Thoracic Epidural Analgesia Is Not Associated With Improved Survival After Pancreatic Surgery: Long-Term Follow-Up of the Randomized Controlled PAKMAN Trial

Rosa Klotz; Azaz Ahmed; Anja Tremmel; Christopher Büsch; Solveig Tenckhoff; Colette Doerr-Harim; Johan F Lock; Elmar-Marc Brede; Jörg Köninger; Jan-Henrik Schiff; Uwe A Wittel; Alexander Hötzel; Tobias Keck; Carla Nau; Anca-Laura Amati; Christian Koch; Markus K Diener; Markus A Weigand; Markus W Büchler; Phillip Knebel; Jan Larmann

doi:10.1213/ANE.0000000000006812

Thoracic Epidural Analgesia Is Not Associated With Improved Survival After Pancreatic Surgery: Long-Term Follow-Up of the Randomized Controlled PAKMAN Trial

Anesth Analg. 2024 Feb 9. doi: 10.1213/ANE.0000000000006812. Online ahead of print.

Authors

Rosa Klotz^{1

2}, Azaz Ahmed^{3

4}, Anja Tremmel⁵, Christopher Büsch⁶, Solveig Tenckhoff², Colette Doerr-Harim⁷, Johan F Lock⁸, Elmar-Marc Brede⁹, Jörg Köninger¹⁰, Jan-Henrik Schiff^{11

12}, Uwe A Wittel¹³, Alexander Hötzel¹⁴, Tobias Keck¹⁵, Carla Nau¹⁶, Anca-Laura Amati¹⁷, Christian Koch¹⁸, Markus K Diener¹³, Markus A Weigand⁵, Markus W Büchler¹, Phillip Knebel¹, Jan Larmann⁵

Affiliations

¹ From the Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany.
² The Study Center of the German Surgical Society, Heidelberg University Hospital, Heidelberg, Germany.
³ Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg, Germany.
⁴ Translational Immunotherapy, German Cancer Research Center, Heidelberg, Germany.
⁵ Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany.
⁶ Institute of Medical Biometry, University of Heidelberg, Heidelberg, Germany.
⁷ Department of General Surgery, University of Ulm, Ulm, Germany.
⁸ Department of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital of Würzburg, Würzburg, Germany.
⁹ General Medicine, Gemeinschaftspraxis für Allgemeinmedizin, Veitshöchheim, Germany.
¹⁰ Department of General, Visceral, Thorax and Transplantation Surgery, Stuttgart, Germany.
¹¹ Department of Anesthesiology, Intensive Care Medicine, Emergency Medicine and Pain Therapy, Stuttgart, Germany.
¹² Department of Anesthesiology and Intensive Care, Philipps-University Marburg, Marburg, Germany.
¹³ Department of General and Visceral Surgery, Medical Centre, University of Freiburg, Freiburg, Germany.
¹⁴ Department of Anesthesiology and Critical Care, Medical Centre, University of Freiburg, Freiburg, Germany.
¹⁵ Department of Surgery, University Medical Centre Schleswig-Holstein, Campus Lübeck, Germany.
¹⁶ Department of Anesthesiology and Intensive Care, University Medical Centre Schleswig-Holstein, Campus Lübeck, Germany.
¹⁷ Department of Visceral, Thoracic, Transplant and Pediatric Surgery, Justus Liebig University of Giessen, Giessen, Germany.
¹⁸ Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, Justus Liebig University of Giessen, Giessen, Germany.

PMID: 38335141
DOI: 10.1213/ANE.0000000000006812

Abstract

Background: Perioperative thoracic epidural analgesia (EDA) and patient-controlled intravenous analgesia (PCIA) are common forms of analgesia after pancreatic surgery. Current guidelines recommend EDA over PCIA, and evidence suggests that EDA may improve long-term survival after surgery, especially in cancer patients. The aim of this study was to determine whether perioperative EDA is associated with an improved patient prognosis compared to PCIA in pancreatic surgery.

Methods: The PAKMAN trial was an adaptive, pragmatic, international, multicenter, randomized controlled superiority trial conducted from June 2015 to October 2017. Three to five years after index surgery a long-term follow-up was performed from October 2020 to April 2021.

Results: For long-term follow-up of survival, 109 patients with EDA were compared to 111 patients with PCIA after partial pancreatoduodenectomy (PD). Long-term follow-up of quality of life (QoL) and pain assessment was available for 40 patients with EDA and 45 patients with PCIA (questionnaire response rate: 94%). Survival analysis revealed that EDA, when compared to PCIA, was not associated with improved overall survival (OS, HR, 1.176, 95% HR-CI, 0.809-1.710, P = .397, n = 220). Likewise, recurrence-free survival did not differ between groups (HR, 1.116, 95% HR-CI, 0.817-1.664, P = .397, n = 220). OS subgroup analysis including only patients with malignancies showed no significant difference between EDA and PCIA (HR, 1.369, 95% HR-CI, 0.932-2.011, P = .109, n = 179). Similar long-term effects on QoL and pain severity were observed in both groups (EDA: n = 40, PCIA: n = 45).

Conclusions: Results from this long-term follow-up of the PAKMAN randomized controlled trial do not support favoring EDA over PCIA in pancreatic surgery. Until further evidence is available, EDA and PCIA should be considered similar regarding long-term survival.