Volume Kinetics for 20% Albumin in Different Clinical Situations (Albumin)

Volume Kinetics for 20% Albumin in Conscious and Anesthetized Humans With and Without Inflammation

The study aims to determine the degree of plasma volume expansion and the half-life of the plasma volume expansion when 3 mL/kg of hyperoncotic (20%) albumin if infused over 30 minutes in conscious healthy volunteers, in patients undergoing surgery under general anesthesia, and on the day after major surgery when the patient is in a post surgical inflammatory state. The study also examines the increase in the plasma colloid osmotic pressure as a result of this infusion and its possible influence on markers of kidney damage.

Study Overview

• Status: Unknown
• Conditions: Inflammation; Unconscious
• Intervention / Treatment: Drug: Albumin 20%

Detailed Description

15 volunteers, 15 patients undergoing surgery and 15 patients in the post-surgical phase will be recruited for this study because they have different degrees of vasodilatation and inflammation, which are factors of potential importance to the effectiveness of plasma volume expansion with albumin 20%. Hyperoncotic albumin should logically recruit fluid from the interstitial fluid space, but this possibility has recently been questioned in the "revised Starling equation".

The degree of plasma volume expansion and also the half-life will be estimated by population volume kinetics which uses serial analyses of the blood hemoglobin concentration and a summary measure of the excreted urine during the 5-hour experiment to calculate these outcome measures.

There is a risk that hyperoncotic solutions cause pre-renal anuria due to the rise in plasma oncotic pressure. As a safety measure we will assess the plasma oncotic pressure and relevant biomarkers of renal function during the experiments. The experiments will be ended with a slow infusion of 1 L of Ringer´s acetate to dilute any raised oncotic pressure.

• Study Type: Interventional
• Enrollment (Anticipated): 45
• Phase: Phase 4

Contacts and Locations

Study Locations

• Sweden
  • Linköping, Sweden, 581 85
    • Recruiting
    • Linköping University Hospital
    • Contact: Joachim Zdolsek, MD, PhD; Phone Number: 0046 70 3031434; Email: joachim.zdolsek@regionostergotland.se
  • Stockholm, Sweden, 171 64
    • Completed
    • Karolinska University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy volunteers.
• Patients in ASA classes I-II scheduled for surgery.

Exclusion Criteria:

• Expected major hemorrhage during surgery.
• Blood hemoglobin concentration of < 10 g/dL.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Conscious healthy volunteers; Intervention: intravenious infusion Drug: albumin 20%	Drug: Albumin 20%; Intervention: intravenious infusion Drug: albumin; Other Names: Albumin in healthy volunteers
Experimental: Surgery under general anesthesia; Intervention: intravenious infusion Drug: albumin 20%	Drug: Albumin 20%; Intervention: intravenious infusion Drug: albumin; Other Names: Albumin in healthy volunteers
Experimental: Post-surgical inflammation; Intervention: intravenious infusion Drug: albumin 20%	Drug: Albumin 20%; Intervention: intravenious infusion Drug: albumin; Other Names: Albumin in healthy volunteers

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Degree of plasma volume expansion	Calculated by volume kinetics	5 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Increase in plasma oncotic pressure	Measured by oncometer	5 hours
Possible effect on biomarkers of kidney injury	Urinary albumin excretion (unit: mmol of albumin per mmol of urinary creatinine) and urinary neutrophil gelatinase-associated lipocalin (NGAL) excretion (unit: µg/L per mmol of creatinine).	5 hours
Half-life of plasma volume expansion	Calculated from the restoration of the diluted blood hemoglobnin concentration	5 hours

Collaborators and Investigators

• Sponsor: Sodertalje Hospital
• Collaborators: Karolinska University Hospital; University Hospital, Linkoeping
• Investigators: Principal Investigator: Robert G Hahn, MD, PhD, Research Director, Södertälje sjukhus

Publications and helpful links

General Publications

• Hedin A, Hahn RG. Volume expansion and plasma protein clearance during intravenous infusion of 5% albumin and autologous plasma. Clin Sci (Lond). 2005 Mar;108(3):217-24. doi: 10.1042/CS20040303.
• Woodcock TM, Woodcock TE. Revised Starling equation predicts pulmonary edema formation during fluid loading in the critically ill with presumed hypovolemia. Crit Care Med. 2012 Sep;40(9):2741-2; author reply 2742. doi: 10.1097/CCM.0b013e31825ae6c9. No abstract available.
• Wiedermann CJ, Dunzendorfer S, Gaioni LU, Zaraca F, Joannidis M. Hyperoncotic colloids and acute kidney injury: a meta-analysis of randomized trials. Crit Care. 2010;14(5):R191. doi: 10.1186/cc9308. Epub 2010 Oct 28.
• Gunnstrom M, Zdolsek JH, Hahn RG. Plasma Volume Expansion and Fluid Kinetics of 20% Albumin During General Anesthesia and Surgery Lasting for More Than 5 Hours. Anesth Analg. 2022 Jun 1;134(6):1270-1279. doi: 10.1213/ANE.0000000000005802. Epub 2021 Nov 18.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2016
• Primary Completion (Anticipated): December 31, 2018
• Study Completion (Anticipated): April 1, 2019

Study Registration Dates

• First Submitted: May 24, 2015
• First Submitted That Met QC Criteria: September 21, 2015
• First Posted (Estimate): September 22, 2015

Study Record Updates

• Last Update Posted (Actual): March 20, 2018
• Last Update Submitted That Met QC Criteria: March 19, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: surgery; albumin; inflammation; volume kinetics
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation
• Other Study ID Numbers: Albumin April 2015

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: When the study is completed.
• IPD Sharing Time Frame: Data from the volunteer and postoperative patients are available in March 2018. The intraoperative patients are still being recruited
• IPD Sharing Access Criteria: Contact the Project Leader
• IPD Sharing Supporting Information Type: Study Protocol; Informed Consent Form (ICF); Clinical Study Report (CSR)