Sample Asymmetry Analysis of Heart Rate Characteristics with Application to Neonatal Sepsis and Systemic Inflammatory Response Syndrome

Kovatchev, Boris; Farhy, Leon S.; Cao, Hanqing; Griffin, M. L.; Lake, Douglas E.; Moorman, J. Randall

doi:10.1203/01.pdr.0000088074.97781.4f

Cited by 127 publications

(112 citation statements)

References 20 publications

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“…We estimated the observed burden of illness using a regression model relating input variables of HRC measures [SD, sample asymmetry (27), and sample entropy (28)] to the outcome of episodes of sepsis and SIRS. These are measures of variability (SD), asymmetry of histograms of RR intervals (sample asymmetry), and repeating patterns of RR intervals (sample entropy).…”

Section: Methodsmentioning

confidence: 99%

Abnormal Heart Rate Characteristics Are Associated with Neonatal Mortality

Griffin

OʼShea

Bissonette³

et al. 2004

Pediatr Res

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Estimating the risk of in-hospital mortality in the newborn intensive care unit can provide important information for healthcare providers, and illness severity scores have been devised to provide mortality risk estimates. Calculation of illness severity scores is time-consuming, and the information used to predict mortality is collected only for the first 12 to 24 h of life. A noninvasive continuous measure that uses information collected throughout the hospitalization and that requires no data entry could be less costly and more informative. We have previously shown that the abnormal heart rate characteristics (HRC) of reduced variability and transient decelerations accompany neonatal illness such as late-onset sepsis. We hypothesized that more frequent and severe abnormal HRC are associated with an increased risk of death. We tested this hypothesis in two ways. Using data on infants older than 7 d of age, we first determined the association of the HRC index with death in the next week. Second, we devised a cumulative HRC score and determined its association with in-hospital death. There were 37 deaths in the 685 patients. The major findings were 1) the HRC index showed highly significant association with death in the succeeding 7 d (receiver-operating characteristic area Ͼ 0.7, p Ͻ 0.001), and 2) the cumulative HRC was highly significantly associated with neonatal in-hospital mortality (receiver-operating characteristic area Ͼ 0.80, p Ͻ 0.001). In both analyses, HRC added information to birth weight, gestational age, and postnatal age (p Ͻ 0.01). The HRC index provides independent information about the risk of neonatal death in the upcoming 7 d, and the cumulative HRC is an estimate of the risk of in-hospital neonatal mortality. Abbreviations NICU, newborn intensive care unit HRC, heart rate characteristics ROC, receiver-operating characteristic HR, heart rate SIRS, systemic inflammatory response syndrome UVa, University of Virginia WFU, Wake Forest University BW, birth weight GA, gestational age cHRC, cumulative heart rate characteristics SNAP, Score for Acute Neonatal Physiology RR interval, interval between heartbeats Estimations of the risk of mortality, the illness severity, and the burden of illness are important in planning patient care and providing health-care resources in clinical neonatology. Although standard neonatal illness severity scores correlate with neonatal mortality (1-5), their day-to-day use is limited by the large amount of data collection that is required. In addition, the accuracy of these standard scoring systems diminishes after the first few days (6). A simpler and more informative method for estimating in-hospital mortality in neonates is needed.Early in the course of sepsis and SIRS, newborn infants have abnormal HRC, with reduced HR variability and transient decelerations similar to those of distressed fetuses (7). Predictive mathematical models based on logistic regression that use HRC are significantly associated with neonatal sepsis and SIRS in the subsequent 12 to 24 h (8)....

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Section: Methodsmentioning

confidence: 99%

Abnormal Heart Rate Characteristics Are Associated with Neonatal Mortality

Griffin

OʼShea

Bissonette³

et al. 2004

Pediatr Res

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“…HR characteristics such as SD, centiles and skewness [7] and sample asymmetry [3,22] have been associated with sepsis or isolated inflammatory response. We were unable to find a correlation between these parameters and sepsis.…”

Section: Meaning Of the Studymentioning

confidence: 99%

Uncorrelated Randomness of the Heart Rate Is Associated with Sepsis in Sick Premature Infants

