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

Diabetes Mellitus, Type 2 Clinical Trial

— QUANCAN  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03071432
• Other study ID #: MEC2016_116
• Status: Completed
• Phase: N/A
• First received: February 20, 2017
• Last updated: January 30, 2018
• Start date: August 30, 2016
• Est. completion date: September 8, 2017

Study information

• Verified date: January 2018
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: September 8, 2017
• Est. primary completion date: September 7, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Anesthesia
• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Diagnostic Test:
• Paced breathing at 6, 10 and 15 breaths per minute

Locations

Country	Name	City	State
Netherlands	Academic Medical Center	Amsterdam	Noord-Holland

Sponsors (2)

Lead Sponsor	Collaborator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)	European Society of Anaesthesiology

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Clinical outcome	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