Rosa Klotz1,2, Jan Larmann3, Christina Klose4, Thomas Bruckner4, Laura Benner4, Colette Doerr-Harim2, Solveig Tenckhoff2, Johan F Lock5, Elmar-Marc Brede6, Roberto Salvia7, Enrico Polati8, Jörg Köninger9, Jan-Henrik Schiff10,11, Uwe A Wittel12, Alexander Hötzel13, Tobias Keck14, Carla Nau15, Anca-Laura Amati16, Christian Koch17, Thomas Eberl18, Michael Zink19, Ales Tomazic20, Vesna Novak-Jankovic21, Stefan Hofer3, Markus K Diener1,2, Markus A Weigand3, Markus W Büchler1, Phillip Knebel1,2. 1. Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany. 2. The Study Centre of the German Surgical Society, Heidelberg University Hospital, Heidelberg, Germany. 3. Department of Anaesthesiology, Heidelberg University Hospital, Heidelberg, Germany. 4. Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany. 5. Department of General, Visceral, Transplant, Vascular and Paediatric Surgery, University Hospital of Würzburg, Würzburg, Germany. 6. Department of Anaesthesiology and Critical Care, University Hospital of Würzburg, Würzburg, Germany. 7. Surgical and Oncological Department, Pancreas Institute, University Hospital Trust, Verona, Italy. 8. Department of Anaesthesiology and Intensive Care, Verona University Hospital, Verona, Italy. 9. Department of General, Visceral, Thorax and Transplantation Surgery, Klinikum Stuttgart, Katharinenhospital, Stuttgart, Germany. 10. Department of Anaesthesiology and Operative Intensive Care, Klinikum Stuttgart, Katharinenhospital, Stuttgart, Germany. 11. Department of Anesthesiology and Intensive Care, Philipps-University Marburg, Marburg, Germany. 12. Department of General and Visceral Surgery, Medical Centre, University of Freiburg, Freiburg, Germany. 13. Department of Anaesthesiology and Critical Care, Medical Centre, University of Freiburg, Freiburg, Germany. 14. Department of Surgery, University Medical Centre Schleswig-Holstein, Campus Lübeck, Lübeck, Germany. 15. Department of Anaesthesiology and Intensive Care, University Medical Centre Schleswig-Holstein, Campus Lübeck, Lübeck, Germany. 16. Department of Visceral, Thoracic, Transplant and Paediatric Surgery, Justus Liebig University of Giessen, Giessen, Germany. 17. Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, Justus Liebig University of Giessen, Giessen, Germany. 18. Department of Surgery, General Public Hospital of the Brothers of St John of God, St Veit/Glan, Austria. 19. Department of Anaesthesiology and Intensive Care Medicine, General Public Hospital of the Brothers of St John of God, St Veit/Glan, Austria. 20. Department of Abdominal Surgery, University Medical Centre Ljubljana, Ljubljana, Slovenia. 21. Clinical Department of Anaesthesiology and Intensive Therapy, University Medical Centre Ljubljana, Ljubljana, Slovenia.
