Infusion of Argipressin during hepatic resection surgery may reduce blood loss. It may also reduce transfusion requirements, and mitigate the perioperative inflammatory response compared to placebo. Subjects will be randomized to infusion of Argipressin or placebo during surgery. Blood loss, transfusion requirements, surgical data including length of stay in hsopital, inflammatory markers and markers of renal- intestinal- and cardiac injury will be assessed. Two sub-studies has been added; one for evaluation of coagulation function, and one for assessment of pain scores and morphine consumption.
Hepatic resection is a major surgical intervention with high risk of substantial blood loss. The surgical means to reduce blood loss may impair perfusion and induce intestinal congestion. If blood flow to the liver can be influenced by pharmacological means, blood loss and transfusion requirements may be reduced. Moreover, the inflammatory system is involved in cancer development, and the anti-inflammatory properties of Argipressin may decrease the inflammatory response after hepatic surgery. Argipressin is an endogenous substance, and part of the body's response to stress and trauma. Argipressin affects V1-receptors to produce vasoconstriction. It is also involved in inflammatory reactions and affects platelets. Patients will be stratified according to planned type of surgery (open/laparoscopic) and planned extent of resection, and randomized to etiher infusion of Argipressin or placebo (normal saline) during surgery. In all other aspects, the participants will be treated according to the institution protocol for hepatic resection. The study drug will be started as soon as the central line is placed, and discontinued at the end of surgery. Hemodynamic data will be collected during surgery, and blood and urine-samples will be obtained during and after surgery for analysis of inflammatory markers and markers of organ injury.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
248
Infusion of Argipressin 0.8 U/ml, 0.056 ml/kg/h will be started as soon as the central line is placed, and continued until the end of surgery in the treatment arm.
Infusion of Normal Saline 0.056 ml/kg/h will be started as soon as the central line is placed, and continued until the end of surgery in the placebo arm.
Sahlgrenska University Hospital
Gothenburg, Sweden
Blood loss
Blood loss at the end of surgery, measured according to the investigator's instructions, by visual assessment of suction devises and gauze, and subtraction of ascites and irrigation fluids.
Time frame: through surgery, an average of 8 hours
Blood transfusion
Blood transfusion (ml) at the end of surgery and at postoperative day 1 and 2 and 5 respectively.
Time frame: At end of surgery and until postoperative day 2 or 5 respectively
Inflammatory markers-regular
Levels of White Blood Cell count, C Reactive Protein, Platelet count and Albumin at the end of surgery and postoperative day 1-5
Time frame: Measured throughout the study until postoperative day 2 (laparoscopic resection) or postoperative day 5 (open resection)
Inflammatory markers- extended
Levels of Interleukin (IL)-1 Beta, IL-6, IL-8, IL-10, Monocyte chemoattractant protein-1, Stromal Cell-Derived Factor-1 alpha, Intercellular Adhesion Molecule, Complement (C) 3a, C5b-9 at the end of surgery and postoperative day 1 and 2.
Time frame: Measured at throughout the study until postoperative day 2.
surgical data
duration of Pringles manouvre (min), duration of resection phase (min) and surgery (min)
Time frame: at the end of surgery, approximately 5 hours after start of surgery
Tranexamic Acid
use of tranexamic acid (mg)
Time frame: at the end of surgery, approximately 5 hours after start of surgery
CVP (anesthesiological data)
achievement of CVP (central venous pressure) goal (mmHg), as recorded on the Phillips monitor.
Time frame: during surgery
Noradrenaline use (anesthesiologigal data)
Total use of noradrenaline (micrograms/minutes of surgery/ bodyweight)
Time frame: during surgery
use of diuretics
Furosemide use (mg)
Time frame: until postoperative day 1
urine output
urine output (ml)
Time frame: until postoperative day 1
postoperative complications
Postoperative complications including death and radicality of resection at 30-day follow up.
Time frame: 30 days after surgery
Length of stay
Length of stay in hospital
Time frame: From admission in hospital to discharge, expected time 2-5 days but will be followed until actual discharge, which may be several months.
Plasma Creatinine (change in organ damage markers)
Change in plasma creatinine (micro-mole/L)
Time frame: from baseline (before surgery) to postoperative day 2 and 5 respectively.
Urine samples (change in organ damage markers)
Change in urine creatinine and urine \[TIMP-2\] x \[IGFBP-7\] (quota, no unit)
Time frame: from baseline to end of surgery, approximately 5 hours
Cardiac marker (change in organ damage markers)
Change in hs- TNI (ng/L)
Time frame: from baseline to postoperative day 1
Lactate (change in organ damage markers)
change in plasma lactate
Time frame: from baseline to postoperative day 1
I-FABP (change in organ damage markers)
Change in I-FABP (ng/L)
Time frame: from baseline to postoperative day 1
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