Volume Kinetics for Starch Solution and Acetated Ringers

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Volume Kinetics for Starch Solution and Acetated Ringers

Conditions
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Blood Volume, Blood Coagulation

Intervention / Treatment
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* Drug: acetated Ringers
* Drug: colloid
* Drug: colloid+acetated Ringer
* Device: Non-invasive hemoglobin with pulse-oximeter (SpHb)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: A.acetatedRingers, B.colloid & C.colloid+acetatedRingers<br>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<br>* Infusion of Ringer acetate 20 ml/kg over 30 min<br>Drug: colloid<br>* Infusion of starch 10 ml/kg over 30 min<br>* Other names: Voluven;Drug: colloid+acetated Ringer<br>* 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.<br>* Other names: acetated Ringers;Device: Non-invasive hemoglobin with pulse-oximeter (SpHb)<br>* Non-invasive hemoglobin with pulse-oximeter (SpHb) was measured in all subjects, during all infusions.<br>* Other names: Radical 7, Masimo;|
| Other: A.colloid, B.colloid+acetatedRinger & C.acetatedRingers<br>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<br>* Infusion of Ringer acetate 20 ml/kg over 30 min<br>Drug: colloid<br>* Infusion of starch 10 ml/kg over 30 min<br>* Other names: Voluven;Drug: colloid+acetated Ringer<br>* 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.<br>* Other names: acetated Ringers;Device: Non-invasive hemoglobin with pulse-oximeter (SpHb)<br>* Non-invasive hemoglobin with pulse-oximeter (SpHb) was measured in all subjects, during all infusions.<br>* Other names: Radical 7, Masimo;|
| Other: A.acetatedRingers, B.acetatedRingers+colloid & C.colloid<br>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<br>* Infusion of Ringer acetate 20 ml/kg over 30 min<br>Drug: colloid<br>* Infusion of starch 10 ml/kg over 30 min<br>* Other names: Voluven;Drug: colloid+acetated Ringer<br>* 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.<br>* Other names: acetated Ringers;Device: Non-invasive hemoglobin with pulse-oximeter (SpHb)<br>* Non-invasive hemoglobin with pulse-oximeter (SpHb) was measured in all subjects, during all infusions.<br>* Other names: Radical 7, Masimo;|
| Other: A.colloid, B.acetatedRingers & C.colloid+acetatedRingers<br>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<br>* Infusion of Ringer acetate 20 ml/kg over 30 min<br>Drug: colloid<br>* Infusion of starch 10 ml/kg over 30 min<br>* Other names: Voluven;Drug: colloid+acetated Ringer<br>* 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.<br>* Other names: acetated Ringers;Device: Non-invasive hemoglobin with pulse-oximeter (SpHb)<br>* Non-invasive hemoglobin with pulse-oximeter (SpHb) was measured in all subjects, during all infusions.<br>* Other names: Radical 7, Masimo;|
| Other: A.colloid+acetatedRingers, B.colloid & C.acetated Ringers<br>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<br>* Infusion of Ringer acetate 20 ml/kg over 30 min<br>Drug: colloid<br>* Infusion of starch 10 ml/kg over 30 min<br>* Other names: Voluven;Drug: colloid+acetated Ringer<br>* 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.<br>* Other names: acetated Ringers;Device: Non-invasive hemoglobin with pulse-oximeter (SpHb)<br>* Non-invasive hemoglobin with pulse-oximeter (SpHb) was measured in all subjects, during all infusions.<br>* Other names: Radical 7, Masimo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Volume Effects for Hydroxyethyl Starch, Ringer's Solution or a Combination of Both. | 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. | 420 minutes | 
| Elimination Half Life for Different Fluids Alone or When Combined | Volume kinetic analyses of the dilution of hemoglobin for different infusion fluids alone or in combination. | 420 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Accuracy of Non-invasive Hemoglobin Monitoring for Different Fluids | 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). | 420 min | 
| Accuracy of Noninvasive Haemoglobin Measurement by Pulse Oximetry, for Different Fluids (Start to End of Infusion) | 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 | 30 min | 
| Variation of Coagulation Factors and Plasma Proteins During and After Infusion of Crystalloid and Colloid Solutions. | 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. | 420 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Blood volume, blood coagulation, volume kinetics