Argipressin's Influence on Blood Loss During Hepatic Resection
- Conditions
- Vasopressin Causing Adverse Effects in Therapeutic UseColon Cancer Liver MetastasisInflammatory Response
- Interventions
- Drug: Placebo
- Registration Number
- NCT05293041
- Lead Sponsor
- Kristina Svennerholm
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 248
- Participant planned for hepatic resection (open or laparoscopic, regardless of indication for surgery).
- Age ≥18 years.
- ASA class I-III.
- Signed informed consent form
- Participant does not understand the given information, and/ or cannot give written informed consent.
- Simultaneous operation of tumor with other localization, or surgery for superficial single hepatic tumor less than 2 cm, expected to be of short duration and with minimal blood loss.
- Terminal kidney failure (estimated preoperative GFR< 15 ml/min)
- Pregnancy or lactation.
- Known allergy to Empressin®.
- Patient included in other interventional study, interacting with the endpoints in the present study, or previous randomization in this study.
- Hyponatremia (S-Na < 130 mmol/L)
- Patient considered ineligible for other surgical or medical reason.
- Present infection. Patients with systemic inflammatory disease, inflammatory bowel disease or preoperative corticosteroid treatment will not be eligible for the subgroups where cytokines and interleukins are investigated.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Patients will receive normal saline 0.056 ml/kg/h during surgery. Argipressin Argipressin Patients will be treated with Empressin® 0.8 U/ml, 0.056 ml/kg/h during surgery.
- Primary Outcome Measures
Name Time Method Blood loss through surgery, an average of 8 hours 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.
- Secondary Outcome Measures
Name Time Method Blood transfusion At end of surgery and until postoperative day 2 or 5 respectively Blood transfusion (ml) at the end of surgery and at postoperative day 1 and 2 and 5 respectively.
Inflammatory markers-regular Measured throughout the study until postoperative day 2 (laparoscopic resection) or postoperative day 5 (open resection) Levels of White Blood Cell count, C Reactive Protein, Platelet count and Albumin at the end of surgery and postoperative day 1-5
I-FABP (change in organ damage markers) from baseline to postoperative day 1 Change in I-FABP (ng/L)
surgical data at the end of surgery, approximately 5 hours after start of surgery duration of Pringles manouvre (min), duration of resection phase (min) and surgery (min)
Noradrenaline use (anesthesiologigal data) during surgery Total use of noradrenaline (micrograms/minutes of surgery/ bodyweight)
use of diuretics until postoperative day 1 Furosemide use (mg)
Inflammatory markers- extended Measured at throughout the study until postoperative day 2. 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.
Lactate (change in organ damage markers) from baseline to postoperative day 1 change in plasma lactate
CVP (anesthesiological data) during surgery achievement of CVP (central venous pressure) goal (mmHg), as recorded on the Phillips monitor.
urine output until postoperative day 1 urine output (ml)
Length of stay From admission in hospital to discharge, expected time 2-5 days but will be followed until actual discharge, which may be several months. Length of stay in hospital
Cardiac marker (change in organ damage markers) from baseline to postoperative day 1 Change in hs- TNI (ng/L)
postoperative complications 30 days after surgery Postoperative complications including death and radicality of resection at 30-day follow up.
Plasma Creatinine (change in organ damage markers) from baseline (before surgery) to postoperative day 2 and 5 respectively. Change in plasma creatinine (micro-mole/L)
Urine samples (change in organ damage markers) from baseline to end of surgery, approximately 5 hours Change in urine creatinine and urine \[TIMP-2\] x \[IGFBP-7\] (quota, no unit)
Tranexamic Acid at the end of surgery, approximately 5 hours after start of surgery use of tranexamic acid (mg)
Trial Locations
- Locations (1)
Sahlgrenska University Hospital
🇸🇪Gothenburg, Sweden
Sahlgrenska University Hospital🇸🇪Gothenburg, Sweden