Effect of Perioperative IV Ibuprofen on Cerebral Oxygenation and Postoperative Cognition During One-Lung Ventilation

During one-lung ventilation (OLV) in thoracic surgery, cerebral oxygenation may decrease due to hypoxia, and this condition can be evaluated noninvasively using near-infrared spectroscopy (NIRS) . The ability of near-infrared light to penetrate tissues and be absorbed by oxyhemoglobin and deoxyhemoglobin forms the basic principle of measuring regional cerebral oxygen saturation. With this method, the balance between oxygen supply and demand in cerebral tissue can be continuously and dynamically assessed in real time. During measurements, it is assumed that the blood volume within the venous, capillary, and arterial compartments of the brain remains constant. Therefore, cerebral oximeters provide an average value reflecting oxygenation across these compartments. Low regional cerebral oxygen saturation values have been associated with cerebral hypoxia and/or ischemia.

Cerebral hypoxia is a well-known risk factor for postoperative delirium (POD) . While anesthesia has traditionally been considered the primary cause of postoperative delirium, animal studies suggest that surgery-induced inflammation may be an important contributor to neurological disorders associated with postoperative delirium. The peripheral inflammatory response affects the brain and contributes to the pathogenesis of postoperative delirium. Cytokines, particularly IL-1β, TNF-α, and IL-6, are believed to interact with the brain . The mechanisms by which peripheral cytokines reach the brain are thought to involve the blood-brain barrier or the circumventricular regions. These peripheral cytokines trigger microglia-derived cytokine synthesis, leading to a cycle of neuroinflammation. A recent meta-analysis of human observational studies has shown that both peripheral and cerebrospinal fluid (CSF) inflammatory markers, such as CRP and IL-6, are associated with postoperative delirium and postoperative cognitive dysfunction . Postoperative delirium occurs at a rate of 10-20% and prolongs hospital stay by 2-3 days and intensive care unit stay by approximately 2 days .

Due to surgery-induced systemic inflammatory responses, patients may also experience postoperative cognitive dysfunction (POCD). POCD is usually observed in the immediate postoperative period and manifests as a transient cognitive impairment. This condition may range from fatigue, social withdrawal, and decreased concentration to severe cognitive dysfunction. POCD may also lead to fluctuating levels of consciousness and disturbances in the sleep-wake cycle.

The incidence of POCD is highest among elderly patients. It has been observed in up to 40% of patients aged 60 years and older who undergo surgery. Although postoperative cognitive fluctuations are often not considered alarming, POCD is thought to predict the future onset of dementia and may contribute to chronic neurodegeneration with repeated surgical procedures.

Increases in pro-inflammatory cytokines during surgery trigger short-term cognitive impairment. Additionally, evidence from animal studies suggests that TNF-α-mediated dysfunction of the blood-brain barrier and migration of leukocytes into the hippocampus may lead to memory impairment. Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used as a component of multimodal postoperative analgesia, and it has been suggested that these agents may prevent postoperative delirium by directly alleviating neuroinflammation. The primary mechanism of action of NSAIDs is the inhibition of the cyclooxygenase (COX) enzyme responsible for prostaglandin synthesis. The constitutive isoform, COX-1, plays a role in intercellular signaling and tissue homeostasis, whereas COX-2, which is induced in inflammatory cells, is responsible for the production of prostanoids involved in inflammation. Ibuprofen exerts its effects by inhibiting both COX-1 and COX-2. Inhibition of COX-1 may be responsible for undesirable gastrointestinal side effects ; however, inhibition of COX-2 provides ibuprofen with its analgesic, antipyretic, and anti-inflammatory properties. In a study conducted by Huang et al. in mice, perioperative use of ibuprofen was shown to improve cognitive performance, reduce systemic inflammation, and decrease glial activation . In clinical settings, preoperative administration of intravenous ibuprofen has been shown to improve postoperative cognitive function in association with reduced levels of cytokines, cortisol, and catecholamines. Additionally, another study demonstrated that the use of the NSAID flurbiprofen increased PaO₂ levels .

However, no studies have investigated the effects of ibuprofen on PaO₂, cerebral oxygenation, postoperative delirium, or postoperative cognitive dysfunction in patients undergoing one-lung ventilation.The aim of this study is to investigate the effects of administered intravenous ibuprofen on intraoperative cerebral oxygenation and subsequent postoperative cognitive function changes in patients undergoing lobectomy or segmentectomy via VATS with one-lung ventilation.

Inclusion criteria

• Patients aged 18-75 years
• American Society of Anesthesiologists (ASA) Physical Status Classification System I-III
• Patients scheduled for lobectomy or segmentectomy via Video-Assisted Thoracic Surgery (VATS ) with one-lung ventilation
• New York Heart Association (NYHA) class I-II
• Patients who have been informed about the study and have provided written informed consent will be included.

Exclusion criteria

• Patients younger than 18 years or older than 75 years
• History of alcohol or substance abuse
• Patients with chronic NSAID use and/or NSAID use within the last 30 days, or NSAID allergy
• Allergy to other drugs used in the study (e.g., bupivacaine)
• ASA Physical Status IV-V
• Severe hearing, visual, or speech impairment
• Dementia, Alzheimer's disease, or psychiatric disorders (psychosis, bipolar disorder, schizophrenia)
• History of previous head trauma
• Chronic liver disease
• Pregnancy
• History of cerebrovascular disease
• Moderate-to-severe chronic obstructive pulmonary disease (COPD) (predicted FEV₁ <50%)
• GFR <60 mL/min/1.73 m²
• Patients who do not provide written informed consent
• Conditions that may cause inaccurate cerebral oximetry readings (subdural and/or extracranial hematoma, intracranial arteriovenous shunts, hyperbilirubinemia)
• Patients undergoing emergency surgery
• Patients in whom surgery is initiated as thoracotomy or converted to thoracotomy
• Patients unable to complete the preoperative MMSE (total score ≤24) will be excluded.