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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| A.acetatedRingers, B.colloid & C.colloid+acetatedRingers | Other | 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. |
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| A.colloid, B.colloid+acetatedRinger & C.acetatedRingers | Other | 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. |
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| A.acetatedRingers, B.acetatedRingers+colloid & C.colloid | Other | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| acetated Ringers | Drug | Infusion of Ringer acetate 20 ml/kg over 30 min |
|
| 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 |
| 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) |
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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
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| Name | Affiliation | Role |
|---|---|---|
| Joachim Zdolsek, MD, PhD | University Hospital, Linköping, Sweden | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital, Intensive care unit | Linköping | Linköping | 581 85 | Sweden |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33957864 | Derived | Hahn RG, Wuethrich PY, Zdolsek JH. Can perioperative hemodilution be monitored with non-invasive measurement of blood hemoglobin? BMC Anesthesiol. 2021 May 6;21(1):138. doi: 10.1186/s12871-021-01351-4. | |
| 23718743 | Derived | Hahn RG, Bergek C, Geback T, Zdolsek J. Interactions between the volume effects of hydroxyethyl starch 130/0.4 and Ringer s acetate. Crit Care. 2013 May 29;17(3):R104. doi: 10.1186/cc12749. |
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Random crossover study, with at least one week between every study occasion.
10 Healthy male volunteers 18 to 50 years old
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| ID | Title | Description |
|---|---|---|
| FG000 | A. Acetated Ringers, B.Colloid and C. Colloid+Acetated Ringers | 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 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. |
| FG001 | A. Colloid, B. Colloid+Acetated Ringers and C.Acetated Ringers | 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 |
| FG002 | A. Acetated Ringers, B. Colloid+Acetated Ringers and C.Colloid | 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 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. |
| FG003 | A.Colloid, B. Acetated Ringers and C. Colloid+Acetated Ringers | 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. 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. |
| FG004 | A. Colloid+Acetated Ringers, B.Colloid and 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention A |
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| Second Intervention B |
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| Third Intervention C |
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| ID | Title | Description |
|---|---|---|
| BG000 | Dilution Effects of iv Fluids | Three experiments: A. acetated Ringers 20 ml/kg bodyweight during 30 minutes B. Hydroxy ethyl starch (HES) 6% 10 mL/kg bodyweight during 30 min C. A combination of A and B. HES during 0-30 min and Ringer's during 105-135 minutes. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | All the 10 participating subjects. Analysis studying the summary of each of the included infusion occasions. Only acetated Ringers, only colloid and finally a combination of colloid and acetated Ringers. Each experiment generated one distribution volume. (In experiment C one for acetated Ringer's and one for Starch (HES 6%)). | Posted | Median | Inter-Quartile Range | Litre | 420 minutes |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Colloid-, Acetated Ringers and Combined | Voluven, acetated Ringers: Infusions at three different occasions separated by at least one week. A. acetated Ringers 25 ml/kg bodyweight during 30 minutes B. Voluven 6 % (starch solution) 10 ml/kg bodyweight during 30 minutes. C. Voluven 6 % (starch solution) 10 ml/kg bodyweight during 30 minutes followed 90 minutes later by acetated Ringers 15 ml/kg bodyweight during 30 minutes. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Joachim Zdolsek | University Hospital Linköping | +46101030000 | joachim.zdolsek@lio.se |
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| ID | Term |
|---|---|
| D013927 | Thrombosis |
| ID | Term |
|---|---|
| D016769 | Embolism and Thrombosis |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D003102 | Colloids |
| C485123 | HES 130-0.4 |
| ID | Term |
|---|---|
| D045424 | Complex Mixtures |
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |
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| A.colloid, B.acetatedRingers & C.colloid+acetatedRingers | Other | 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. |
|
| A.colloid+acetatedRingers, B.colloid & C.acetated Ringers | Other | 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. |
|
| colloid | Drug | Infusion of starch 10 ml/kg over 30 min |
|
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| colloid+acetated Ringer | Drug | 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. |
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| Non-invasive hemoglobin with pulse-oximeter (SpHb) | Device | Non-invasive hemoglobin with pulse-oximeter (SpHb) was measured in all subjects, during all infusions. |
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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 |
| 23303244 | Derived | Bergek C, Zdolsek JH, Hahn RG. Accuracy of noninvasive haemoglobin measurement by pulse oximetry depends on the type of infusion fluid. Eur J Anaesthesiol. 2013 Feb;30(2):73-9. doi: 10.1097/EJA.0b013e3283592733. |
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| 23047301 | Derived | Bergek C, Zdolsek JH, Hahn RG. Accuracy of noninvasive haemoglobin measurement by pulse oximetry depends on the type of infusion fluid. Eur J Anaesthesiol. 2012 Dec;29(12):586-92. doi: 10.1097/EJA.0b013e3283592733. |
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| Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Secondary | 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). | The study was analysed per protocol and missing values were not replaced. All pairs of all collected data in one series of experiments. The number of analysed data points for each subject was in experiment A: 26, in experiment B: 32 and in experiment C: 42. | Posted | Median | Inter-Quartile Range | percentage of relative difference | 420 min | Hemoglobin measurements (pairs) | Participants |
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| Secondary | 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 | Only the pure experiments were included in this analysis. The combined experiment is not included since infusions were performed in sequence, which made the comparison of the bias for the two different fluids irrelevant. | Posted | Median | Inter-Quartile Range | percentage of relative difference | 30 min | SpHb - B-Hgb | Participants |
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| Secondary | 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. | Not Posted | May 2015 | 420 minutes |
| Primary | 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. | All the 10 participating subjects. Analysis studying the summary of each of the included infusion occasions. Only acetated Ringers, only colloid and finally a combination of colloid and acetated Ringers. Each experiment generated one elimination half-life (In experiment C one for acetated Ringer's and one for starch (HES 6%)). | Posted | Median | Inter-Quartile Range | Minutes | 420 minutes | Infusion protocols | Participants |
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| 0 |
| 10 |
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| 10 |
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| Title | Measurements |
|---|---|
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| Elimination half life for Ringer's (+ HES) |
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