A Systematic Review of Randomized Controlled Trials on Virtual Reality Application in Pediatric Patients

Virtual reality is a novel approach for distracting and alleviating anxiety, pain, and other complications during medical procedures, and it can be more effective than conventional methods. In virtual reality, the patient is completely immersed in the virtual environment, which is used to make patients feel more comfortable and can provide a positive prognosis. The data were searched by using the Boolean operator “AND” between the search phrases “Virtual reality,” and “Pediatrics” and the relevant literature was extracted. The inclusion criteria were the free full text, randomized controlled trials, studies between 2016 and 2022 and pediatric patients. This systematic review was conducted to compare randomized controlled trials of virtual reality applications in pediatric patients in different clinical settings. Of the included 15 randomized controlled trials, 12 studies were on pain and anxiety, two on brain injury and cerebral palsy, and one on awareness among asthmatic patients. This review concluded that virtual reality exposure has a beneficial effect on pediatric patients in reducing pain and anxiety, improving muscle strength and dexterity, and awareness among asthmatic patients.


Introduction And Background
Pain, anxiety, and stress are generally observed during medical procedures in pediatric patients with poor prognosis, nervousness, loss of appetite, sleep disturbances, the effort to escape, and post-traumatic stress manifestations. Moreover, negligence toward health is a result of altogether pain, anxiety, and stress. Hence, new therapies are crucial to alleviate pain and anxiety in children and can be achieved by distraction during clinical procedures [1].
Distraction methods such as the use of music, movies, and toys have been shown to have a positive impact on decreasing pain and anxiety. Virtual reality (VR) is the newest technique to provide distraction during medical procedures and has been proven to be more efficacious than other conventional methods, and is usually made up of a computer-generated environment, and three-dimensional use and orientation are feasible [2]. The user views this environment through advanced head-mounted displays (HMDs), which feature a vivid range of sight and a movement trailing system. The perception of living in VR was due to total immersion which promotes less pain during the procedure using greater immersion and less attention to pain perception. VR is specially created for children, as they are more attracted to imaginative games and play [1,2].
VR is usually divided into non-immersive, fully immersive, semi-immersive, and augmented VR which is widely used in clinical practice for distraction and to keep patients calm [3]. Hence, this review was conducted to highlight the VR applications in pediatric patients with different clinical symptoms.

Research methodology
For the purpose of performing this systematic review, the PRISMA-S statement for reporting systematic reviews was utilized [4]. Randomized Controlled Trials (RCTs) that were released between 2016 and July 2022 were looked for in PubMed and Google Scholar. Using the Boolean operator "AND," the search phrases from the two search themes were merged to search the databases. The use of the text phrases "virtual reality" and "pediatrics," aimed to quantify VR exposure (VRE) in pediatric patients. This review included Englishlanguage studies that examined the applications of VR distractions and improvements among pediatric patients and evaluated the impact of VR on pain management, nervousness, neurorehabilitation, and dental surgeries. The articles enlisted, were with the title "virtual reality" AND "pediatrics" AND "children," free full abstract, and, randomized controlled trials. The peer review, observational studies, case reports, trials that were before 2016, trial data and results that were not declared or incomplete trials, and studies of children's parents, nursing staff, and adults were excluded. Figure 1 shows the RCTs selection method and inclusion criteria.

Results
Only 15 RCTs were enrolled in this study from the PubMed database. Various variables related to VR applications were investigated and enlisted in this systematic review. Meta-analysis was not feasible due to differences in setting, inclusion criteria, and outcome characterization and assessment. However, comparisons among similar studies provide a guide for VR use in pediatric patients and relevant practices in real-life settings. Information regarding the author's name, names of journals, place of study, and year of publication were mentioned in Table 1.   -Determined anxiety reported by child and caregiver.
No clinically relevant differences in the outcome were seen in the intervention and control group in reducing anxiety in children. Caregiver were satisfied with the virtual reality magnetic resonance imaging (VR-MRI) app as compared to standard preparatory manual (SPM) 9 Hundert et al. [11] 40 VR=20 CG=20   All study designs were interventional and consistent with the inclusion criteria for this review. All studies used a randomized controlled design to demonstrate the effectiveness of VR in several parameters in pediatric patients. The majority of studies (n=12) evaluated patients' experiences with venipuncture, peripheral intravenous catheter (PIVC) installation, dental extraction, elective surgery under general anesthesia, and pain and anxiety related to those procedures. Two RCTs (n=2) assessed dexterity and muscular power in patients with cerebral palsy (CP) and one RCT (n=1) demonstrated the use of VR for creating awareness among asthmatic patients.

