Virtual reality and hypnosis to alleviate anxiety and pain in patients undergoing bone marrow aspiration and biopsy: A randomized controlled trial

Abstract Background: Bone marrow aspiration and biopsy (BMAB) is an essential diagnostic procedure in hematology. Despite standard pharmacological approaches, anxiety and pain remain significant patient concerns, negatively affecting patient experience. Non-pharmacological interventions such as hypnosis and virtual reality (VR) have shown promise in managing procedural anxiety but have rarely been directly compared. Methods: We conducted a three-arm, open-label randomized controlled trial (NCT05982249) involving adult patients undergoing BMAB at Bnai Zion Medical Center, Haifa, Israel. Patients were randomized (1:1:1) to hypnosis (n=22), VR (n=24), or standard-of-care (SOC) control group (n=21). Hypnosis involved a tailored, 7-minute guided audio script delivered through headphones. The VR intervention provided a calming 3D visual and auditory experience for approximately 7 minutes. All participants received SOC, including local anesthesia (lidocaine 2%) and optional sedation (midazolam). Primary outcomes were changes in anxiety-related concerns, assessed by the Measure Yourself Concerns and Wellbeing (MYCAW) questionnaire at baseline (T1), post-intervention (T2), and post-procedure (T3). Secondary outcomes included sedation and analgesic use, physiological parameters, and psychological variables. Results: Sixty-seven patients (mean age 61±18 years, 45% female) participated. Main concerns at baseline included anxiety about the procedure (29%), fear of results (24%), and pain anticipation (16%). Baseline MYCAW scores were significantly higher in the hypnosis (4.9±1.2) and VR groups (4.3±1.7) compared to the control group (3.3±1.7; p<0.001). MYCAW scores decreased significantly across all groups from T1 to T3 (p<0.001). The VR group demonstrated a significant immediate reduction in anxiety concerns from T1 to T2 compared to the control group (p=0.003), particularly evident among younger patients, those with fewer comorbidities, and patients with higher psychological absorption capacity (p<0.001). No significant immediate advantage was observed for hypnosis compared to SOC. Physiological variables including mean arterial pressure, heart rate, respiratory rate, and oxygen saturation did not differ significantly among groups. Although not statistically significant, there was a trend toward lower sedation requirements (midazolam dose) in the VR group (4.6±2.6 mg) compared to hypnosis (5.5±2.5 mg) and control (5.3±2.3 mg; p=0.48), and a trend toward higher local anesthetic use in the control group (12.9±5.6 cc) compared to VR (10.7±2.9 cc) and hypnosis (10.4±3.7 cc; p=0.13). Conclusions: VR effectively reduced immediate pre-procedural anxiety in patients undergoing BMAB, highlighting its potential as a feasible, non-pharmacological adjunctive intervention. Further studies should explore optimal timing and customization of these interventions to maximize patient benefit.