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Admission Heart Rate Variability is Associated with Fever Development in Patients with Intracerebral Hemorrhage

  • Dionne E. Swor
  • Leena F. Thomas
  • Matthew B. Maas
  • Daniela Grimaldi
  • Edward M. Manno
  • Farzaneh A. Sorond
  • Ayush Batra
  • Minjee Kim
  • Shyam Prabhakaran
  • Andrew M. Naidech
  • Eric M. LiottaEmail author
Commentary

Abstract

Background

Fever is associated with worse outcome after intracerebral hemorrhage (ICH). Autonomic dysfunction, commonly seen after brain injury, results in reduced heart rate variability (HRV). We sought to investigate whether HRV was associated with the development of fever in patients with ICH.

Methods

We prospectively enrolled consecutive patients with spontaneous ICH in a single-center observational study. We included patients who presented directly to our emergency department after symptom onset, had a 10-second electrocardiogram (EKG) performed within 24 h of admission, and were in sinus rhythm. Patient temperature was recorded every 1–4 h. We defined being febrile as having a temperature of ≥ 38 °C within the first 14 days, and fever burden as the number of febrile days. HRV was defined by the standard deviation of the R-R interval (SDNN) measured on the admission EKG. Univariate associations were determined by Fisher’s exact, Mann–Whitney U, or Spearman’s rho correlation tests. Variables associated with fever at p ≤ 0.2 were entered in a logistic regression model of being febrile within 14 days.

Results

There were 248 patients (median age 63 [54–74] years, 125 [50.4%] female, median ICH Score 1 [0–2]) who met the inclusion criteria. Febrile patients had lower HRV (median SDNN: 1.72 [1.08–3.60] vs. 2.55 [1.58–5.72] msec, p = 0.001). Lower HRV was associated with more febrile days (R = − 0.22, p < 0.001). After adjustment, lower HRV was independently associated with greater odds of fever occurrence (OR 0.92 [95% CI 0.87–0.97] with each msec increase in SDNN, p = 0.002).

Conclusions

HRV measured on 10-second EKGs is a potential early marker of parasympathetic nervous system dysfunction and is associated with subsequent fever occurrence after ICH. Detecting early parasympathetic dysfunction may afford opportunities to improve ICH outcome by targeting therapies at fever prevention.

Keywords

Intracerebral hemorrhage Fever Autonomic dysfunction Heart rate variability 

Notes

Author Contributions

DES analyzed and interpreted the data, collected study data, and drafted and revised the manuscript for important intellectual content. LFT collected study data and revised the manuscript for important intellectual content. MBM originated the idea for the study, analyzed and interpreted the data, collected study data, and revised the manuscript for important intellectual content. DG revised the manuscript for important intellectual content. EMM revised the manuscript for important intellectual content. FAS revised the manuscript for important intellectual content. AB revised the manuscript for important intellectual content. MK revised the manuscript for important intellectual content. SP collected study data and revised the manuscript for important intellectual content. AMN designed and conceptualized the study, collected study data, and revised the manuscript for important intellectual content. EML originated the idea for the study, designed and conceptualized the study, analyzed and interpreted the data, collected study data, and drafted and revised the manuscript for important intellectual content.

Source of Support

Dr. Liotta receives support from the National Institutes of Health National Center for Advancing Translational Sciences grant KL2TR001424 and the National Institute of Health grant L30 NS098427. Dr. Naidech receives support from Agency for Healthcare Research and Quality grant K18 HS023437. Research reported in this publication was supported, in part, by the National Institutes of Health’s National Center for Advancing Translational Sciences grant UL1 TR000150. Dr. Maas receives support from National Institutes of Health grants K23 NS092975. Dr. Sorond receives support from National Institute of Neurological Disorders and Stroke (NINDS; R01-NS0850). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Agency for Healthcare Research and Quality.

Conflict of interest

All the authors declare that they have no conflict of Interest.

Ethical Approval

Ethical guidelines were adhered to, and our institutional review board (IRB) approved this study.

