RAPID-II: The Effect of Desflurane Versus Sevoflurane Versus Propofol on Postoperative Delirium
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
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 Design
Arms and Interventions
| 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.
|
Outcome Measures
Primary Outcome Measures
- Incidence of postoperative delirium [First five postoperative days]
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.
Secondary Outcome Measures
- Digit Symbol-Substitution-Test for the incidence of postoperative cognitive dysfunction (POCD) [First five postoperative days]
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).
- Trail Making Test (TMT) for the incidence of postoperative cognitive dysfunction (POCD) [First five postoperative days]
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).
- Postoperative need of supplemental oxygen [During PACU/ICU stay after surgery (max. of first 24 hours after surgery)]
We will record postoperative need for administration of supplemental oxygen to maintain a SpO2 of 93% during PACU or ICU stay.
- Length of stay in ICU [First 30 days after surgery]
Length of stay in ICU after surgery.
- Incidence of Postoperative nausea and vomiting in the early postoperative period [First two hours after surgery]
Episode of nausea and/or vomiting within the first two hours after surgery
- Incidence of Postoperative nausea and vomiting in the late postoperative period [First five postoperative days]
Episode of nausea and/or vomiting from two hours after surgery until the fifth postoperative day.
- Intraoperative hypotension [During surgery]
Intraoperative duration of mean arterial pressure <65mmHg and overall amount of intraoperatively administered catecholamines (including phenylephrine, norepinephrine, epinephrine, etilefrine, ephedrine).
- Death within 5 days after surgery [First five postoperative days]
Mortality in the first five postoperative days.
Other Outcome Measures
- Days at home in the first month after surgery [First 30 days after surgery]
Number of days at home within the first 30 postoperative days.
- Long-term postoperative cognitive dysfunction [One year after surgery]
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.
- Postoperative IL-6 concentrations (pg/ml) [First two postoperative days]
Postoperative area under the curve (AUC) within the first two postoperative days of concentrations of Interleukin 6 (IL-6).
- Postoperative PCT concentrations (ng/ml) [First two postoperative days]
Postoperative area under the curve (AUC) within the first two postoperative days of concentrations of Procalcitonin (PCT).
- Postoperative CRP concentrations (mg/dl) [First two postoperative days]
Postoperative area under the curve (AUC) within the first two postoperative days of concentrations of C-reactive protein (CRP).
- Postoperative Copeptin concentrations (pmol/L) [First two postoperative days]
AUC within the first two postoperative days of concentrations of Copeptin.
- Postoperative TnT concentrations (ng/L) [First two postoperative days]
AUC within the first two postoperative days of concentrations of TnT.
- Postoperative NT-proBNP concentrations (pg/ml) [First two postoperative days]
AUC within the first two postoperative days of concentrations of NT-proBNP.
- Postoperative S100-B concentrations (µg/L) [First two postoperative days]
AUC within the first two postoperative days of concentrations of S100-B.
- Postoperative NSE concentrations (µg/L) [First two postoperative days]
AUC within the first two postoperative days of concentrations of NSE.
- All-cause death within one year after surgery [One year after surgery]
All cause one-year mortality.
Eligibility Criteria
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:
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Patients undergoing emergency surgery
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BMI > 45 kg/m^2
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History of diagnosed dementia
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Language, vision, or hearing impairments that may compromise cognitive assessments
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History of malignant hyperthermia
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History of structural muscle disease
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History of organ transplantation (kidney, liver, lung, heart)
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Patients undergoing hyperthermic intraperitoneal chemotherapy
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ICU patients undergoing surgery
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Medical University of Vienna | Vienna | Austria | 1090 |
Sponsors and Collaborators
- Medical University of Vienna
Investigators
- Principal Investigator: Christian Reiterer, Prof. MD, Medical University of Vienna
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- RAPIDII_01