The Effect of Desflurane Versus Sevoflurane Versus Propofol on Postoperative Delirium (RAPID-II)

The Effect of Desflurane Versus Sevoflurane Versus Propofol on Postoperative Delirium in Elderly Patients Undergoing Moderate- to High-risk Major Noncardiac Surgery - a Prospective, Observer-blinded, Randomized, Clinical Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Postoperative Delirium; Postoperative Cognitive Dysfunction; Major Noncardiac Surgery
• Intervention / Treatment: Drug: Desflurane; Drug: Sevoflurane; Drug: Propofol

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.

• Study Type: Interventional
• Enrollment (Estimated): 1332
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Alexander Taschner, MD; Phone Number: 20760 0043 1 40400; Email: alexander.taschner@meduniwien.ac.at

Study Locations

• Austria
  • Innsbruck, Austria, 6020
    • Recruiting
    • Medical University of Innsbruck
    • Contact: Barbara Sinner, Prof.; Phone Number: 004351250428503; Email: barbara.sinner@i-med.ac.at
  • Vienna, Austria, 1090
    • Recruiting
    • Medical University of Vienna
    • Contact: Christian Reiterer, MD; Phone Number: 20760 0043 1 40400; Email: christian.reiterer@meduniwien.ac.at

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: 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.
Active Comparator: 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.	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.
Active Comparator: 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.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of postoperative delirium	Delirium will be assessed via 3D-cognitive assessment method (3D-CAM) test as early in the morning as practical and in the early evening for the initial five postoperative days while the patients remain hospitalized according to current recommendations. In patients in the intensive care unit (ICU), we will perform the 3D-CAM-ICU. Any positive CAM test will be considered evidence of delirium, which will be analyzed dichotomously.	First five postoperative days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Digit Symbol-Substitution-Test for the incidence of postoperative cognitive dysfunction (POCD)	POCD will be assessed using the Digit-Symbol-Substitution-Test (DSST). The occurrence of POCD will be defined when a patient has a Z score on two or all tests or the combined Z score is below -1.96 standard deviation (SD).	First five postoperative days
Trail Making Test (TMT) for the incidence of postoperative cognitive dysfunction (POCD)	POCD will be assessed using the Trail Making Test (TMT). The occurrence of POCD will be defined when a patient has a Z score on two or all tests or the combined Z score is below -1.96 standard deviation (SD).	First five postoperative days
Postoperative need of supplemental oxygen	We will record postoperative need for administration of supplemental oxygen to maintain a SpO2 of 93% during PACU or ICU stay.	During PACU/ICU stay after surgery (max. of first 24 hours after surgery)
Length of stay in ICU	Length of stay in ICU after surgery.	First 30 days after surgery
Incidence of Postoperative nausea and vomiting in the early postoperative period	Episode of nausea and/or vomiting within the first two hours after surgery	First two hours after surgery
Incidence of Postoperative nausea and vomiting in the late postoperative period	Episode of nausea and/or vomiting from two hours after surgery until the fifth postoperative day.	First five postoperative days
Intraoperative hypotension	Intraoperative duration of mean arterial pressure <65mmHg and overall amount of intraoperatively administered catecholamines (including phenylephrine, norepinephrine, epinephrine, etilefrine, ephedrine).	During surgery
Death within 5 days after surgery	Mortality in the first five postoperative days.	First five postoperative days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Days at home in the first month after surgery	Number of days at home within the first 30 postoperative days.	First 30 days after surgery
Long-term postoperative cognitive dysfunction	Long-term postoperative cognitive dysfunction will be assessed via Montreal cognitive assessment (MoCA). We will assess the baseline MoCA a day before surgery and one year after surgery via phone interview. Minimum score of the MoCA is 0 points. Maximum score of the MoCA is 22 points. Postoperative cognitive dysfunction is defined as a reduction of at least 2 points as compared to baseline.	One year after surgery
Postoperative IL-6 concentrations (pg/ml)	Postoperative area under the curve (AUC) within the first two postoperative days of concentrations of Interleukin 6 (IL-6).	First two postoperative days
Postoperative PCT concentrations (ng/ml)	Postoperative area under the curve (AUC) within the first two postoperative days of concentrations of Procalcitonin (PCT).	First two postoperative days
Postoperative CRP concentrations (mg/dl)	Postoperative area under the curve (AUC) within the first two postoperative days of concentrations of C-reactive protein (CRP).	First two postoperative days
Postoperative Copeptin concentrations (pmol/L)	AUC within the first two postoperative days of concentrations of Copeptin.	First two postoperative days
Postoperative TnT concentrations (ng/L)	AUC within the first two postoperative days of concentrations of TnT.	First two postoperative days
Postoperative NT-proBNP concentrations (pg/ml)	AUC within the first two postoperative days of concentrations of NT-proBNP.	First two postoperative days
Postoperative S100-B concentrations (µg/L)	AUC within the first two postoperative days of concentrations of S100-B.	First two postoperative days
Postoperative NSE concentrations (µg/L)	AUC within the first two postoperative days of concentrations of NSE.	First two postoperative days
All-cause death within one year after surgery	All cause one-year mortality.	One year after surgery
Sub-Study Advanced Neurobiomarkers	Difference of serum Neurofilament light-chain (sNFL)and Glial fibrillary acidic protein (GFAP) concentrations between the groups.	Baseline and third postoperative day.
Sub-Study Analgesia Nociception Index (ANI)	Association between ANI and postoperative delirium.	Intraoperative

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Collaborators: Medical University Innsbruck
• Investigators: Principal Investigator: Christian Reiterer, Prof. MD, Medical University of Vienna

Study record dates

Study Major Dates

• Study Start (Actual): September 3, 2023
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: July 17, 2023
• First Submitted That Met QC Criteria: August 11, 2023
• First Posted (Actual): August 14, 2023

Study Record Updates

• Last Update Posted (Actual): April 30, 2025
• Last Update Submitted That Met QC Criteria: April 27, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Propofol; Desflurane; Sevoflurane
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Postoperative Complications; Pathologic Processes; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Cognition Disorders; Postoperative Cognitive Complications; Emergence Delirium; Delirium; Cognitive Dysfunction; Physiological Effects of Drugs; Anesthetics; Central Nervous System Depressants; Platelet Aggregation Inhibitors; Hypnotics and Sedatives; Anesthetics, Intravenous; Anesthetics, General; Anesthetics, Inhalation; Desflurane; Sevoflurane; Propofol
• Other Study ID Numbers: RAPIDII_01

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