Albumin Mass Balance in Liver Transplantation

• Conditions: Liver Transplant; Complications; Fluid Overload
• Interventions: Other: General anesthesia and surgery (liver transplantation)

• Registration Number: NCT03441035
• Lead Sponsor: Ake Norberg

Brief Summary

This clinical observational cohort study assess the loss of albumin from blood circulation during and after liver transplantation by mass balance of albumin. The overall assumption of this method is that if albumin is more diluted than hemoglobin, it must have left the plasma, presumably into the interstitial space. Predictors of albumin leakage will be assessed, including biomarkers of inflammation and of endothelial damage and dysfunction. The sub cohorts children and patients with complications, defined as prolonged postoperative treatment in the intensive care unit, respectively, will be focused in separate publications.

Detailed Description

Background Capillary leakage has been recognized to be associated with surgery and inflammation \[Fleck 1985\]. In liver transplantation considerable amounts of exogenous albumin is administered to support circulatory stability and a post operative plasma albumin concentration of 25 g/L to facilitate interpretation of immuno suppressive drug concentrations. However, the long term effects of exogenous albumin is not well characterized in the literature, and extravasation might promote edema formation and impair wound healing. In previous studies we have demonstrated the ability of the albumin mass balance method to identify leakage of albumin in major abdominal surgery \[Norberg 2016\].

In a pilot study in patients undergoing liver transplantation (n=11) we found a net leakage of albumin from plasma of 37 ± 17 g at end of surgery and 48 ± 33 g at postoperative day 3.

The primary aim of the new study is to find if this net leakage is still there at postoperative day 7. We are also looking into predictors of positive albumin shift from plasma including markers of inflammation and endothelial injury or dysfunction. Focus will also be put on the subgroup of children during and after liver transplantation. Finally a subgroup of patients in need of prolonged ICU stay after liver transplantation will be investigated to see the prolonged effects of our present routines, and these patients ability to synthetize albumin.

All patients undergoing liver transplantation at Karolinska University Hospital are eligible.

Recruitment will be made in advance as soon as patients are put on the transplant waiting list. In adults, at the day of surgery, blood samples will be taken repeatedly for estimation of plasma albumin. In all patients we will keep track of any gains or losses of albumin or hemoglobin in suction bottles, drains, exogenous blood products, exogenous albumin etc. This sampling will proceed during the study period that will end at hospital discharge or not later than post-operative day 21. Adult patients that are still in the ICU on postoperative day 3 will be subjected to a measurement of albumin synthesis rate by the flooding method \[Ballmer 1993\]. All subjects, even children, will have blood sampled for ELISAs of markers of inflammation and endothelial injury or dysfunction.

Total study specific blood sampling will be limited to 100 mL in adults and 6 mL in children.

Study Timeline

• Study First Submitted: 2018-02-15
• Study First Submitted QC: 2018-02-15
• Study First Posted: 2018-02-22
• Study Start: 2018-03-27
• Status Verified: 2020-09
• Last Update Submitted: 2020-09-02
• Last Update Posted: 2020-09-03
• Primary Completion: 2021-02-28
• Study Completion: 2021-06-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

All patients undergoing liver transplantation are eligible

Exclusion Criteria

No consent Unability to understand the study information (language or consciousness)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Children	General anesthesia and surgery (liver transplantation)	Children undergoing liver transplantation. Mass balance of albumin will be undertaken by sampling of albumin in in all fluids that is infused or lost from the body to keep track of albumin and hemoglobin changes until postoperative day 7. P-albumin and B-Hb is only taken routinely and not study specific samples. Plasma for ELISAs is taken at 2-3 time points.
Adults, complicated	General anesthesia and surgery (liver transplantation)	Adults undergoing liver transplantation. Mass balance of albumin will be undertaken by sampling of albumin in plasma and in all fluids that is infused or lost from the body to keep track of albumin and hemoglobin changes until hospital discharge or postoperative day 21. B-Hb is taken routinely and not study specific samples. Plasma for ELISAs is taken at 2-3 time points. A infusion of deuterium labeled phenylalanine will be given in the ICU at 1-3 occasions to determine the synthesis rate of albumin.
Adults, uncomplicated	General anesthesia and surgery (liver transplantation)	Adults undergoing liver transplantation. Mass balance of albumin will be undertaken by sampling of albumin in plasma and in all fluids that is infused or lost from the body to keep track of albumin and hemoglobin changes until postoperative day 7. B-Hb is taken routinely and not study specific samples. Plasma for ELISAs is taken at 2-3 time points.

Primary Outcome Measures

Name	Time	Method
Cumulative perioperative shift of albumin	Post-operative day 7 after liver transplantation	By mass balance of albumin (i.e keeping track of all gains and losses of albumin and compare these to hemoglobin) it is possible to estimate the loss of albumin from plasma that is not explained by losses in bleeding or drains.

Secondary Outcome Measures

Name	Time	Method
Predictors of prolonged need for ICU stay	from pre-operative risk assessment until post-operative day 21	anthropometric and laboratory values including markers of inflammation and endothelial injury or dysfunction will be analyzed by regression analysis to Patients in need or not in need of prolonged ICU treatment
Albumin synthesis rate	postoperative days 3-21 after liver transplantation	By deuterium labeled phenylalanine it is possible to assess albumin synthesis rate by the "flooding technique"
Cumulative perioperative shift of albumin in children	during and after liver transplantation until postoperative day 21	By mass balance of albumin (i.e keeping track of all gains and losses of albumin and compare these to hemoglobin) it is possible to estimate the loss of albumin from plasma that is not explained by losses in bleeding or drains.
Predictors of cumulative perioperative shift of albumin	from pre-operative risk assessment until post-operative day 7	anthropometric and laboratory values including markers of inflammation and endothelial injury or dysfunction will be analyzed by regression analysis to cumulative perioperative shift of albumin

Trial Locations

Locations (1)

Karolinska University Hospital, Huddinge; 🇸🇪 Huddinge, Sweden