Donor-site pain relief without intraoperative opioid sparing: liposomal bupivacaine popliteal sciatic nerve block in fibula free flap maxillofacial reconstruction

Introduction

In the June 2025 issue of BMC Anesthesiology, Wu et al. present a rigorously designed randomized controlled trial evaluating whether a popliteal sciatic nerve block (PSNB) using liposomal bupivacaine (LB) reduces opioid use and improves postoperative recovery in maxillofacial reconstruction with fibula free flap (1). Their study addresses a meaningful clinical problem where donor-site pain after fibular harvest is often more intense than pain at the primary surgical site (2). Because fibular graft harvest involves deep periosteal and soft-tissue dissection, poorly controlled donor-site pain can delay mobilization, worsen sleep, and increase opioid requirements. This trial aligns with the contemporary emphasis on multimodal, opioid-sparing perioperative care, and a closer examination of its strengths and limitations is necessary to interpret the findings within an appropriate clinical and scientific context.

Strengths of the study

The investigators followed CONSORT methodology and ensured adequate randomization and blinding, with balanced baseline characteristics between groups (1). LB was used due to its prolonged duration of action up to 84 hours (Table 1). This slow release is achieved through a multivesicular liposomal structure that gradually delivers bupivacaine over time (3). By selecting a popliteal sciatic approach, Wu et al. targeted the tibial and common peroneal nerve branches that innervate the fibular donor site. The authors also assessed multiple patient-centered outcomes, including pain intensity, sleep quality, postoperative nausea and vomiting (PONV), and opioid rescue use, not just total opioid administration. This comprehensive approach allows for a more holistic understanding of the patient experience and recovery trajectory. Finally, the investigators performed the PSNB after induction of general anesthesia to ensure complete patient blinding to group allocation. While this method is not generally preferred because it prevents patient feedback during needle placement, it maintained blinding and supported the methodological rigor of the study.

Key findings and interpretation

Although total perioperative opioid consumption did not differ between the PSNB and control groups, several secondary outcomes demonstrated clear benefits in those who received LB. The proportion of patients reporting moderate-to-severe donor-site pain was significantly lower in the block group (8.1% vs. 48.6%). This aligns with prior randomized and observational studies showing that popliteal blocks decrease pain and opioid requirements after fibular graft harvest (7). Patients receiving LB also required fewer postoperative rescue opioids, indicating improved control of breakthrough pain, a more patient-centered metric than cumulative opioid totals. Improved sleep quality during the first two postoperative nights likely reflects better nighttime analgesia, which is critical following surgery as interrupted sleep schedules can impair healing and worsen postoperative recovery (8). Notably, none of the patients in the PSNB group experienced PONV, whereas 13.5% did in the control group. These findings collectively highlight that even without reducing intraoperative opioid use, regional anesthesia with LB improves postoperative comfort, decreases opioid-related side effects, and enhances sleep, underscoring its value within multimodal analgesia.

Limitations and critique

Despite its many strengths, several limitations of this study temper the conclusions. The PSNB was performed after induction, less than 1 hour before incision. As LB has a delayed onset, this timing likely prevented intraoperative benefit and contributed to the lack of observed difference in intraoperative opioid use (3,9). Furthermore, since the block was placed under general anesthesia, there was no opportunity for patient feedback about paresthesia or pain during needle advancement, which is an important safeguard advised by the American Society of Regional Anesthesia and Pain Medicine. While ultrasound can confirm injectate spread, it does not verify effective blockade. Given LB’s known variability and patchy sensory distribution (5,10), partial or failed blocks cannot be excluded. Additionally, the LB dose used (133 mg in 10 mL) may not provide sufficient volume to circumferentially surround both tibial and common peroneal components of the sciatic nerve. Several studies evaluating LB for popliteal block use 266 mg in 20 mL to improve spread and clinical efficacy (9). Maxillofacial reconstruction is also a complex procedure involving multiple painful sites, including tumor resection, neck dissection, tracheostomy, and donor harvest, making it unlikely that improving donor-site pain alone could significantly affect total opioid administration. Longer-term outcomes, such as chronic pain development, functional recovery, opioid use after discharge, sustained sleep quality, and return visits to the emergency department, were not captured, as follow-up ended at 48 hours postoperatively (11). Finally, the single-center design at a tertiary hospital in China limits generalizability, as variations in surgical technique, perioperative pathways, and available resources across institutions may influence both feasibility and effectiveness.

