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  • Clinical Research Article
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Assessing bedside measures of autonomic nervous system dysregulation in the PICU

Pediatric Research volume 98, pages 983–988 (2025)Cite this article

Abstract

Background

Autonomic nervous system (ANS) dysregulation is common during critical illness and is often measured using heart rate variability (HRV). It is unknown if other forms of ANS function, such as pupillary light reflex and thermoregulation, are altered in critically ill children. We aimed to determine whether automated pupillometry and delta (central-to-peripheral) skin temperatures were associated with HRV.

Methods

In this prospective observational pilot, inclusion criteria were admission to the pediatric intensive care unit (ICU) and mechanical ventilation. HRV was calculated using age-adjusted integer HRV (HRVi). Automated pupillometry and skin temperatures were recorded during the first 72 h of admission. The primary outcomes were: (1) correlation between HRVi and Neurological Pupil index (NPi), and (2) correlation between HRVi and delta skin temperature.

Results

Of 29 patients enrolled, 18 had pupillometer data and 20 had temperature data. There were significant, small correlations between left and right NPi values and HRVi (r = 0.13, r = 0.12; p < 0.001), and delta skin temperatures and HRVi (r = 0.15, p < 0.001), which persisted after adjusting for confounders.

Conclusions

Abnormal pupillary light response and decreased delta skin temperatures are associated with lower HRVi. If validated, pupillometry and skin temperature could be considered physiologic biomarkers of ANS dysregulation in critically ill children.

Impact

  • While heart rate variability has strong associations with outcomes in critically ill children, there are limited data on other bedside tools of autonomic function in critically ill children.

  • In this study, we found that pupillometry and skin temperature sensors correlate with heart rate variability in critically ill children.

  • These physiological biomarkers may have a role in early detection of autonomic nervous system dysregulation.

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Fig. 1: Patient Enrollment.
Fig. 2: Correlation between median normalized HRVi and NPi values.
Fig. 3: Delta skin temperature and HRVi.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Badke, C. M., Marsillio, L. E., Weese-Mayer, D. E. & Sanchez-Pinto, L. N. Autonomic Nervous System Dysfunction in Pediatric Sepsis. Front. Pediatr. 6, 280 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  2. Dunser, M. W. & Hasibeder, W. R. Sympathetic overstimulation during critical illness: adverse effects of adrenergic stress. J. Intensive Care Med. 24, 293–316 (2009).

    Article  PubMed  Google Scholar 

  3. Moorman, J. R. et al. Mortality reduction by heart rate characteristic monitoring in very low birth weight neonates: a randomized trial. J. Pediatr. 159, 900–906.e901 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Goldstein, B. et al. Decomplexification in critical illness and injury: relationship between heart rate variability, severity of illness, and outcome. Crit. Care Med. 26, 352–357 (1998).

    Article  CAS  PubMed  Google Scholar 

  5. Badke, C. M., Marsillio, L. E., Carroll, M. S., Weese-Mayer, D. E. & Sanchez-Pinto, L. N. Development of a Heart Rate Variability Risk Score to Predict Organ Dysfunction and Death in Critically Ill Children. Pediatr. Crit. Care Med. 22, e437–e447 (2021).

  6. Olson, D. M. et al. Interrater Reliability of Pupillary Assessments. Neurocrit Care 24, 251–257 (2016).

    Article  PubMed  Google Scholar 

  7. Nyholm, B. et al. Superior reproducibility and repeatability in automated quantitative pupillometry compared to standard manual assessment, and quantitative pupillary response parameters present high reliability in critically ill cardiac patients. PLoS One 17, e0272303 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Nyholm, B. et al. Specific thresholds of quantitative pupillometry parameters predict unfavorable outcome in comatose survivors early after cardiac arrest. Resusc. Plus. 14, 100399 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Patwari, P. P. et al. Pupillometry in congenital central hypoventilation syndrome (CCHS): quantitative evidence of autonomic nervous system dysregulation. Pediatr. Res. 71, 280–285 (2012).

    Article  CAS  PubMed  Google Scholar 

  10. Yanovich, R., Ketko, I. & Charkoudian, N. Sex Differences in Human Thermoregulation: Relevance for 2020 and Beyond. Physiol. 35, 177–184 (2020).

    Article  CAS  Google Scholar 

  11. Sessler, D. I. Thermoregulatory defense mechanisms. Crit. Care Med. 37, S203–S210 (2009).

    Article  CAS  PubMed  Google Scholar 

  12. Saiyed, R. et al. Congenital central hypoventilation syndrome (CCHS): Circadian temperature variation. Pediatr. Pulmonol. 51, 300–307 (2016).

