Perioperative Argon Inhalation to Improve Neurocognitive Recovery After Carotid Surgery

Официальное название

Perioperative Argon Inhalation to Improve Neurocognitive Recovery After Carotid Surgery (PAIRS Trial)

Обзор

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.

Вмешательства

• Препарат Аrgon-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
• Препарат Nitrogen-oxygen breathing mixture
  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

Первичные конечные точки

• Incidence of postoperative delirium [Срок оценки: 30 days]

Вторичные конечные точки (11)

• Incidence of emergence delirium [Срок оценки: 30 days]
• Incidence of postoperative agitation [Срок оценки: 30 days]
• Duration of postoperative delirium [Срок оценки: until 1 month after surgery]
• Incidence of cognitive dysfunction [Срок оценки: 30 days]
• Incidence of overt stroke [Срок оценки: 30 days]
• Incidence of covert stroke [Срок оценки: 30 days]
• Length of stay in the intensive care unit [Срок оценки: 30 days]
• Length of hospitalization [Срок оценки: 30 days]
• Serum level of S100 beta protein [Срок оценки: 2 days after surgery]
• Serum level of neuron-specific enolase [Срок оценки: 2 days after surgery]
• Serum level of interleukin-6 [Срок оценки: 2 days after surgery]

Критерии участия

Критерии включения

• age > 18 years
• elective carotid artery surgery
• general anesthesia
• written informed consent

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Профилактика

Центры проведения

Россия · 2 центра

• GBWZ of Moscow city hospital n.a. S.P. Botkin — Moscow
• Demikhov Municipal Clinical Hospital 68 — Moscow

Идентификаторы

NCT: NCT07200180 · PAIRS

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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