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Renal Perfusion, Filtration and Oxygenation After Liver Transplantation -Effects of av Postoperative Blood Pressure

Primary Purpose

Acute Kidney Injury, Liver Failure

Status
Completed
Phase
Not Applicable
Locations
Sweden
Study Type
Interventional
Intervention
Alternating mean arterial pressure
Norepinephrine
Chromium ethylenediaminetetraacetic acid
Sponsored by
Sahlgrenska University Hospital, Sweden
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Kidney Injury focused on measuring Acute kidney injury, Liver transplantation, Postoperative care, Glomerular filtration rate, Renal blood flow, Vasopressor, Norepinephrine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Uncomplicated liver transplantation
  • Age over 18 years
  • Given informed consent preoperatively

Exclusion Criteria:

  • Veno-venous bypass intraoperatively
  • Uncontrolled postoperative bleeding
  • Circulatory stability without need for vasopressor treatment
  • Pronounced circulatory or respiratory instability

Sites / Locations

  • Sahlgrenska University Hospital, dpt of anesthesiology and intensive care

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

60 mmHg

75 mmHg

90 mmHg

Arm Description

Alternating mean arterial pressure by lowering of the infusion rate of norepinephrine

Alternating mean arterial pressure by adjust of the infusion rate of norepinephrine

Alternating mean arterial pressure by augmentation of the infusion rate of norepinephrine

Outcomes

Primary Outcome Measures

Change in Glomerular filtration rate (ml/min)
Change from baseline 75 mmHg to 60 and 90 mmHg, respectively

Secondary Outcome Measures

Change in Renal blood flow (ml/min)
Measured via retrograde thermodilution catheter placed in renal vein. Change from baseline 75 mmHg to 60 and 90 mmHg, respectively.
Change in Renal oxygen consumption (ml/min)
Blood samples and measurements of blood flow via retrograde thermodilution catheter placed in renal vein. RBF × (CaO2-CrvO2) Change from baseline 75 mmHg to 60 and 90 mmHg, respectively
Change in Filtration fraction (%)
Extraction of Cr-EDTA, blood samples from renal vein catheter. Change from baseline 75 mmHg to 60 and 90 mmHg, respectively.
Change in Renal oxygen supply/demand relationship
Renal oxygen consumption compared to renal oxygen delivery (CaO2-CrvO2/CaO2). Change from baseline 75 mmHg to 60 and 90 mmHg, respectively.

Full Information

First Posted
April 23, 2015
Last Updated
September 26, 2016
Sponsor
Sahlgrenska University Hospital, Sweden
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1. Study Identification

Unique Protocol Identification Number
NCT02455115
Brief Title
Renal Perfusion, Filtration and Oxygenation After Liver Transplantation -Effects of av Postoperative Blood Pressure
Official Title
Renal Perfusion, Filtration and Oxygenation After Liver Transplantation -Effects of av Postoperative Blood Pressure
Study Type
Interventional

2. Study Status

Record Verification Date
September 2016
Overall Recruitment Status
Completed
Study Start Date
January 2015 (undefined)
Primary Completion Date
February 2016 (Actual)
Study Completion Date
February 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sahlgrenska University Hospital, Sweden

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Comparing the effects of MAP 60, 75 and 90 mmHg, respectively, on renal blood flow, glomerular filtration rate and renal oxygen demand in patients with terminal liver failure directly after liver transplantation.
Detailed Description
Patients with terminal liver failure are at risk to develop postoperative acute kidney injury (AKI) after liver transplantation. This is associated with augmented morbidity (CRRT/HD), and mortality. Hypotension perioperatively is a risk factor for the development of postoperative AKI. In the investigators' study, the researchers aim to investigate the importance of the level of mean arterial pressure (MAP) on functional renal parameters directly after liver transplantation. 12 patients will be included after given informed and written consent. Directly after the operation, the patients stay sedated and ventilated, have reached normovolaemia and are in need of vasopressor for adequate blood pressure. MAP is varied using the vasopressor norepinephrine. Central hemodynamics will be measured using arterial catheter, PiCCO and a central vein catheter. Renal data measures (RBF (renal blood flow), RPF (renal plasma flow), FF (filtration fraction), GFR (glomerular filtration rate), RVR (renal vascular resistance), Arterial-renal vein oxygen content difference, RVO2 (renal oxygen consumption), and RO2extr (Renal oxygen extraction)), are conducted via a renal vein thermodilution catheter: A 8-Fr catheter is introduced into the left or right renal vein, via the right femoral vein under fluoroscopic guidance, position being confirmed by venography using ultra-low doses of iohexol. After the collection of blood and urine blanks, an intravenous priming dose of chromium ethylenediaminetetraacetic acid (51Cr-EDTA) is given, followed by an infusion at a constant rate, individualized to BSA and preoperative serum creatinine. Serum 51Cr-EDTA activity from arterial and renal vein blood is measured using a well counter. FF is measured as extraction of Cr-EDTA. After one hour and two control measurements and urine/blood sampling on baseline MAP 75 mmHg, the investigators will randomise to continue to MAP 90 mmHg or 60 mmHg reached by altering the infusion rate of norepinephrine. Measurements, blood sampling and urine collection according to the above description, are performed after 30 min at each level, finishing at 75 mmHg with two control measurements with 30 mins in between.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Kidney Injury, Liver Failure
Keywords
Acute kidney injury, Liver transplantation, Postoperative care, Glomerular filtration rate, Renal blood flow, Vasopressor, Norepinephrine

