Clinical trial NCT05990790: The Effect of Desflurane Versus Sevoflurane Versus Propofol on Postoperative Delirium
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Postoperative Delirium
Major Noncardiac Surgery
Postoperative Cognitive Dysfunction
Keywords: Propofol
Sevoflurane
Desflurane
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
Collaborators: name: Medical University Innsbruck
First posted: 2023-08-14
Enrollment: 1332
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Incidence of postoperative delirium
timeFrame: First five postoperative days
Secondary outcomes:
measure: Digit Symbol-Substitution-Test for the incidence of postoperative cognitive dysfunction (POCD)
timeFrame: First five postoperative days
measure: Trail Making Test (TMT) for the incidence of postoperative cognitive dysfunction (POCD)
timeFrame: First five postoperative days
measure: Postoperative need of supplemental oxygen
timeFrame: During PACU/ICU stay after surgery (max. of first 24 hours after surgery)
measure: Length of stay in ICU
timeFrame: First 30 days after surgery
measure: Incidence of Postoperative nausea and vomiting in the early postoperative period
timeFrame: First two hours after surgery
measure: Incidence of Postoperative nausea and vomiting in the late postoperative period
timeFrame: First five postoperative days
measure: Intraoperative hypotension
timeFrame: During surgery
measure: Death within 5 days after surgery
timeFrame: First five postoperative days
Other outcomes:
measure: Days at home in the first month after surgery
timeFrame: First 30 days after surgery
measure: Long-term postoperative cognitive dysfunction
timeFrame: One year after surgery
measure: Postoperative IL-6 concentrations (pg/ml)
timeFrame: First two postoperative days
measure: Postoperative PCT concentrations (ng/ml)
timeFrame: First two postoperative days
measure: Postoperative CRP concentrations (mg/dl)
timeFrame: First two postoperative days
measure: Postoperative Copeptin concentrations (pmol/L)
timeFrame: First two postoperative days
measure: Postoperative TnT concentrations (ng/L)
timeFrame: First two postoperative days
measure: Postoperative NT-proBNP concentrations (pg/ml)
timeFrame: First two postoperative days
measure: Postoperative S100-B concentrations (µg/L)
timeFrame: First two postoperative days
measure: Postoperative NSE concentrations (µg/L)
timeFrame: First two postoperative days
measure: All-cause death within one year after surgery
timeFrame: One year after surgery
measure: Sub-Study Advanced Neurobiomarkers
timeFrame: Baseline and third postoperative day.
measure: Sub-Study Analgesia Nociception Index (ANI)
timeFrame: Intraoperative
Locations:
city: Innsbruck
country: Austria
facility: Medical University of Innsbruck
city: Vienna
country: Austria
facility: Medical University of Vienna
Study officials:
affiliation: Medical University of Vienna
name: Christian Reiterer, Prof. MD
role: PRINCIPAL_INVESTIGATOR
References: