Blood Volume, Blood Coagulation
Conditions
Keywords
Blood volume, blood coagulation, volume kinetics
Brief summary
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
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.
Interventions
DRUGacetated Ringers
Infusion of Ringer acetate 20 ml/kg over 30 min
DRUGcolloid
Infusion of starch 10 ml/kg over 30 min
DRUGcolloid+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.
DEVICENon-invasive hemoglobin with pulse-oximeter (SpHb)
Non-invasive hemoglobin with pulse-oximeter (SpHb) was measured in all subjects, during all infusions.
Sponsors
University Hospital, Linkoeping
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Volume Effects for Hydroxyethyl Starch, Ringer's Solution or a Combination of Both. | 420 minutes | 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 | 420 minutes | Volume kinetic analyses of the dilution of hemoglobin for different infusion fluids alone or in combination. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Accuracy of Non-invasive Hemoglobin Monitoring for Different Fluids | 420 min | 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) | 30 min | 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. | 420 minutes | 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. |
Countries
Sweden
Participant flow
Recruitment details
10 Healthy male volunteers 18 to 50 years old
Pre-assignment details
Random crossover study, with at least one week between every study occasion.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Dilution Effects of iv Fluids |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Age, Continuous | 22 years STANDARD_DEVIATION 3.4 |
| Region of Enrollment Sweden | 10 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
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.
Time frame: 420 minutes
Population: 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%)).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Hydroxyethyl Starch, Ringers and a Combination of Both. | Elimination Half Life for Different Fluids Alone or When Combined | Elimination half life for Ringer's | 88 Minutes |
| Hydroxyethyl Starch, Ringers and a Combination of Both. | Elimination Half Life for Different Fluids Alone or When Combined | Elimination half life for HES | 116 Minutes |
| Hydroxyethyl Starch, Ringers and a Combination of Both. | Elimination Half Life for Different Fluids Alone or When Combined | Elimination half life for HES (+ Ringer's) | 126 Minutes |
| Hydroxyethyl Starch, Ringers and a Combination of Both. | Elimination Half Life for Different Fluids Alone or When Combined | Elimination half life for Ringer's (+ HES) | 497 Minutes |
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.
Time frame: 420 minutes
Population: 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%)).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Hydroxyethyl Starch, Ringers and a Combination of Both. | Volume Effects for Hydroxyethyl Starch, Ringer's Solution or a Combination of Both. | Distribution volume of Acetated Ringers | 5.53 Litre |
| Hydroxyethyl Starch, Ringers and a Combination of Both. | Volume Effects for Hydroxyethyl Starch, Ringer's Solution or a Combination of Both. | Distribution volume for HES 6% | 2.94 Litre |
| Hydroxyethyl Starch, Ringers and a Combination of Both. | Volume Effects for Hydroxyethyl Starch, Ringer's Solution or a Combination of Both. | Distribution vol for HES combined with Ringer's | 3.12 Litre |
| Hydroxyethyl Starch, Ringers and a Combination of Both. | Volume Effects for Hydroxyethyl Starch, Ringer's Solution or a Combination of Both. | Distribution vol for Ringers combined with HES | 4 Litre |
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
Time frame: 30 min
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Hydroxyethyl Starch, Ringers and a Combination of Both. | Accuracy of Noninvasive Haemoglobin Measurement by Pulse Oximetry, for Different Fluids (Start to End of Infusion) | Ringer's acetate | 7 percentage of relative difference |
| Hydroxyethyl Starch, Ringers and a Combination of Both. | Accuracy of Noninvasive Haemoglobin Measurement by Pulse Oximetry, for Different Fluids (Start to End of Infusion) | Hydroxy ethyl starch 6% | -4.3 percentage of relative difference |
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).
Time frame: 420 min
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Hydroxyethyl Starch, Ringers and a Combination of Both. | Accuracy of Non-invasive Hemoglobin Monitoring for Different Fluids | Ringers acetate | -5.3 percentage of relative difference |
| Hydroxyethyl Starch, Ringers and a Combination of Both. | Accuracy of Non-invasive Hemoglobin Monitoring for Different Fluids | HES 6% | 0.0 percentage of relative difference |
| Hydroxyethyl Starch, Ringers and a Combination of Both. | Accuracy of Non-invasive Hemoglobin Monitoring for Different Fluids | HES 6% + Ringers acetate | 1.5 percentage of relative difference |
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.
Time frame: 420 minutes