title: 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: BACKGROUND
  Despite 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
  The 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.
  
  
  CONCLUSIONS
  Several 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.
  
  
  BACKGROUND
  German Clinical Trials Register, DRKS00007784.
authors.affiliation: Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany.|The Study Center of the German Surgical Society (SDGC), Heidelberg University Hospital, Im Neuenheimer Feld 130.3, 69120, Heidelberg, Germany.
authors.forename: Rosa
authors.initials: R
authors.lastname: Klotz
authors.affiliation: Department of Anesthesia, Heidelberg University Hospital, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hofer
authors.affiliation: Department of Anesthesia, Intensive Care and Emergency Medicine, Red Cross Hospital Kassel, Hansteinstrasse 29, 34121, Kassel, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Schellhaaß
authors.affiliation: The Study Center of the German Surgical Society (SDGC), Heidelberg University Hospital, Im Neuenheimer Feld 130.3, 69120, Heidelberg, Germany.
authors.forename: Colette
authors.initials: C
authors.lastname: Dörr-Harim
authors.affiliation: The Study Center of the German Surgical Society (SDGC), Heidelberg University Hospital, Im Neuenheimer Feld 130.3, 69120, Heidelberg, Germany.
authors.forename: Solveig
authors.initials: S
authors.lastname: Tenckhoff
authors.affiliation: Institute of Medical Biometry and Informatics, University of Heidelberg, Im Neuenheimer Feld 130.3, 69120 Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bruckner
authors.affiliation: Institute of Medical Biometry and Informatics, University of Heidelberg, Im Neuenheimer Feld 130.3, 69120 Heidelberg, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Klose
authors.affiliation: Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany.|The Study Center of the German Surgical Society (SDGC), Heidelberg University Hospital, Im Neuenheimer Feld 130.3, 69120, Heidelberg, Germany.
authors.forename: Markus K
authors.initials: MK
authors.lastname: Diener
authors.affiliation: Department of Anesthesia, Heidelberg University Hospital, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany.
authors.forename: Markus A
authors.initials: MA
authors.lastname: Weigand
authors.affiliation: Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany.
authors.forename: Markus W
authors.initials: MW
authors.lastname: Büchler
authors.affiliation: Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany. phillip.knebel@med.uni-heidelberg.de.|The Study Center of the German Surgical Society (SDGC), Heidelberg University Hospital, Im Neuenheimer Feld 130.3, 69120, Heidelberg, Germany. phillip.knebel@med.uni-heidelberg.de.
authors.forename: Phillip
authors.initials: P
authors.lastname: Knebel
mesh_terms: D061605:Administration, Intravenous; D015360:Analgesia, Epidural / Q000009:adverse effects / Q000379:methods*; D016058:Analgesia, Patient-Controlled / Q000009:adverse effects / Q000379:methods*; D002985:Clinical Protocols; D017558:Elective Surgical Procedures; D005767:Gastrointestinal Diseases / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D005858:Germany; D006801:Humans; D010149:Postoperative Pain / Q000209:etiology / Q000517:prevention & control*; D016577:Pancreaticoduodenectomy / Q000009:adverse effects*; D012107:Research Design; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
keywords: Epidural analgesia; Pancreatoduodenectomy; Patient-controlled intravenous analgesia; Postoperative complication; Postoperative pain management; Randomized controlled trial