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



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.


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.


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).


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.


Intracerebral hemorrhage Fever Autonomic dysfunction Heart rate variability 


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)


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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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