The Effect of Desflurane Versus Sevoflurane Versus Propofol on Postoperative Delirium

NCT ID: NCT05990790

Last Updated: 2025-04-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 1332 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-03
• Study Completion Date: 2028-12-31

Brief Summary

Patients over the age of 65 years are at increased risk for developing delirium after noncardiac surgeries, resulting in increased morbidity and mortality. The prevention of postoperative delirium has been classified as a public health priority. However, so far data regarding possible intraoperative interventions to reduce the incidence of postoperative delirium is very scarce. Due to the more rapid wash-in and wash-out times of desflurane as compared to sevoflurane or propofol it seems reasonable that desflurane might be beneficial for the prevention of postoperative delirium. Therefore, we evaluate the effect of maintenance of anesthesia using desflurane, sevoflurane or propofol on postoperative delirium in elderly patients undergoing moderate- to high-risk major noncardiac surgery.

Detailed Description

Background: Postoperative delirium occurs in approximately 25% of patients over the age of 60 years undergoing major noncardiac surgery and is significantly associated with an increase in postoperative neurocognitive decline, morbidity, and mortality. The prevention of postoperative delirium has been classified as a public health priority. However, so far data regarding possible intraoperative interventions to reduce the incidence of postoperative delirium is very scarce. Previous small studies compared the effect of administration of sevoflurane versus propofol for maintenance of anesthesia on postoperative delirium and found beneficial effects of volatile anesthesia for the prevention of postoperative delirium. Furthermore, in small studies the administration of desflurane led to significantly shorter recovery periods after noncardiac surgery as compared to sevoflurane. Due to the more rapid wash-in and wash-out times of desflurane as compared to sevoflurane or propofol it seems reasonable that desflurane might be beneficial for the prevention of postoperative delirium. Therefore, we evaluate the effect of maintenance of anesthesia using desflurane, sevoflurane or propofol on postoperative delirium in elderly patients undergoing moderate- to high-risk major noncardiac surgery.

Methods: We will include 1332 patients ≥ 65 years of age undergoing moderate- to high-risk major noncardiac surgery lasting at least two hours in this prospective observer-blinded randomized controlled clinical trial. After induction of anesthesia patients will be randomly assigned to receive desflurane, sevoflurane or propofol for maintenance of anesthesia. Our primary outcome will be the incidence of postoperative delirium in the first five postoperative days. Postoperative delirium will be diagnosed using the 3D-CAM or 3D-CAM-ICU in the morning and evening of the first five postoperative days as appropriate assessed by blinded study personnel. Two-interim analyses after 1/3 and 2/3 of recruitment are pre-planned.

Statistics: The primary outcome, the incidence of postoperative delirium in the first five postoperative days, will be compared between the groups using a Chi-Square-test as well as a logistic regression model for the incidence of postoperative delirium will be performed accounting for randomized group, age and other possible confounding factors.

Level of originality: Data regarding possible intraoperative interventions for the prevention of postoperative delirium are scarce. In detail, the effects of commonly used anesthetics on the incidence of postoperative delirium and neurocognitive dysfunction have only been studied in retrospective analyses or small prospective studies, which showed inconsistent results. Nevertheless, delirium is a major event after surgery and is associated with postoperative complications, worse neurocognitive recovery and increased mortality, especially in elderly patients. Thus, the results of this trial will help to choose the right anesthetic according to individual patients' requirements to reduce the risk for postoperative delirium in future.

Conditions

Postoperative Delirium; Major Noncardiac Surgery; Postoperative Cognitive Dysfunction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Desflurane Group

After induction of anesthesia, maintenance of anesthesia will be performed using goal-directed administration of desflurane with an intraoperative goal of bispectral index (BIS) 50±10.

Group Type: EXPERIMENTAL

Desflurane

Intervention Type: DRUG

After induction of anesthesia, maintenance of anesthesia will be performed using goal-directed administration of desflurane with an intraoperative goal of bispectral index (BIS) 50±10.

Sevoflurane Group

After induction of anesthesia, maintenance of anesthesia will be performed using goal-directed administration of sevoflurane with an intraoperative goal of bispectral index (BIS) 50±10.

Group Type: ACTIVE_COMPARATOR

Sevoflurane

Intervention Type: DRUG

After induction of anesthesia, maintenance of anesthesia will be performed using goal-directed administration of sevoflurane with an intraoperative goal of bispectral index (BIS) 50±10.

Propofol Group

After induction of anesthesia, maintenance of anesthesia will be performed using goal-directed administration of propofol with an intraoperative goal of bispectral index (BIS) 50±10.

Group Type: ACTIVE_COMPARATOR

Propofol

Intervention Type: DRUG

After induction of anesthesia, maintenance of anesthesia will be performed using goal-directed administration of propofol with an intraoperative goal of bispectral index (BIS) 50±10.

Interventions

Desflurane

After induction of anesthesia, maintenance of anesthesia will be performed using goal-directed administration of desflurane with an intraoperative goal of bispectral index (BIS) 50±10.

Intervention Type: DRUG

Sevoflurane

After induction of anesthesia, maintenance of anesthesia will be performed using goal-directed administration of sevoflurane with an intraoperative goal of bispectral index (BIS) 50±10.

Intervention Type: DRUG

Propofol

After induction of anesthesia, maintenance of anesthesia will be performed using goal-directed administration of propofol with an intraoperative goal of bispectral index (BIS) 50±10.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Provide written informed consent
• ≥65 years of age
• Scheduled for elective major noncardiac surgery with estimated time of surgery ≥ 2 hours

Exclusion Criteria

• Patients undergoing emergency surgery
• BMI > 45 kg/m^2
• History of diagnosed dementia
• Language, vision, or hearing impairments that may compromise cognitive assessments
• History of malignant hyperthermia
• History of structural muscle disease
• History of organ transplantation (kidney, liver, lung, heart)
• Patients undergoing hyperthermic intraperitoneal chemotherapy
• ICU patients undergoing surgery

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical University Innsbruck

OTHER

Sponsor Role: collaborator

Medical University of Vienna

OTHER

Sponsor Role: lead

Responsible Party

Christian Reiterer

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Christian Reiterer, Prof. MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of Vienna

Locations

Medical University of Innsbruck

Innsbruck, , Austria

Site Status: RECRUITING

Medical University of Vienna

Vienna, , Austria

Site Status: RECRUITING

Countries

Austria

Central Contacts

Alexander Taschner, MD

Role: CONTACT

alexander.taschner@meduniwien.ac.at

0043 1 40400 ext. 20760

Facility Contacts

Barbara Sinner, Prof.

Role: primary

barbara.sinner@i-med.ac.at

004351250428503

Christian Reiterer, MD

Role: primary

christian.reiterer@meduniwien.ac.at

0043 1 40400 ext. 20760

References

Taschner A, Fleischmann E, Kabon B, Sinner B, Eckhardt C, Horvath K, Adamowitsch N, Hantakova N, Hochreiter B, Zotti O, Fraunschiel M, Graf A, Reiterer C; RAPID II Trial investigators. Effect of desflurane, sevoflurane or propofol on the incidence of postoperative delirium in older adults undergoing moderate- to high-risk major non-cardiac surgery: study protocol for a prospective, randomised, observer-blinded, clinical trial (RAPID-II trial). BMJ Open. 2024 Nov 27;14(11):e092611. doi: 10.1136/bmjopen-2024-092611.

Reference Type: DERIVED

PMID: 39609026 (View on PubMed)

Other Identifiers

RAPIDII_01

Identifier Type: -

Identifier Source: org_study_id