NCT03071432

Brief Summary

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. 1.To study whether peri-operative haemodynamics fluctuate more in patients with DM2 and CAN.
  2. 2.To study whether CAN further worsens cerebral perfusion in addition to impaired CA.
  3. 3.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).
  4. 4.INTRA-operative: we repeat the 3 minute paced breathing test and the CO2-reactivity test.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
46

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Aug 2016

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 30, 2016

Completed
6 months until next milestone

First Submitted

Initial submission to the registry

February 20, 2017

Completed
15 days until next milestone

First Posted

Study publicly available on registry

March 7, 2017

Completed
6 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 7, 2017

Completed
1 day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 8, 2017

Completed
Last Updated

February 1, 2018

Status Verified

January 1, 2018

Enrollment Period

1 year

First QC Date

February 20, 2017

Last Update Submit

January 30, 2018

Conditions

AnesthesiaDiabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (2)

  • Change from baseline in baroreflex sensitivty after induction of anesthesia

    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

    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 Outcomes (1)

  • Clinical outcome

    Intra-operative till 30 days postoperative

Study Arms (3)

Non-diabetic patients

ACTIVE COMPARATOR

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

Diabetic patients with cardiovascular autonomic neuropathy

ACTIVE COMPARATOR

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

Diabetic patients without cardiovascular autonomic neuropathy

ACTIVE COMPARATOR

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

Interventions

Paced breathing at 6, 10 and 15 breaths per minuteDIAGNOSTIC_TEST
Diabetic patients with cardiovascular autonomic neuropathyDiabetic patients without cardiovascular autonomic neuropathyNon-diabetic patients

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Academic Medical Center

Amsterdam, North Holland, 1105AZ, Netherlands

Location

Related Publications (2)

  • Sperna Weiland NH, Hermanides J, van der Ster BJP, Hollmann MW, Preckel B, Stok WJ, van Lieshout JJ, Immink RV. Sevoflurane based anaesthesia does not affect already impaired cerebral autoregulation in patients with type 2 diabetes mellitus. Br J Anaesth. 2018 Dec;121(6):1298-1307. doi: 10.1016/j.bja.2018.07.037. Epub 2018 Sep 6.

    PMID: 30442257DERIVED

  • Sperna Weiland NH, Hermanides J, Hollmann MW, Preckel B, Stok WJ, van Lieshout JJ, Immink RV. Novel method for intraoperative assessment of cerebral autoregulation by paced breathing. Br J Anaesth. 2017 Dec 1;119(6):1141-1149. doi: 10.1093/bja/aex333.

    PMID: 29028933DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
DIAGNOSTIC
Intervention Model
PARALLEL
Model Details: Non-diabetic patients, n=15 Diabetic patients with cardiovascular autonomic neuropathy, n=15 Diabetic patients without cardiovascular autonomic neuropathy, n=15
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor in anesthesiology

Study Record Dates

First Submitted

February 20, 2017

First Posted

March 7, 2017

Study Start

August 30, 2016

Primary Completion

September 7, 2017

Study Completion

September 8, 2017

Last Updated

February 1, 2018

Record last verified: 2018-01

Data Sharing

IPD Sharing
Will not share

Locations

NL(1)