Volume Kinetics for Starch Solution and Acetated Ringers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Joachim Zdolsek, University Hospital, Linkoeping
ClinicalTrials.gov Identifier:
NCT01195025
First received: August 31, 2010
Last updated: October 16, 2014
Last verified: October 2014
  Purpose

Volume kinetics is a method mostly used, so far, to study the distribution and elimination of crystalloid solutions. Voluven (in Sweden the most commonly used colloid for replacement of bleeding during surgery) is poorly studied, though. Also, a recent study showed unexpected volume kinetics for a crystalloid solution when it was given after a colloid solution. The investigators aim to study the volume kinetics of crystalloids and colloids and also the combination of the two in more detail. The investigators will also compare the invasive hemoglobin measurements with measurements from a new non-invasive tool (Radical 7, from Masimo Inc.) which could help to make volume kinetics more practical for everyday use. Finally the investigators will also study the concentrations of a few coagulation factors to see if they can explain the variations in coagulability that has been described in earlier studies of infusion solutions.


Condition Intervention
Blood Volume
Blood Coagulation
Drug: acetated Ringers
Drug: colloid
Drug: colloid+acetated Ringer
Device: Non-invasive hemoglobin with pulse-oximeter (SpHb)

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Volume Kinetics for Starch Solution and Acetated Ringers

Resource links provided by NLM:


Further study details as provided by University Hospital, Linkoeping:

Primary Outcome Measures:
  • Volume Effects for Hydroxyethyl Starch, Ringer's Solution or a Combination of Both. [ Time Frame: 420 minutes ] [ Designated as safety issue: No ]

    volume kinetics: mathematical calculation from hemoglobin variations during and after an infusion.

    Degree of plasma dilution depending on which solution(s) and how much solution is/are given.


  • Elimination Half Life for Different Fluids Alone or When Combined [ Time Frame: 420 minutes ] [ Designated as safety issue: No ]
    Volume kinetic analyses of the dilution of hemoglobin for different infusion fluids alone or in combination.


Secondary Outcome Measures:
  • Accuracy of Non-invasive Hemoglobin Monitoring for Different Fluids [ Time Frame: 420 min ] [ Designated as safety issue: No ]

    Pulse-oximeter based measurements compared with invasive hemoglobin measurements. All paired in the study.

    Accuracy depending on which infusion is selected (Ringer's, Hydroxyethyl starch or a combination of both).


  • Accuracy of Noninvasive Haemoglobin Measurement by Pulse Oximetry, for Different Fluids (Start to End of Infusion) [ Time Frame: 30 min ] [ Designated as safety issue: No ]

    Difference between true hemoglobin B-Hb and measured hemoglobin with pulseoximeter (SpHb)at the end of an infusion in relation to the initial measured values SpHb and B-Hb at the start of the infusion.

    Relative difference (%) = (SpHb - Hb)/((Hb+SpHb)/2) x 100


  • Variation of Coagulation Factors and Plasma Proteins During and After Infusion of Crystalloid and Colloid Solutions. [ Time Frame: 420 minutes ] [ Designated as safety issue: No ]
    The investigators will measure a few markers of coagulation (fibrinogen, thrombocytes, D-Dimer, PK-INR, aPTT, and coagulation factor VII) as well as Cystatin C, serum albumine and hemoglobin and how the concentration of these vary with the different dilutions of blood during and after infusion of a colloid and/or a crystalloid solution.


Enrollment: 10
Study Start Date: August 2010
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
A.acetatedRingers, B.colloid & C.colloid+acetatedRingers

First intervention: A. acetated Ringers 20 ml/kg bodyweight during 30 minutes followed by 150 minutes of equilibration, when blood samples were collected.

Washout >7 days

Second intervention: B. Voluven 6 % (starch solution) 10 ml/kg bodyweight during 30 minutes followed by 390 minutes of equilibration and blood samples.

Washout > 7 Days

Third intervention: C. Voluven 6 % (starch solution) 10 ml/kg bodyweight during 30 minutes followed 90 minutes later by acetated Ringers 20 ml/kg bodyweight during 30 minutes. thereafter the subjects stayed for Another 285 minutes of equilibration and blood samples.

