Clinical trial NCT02697786: Neuromonitoring in Patients During Aortic Valve Replacement
Official title: The Impact of Intraoperative Microemboli Load on Postoperative Brain Injury in Patients Undergoing Aortic Valve Replacement Preformed With Two Different Surgical Approaches
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Brain Injury
Keywords: Aortic valve surgery
Lead sponsor: University Medical Centre Ljubljana
Sponsor class: OTHER
Collaborators: name: Slovenian Research Agency
First posted: 2016-03-03
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Postoperative brain damage and neuropsychological disorders have been observed in 30 - 80 % of patients after heart surgery with the use of cardiopulmonary bypass (CPB).They can persist up to a year after cardiac surgery and are associated with increased hospital mortality and prolonged intrahospital stay.

Hypoperfusion,hyperthermia,atrial fibrillation,genetic predisposition and systemic inflammatory response associated with CPB have been identified as pathophysiological mechanisms.However, some authors consider cerebral embolisation to be the prevalent mechanism of intraoperative brain injury after cardiac surgery,as gaseous or solid cerebral emboli can cause ischemia, inflammation and edema,consequently causing cerebral infarctions usually resulting with stroke,coma,encephalopathy, delirium and cognitive decline. Additionally,they may impair cerebrovascular reactivity (CVR).

Aortic valve replacement (AVR) preformed by full sternotomy is the standard approach in the treatment of aortic valve disease. Minimally invasive (MIS) aortic valve replacement has been shown to reduce postoperative mortality, morbidity, and pain while providing faster recovery, a shorter hospital stay, and better cosmetic results. However, due to technically more demanding procedure, MIS may lead to prolonged CPB time and incomplete de-airing of the heart with an increased risk for cerebral gas embolization. Therefore, the choice of MIS might bear an augmented risk for brain injury.

Transcranial Doppler (TCD) enables real time detection of intraoperative emboli in the cerebral arteries seen as microembolic signals (MES), and is an essential neuromonitoring tool. Several studies demonstrated correlation between the number of MES and the occurrence as well as severity of postoperative neurological complications. However, the factors contributing to brain injury have not been elucidated in those studies. The investigators speculate that impairment of CVR is an important mechanism that persists and prolongs the duration of brain injury into postoperative period.

The aim of the study is to compare two surgical approaches used for AVR, with focus on the number of MES and their impact on levels of protein S100B (marker of brain tissue damage),postoperative CVR and cognitive function With the results,the investigators aim to help surgeons in selecting the appropriate technique for AVR in individual participants,as well as to clarify the effect of aortic valve surgery on the brain.

Detailed description: Patients undergoing for aortic valve replacement will be enrolled in the study after giving the signed informed consent and will be divided in two groups depending on the type of the surgical technique. Either full sternotomy (FS) or minimal invasive sternotomy (MIS) will be performed, both with the use of cardio-pulmonary bypass (CPB).One week before and one week after the surgery patients will undergo mini mental test and measurement of visually evoked cerebral blood flow velocity response (VEFR).Levels of S100B, interleukin (IL) 1, IL 6, IL 8, IL 10 and microparticles will be determined before induction of anesthesia,as well as 6 h, 24 h, 48 h and 7 days after CPB.Each patient will have invasive and non invasive monitoring that will include near infrared spectroscopy (NIRS), bispectral index (BIS) and TCD during surgery.MES will be detected using TCD at the following time-points: beginning of surgery, after sternotomy, during aortic cannulation, during CPB, during de-airing, opening of the clamp on the aorta and after CBP removal before chest closure.All of this data will be documented as well as the demographic characteristics of patients, their preoperative medical status, and intraoperative data (duration of surgery, duration of CPB, hemodynamic parameters, inotropic/vasoactive support,blood and blood components); duration of mechanical ventilation in intensive care unit (ICU), duration of ICU stay, 30-day mortality and morbidity, as well as postoperative complications.

Eligibility criteria: Inclusion Criteria:

* Isolated aortic valve stenosis as well as asymptomatic patients with depressed systolic function
* Symptomatic patients with normal or depressed left ventricular function
* Patients with American Society of Anesthesiologist (ASA) physical status classification 2 or 3

Exclusion Criteria:

* History of brain stroke
* EF less than 20%
* History of alcohol abuse
* Epilepsy of history of psychiatric illness and antipsychotic drugs
* Patients with stenosis on carotid arteries
* Patients with preformed surgery or already stented carotid arteries
* Patients with poor or absent acoustic temporal window
* Diagnosed dementia

Primary outcomes:
measure: Detection of the intraoperative microembolic signals during minimal invasive sternotomy compared to full sternotomy with TCD during aortic valve surgery
timeFrame: Intraoperative detection:Beginning of surgery, after sternotomy, during aortic cannulation, during CPB, during de-aeration, opening of the clamp on the aorta and after CBP removal before chest closure.
measure: Detection of S100B serum protein, marker of brain tissue damage
timeFrame: Before induction of anesthesia, 6 h , 24 h, 48h and 7 days after CPB
measure: Detection of serum interleukin IL-1, IL-6,IL-8,Il-10 and Microparticles
timeFrame: Before induction of anesthesia, 6 h , 24 h, 48h and 7 days after CPB
Secondary outcomes:
measure: Assessment of cerebrovascular reactivity using visually evoked cerebral blood flow velocity response (VEFR) measurements
timeFrame: 7 days before and 7 days after surgery
measure: Assessment of neurologic and cognitive function in patients undergoing AVR
timeFrame: 7 days before and 7 days after surgery
Other outcomes:
measure: Length of ICU stay
timeFrame: Post operative period, an expected average of 2 days
measure: Requirement for inotropic and vasoactive therapy
timeFrame: 1)After induction of anesthesia, 2)at the end of CPB ,3) postoperative period
measure: Duration of mechanical ventilation
timeFrame: postoperative period, an expected average 2 days
measure: 30 days mortality
timeFrame: 30 days
Locations:
city: Ljubljana
country: Slovenia
facility: University Clinical center
Study officials:
affiliation: University Medical Centre Ljubljana
name: Maja Sostaric, MD, PhD
role: STUDY_DIRECTOR
affiliation: University Medical Centre Ljubljana
name: Matej Podbregar, MD, PhD
role: STUDY_DIRECTOR
affiliation: University Medical Centre Ljubljana
name: Tomislav Klokocovnik, MD,PhD
role: STUDY_DIRECTOR
affiliation: University Medical Centre Ljubljana
name: Borut Gersak, MD, PhD
role: STUDY_DIRECTOR
affiliation: University Medical Centre Ljubljana
name: Marija Bozhinovska, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bozhinovska M, Jenko M, Stupica GT, Klokocovnik T, Ksela J, Jelenc M, Podbregar M, Fabjan A, Sostaric M. Cerebral microemboli in mini-sternotomy compared to mini- thoracotomy for aortic valve replacement: a cross sectional cohort study. J Cardiothorac Surg. 2021 May 24;16(1):142. doi: 10.1186/s13019-021-01509-8.