An interventional study of acetated Ringers and colloid in Blood Volume and Blood Coagulation, sponsored by University Hospital, Linkoeping. Completed at 1 site in Sweden. Open to male participants aged 18 Years to 50 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2014-10-22.
Sponsored by University Hospital, Linkoeping · Not applicable, Interventional, and Treatment
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.
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.
University Hospital, Linkoeping is the lead sponsor of 118 studies on the registry; 16 are open to participants now.
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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
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 · Drug: colloid · Drug: colloid+acetated Ringer · Device: Non-invasive hemoglobin with pulse-oximeter (SpHb)
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 · Drug: colloid · Drug: colloid+acetated Ringer · Device: Non-invasive hemoglobin with pulse-oximeter (SpHb)
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 · Drug: colloid · Drug: colloid+acetated Ringer · Device: Non-invasive hemoglobin with pulse-oximeter (SpHb)
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 · Drug: colloid · Drug: colloid+acetated Ringer · Device: Non-invasive hemoglobin with pulse-oximeter (SpHb)
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 · Drug: colloid · Drug: colloid+acetated Ringer · Device: Non-invasive hemoglobin with pulse-oximeter (SpHb)
Infusion of Ringer acetate 20 ml/kg over 30 min
Infusion of starch 10 ml/kg over 30 min
Also known as: Voluven
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.
Also known as: Voluven, acetated Ringers
Non-invasive hemoglobin with pulse-oximeter (SpHb) was measured in all subjects, during all infusions.
Also known as: Radical 7, Masimo
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.
Time frame: 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.
Time frame: 420 minutes
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).
Time frame: 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
Time frame: 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.
Time frame: 420 minutes
10 Healthy male volunteers 18 to 50 years old
| Milestone | A. Acetated Ringers, B.Colloid and C. Colloid+Acetated Ringers | A. Colloid, B. Colloid+Acetated Ringers and C.Acetated Ringers | A. Acetated Ringers, B. Colloid+Acetated Ringers and C.Colloid | A.Colloid, B. Acetated Ringers and C. Colloid+Acetated Ringers | A. Colloid+Acetated Ringers, B.Colloid and C. Acetated Ringers |
|---|---|---|---|---|---|
| Started | 2 | 3 | 2 | 2 | 1 |
| Completed | 2 | 3 | 2 | 2 | 1 |
| Not completed | 0 | 0 | 0 | 0 | 0 |
| Milestone | A. Acetated Ringers, B.Colloid and C. Colloid+Acetated Ringers | A. Colloid, B. Colloid+Acetated Ringers and C.Acetated Ringers | A. Acetated Ringers, B. Colloid+Acetated Ringers and C.Colloid | A.Colloid, B. Acetated Ringers and C. Colloid+Acetated Ringers | A. Colloid+Acetated Ringers, B.Colloid and C. Acetated Ringers |
|---|---|---|---|---|---|
| Started | 2 | 3 | 2 | 2 | 1 |
| Completed | 2 | 3 | 2 | 2 | 1 |
| Not completed | 0 | 0 | 0 | 0 | 0 |
| Milestone | A. Acetated Ringers, B.Colloid and C. Colloid+Acetated Ringers | A. Colloid, B. Colloid+Acetated Ringers and C.Acetated Ringers | A. Acetated Ringers, B. Colloid+Acetated Ringers and C.Colloid | A.Colloid, B. Acetated Ringers and C. Colloid+Acetated Ringers | A. Colloid+Acetated Ringers, B.Colloid and C. Acetated Ringers |
|---|---|---|---|---|---|
| Started | 2 | 3 | 2 | 2 | 1 |
| Completed | 2 | 3 | 2 | 2 | 1 |
| Not completed | 0 | 0 | 0 | 0 | 0 |
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.
| Litre | Hydroxyethyl Starch, Ringers and a Combination of Both. |
|---|---|
| Distribution volume of Acetated Ringers | 5.53 (4.25 to 7.31) |
| Distribution volume for HES 6% | 2.94 (2.65 to 3.31) |
| Distribution vol for HES combined with Ringer's | 3.12 (3.01 to 3.45) |
| Distribution vol for Ringers combined with HES | 4 (3.05 to 4.82) |
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).
| percentage of relative difference | Venous Hemoglobin and Non-invasive Hemoglobin (SpHb) |
|---|---|
| Ringers acetate | -5.3 (-10.4 to 1.5) |
| HES 6% | 0.0 (-6.8 to 4.6) |
| HES 6% + Ringers acetate | 1.5 (-4.9 to 10.9) |
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
| percentage of relative difference | Colloid (Voluven), Acetated Ringers and a Combination of Both. |
|---|---|
| Ringer's acetate | 7 (2.5 to 11.1) |
| Hydroxy ethyl starch 6% | -4.3 (-7.2 to -0.9) |
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.
Results for this outcome have not been posted.
Volume kinetic analyses of the dilution of hemoglobin for different infusion fluids alone or in combination.
| Minutes | Hydroxyethyl Starch, Ringers and a Combination of Both. |
|---|---|
| Elimination half life for Ringer's | 88 (54 to 150) |
| Elimination half life for HES | 116 (87 to 152) |
| Elimination half life for HES (+ Ringer's) | 126 (75 to 150) |
| Elimination half life for Ringer's (+ HES) | 497 (146 to 805) |
Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Colloid-, Acetated Ringers and Combined | — | 0/10 (0%) | 0/10 (0%) |
| Age, Categorical(Participants) | Dilution Effects of iv Fluids |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 10 |
| >=65 years | 0 |
| Age, Continuous(years) | Dilution Effects of iv Fluids |
|---|---|
| Mean | 22 ± 3.4 |
| Sex: Female, Male(Participants) | Dilution Effects of iv Fluids |
|---|---|
| Female | 0 |
| Male | 10 |
| Region of Enrollment(participants) | Dilution Effects of iv Fluids |
|---|---|
| Sweden | 10 |
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University Hospital, Linkoeping