Quantification of Dynamic and Static Cerebral Autoregulation (CA) Under Anaesthesia

Study Overview
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Brief Summary
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Cerebral autoregulation (CA) is the mechanism by which the brain vasculature maintains constancy of cerebral blood flow (CBF). Reliable direct measurements of CBF at different blood pressure levels are difficult because they are invasive and time-consuming. This type of measurement to quantify CA is generally referred to as static cerebral autoregulation (sCA). Alternatively, it is possible to measure CA indirectly from blood pressure oscillations. Dynamic cerebral autoregulation (dCA) measures how quickly the cerebral vessels react to a change in blood pressure to normalize CBF. Since the introduction of transcranial Doppler ultrasound (TCD), it has become possible to estimate CBF velocity relatively easy, which in turn correlates well with CBF changes. This method is widely used to quantify dCA. However, it is not clear how sCA correlates with dCA over a range of physiologic mean blood pressure (MBP). It is important to compare different methods of assessing CA, because impaired CA may result in increased risk of perioperative complications such as stroke. In this study, the investigators were interested in establishing the relationship between sCA and dCA during surgery under general anesthesia. The investigators aim to compare these methods during propofol and sevoflurane anesthesia.

Official Title
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Simultaneous Quantification of Dynamic and Static Cerebral Autoregulation (CA) at Different Steady-state Mean Blood Pressures Under Anaesthesia.

Conditions
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Cerebrovascular Circulation

Intervention / Treatment
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* Drug: Phenylephrine infusion
* Other: Mechanical ventilation
* Drug: Propofol
* Drug: Sevoflurane


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ASA-I or ASA-II, willing and able to give written informed consent, scheduled for elective, non-cardiothoracic surgery under general anaesthesia and age 18 years and above. Exclusion Criteria: Patient related Unable/ unwilling to participate ASA-III or higher Age < 18 years History of: uncontrolled hypertension, diabetes, Parkinson's disease, uncontrolled cardiac arrhythmia, Pure autonomic failure (formerly called idiopathic orthostatic hypotension), Multiple system atrophy with autonomic failure (formerly called Shy-Drager syndrome), Addison's disease and hypopituitarism, pheochromocytoma, peripheral autonomic neuropathy (e.g., amyloid neuropathy, idiopathic autonomic neuropathy), known cardiomyopathy, extreme left ventricle hypertrophy or ejection fraction < 30%, proven or suspected allergy for any of the medication used during induction of anaesthesia, malignant hyperthermia. Unability to record transcranial Doppler ultrasound due to anatomical variance ( 5% of population) Contra-indications for intravenous or inhalational anaesthesia. Contra-indications for phenylephrine: severe hypertension, peripheral vascular illness, severe hyperthyroidism Simultaneous use of MAO-inhibitors, dopaminergic or vasoconstrictor ergot alkaloids (bromocriptine, cabergoline, pergolide, ergotamine, methylergometrine, methysergide), linezolid, tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, digoxin, quinidine, oxytocin. Surgery related Day case surgery Laparoscopy with CO2 insufflation Extreme positioning during surgery (head-down/up tilt, lateral decubitus position, prone) Surgery < 60 minutes.

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients receive either propofol or sevoflurane to maintain anaesthesia. Both treatment groups receive the same phenylephrine and mechanical ventilation regimens.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Propofol<br>ASA-I/II patients undergoing elective, non-cardiothoracic surgery with intravenous anaesthesia (propofol). | Drug: Phenylephrine infusion<br>* Correction of anesthesia induced hypotension with phenylephrine to obtain sCA and dCA measurements at 60, 70, 80, 90 and 100 mmHg mean blood pressure. This is achieved by stepwise increases in phenylephrine infusion dose.<br>Other: Mechanical ventilation<br>* Patientes are mechanically ventilated at 6 bpm to obtain low frequency blood pressure oscillations ( 0.1 Hz).<br>Drug: Propofol<br>* Propofol<br>|
| Active Comparator: Sevoflurane<br>ASA-I/II patients undergoing elective, non-cardiothoracic surgery with inhalational anaesthesia (sevoflurane). | Drug: Phenylephrine infusion<br>* Correction of anesthesia induced hypotension with phenylephrine to obtain sCA and dCA measurements at 60, 70, 80, 90 and 100 mmHg mean blood pressure. This is achieved by stepwise increases in phenylephrine infusion dose.<br>Other: Mechanical ventilation<br>* Patientes are mechanically ventilated at 6 bpm to obtain low frequency blood pressure oscillations ( 0.1 Hz).<br>Drug: Sevoflurane<br>* Sevoflurane<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in dCA after several MBP-increasing steps. |  | Intraoperatively | 
| Differences in dCA between sevoflurane and propofol at different steady-state MBP's. |  | Intraoperatively |