Discussion
This novel systematic analysis emphasizes randomized controlled research that details VR technology applications. The current medical uses of VR technology are pain distraction, anxiety relief, and rehabilitation, as revealed by data from 15 studies that were eligible for this review.
Procedure-related pain that is not properly handled is extremely upsetting and can increase pain sensitivity over time, decreasing the probability that an adult would seek medical attention and even fewer possibilities in pediatric patients [13]. VR is an experimentally established, practical, and economical intervention to alleviate pain and anxiety during regular venipuncture operations in the pediatric setting. Interventions using VR can help patients feel more satisfied with their care, caregivers, and overall health by reducing needle anxiety, traumatic reactions to medical procedures, and adverse reactions [10].
The goal of the previously conducted RCT was to identify less risky and non-pharmacological alternatives to treat pain and discomfort caused by repeated treatments when sedation is unnecessary. VRE has not, however, demonstrated any appreciable differences and patients frequently required the use of pharmaceutical treatments and analgesics (morphine), hence the use of immersive VR such as headset and audiovisual distraction led to a reduction in anxiety in the operating room before elective surgery, as the study was a pragmatic implementation, and it used established outcome scale that was validated and showed less observer bias [3].
Another RCT reported that VR did not significantly reduce pain or anxiety in patients undergoing elective surgery. A single evaluation performed before entering the recovery room did not provide a thorough understanding of the postoperative effects of VRE. The study was discontinued in 21 children by removing the headset and was heavy and larger in size, which might have caused discomfort to the patients, as the majority of subjects were 4-5 years of age, and minor procedures were included [1]. Compared to traditional ways of managing behavior in the field of medical and dental sciences, VR distraction is beneficial in reducing pain and anxiety. According to a study by Gold et al., VR decreased anxiety and acute procedural pain during phlebotomy procedures [2].
Chances of dentist phobia, non-cooperative conduct at the time of treatment, and the potential to avoid future dental appointments have all been linked to unpleasant prior dental experiences, including the use of local anesthetics [18]. The Heart Rate (HR) was used to illustrate anxiety as a physiological measurement, and it showed significant elevations after screen use when compared to the control group, as well as increased mean HR levels during the administration of the local anesthetic and its procedures. The study investigated pain during anesthesia utilization, which may have created fear in children and may have contributed to the elevated level of HR in the test group. There was inadequate blinding of the investigator, no direct observation, and increased inconsistency due to the administration of local anesthesia by different clinicians for the assessment of the Face, Legs, Activity, Cry, Consolability (FLACC) Behavioral Pain Assessment Scale [5].
Similarly, the positive influence of VR on pain, distress, needle phobia, and treatment in patients who routinely undergo PIVC procedures irrespective of their chronic status has been demonstrated [9]. According to Hundert et al. findings, children and adolescents utilized VR as an intervention and desired to use VR for subsequent Subcutaneous Port (SCP) insertions in cancer patients. Due to the limited sample size, wide confidence intervals, and dichotomized results, the findings were described conservatively [11].
Another RCT reported that VR using a dome screen is a practical means of diverting young children during intravenous (IV) insertion; however, its efficacy could not be validated because of the limited sample size [12]. Similar to this study, the use of VR headgear during local anesthesia and the removal of deciduous teeth can considerably reduce children's fear of the dentist and their perception of pain without the development of simulator sickness [12], which is similar to the findings of Lahti et al. [19]. In another study, most participants concluded that the procedures were associated with less discomfort, and some groups of patients reported high levels of pain across interventions. Children with a history of chronic pain and perception of the predisposing pain responded more favorably to VR. The limitations of this study include its heterogeneous sample and the absence of intervention [12]. Aztori et al. conducted RCT on children with chronic kidney disease, it involved the use of an immersive VR venipuncture on a psychological pain management strategy during venipuncture, and throughout this process, VR considerably increased fun while significantly reducing the greatest pain and pain unpleasantness. The children who participated in the study were younger than eight years; therefore, they were unable to discern between different pain levels, fear was not examined, and only one venipuncture was used to test pain [15].
There is not much research that determined the VR distraction outcome on anxiety, pain, gender, and age respectively. Similarly, another study examined the effects of audio distraction visually on anxiety in children aged four to six years compared to those aged six to eight years and discovered that it effectively reduced anxiety in the treatment groups [20]. Hence, in this systematic review, it was unclear, whether VR applications significantly decreased pain and anxiety.
A major objective for pediatric patients with CP is independent walking, which was covered in this review on the use of VR in children with brain injuries and subjected to clinical and community-focused rehabilitation [21]. This study examined how children with CP walked, balanced themselves, developed their muscles, and used their gross motor skills after treadmill training [16]. Since the children were able to walk without the aid of walkers after using VR treadmill training, it was employed without partial body weight support. This improved muscular strength is evidenced by the children's increased walking speed and lower limb weightbearing capacity. The VR Treadmill Training (VRTT) group's walking activities greatly improved as a result of the transfer of VR walking training skills to actual walking surroundings. However, given that the intervention lasted for only eight weeks, the results may not necessarily indicate possible long-term therapeutic success [16]. According to Schlough et al. children with CP who combine aerobic exercise with treadmill gait training has noticeably increased muscle strength [21].
Similarly, VR games effectively motivate children with CP and, as a result, represent a therapeutic approach that can be utilized to speed up rehabilitation training [22]. The execution of daily tasks, dexterity, and active forearm supination motion improved more effectively with VR training. Children with more severe motor deficits benefit considerably from VR training [23]. By providing implicit learning, tangible activities, and concentrated attention, VR-based rehabilitation improves the motor learning processes. Choi et al. used game content for training purposes, such as the performance of daily living activities such as eating, pouring water, and cooking [6]. A fundamental concept in rehabilitation is task-specific training, which focuses on repeatedly performing certain functional tasks. For task-specific training, it has been recommended that tasks be repetitive, pertinent to the patient, randomly allocated, and reinforced with a positive review [6,24].
It is possible to use therapeutic techniques like task-directed exercise for VR rehabilitation. Thus, more engagement in daily activities, as determined by the Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT) in the study, may have resulted from improvements in upper limb function [24]. Another study concluded that VR might be challenging to show improvements in the quality of CP therapy. For instance, spastic quadriplegia and diplegia patients between the ages of eight and 12 years were treated for eight weeks for one and a half hours each week of treatment was given [24,25]. Similarly, Chen et al. examined how VR could help four children with CP between the ages of four and eight years to meet their activity goals. Additionally, it is critical to use home-based treatment strategies to extend the duration of interventions and boost the effectiveness of VR intervention [23].
The establishment and comparison of awareness and education among asthma patients showed an efficacious impact of immersive VR content. Additionally, the asthma control status of the experimental and control groups was compared and was informative for the participants [14]. The positive side of this review, it has included the generalizability of the study, because of the use of diverse inclusion criteria, and also involved cases from dentistry, oncology, surgeries, hematology, physiotherapy, and neurology. The only drawback of this systematic review is that, although relatively few articles were included and several parameters were investigated simultaneously, the overall utilization of VR cannot be examined and understood in general. Some studies have demonstrated the advantages of alternative therapies over conventional therapies, and vice versa. The adverse effects among pediatrics using VR were not included in the systematic review and could not provide a definitive conclusion that VR therapy is superior to standard care or traditional practices.

Conclusions
In this study, the use of VRE among pediatric patients showed a beneficial impact, and in some RCTs, it did not cause any significant difference when compared with the usual care. Gamification and VR applications can be helpful for pediatric patients. However, there is currently little empirical data and poor evidence. Future research can be conducted by including more than two databases and including more searching terms with combination and permutation for accessing and analyzing more relevant literature.

Conflicts of interest:
In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.