Association between Serum Cortisol Levels and Autonomic Nervous System Function during Anesthesia in Adults with Chronic Migraine

Abstract

Background: Chronic migraine is associated with autonomic dysregulation and altered hypothalamic–pituitary–adrenal activity. The perioperative interaction between cortisol responses and autonomic function remains poorly defined.

Objective: To evaluate the association between serum cortisol concentrations and heart rate variability during general anesthesia in adults with chronic migraine.

Methods: This prospective observational study included 120 adults with chronic migraine undergoing elective surgery at Khawaja Muhammad Safdar Medical College, Sialkot, and Jinnah Hospital, Lahore, from January 2025 to January 2026. Serum cortisol and five-minute electrocardiographic recordings were obtained before induction, after induction, 30 minutes after incision, and near the end of surgery. Autonomic function was assessed using RMSSD, HF-HRV, and SDNN. Associations were examined using correlation analysis and multivariable linear mixed-effects modeling.

Results: Mean age was 39.2 ± 10.4 years, and 72.5% were women. Cortisol decreased after induction from 14.1 ± 4.3 to 11.9 ± 3.8 μg/dL, then increased to 17.4 ± 5.1 μg/dL after incision and 19.2 ± 5.6 μg/dL near surgery completion. RMSSD declined significantly across the same period. Cortisol correlated inversely with RMSSD after incision (r=−0.46, p<0.001) and near surgery completion (r=−0.43, p<0.001). Each 1-μg/dL increase in cortisol was independently associated with a 2.1% reduction in RMSSD. Greater headache frequency was also associated with lower RMSSD, suggesting reduced autonomic adaptability with increasing migraine burden.

Conclusion: Higher perioperative cortisol concentrations were independently associated with reduced vagally mediated heart rate variability, indicating coordinated neuroendocrine and autonomic stress responses in adults with chronic migraine.