The Effect of Desflurane Versus Sevoflurane Versus Propofol on Postoperative Delirium

Postoperative Delirium Clinical Trial

— RAPID-II  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05990790
• Other study ID #: RAPIDII_01
• Status: Recruiting
• Phase: Phase 4
• Start date: September 3, 2023
• Est. completion date: December 31, 2028

Study information

• Verified date: September 2023
• Source: Medical University of Vienna
• Contact: Alexander Taschner, MD
• Phone: 0043 1 40400
• Email: alexander.taschner[@]meduniwien.ac.at
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1332
• Est. completion date: December 31, 2028
• Est. primary completion date: December 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Delirium
• Emergence Delirium
• Postoperative Cognitive Complications
• Postoperative Cognitive Dysfunction
• Postoperative Delirium

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
Austria	Medical University of Vienna	Vienna

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Vienna

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	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
Other	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
Other	Postoperative Copeptin concentrations (pmol/L)	AUC within the first two postoperative days of concentrations of Copeptin.	First two postoperative days
Other	Postoperative TnT concentrations (ng/L)	AUC within the first two postoperative days of concentrations of TnT.	First two postoperative days
Other	Postoperative NT-proBNP concentrations (pg/ml)	AUC within the first two postoperative days of concentrations of NT-proBNP.	First two postoperative days
Other	Postoperative S100-B concentrations (µg/L)	AUC within the first two postoperative days of concentrations of S100-B.	First two postoperative days
Other	Postoperative NSE concentrations (µg/L)	AUC within the first two postoperative days of concentrations of NSE.	First two postoperative days
Other	All-cause death within one year after surgery	All cause one-year mortality.	One year after surgery
Primary	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	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
Secondary	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
Secondary	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)
Secondary	Length of stay in ICU	Length of stay in ICU after surgery.	First 30 days after surgery
Secondary	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
Secondary	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
Secondary	Intraoperative hypotension	Intraoperative duration of mean arterial pressure <65mmHg and overall amount of intraoperatively administered catecholamines (including phenylephrine, norepinephrine, epinephrine, etilefrine, ephedrine).	During surgery
Secondary	Death within 5 days after surgery	Mortality in the first five postoperative days.	First five postoperative days