Effect of Low Tidal Volume Ventilation on Postoperative Delirium (CLEVER)

The Effect of Continuous Low Tidal Volume Ventilation During Cardiopulmonary Bypass on Postoperative Delirium: A Prospective Randomized Controlled Trial

This study aims to evaluate the effect of low tidal volume (LTV) ventilation during cardiopulmonary bypass (CPB) on postoperative delirium. It is hypothesized that the risk of delirium, which negatively impacts recovery following cardiac surgeries, can be reduced by improving cerebral perfusion and oxygenation through LTV. The study is designed as a prospective, randomized, controlled trial comparing delirium incidence, ICU stay duration, and 30-day mortality/morbidity rates between LTV and apnea groups. Primary outcomes will be assessed using the 3D-CAM method, while secondary outcomes include ICU stay duration and mortality/morbidity rates.

Study Overview

• Status: Completed
• Conditions: Cardiopulmonary Bypass; Postoperative Delirium (POD); Low Tidal Volume Ventilation; Cognitive Dysfunction, Postoperative
• Intervention / Treatment: Procedure: Group B: Low tidal volume

Detailed Description

Introduction and Objectives:

This protocol aims to evaluate the effect of low tidal volume (LTV) ventilation during cardiopulmonary bypass (CPB) on postoperative delirium. Postoperative delirium, commonly seen after cardiac surgeries, negatively impacts patient recovery. It is hypothesized that LTV reduces the risk of delirium by improving cerebral perfusion and oxygenation. The study objectives include comparing the incidence of delirium, ICU stay duration, and 30-day mortality/morbidity rates between groups.

Study Design and Methods:

This prospective, randomized, controlled trial will involve two groups: patients receiving LTV ventilation and those undergoing apnea during CPB. Inclusion criteria target CABG patients over 18 years of age, while exclusion criteria include emergent surgeries and cognitive impairments. Randomization will ensure balanced group allocation through computer-based methods. Mechanical ventilation parameters will follow standard protocols for both groups.

Measurements and Hypotheses:

The primary outcome is delirium, assessed using the 3D-CAM method, while secondary outcomes include ICU stay duration and 30-day composite mortality/morbidity rates. LTV ventilation is expected to reduce delirium incidence, shorten ICU stay, and lower mortality/morbidity rates. Statistical analyses will include multivariable models to account for potential confounding factors.

Substudies and Limitations:

The protocol includes two substudies to evaluate microcirculation and renal perfusion. Limitations may arise from the overlap of sedation effects with delirium symptoms, variations in surgical techniques, and potential data loss during patient follow-ups. Interim analyses are planned to assess the study's safety and effectiveness. The study will be conducted without external funding, adhering to routine clinical practices.

• Study Type: Interventional
• Enrollment (Actual): 130
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Turkey (Türkiye)
  • Karatay
    • Konya, Karatay, Turkey (Türkiye), 42030
      • Konya City Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• All male or female patients over the age of 18
• Patients undergoing planned cardiac surgeries including CABG
• Patients with an American Society of Anesthesiologists (ASA) physical status of II, III, or IV

Exclusion Criteria:

• Emergency surgeries will be excluded due to the high likelihood of non-compliance with the protocol and the potential lack of essential patient information.
• Surgeries requiring single-lung ventilation will be excluded as they may cause confusion in determining any effects of the intervention due to the inability to apply the study intervention and the differential treatment of the lungs.
• Patients who meet delirium criteria according to 3D-CAM measurements during the initial visit will be excluded.
• Patients with a life expectancy of less than 6 months or a history of psychiatric or neurological diseases (including depression, severe central nervous system depression, schizophrenia, epilepsy, Parkinson's disease, and Alzheimer's disease) will be excluded.
• Severe impairments such as blindness, severe deafness, or dementia that may hinder cognitive testing will be excluded.
• Patients using psychotropic or opioid medications, those with a history of delirium, or those with a history of alcohol abuse or withdrawal within the past 6 months will be excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Group A: Apnea; The apnea group serves as the control group. In routine Coronary Artery Bypass Grafting (CABG) surgery, after the cross clamp procedure, the mechanical ventilator is turned off, and the process is maintained by cardiopulmonary bypass (CPB). In this group, no mechanical ventilation will be provided after the cross clamp procedure, and apnea will be applied as part of routine care. The process will be entirely maintained by CPB.
Experimental: Group B: Low Tidal Volume (LTV); In the LTV group, mechanical ventilation will be maintained with low tidal volume parameters after the aortic cross-clamp procedure. This intervention includes a tidal volume of 3-4 mL/kg, respiratory rate of 12-14 breaths/min, PEEP of 5-8 cmH₂O, and FiO₂ of 50%. Minute ventilation (MV) will not exceed 12 L, and the parameters are adjusted according to ideal body weight. This group is designed to evaluate the protective effects of low tidal volume ventilation during surgery.	Procedure: Group B: Low tidal volume; In the LTV group, mechanical ventilation will be maintained with low tidal volume parameters after the aortic cross-clamp procedure. This intervention includes a tidal volume of 3-4 mL/kg, respiratory rate of 12-14 breaths/min, PEEP of 5-8 cmH₂O, and FiO₂ of 50%. Minute ventilation (MV) will not exceed 12 L, and the parameters are adjusted according to ideal body weight. This group is designed to evaluate the protective effects of low tidal volume ventilation during surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative delirium incidence	The main objective of the study is to compare the rates of postoperative delirium between patients who received low tidal volume (LTV) ventilation and those who were apnea-induced during CABG surgeries. This will be measured by the incidence of delirium, and it will be statistically analyzed to determine whether there is a significant difference between the two groups.	From the point where the RASS score evaluating wakefulness is -3, for a duration of 48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of stay in the intensive care unit (ICU)	The duration of postoperative ICU stay will be measured and compared between the groups.	The duration will be recorded in hours, starting from the time of ICU admission to the time of discharge.
30-day mortality rate	Mortality (death from any cause) rate occurring within the first 30 days post-surgery will be compared between the two groups .	In the first 30 days after surgery
30-day morbidity rate	morbidity (complications such as infections, cardiac events, respiratory failure, renal dysfunction, etc.) rate occurring within the first 30 days post-surgery will be compared between the two groups .	In the first 30 days after surgery

Collaborators and Investigators

• Sponsor: Nevsehir Public Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2025
• Primary Completion (Actual): December 8, 2025
• Study Completion (Actual): February 28, 2026

Study Registration Dates

• First Submitted: December 21, 2024
• First Submitted That Met QC Criteria: December 27, 2024
• First Posted (Actual): December 30, 2024

Study Record Updates

• Last Update Posted (Actual): March 31, 2026
• Last Update Submitted That Met QC Criteria: March 29, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Cardiopulmonary Bypass; Cognitive Dysfunction; Postoperative Delirium; low tidal volume ventilation
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Postoperative Complications; Pathologic Processes; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Cognition Disorders; Delirium; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Postoperative Cognitive Complications; Emergence Delirium; Cognitive Dysfunction
• Other Study ID Numbers: TABED-24-851

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
• product manufactured in and exported from the U.S.: No