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

February 8, 2026 updated by: Elif Bengi SENER, Ondokuz Mayıs University

Comparison of the Effects of Ibuprofen on Cerebral Oxygenation, Postoperative Cognitive Dysfunction, and Delirium in One-Lung Ventilation

This study compares the effects of ibuprofen administered during surgery and within the first 24 hours after surgery, versus no ibuprofen, on cerebral oxygenation, postoperative changes in consciousness (postoperative delirium and cognitive dysfunction), length of stay in the intensive care unit, and the incidence of postoperative pain, nausea, vomiting, and pruritus in patients undergoing lung lobectomy or segmentectomy using a closed (video-assisted) method (VATS - video-assisted thoracoscopic surgery), in whom one-lung ventilation is applied.

The aim of this study is to evaluate the effects of ibuprofen on cerebral oxygenation, postoperative cognitive changes, and delirium in patients undergoing one-lung ventilation.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

54

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: IBUPROFEN (GROUP B)
In the study, patients will be randomized into two groups (Group B: ibuprofen group; Group C: control group). Patients in Group B will receive 400 mg intravenous ibuprofen administered by the anesthesia research resident 15 minutes before the surgical incision. Group B patients will also receive postoperative intravenous ibuprofen at a dose of 400 mg three times daily. No intraoperative or postoperative ibuprofen treatment will be administered to patients in Group C.
Drug: ibuprofen
In the study, patients in Group B will receive a single intraoperative dose of 400 mg IV ibuprofen, followed by postoperative administration of 400 mg IV ibuprofen three times daily for 24 hours. We hypothesize that, by benefiting from the anti-inflammatory effects of ibuprofen, intraoperative cerebral oxygenation will be preserved, thereby reducing the incidence of postoperative delirium and cognitive dysfunction.
Other Names:
  • IV ibuprofen
No Intervention: CONTROL (GROUP C)
In this study, patients will be randomized into two groups (Group B: ibuprofen group; Group C: control group). Patients in Group B will receive 400 mg IV ibuprofen administered by the anesthesia research resident 15 minutes before the surgical incision. Group B patients will also receive postoperative IV ibuprofen at a dose of 400 mg three times daily. No intraoperative or postoperative ibuprofen treatment will be administered to patients in Group C.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Right and left intraoperative cerebral oxygenation values (rScO₂)
Time Frame: preoperative and intraoperative
The primary outcome of this study is the preoperative and intraoperative right and left regional cerebral oxygenation values. Cerebral oxygenation is measured using near-infrared spectroscopy (NIRS). The ability of near-infrared light to penetrate biological tissues and to be absorbed by oxyhemoglobin and deoxyhemoglobin constitutes the basic principle of regional cerebral oxygen saturation measurement. Using this method, the balance between oxygen supply and demand in cerebral tissue can be continuously evaluated 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 the oxygenation of these compartments. Low regional cerebral oxygen saturation values have been associated with cerebral hypoxia and/or ischemia.
preoperative and intraoperative

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Postoperative cognitive dysfunction (MMSE score)
Time Frame: until the end of postoperative day 2 and preoperative day
Cognitive functions in the preoperative and postoperative periods will be assessed using the Mini-Mental State Examination (MMSE) for patients with at least 5 years of education, and the MMSE for uneducated individuals for those with less than 5 years of education. Patients unable to complete the test (total score ≤24) will be excluded from the study.
until the end of postoperative day 2 and preoperative day
Postoperative delirium score (NU-DESC)
Time Frame: until the end of postoperative day 2
NU-DESC is a delirium screening tool. A total score of 2 or higher will be considered clinically significant for delirium.
until the end of postoperative day 2
Postoperative Resting and activity NRS score (Numeric Rating Scale)
Time Frame: until the end of postoperative day 1
Patients' pain will be assessed using the Resting and activity NRS (Numeric Rating Scale), scored from 0 to 10. Rescue analgesia will be administered if the score is 4 or higher.
until the end of postoperative day 1
Postoperative nausea and vomiting status
Time Frame: until the end of postoperative day 1
Nausea and vomiting will be assessed using the Verbal Descriptive Scale (VDS), with scores ranging from 0 to 4. Accordingly, patients with a score of 3 or higher will receive IV ondansetron at a dose of 0.05 mg/kg.
until the end of postoperative day 1

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ondokuz Mayıs University

Investigators

  • Study Director: Canan ASAR SAHIN, Ondokuz Mayıs University Faculty of Medicine Department of Anesthesiology and Reanimation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

February 15, 2026

Primary Completion (Estimated)

August 1, 2026

Study Completion (Estimated)

September 1, 2026

Study Registration Dates

First Submitted

February 2, 2026

First Submitted That Met QC Criteria

February 8, 2026

First Posted (Actual)

February 10, 2026

Study Record Updates

Last Update Posted (Actual)

February 10, 2026

Last Update Submitted That Met QC Criteria

February 8, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IBU2025

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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