Albumin Mass Balance in Liver Transplantation

NCT ID: NCT03441035

Last Updated: 2020-09-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

200 participants

Study Classification

OBSERVATIONAL

Study Start Date

2018-03-27

Study Completion Date

2021-06-30

Brief Summary

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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

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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.

Conditions

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Liver Transplant; Complications Fluid Overload

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Adults, uncomplicated

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.

General anesthesia and surgery (liver transplantation)

Intervention Type OTHER

The effects of general anesthesia and surgery under the hospital routine of albumin administration during and after liver transplantation is studied with the mass balance of albumin method.

Adults, complicated

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.

General anesthesia and surgery (liver transplantation)

Intervention Type OTHER

The effects of general anesthesia and surgery under the hospital routine of albumin administration during and after liver transplantation is studied with the mass balance of albumin method.

Children

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.

General anesthesia and surgery (liver transplantation)

Intervention Type OTHER

The effects of general anesthesia and surgery under the hospital routine of albumin administration during and after liver transplantation is studied with the mass balance of albumin method.

Interventions

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General anesthesia and surgery (liver transplantation)

The effects of general anesthesia and surgery under the hospital routine of albumin administration during and after liver transplantation is studied with the mass balance of albumin method.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

All patients undergoing liver transplantation are eligible

Exclusion Criteria

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

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ake Norberg

OTHER

Sponsor Role lead

Responsible Party

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Ake Norberg

Associate professor, Senior Consultant

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Åke Norberg, Ass Prof

Role: PRINCIPAL_INVESTIGATOR

Perioperative Medicine and Intensive Care, Karolinska University Hospital Huddinge

Locations

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Karolinska University Hospital, Huddinge

Huddinge, , Sweden

Site Status RECRUITING

Countries

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Sweden

Central Contacts

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Åke Norberg, Ass Prof

Role: CONTACT

+46739661152

Facility Contacts

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Åke Norberg, MD PhD

Role: primary

+46739661152

References

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Fleck A, Raines G, Hawker F, Trotter J, Wallace PI, Ledingham IM, Calman KC. Increased vascular permeability: a major cause of hypoalbuminaemia in disease and injury. Lancet. 1985 Apr 6;1(8432):781-4. doi: 10.1016/s0140-6736(85)91447-3.

Reference Type BACKGROUND
PMID: 2858667 (View on PubMed)

Norberg A, Rooyackers O, Segersvard R, Wernerman J. Leakage of albumin in major abdominal surgery. Crit Care. 2016 Apr 26;20(1):113. doi: 10.1186/s13054-016-1283-8.

Reference Type BACKGROUND
PMID: 27117323 (View on PubMed)

Ballmer PE, McNurlan MA, Milne E, Heys SD, Buchan V, Calder AG, Garlick PJ. Measurement of albumin synthesis in humans: a new approach employing stable isotopes. Am J Physiol. 1990 Dec;259(6 Pt 1):E797-803. doi: 10.1152/ajpendo.1990.259.6.E797.

Reference Type BACKGROUND
PMID: 2260648 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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4-3344/2017

Identifier Type: OTHER

Identifier Source: secondary_id

K2017-4774

Identifier Type: -

Identifier Source: org_study_id

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