Clinical trials

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.

Total knee replacement (TKR) is considered the most effective and safe method of radical treatment of late stages of knee osteoarthritis. A well-known problem of TKR is a severe postoperative pain syndrome, which is observed in more than 50% of patients. Femoral nerve block (FNB) is the "gold standard" for continuous postoperative analgesia after total knee replacement, as it is effective in reducing the frequency of use of opioid analgetics and reduce the duration of hospitalization. At the same time, the negative effect of this method is the motor blockade of the quadriceps femoris muscle which leads to functional impairment and is associated with an increased risk of falling. Adductor canal block (ACB) provides adequate analgesia comparable to femoral nerve block. Moreover, ACB doesn't affect the motor function of the quadriceps femoris muscle. The possibility of enhanced recovery after total knee replacement is the reason to compare single-shot adductor canal block and continuous femoral nerve block.