Supplementary material

12028_2019_684_MOESM1_ESM.docx (15 kb)
Supplementary material 1 (DOCX 14 kb)

References

  1. 1.
    Flaherty ML, Haverbusch M, Sekar P, et al. Long-term mortality after intracerebral hemorrhage. Neurology. 2006;66(8):1182–6.CrossRefGoogle Scholar
  2. 2.
    Fogelholm R, Murros K, Rissanen A, Avikainen S. Long term survival after primary intracerebral haemorrhage: a retrospective population based study. J Neurol Neurosurg Psychiatry. 2005;76(11):1534–8.CrossRefGoogle Scholar
  3. 3.
    Schwarz S, Hafner K, Aschoff A, Schwab S. Incidence and prognostic significance of fever following intracerebral hemorrhage. Neurology. 2000;54(2):354–61.CrossRefGoogle Scholar
  4. 4.
    Greer DM, Funk SE, Reaven NL, Ouzounelli M, Uman GC. Impact of fever on outcome in patients with stroke and neurologic injury: a comprehensive meta-analysis. Stroke. 2008;39(11):3029–35.CrossRefGoogle Scholar
  5. 5.
    Lord AS, Gilmore E, Choi HA, Mayer SA, Collaboration V-I. Time course and predictors of neurological deterioration after intracerebral hemorrhage. Stroke. 2015;46(3):647–52.CrossRefGoogle Scholar
  6. 6.
    Hilz MJ, Moeller S, Akhundova A, et al. High NIHSS values predict impairment of cardiovascular autonomic control. Stroke. 2011;42(6):1528–33.CrossRefGoogle Scholar
  7. 7.
    Lees T, Shad-Kaneez F, Simpson AM, Nassif NT, Lin Y, Lal S. Heart rate variability as a biomarker for predicting stroke, post-stroke complications and functionality. Biomark Insights. 2018;13:1177271918786931.CrossRefGoogle Scholar
  8. 8.
    Szabo J, Smielewski P, Czosnyka M, et al. Heart rate variability is associated with outcome in spontaneous intracerebral hemorrhage. J Crit Care. 2018;48:85–9.CrossRefGoogle Scholar
  9. 9.
    Yperzeele L, van Hooff RJ, Nagels G, De Smedt A, De Keyser J, Brouns R. Heart rate variability and baroreceptor sensitivity in acute stroke: a systematic review. Int J Stroke. 2015;10(6):796–800.CrossRefGoogle Scholar
  10. 10.
    Liotta EM, Prabhakaran S, Sangha RS, et al. Magnesium, hemostasis, and outcomes in patients with intracerebral hemorrhage. Neurology. 2017;89(8):813–9.CrossRefGoogle Scholar
  11. 11.
    Hwang BY, Bruce SS, Appelboom G, et al. Evaluation of intraventricular hemorrhage assessment methods for predicting outcome following intracerebral hemorrhage. J Neurosurg. 2012;116(1):185–92.CrossRefGoogle Scholar
  12. 12.
    Wilson JT, Hareendran A, Grant M, et al. Improving the assessment of outcomes in stroke: use of a structured interview to assign grades on the modified Rankin Scale. Stroke. 2002;33(9):2243–6.CrossRefGoogle Scholar
  13. 13.
    Wilson JT, Hareendran A, Hendry A, Potter J, Bone I, Muir KW. Reliability of the modified Rankin Scale across multiple raters: benefits of a structured interview. Stroke. 2005;36(4):777–81.CrossRefGoogle Scholar
  14. 14.
    Shaffer F, Ginsberg JP. An overview of heart rate variability metrics and norms. Front Public Health. 2017;5:258.CrossRefGoogle Scholar
  15. 15.
    Mahinrad S, Jukema JW, van Heemst D, et al. 10-Second heart rate variability and cognitive function in old age. Neurology. 2016;86(12):1120–7.CrossRefGoogle Scholar
  16. 16.
    Munoz ML, van Roon A, Riese H, et al. Validity of (ultra-)short recordings for heart rate variability measurements. PLoS ONE. 2015;10(9):e0138921.CrossRefGoogle Scholar
  17. 17.
    Naidech AM, Bendok BR, Bernstein RA, et al. Fever burden and functional recovery after subarachnoid hemorrhage. Neurosurgery. 2008;63(2):212–7 discussion 217-218.CrossRefGoogle Scholar
