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Clinical review: A review and analysis of heart rate variability and the diagnosis and prognosis of infection
Open accessAbstract
Bacterial infection leading to organ failure is the most common cause of death in critically ill patients. Early diagnosis and expeditious treatment is a cornerstone of therapy. Evaluating the systemic host response to infection as a complex system provides novel insights: however, bedside application with clinical value remains wanting. Providing an integrative measure of an altered host response, the patterns and character of heart rate fluctuations measured over intervals-in-time may be analysed with a panel of mathematical techniques that quantify overall fluctuation, spectral composition, scale-free variation, and degree of irregularity or complexity. Using these techniques, heart rate variability (HRV) has been documented to be both altered in the presence of systemic infection, and correlated with its severity. In this review and analysis, we evaluate the use of HRV monitoring to provide early diagnosis of infection, document the prognostic implications of altered HRV in infection, identify current limitations, highlight future research challenges, and propose improvement strategies. Given existing evidence and potential for further technological advances, we believe that longitudinal, individualized, and comprehensive HRV monitoring in critically ill patients at risk for or with existing infection offers a means to harness the clinical potential of this bedside application of complex systems science.
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“This finding is consistent with the theory of “critical slowing down,” where decreasing variability in biological systems signals impending state transitions20.”
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Cites
Heart Rate Variability: Standards of Measurement, Physiological Interpretation, and Clinical Use
Electrophysiology, T. F. O. T. E. S. O. C. T. N. A. (1996) · Circulation · doi:10.1161/01.cir.93.5.1043 · Cited by 17,159
Heart rate variability: Standards of measurement, physiological interpretation, and clinical use
Malik, M., Bigger, J. T., Camm, A. J., Kleiger, R. E., Malliani, A., Moss, A. J., & Schwartz, P. J. (1996) · European Heart Journal · doi:10.1093/oxfordjournals.eurheartj.a014868 · Cited by 15,289
Bone, R. C., BALK, R. A., Cerra, F. B., Dellinger, R. P., Fein, A. M., Knaus, W. A., Schein, R. M. H., & Sibbald, W. J. (1992) · CHEST Journal · doi:10.1378/chest.101.6.1644 · Cited by 13,335
Early goal-directed therapy in the treatment of severe sepsis and septic shock
Rivers, E., Nguyen, B., Havstad, S., Ressler, J., Muzzin, A., Knoblich, B., Peterson, E., & Tomlanovich, M. (2001) · New England Journal of Medicine · doi:10.1056/nejmoa010307 · Cited by 10,743
Angus, D. C., Linde-Zwirble, W. T., Lidicker, J., Clermont, G., Carcillo, J., & Pinsky, M. R. (2001) · Critical Care Medicine · doi:10.1097/00003246-200107000-00002 · Cited by 8,503
Kumar, A., Roberts, D., Wood, K. E., Light, B., Parrillo, J. E., Sharma, S., Suppes, R., Feinstein, D., Zanotti, S., Taiberg, L., et al. (2006) · Critical Care Medicine · doi:10.1097/01.ccm.0000217961.75225.e9 · Cited by 6,109
Mosaic organization of DNA nucleotides
Peng, C., Buldyrev, S. V., Havlin, S., Simons, M., Stanley, E., & Goldberger, A. L. (1994) · Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics · doi:10.1103/physreve.49.1685 · Cited by 5,002
Multiscale entropy analysis of biological signals
Costa, M., Goldberger, A. L., & Peng, C.-K. (2005) · Physical Review E · doi:10.1103/physreve.71.021906 · Cited by 2,482
Physiological time-series analysis: what does regularity quantify?