Clinical implications

Wu et al.’s trial aligns with ongoing interest in optimizing pain management via regional anesthesia techniques and opioid-sparing strategies. Intraoperative opioid totals, while quantifiable, are not the most important clinical outcomes. Sleep preservation, reduced nausea and vomiting, and donor-site pain control more directly influence patients’ early recovery experience, mobility, and satisfaction. While systematic reviews suggest that LB does not consistently outperform plain bupivacaine across all peripheral nerve blocks (6), its benefit in procedures with prolonged postoperative pain remains clinically relevant. The 2024 triple-blinded pharmacodynamic study by Zadrazil et al. showed that LB has a delayed onset and less consistent sensory blockade than plain bupivacaine (5). Even so, its prolonged postoperative analgesia can improve patient comfort, reinforcing the importance of tailoring regional anesthesia to the procedure and pain distribution. In reconstructive surgery, for example, where donor-site pain may exceed recipient-site pain, targeted or dual-site blocks may provide more comprehensive analgesia and support opioid-sparing, patient-centered care.

Future directions

Several study design refinements could enhance future trials. First, performing the PSNB before the induction of general anesthesia would allow LB adequate time to reach full effect (Figure 1). Blinding can be preserved using saline placebo injections at the same anatomical location (12). Additionally, sensory testing should be performed preoperatively to confirm block success and reduce the influence of failed or incomplete blocks on trial outcomes. Since donor-site pain may not be the only driver of opioid use, multisite regional strategies warrant additional study. Trigeminal nerve block, for instance, has been shown to reduce anesthetic requirements and postoperative opioid use in orthognathic surgery (13). Combining a trigeminal nerve block with PSNB could provide more comprehensive pain control in complex microsurgical reconstruction.

Figure 1 Proposed timeline of popliteal sciatic nerve block with liposomal bupivacaine before surgery.

Cost-benefit considerations for LB remain uncertain as its higher price is justified only if improvements in pain, PONV, and recovery meaningfully reduce downstream resource use, and current cost-savings claims are based primarily on comparisons to catheter-based blocks rather than the single-shot technique used by Wu et al. Moreover, the relatively short follow-up period does not capture the longer-term benefits or drawbacks that might tip this economic balance. Emerging treatment alternatives such as suzetrigine, a potent non-opioid analgesic, may further influence the value of LB by reducing opioid needs without requiring prolonged regional techniques. Larger multicenter studies comparing LB with plain bupivacaine and catheter-based approaches, with longer follow-up and broader patient inclusion, are needed to clarify its true clinical and economic role in perioperative care.

Conclusions

Wu et al. provide important evidence supporting the use of PSNB with LB in maxillofacial reconstruction using a fibula free flap. Although intraoperative opioid use did not change, the block significantly improved sleep and reduced donor-site pain, PONV, and the need for rescue opioids. Future trials should optimize timing, confirm block success, and consider multimodal regional strategies. The LB-based popliteal block represents a valuable tool in opioid-sparing analgesia and should be considered in reconstructive surgery pathways.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Journal of Oral and Maxillofacial Anesthesia. The article has undergone external peer review.

Peer Review File: Available at https://joma.amegroups.com/article/view/10.21037/joma-2025-31/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://joma.amegroups.com/article/view/10.21037/joma-2025-31/coif). A.N. serves as an unpaid editorial board member of Journal of Oral and Maxillofacial Anesthesia from April 2025 to March 2027. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

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