Heart Rate Variability Changes and Postoperative Delirium After Major Abdominal Surgery

Postoperative delirium (POD) is a common neurocognitive complication following major surgery in older adults and is associated with increased morbidity, prolonged hospitalization, and adverse clinical outcomes. However, objective and easily obtainable biomarkers for early identification of patients at high risk of POD remain limited.

Heart rate variability (HRV) reflects autonomic nervous system regulation and may provide a non-invasive marker of physiological stress and impaired autonomic adaptability. Major abdominal surgery induces substantial systemic stress responses, including inflammation, neuroendocrine activation, and autonomic disturbances. Whether early postoperative alterations in HRV are associated with subsequent POD development remains unclear.

This is a single-center, prospective observational cohort study. Patients aged 65-85 years undergoing elective major abdominal surgery under general anesthesia will be consecutively enrolled. Baseline demographic characteristics, comorbidities, frailty status, cognitive function, and perioperative clinical variables will be collected.

Resting HRV will be measured at 10:00 AM on the day of surgery before anesthesia induction and again at the same time point on the first postoperative day using a validated heart rate monitoring device. HRV analysis will be performed based on standardized 5-minute recordings in accordance with established recommendations for short-term HRV assessment. Time-domain, frequency-domain, and nonlinear HRV parameters will be calculated.

Postoperative delirium will be assessed daily from 24 hours after surgery to postoperative day 7 using the 3-Minute Diagnostic Interview for Confusion Assessment Method (3D-CAM). Additional clinical outcomes include delirium severity, delirium duration, postoperative cognitive function, quality of recovery, postoperative nausea and vomiting, and length of hospital stay.

The primary objective is to evaluate the association between early postoperative HRV changes and the occurrence of POD after adjustment for clinically relevant confounding factors, including age, baseline cognitive function, frailty status, surgical duration, and baseline HRV. Secondary analyses will explore the relationship between representative HRV markers and postoperative clinical outcomes and assess their potential utility for early POD risk stratification.

Inclusion criteria

• Patients admitted to Jiangsu Provincial People's Hospital who are scheduled to undergo elective major abdominal surgery under general anesthesia.
• Older patients aged 65 to 85 years.
• Expected postoperative hospital stay of ≥7 days.
• Body mass index (BMI) between 18.5 and 28.0 kg/m².
• American Society of Anesthesiologists (ASA) physical status classification I-III.
• Patients who are conscious, mentally competent, and able to cooperate with heart rate variability (HRV) measurements, questionnaire assessments, and follow-up evaluations.
• Patients who voluntarily participate in the study and provide written informed consent.

Exclusion criteria

• Patients with ASA physical status classification ≥IV or patients with end-stage cancer.
• Patients with implanted cardiac pacemakers, implantable cardioverter-defibrillators, or other electronic devices that may interfere with ECG signal acquisition.
• Patients with severe or unstable cardiovascular diseases, including but not limited to acute coronary syndrome, symptomatic bradycardia, sick sinus syndrome, second-degree or higher atrioventricular block, atrial fibrillation, atrial flutter, frequent premature beats, or other arrhythmias that may affect heart rate variability analysis.
• Patients with diseases affecting autonomic nervous system function, including confirmed primary or secondary autonomic dysfunction, such as Parkinson's disease, multiple system atrophy, severe diabetic autonomic neuropathy, severe peripheral neuropathy, poorly controlled hyperthyroidism or hypothyroidism, and systemic amyloidosis.
• Patients with a history of organic central nervous system diseases or psychiatric disorders, including major traumatic brain injury, stroke (ischemic or hemorrhagic), intracranial mass lesions, epilepsy, schizophrenia, bipolar disorder, major depressive disorder, or other severe psychiatric disorders.
• Patients with severe baseline cognitive impairment or inability to complete cognitive assessments, including any of the following: (1) preoperative baseline Montreal Cognitive Assessment (MoCA) score <14 points; (2) previously diagnosed dementia, preoperative delirium, coma, or other severe disturbances of consciousness; or (3) inability to complete standardized cognitive assessments due to severe visual impairment, hearing impairment, language barriers, or other causes.
• Patients unable to undergo HRV measurement within 24 hours after surgery, including those with severe perioperative complications, emergency reoperation, extremely unstable vital signs, or requiring continuous deep sedation after surgery.
• Patients who have taken anticholinergic medications, beta-blockers, antiarrhythmic drugs, or other medications that may significantly affect autonomic function within 1 month before study enrollment.
• Patients who are currently participating in any other clinical trial.