a patient has to undergo. For example, VR exposure

could have less impact in case of major surgeries (or the other way

around). Differences in the “care as usual” preoperative preparation

could also influence the effect of VR interventions. In case of a very

thorough standard preparation, the effect of VR could be limited.

Fourth, VR software and hardware differed between the studies and

this might influence the amount of immersion and effectivity as well.

Some studies used advanced, expensive headsets like Oculus Rift,

while others used simple, inexpensive headsets. On the contrary, as

Eijlers et al.

pointed out, it is possible that VR hardware only plays

a small role.

5 | CONCLUSIONS

The current systematic review and meta- analysis indicates that VR

may be a useful tool to reduce pain and anxiety in pediatric patients

undergoing a range of medical procedures, especially when used in a

way of distraction. This was also found when caregivers and/or pro-

fessionals reported pain and anxiety levels of the child. Regarding

exposure, results from a small number of studies suggest that VR

may also be useful as a way of exposure. Thus far, VR seems to be

an innovative, easy- to- use, and accessible tool to reduce anxiety and

pain in children before and during medical procedures, but further

research into using VR as an exposure tool is still needed.

AUTHOR CONTRIBUTIONS

Floris Q. Tas helped perform the literature searches, study selection,

and statistical analyses, as well as extracting the data and writing

the final article. Cynthia A.M. van Eijk helped perform the literature

searches, study selection, and statistical analyses, as well as extract-

ing the data and writing the final article. Lonneke M. Staals helped

provide important intellectual content and approve the final version

of the manuscript. Jeroen S. Legerstee helped interpret the results

of statistical analyses, provide important intellectual content, and

approve the final version of the manuscript. Bram Diercxk helped

extract the data, perform statistical analyses, provide important in-

tellectual content, and approve the final version of the manuscript.

ACKNOWLEDGMENTS

We wish to thank biomedical information specialist Wichor M.

Bramer, MSc, of the Medical Library, Erasmus Medical Center,

University Medical Center Rotterdam, Rotterdam, the Netherlands,

for developing and updating the search strategies.

CONFLICT OF INTEREST

The authors have declared no conflicts of interest for this article.

DATA AVAIL ABILIT Y STATEMENT

There is no data availability statement.

ORCID

Floris Q. Tas https://orcid.org/0000-0003-1850-9051

Lonneke M. Staals https://orcid.org/0000-0001-7867-971X

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