Pincus, S. M., & Goldberger, A. L. (1994) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1994.266.4.h1643 · Cited by 1,322
Sample entropy analysis of neonatal heart rate variability
Lake, D. E., Richman, J., Griffin, M. P., & Moorman, J. R. (2002) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00069.2002 · Cited by 1,238
Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock
&NA; (2002) · Survey of Anesthesiology · doi:10.1097/00132586-200210000-00014 · Cited by 665
The epidemiology of the systemic inflammatory response
Brun‐Buisson, C. (2000) · Intensive Care Medicine · doi:10.1007/s001340051121 · Cited by 534
Insights from the Study of Heart Rate Variability
Stein, P. K., & Kleiger, R. E. (1999) · Annual Review of Medicine · doi:10.1146/annurev.med.50.1.249 · Cited by 525
Complex systems and the technology of variability analysis
SEELY, A. J. E., & Macklem, P. T. (2004) · Critical Care · doi:10.1186/cc2948 · Cited by 456
Self-citationGuzzetti, S., Piccaluga, E., Casati, R., Cerutti, S., Lombardi, F., Pagani, M., & Malliani, A. (1988) · Journal of Hypertension · doi:10.1097/00004872-198809000-00004 · Cited by 417
Time Domain Measurements of Heart Rate Variability
Kleiger, R. E., Stein, P. K., Bosner, M. S., & Rottman, J. N. (1992) · Cardiology Clinics · doi:10.1016/s0733-8651(18)30230-3 · Cited by 387
Absence of Low-Frequency Variability of Sympathetic Nerve Activity in Severe Heart Failure
van de Borne, P., Montano, N., Pagani, M., Oren, R. M., & Somers, V. K. (1997) · Circulation · doi:10.1161/01.cir.95.6.1449 · Cited by 376
Griffin, M. P., & Moorman, J. R. (2001) · PEDIATRICS · doi:10.1542/peds.107.1.97 · Cited by 320
Inappropriate Sympathetic Activation at Onset of Septic Shock: A Spectral Analysis Approach
Annane, D., Trabold, F., Sharshar, T., Jarrin, I., BLANC, A.-S., Raphaël, J., & Gajdos, P. (1999) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.160.2.9810073 · Cited by 303
Early Goal-Directed Therapy in Severe Sepsis and Septic Shock Revisited
Otero, R., Nguyen, H. B., Huang, D. T., Gaieski, D. F., Goyal, M. K., Gunnerson, K. J., Trzeciak, S. W., Sherwin, R. L., Holthaus, C. V., Osborn, T. M., et al. (2006) · CHEST Journal · doi:10.1378/chest.130.5.1579 · Cited by 295
Continuous Multi-Parameter Heart Rate Variability Analysis Heralds Onset of Sepsis in Adults
Ahmad, S. S., Ramsay, T., Huebsch, L. B., Flanagan, S., McDiarmid, S. A., Batkin, I., McIntyre, L., Sundaresan, S. R., Maziak, D. E., Shamji, F. M., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006642 · Cited by 292
Self-citationZanotti-Cavazzoni, S. L. (2007) · Yearbook of Critical Care Medicine · doi:10.1016/s0734-3299(08)70339-3 · Cited by 291
Multiple organ dysfunction syndrome: exploring the paradigm of complex nonlinear systems
Seely, A. J. E., & Christou, N. V. (2000) · Critical Care Medicine · doi:10.1097/00003246-200007000-00003 · Cited by 287
Self-citationAbnormal Heart Rate Characteristics Preceding Neonatal Sepsis and Sepsis-Like Illness
Griffin, M. P., O’Shea, T. M., Bissonette, E. A., Harrell, F. E., Lake, D. E., & Moorman, J. R. (2003) · Pediatric Research · doi:10.1203/01.pdr.0000064904.05313.d2 · Cited by 250
Brunkhorst, F. M., Wegscheider, K., Forycki, Z. F., & Brunkhorst, R. R. (2000) · Intensive Care Medicine · doi:10.1007/bf02900728 · Cited by 222
