Non-pharmacological techniques complementary to sedation administration decrease pain and anxiety during gastrointestinal endoscopic procedures: a meta-analysis

Introduction

Sedation and analgesia administration during gastrointestinal (GI) endoscopy contributes to procedural quality and improves patient satisfaction, in everyday clinical practice [1]. GI endoscopy is perceived as uncomfortable and anxiety-provoking, while the risk of serious sedation-induced adverse events, i.e., cardiopulmonary reactions, is always imminent, especially in those of advanced age and with comorbidities [2,3]. Irrespective of the specific sedative drug used in procedural sedation, hypoxia, hypotension and bradycardia are the most frequently observed adverse events [4]; however, efficacious and safe combinations of sedative/analgesic medications that facilitate the performance of GI endoscopy are readily available [5]. The need for intravenous access, potentially allergic reactions to medication, and time spent in the recovery area are drawbacks of pharmacological sedation.

Hence, the application of non-pharmacological interventions, such as listening to music or the use of virtual reality (VR) glasses, in addition to standard pharmacological sedation might be a valuable tool. Among these, music is perhaps the one with the most evidence available; however, its exact impact on patient-reported outcomes compared to standard care remains ambiguous, since individual studies and meta-analyses face flaws in their performance that have attracted criticism [6-8]. Furthermore, data regarding the role of currently available VR modalities are inconclusive. In this context, we performed an updated systematic review with meta-analysis incorporating data exclusively from recent randomized controlled trials (RCTs) to evaluate the effect of non-pharmacological interventions, namely music and VR, as adjuncts to conventional sedation administration on patients’ reported outcomes for endoscopic procedures.

Materials and methods

This study was carried out according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement [9] (Supplementary Table 1). The review protocol is available at the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD420250650749.

Results

Study selection

The initial search yielded 221 citations. Of these, 200 were excluded after title and abstract review as irrelevant to the study’s aim, or as duplicates, leaving 21 articles eligible for full-text assessment. Three non-randomized studies, 5 where no sedation was delivered, and 1 study with a different endpoint (endoscopist performance instead of patient satisfaction) were excluded; thus, 12 studies [12-23] were included in the final analysis. The PRISMA flowchart showing the study selection is depicted in Fig. 1.

Figure 1 Flow diagram of assessment of eligible studies identified

Characteristics of studies included

Table 1 summarizes the main characteristics of the included studies. One study assessed the effect of VR distraction methods [23], 9 studies assessed the effect of music therapy [12,14-19,21,22], while the effects of both auditory and visual distraction were assessed in 2 studies [13,20]. The vast majority of studies (n=11) enrolled individuals undergoing colonoscopy for various indications, while 1 study included patients undergoing diagnostic endoscopic ultrasound [17].

Table 1 Characteristics of the included studies

Methodological quality and risk of bias

A summarized assessment of the risk of bias per study using the Cochrane Collaboration’s risk of bias assessment tool is illustrated in Fig. 2. Participating physicians and patients were blinded neither to the equipment used, nor to the outcomes measured, in the majority (n=9/12) of the studies; hence, we noted high concern regarding measurement bias.

Figure 2 Risk of bias of included trials

Endpoints

Primary endpoint: pain

Eleven studies [12,13,15-23] provided data regarding reported pain during GI endoscopy. Overall, 1511 patients were included: 762 received non-pharmacological techniques while 749 received standard sedation. Compared to standard sedation, addition of non-pharmacological techniques resulted in significantly lower pain (MD -1.02; 95%CI -1.63 to 0.41; Ι²=64%) (Fig. 3). In an effort to address heterogeneity, the step-by-step, leave-one-out sensitivity analysis showed that the pooled effect size remained significant after exclusion of any single study. When studies were assessed according to the modality used (VR or music), heterogeneity was eliminated (χ²=0.77; Df=2; P=0.68) for the subgroup of studies analyzing VR technology [13,20,23], and the measured effect was further strengthened (MD -1.05, 95%CI -1.74 to -0.37; I²=0%). Visual assessment of the funnel plot showed no evidence of publication bias (Supplementary Fig. 1), while the certainty of evidence derived from the meta-analysis indicated that quality of evidence supporting lower reported pain with non-pharmacological techniques was low, given the serious risk of bias, serious inconsistency and indirectness (Supplementary Table 2).

