QUANtification of Cardiovascular Autonomic Neuropathy (CAN) and the Effects of Anaesthesia on Haemodynamics and Cerebral Perfusion (QUANCAN)

January 30, 2018 updated by: B Preckel, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Rationale: Complications of chronic hyperglycaemia associated with Diabetes Mellitus type 2 (DM2) include macro- and microvascular angiopathy. Cerebral Autoregulation (CA), the capability of the brain to maintain constant cerebral blood flow (CBF) despite changes in blood pressure, is impaired early in DM2 implicating that CBF becomes dependent on blood pressure. In addition, 20-60% of all patients with DM2 suffers from cardiovascular autonomic neuropathy (CAN) resulting in more unstable blood pressure regulation. In patients without DM2 or CAN, induction of anaesthesia results in slightly decreased blood pressure, but cerebral perfusion is maintained through CA. In contrast, patients with DM2 and CAN may display greater reductions in blood pressure and cerebral perfusion may become jeopardized due to impaired CA. This could be an explanation for the increased incidence of stroke in patients with DM2.

Objective:

  1. To study whether peri-operative haemodynamics fluctuate more in patients with DM2 and CAN.
  2. To study whether CAN further worsens cerebral perfusion in addition to impaired CA.

Study design: Prospective, observational cohort trial. Study population: A total of 45 patients, 30 with DM2 and 15 healthy controls scheduled for elective, non-cardiothoracic surgery under general anesthesia and age 18 years and above will be included in the study. After inclusion, DM2-patients will be categorized in two groups (both 15 patients): patients with and patients without CAN. Given the prevalence of 20-60% CAN, we plan to screen at most 100 patients and include 15 patients in each study group.

Intervention (if applicable):

  1. PRE-operative: chart review, short physical examination, autonomic function tests to determine the presence of CAN. These tests are simple physiological tests that can be performed on a regular ward and involve a Vasalva manoeuvre, 3 minute paced breathing with a frequency of 6·min-1 and tests for orthostatic hypotension. Also, we test the sensitivity of the cerebral vasculature to CO2 by measuring during one-minute hyperventilation and one minute CO2-rebreathing. Continuous blood pressure monitoring will be obtained using ccNexfin, a non-invasive monitor that comprises a single inflatable finger cuff. Cerebral perfusion will be assessed non-invasively using transcranial Doppler attached with a headband to the temporal skin area and (non-invasive) measurement of cerebral oxygenation using near-infrared spectroscopy (NIRS).
  2. INTRA-operative: we repeat the 3 minute paced breathing test and the CO2-reactivity test.

Main study parameters/endpoints: Between group difference in haemodynamic parameters and cerebral perfusion parameters.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

46

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
    • Noord-Holland
      • Amsterdam, Noord-Holland, Netherlands, 1105AZ
        • Academic Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • Willing and able to give written informed consent
  • Scheduled for elective, non-cardiothoracic surgery under general anesthesia
  • Age 18 years and above

Exclusion criteria:

  • Day case surgery
  • laparoscopic procedure
  • DM type 1
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Non-diabetic patients
Study interventions include a medical history and short physical examination as well as autonomic function tests and cerebral autoregulation tests on the day before surgery. In addition we determine CO2 sensitivity of the cerebral vasculature by three minutes hyperventilation and three minutes CO2 rebreathing. Perioperatively, continuous measurement of heart rate, blood pressure, stroke volume and cardiac output is aquired using the ccNexfin monitor, a non-invasive device using a single finger cuff. Continuous monitoring of cerebral perfusion parameters using transcranial Doppler ultrasound (TCD) of the middle cerebral artery (MCA) and cerebral oxygenation using near-infrared-spectroscopy (NIRS) will be obtained. BRS and condition of CA will be determined preoperatively during autonomic function testing (see below) and 30 minutes after induction of anaesthesia.
Diagnostic test: Paced breathing at 6, 10 and 15 breaths per minute
Active Comparator: Diabetic patients with cardiovascular autonomic neuropathy
Study interventions include a medical history and short physical examination as well as autonomic function tests and cerebral autoregulation tests on the day before surgery. In addition we determine CO2 sensitivity of the cerebral vasculature by three minutes hyperventilation and three minutes CO2 rebreathing. Perioperatively, continuous measurement of heart rate, blood pressure, stroke volume and cardiac output is aquired using the ccNexfin monitor, a non-invasive device using a single finger cuff. Continuous monitoring of cerebral perfusion parameters using transcranial Doppler ultrasound (TCD) of the middle cerebral artery (MCA) and cerebral oxygenation using near-infrared-spectroscopy (NIRS) will be obtained. BRS and condition of CA will be determined preoperatively during autonomic function testing (see below) and 30 minutes after induction of anaesthesia.
Diagnostic test: Paced breathing at 6, 10 and 15 breaths per minute
Active Comparator: Diabetic patients without cardiovascular autonomic neuropathy
Study interventions include a medical history and short physical examination as well as autonomic function tests and cerebral autoregulation tests on the day before surgery. In addition we determine CO2 sensitivity of the cerebral vasculature by three minutes hyperventilation and three minutes CO2 rebreathing. Perioperatively, continuous measurement of heart rate, blood pressure, stroke volume and cardiac output is aquired using the ccNexfin monitor, a non-invasive device using a single finger cuff. Continuous monitoring of cerebral perfusion parameters using transcranial Doppler ultrasound (TCD) of the middle cerebral artery (MCA) and cerebral oxygenation using near-infrared-spectroscopy (NIRS) will be obtained. BRS and condition of CA will be determined preoperatively during autonomic function testing (see below) and 30 minutes after induction of anaesthesia.
Diagnostic test: Paced breathing at 6, 10 and 15 breaths per minute

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline in baroreflex sensitivty after induction of anesthesia
Time Frame: Pre-operative versus Intra-operative
Baroreflex sensitivity (BRS; expressed as ms change in R-R-interval per mmHg blood pressure change) can be seen as a measure of hemodynamic homeostatic control. We calculate BRS preoperatively (baseline) and compare it to intra-operative values (after induction of anesthesia).
Pre-operative versus Intra-operative
Change from baseline in dynamic cerebral autoregulation after induction of anesthesia
Time Frame: Pre-operative versus Intra-operative
Dynamic Cerabral Autoregulation (dCA; expressed as MCAVmean-to-MAP phase lead) can be seen as the ability of the brain to compensate for blood pressure changes. We calculate dCA pre-operatively (baseline) and compare it to intra-operative values (after induction of anesthesia).
Pre-operative versus Intra-operative

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical outcome
Time Frame: Intra-operative till 30 days postoperative
The relationship between autonomic function tests and clinical outcome during 30-postoperative days (observational). Outcome measures include frequency of all adverse and serious adverse events.
Intra-operative till 30 days postoperative

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Collaborators

European Society of Anaesthesiology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 30, 2016

Primary Completion (Actual)

September 7, 2017

Study Completion (Actual)

September 8, 2017

Study Registration Dates

First Submitted

February 20, 2017

First Submitted That Met QC Criteria

March 1, 2017

First Posted (Actual)

March 7, 2017

Study Record Updates

Last Update Posted (Actual)

February 1, 2018

Last Update Submitted That Met QC Criteria

January 30, 2018

Last Verified

January 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MEC2016_116

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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