Heart Rate Characteristics: Novel Physiomarkers to Predict Neonatal Infection and Death
Griffin, M. P., Lake, D. E., Bissonette, E. A., Harrell, F. E., O’Shea, T. M., & Moorman, J. R. (2005) · PEDIATRICS · doi:10.1542/peds.2004-2461 · Cited by 201
Mesters, R. M., Helterbrand, J., Utterback, B. G., Yan, S.-C. B., Chao, Y., Fernández, J. A., Griffin, J. H., & Hartman, D. (2000) · Critical Care Medicine · doi:10.1097/00003246-200007000-00005 · Cited by 200
Heart rate variability as early marker of multiple organ dysfunction syndrome in septic patients
Pontet, J., Contreras, P., Curbelo, A., Medina, J., Noveri, S., Bentancourt, S., & Migliaro, E. R. (2003) · Journal of Critical Care · doi:10.1016/j.jcrc.2003.08.005 · Cited by 195
Stefan Thurner, A., Feurstein, M., & Teich, M. C. (1998) · Physical Review Letters · doi:10.1103/physrevlett.80.1544 · Cited by 185
Brunkhorst, F. M., Wegscheider, K., Forycki, Z. F., & Brunkhorst, R. R. (2000) · Intensive Care Medicine · doi:10.1007/s001340051134 · Cited by 181
Cardiac variability in critically ill adults: Influence of sepsis
Korach-André, M., Sharshar, T., Jarrin, I., Fouillot, J.-P., Raphaël, J., Gajdos, P., & Annane, D. (2001) · Critical Care Medicine · doi:10.1097/00003246-200107000-00013 · Cited by 170
Heart Rate Variability in Emergency Department Patients with Sepsis
Barnaby, D. P., Ferrick, K. J., Kaplan, D. T., Shah, S. P., Bijur, P. E., & Gallagher, E. J. (2002) · Academic Emergency Medicine · doi:10.1111/j.1553-2712.2002.tb02143.x · Cited by 162
Yien, H.-W., Hseu, S., Lee, L.-C., Kuo, T. B. J., Lee, T.-Y., & Chan, S. H. H. (1997) · Critical Care Medicine · doi:10.1097/00003246-199702000-00011 · Cited by 153
Patients with severe sepsis vary markedly in their ability to generate activated protein C
Liaw, P. C., Esmon, C. T., Kahnamoui, K., Schmidt, S. L., Kahnamoui, S., Ferrell, G. L., Beaudin, S. M., Julian, J. A., Weitz, J. I., Crowther, M. A., et al. (2004) · Blood · doi:10.1182/blood-2004-03-1203 · Cited by 152
Spectral analysis of heart rate variability in the sepsis syndrome
Garrard, C. S., Kontoyannis, D. A., & Piepoli, M. F. (1993) · Clinical Autonomic Research · doi:10.1007/bf01819137 · Cited by 146
Autonomic dysfunction in the ICU patient
Schmidt, H. B., Werdan, K., & Müller-Werdan, U. (2001) · Current Opinion in Critical Care · doi:10.1097/00075198-200110000-00002 · Cited by 138
Heart Rate Characteristics and Laboratory Tests in Neonatal Sepsis
Griffin, M. P., Lake, D. E., & Moorman, J. R. (2005) · PEDIATRICS · doi:10.1542/peds.2004-1393 · Cited by 136
Antibiotic Induced Endotoxin Release and Clinical Sepsis: a Review
Holzheimer, R. G. (2001) · Journal of Chemotherapy · doi:10.1179/joc.2001.13.supplement-2.159 · Cited by 135
Castelli, G. P., Pognani, C., Cita, M., Stuani, A., Sgarbi, L., & Paladini, R. (2006) · PubMed · Cited by 135
Kovatchev, B. P., Farhy, L. S., Cao, H., Griffin, M. P., Lake, D. E., & Moorman, J. R. (2003) · Pediatric Research · doi:10.1203/01.pdr.0000088074.97781.4f · Cited by 132
Heart rate variability and its determinants in patients with severe or mild essential hypertension
Mussalo, H., Vanninen, E. J., Ikäheimo, R., Laitinen, T. P., Laakso, M., Länsimies, E., & Hartikainen, J. E. K. (2001) · Clinical Physiology · doi:10.1046/j.1365-2281.2001.00359.x · Cited by 126