  18. 18.
    Perkes I, Baguley IJ, Nott MT, Menon DK. A review of paroxysmal sympathetic hyperactivity after acquired brain injury. Ann Neurol. 2010;68(2):126–35.CrossRefGoogle Scholar
  19. 19.
    Kenney MJ, Ganta CK. Autonomic nervous system and immune system interactions. Compr Physiol. 2014;4(3):1177–200.CrossRefGoogle Scholar
  20. 20.
    Kox M, Pickkers P. Modulation of the innate immune response through the vagus nerve. Nephron. 2015;131(2):79–84.CrossRefGoogle Scholar
  21. 21.
    Chavan SS, Pavlov VA, Tracey KJ. Mechanisms and therapeutic relevance of neuro-immune communication. Immunity. 2017;46(6):927–42.CrossRefGoogle Scholar
  22. 22.
    Berntson GG, Bigger JT Jr, Eckberg DL, et al. Heart rate variability: origins, methods, and interpretive caveats. Psychophysiology. 1997;34(6):623–48.CrossRefGoogle Scholar
  23. 23.
    Chen CH, Tang SC, Lee DY, et al. Impact of supratentorial cerebral hemorrhage on the complexity of heart rate variability in acute stroke. Sci Rep. 2018;8(1):11473.CrossRefGoogle Scholar
  24. 24.
    Ho YL, Lin C, Lin YH, Lo MT. The prognostic value of non-linear analysis of heart rate variability in patients with congestive heart failure–a pilot study of multiscale entropy. PLoS ONE. 2011;6(4):e18699.CrossRefGoogle Scholar
  25. 25.
    Hamilton RM, McKechnie PS, Macfarlane PW. Can cardiac vagal tone be estimated from the 10-second ECG? Int J Cardiol. 2004;95(1):109–15.CrossRefGoogle Scholar
  26. 26.
    de Bruyne MC, Kors JA, Hoes AW, et al. Both decreased and increased heart rate variability on the standard 10-second electrocardiogram predict cardiac mortality in the elderly: the Rotterdam Study. Am J Epidemiol. 1999;150(12):1282–8.CrossRefGoogle Scholar
  27. 27.
    Ogliari G, Mahinrad S, Stott DJ, et al. Resting heart rate, heart rate variability and functional decline in old age. CMAJ. 2015;187(15):E442–9.CrossRefGoogle Scholar
  28. 28.
    Hooper VD, Andrews JO. Accuracy of noninvasive core temperature measurement in acutely ill adults: the state of the science. Biol Res Nurs. 2006;8(1):24–34.CrossRefGoogle Scholar
  29. 29.
    Schmitz T, Bair N, Falk M, Levine C. A comparison of five methods of temperature measurement in febrile intensive care patients. Am J Crit Care. 1995;4(4):286–92.Google Scholar
  30. 30.
    Sethi A, Callaway CW, Sejdic E, Terhorst L, Skidmore ER. Heart rate variability is associated with motor outcome 3-months after stroke. J Stroke Cerebrovasc Dis. 2016;25(1):129–35.CrossRefGoogle Scholar
  31. 31.
    Tang SC, Jen HI, Lin YH, et al. Complexity of heart rate variability predicts outcome in intensive care unit admitted patients with acute stroke. J Neurol Neurosurg Psychiatry. 2015;86(1):95–100.CrossRefGoogle Scholar
  32. 32.
    Graff B, Gasecki D, Rojek A, et al. Heart rate variability and functional outcome in ischemic stroke: a multiparameter approach. J Hypertens. 2013;31(8):1629–36.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society 2019

Authors and Affiliations

  • Dionne E. Swor
    • 1
  • Leena F. Thomas
    • 1
  • Matthew B. Maas
    • 1
  • Daniela Grimaldi
    • 1
  • Edward M. Manno
    • 1
  • Farzaneh A. Sorond
    • 1
  • Ayush Batra
    • 1
  • Minjee Kim
    • 1
  • Shyam Prabhakaran
    • 1
  • Andrew M. Naidech
    • 1
  • Eric M. Liotta
    • 1
    Email author
  1. 1.Department of NeurologyNorthwestern UniversityChicagoUSA

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