Intravenous versus epidural analgesia to reduce the incidence of gastrointestinal complications after elective pancreatoduodenectomy (the PAKMAN trial, DRKS 00007784): study protocol for a randomized controlled trial

Abstract

BackgroundDespite substantial improvements in surgical and anesthesiological practices leading to decreased mortality of less than 5 % at high-volume centers, pancreatic surgery is still associated with high morbidity rates of up to 50 %. Attention is increasingly directed toward the optimization of perioperative management to reduce complications and enhance postoperative recovery. Currently, two different strategies for postoperative pain management after pancreatoduodenectomy are being routinely used: patient-controlled intravenous analgesia and thoracic epidural analgesia. Evidence is lacking to assess which strategy entails fewer postoperative complications.Methods/designThe PAKMAN trial is designed as an adaptive, pragmatic, randomized, controlled, multicenter, open-label, superiority trial with two parallel study groups. A total of 370 patients scheduled for elective pancreatoduodenectomy will be randomized after giving written informed consent, and 278 patients are needed for analysis. Patients with chronic pancreatitis, severe chronic obstructive pulmonary disease (COPD), American Society of Anesthesiologists (ASA) physical status classification ≥ IV, or chronic pain syndrome will be excluded. The group A intervention includes intraoperative general anesthesia and postoperative patient-controlled intravenous analgesia; the group B intervention comprises combined intraoperative general anesthesia and epidural analgesia with postoperative epidural analgesia. The primary endpoint of this trial is a composite of the gastrointestinal complications (delayed gastric emptying, pancreatic fistula, biliary leak, gastrointestinal bleeding, and postoperative ileus) up to postoperative day 30. The aim is to investigate whether the frequency of gastrointestinal complications following pancreatoduodenectomy can be reduced by 15 % using postoperative, patient-controlled intravenous analgesia compared with epidural analgesia.DiscussionSeveral previous studies investigating the two different strategies for postoperative pain management have mainly focused on their effectiveness in pain control. However, the PAKMAN trial is the first to compare them with regard to their impact on the surgical endpoint “postoperative gastrointestinal complications” after pancreatoduodenectomy.Trial registrationGerman Clinical Trials Register, DRKS00007784Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1306-4) contains supplementary material, which is available to authorized users.

Surgical approach and the impact of epidural analgesia on survival after esophagectomy for cancer: A population-based retrospective cohort study

“…[47] Nonetheless, an ongoing study comparing epidural analgesia to intravenous patient-controlled analgesia for pancreatoduodenectomy demonstrates that randomized controlled trials comparing alternative approaches in acute pain management are possible. [48]…”

Meta‐analysis of epidural analgesia in patients undergoing pancreatoduodenectomy

“…There are two ongoing RCTs comparing EA with intravenous morphine 43 and with intravenous hydromorphone 44 , designed to determine how analgesic technique influences the incidence of complications and mortality after pancreatoduodenectomy. It will be interesting to see how the increasing use of minimally invasive surgery will influence indications for analgesic techniques 45 .…”

Gastrointestinal Complications After Pancreatoduodenectomy With Epidural vs Patient-Controlled Intravenous Analgesia

“…The trial was conducted from June 30, 2015, to October 1, 2017, in 9 centers for pancreatic surgery located in Germany (n = 6), Austria (n = 1), Slovenia (n = 1), and Italy (n = 1). Detailed information about inclusion and exclusion criteria as well as trial visits is provided in the trial protocol . After providing written informed consent, adult patients scheduled to undergo elective partial pancreatoduodenectomy were included unless they had known chronic pancreatitis, chronic pain syndrome, severe chronic obstructive pulmonary disease (Global Initiative for Chronic Obstructive Lung Disease stage≥III), American Society of Anesthesiologists status IV or more, or any contraindication to the use of PCIA or EDA .…”

“…After providing written informed consent, adult patients scheduled to undergo elective partial pancreatoduodenectomy were included unless they had known chronic pancreatitis, chronic pain syndrome, severe chronic obstructive pulmonary disease (Global Initiative for Chronic Obstructive Lung Disease stage≥III), American Society of Anesthesiologists status IV or more, or any contraindication to the use of PCIA or EDA . The PAKMAN trial protocol and other relevant documents were approved by the independent ethics committee of all participating institutions (Ethikkommission der Medizinischen Fakultät Heidelberg, Comitato Etico delle Province di Verona e Rovigo, Ethikkommission der Landesärztekammer Baden-Württemberg, Ethikkommission der Albert-Ludwigs-Universität Freiburg, Ethikkommission der Universität zu Lübeck, Ethikkommission am Fachbereich Medizin der Justus-Liebig Universität Gießen, Ethikkommission des Landes Kärnten, Komisija za medicinsko etiko [KME], rebublika slovenija, ministrstvo za sdravje) (trial protocol in Supplement 1). The trial was conducted in accordance with the ethical principles of the Declaration of Helsinki and the principles of Good Clinical Practice .…”