1. Objective and Selection We refer to our research project as the "research project" in this information sheet. If you participate, you will be a participant.

   In this research project, we aim to investigate the effect of the medication dexmedetomidine on blood pressure during surgery on your carotid artery. We are inviting you because all individuals undergoing carotid artery surgery may participate.

2. General Information Due to your narrowing of the carotid artery, you require a planned procedure under general anesthesia. During this, your circulatory system and heart function will be continuously monitored through ongoing measurements to constantly track your condition. At the start of general anesthesia, heart rate, blood oxygen levels, and blood pressure will be monitored. Strong painkillers and anesthetic agents will then be administered for the general anesthesia. Additional medications will be given to maintain the anesthesia. Your condition will be closely and continuously monitored throughout the general anesthesia. At the end of the surgery, the anesthetic agents will be gradually reduced, allowing you to awaken from the anesthesia. In this context, we want to examine whether the additional administration of dexmedetomidine during carotid artery surgery reduces blood pressure fluctuations that may occur during such anesthesia.

   The medication dexmedetomidine is approved for the Swiss market by Swissmedic and is commonly used today in many areas of anesthesia and intensive care medicine. It is even administered to pediatric patients in anesthesia. The goal of continuous dexmedetomidine administration during surgery is twofold: to reduce the need for other anesthetic agents while simultaneously minimizing blood pressure fluctuations that may arise during different surgical phases.

   The scientific question is: Does additional administration of dexmedetomidine influence the intraoperative hemodynamic course and thus the clinical outcome after surgery? The study will be conducted over approximately 24 months at Inselspital Bern (single-center) with 44 patients. We are conducting this study in accordance with Swiss laws and all internationally recognized guidelines. The responsible cantonal ethics committee (KEK Bern, Murtenstrasse, Bern) has reviewed and approved the study. A description of this study is also available on the website of the Federal Office of Public Health: www.kofam.ch.

3. Procedure The planned surgery will be performed independently of this study. Upon the patient's arrival in the operating room, they will be randomly assigned to one of two groups. One group will serve as the control group and receive standard general anesthesia according to our current hospital guidelines. The second group will receive the standard anesthesia plus the study medication dexmedetomidine in a precisely defined dose. Group allocation will be randomized and blinded (not disclosed to participants). The number of patients in both groups will be equal. Both groups will be treated and monitored in accordance with the recommendations and standards of the Department of Anesthesia and Pain Medicine at Inselspital Bern, as well as those of the Swiss Society for Anaesthesiology and Perioperative Medicine (SSAPM). Hemodynamic and cardiac function parameters will be closely monitored and recorded for all study participants. These data will be collected by the attending anesthesiologist.

At a precisely defined time point during the surgery (achievement of "burst suppression"), administration of the study medication will be stopped, and anesthesia will be adjusted according to surgical progress. After emergence from general anesthesia, you will be immediately assessed and then transferred to the recovery unit. During your stay on the recovery unit, circulatory parameters and your neurological status will be assessed at regular intervals.

Prior to transfer to the regular ward the following day, a questionnaire regarding your neurological status will be completed, and all medications administered during your recovery unit stay will be recorded. The study will then be finished for all participating patients.

Hemodynamic stability is paramount during, and after carotid endarterectomy (CEA). Maintenance of cerebral perfusion pressure is required before, and during cross-clamping of the internal carotid artery (ICA) to prevent ischemia. After declamping, arterial hypertension must be avoided to prevent cerebral hyperperfusion syndrome (CHS), a rare, but serious complication after cerebral revascularisation procedures. CHS is associated with increased arterial blood pressure and characterised by headaches, neurological deficits, and seizures not caused by cerebral ischemia.

Recently, our group has demonstrated the significant propofol-sparing effect of the centrally acting alpha agonist dexmedetomidine during CEA. We also found significantly decreased requirements for the vasopressor norepinephrine, which may be well explained by the propofol sparing effect of dexmedetomidine in addition to its peripheral alpha-agonistic action (5).

Dexmedetomidine is known to exert a biphasic effect on arterial blood pressure (ABP); at higher concentrations, or when administered as an intravenous bolus, dexmedetomidine increases vascular resistance via peripheral alpha-adren-ergic receptors. After prolonged administration, and at lower concentrations, its central sympatholytic effects prevail (6-8), which may predispose dexmedetomidine as a well-suited adjunct to general anaesthesia for CEA. Recently, low-dose dexmedetomidine has been found to prevent CHS after stenting of the ICA (9).

In addition to its favorable hemodynamic profile, other beneficial effects of dexmedetomidine for CEA have been reported. Frequently, patients undergoing CEA have suffered recent stroke, which itself represents a high risk of delirium (POD) (10). In 700 elderly patients undergoing non-cardiac interventions8, low-dose dexmedetomidine was found to reduce the incidence of delirium from 23% to 9%. Moreover, there is growing evidence for neuroprotective effects of dexmedetomidine in the context of ischemia and reperfusion5,6 Proposed mechanisms include modulation of neuroinflammation, apoptosis, oxidative stress, and synaptic plasticity via the α2-adrenergic receptor (11).

Our previous study was designed to measure the effects of dexmedetomidine on intraoperative requirements of propofol. While the decreased requirements for norepinephrine were clinically significant, it was not defined as primary outcome measure. Also, most of the parameters have been collected only during the immediate perioperative period. The only assessment on postoperative day 1 was CAM-ICU for delirium.

The main purpose of the present follow-up study is to measure the effects of dexmedetomidine on systemic haemodynamics during, and after CEA, with a particular focus on 1) maintenance of cerebral perfusion pressure before and during cross-clamping of the ICA and 2) maintenance of an upper limit of systolic arterial blood pressure for prevention of CHS.

To evaluate the haemodynamic stability during and after CEA with co-administration of dexmedetomidine compared to a standard therapy.

Inclusion Criteria:

• age ≥18 years
• ASA physical status 1-4
• written informed consent provided.

Exclusion Criteria:

• Age <18 years, Rapid sequence induction needed for surgery, higher grade atrioventricular block without pacemaker, severe hypovolaemia or bradycardia, uncontrolled hyper or hypotension, hypersensibility concerning the active substance Dexmedetomidine or any other component, serve liver disease, known malignant hyperthermia, cardiovascular instability or severe heart failure (EF ≤ 30% or > NYHA III), limited peripheral autonomic activity, pregnancy, rejection or lack of consent of the patient.

during the operation the praticipant will recieve dexmedetomidine or not.