Effects of immersive virtual reality intervention on pain and anxiety among pediatric patients undergoing venipuncture: a study protocol for a randomized controlled trial

Various studies have suggested non-pharmacological interventions, such as distraction, procedural information provision, hypnosis, and cognitive behavioral therapy, to manage the pain and anxiety experienced by pediatric patients undergoing needle-related procedures [14‐16]. However, distraction and information provision are more feasible to implement than previously suggested interventions because many clinicians are not trained in hypnosis or cognitive behavioral therapy.

Distraction is the most effective non-pharmacological intervention for mitigating the pain and anxiety experienced by pediatric patient undergoing needle-related procedures [14‐16], particularly in children aged < 12 years [16]. A review of 26 studies involving 2548 children aged 2–19 years showed that needle-related procedures have been performed with various distractors, such as listening to music, watching cartoons, playing with toys, and mother-directed distractions, such as soothing [14]. The review suggested that distractions without adult involvement (supportive role articulated for the adult within the intervention) and child choice effectively reduce the intensity of self-reported distress [14]. Two recent studies further confirmed that distraction intervention integrated with procedural information produces significant outcomes [17, 18]. However, simultaneously providing age-appropriate distraction and procedural information may be difficult and may likely increase the workload of hospital staff. Most importantly, previously employed distractors (e.g. music, cartoon, or toys) failed to provide complete distraction because children could still see the needles, which is the most distress-evoking experience in needle-related procedures [5, 6]. Thus, an intervention that can provide age-appropriate procedural information and completely distract the attention of children from painful stimuli should be identified.

Immersive virtual reality (IVR) may help overcome the above obstacles. It provides a means of human/computer interaction, wherein a human becomes an active participant in a virtual environment created through a head-mounted display [19]. The user is immersed and actively participates in the virtual environment as it changes in real time with the user’s movements [20]. Moreover, it can be used at any time and place in clinical settings without requiring extra manpower. IVR modules can also be tailored to provide health information to the user. The cost of IVR equipment has also become increasingly affordable. Distraction-based IVR intervention has already been implemented in the Lucile Packard Children’s Hospital at Stanford in the United States [21].

A large body of evidence supports the efficacy of IVR in reducing pain, anxiety, and stress among pediatric patients undergoing burn care or cancer treatments [19, 20]. With regard to needle-related procedures, a randomized control trial (RCT) was conducted with 20 pediatric patients aged 8–12 years and who required peripheral intravenous access [11]. The intervention group received IVR for 5 min before the procedure, whereas the control group received local anesthetic spray without IVR. Pain was measured using the Faces Pain Scale-Revised (FPS-R). Participants in the intervention group reported that their perceived pain was not significantly different, whereas those in the control group reported a fourfold increase in pain following the procedure [11]. Two studies involved pediatric oncology patients aged 7–19 years and who were undergoing port access (insertion of a needle into an implanted device to facilitate blood collection or injections). Participants in the intervention group were immersed in a virtual gorilla habitat. Results found that the heart rates of participants in the intervention group significantly decreased, indicating that children in the intervention group did not experience as much pain and anxiety as those in the control group [22, 23]. Another study on children with cancer (aged 5–18 years) undergoing venipuncture (n = 4) or port access (n = 46) allowed patients in the intervention group to select from various immersive and non-immersive distractors (such as books, IVR, music, and video games) [24]. The self-reported pain of patients in the IVR group was no different. However, a reduction of fear and distress was reported by the outcome assessors in IVR group.

Although previous studies have provided some positive findings regarding the effects of IVR on needle-related procedural pain and anxiety, these studies involved small sample sizes (n = 20 to 59) [11, 22‐24] and recruited children of various developmental ages (5–19 years) without using age-appropriate IVR modules [11, 22‐24]. Most importantly, all these studies adopted IVR as a distraction intervention only. To our knowledge, no study has utilized IVR to provide distraction and procedural information to patients undergoing venipuncture. Given that venipuncture is the most painful and fearful procedure for pediatric patients [1‐4], future large-scale studies on the efficacy of IVR to provide complete distraction and procedural information to pediatric patients undergoing venipuncture may offer crucial insight on the application of this approach.

The gate control theory and Lazarus and Folkman’s theory provide the theoretical underpinning of this study [25, 26]. The gate control theory suggests that peripheral nerves become excited when cells are damaged. Impulses from nerves pass along to spinal cord systems and other neuroanatomical structures before reaching the cerebral cortex where pain is perceived. The gate control system in the spinal cord opens and closes to modulate pain perception. If non-nociceptive input (IVR) exceeds the nociceptive (pain) input, then the gate can partially or entirely close, blocking the transmission of the pain signal to the brain. The theory also proposes that pain signals that descend from the brain through the gate can be amplified by emotional experiences, such as anxiety and stress. Lazarus and Folkman’s theory [26] states that an individual’s evaluations of anxiety and stress-provoking experiences are influenced by their perceptions of control over a potential threat. Providing information may help improve pediatric patients’ sense of control over a procedure [17, 18, 27].

In the context of these two theories, IVR functions by providing multisensory input to divert the children’s conscious attention from venipuncture-associated pain, thus helping close gate control and decreasing pain perception [28]. The analgesic effects of IVR have been supported by the results of functional magnetic resonance imaging assessment [29].

This is a two-arm parallel RCT.

This study will be conducted in the pediatric unit of a public hospital. The unit admit general pediatric patients. Venipuncture will be performed by a doctor or trained phlebotomist and will be conducted in the treatment room. No local analgesics will be applied before the procedure. Usually at least one staff (nurse or healthcare assistant) will assist in the procedure (by saying comfort words and restraining the child from vigorous movement). Parents will wait outside the treatment room during the procedures.

Eligible pediatric patients: (1) aged 4–12 years; (2) scheduled to undergo venipuncture; and (3) can understand Chinese and follow instructions. Potential participants will be excluded according to the following: (1) identified cognitive and learning problems in their medical record; (2) sensory impairment to pain (such as spinal bifida); (3) identified contact precautions; and (4) previous history of seizures or motion sickness. This study selects 4–12-year-old patients because they experience high level of distress in venipuncture procedure (4) and distraction is efficacious in this age group [14]. Younger patients will not be included because of their possible limited cognitive and verbal capacity to respond to the questionnaires.

In 2016, about 250 hospitalized patients aged 4–12 years were admitted to the unit and required venipuncture. Sample size estimation was based on the effect estimated from a previous IVR study using the FPS-R Scale as a primary outcome measure [11]. By using the power analysis software, GPower 3.1, it was estimated that a sample size of 85 participants per group would enable a two-arm RCT to detect a between-group difference of 0.8 in FPS-R scale with a pooled standard deviation of 1.84 with 80% power at 5% level of significance. Taking into account an attrition rate of up to 15% [23], 200 children will be recruited for the experimental and control groups, with 100 children in each group.

Eligible participants will be randomly assigned in a 1:1 ratio to the intervention group who will receive the IVR intervention or a control group that will receive standard care only using stratified permuted block randomization with a block size of 10 to maintain a good balance of participants between the two groups throughout the participant recruitment period. Randomization will be stratified by age group (4–7 years, 8–12 years) in equal numbers. According to Piaget’s theory, children aged 4–7 years belong to the same pre-operational stage, whereas those aged 8–12 years belong to the concrete operational stage [30]. Children in different stages differently perceive information and pain stimuli sensitivity [31].

A sequence of grouping identifiers (I = intervention group or C = control group) will be prepared in advance by an independent statistician, using computer-generated random codes for each of the two strata of age group. The group identifiers for each age group will then be put in serially numbered sealed opaque envelopes according to the underlying random sequence list by the statistician. The group allocation of the patients will be assigned according their ages, sequence of enrolment in the study, and the group identifier contained in the corresponding numbered envelopes. Group allocation will be concealed from the research assistant (RA), ward staff, child, and parent until consent and baseline assessment data have been obtained. Blinding of participants will be difficult but will not necessarily contribute to a source of bias because children are unlikely to change their behavior even when they know they are participating in a certain intervention [32].

In addition to standard care, children in the intervention group will receive IVR intervention through a commercially available disposable headset (Google cardboard goggle), which can be fitted into majority of commonly available smartphones. Although other latest headsets, such as Oculus Rift or HTC Vive, can provide a high-quality immersion experience, they likewise increase the risk of contact infection and require a high spectrum personal computer to operate. Therefore, these devices will not be used in this study.

With regard to the IVR modules, pilot work conducted by our research team found that cartoon animation was preferred by young patients, whereas the interactive game was preferred by adolescents; these results concurred with a previous study [24]. An IVR module that presents procedural information through a customized and child-friendly design more effectively mitigates pain and distress than that with off-the-shelf content [17, 29, 33]. However, these freely downloaded IVR modules that were developed in Western countries with English as the medium may not be completely appropriate for pediatric patients in Hong Kong. In the proposed study, an IVR module will be designed on the basis of suggestions to use age-appropriate modules for patients [16, 34] and the experiences of the PI, who has successfully developed six cartoon animations in previous studies [35]. The PI produced two developmentally appropriate animation modules: one for children aged 4–7 years and one for children aged 8–12 years; module content were validated by an expert panel (consists of pediatricians, nurses, and professors) and children. The two modules share the following common characteristics with those used in previous studies: (1) a wide range of visual and auditory stimuli [11, 22, 23]; (2) requiring minimum movement of head and hand to allow the procedures to proceed unhindered [36]; and (3) provision of procedural information. Each module is about 10 min in duration.

