Carotid Artery Disease, Carotid Artery Stenoses
Conditions
Keywords
Carotid artery disease, Carotid artery stenosis, Carotid artery surgery, Neurocognitive disorders, postoperative delirium, Stroke, Neuroinflammation, Argon, Organ protection
Brief summary
Currently, over 400,000 reconstructive surgeries on carotid arteries are performed annually worldwide, including carotid endarterectomy (CEA) and carotid stenting. These interventions have proven effective in preventing ischemic stroke in patients with hemodynamically significant carotid artery stenoses. However, even following a technically successful procedure, the risk of perioperative ischemic brain injury persists. According to meta-analyses, one in five patients exhibits covert ("silent") strokes after reconstructive interventions, with their frequency being ten times higher than that of clinically manifest events. Such lesions are associated with cognitive decline and an increased risk of dementia. An additional risk factor is the "no-reflow" phenomenon-an impairment of microcirculatory reperfusion that occurs even after the restoration of macrovascular blood flow, thereby limiting the effectiveness of surgical revascularization. Cognitive disorders and postoperative delirium, observed in 15-30% of patients after CEA, adversely affect rehabilitation and long-term prognosis. To date, there are no reliable pharmacological strategies to prevent these complications. In this context, inert gases have attracted significant interest as potential neuroprotective agents. Xenon, despite its proven efficacy, is limited by high cost and challenges in industrial production. Argon, in contrast, is accessible, safe, and technologically straightforward to administer. In preclinical models of stroke and ischemia-reperfusion, argon has demonstrated pronounced anti-apoptotic, anti-inflammatory, and antioxidant effects, mediated through the regulation of TLR2/4-, ERK1/2-, Nrf2-, and NF-κB-dependent signaling pathways. Its ability to suppress microglial activation towards the M1 phenotype and inhibit the NLRP3 inflammasome has been noted, which reduces neuroinflammation and decreases the volume of secondary neuronal damage. Short-term argon inhalation in healthy volunteers has shown a favorable safety profile with no adverse effects on cerebral hemodynamics. Thus, it is highly relevant to clinically test the hypothesis that perioperative inhalation of an argon-containing gas mixture can reduce the incidence of ischemic brain injuries and cognitive impairments in patients undergoing CEA.
Interventions
DRUGАrgon-oxygen breathing mixture
Patients receive a course of inhalations with an argon-oxygen mixture according to the following protocol: 60 minutes on day 1 prior to surgery, 60 minutes one hour before being transferred to the operating room, and 60 minutes on the first postoperative day
Patients receive a course of inhalations with an nitrogen-oxygen mixture according to the following protocol: 60 minutes on day 1 prior to surgery, 60 minutes one hour before being transferred to the operating room, and 60 minutes on the first postoperative day
Sponsors
Negovsky Reanimatology Research Institute
GBWZ of Moscow city hospital n.a. S.P. Botkin
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* age \> 18 years * elective carotid artery surgery * general anesthesia * written informed consent
Exclusion criteria
* The presence of any mental disorder according to the International Classification of Diseases 10th Revision which is confirmed by a psychiatrist. * The presence of any neuromuscular disease according to the International Classification of Diseases 10th Revision * Heart failure equal 3 or 4 class according to the New York Heart Association Functional Classification * Pregnant or breast-feeding women * Inability to undergo a preoperative assessment for any reason * Previously enrolled in this trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of postoperative delirium | 30 days | Number of patients with even one positive confusion assessment method for the intensive care unit or 3-minute confusion assessment method |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of emergence delirium | 30 days | Number of patients with positive the confusion assessment method for the intensive care unit as soon as they reach Aldrete score of 9 points |
| Incidence of postoperative agitation | 30 days | Richmond agitation-sedation scale more or equal +2 evaluated from the end of volatile anesthetic supply to the moment when a patient reaches Aldrete score of 9 points Richmond agitation-sedation scale: minimum value = -5 (Unarousable - no response to voice or physical stimulation) maximum value = +4 (Combative - overtly combative or violent; immediate danger to staff) Adequate patients have the results of Richmond agitation-sedation score equal 0 (Alert and calm; Spontaneously pays attention to caregiver) |
| Duration of postoperative delirium | until 1 month after surgery | 30 days - number of days in which patient had positive confusion assessment method for the intensive care unit or 3-minute confusion assessment method |
| Incidence of cognitive dysfunction | 30 days | reduction of ≥1 standard deviation in the Montreal Cognitive Assessment (MoCA) total z-score compared to the preoperative assessment |
| Incidence of overt stroke | 30 days | Number of overt strokes |
| Incidence of covert stroke | 30 days | Number of covert strokes |
| Length of stay in the intensive care unit | 30 days | Number of days in intensive care unit |
| Length of hospitalization | 30 days | Number of days in hospital |
| Serum level of S100 beta protein | 2 days after surgery | Serum level of S100 beta protein |
| Serum level of neuron-specific enolase | 2 days after surgery | Serum level of neuron-specific enolase |
| Serum level of interleukin-6 | 2 days after surgery | Serum level of interleukin-6 |
Countries
Russia
Contacts
CONTACTOleg Grebenchikov, MD, PhD
PRINCIPAL_INVESTIGATOROleg Grebenchikov, MD, PhD
Negovsky Reanimatology Research Institute
Outcome results
None listed