Chen, W.-L., & Kuo, C. (2007) · Academic Emergency Medicine · doi:10.1197/j.aem.2006.12.015 · Cited by 124
Simon, L., Saint-Louis, P., Amre, D. K., Lacroix, J., & Gauvin, F. (2008) · Pediatric Critical Care Medicine · doi:10.1097/pcc.0b013e31817285a6 · Cited by 120
Heart Rate Characteristics Monitoring for Neonatal Sepsis
Moorman, J. R., Lake, D. E., & Griffin, M. P. (2005) · IEEE Transactions on Biomedical Engineering · doi:10.1109/tbme.2005.859810 · Cited by 110
Bonaduce, D., Petretta, M., Marcianò, F., Vicario, M. L. E., Apicella, C., Rao, M. A. E., Nicolai, E., & Volpe, M. (1999) · American Heart Journal · doi:10.1016/s0002-8703(99)70112-2 · Cited by 110
Approximate entropy of respiratory rate and tidal volume during weaning from mechanical ventilation
Engoren, M. (1998) · Critical Care Medicine · doi:10.1097/00003246-199811000-00021 · Cited by 108
Autonomic control of the heart and peripheral vessels in human septic shock
Piepoli, M. F., Garrard, C. S., Kontoyannis, D. A., & Bernardi, L. (1995) · Intensive Care Medicine · doi:10.1007/bf01726532 · Cited by 94
Mild hypovolemic stress alters autonomic modulation of heart rate.
Triedman, J. K., Cohen, R. J., & Saul, J. P. (1993) · Hypertension · doi:10.1161/01.hyp.21.2.236 · Cited by 89
Linear and non-linear 24 h heart rate variability in chronic heart failure
Guzzetti, S., Mezzetti, S., Magatelli, R., Porta, A., Angelis, G. D., Rovelli, G., & Malliani, A. (2000) · Autonomic Neuroscience · doi:10.1016/s1566-0702(00)00239-3 · Cited by 87
Abnormal Heart Rate Characteristics Are Associated with Neonatal Mortality
Griffin, M. P., O’Shea, T. M., Bissonette, E. A., Harrell, F. E., Lake, D. E., & Moorman, J. R. (2004) · Pediatric Research · doi:10.1203/01.pdr.0000119366.21770.9e · Cited by 78
Boven, A. J. V., Jukema, J. W., Haaksma, J., Zwinderman, A. H., Crijns, H. J. G. M., & Lie, K. I. (1998) · American Heart Journal · doi:10.1016/s0002-8703(98)70269-8 · Cited by 73
Increased Nonstationarity of Neonatal Heart Rate Before the Clinical Diagnosis of Sepsis
Cao, H., Lake, D. E., Griffin, M. P., & Moorman, J. R. (2004) · Annals of Biomedical Engineering · doi:10.1023/b:abme.0000012743.81754.0b · Cited by 64
Marik, P. E., & Varón, J. (2001) · Disease-a-Month · doi:10.1067/mda.2001.119745 · Cited by 62
Endo, S., Aikawa, N., Fujishima, S., Sekine, I., Kogawa, K., Yamamoto, Y., Kushimoto, S., Yukioka, H., Kato, N., Totsuka, K., et al. (2008) · Journal of Infection and Chemotherapy · doi:10.1007/s10156-008-0608-1 · Cited by 61
Kandil, E. H. (2008) · Archives of Surgery · doi:10.1001/archsurg.2007.69 · Cited by 60
Pichot, V., Buffière, S., Gaspoz, J., Costes, F., Molliex, S. B., Duverney, D., Roche, F., & Barthélemy, J. (2001) · Canadian Journal of Anesthesia/Journal canadien d anesthésie · doi:10.1007/bf03017350 · Cited by 56
Poulsen, S. H., Jensen, S. E., Møller, J. E., & Egstrup, K. (2001) · Heart · doi:10.1136/heart.86.4.376 · Cited by 53
Heart rate variability depression in patients with unstable angina
Huang, J., Sopher, S. M., Leatham, E. W., Redwood, S. R., Camm, A. J., & Kaski, J. C. (1995) · American Heart Journal · doi:10.1016/0002-8703(95)90076-4 · Cited by 49
Assessing Heart Rate Variability from Real-World Holter Reports