Beuchée¹,

Carrault

Bansard

et al. 2009

Neonatology

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Background: Late-onset sepsis in the premature infant is frequently revealed by severe, unusual and recurrent bradycardias. In view of the high morbidity and mortality associated with infection, reliable markers are needed. Objectives: It was the aim of this study to determine if heart rate (HR) behavior may help the diagnosis of infection in premature infants with such cardiac decelerations. Methods: Electrocardiogram recordings were collected in 51 premature infants with a postmenstrual age <33 weeks with frequent bradycardias. Newborns in the sepsis group (C-reactive protein increase and positive blood culture) were compared with a no-sepsis group (C-reactive protein <5 mg/l before and 24 h after recording and negative blood cultures) for their HR characteristics, i.e. RR series distribution (mean, median, skewness, kurtosis, sample asymmetry), magnitude of variability in time and frequency domain, fractal exponents (α₁, α₂) and complexity measurements (approximate and sample entropy). Results are presented as the median (25%, 75%). Results: Gestational, chronological and postmenstrual age and gender were similar in the sepsis (n = 10) and no-sepsis group (n = 38). Three infants had an increase in C-reactive protein but negative cultures. Low entropy measurements [approximate entropy 0.4 (0.3, 0.5) vs. 0.8 (0.6, 1); p < 0.001] and long-range fractal exponent [α₂ 0.78 (0.71, 0.83) vs. 0.92 (0.8, 1.1); p < 0.05] were significantly associated with sepsis. No other HR characteristic was associated with sepsis. The decrease in 0.1 units of approximate entropy was associated with an over 2-fold increase in the odds of sepsis. Conclusion: Late-onset sepsis is associated with uncorrelated randomness of the HR. This abnormal HR behavior may help to monitor premature infants presenting with frequent and severe bradycardias.

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“…For each we calculate SD, sample asymmetry (the characteristic abnormality is increased asymmetry due to more decelerations and fewer accelerations (13)) and sample entropy (SampEn, and the characteristic abnormality is a reduction due to outliers (14,15,21)). We select the median SD and sample asymmetry values over the preceding 12 h, and the 10 th percentile lowest SampEn value.…”

Section: Patient Populationmentioning

confidence: 99%

“…Heart rate measures optimized to detect these abnormal heart rate characteristics (HRC) (11,(13)(14)(15) were used to develop an HRC index at one NICU and then validated at another as a predictor of neonatal infection and death (16 -18).…”

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confidence: 99%

Heart Rate Characteristics and Clinical Signs in Neonatal Sepsis

et al. 2007

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ABSTRACT:To test the hypothesis that heart rate characteristic (HRC) monitoring adds information to clinical signs of illness in diagnosing neonatal sepsis, we prospectively recorded clinical data and the HRC index in 76 episodes of proven sepsis and 80 episodes of clinical sepsis in 337 infants in the University of Virginia NICU more than 7 d old. We devised an illness severity score based on clinical findings and tests relevant to sepsis. Point scores were derived from coefficients of multivariable regression models, and we internally validated a total score. We determined relationships of the HRC index with individual clinical signs, laboratory tests, and the total score. We found highly significant correlations of the clinical score and individual clinical signs with the HRC index. The clinical score and HRC index added independent information in predicting sepsis, and were similar in clinical and proven sepsis. The clinical score and the HRC index rose before sepsis, and the HRC index rose first. We conclude that clinical signs of illness and HRC monitoring add independent information to one another in the diagnosis of neonatal sepsis. A cute clinical deterioration of infants in the NICU occurs frequently, especially in those of very low birth weight (Ͻ1500 g, VLBW), and late-onset bacterial sepsis is a common cause (1). Early diagnosis, before obvious clinical signs of illness, is an important goal but is difficult to achieve. The clinical signs of neonatal sepsis are neither specific nor uniform. Fanaroff et al. in the NICHD Neonatal Research Network found that increasing apnea, feeding intolerance, abdominal distension or guaiac-positive stools, increased respiratory support, lethargy and hypotonia were the most common presenting signs of sepsis, but none were found to have high predictive accuracy (2).Diagnosis of late-onset neonatal sepsis is difficult even when infants appear ill because blood cultures have a substantial false-negative rate, especially when based on small volumes of blood (3-7). Accordingly, the Centers for Disease Control recognizes "clinical sepsis" in infants, which requires only signs of illness with antibiotic therapy but no positive blood culture (8). The NICHD Neonatal Research Network found that both proven sepsis and clinical sepsis were associated with neurodevelopmental impairment in extremely low birth weight (Ͻ1000 g, ELBW) infants (9). The common denominator is the systemic inflammatory response syndrome (SIRS), the result of the host response to infectious and noninfectious insults (10). Clearly, new approaches to the early diagnosis of both proven and clinical neonatal sepsis are required.Before physician suspicion of sepsis and SIRS, neonates have reduced heart rate variability and transient decelerations similar to the findings in distressed fetuses (11,12). Heart rate measures optimized to detect these abnormal heart rate characteristics (HRC) (11,13-15) were used to develop an HRC index at one NICU and then validated at another as a predictor of neonatal infection ...

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Sample Asymmetry Analysis of Heart Rate Characteristics with Application to Neonatal Sepsis and Systemic Inflammatory Response Syndrome

Cited by 127 publications

References 20 publications

Abnormal Heart Rate Characteristics Are Associated with Neonatal Mortality

Abnormal Heart Rate Characteristics Are Associated with Neonatal Mortality

Uncorrelated Randomness of the Heart Rate Is Associated with Sepsis in Sick Premature Infants

Heart Rate Characteristics and Clinical Signs in Neonatal Sepsis

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