The animation follows the story of a young character called “DD,” who resides in outer space and is a fellow patient at the hospital. Like the patient, DD is also about to receive the venipuncture treatment and she wants to support other pediatric patients in the treatment. DD mentions her satisfaction and comfort with the hospital staff environment before introducing the procedures of the venipuncture, which is described as an adventurous mission. DD reminds the patient to remain calm and to be courageous in order to complete the mission and also describes certain sensations that the patient may feel. After the procedure is over, DD congratulates and awards the patient, and then guides the patient around outer space.

The venipuncture procedure will be conducted in the treatment room while parents wait outside. Patients assigned to the intervention group will receive IVR intervention 5 min before the start of venipuncture until the end of the procedure [11, 22]. The RA will provide simple and standard instruction on how to use the equipment. The headset will then be placed on patient’s head and adjusted to ensure a comfortable and secure fit. Patients will be allowed to view the IVR module according to their age group (4–7 years, 8–12 years). During the intervention, the head movement of the patient will control the IVR module. The patients will also be told that the intervention will be discontinued if they experience motion sickness, eye discomfort, or headaches.

After receiving IVR intervention for 5 min, the RA will invite the doctor/phlebotomist to start the venipuncture. The beginning of the procedure is indicated by doctor/phlebotomist disinfecting the venipuncture site. The RA will note the time of first attempt at venipuncture. The end of the procedure is indicated by application of band aid to the venipuncture site. The RA will remove the IVR equipment from the child after the procedure. The protocol follows for the first venipuncture attempt only. If the first attempt is unsuccessful, additional attempts occurring after the protocol will be completed, but participants will be withdrawn from study.

The fidelity of the intervention will be ensured by recruiting a RA with a minimum of two years of experiences in pediatric care. She will undergo two days of training conducted by the PI. The training will include: (1) basic knowledge about and application of IVR; (2) procedures of implementing the intervention and collecting data; and (3) management of untoward reactions, such as motion sickness. A minimum of one session conducted by the RA each month will be randomly selected to assess compliance with the implementation protocol by the PI. The PI and RA will meet monthly to discuss the delivery of IVR intervention and study progress. Feedback will be given accordingly.

Participants in the control group will receive standard care without IVR intervention. Standard care includes explaining why and what is being done and saying comforting and supportive words during procedures.

Ethical approval will be sought from the Ethical Committees of the study institutions. Written informed consent from parents, healthcare providers involved in venipuncture procedures, and assent from child will be obtained. Participants and parents will be informed that the care will not be affected by their participation status.

IBM SPSS 24 will be used for data analysis. Continuous demographic and clinical variables will be presented by their means and standard deviations, whereas categorical data (e.g. sex) will be presented in frequencies and percentages, as appropriate. The intention-to-treat principle will be adopted for the outcome comparisons between the intervention and control arms. Since the anxiety levels of the two age groups will be assessed by two different instruments, the anxiety scores assessed by each instrument will therefore be converted to z scores before pooling for outcome analysis. The generalized estimating equations (GEE) model will be used to compare each of the outcome measures, except the staff satisfaction, across the time points between the two study arms with the dichotomous age group variable set as a covariate to make adjustment for the stratified randomization by age group. GEE model can account for intra-correlated repeated measures data and produce unbiased estimates even if there are missing data, provided that the data are missing at completely random. For the staff satisfaction outcome, depending on the number of staff involved in satisfaction ratings, a mixed-effects model or simply a linear regression model will be used to compare the outcome between the two arms with adjustment for raters’ effects. As the means and standard deviations involved in the z scores conversion of the anxiety scale scores are based on sample’s instead of population’s means and standards, the calculated z scores may not truly reflect the deviations from population mean in units of population standard deviation. Sensitivity analysis will be conducted to examine if the intervention effects on the anxiety level in the two age groups are consistent with the pooled age group. Cohen’s d values will also be calculated to estimate the effect sizes of the IVR intervention on the outcome variables. All statistical analyses are two-sided and level of significance will be set at 0.05.

The proposed IVR intervention will potentially provide significant practical implications in addressing pain, anxiety, and stress of the patients. The ultimate impact of this intervention is to increase procedural compliance, consequently decreasing the length and cost of the procedure while possibly improving the satisfaction of the healthcare providers with the procedure.

This trial will commence on 1 January 2019. The anticipated end date of the study is 31 December 2020.