Evaluating local anesthetic strategies in ambulatory urologic surgery: insights from the Baby ORIOLES randomized clinical trial

Gabrielson et al. conducted a single-blinded, randomized phase III clinical trial to evaluate the impact of adding liposomal bupivacaine to bupivacaine hydrochloride on postoperative pain scores and opioid-free rates in children undergoing ambulatory urologic surgeries requiring a dorsal penile nerve or spermatic cord block (1). The study utilized a factorial design and included otherwise healthy children aged 6 to 18 years who underwent surgery at a single institution. A total of 104 patients were randomized 1:1 into an intervention group, receiving both bupivacaine hydrochloride and liposomal bupivacaine, and a control group, receiving only bupivacaine hydrochloride as standard care. Outcomes assessed included the proportion of patients who remained opioid-free for 48 hours postoperatively, parent-reported postoperative pain measure (PPPM) scores, and weight-based oral morphine equivalents consumed at 48 hours and 10–14 days postoperatively. Results were analyzed on an intention-to-treat basis. No significant differences were observed between the intervention and control groups in opioid-free rates (60% vs. 62%, P=0.8) or in weight-based oral morphine equivalents administered (estimated difference: −0.01, P=0.3). While the PPPM scores in the intervention group were slightly lower at 48 hours postoperatively (estimated difference: −0.7, 95% confidence interval: −1.4 to 0.01, P=0.05), the difference did not reach statistical significance. Overall, Gabrielson et al. concluded that the addition of liposomal bupivacaine to bupivacaine hydrochloride did not confer significant benefits in terms of opioid-sparing effects or reductions in postoperative pain. While the study did not yield statistically significant results, it represents a meaningful contribution toward refining non-opioid pain management strategies in urologic surgery. As urologic care increasingly transitions to ambulatory surgical settings, conscious sedation combined with local anesthesia is often favored over general anesthesia and analgesia (2). However, there remains a notable lack of high-quality, clinical trial data comparing the opioid-sparing benefits of various local anesthetic techniques employed in ambulatory surgery. This gap is further complicated by the diversity of urological procedures, which presents additional challenges in establishing an optimal local anesthetic regimen (2). Multiple non-opioid pain strategies have been proposed, some of which may be more cost-effective than others. Furthermore, pediatric-specific literature in surgical pain control is sparse and data are largely extrapolated from adult data. This reflects a broader problem in pediatric pharmacology, where clinical interventions are frequently implemented without sufficient pediatric-specific trials (3,4). In this context, Gabrielson et al. implemented a high-quality study design, rigorously implementing a multi-arm clinical trial with robust participant follow-up, adhering to CONSORT guidelines to determine superiority of liposomal bupivacaine with bupivacaine hydrochloride across multiple real-world objective and subjective endpoints. Although the study demonstrated no significant advantages of the liposomal formulation across multiple objective and subjective endpoints, its robust methodology serves as a valuable proof-of-concept. This approach should be extended to future investigations, including multi-center studies and trials involving adult populations, to better inform the development of effective local anesthesia strategies in urologic surgery.

The findings of the Baby ORIOLES trial contribute to the ongoing effort to minimize opioid use in pediatric surgery by advocating for multimodal, opioid-sparing techniques incorporating agents such as ibuprofen, acetaminophen, and ketorolac. Interestingly, a previous study conducted at the same institution noted a significantly lower rate of children requiring no opioids postoperatively (60% compared to 28%). This discrepancy may be attributed to the overuse of rescue opioids, highlighting the importance of limiting their use to enhance opioid-free recovery rates (5). As Gabrielson et al. suggest, future studies can expand upon their work by exploring the analgesic and pharmacokinetic profile of liposomal bupivacaine within specific urological procedures, so that vascularity can be standardized. Liposomal formulations may offer enhanced efficacy in surgical procedures of less vascularized regions, such as single-port robotic surgery, where the agent is less likely to diffuse into systemic circulation rapidly (6,7). Additionally, robust clinical trials are needed to determine the utility of liposomal bupivacaine in urological surgeries with high nociceptive load, especially open radical and partial nephrectomy and cystectomy with urinary diversion (8). Given the global opioid epidemic, which continues to affect millions (9), identifying safe and effective alternatives to opioids for postoperative pain management remains a critical priority. Well-designed, large-scale clinical trials are essential to advancing this field and providing evidence-based strategies for optimal pain control while reducing reliance on opioids.

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Provenance and Peer Review: This article was commissioned by the editorial office, Translational Andrology and Urology. The article has undergone external peer review.

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