Heart rate variability (HRV), as a non-invasive indicator for assessing autonomic nervous system (ANS) function, has accumulated substantial evidence in prognostic prediction research among critically ill patients. However, its clinical translation has lagged significantly behind, resulting in a pronounced "research-to-practice gap". This review systematically analyzes the specific barriers to HRV monitoring imposed by the intensive care unit setting: (1) intensive therapeutic interventions (sedation and analgesia, vasoactive agents, mechanical ventilation) introduce confounding effects, rendering the HRV signal an amalgam of disease and treatment effects; (2) heterogeneity of extreme pathophysiological states leads to highly individualized variations in ANS response patterns; (3) signal quality impairment caused by high-frequency arrhythmias and electrical interference. In light of these challenges, the conventional HRV analytical paradigm exhibits limitations in the ICU setting, including loss of parameter interpretability, mismatch between static measurements and dynamic clinical conditions, and infeasibility of standardized measurement conditions. This article proposes four strategic approaches: transitioning toward dynamic trend analysis, establishing ICU-specific reporting standards, advancing multimodal data integration, and exploring novel interference-resistant metrics. These strategies aim to provide a roadmap for high-quality research enabling robust clinical application of HRV.

Xixi Liao, Linlin Xiao, Jing Zhang, Xueping Hou, Dan Zhang. Heart Rate Variability in Intensive Care Unit: Clinical Applications and Challenges. International Journal of Frontiers in Medicine (2026), Vol. 8, Issue 1: 51-59. https://doi.org/10.25236/IJFM.2026.080106.

[1] Wehrwein EA, Orer HS, Barman SM. Overview of the Anatomy, Physiology, and Pharmacology of the Autonomic Nervous System. Comprehensive Physiology 2016; 6:1239-1278.

[2] Carrara M, Ferrario M, Bollen Pinto B, Herpain A. The autonomic nervous system in septic shock and its role as a future therapeutic target: a narrative review. Ann Intensive Care 2021; 11:80.

[3] Xhyheri B, Manfrini O, Mazzolini M et al. Heart rate variability today. Progress in cardiovascular diseases 2012; 55:321-331.

[4] van Wijk RJ, Quinten VM, van Rossum MC et al. Predicting deterioration of patients with early sepsis at the emergency department using continuous heart rate variability analysis: a model-based approach. Scandinavian journal of trauma, resuscitation and emergency medicine 2023; 31:15.

[5] Zhang P, Roberts T, Richards B, Haseler LJ. Utilizing heart rate variability to predict ICU patient outcome in traumatic brain injury. BMC bioinformatics 2020; 21:481.

[6] Lee H, Yang HL, Ryu HG et al. Real-time machine learning model to predict in-hospital cardiac arrest using heart rate variability in ICU. NPJ digital medicine 2023; 6:215.

[7] Bodenes L, N'Guyen QT, Le Mao R et al. Early heart rate variability evaluation enables to predict ICU patients' outcome. Scientific reports 2022; 12:2498.

[8] Khan MS, Javaid SS, Mentz RJ et al. Heart rate variability in patients with cardiovascular diseases. Progress in cardiovascular diseases 2025; 91:67-79.

[9] Islam S, Kim D, Lee YS, Moon SS. Association between diabetic peripheral neuropathy and heart rate variability in subjects with type 2 diabetes. Diabetes research and clinical practice 2018; 140:18-26.

[10] Reyes del Paso GA, Langewitz W, Mulder LJ et al. The utility of low frequency heart rate variability as an index of sympathetic cardiac tone: a review with emphasis on a reanalysis of previous studies. Psychophysiology 2013; 50:477-487.

[11] Schwartz P J, Levy M N. Vagal Control of the Heart: Experimental Basis and Clinical Implications. United States: Armonk, NY : Futura Pub. Co., 1994.

