Heart Rate Variability and Biochemical Biomarkers as Predictors of Autonomic Dysfunction during Pediatric General Anesthesia

Abstract

Background: Autonomic dysfunction during pediatric general anesthesia may contribute to intraoperative hemodynamic instability and adverse postoperative outcomes. Heart rate variability (HRV) is a non-invasive marker of autonomic nervous system activity, while biochemical biomarkers reflecting inflammation, oxidative stress, and neuroendocrine responses may provide complementary information regarding perioperative autonomic regulation. This study evaluated the predictive value of HRV parameters and selected biochemical biomarkers for autonomic dysfunction in children undergoing general anesthesia.

Methods: A prospective observational study was conducted on 120 pediatric patients aged 2–12 years undergoing elective surgery under general anesthesia. Preoperative HRV was assessed using a five-minute electrocardiographic recording, and time-domain (SDNN, RMSSD) and frequency-domain (LF, HF, LF/HF ratio) parameters were analyzed. Blood samples collected before anesthesia induction were analyzed for serum cortisol, high-sensitivity C-reactive protein (hs-CRP), malondialdehyde (MDA), and total antioxidant capacity (TAC). Autonomic dysfunction was defined by the occurrence of significant intraoperative hypotension, bradycardia, or marked heart rate fluctuations requiring pharmacological intervention. Multivariate logistic regression and receiver operating characteristic (ROC) curve analyses were performed.

Results: Autonomic dysfunction occurred in 34 (28.3%) patients. These patients demonstrated significantly lower SDNN (31.4 ± 8.2 vs. 46.8 ± 10.6 ms, p < 0.001) and RMSSD (24.7 ± 7.1 vs. 39.2 ± 9.4 ms, p < 0.001), together with higher LF/HF ratios (2.38 ± 0.69 vs. 1.52 ± 0.48, p < 0.001). Serum cortisol (18.6 ± 4.3 vs. 13.4 ± 3.8 μg/dL), hs-CRP (3.8 ± 1.2 vs. 2.1 ± 0.9 mg/L), and MDA (4.7 ± 0.8 vs. 3.2 ± 0.7 nmol/mL) were significantly elevated, whereas TAC (0.92 ± 0.19 vs. 1.28 ± 0.24 mmol/L) was significantly reduced (all p < 0.001). Multivariate analysis identified reduced SDNN (OR = 2.89, 95% CI: 1.74–4.81), elevated cortisol (OR = 2.36, 95% CI: 1.39–4.02), and increased MDA (OR = 2.71, 95% CI: 1.58–4.63) as independent predictors of autonomic dysfunction. The combined HRV–biomarker model demonstrated excellent predictive performance with an AUC of 0.91 (95% CI: 0.85–0.96), sensitivity of 88.2%, and specificity of 84.9%.

Conclusion: Reduced heart rate variability combined with elevated biochemical markers of stress, inflammation, and oxidative stress independently predicted autonomic dysfunction during pediatric general anesthesia. Integrating HRV analysis with biochemical biomarkers may improve perioperative risk stratification and facilitate individualized anesthetic management in pediatric surgical patients.