Response to two invited commentaries on ‘Paravertebral versus EPidural Analgesia in Minimally Invasive Esophageal resectioN (PEPMEN): A Randomized Controlled Multicenter Trial’

We appreciate the insightful commentaries by Dr. Andrew Owen and Dr. Kurt Ruetzler on our manuscript on paravertebral versus epidural analgesia in minimally invasive esophagectomy (MIE) (1). Their perspectives on the use of these analgesia modalities in MIE provide valuable insights into the feasibility and benefits of paravertebral analgesia while also recognizing potential challenges and directions for future research. In this response, we aim to expand upon their discussions by addressing key aspects related to the use of paravertebral analgesia in MIE.

As highlighted in both commentaries and our study, esophagectomy presents unique challenges due to its combined thoracic and abdominal components. This results in greater tissue trauma compared to lung resection, where previous research has shown similar analgesic outcomes between paravertebral and epidural analgesia (2). In addition, esophagectomy involves abdominal manipulation and intestinal anastomosis leading to visceral postoperative abdominal pain.

Our PEPMEN trial not only demonstrates that paravertebral analgesia is a viable option with potentially fewer adverse effects, including a non-significantly lower anastomotic leakage rate (6.1% versus 13.8%, P=0.828), than epidural analgesia, but it also challenges conventional approaches encouraging both the surgical and anesthesiology communities to rethink pain management in MIE (1). This represents a step forward toward patient-centered, evidence-based care. Furthermore, we agree that its implications go beyond the operating room, especially as healthcare increasingly prioritizes enhanced recovery pathways, minimizing opioid use and promoting early mobilization. With its favorable risk-benefit profile, paravertebral analgesia presents a strong alternative for institutions aiming to optimize postoperative care in MIE (3).

Nevertheless, both commentaries explore potential modifications or additions to the paravertebral analgesia regimen to enhance its effectiveness. One proposed modification is the use of programmed intermittent bolus delivery instead of continuous infusion within the paravertebral space to improve the spread of local anesthetics (4). A previous randomized, controlled, double-blind trial in patients undergoing video-assisted thoracic surgery demonstrated that programmed intermittent paravertebral boluses of levobupivacaine provided a wider dermatomal spread of sensory block compared to continuous paravertebral infusion with an identical hourly dose of levobupivacaine (5). This suggests that intermittent boluses may improve the distribution of local anesthetics, potentially optimizing the analgesic effect of paravertebral blockade, which may also be beneficial in MIE.

Additionally, both commentaries address the challenge of abdominal pain and suggest incorporating a subcostal transversus abdominis plane (TAP) block (4), or alternative techniques such as the quadratus lumborum block (3). In our daily practice, abdominal wound pain appears to be less of an issue, whereas the most significant pain often originates from the thoracic wound created for specimen removal. However, combining paravertebral analgesia with a subcostal TAP block may help reduce morphine consumption and pain severity in MIE (6). Future research should further explore these modifications—both the shift to intermittent bolus delivery and the addition of regional blocks—not only to assess their efficacy but also to evaluate the potential toxicity of increased local anesthetic use.

We completely agree with the suggestion by Ruetzler et al. to standardize opioid administration for more accurate comparisons of analgesic outcomes. This point was already acknowledged in the trial’s discussion section.

Finally, long-term outcomes for patients recovering from esophagectomy, particularly concerning chronic pain and quality of life, remain insufficiently explored in relation to analgesia modality. Various factors—such as preoperative quality of life, postoperative complications, and post-surgical anti-cancer treatments—significantly influence these outcomes, making it difficult to directly attribute them to a specific analgesic approach. Nevertheless, further research into the potential long-term benefits of different analgesic strategies is a valuable step toward refining pain management and improving overall patient outcomes. Of note is that after completion of the trial, all participating centers have now implemented paravertebral analgesia in MIE as their standard of care with very satisfying results.

In conclusion, the discussions outlined above are essential for advancing patient care. We are pleased that our PEPMEN trial confirms the feasibility of paravertebral analgesia in clinical practice, providing a solid foundation for its broader implementation. Rather than questioning its viability, the focus can now shift toward refining and optimizing its use.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, AME Surgery Journal. The article did not undergo external peer review.

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://asj.amegroups.com/article/view/10.21037/asj-25-39/coif). The authors report that the PEPMEN trial was funded by ZonMw (The Netherlands Organization for Health Research and Development, project number 852002004); however, this funding is separate from the current work. M.I.v.B.H. reports consulting or advisory roles for Viatris, Johnson & Johnson, BBraun, Stryker, and Medtronic. R.v.H. reports consulting or advisory roles for Intuitive Surgical, Ethicon, Medtronic and Olympus. The authors have no other 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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3. Khudirat M, Ruetzler K. PEPMEN Trial: Redefining Pain Management in Minimally Invasive Esophageal Surgery. AME Surg J 2025;5:13.
4. Alshahrani M, Costescu F, Owen A. Can video-guided paravertebral block replace thoracic epidural analgesia in minimally invasive esophagectomy? AME Surg J 2025;5:5. [Crossref]
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6. Li NL, Liu CC, Cheng SH, et al. Feasibility of combined paravertebral block and subcostal transversus abdominis plane block in postoperative pain control after minimally invasive esophagectomy. Acta Anaesthesiol Taiwan 2013;51:103-7. [Crossref] [PubMed]