Changes in Measured Plasma Volume, Glycocalyx and Atrial Natriuretic Peptide During Anaesthesia

Study Overview
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Brief Summary
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The arterial blood pressure is thought to affect the ratio between filtration and reabsorption of fluids in the circulating blood volume and thereby the plasma volume. During induction of anesthesia blood pressure, hemoglobin level and hematocrits decreases and the plasma volume increases. The aim of the study is to evaluate weather a maintained blood pressure with norepinephrine during anesthesia induction reduces the increase in 125 iodine-labeled human serum albumine (125I-HSA) measured plasma volume.

Detailed Description
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24 patients scheduled for coronary artery bypass surgery will be included and randomized to receive either norepinephrine in the dose needed to maintain pre-anesthesia blood pressure or to a control group and receive norepinephrine only if mean arterial pressure decreases below 60 mmHg. Equal anesthesia in both groups will be monitored. No fluids will be infused. Changes in vascular resistance and cardiac output will be measured with thermodilution and changes in plasma volume will be measured with 125I-HSA. Endothelial cell function will be evaluated by measuring leakage of 125I-HSA and the plasma concentration of endothelial cell markers. Hormonal effects will be evaluated by measuring the plasma concentration of atrial natriuretic peptide (ANP). Shedding of glycocalyx will be evaluated by measuring heparan sulphate. The level of fibrinogen and platelet function will be evaluated by thromboelastography/multiplate.

Official Title
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Changes in Measured Plasma Volume, Glycocalyx and Atrial Natriuretic Peptide During Anaesthesia, a Randomised Clinical Trial

Conditions
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Blood Pressure, Anesthesia

Intervention / Treatment
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* Drug: Norepinephrine
* Procedure: Maintained blood pressure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Elective coronary artery surgery patients Exclusion Criteria: Age under 40 years Untreated hypertension A reduced left ventricular systolic ejection fraction of 45% or less Diabetes mellitus Former stroke and/or a known carotid artery stenosis

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>Ordinary anesthesia, mean arterial pressure allowed to decrease to 60 mmHg. If it is lower the patients will receive a norepinephrine infusion in order to raise the mean arterial pressure to 60 mmHg. | |
| Active Comparator: Maintained blood pressure<br>Ordinary anaesthesia and maintained preanesthetic blood pressure by norepinephrine infusion | Drug: Norepinephrine<br>* Ordinary anaesthesia and maintained preanesthetic blood pressure by norepinephrine infusion<br>* Other names: Vasopressor;Procedure: Maintained blood pressure<br>* Norepinephrine therapy to maintain preanesthesia blood pressure<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change of plasma volume measured by 125I-HSA before anesthesia induction until 50 minutes after anesthesia induction. | To assess if the increase in plasma volume measured by 125I-HSA can be reduced by maintaining the blood pressure with vasopressor infusion. | 50 minutes from anesthesia induction | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in 125I-HSA leakage | To assess if there is a difference in 125I-HSA leakage in between the control and intervention groups before and after anaesthesia induction | 50 minutes from anesthesia induction | 
| ANP, heparan sulphate, thrombomodulin, fibrinogen, ROTEM | To assess if there is a difference in the plasma concentration of ANP, heparan sulphate, thrombomodulin, fibrinogen and ROTEM before and after anaesthesia induction in the intervention group compared to the control group | 50 minutes from anesthesia induction | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anesthesia, Blood pressure, Plasma Volume, Vasopressor agents, Coronary artery bypass, Glycocalyx, ANP, Coagulation