The Effect of Blood Pressure on Cerebral Perfusion During Vascular Surgery

Study Overview
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Brief Summary
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Anesthesia reduces blood pressure and cerebral blood flow is normally considered to be maintained despite marked changes in blood pressure. Vascular surgical patients are often elderly, have high blood pressure and atherosclerosis and in these patients cerebral blood flow may decrease if blood pressure is reduced during anesthesia. The purpose of this study is to assess the effect of blood pressure for preservation of cerebral blood flow during anesthesia in vascular surgery. The hypothesis is that in vascular surgical patients, during anesthesia, cerebral blood flow is higher with blood pressure maintained at a higher level than that used in normal clinical practice.

Detailed Description
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Background: Induction of anesthesia reduces mean arterial pressure (MAP) and cerebral blood flow is normally considered to be maintained by cerebral autoregulation despite changes in MAP between 60 - 150 mmHg and standard of care during anesthesia is to maintain MAP above 60 mmHg. Vascular surgical patients are often elderly with hypertension and atherosclerotic manifestations that may impair cerebral autoregulation of importance for anesthesia-induced reduction in blood pressure. Objective: To assess the effect of MAP for preservation of cerebral blood flow and oxygenation during vascular surgery. Hypothesis: The primary hypothesis is that during general anesthesia in vascular surgical patients, cerebral blood flow velocity and oxygenation is higher with MAP maintained at 80-90 mmHg, compared with a MAP maintained at a minimum of 60 mmHg. MAP is controlled in both groups using continuous infusion of phenylephrine. Phenylephrine is used as a tool in order to assess the effect of MAP on the cerebral circulation. In both groups, central blood volume is optimized by infusion of lactated Ringer´s solution using a goal directed fluid therapy following induction of anaesthesia and before commencement of phenylephrine infusion. Trial size: The investigators will include 40 participants (2 x 20) in order to detect or reject a 20% difference in middle cerebral artery velocity with a type I error risk of 5% and a type II error risk of 20% (power at 80%). Interim analysis will be conducted after inclusion of 20 patients (2 x 10). Excluded patients will be replaced.

Official Title
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The Effect of Blood Pressure on Cerebral Perfusion and Oxygenation During Vascular Surgery

Conditions
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Anesthesia, Peripheral Arterial Diseases

Intervention / Treatment
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* Other: MAP maintained at 80 mmHg
* Other: MAP maintained at 60 mmHg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing one of the following vascular surgical interventions in general anesthesia: Infra-inguinal bypass, femoro-femoral cross-over bypass or iliofemoral bypass surgery. Age > 18 years. Informed consent Exclusion Criteria: Use of monoamine oxidase inhibitors Allergy to phenylephrine Patients that cannot cooperate during examination Dementia defined as Mini-Mental State Examination < 24 Anesthesia within the last 30 days Alcohol consumption at or above 420 grams per week Lack of fluency in written and spoken Danish Severe hearing and vision impairment Neurological disease

Ages Eligible for Study
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Minimum Age: 19 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MAP maintained at 80 mmHg<br>During anesthesia MAP is maintained at 80 - 90 mmHg MAP using continuous infusion of phenylephrine. | Other: MAP maintained at 80 mmHg<br>* Intervention group, MAP is maintained at 80 - 90 mmHg during anesthesia using continuous infusion of phenylephrine.<br>|
| Active Comparator: MAP maintained at 60 mmHg<br>During anesthesia MAP is maintained at minimum of 60 mmHg using continuous infusion of phenylephrine. | Other: MAP maintained at 60 mmHg<br>* Control group, MAP is maintained at minimum of 60 mmHg during anesthesia using continuous infusion of phenylephrine.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Middle cerebral artery blood velocity | Middle cerebral artery blood velocity measured in [cm/s] assessed by transcranial Doppler. Changes in middle cerebral artery blood velocity reflects changes in cerebral blood flow. | During surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in serum S100B as compared between subjects in the control- and intervention groups | Serum concentrations of S100B, a marker of neuronal injury | Blood is sampled 10 min prior to induction of anesthesia and at the end of surgery | 
| Change in serum neuron-specific enolase as compared between subjects in the control- and intervention groups | Serum concentrations of neuron-specific enolase, a marker of neuronal injury | Blood is sampled 10 min prior to induction of anesthesia and at the end of surgery | 
| Regional cerebral oxygenation as compared between subjects in the control- and intervention groups | Frontal lobe oxygenation measured as the percentage of oxyhemoglobin of total hemoglobin [%] evaluated by near-infrared spectroscopy | During surgery | 
| Cardiac output as compared between subjects in the control- and intervention groups | Cardiac output measured in [l/min] evaluated by pulse contour analysis of the arterial blood pressure curve | During surgery | 
| Stroke volume as compared between subjects in the control- and intervention groups | Stroke volume measured in [ml/min] evaluated by pulse contour analysis of the arterial blood pressure curve | During surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cerebrovascular Circulation, Anesthesia, Blood pressure, Peripheral Arterial Diseases