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| Name | Class |
|---|---|
| Medical University Innsbruck | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Desflurane Group | Experimental | 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 | Active Comparator | 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 | Active Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Desflurane | 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. |
| 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 |
| 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 |
| 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. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Alexander Taschner, MD | Contact | 0043 1 40400 | 20760 | alexander.taschner@meduniwien.ac.at |
| Name | Affiliation | Role |
|---|---|---|
| Christian Reiterer, Prof. MD | Medical University of Vienna | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medical University of Innsbruck | Recruiting | Innsbruck | 6020 | Austria |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39609026 | Derived | 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. |
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| ID | Term |
|---|---|
| D000071257 | Emergence Delirium |
| D000079690 | Postoperative Cognitive Complications |
| ID | Term |
|---|---|
| D003693 | Delirium |
| D003221 | Confusion |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
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| ID | Term |
|---|---|
| D000077335 | Desflurane |
| D000077149 | Sevoflurane |
| D015742 | Propofol |
| ID | Term |
|---|---|
| D005019 | Ethyl Ethers |
| D004987 | Ethers |
| D009930 | Organic Chemicals |
| D008738 | Methyl Ethers |
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| Sevoflurane | 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 | 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. |
|
| 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 |
| 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 |
| Medical University of Vienna | Recruiting | Vienna | 1090 | Austria |
|
| D009422 |
| Nervous System Diseases |
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012816 | Signs and Symptoms |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D060825 | Cognitive Dysfunction |
| D003072 | Cognition Disorders |
| D006845 |
| Hydrocarbons, Fluorinated |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |