Medication Effects on Heart Rate Variability in Critical Illness: The Overlooked Confounder.

Heart rate variability (HRV) reflects autonomic nervous system function and has emerged as a potential noninvasive biomarker for early detection of physiologic deterioration in critical illness. HRV-based prediction models show promise; however, translation into routine ICU practice has been limited. A major barrier is the insufficient characterization of medication effects on HRV. Pharmacologic agents commonly used in critical care, including vasopressors, steroids, and antiarrhythmics, can directly or indirectly alter autonomic tone, yet existing studies rarely account for these influences. As a result, medication-induced HRV changes may represent meaningful therapeutic response or misleading confounding noise, complicating interpretation. Current studies do not adequately account for medication exposure when evaluating HRV in critical illness. We outline research priorities focused on quantifying medication effects, integrating medication exposure into predictive modeling, evaluating HRV as a marker of treatment response, and determining the utility of HRV as a treatment target.