    Article  PubMed  Google Scholar 

  13. Olson, D. M. et al. Establishing Normative Data for Pupillometer Assessment in Neuroscience Intensive Care: The “END-PANIC” Registry. J. Neurosci. Nurs. 49, 251–254 (2017).

    Article  PubMed  Google Scholar 

  14. Hasselberg, M. J., McMahon, J. & Parker, K. The validity, reliability, and utility of the iButton(R) for measurement of body temperature circadian rhythms in sleep/wake research. Sleep. Med. 14, 5–11 (2013).

    Article  PubMed  Google Scholar 

  15. Pollack, M. M. et al. The Pediatric Risk of Mortality Score: Update 2015. Pediatr. Crit. Care Med. 17, 2–9 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Muppidi, S. et al. Dynamic pupillometry as an autonomic testing tool. Clin. Auton. Res. 23, 297–303 (2013).

    Article  PubMed  Google Scholar 

  17. Larson, M. D. & Singh, V. Portable infrared pupillometry in critical care. Crit. Care 20, 161 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  18. Privitera, C. M. et al. A differential of the left eye and right eye neurological pupil index is associated with discharge modified Rankin scores in neurologically injured patients. BMC Neurol. 22, 273 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  19. Winston, M. et al. Pupillometry measures of autonomic nervous system regulation with advancing age in a healthy pediatric cohort. Clin. Auton. Res. 30, 43–51 (2020).

    Article  PubMed  Google Scholar 

  20. Khaytin, I. et al. Evolution of physiologic and autonomic phenotype in rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation over a decade from age at diagnosis. J. Clin. Sleep. Med. 18, 937–944 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  21. Carroll, M. S., Ramirez, J. M. & Weese-Mayer, D. E. Diurnal variation in autonomic regulation among patients with genotyped Rett syndrome. J. Med. Genet. 57, 786–793 (2020).

    Article  CAS  PubMed  Google Scholar 

  22. Frank, S. M., El-Rahmany, H. K., Tran, K. M., Vu, B. & Raja, S. N. Comparison of lower extremity cutaneous temperature changes in patients receiving lumbar sympathetic ganglion blocks versus epidural anesthesia. J. Clin. Anesth. 12, 525–530 (2000).

    Article  CAS  PubMed  Google Scholar 

  23. Larson, M. D. & Behrends, M. Portable infrared pupillometry: a review. Anesth. Analg. 120, 1242–1253 (2015).

    Article  PubMed  Google Scholar 

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Acknowledgements

We would like to acknowledge the PICU nurses at Lurie Children’s Hospital for facilitating patient enrollment and participation in this study.

Funding

Dr. Badke received an internal grant from Stanley Manne Children’s Research Institute to support this work. The other authors have no relevant funding to report.

Author information

Authors and Affiliations

  1. Division of Critical Care Medicine, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA

    Colleen M. Badke & L. Nelson Sanchez-Pinto

  2. Stanley Manne Children’s Research Institute, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA

    Colleen M. Badke, Michael S. Carroll, Debra E. Weese-Mayer & L. Nelson Sanchez-Pinto

  3. Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Colleen M. Badke, Michael S. Carroll, Debra E. Weese-Mayer & L. Nelson Sanchez-Pinto

  4. Department of Anesthesia, University of Michigan, Ann Arbor, MI, USA

    Tricia R. Pendergrast

  5. Division of Autonomic Medicine, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA

    Debra E. Weese-Mayer

Authors
  1. Colleen M. Badke
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  2. Michael S. Carroll
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  3. Tricia R. Pendergrast
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  4. Debra E. Weese-Mayer
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  5. L. Nelson Sanchez-Pinto
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Contributions

Substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data: C.B., T.P., D.W.P., N.S.P. Drafting the article or revising it critically for important intellectual content: C.B., M.C., T.P., D.W.M., N.S.P. Final approval of the version to be published: C.B., M.C., T.P., D.W.M., N.S.P.

Corresponding author

Correspondence to Colleen M. Badke.

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Competing interests

The authors declare no competing interests.

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Parents or legal guardians gave consent for their children to be enrolled in this study.

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Badke, C.M., Carroll, M.S., Pendergrast, T.R. et al. Assessing bedside measures of autonomic nervous system dysregulation in the PICU. Pediatr Res 98, 983–988 (2025). https://doi.org/10.1038/s41390-024-03778-0

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