[12] Benarroch EE. The central autonomic network: functional organization, dysfunction, and perspective. Mayo Clinic proceedings 1993; 68:988-1001.

[13] Julien C. The enigma of Mayer waves: Facts and models. Cardiovascular research 2006; 70:12-21.

[14] Hayano J, Sakakibara Y, Yamada M et al. Decreased magnitude of heart rate spectral components in coronary artery disease. Its relation to angiographic severity. Circulation 1990; 81:1217-1224.

[15] Hirsch JA, Bishop B. Respiratory sinus arrhythmia in humans: how breathing pattern modulates heart rate. The American journal of physiology 1981; 241:H620-629.

[16] Costa MD, Davis RB, Goldberger AL. Heart Rate Fragmentation: A New Approach to the Analysis of Cardiac Interbeat Interval Dynamics. Frontiers in physiology 2017; 8:255.

[17] Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. PubMed 1996.

[18] Kleiger RE, Stein PK, Bigger JT, Jr. Heart rate variability: measurement and clinical utility. Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc 2005; 10:88-101.

[19] Akselrod S, Gordon D, Ubel FA et al. Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control. Science (New York, N.Y.) 1981; 213:220-222.

[20] Peng CK, Havlin S, Stanley HE, Goldberger AL. Quantification of scaling exponents and crossover phenomena in nonstationary heartbeat time series. Chaos (Woodbury, N.Y.) 1995; 5:82-87.

[21] Wang X, Huang ZG, Gold A et al. Propofol modulates gamma-aminobutyric acid-mediated inhibitory neurotransmission to cardiac vagal neurons in the nucleus ambiguus. Anesthesiology 2004; 100:1198-1205.

[22] Fabus MS, Sleigh JW, Warnaby CE. Effect of Propofol on Heart Rate and Its Coupling to Cortical Slow Waves in Humans. Anesthesiology 2024; 140:62-72.

[23] Hasegawa G, Hirata N, Yoshikawa Y, Yamakage M. Differential effects of remimazolam and propofol on heart rate variability during anesthesia induction. Journal of anesthesia 2022; 36:239-245.

[24] Vettorello M, Colombo R, De Grandis CE et al. Effect of fentanyl on heart rate variability during spontaneous and paced breathing in healthy volunteers. Acta anaesthesiologica Scandinavica 2008; 52:1064-1070.

[25] Ahmed MW, Kadish AH, Parker MA, Goldberger JJ. Effect of physiologic and pharmacologic adrenergic stimulation on heart rate variability. J Am Coll Cardiol 1994; 24:1082-1090.

[26] Maki KA, Goodyke MP, Rasmussen K, Bronas UG. An Integrative Literature Review of Heart Rate Variability Measures to Determine Autonomic Nervous System Responsiveness Using Pharmacological Manipulation. The Journal of cardiovascular nursing 2024; 39:58-78.

[27] Ritz T. Putting back respiration into respiratory sinus arrhythmia or high-frequency heart rate variability: Implications for interpretation, respiratory rhythmicity, and health. Biological psychology 2024; 185:108728.

[28] Nunan D, Sandercock GR, Brodie DA. A quantitative systematic review of normal values for short-term heart rate variability in healthy adults. Pacing and clinical electrophysiology : PACE 2010; 33:1407-1417.

[29] Meehan ZM, Shaffer F. Do Longer Exhalations Increase HRV During Slow-Paced Breathing? Applied psychophysiology and biofeedback 2024; 49:407-417.

[30] Bae D, Matthews JJL, Chen JJ, Mah L. Increased exhalation to inhalation ratio during breathing enhances high-frequency heart rate variability in healthy adults. Psychophysiology 2021; 58:e13905.

[31] Laborde S, Iskra M, Zammit N et al. Slow-Paced Breathing: Influence of Inhalation/Exhalation Ratio and of Respiratory Pauses on Cardiac Vagal Activity. Sustainability 2021; 13:7775.