Figure 3 Forest plot for studies assessing the effect of non-pharmacological techniques complementary to sedation administration on reported pain CI, confidence interval

Secondary endpoints

Anxiety: Nine studies provided data regarding reported anxiety during GI endoscopy [12,14-16,18-20,22,23]. A total of 1255 patients were included in the analysis: 629 received non-pharmacological techniques while 626 received standard sedation. Compared to standard sedation, the addition of non-pharmacological techniques resulted in significantly lower anxiety (MD -1.07, 95%CI -1.75 to -0.39; Ι²=20%) (Fig. 4A). Sensitivity analysis did not detect any study responsible for the detected heterogeneity. No evidence of publication bias was evident (data not shown).

Figure 4 Forest plot for studies assessing the effect of non-pharmacological techniques complementary to sedation administration on reported (A) anxiety and (B) patient satisfaction

CI, confidence interval

Patient satisfaction: Six studies provided data regarding reported satisfaction during GI endoscopy [12,15,18-20,23]. This analysis included 834 patients: 421 underwent non-pharmacological techniques while 413 received standard sedation. Compared to standard sedation, the addition of non-pharmacological techniques resulted in significantly higher levels of satisfaction (MD 1.67, 95%CI 0.50-2.84; Ι²=94%) (Fig. 4B). The sensitivity analysis, excluding 1 study at a time, did not identify a single study accountable for this effect. No evidence of publication bias was evident (data not shown).

Sedation/analgesia medication doses: Sedation/analgesia medication dosages were provided in 6 studies [12-14,18,22,23], referring to 891 patients: 438 underwent non-pharmacological techniques, while 453 received standard sedation. Additional non-pharmacological techniques were associated with a lower mean dose of midazolam compared to standard sedation, although the difference was non-significant (MD -0.43, 95%CI -0.88 to 0.02; Ι²=93%) (Supplementary Fig. 2A). Similarly, the mean dose of analgesia did not differ significantly between the 2 arms (MD -1.41, 95%CI -4.14 to 1.32; Ι²=51%) (Supplementary Fig. 2B). The sensitivity analysis, excluding 1 study at a time, did not identify a single study accountable for this effect. No evidence of publication bias was evident (data not shown).

Discussion

Sedation and analgesia have revolutionized the procedural quality of GI endoscopy, contributing at the same time to better patient satisfaction and more willingness to undergo an endoscopic procedure [3]. Over the last 10 years, digital access to music (and, to a lesser extent, to VR) has become widely and easily available, with numerous online streaming platforms, and small portable devices such as music boxes and in-ear headphones.

Our systematic review and meta-analysis demonstrated that provision of music or VR complementary to standard sedation administration not only resulted in a significant decrease in patients’ procedure-related pain levels, but also mitigated anxiety during the preprocedural period, leading to greater satisfaction. Notably, this effect was more prominent for VR than for music, implying that the heterogeneity derives principally from studies evaluating music; this could be attributed to the different types of music types, or to different modes of music application—i.e., headphones, music in room. However, further subgroup analyses to address this issue in detail were not possible, in view of the poor reporting. Changes in the visual analogue scale of more than 9 mm were found to be clinically significant, irrespective of sex, age or cause of pain [24]. As control of pain and anxiety is a high priority for patients [3], reductions in pain and anxiety are most likely to be clinically meaningful. Initially, no difference was observed with patient-selected music [25]; more recently, however, patient-selected music appears to be more effective than researcher-selected music [26]. The involvement of the patient’s contribution and choice is beneficial during the assessment and information gathering prior to endoscopic procedures [27,28].

