title: The effect of intraoperative and 6-h postoperative intravenous administration of low-dose prostacyclin on the endothelium, hemostasis, and hemodynamics in patients undergoing a pancreaticoduodenoctemy: a randomized-controlled pilot study.
abstract: BACKGROUND
  Capillary leakage, secondary to endothelial breakdown, is common in patients undergoing major surgical procedures with extensive tissue injury and this is associated with increased morbidity and mortality. Prostacyclin has been ascribed cytoprotective properties together with its vasodilatory and antiplatelet effects. The present pilot study investigated the safety and endothelial protective effects of low-dose prostacyclin infusion.
  
  
  METHODS
  A randomized placebo-controlled pilot study evaluating the effect of prostacyclin (iloprost) infusion (1.0 ng/kg/min) versus placebo (saline infusion) intraoperatively and 6 h postoperatively in patients undergoing a pancreaticoduodenoctemy was carried out. Hemodynamics were evaluated by Nexfin, hemostasis was evaluated by thrombelastography, and transfusion requirements were registered. Endothelial damage was evaluated by circulating sE-selectin, soluble thrombomodulin, and nucleosomes.
  
  
  RESULTS
  Comparable baseline demography and surgical time were found. Hemodynamics were comparable between groups. The placebo group received more red blood cells, median 115 ml [interquartile range (IQR): 0-296 ml] versus 0 ml (IQR: 0-0 ml), P=0.027, at the postoperative ward and after 6 h. Thrombelastography maximum clot firmness decreased intraoperatively only in the placebo group (P=0.034)). Soluble thrombomodulin increased more in the placebo group postoperatively [1.63 ng/ml (IQR: 0.65-2.55 ng/ml) versus 0.40 ng/ml (IQR: 0.21-0.63 ng/ml), P=0.027] and 6 h postoperatively [1.83 (1.1-2.36) versus 0.67 (0.42-0.91), P=0.027]. Nucleosomes increased intraoperatively and postoperatively only in the placebo group; thus, the overall level of nucleosomes was higher in the placebo group (P=0.019).
  
  
  CONCLUSIONS
  Intraoperative and postoperative low-dose prostacyclin infusion is safe and associated with reduced endothelial cell damage in patients undergoing a pancreaticoduodenoctemy compared with those receiving placebo.
authors.affiliation: aDepartment of Surgery, University of Texas Health Medical School, Houston, Texas, USA bCapital Region Blood Bank Departments of cAnaesthesiology, Abdominal Centre dAnaesthesia, Centre of Head and Orthopedics eSurgical Gastroenterology, Rigshospitalet, University Hospital of Copenhagen, Denmark.
authors.forename: Pär I
authors.initials: PI
authors.lastname: Johansson
authors.forename: Christian R
authors.initials: CR
authors.lastname: Mortensen
authors.forename: Tatiana
authors.initials: T
authors.lastname: Nielsen
authors.forename: Carsten
authors.initials: C
authors.lastname: Tollund
authors.forename: Jakob
authors.initials: J
authors.lastname: Stensballe
authors.forename: Carsten P
authors.initials: CP
authors.lastname: Hansen
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Frederiksen
authors.forename: Sisse R
authors.initials: SR
authors.lastname: Ostrowski
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001803:Blood Transfusion / Q000379:methods; D019610:Cytoprotection; D004334:Drug Administration Schedule; D004379:Duodenal Neoplasms / Q000601:surgery; D004730:Endothelium, Vascular / Q000187:drug effects*; D011464:Epoprostenol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005440:Fluid Therapy / Q000379:methods; D006439:Hemodynamics / Q000187:drug effects*; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000601:surgery; D016577:Pancreaticoduodenectomy / Q000379:methods*; D019990:Perioperative Care / Q000379:methods; D010865:Pilot Projects; D013916:Thrombelastography / Q000379:methods
chemical_list: D015415:Biomarkers; D011464:Epoprostenol