Dexmedetomidine During Carotid Endarterectomy: a Registry on Safety and Satisfaction of Patients and Operators (DexTEA)

Carotid endarterectomy (CEA) is one of the most common procedures in vascular surgery, along with lower limb revascularization, and endovascular surgery. It has long been considered a standard for the treatment of carotid artery disease; it is currently considered the most valid medical approach for significantly decreasing the risk of ischemic stroke in symptomatic patients and a 'quasi standard' for the treatment in patients with high-grade carotid stenosis. From an anesthesiological perspective, it is a procedure than can be approached in different ways, i.e., with the patient under a state of general anaesthesia or with locoregional techniques (with possible sedation).

Although the recent General Anesthesia vs. Local Anesthesia (GALA) trial did not demonstrate the superiority of either of the above mentioned anaesthesiological management methods for this type of surgery, there are differences between the two techniques, including the risk of postoperative cognitive impairment.

Considering the type of surgery, for greater control of haemodynamic management without excessive hypotension or hypertension, at our Unit (Sant'Eugenio Hospital, Rome, Italy), the surgery is performed through the locoregional approach, sedating the patient only to keep it still during the procedure but awake to be able to evaluate haemodynamic compensation.

Under locoregional anaesthesia, a standard for anesthesia in this procedure is the intermediate cervical| plexus block. The cervical plexus block provides anaesthesia and analgesia for neck and head surgery, including CEA procedures. Usually, along with peripheral blockade, the use of hypnotics with a sedative dosage is preferred to increase patient compliance. There are numerous drugs used to sedate patients during a procedure, starting with the most widely used drugs, such as midazolam and propofol, followed by the most recently introduced drug, dexmedetomidine. The latter is a well-known superselective a2-agonist drug with hypnotic, sedative, anxiolytic, sympatholytic and analgesic activity that suppresses the neuronal noradrenergic cascade at the locus coeruleus level without inducing respiratory depression. It has no rebound effects even after 24 hours of continuous infusion and, therefore, lends itself well to administration even for short-term procedures. It also possesses a good safety margin. The purpose of this observational study is to compare the two major sedation techniques and protocols currently used and the usefulness of dexmedetomidine during carotid endarterectomy in terms of minor and major adverse events and patient, anaesthetist, and surgeon satisfaction, as well as the possible reduction in clamping time and the number of times the surgeon needs to administer additional local anaesthesia.

Study Design and Population A single-center, prospective observational study was conducted entirely within the Sant'Eugenio Hospital. All methods were performed in accordance with the guidelines and regulations of the Declaration of Helsinki, and this prospective observational study was approved by the Independent Ethics Committee of the Sant'Eugenio Hospital. Written informed consent was obtained from all patients whose data were collected. The minimum target set to start the study was the enrolment of 60 patients to be divided equally into two groups, since our group of anesthetists uses, without preference, two sedation protocols, in addition to cervical plexus blockade, for TEA operations in vascular surgery, both of which are approved in the literature and in internal hospital procedures. This process took place from January 2021 to December 2023. All patients referred to the Vascular Surgery of the hospital who were candidates for carotid endoarterectomy surgery were considered eligible for the study. The exclusion criteria included: severe liver failure (Child-Pugh classes B or C) or severe hypoproteinemia (albuminemia < 3.0 g/di); age <18 yr; baseline heart rate <50 bpm; Il or Ill grade atrioventricular block without a pacemaker; malignant hyperthermia suspected or established; psychiatric disorders; emergency surgery, inability to provide consent for tie procedure.

Endpoints The study has primary endpoints and secondary endpoints. Primary endpoints: An anaesthetist and surgeon evaluated the usefulness of dexmedetomidine during carotid endarterectomy in terms of minor and major adverse events and patients, anaesthetists and surgeons' satisfaction. This evaluation was carried out on a graded scale from 1 to 4 (4=very satisfied, 3=satisfied, 2=slightly satisfied, 1=not satisfied), which was specifically used for this observational study.

The secondary endpoints were possible reduction in clamping time and the number of times the surgeon had to administer local anaesthesia (in our study, 0.5% lidocaine).

Anaesthesia protocol In the preprocedural phase, after signing the informed consent, the patient was cannulated with peripheral venous access and a peripheral artery for monitoring. In accordance with the perioperative fluid management in the Enhanced Recovery After Surgery (ERAS) protocol, the patient fasted with clear fluid for at least two hours before induction of anaesthesia, and Ringer's lactate was used to maintain volemia.

All patients were given a nerve block of both the intermediate and superficial cervical plexus with an ultrasound-guided needle using levobupivacaine 0.33% + mepivacaine 1.5% as a local anaesthetic, for a total volume of 15ml. The block was executed when the patient was fully awake and collaborating; in case of excessive agitation, a premedication with Midazolam 0,03 mg/kg for a maximum of 2 mg was used.

Once the preliminary phase was completed, the investigators took note of the type of sedation chosen between the two methods under analysis that are both used in our hospital, the choice of sedation protocol was at the discretion of the attending anesthetist. To standardize the procedure, for drug dosages, in addition to in-house protocols, data from the literature were used.

• GROUP 1: standard sedation with 1 mcg/kg fentanyl + 0.03 mg/kg midazolam in boluses until a Richmond Agitation-Sedation Scale (RASS) equivalent to -1/-2 was achieved.
• GROUP 2: sedation with dexmedetomidine 1 mcg/kg/h for 10 minutes and then 0.3-0.5 mcg/kg/h until RASS -1/-2.

Sedation was initiated once vital parameters were stabilized on the operating table, until the end of surgical procedure.

Typically, once on the operating table, the patient was started on continuous monitoring of cardiac, respiratory and neurological activity. At the end of surgery, the patient was then monitored over the following 4 hours in the recovery room and discharged according to Aldrete's criteria, noting the discharge times for each patient.

Data collection The data were collected from individual patient records. These included physical status, medical history, American Society of Anesthesiologists (ASA) risk score assessment, home therapy, any adverse events recorded during previous anaesthesia, recent blood test results, recent EKG and preoperative imaging (chest X-ray), if necessary. For this study, the following data were examined: medical history of comorbidities present, surgical time, clamping time, percentage of shunts and conversion to general anaesthesia, any intraoperative use of local anaesthetics (lidocaine 0.5 %), intraprocedural complications and follow-up at 180 days to observe any residual deficits.

Statistical analysis To assess the best sample size, the investigators calculated it on the number of patients with carotid pathology referred to the vascular surgery department, with a 95% confidence interval and a 5% margin of error. The study involved the enrolment of 60 patients, divided into two groups according to the anaesthesia performed in the operating room, who were compared according to the parameters assessed and recorded.

Statistical analysis was performed using chi-square tests and Fisher's exact tests for comparing proportions and Student's t tests for comparing means ÷ Standard Deviation (SD). A P value <0.05 was considered to indicate statistical significance. Statistical analysis was performed using IBM SPSS Statistics 25 (IBM).