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

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

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.

Study Overview

• Status: Completed
• Conditions: Cerebrovascular Circulation
• Intervention / Treatment: Drug: Sevoflurane; Drug: Propofol; Drug: Phenylephrine infusion; Other: Mechanical ventilation

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1105 AZ
      • Amsterdam UMC, location AMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Propofol; ASA-I/II patients undergoing elective, non-cardiothoracic surgery with intravenous anaesthesia (propofol).	Drug: Propofol; Propofol; Drug: Phenylephrine infusion; 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.; Other: Mechanical ventilation; Patientes are mechanically ventilated at 6 bpm to obtain low frequency blood pressure oscillations (~0.1 Hz).
Active Comparator: Sevoflurane; ASA-I/II patients undergoing elective, non-cardiothoracic surgery with inhalational anaesthesia (sevoflurane).	Drug: Sevoflurane; Sevoflurane; Drug: Phenylephrine infusion; 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.; Other: Mechanical ventilation; Patientes are mechanically ventilated at 6 bpm to obtain low frequency blood pressure oscillations (~0.1 Hz).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Investigators: Principal Investigator: Jeroen Hermanides, Dr., Amsterdam UMC, location AMC

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2019
• Primary Completion (Actual): September 23, 2019
• Study Completion (Actual): September 23, 2019

Study Registration Dates

• First Submitted: January 21, 2019
• First Submitted That Met QC Criteria: January 24, 2019
• First Posted (Actual): January 25, 2019

Study Record Updates

• Last Update Posted (Actual): May 27, 2021
• Last Update Submitted That Met QC Criteria: May 25, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Platelet Aggregation Inhibitors; Protective Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Cardiotonic Agents; Hypnotics and Sedatives; Respiratory System Agents; Anesthetics, Inhalation; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Nasal Decongestants; Adrenergic alpha-1 Receptor Agonists; Propofol; Sevoflurane; Phenylephrine; Oxymetazoline
• Other Study ID Numbers: METC 2018_230

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No