Gastrointestinal Complications After Pancreatoduodenectomy With Epidural vs Patient-Controlled Intravenous Analgesia
Authors: Rosa Klotz, Jan Larmann, Christina Klose, Thomas Bruckner, Laura Benner, Colette Doerr-Harim, Solveig Tenckhoff, Johan F. Lock, Elmar-Marc Brede, Roberto Salvia, Enrico Polati, Jörg Köninger, Jan-Henrik Schiff, Uwe A. Wittel, Alexander Hötzel, Tobias Keck, Carla Nau, Anca-Laura Amati, Christian Koch, Thomas Eberl, Michael Zink, Ales Tomazic, Vesna Novak-Jankovic, Stefan Hofer, Markus K. Diener, Markus A. Weigand, Markus W. Büchler, Phillip Knebel
Journal: JAMA Surgery (2020)

<h3>Importance</h3> 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. <h3>Objective</h3> To determine whether postoperative PCIA decreases the occurrence of gastrointestinal complications after pancreatic surgery compared with EDA. <h3>Design, Setting, and Participants</h3> 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. <h3>Interventions</h3> 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. <h3>Main Outcomes and Measures</h3> 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. <h3>Results</h3> 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<i>P</i> = .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;<i>P</i> = .03) and received more vasopressors (46 [37.1%] vs 31 [25.0%];<i>P</i> = .04). Failure of EDA occurred in 23 patients (18.5%). <h3>Conclusions and Relevance</h3> 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. <h3>Trial Registration</h3> German Clinical Trials Register:DRKS00007784