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
60 mmHg
Arm Type
Experimental
Arm Description
Alternating mean arterial pressure by lowering of the infusion rate of norepinephrine
Arm Title
75 mmHg
Arm Type
Experimental
Arm Description
Alternating mean arterial pressure by adjust of the infusion rate of norepinephrine
Arm Title
90 mmHg
Arm Type
Experimental
Arm Description
Alternating mean arterial pressure by augmentation of the infusion rate of norepinephrine
Intervention Type
Other
Intervention Name(s)
Alternating mean arterial pressure
Other Intervention Name(s)
Norepinephrine
Intervention Description
In normovolemic patients directly after liver transplantation, target mean arterial pressure is altered using norepinephrine according to study protocol.
Intervention Type
Drug
Intervention Name(s)
Norepinephrine
Other Intervention Name(s)
Blood pressure control
Intervention Description
Infusion rate of norepinephrine is raised and lowered, respectively, in order to reach MAP 60, 75 and 90 mmHg in patients already requiring vasopressor for adequate blood pressure control.
Intervention Type
Drug
Intervention Name(s)
Chromium ethylenediaminetetraacetic acid
Other Intervention Name(s)
Infusion of 51Cr-EDTA
Intervention Description
Extraction of 51Cr-EDTA measured for FF and GFR
Primary Outcome Measure Information:
Title
Change in Glomerular filtration rate (ml/min)
Description
Change from baseline 75 mmHg to 60 and 90 mmHg, respectively
Time Frame
60 min at baseline (75 mmHg), 30 min at randomized level 1(either 60 or 90 mmHg), 30 min at randomized level 2 (either 60 or 90 mmHg), 60 min after returning to baseline 75 mmHg again
Secondary Outcome Measure Information:
Title
Change in Renal blood flow (ml/min)
Description
Measured via retrograde thermodilution catheter placed in renal vein. Change from baseline 75 mmHg to 60 and 90 mmHg, respectively.
Time Frame
60 min at baseline (75 mmHg), 30 min at randomized level 1(either 60 or 90 mmHg), 30 min at randomized level 2 (either 60 or 90 mmHg), 60 min after returning to baseline 75 mmHg again
Title
Change in Renal oxygen consumption (ml/min)
Description
Blood samples and measurements of blood flow via retrograde thermodilution catheter placed in renal vein. RBF × (CaO2-CrvO2) Change from baseline 75 mmHg to 60 and 90 mmHg, respectively
Time Frame
60 min at baseline (75 mmHg), 30 min at randomized level 1(either 60 or 90 mmHg), 30 min at randomized level 2 (either 60 or 90 mmHg), 60 min after returning to baseline 75 mmHg again
Title
Change in Filtration fraction (%)
Description
Extraction of Cr-EDTA, blood samples from renal vein catheter. Change from baseline 75 mmHg to 60 and 90 mmHg, respectively.
Time Frame
60 min at baseline (75 mmHg), 30 min at randomized level 1(either 60 or 90 mmHg), 30 min at randomized level 2 (either 60 or 90 mmHg), 60 min after returning to baseline 75 mmHg again
Title
Change in Renal oxygen supply/demand relationship
Description
Renal oxygen consumption compared to renal oxygen delivery (CaO2-CrvO2/CaO2). Change from baseline 75 mmHg to 60 and 90 mmHg, respectively.
Time Frame
60 min at baseline (75 mmHg), 30 min at randomized level 1(either 60 or 90 mmHg), 30 min at randomized level 2 (either 60 or 90 mmHg), 60 min after returning to baseline 75 mmHg again

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Uncomplicated liver transplantation Age over 18 years Given informed consent preoperatively Exclusion Criteria: Veno-venous bypass intraoperatively Uncontrolled postoperative bleeding Circulatory stability without need for vasopressor treatment Pronounced circulatory or respiratory instability
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jenny Skytte Larsson, MD
Organizational Affiliation
Sahlgrenska University Hospital, Sweden
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Sven-Erik Ricksten, Professor
Organizational Affiliation
Sahlgrenska University Hospital, Sweden
Official's Role
Study Chair
Facility Information:
Facility Name
Sahlgrenska University Hospital, dpt of anesthesiology and intensive care
City
Göteborg
State/Province
VGR
ZIP/Postal Code
41345
Country
Sweden

12. IPD Sharing Statement

Citations:
PubMed Identifier
28395663
Citation
Skytte Larsson J, Bragadottir G, Redfors B, Ricksten SE. Renal function and oxygenation are impaired early after liver transplantation despite hyperdynamic systemic circulation. Crit Care. 2017 Apr 11;21(1):87. doi: 10.1186/s13054-017-1675-4.
Results Reference
derived

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Renal Perfusion, Filtration and Oxygenation After Liver Transplantation -Effects of av Postoperative Blood Pressure

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