Development of a Heart Rate Variability Risk Score to Predict Organ Dysfunction and Death in Critically Ill Children

OBJECTIVES: Determine whether the Heart Rate Variability Dysfunction score, a novel age-normalized measure of autonomic nervous system dysregulation, is associated with the development of new or progressive multiple organ dysfunction syndrome or death in critically ill children. DESIGN, SETTING, AND PATIENTS: This was a retrospective, observational cohort study from 2012 to 2018. Patients admitted to the PICU with at least 12 hours of continuous heart rate data available from bedside monitors during the first 24 hours of admission were included in the analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Heart rate variability was measured using the integer heart rate variability, which is the sd of the heart rate sampled every 1 second over 5 consecutive minutes. The Heart Rate Variability Dysfunction score was derived from age-normalized values of integer heart rate variability and transformed, so that higher scores were indicative of lower integer heart rate variability and a proxy for worsening autonomic nervous system dysregulation. Heart Rate Variability Dysfunction score performance as a predictor of new or progressive multiple organ dysfunction syndrome and 28-day mortality were determined using the area under the receiver operating characteristic curve. Of the 7,223 patients who met inclusion criteria, 346 patients (4.8%) developed new or progressive multiple organ dysfunction syndrome, and 103 (1.4%) died by day 28. For every one-point increase in the median Heart Rate Variability Dysfunction score in the first 24 hours of admission, there was a 25% increase in the odds of new or progressive multiple organ dysfunction syndrome and a 51% increase in the odds of mortality. The median Heart Rate Variability Dysfunction score in the first 24 hours had an area under the receiver operating characteristic curve to discriminate new or progressive multiple organ dysfunction syndrome of 0.67 and to discriminate mortality of 0.80. These results were reproducible in a temporal validation cohort. CONCLUSIONS: The Heart Rate Variability Dysfunction score, an age-adjusted proxy for autonomic nervous system dysregulation derived from bedside monitor data is independently associated with new or progressive multiple organ dysfunction syndrome and mortality in PICU patients. The Heart Rate Variability Dysfunction score could potentially be used as a single continuous physiologic biomarker or as part of a multivariable prediction model to increase awareness of at-risk patients and augment clinical decision-making.