Stein, P. K. (2002) · Cardiac Electrophysiology Review · doi:10.1023/a:1016376924850 · Cited by 43
Jensen, J. S., Lundgren, B., Hein, L., Mohr, T. T., Petersen, P. L., Andersen, L. H., Lauritsen, A. Ø., Hougaard, S., Mantoni, T., Bømler, B. K., et al. (2008) · BMC Infectious Diseases · doi:10.1186/1471-2334-8-91 · Cited by 43
Pardo, Y., Merz, C. N. B., Paul-Labrador, M. J., Velasquez, I., Gottdiener, J. S., Kop, W. J., Krantz, D. S., Rozanski, A., Klein, J., & Peter, T. C. (1996) · The American Journal of Cardiology · doi:10.1016/s0002-9149(96)00458-4 · Cited by 41
Endogenous protein C activation in patients with severe sepsis
Liaw, P. C. (2004) · Critical Care Medicine · doi:10.1097/01.ccm.0000126125.79861.d3 · Cited by 37
Sepsis Strategies in Development
LaRosa, S. P., & Opal, S. M. (2008) · Clinics in Chest Medicine · doi:10.1016/j.ccm.2008.06.007 · Cited by 34
Procalcitonin as a useful marker of infection in hemato-oncological patients with fever.
Sandri, M. T., Passerini, R., Leon, M. E., Peccatori, F. A., Zorzino, L., Salvatici, M., Riggio, D., Cassatella, C., Cinieri, S., & Martinelli, G. (2008) · PubMed · Cited by 28
The applications of B-type natriuretic peptide measurement in the intensive care unit
McLean, A. S., & Huang, S. (2005) · Current Opinion in Critical Care · doi:10.1097/01.ccx.0000176695.92883.87 · Cited by 16
Heart Rate Characteristics in Neonatal Sepsis: A Promising Test That Is Still Premature
Goldstein, B. (2005) · PEDIATRICS · doi:10.1542/peds.2005-0182 · Cited by 14
Heart dysfunction and heart rate variability prognoses in sepsis
Soriano, F. G., Nogueira, A., Cappi, S. B., Lins, M., Hoshino, W. T., & Gonzaga, L. (2004) · Critical Care · doi:10.1186/cc2542 · Cited by 4
Research works printed but not linked: 1
- Pramod J Singh A Sepsis biomarkers Am J Med 2008 121 e11 author reply e13 10.1016/j.amjmed.2007.12.009 18501208 · DOI
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Metadata
- Authors
- Ahmad, S., Tejuja, A., Newman, K. D., Zarychanski, R., & Seely, A. J.
- Affiliations
- Ottawa Hospital Research Institute (CA)
- CancerCare Manitoba (CA)
- University of Ottawa (CA)
- Corresponding author
- Seely, Andrew JE
- Venue
- Critical Care
- Published
- 2009
- Volume
- 13
- Issue
- 6
- Pages
- 232
- ISSN
- 1364-8535 (ISSN-L)
- PMC
- PMC2811891
- OpenAlex
- W2112011799
- Cited by
- 151
- References
- 68
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 7 · 2023: 6 · 2022: 12 · 2021: 17 · 2020: 17 · 2019: 11 · 2018: 7 · 2017: 9 · 2016: 11 · 2015: 9 · 2014: 8 · 2013: 11 · 2012: 7
- FWCI
- 0.85
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Critical Care (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Ottawa
- Ottawa Hospital Research Institute
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Sepsis Diagnosis and Treatment
- Physical Sciences › Engineering › Biomedical Engineering › Non-Invasive Vital Sign Monitoring
- Keywords
- heart rate variability, bacterial infection, sepsis, early infection detection, prognosis, critically ill patients, complex systems science, spectral analysis of HRV, infection severity
- MeSH terms
- Bacterial Infections, Heart Rate, Humans, Prognosis, Resuscitation, Observer Variation, Critical Illness
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