[32] Kiryachkov YY, Bosenko SA, Muslimov BG, Petrova MV. Dysfunction of the Autonomic Nervous System and its Role in the Pathogenesis of Septic Critical Illness (Review). Sovremennye tekhnologii v meditsine 2021; 12:106-116.

[33] Williams DP, Koenig J, Carnevali L et al. Heart rate variability and inflammation: A meta-analysis of human studies. Brain, behavior, and immunity 2019; 80:219-226.

[34] Wybraniec MT, Mizia-Stec K, Krzych Ł. Neurocardiogenic injury in subarachnoid hemorrhage: A wide spectrum of catecholamin-mediated brain-heart interactions. Cardiology journal 2014; 21:220-228.

[35] Megjhani M, Kaffashi F, Terilli K et al. Heart Rate Variability as a Biomarker of Neurocardiogenic Injury After Subarachnoid Hemorrhage. Neurocritical care 2020; 32:162-171.

[36] Meyfroidt G, Baguley IJ, Menon DK. Paroxysmal sympathetic hyperactivity: the storm after acute brain injury. The Lancet. Neurology 2017; 16:721-729.

[37] Baguley IJ, Heriseanu RE, Cameron ID et al. A critical review of the pathophysiology of dysautonomia following traumatic brain injury. Neurocritical care 2008; 8:293-300.

[38] Baguley IJ, Heriseanu RE, Felmingham KL, Cameron ID. Dysautonomia and heart rate variability following severe traumatic brain injury. Brain injury 2006; 20:437-444.

[39] Eraky AM, Yerramalla Y, Khan A et al. Beta-Blockers as an Immunologic and Autonomic Manipulator in Critically Ill Patients: A Review of the Recent Literature. International journal of molecular sciences 2024; 25.

[40] Khodadadi F, Punait S, Ketabchi F et al. Comparison of heart rate variability, hemodynamic, metabolic and inflammatory parameters in various phases of decompansatory hemorrhagic shock of normal and vagotomized conscious male rats. BMC Cardiovasc Disord 2024; 24:661.

[41] Seely AJ, Macklem PT. Complex systems and the technology of variability analysis. Critical care (London, England) 2004; 8:R367-384.

[42] Godin PJ, Buchman TG. Uncoupling of biological oscillators: a complementary hypothesis concerning the pathogenesis of multiple organ dysfunction syndrome. Critical care medicine 1996; 24:1107-1116.

[43] Seely AJ, Christou NV. Multiple organ dysfunction syndrome: exploring the paradigm of complex nonlinear systems. Critical care medicine 2000; 28:2193-2200.

[44] Lu L, Zhu T, Morelli D et al. Uncertainties in the Analysis of Heart Rate Variability: A Systematic Review. IEEE reviews in biomedical engineering 2024; 17:180-196.

[45] Qian T, Masino AJ. Latent Patient Cluster Discovery for Robust Future Forecasting and New-Patient Generalization. PloS one 2016; 11:e0162812.

[46] Karmali SN, Sciusco A, May SM, Ackland GL. Heart rate variability in critical care medicine: a systematic review. Intensive care medicine experimental 2017; 5:33.

[47] Moghtadaei M, Dorey TW, Rose RA. Evaluation of non-linear heart rate variability using multi-scale multi-fractal detrended fluctuation analysis in mice: Roles of the autonomic nervous system and sinoatrial node. Frontiers in physiology 2022; 13:970393.

[48] Heckbert SR, Jensen PN, Erus G et al. Heart rate fragmentation and brain MRI markers of small vessel disease in MESA. Alzheimer's & dementia : the journal of the Alzheimer's Association 2024; 20:1397-1405.

[49] Costa MD, Goldberger AL. Heart rate fragmentation: using cardiac pacemaker dynamics to probe the pace of biological aging. American journal of physiology. Heart and circulatory physiology 2019; 316:H1341-h1344.