Clinical trial NCT03071432: QUANtification of Cardiovascular Autonomic Neuropathy (CAN) and the Effects of Anaesthesia on Haemodynamics and Cerebral Perfusion
Official title: QUANtification of Cardiovascular Autonomic Neuropathy (CAN) and the Effects of Anaesthesia on Haemodynamics and Cerebral Perfusion
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Anesthesia
Diabetes Mellitus, Type 2
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
Collaborators: name: European Society of Anaesthesiology
First posted: 2017-03-07
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Non-diabetic patients, n=15 Diabetic patients with cardiovascular autonomic neuropathy, n=15 Diabetic patients without cardiovascular autonomic neuropathy, n=15
Primary purpose: DIAGNOSTIC

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. 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change from baseline in baroreflex sensitivty after induction of anesthesia
timeFrame: Pre-operative versus Intra-operative
measure: Change from baseline in dynamic cerebral autoregulation after induction of anesthesia
timeFrame: Pre-operative versus Intra-operative
Secondary outcomes:
measure: Clinical outcome
timeFrame: Intra-operative till 30 days postoperative
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
state: Noord-Holland
Study officials:
References:
citation: 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.
citation: 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.