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Early Heart Rate Variability and Electroencephalographic Abnormalities in Acutely Brain-Injured Children Who Progress to Brain Death*

Piantino, Juan A., MD1; Lin, Amber, MS2; Crowder, Daniel, MD1; Williams, Cydni N., MD3; Perez-Alday, Erick, PhD4; Tereshchenko, Larisa G., MD, PhD4; Newgard, Craig D., MD, MPH2

Pediatric Critical Care Medicine: January 2019 - Volume 20 - Issue 1 - p 38–46
doi: 10.1097/PCC.0000000000001759
Neurocritical Care

Objectives: Heart rate variability is controlled by the autonomic nervous system. After brain death, this autonomic control stops, and heart rate variability is significantly decreased. However, it is unknown if early changes in heart rate variability are predictive of progression to brain death. We hypothesized that in brain-injured children, lower heart rate variability is an early indicator of autonomic system failure, and it predicts progression to brain death. We additionally explored the association between heart rate variability and markers of brain dysfunction such as electroencephalogram and neurologic examination between brain-injured children who progressed to brain death and those who survived.

Design: Retrospective case-control study.

Setting: PICU, single institution.

Patients: Children up to 18 years with a Glasgow Coma Scale score of less than 8 admitted between August of 2016 and December of 2017, who had electrocardiographic data available for heart rate variability analysis, were included. Exclusion criteria: patients who died of causes other than brain death. Twenty-three patients met inclusion criteria: six progressed to brain death (cases), and 17 survived (controls). Five-minute electrocardiogram segments were used to estimate heart rate variability in the time domain (SD of normal-normal intervals, root mean square successive differences), frequency domain (low frequency, high frequency, low frequency/high frequency ratio), Poincaré plots, and approximate entropy.

Interventions: None.

Measurements and Main Results: Patients who progressed to brain death exhibited significantly lower heart rate variability in the time domain, frequency domain, and Poincaré plots (p < 0.01). The odds of death increased with decreasing low frequency (odds ratio, 4.0; 95% CI, 1.2–13.6) and high frequency (odds ratio, 2.5; 95% CI, 1.2–5.4) heart rate variability power (p < 0.03). Heart rate variability was significantly lower in those with discontinuous or attenuated/featureless electroencephalogram versus those with slow/disorganized background (p < 0.03).

Conclusions: These results support the concept of autonomic system failure as an early indicator of impending brain death in brain-injured children. Furthermore, decreased heart rate variability is associated with markers of CNS dysfunction such as electroencephalogram abnormalities.

1Department of Pediatrics, Division of Child Neurology, Doernbecher Children’s Hospital, Oregon Health and Science University, Portland, OR.

2Center for Policy and Research in Emergency Medicine, Department of Emergency Medicine, Oregon Health and Science University, Portland, OR.

3Department of Pediatrics, Division of Pediatric Critical Care, Doernbecher Children’s Hospital, Oregon Health and Science University, Portland, OR.

4Department of Medicine, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR.

*See also p. 84.

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Supported, in part, by the National Institutes of Health K12HL133115 (to Dr. Piantino), K12HS022981 (to Dr. Williams), and R01HL118277 (to Dr. Tereshchenko).

Dr. Piantino’s institution received funding from the National Heart, Lung, and Blood Institute (NHLBI). Drs. Piantino, Lin, Tereshchenko, and Newgard received support for article research from the National Institutes of Health (NIH). Dr. Williams’ institution received funding from, and she received support for article research from, the Agency for Healthcare Research and Quality K12HS022981. Dr. Tereshchenko is supported by supported by NIH 1R01HL118277. Dr. Newgard’s institution received funding from NIH/NHLBI grant number K12HL133115. The remaining authors have disclosed that they do not have any potential conflicts of interest.

This work was performed at Oregon Health and Science University.

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©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies