Effects of an Immersive Virtual Reality Intervention on Pain and Anxiety Among Pediatric Patients Undergoing Venipuncture

Key Points Question Compared with standard care, do distraction and procedural information provided through immersive virtual reality (IVR) improve pain among pediatric patients undergoing venipuncture? Findings In this randomized clinical trial of 149 pediatric patients undergoing venipuncture, an IVR intervention significantly improved patient-reported pain. Meaning These findings suggest that IVR was more effective than standard care in improving pain among pediatric patients undergoing venipuncture.


Introduction
2][3] Pediatric patients undergoing this procedure, particularly those aged 4 to 12 years, often display high levels of pain and anxiety. 4Evidence has also shown that procedural anxiety is positively associated with increased self-reported pain. 5However, the effect of pharmacological and nonpharmacological management of procedural pain and anxiety remains understudied. 6,7][8][9][10][11] Therefore, clinical guidelines emphasize the importance of managing procedural pain and anxiety in pediatric patients. 124][15] Previous studies have used various types of distractors, such as watching cartoons, playing with toys, or soothing by adults, to distract pediatric patients during procedures. 13 particular, age-appropriate distractors appear to enhance the effectiveness of pain management. 15,16Two studies 17,18 found that distraction combined with procedural information yields better results.Nevertheless, offering age-appropriate distraction and procedural information at the same time is difficult.Furthermore, previous distractors have failed to completely pull a patient's attention away from the needle, which is the most anxiety-provoking scene during such procedures. 6,7Therefore, identifying a distractor that can totally block children's attention to pain and anxiety stimuli is of utmost importance.
Emerging evidence suggests that immersive virtual reality (IVR) interventions can help completely distract patients during medical procedures. 19,20IVR provides a form of humancomputer interaction in which users engage in a computer-generated 3-dimensional virtual world through a head-mounted display. 19IVR interventions can be used anytime and anywhere without additional manpower.VR scenarios can also be customized to provide users with health information.
2][23][24] Most importantly, no studies have simultaneously adopted IVR to provide procedural information and complete distraction for pediatric patients undergoing venipuncture.Guided by Melzack and Wall's gatecontrol theory 25 and Lazarus and Folkman's stress and coping theory, 26 we have developed an IVR intervention to address these literature gaps.The theoretical framework has been described previously. 27In brief, we posit that IVR offers visual and auditory stimuli that can effectively close the patients' pain gate 25,28 while the procedural information can enhance patients' sense of control, thereby reducing their anxiety. 29e present study aimed to examine the effects of the IVR intervention on pain, anxiety, stress, and length of procedure among pediatric patients undergoing venipuncture.Health care professional satisfaction with the procedures was also examined.

JAMA Network Open | Pediatrics
Effects of Immersive Virtual Reality on Pain in Pediatric Patients Undergoing Venipuncture

Study Design
This study was a 2-group randomized clinical trial.The detailed protocol is reported elsewhere. 27hical approval was obtained from the Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee.The protocol is provided in Supplement 1.This report follows the Consolidated Standards of Reporting Trials (CONSORT) reporting guideline.Written informed consent was obtained from parents of participating children.

Setting and Participants
This study was conducted in the pediatric unit of a regional public hospital in Hong Kong.For patients younger than 12 years, venipuncture was performed by a medical intern or medical officer with the assistance of a nurse or patient-care assistant in a treatment room.We included pediatric patients who (1) were aged between 4 and 12 years, (2) planned to undergo venipuncture, and (3) were able to communicate in Chinese and follow instructions.Exclusion criteria were as follows: (1) identified cognitive or learning problems or sensory impairments to pain, (2) identified contact precautions, and (3) history of seizures or motion sickness.Health care professionals participating in the procedure (eg, medical interns and officers, nurses, and patient-care assistants) were also invited to rate their satisfaction with the venipuncture procedure.
The sample size calculation was based on the effect estimated from a previous VR study using the Faces Pain Scale-Revised (FPR-S) as a primary outcome measure. 21By using the power analysis software GPower version 3.4, it was estimated that a sample size of 85 participants per group would enable a 2-group randomized clinical trial to detect a between-group difference of 0.8 points on the FPS-R scale, with a pooled standard deviation of 1.84 and 80% power at 5% level of significance.
Accounting for an attrition rate of up to 15%, we aimed to recruit 200 pediatric patients, with 100 patients in each group.

Randomization and Masking
Eligible participants were randomly assigned to the intervention or control groups by using stratified permuted block randomization (block size = 10) in a 1:1 ratio.Randomization was stratified by age group (4-7 and 8-12 years) considering the potential difference in pain-stimulus sensitivity in these 2 developmental stages. 30,31A random sequence list of group identifiers was generated by an independent statistician using computer-generated random codes for each age group.These identifiers were placed in a sealed opaque envelope with a serial number.Pediatric patients were allocated based on their age, order of enrollment in the trial, and group identifier contained in the corresponding numbered envelope.Research assistants (RAs), ward staff, patients, and parents were blinded to the group assignment until consent and baseline assessment data were obtained.
However, owing to the nature of the intervention, blinding the participants, RAs, and health care professionals was difficult.

Standard Care and IVR
Patients in the control group received standard care, including explanation of the venipuncture procedure and comforting wordings.Patients in the intervention group received the IVR intervention in addition to standard care.The IVR intervention aimed to instill a sense of control by offering patients procedural information and distracting them from an anxiety-provoking venipuncture scene. 8,29,32The details of the intervention have been outlined in the published protocol. 27Briefly, the IVR intervention offered 2 age-appropriate VR scenarios through a disposable headset that can be fitted into smartphones.Both scenarios involved a self-designed cartoon character DD who was going to undergo venipuncture.Given that visual stimuli can effectively distract children, 29,33 the scenario presented screen zooming at various paces, with the cartoon character DD enacting various body movements. 33 stimulation to the patient.For the scenario presented to patients aged 4 to 7 years, procedural information on why DD required venipuncture was presented using simple words and sentences in a child-centered manner.For patients aged 8 to 12 years, more detailed information-such as why the procedure was performed, what to expect, and how the procedure would feel-was explained, followed by an interactive game in which the user played the role of the doctor and prepared the equipment required for the venipuncture procedure.The eFigure in Supplement 2 includes screenshots of the scenarios.
The RA first provided instruction to patients about how to use the VR equipment and then placed the head-mounted display on the patient's head, making adjustments to ensure a comfortable and secure fit.Patients were then allowed to watch the age-appropriate scenarios starting 5 minutes before and until the completion of the venipuncture procedure. 21,22They were also told that if they experienced any discomfort, such as motion sickness and eye discomfort, the intervention would be discontinued.Meanwhile, the medical officers or interns were invited to synchronize the steps of the venipuncture procedure with the script of VR scenario, so that what was going on in the VR scenario actually happened in reality.

Measurements Pain Level
The FPS-R was used to assess the pain level of the participants.It is a 0-to-10 scale comprising 6 horizontally arranged cartoon faces with expressions of 0, indicating no pain, to 10, indicating very painful. 34This scale has been shown to be reliable and valid for evaluating children's self-reported pain. 10,21

Anxiety
The anxiety level of children aged 4 to 7 years was assessed by the visual analogue scale (VAS) for anxiety.It is a 10-cm horizontal line marked with the words "not worried" (low score) at one end and "very worried" (high score) at the other, with different facial expressions drawn along the line.This scale has been shown to be reliable and valid for measuring the subjective feelings of anxiety in children. 35,36e anxiety level of children aged 8 to 12 years was assessed by the short form of the Chinese version of the State Anxiety Scale for Children (CSAS-C). 37,38It is a 3-point Likert scale with scores ranging from 10 to 30.Higher scores indicate greater anxiety levels. 37,38It has been previously used to assess the anxiety level of Chinese children undergoing medical procedures. 36The Cronbach α of this scale in this current study was 0.89.

Additional Measures
Patient heart rate was measured with an automatic heart-rate monitoring machine to assess patients' physiological responses to pain and anxiety. 22,23Children's stress level was assessed by salivary cortisol assay. 39The trained RA collected patients' saliva samples and tested them according to the manufacturer's instructions.The length of procedure, from disinfection to band aid applied to the venipuncture site, was measured using a standard stopwatch.Health care professional satisfaction with the procedure was examined by the Staff Satisfaction Scale. 40It comprises 8 items, each rated by a 5-point scale ranging from 1 (strongly disagree) to 5 (strongly agree).It has been translated and used in a previous study. 38The Cronbach α of this scale in the current study was 0.88.

Data Collection Procedure
A pediatric nurse in the unit screened patients' eligibility.Those who met the inclusion criteria for recruitment and their accompanying parents were referred to the RA, who explained the study, obtained written informed consent from consenting participants, and collected baseline data.

Statistical Analysis
SPSS statistical software version 24 (IBM Corp) was used for data analysis.Continuous and categorical variables were summarized by means (SD) or frequencies (percentages), as appropriate.
The intention-to-treat principle was adopted for outcome comparisons between the 2 groups.The independent t test (or Mann-Whitney test for highly skewed data) was used as appropriate to assess the outcomes (such as length of procedure and staff satisfaction level) between the 2 groups.The generalized estimating equation (GEE) model was used to compare each of the outcome measures across the time points between the 2 groups.Hedges g effect size was used to estimate the effects of IVR intervention on the outcome variables.All statistical analyses were 2-sided, and the level of significance was set at P < .05.

Results
A total of 155 eligible pediatric patients and their parents were approached; of these, 149 patients

JAMA Network Open | Pediatrics
Effects of Immersive Virtual Reality on Pain in Pediatric Patients Undergoing Venipuncture

Pain Level
Table 2 summarizes the primary and secondary outcomes across the study points and the effect sizes.
According to the GEE results, the IVR group showed a significantly greater reduction in anxiety scores at T2 vs T0 compared with the control group (β = −0.41;95% CI, −0.76 to −0.05; P = .03)(Table 3).

Heart Rate and Stress
The intervention group showed smaller increase in heart rate at T1 and T2 with respect to T0 and a greater reduction in salivary cortisol at T3 with respect to T0 compared with the control group.
However, statistical significance was not reached (Table 3).

Staff Satisfaction
Independent t test revealed that staff satisfaction score in the intervention group (mean [SD] score, 34.5 [4.5]) was significantly higher than that in the control group (mean [SD] score, 32.9 [4.0); P = .03).Subgroup analysis suggested similar results among in the older age group only (Table 4).

Discussion
This randomized clinical trial found that an IVR intervention incorporating distraction and procedural information, rather than standard care alone, substantially reduced self-reported pain, selfreported anxiety, and length of procedure among pediatric patients undergoing venipuncture.
Additionally, a statistically significantly higher level of staff satisfaction was noted in the IVR group than in the control group.Although the IVR group showed a smaller increase in heart rate and a greater reduction in salivary cortisol than the control group after the procedure, statistical significance was not observed.
This trial extended previous studies and, to our knowledge, was the first randomized clinical trial to distract pediatric patients while simultaneously offering procedural information during venipuncture using IVR.Overall results showed that the IVR intervention effectively mitigated pain and anxiety in children undergoing venipuncture, which is concordant with previous studies that provided distraction using VR. 41  Abbreviations: FPS-R, Faces Pain Scale-Revised; NA, not applicable; T0, 10 minutes before venipuncture; T1, during venipuncture; T2, after venipuncture; T3, 30 minutes after venipuncture.
a Hedges g effect size, which corresponds to the standardized mean difference of the mean changes at the underlying time with respect to T0 between the intervention and control groups.
Previous studies have used IVR across a broad age range and various needle-related procedures, of which only a few studies have tailored contents according to medical procedures and the developmental level of the children. 13,14,42Nevertheless, the limited evidence on VR equivocally suggests that tailored content is more effective than ready-made content in mitigating pain and distress. 17,32,43As such, the positive results of our intervention may be attributed to the tailored and synchronized VR scenarios.Specifically, our VR scenarios not only provided age-appropriate procedural information, but the contents were synchronized with real-time procedures so that children could gain a sense of control and be prepared when the needle was inserted.
This trial used an objective measure of salivary cortisol to assess children's stress levels before and 30 minutes after venipuncture.However, we did not find significant between-group differences in the changes of salivary cortisol.Similarly, a previous study comparing the effects of pharmacological (jet lidocaine) and nonpharmacological interventions (the Buzzy, bubble-blowing, and inhalation aromatherapy) in children undergoing phlebotomy found no between-group difference in salivary cortisol levels collected 25 minutes after the procedures. 44Given the short duration of the venipuncture, it was possible that the cortisol level was only raised for a short time and had already returned to normal 30 minutes after venipuncture. 45Future studies using other objective measures to assess children's stress level are warranted.
The current study found that IVR intervention shortened the length of procedures and improved staff satisfaction with the procedures.A probable explanation is that patients were fully engaged in IVR and demonstrated higher procedural compliance and cooperativeness, which led to

Implications
Given that venipuncture is one of the most frequently performed and distressing procedures in hospitalized pediatric patients, the results generated in this study may contribute tangible improvements to patient care and outcomes.Our encouraging results imply that an IVR intervention can be adopted as a high-quality clinical intervention for simultaneously offering distraction and procedural information to mitigate pain and anxiety in children undergoing venipuncture.In contrast to previously used approaches (eg, playing with toys and soothing by adults) that are time and resource-intensive, 13 IVR can be used virtually by numerous patients simultaneously at any time and place.Compared with computer-based VR, which is bulky, the use of smartphone-based VR in our study is more practical for clinical implementation. 47Furthermore, the principles of this intervention can be generalized and extended to other needle-related or pain-and anxiety-inducing medical procedures beyond venipuncture.
As IVR devices are becoming increasingly affordable, health care professionals may benefit from integrating IVR interventions into routine practices.However, prior to clinical implementation, measures need to be considered to ensure that strict infection control is maintained in hospital settings, especially during the COVID-19 pandemic, and that staff are trained to supervise interventions and operate IVR equipment.
Pastel-tone colors were used to reduce eye strain while providing visual JAMA Network Open | Pediatrics Effects of Immersive Virtual Reality on Pain in Pediatric Patients Undergoing Venipuncture JAMA Network Open.2023;6(2):e230001.doi:10.1001/jamanetworkopen.2023.0001(Reprinted) February 16, 2023 3/13 Downloaded From: https://jamanetwork.com/ on 09/23/2023 cortisol, FPS-R score, VAS for anxiety score, CSAS-C score, and heart rate were collected.At T1, heart rate data were collected.At T2, FPS-R score, VAS for anxiety score, CSAS-C score, and heart rate were obtained from patients as well as the length of the procedure and health care professional satisfaction.At T3, saliva cortisol, FPS-R score, VAS for anxiety score, CSAS-C score, and heart rate were obtained from patients again.

Table 1 .
Sociodemographic and Clinical Characteristics of the ParticipantsIndependent t test showed that the length of procedure in the IVR group (mean [SD] duration, 4.43[3.47]minutes)wassignificantlyshorterthanthat in the control group (mean [SD] duration, 6.56[7.39]minutes;P=.03).Subgroup analysis by age group suggests similar results, but statistical significance was not reached (Table4).

Table 2 .
Outcome Measures Across Time Between the Control and Intervention Group Among All Children

Table 3 .
6,11,46ized Estimating Equation Models for the Comparison of Each Repeated Outcome Across Time Between the Control and Intervention Groups aEffects of Immersive Virtual Reality on Pain in Pediatric Patients Undergoing Venipuncture reduced procedure duration and increased health care professional satisfaction.Similar findings were noted in previous studies showing that VR decreased the need for restraining pediatric patients during needle-related procedures and increased health care professional satisfaction.6,11,46 a Only the model estimates of regression coefficients (β) of the dummy variables for the group (group 0, control [reference]; group 1, intervention), time points (T1, T2, and T3, with the measurement taken 10 minutes before venipuncture as reference), and time points and group interaction terms (group × T1, group × T2, and group × T3) are shown for the generalized estimating equation models.bFPS-Rpainscore was square root transformed before being entered into the GEE analysis.JAMA Network Open | PediatricsJAMA Network Open.2023;6(2):e230001.doi:10.1001/jamanetworkopen.2023.0001(Reprinted) February 16, 2023 8/13 Downloaded From: https://jamanetwork.com/ on 09/23/2023

Table 4 .
Outcome Measures Across Time Between the Control and Intervention Group Stratified by Age Group Effects of Immersive Virtual Reality on Pain in Pediatric Patients Undergoing Venipuncture a Hedges g effect size, which corresponds to the standardized mean difference between the intervention and control group, or the mean changes at the underlying time point with respect to T0 between the 2 groups.JAMA Network Open | PediatricsJAMA Network Open.2023;6(2):e230001.doi:10.1001/jamanetworkopen.2023.0001(Reprinted) February 16, 2023 9/13 Downloaded From: https://jamanetwork.com/ on 09/23/2023