Abstract
Importance: Morbidity is still high in pancreatic surgery, driven mainly by gastrointestinal complications such as pancreatic fistula. Perioperative thoracic epidural analgesia (EDA) and patient-controlled intravenous analgesia (PCIA) are frequently used for pain control after pancreatic surgery. Evidence from a post hoc analysis suggests that PCIA is associated with fewer gastrointestinal complications. Objective: To determine whether postoperative PCIA decreases the occurrence of gastrointestinal complications after pancreatic surgery compared with EDA. Design, Setting, and Participants: In this adaptive, pragmatic, international, multicenter, superiority randomized clinical trial conducted from June 30, 2015, to October 1, 2017, 371 patients at 9 European pancreatic surgery centers who were scheduled for elective pancreatoduodenectomy were randomized to receive PCIA (n = 185) or EDA (n = 186); 248 patients (124 in each group) were analyzed. Data were analyzed from February 22 to April 25, 2019, using modified intention to treat and per protocol. Interventions: Patients in the PCIA group received general anesthesia and postoperative PCIA with intravenous opioids with the help of a patient-controlled analgesia device. In the EDA group, patients received general anesthesia and intraoperative and postoperative EDA. Main Outcomes and Measures: The primary end point was a composite of pancreatic fistula, bile leakage, delayed gastric emptying, gastrointestinal bleeding, or postoperative ileus within 30 days after surgery. Secondary end points included 30-day mortality, other complications, postoperative pain levels, intraoperative or postoperative use of vasopressor therapy, and fluid substitution. Results: Among the 248 patients analyzed (147 men; mean [SD] age, 64.9 [10.7] years), the primary composite end point did not differ between the PCIA group (61 [49.2%]) and EDA group (57 [46.0%]) (odds ratio, 1.17; 95% CI, 0.71-1.95 P = .54). Neither individual components of the primary end point nor 30-day mortality, postoperative pain levels, or intraoperative and postoperative substitution of fluids differed significantly between groups. Patients receiving EDA gained more weight by postoperative day 4 than patients receiving PCIA (mean [SD], 4.6 [3.8] vs 3.4 [3.6] kg; P = .03) and received more vasopressors (46 [37.1%] vs 31 [25.0%]; P = .04). Failure of EDA occurred in 23 patients (18.5%). Conclusions and Relevance: This study found that the choice between PCIA and EDA for pain control after pancreatic surgery should not be based on concerns regarding gastrointestinal complications because the 2 procedures are comparable with regard to effectiveness and safety. However, EDA was associated with several shortcomings. Trial Registration: German Clinical Trials Register: DRKS00007784.
Importance: Morbidity is still high in pancreatic surgery, driven mainly by gastrointestinal complications such as pancreatic fistula. Perioperative thoracic epidural analgesia (EDA) and patient-controlled intravenous analgesia (PCIA) are frequently used for pain control after pancreatic surgery. Evidence from a post hoc analysis suggests that PCIA is associated with fewer gastrointestinal complications. Objective: To determine whether postoperative PCIA decreases the occurrence of gastrointestinal complications after pancreatic surgery compared with EDA. Design, Setting, and Participants: In this adaptive, pragmatic, international, multicenter, superiority randomized clinical trial conducted from June 30, 2015, to October 1, 2017, 371 patients at 9 European pancreatic surgery centers who were scheduled for elective pancreatoduodenectomy were randomized to receive PCIA (n = 185) or EDA (n = 186); 248 patients (124 in each group) were analyzed. Data were analyzed from February 22 to April 25, 2019, using modified intention to treat and per protocol. Interventions: Patients in the PCIA group received general anesthesia and postoperative PCIA with intravenous opioids with the help of a patient-controlled analgesia device. In the EDA group, patients received general anesthesia and intraoperative and postoperative EDA. Main Outcomes and Measures: The primary end point was a composite of pancreatic fistula, bile leakage, delayed gastric emptying, gastrointestinal bleeding, or postoperative ileus within 30 days after surgery. Secondary end points included 30-day mortality, other complications, postoperative pain levels, intraoperative or postoperative use of vasopressor therapy, and fluid substitution. Results: Among the 248 patients analyzed (147 men; mean [SD] age, 64.9 [10.7] years), the primary composite end point did not differ between the PCIA group (61 [49.2%]) and EDA group (57 [46.0%]) (odds ratio, 1.17; 95% CI, 0.71-1.95 P = .54). Neither individual components of the primary end point nor 30-day mortality, postoperative pain levels, or intraoperative and postoperative substitution of fluids differed significantly between groups. Patients receiving EDA gained more weight by postoperative day 4 than patients receiving PCIA (mean [SD], 4.6 [3.8] vs 3.4 [3.6] kg; P = .03) and received more vasopressors (46 [37.1%] vs 31 [25.0%]; P = .04). Failure of EDA occurred in 23 patients (18.5%). Conclusions and Relevance: This study found that the choice between PCIA and EDA for pain control after pancreatic surgery should not be based on concerns regarding gastrointestinal complications because the 2 procedures are comparable with regard to effectiveness and safety. However, EDA was associated with several shortcomings. Trial Registration: German Clinical Trials Register: DRKS00007784.
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