Major Noncardiac Surgery, Postoperative Cognitive Dysfunction, Postoperative Delirium
Conditions
Keywords
Propofol, Sevoflurane, Desflurane
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.
Interventions
DRUGDesflurane
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.
DRUGSevoflurane
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.
DRUGPropofol
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.
Sponsors
Medical University Innsbruck
Medical University of Vienna
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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). |
| 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. |
| 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| Sub-Study Analgesia Nociception Index (ANI) | Intraoperative | Association between ANI and postoperative delirium. |
| Sub-Study Advanced Neurobiomarkers | Baseline and third postoperative day. | Difference of serum Neurofilament light-chain (sNFL)and Glial fibrillary acidic protein (GFAP) concentrations between the groups. |
| 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. |
Countries
Austria
Contacts
Primary ContactAlexander Taschner, MD
Outcome results
None listed