Drug: acetated Ringers
Infusion of Ringer acetate 20 ml/kg over 30 min
Other Name: acetated Ringers
Drug: colloid
Infusion of starch 10 ml/kg over 30 min
Other Name: Voluven
Drug: colloid+acetated Ringer
Infusion of combined colloid+acetated Ringer; 10 ml/kg of starch was infused between 0 and 30 min, followed by 20 ml/kg of Ringers acetate between 105 and 135 min.
Other Names:
  • Voluven
  • acetated Ringers
Device: Non-invasive hemoglobin with pulse-oximeter (SpHb)
Non-invasive hemoglobin with pulse-oximeter (SpHb) was measured in all subjects, during all infusions.
Other Name: Radical 7, Masimo
A.colloid, B.colloid+acetatedRinger & C.acetatedRingers

First intervention: A. Voluven 6 % (starch solution) 10 ml/kg bodyweight during 30 minutes followed by 390 minutes of equilibration and blood samples.

Washout >7 days

Second intervention: B. Voluven 6 % (starch solution) 10 ml/kg bodyweight during 30 minutes followed 90 minutes later by acetated Ringers 20 ml/kg bodyweight during 30 minutes. thereafter the subjects stayed for Another 285 minutes of equilibration and blood samples.

Washout > 7 Days

Third intervention: C. acetated Ringers 20 ml/kg bodyweight during 30 minutes followed by150 minutes of equilibration, when blood samples were collected.

Drug: acetated Ringers
Infusion of Ringer acetate 20 ml/kg over 30 min
Other Name: acetated Ringers
Drug: colloid
Infusion of starch 10 ml/kg over 30 min
Other Name: Voluven
Drug: colloid+acetated Ringer
Infusion of combined colloid+acetated Ringer; 10 ml/kg of starch was infused between 0 and 30 min, followed by 20 ml/kg of Ringers acetate between 105 and 135 min.
Other Names:
  • Voluven
  • acetated Ringers
Device: Non-invasive hemoglobin with pulse-oximeter (SpHb)
Non-invasive hemoglobin with pulse-oximeter (SpHb) was measured in all subjects, during all infusions.
Other Name: Radical 7, Masimo
A.acetatedRingers, B.acetatedRingers+colloid & C.colloid

First intervention: A. acetated Ringers 20 ml/kg bodyweight during 30 minutes followed by150 minutes of equilibration, when blood samples were collected.

Washout >7 days

Second intervention: B.Voluven 6 % (starch solution) 10 ml/kg bodyweight during 30 minutes followed 90 minutes later by acetated Ringers 20 ml/kg bodyweight during 30 minutes. thereafter the subjects stayed for Another 285 minutes of equilibration and blood samples.

Washout > 7 Days

Third intervention: C. Voluven 6 % (starch solution) 10 ml/kg bodyweight during 30 minutes followed by 390 minutes of equilibration and blood samples.

Drug: acetated Ringers
Infusion of Ringer acetate 20 ml/kg over 30 min
Other Name: acetated Ringers
Drug: colloid
Infusion of starch 10 ml/kg over 30 min
Other Name: Voluven
Drug: colloid+acetated Ringer
Infusion of combined colloid+acetated Ringer; 10 ml/kg of starch was infused between 0 and 30 min, followed by 20 ml/kg of Ringers acetate between 105 and 135 min.
Other Names:
  • Voluven
  • acetated Ringers
Device: Non-invasive hemoglobin with pulse-oximeter (SpHb)
Non-invasive hemoglobin with pulse-oximeter (SpHb) was measured in all subjects, during all infusions.
Other Name: Radical 7, Masimo
A.colloid, B.acetatedRingers & C.colloid+acetatedRingers

First intervention: A. Voluven 6 % (starch solution) 10 ml/kg bodyweight during 30 minutes followed by 390 minutes of equilibration and blood samples.acetated Ringers 20 ml/kg bodyweight during 30 minutes followed by150 minutes of equilibration, when blood samples were collected.

Washout >7 days

Second intervention: B. acetated Ringers 20 ml/kg bodyweight during 30 minutes followed by150 minutes of equilibration, when blood samples were collected.

Washout > 7 Days

Third intervention: C. Voluven 6 % (starch solution) 10 ml/kg bodyweight during 30 minutes followed 90 minutes later by acetated Ringers 20 ml/kg bodyweight during 30 minutes. thereafter the subjects stayed for Another 285 minutes of equilibration and blood samples.

Drug: acetated Ringers
Infusion of Ringer acetate 20 ml/kg over 30 min
Other Name: acetated Ringers
Drug: colloid
Infusion of starch 10 ml/kg over 30 min
Other Name: Voluven
Drug: colloid+acetated Ringer
Infusion of combined colloid+acetated Ringer; 10 ml/kg of starch was infused between 0 and 30 min, followed by 20 ml/kg of Ringers acetate between 105 and 135 min.
Other Names:
  • Voluven
  • acetated Ringers
Device: Non-invasive hemoglobin with pulse-oximeter (SpHb)
Non-invasive hemoglobin with pulse-oximeter (SpHb) was measured in all subjects, during all infusions.
Other Name: Radical 7, Masimo
A.colloid+acetatedRingers, B.colloid & C.acetated Ringers

First intervention: A. Voluven 6 % (starch solution) 10 ml/kg bodyweight during 30 minutes followed 90 minutes later by acetated Ringers 20 ml/kg bodyweight during 30 minutes. thereafter the subjects stayed for Another 285 minutes of equilibration and blood samples.

Washout >7 days

Second intervention: B. Voluven 6 % (starch solution) 10 ml/kg bodyweight during 30 minutes followed by 390 minutes of equilibration and blood samples.

Washout > 7 Days

Third intervention: C. acetated Ringers 20 ml/kg bodyweight during 30 minutes followed by150 minutes of equilibration, when blood samples were collected.

Drug: acetated Ringers
Infusion of Ringer acetate 20 ml/kg over 30 min
Other Name: acetated Ringers
Drug: colloid
Infusion of starch 10 ml/kg over 30 min
Other Name: Voluven
Drug: colloid+acetated Ringer
Infusion of combined colloid+acetated Ringer; 10 ml/kg of starch was infused between 0 and 30 min, followed by 20 ml/kg of Ringers acetate between 105 and 135 min.
Other Names:
  • Voluven
  • acetated Ringers
Device: Non-invasive hemoglobin with pulse-oximeter (SpHb)
Non-invasive hemoglobin with pulse-oximeter (SpHb) was measured in all subjects, during all infusions.
Other Name: Radical 7, Masimo

Detailed Description:

We will study ten volunteers, each one on three occasions. Each volunteer will receive only crystalloid one time, only colloid another time, and on the third occasion first a colloid and then a crystalloid one hour later. The different protocols will be in random order in the different volunteers. During all these tests we will sample the hemoglobin (both invasive and non-invasive) every fifth minute in the beginning (every tenth minute later) after the infusion. On six to nine occasions during each test we will analyse Albumin, Cystatin-C, Ig-G, Ig-M as markers of hemodilution and D-Dimer, Fibrinogen, Factor VII, PK-INR (prothrombin complex international normalized ratio), and aPTT (activated partial thromboplastin time) as markers of coagulation. The volunteers are also monitored regarding non-invasive blood pressure and pulse rate.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria: healthy males between 20 and 50 years were advertised for. Males due to simplified urine collection during supine position.

Exclusion Criteria:

under age < 18 years

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01195025

Locations
Sweden
University Hospital, Intensive care unit
Linköping, Sweden, 581 85
Sponsors and Collaborators
University Hospital, Linkoeping
Investigators
Principal Investigator: Joachim Zdolsek, MD, PhD University Hospital, Linköping, Sweden
  More Information

No publications provided by University Hospital, Linkoeping

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Joachim Zdolsek, MD, PhD, University Hospital, Linkoeping
ClinicalTrials.gov Identifier: NCT01195025     History of Changes
Other Study ID Numbers: VkVR
Study First Received: August 31, 2010
Results First Received: March 12, 2014
Last Updated: October 16, 2014
Health Authority: Sweden: Regional Ethical Review Board

Keywords provided by University Hospital, Linkoeping:
Blood volume
blood coagulation
volume kinetics

Additional relevant MeSH terms:
Pharmaceutical Solutions
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014