Overview
This prospective observational cohort study aims to investigate the relationship between perioperative endogenous melatonin levels and postoperative delirium in patients aged 65 years or older undergoing elective abdominal cancer surgery. The study will also evaluate serotonin, kynurenine, kynurenic acid, and vitamin B12 as potential biomarkers associated with postoperative delirium.
Participants will undergo routine standardized general anesthesia and thoracic epidural analgesia. Venous blood samples will be obtained preoperatively and on postoperative day 3. In participants who develop delirium, an additional blood sample will be obtained as soon as possible after delirium is detected. Postoperative delirium will be assessed using the Confusion Assessment Method (CAM) on postoperative days 1, 3, and 5. No experimental drug or additional therapeutic intervention will be administered as part of the study.
Description
Postoperative delirium is an acute neurocognitive disorder that occurs frequently in older patients after major surgery. Neuroinflammation, alterations in neurotransmitter metabolism, oxidative stress, and disruption of circadian rhythm have been proposed as contributing mechanisms.
The primary objective of this prospective observational cohort study is to evaluate the relationship between perioperative endogenous melatonin levels and the development of postoperative delirium in patients aged 65 years or older undergoing elective abdominal surgery for malignancy. Secondary objectives include evaluation of serotonin, kynurenine, kynurenic acid, and vitamin B12 levels in relation to postoperative delirium.
Eligible participants will receive the routine standardized anesthesia and analgesia protocol used at the study center, including general anesthesia and thoracic epidural analgesia. No experimental drug or treatment will be administered.
Venous blood samples will be obtained during the preoperative period for measurement of melatonin, serotonin, kynurenine, kynurenic acid, and vitamin B12. These biomarkers will be measured again on postoperative day 3. In participants who develop postoperative delirium, an additional sample will be obtained as soon as possible after delirium is detected.
Intraoperative hemodynamic parameters, vasopressor requirements, cerebral oxygenation measured by near-infrared spectroscopy, depth of anesthesia measured by Bispectral Index, estimated blood loss, blood product transfusion, anesthesia duration, and surgical duration will also be recorded.
Postoperative delirium will be prospectively evaluated using the Confusion Assessment Method on postoperative days 1, 3, and 5. Participants will subsequently be classified as having or not having postoperative delirium, and perioperative biomarker levels and clinical variables will be compared between these groups.
Eligibility
Inclusion Criteria:
- Age 65 years or older.
- Scheduled for elective abdominal surgery for malignancy.
- American Society of Anesthesiologists (ASA) physical status II or III.
- Surgery planned under general anesthesia.
- Eligible for thoracic epidural analgesia without contraindications to epidural catheter placement.
- Provision of written informed consent.
Exclusion Criteria:
- Preoperative dementia, Alzheimer disease, Parkinson disease, other known neurodegenerative disease, or a history of preoperative cognitive impairment.
- Emergency surgery.
- Contraindication to epidural analgesia or refusal of epidural catheter placement.
- Chronic use of corticosteroids, melatonin preparations, or medications affecting the serotonergic system, including selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, monoamine oxidase inhibitors, or tricyclic antidepressants.
- Parenteral or high-dose oral vitamin B12 treatment within the previous 3 months.
- Diagnosis of pernicious anemia.
- Communication impairment preventing delirium assessment.
- Advanced liver or kidney failure.
- Intraoperative mean arterial pressure below 65 mmHg.
- Surgical duration longer than 240 minutes.
- Refusal to participate in the study.