Although confidence in the effect estimates was deemed low, our analysis showed a clear-cut benefit from application of the audiovisual distraction techniques in reducing pain and anxiety. Music can distract the patients’ attention from pain and discomfort, but auditory distractions appear to be more effective than visual distractions in reducing the dose of sedation, indicating that music has a greater effect than mere distraction [29]. Music also awakens memories and emotions, further reducing levels of stress and anxiety [30]. Numerous brain areas (e.g., cingulate cortex, periaqueductal gray matter) and neurotransmitters (e.g., endorphins, oxytocin, dopamine) are involved in pain modulation [25,31], and can be modified by listening to music [32,33]. Besides neurotransmitters, other biological processes (noradrenaline, prostaglandins, cytokines, etc.) are also modified by music [31]. Music also facilitates recovery after psychological stress [34].

A handful of meta-analyses have attempted to pool data on the role of listening to music in reducing pain in adults undergoing colonoscopy [6-8,35]. These had conflicting results, but reported a small treatment effect in favor of music to improve overall patient experience, while the role of VR was not studied in those iterations.

Implementation of non-pharmacological techniques complimentary to standard sedation care during GI endoscopic procedures may have favorable implications for everyday clinical practice. These modalities are safe (no complications were reported), easy-to-administer, low-cost and noninvasive interventions, that can be applied in many different clinical settings, underlining the generalizability of their application, regardless of the physician’s expertise, and without any previous dedicated training.

Despite the use of sedation/analgesia as an effective measure to reduce pain and discomfort, serious cardiorespiratory events may occur, especially in patients of advanced age and/or with comorbidities [36]. Optimized sedation not only improves the core quality indicators of the endoscopic procedure itself, but also decreases the burden on patients and endoscopy departments due to a prolonged recovery time [37]. Hence, the possibility of administering smaller quantities of sedatives and analgesic might potentially affect the incidence of cardiopulmonary reactions. Our analysis indeed showed lower levels of sedative medication used in the intervention arm, although the difference was statistically non-significant. Lower doses of sedative medication and/or a shorter recovery time could result in lower costs. In the case of VR goggles, the purchase price, as well as reprocessing and cleaning costs, need to be taken into account regarding cost-effectiveness, while listening to music via the patient’s personal music device and/or earphones would most likely be cost-beneficial.

The principal strength of this meta-analysis is the use of a rigorous and reproducible methodology; we conducted a comprehensive recent literature search, reported in full, and with a strict assessment of study quality and evidence, following recommendations for systematic reviews [38]. Including only studies of the highest quality (RCTs), the exclusion of publication bias, as well as the performance of sensitivity analyses are additional study assets.

There are limitations related to both the analysis and the individual studies that merit further discussion. First, the high level of heterogeneity, the absence of participant blinding and allocation to the endoscopist, and the presence of confounding factors, leading to the low-grade certainty of the evidence, should be considered in any interpretation of the results of our analysis.

Second, there were differences in the technology systems used (i.e., different modes of music administration, different genres of music at the discretion of either the patient or the endoscopist), in the clinical settings (i.e., outpatient vs. inpatients), in the indications for endoscopy, and in the populations enrolled (regarding age distribution, and variations in lifestyle of people from different countries), all of which limited the ability to draw firm conclusions across the spectrum of non-pharmacological techniques. Notably, the primary outcome of interest (pain) was a patient-reported outcome evaluated by different scales in each study. Heterogeneity for the primary endpoint (pain, Ι²=64%) was eliminated when studies were assessed according to the modality used (VR or music), implying that heterogeneity derived principally from studies evaluating music. This could be attributed to the different music types used, or to the different modes of delivery, i.e., headphones or music in room. However, further subgroup analyses to address this issue were not possible, given the poor reporting, and this should also be listed among the limitations of the current study. To address this, we used a random-effects model, allowing a more conservative effect of estimate when a high degree of heterogeneity among RCTs is expected. In addition, most of the included trials suffered bias related to performance and outcome detection, given that blinded assessment was not possible, while the subjectivity of the outcome measurements may have led to performance bias.

Third, a number of patient-, provider- and system-level factors (timing and duration of the intervention, frequency of exposure, timing of outcome variable assessment. level of endoscopist experience) may affect the performance of these technology systems. Finally, it was impossible to perform a cost-benefit analysis.

To conclude, we found that concomitant application of non-pharmacological techniques (VR or music) as adjuncts to standard sedation care for GI endoscopic procedures may result in reduced pain and anxiety, while also improving patient satisfaction.