Evaluation of Desflurane, Sevoflurane, and Propofol on Postoperative Delirium in Elderly Patients Undergoing Major Non-Cardiac Surgery

The primary objective of this clinical trial is to evaluate the effect of maintenance of general anesthesia using **desflurane**, **sevoflurane**, or **propofol** on the incidence of postoperative delirium within the first five postoperative days in elderly patients undergoing moderate- to high-risk major noncardiac surgery. This is clinically relevant as postoperative delirium is a common complication in elderly patients, which can lead to prolonged hospital stays, increased morbidity, and higher healthcare costs.

Secondary objectives include:

• Evaluating the effect of desflurane, sevoflurane, or propofol on the incidence of postoperative cognitive dysfunction (POCD) and long-term POCD.
• Assessing the difference in the incidence of postoperative nausea and vomiting (PONV) in both the early and late postoperative periods between the anesthesia groups.
• Determining the effect of anesthesia maintenance on the postoperative need for supplemental oxygen for SpO2 ≥93%.
• Evaluating the intraoperative duration of mean arterial pressure (MAP) < 65 mmHg and the overall amount of intraoperatively administered catecholamines.
• Determining the difference in the length of stay in the intensive care unit and the number of days at home in the first month after surgery between the study groups.

The clinical trial involves **elderly patients** aged 65 years and older who are scheduled for elective major noncardiac surgery with an estimated surgery duration of at least two hours. The study population includes both male and female participants, and the trial does not focus on a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants were selected based on their ability to provide written informed consent and their scheduled surgery type and duration. The trial aims to evaluate the effect of maintaining general anesthesia using desflurane, sevoflurane, or propofol on the incidence of postoperative delirium within the first five postoperative days. No specific lifestyle considerations such as diet or physical activity are highlighted in the selection criteria.

The clinical trial is designed to evaluate the effect of **desflurane**, **sevoflurane**, and **propofol** on the incidence of postoperative delirium in elderly patients undergoing moderate- to high-risk major noncardiac surgery. This is a prospective, double-blind, randomized, controlled trial. The trial is expected to run from May 1, 2023, to December 31, 2027. Participants will be randomly assigned to receive one of the three anesthetic agents during their surgery, with the primary endpoint being the incidence of postoperative delirium within the first five postoperative days.

Study visits will follow a structured sequence, beginning with an inclusion (screening) visit where eligibility criteria are assessed. Participants must provide written informed consent, be 65 years or older, and be scheduled for elective major noncardiac surgery with an estimated duration of at least two hours. Follow-up visits will occur postoperatively to monitor for delirium and other secondary endpoints, such as postoperative cognitive dysfunction and nausea and vomiting. The end-of-study visit will conclude the participant's involvement, assessing long-term outcomes and overall health status.

The expected length of participant involvement is approximately 30 days post-surgery, with the possibility of early termination if the participant withdraws consent or if any adverse events necessitate discontinuation. The trial is categorized as a low-intervention study, as the anesthetic agents used are standard in clinical practice, minimizing additional risk to participants. The trial's design ensures rigorous assessment of the primary and secondary endpoints, contributing valuable data to the understanding of anesthetic effects on postoperative outcomes in the elderly population.

The clinical trial involves the administration of three **anesthetic** agents: **Propofol**, **Sevoflurane**, and **Desflurane**, each with distinct pharmaceutical forms and administration routes. **Propofol** is provided as an emulsion for injection or infusion, specifically "Propofol 'Fresenius' 2% mit MCT - Emulsion zur Injektion oder Infusion," manufactured by Fresenius Kabi Austria GmbH. It is administered via **intravenous infusion**. The dosage is calculated based on body weight, with a maximum daily dose of 12 mg/kg/h and a maximum treatment period of one day. Compliance with the dosing schedule is monitored through standard clinical practices.

**Sevoflurane** is utilized as an inhalation vapor, liquid form, under the product name "Sevorane – Inhalationsnarkotikum," produced by AbbVie GmbH. It is administered through **inhalation use**. The maximum daily dose is set at 6% (V/V), with the treatment period limited to one day. The administration of Sevoflurane is conducted using standard inhalation devices, and participant compliance is ensured through monitoring of inhalation parameters.

**Desflurane** is also provided as an inhalation vapor, liquid form, marketed as "SUPRANE - Inhalationsnarkotikum" by Baxter Healthcare GmbH. Similar to Sevoflurane, it is administered via **inhalation use**. The maximum daily dose for Desflurane is 15% (V/V), with a treatment duration of one day. The administration is facilitated by standard inhalation equipment, and compliance is monitored by tracking inhalation metrics.

All three substances are chemically derived and are not formulated for pediatric use. The trial is designed to compare the effects of these anesthetics on postoperative delirium in elderly patients undergoing moderate- to high-risk major abdominal surgery. No additional non-experimental treatments, such as placebo or standard-of-care therapy, are specified in the trial protocol. The trial ensures rigorous monitoring of dosing schedules and participant compliance to maintain the integrity of the study outcomes.

Efficacy in this clinical trial will be assessed by evaluating the incidence of **postoperative delirium** within the first five postoperative days. This primary endpoint will be measured in elderly patients undergoing moderate- to high-risk major noncardiac surgery, with anesthesia maintained using desflurane, sevoflurane, or propofol. Secondary endpoints include the incidence of postoperative cognitive dysfunction, both short-term and long-term, as well as the incidence of postoperative nausea and vomiting (PONV) within the first two postoperative hours and from two hours after surgery until the fifth postoperative day. Additional secondary endpoints involve the administration of supplemental oxygen in the post-anesthesia care unit (PACU) or intensive care unit (ICU) for maintaining SpO2 ≥ 93%, the intraoperative duration of mean arterial pressure below 65 mmHg, the overall amount of intraoperatively administered catecholamines, the length of stay in the ICU after surgery until hospital discharge, and the number of days spent at home within the first 30 postoperative days.