Published online April 1, 2005
PEDIATRICS Vol. 115 No. 4 April 2005, pp. 937-941 (doi:10.1542/peds.2004-1393)
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Heart Rate Characteristics and Laboratory Tests in Neonatal Sepsis

M. Pamela Griffin, MD*,{ddagger}, Douglas E. Lake, PhD{ddagger},§ and J. Randall Moorman, MD{ddagger},§,||

* Department of Pediatrics
{ddagger} Cardiovascular Research Center
§ Department of Internal Medicine
|| Department of Molecular Physiology and Biological Physics, University of Virginia Health System, Charlottesville, Virginia

Objective. The evaluation of an infant for suspected sepsis often includes obtaining blood for laboratory tests. The shortcomings of the current practice are that the infant has to appear clinically ill for the diagnosis to be entertained, and the conventional laboratory tests are invasive. We have found that the clinical diagnosis of neonatal sepsis is preceded by abnormal heart rate characteristics (HRC) of reduced variability and transient decelerations, and we have devised a predictive HRC monitoring strategy based on multivariable logistic regression analysis that was developed at one tertiary care NICU and validated at another. We hypothesized that HRC monitoring, which is continuous and noninvasive, might be an adjunct to conventional laboratory tests in the diagnosis of neonatal sepsis. The objective of this study was to test the hypothesis that HRC monitoring adds information to conventional laboratory tests in diagnosing neonatal sepsis.

Methods. We prospectively collected heart rate data in 678 consecutive infants who stayed >7 days in the University of Virginia NICU from July 1999 to July 2003. We prospectively measured HRC and noted 149 episodes of sepsis with positive blood cultures for which data were available in 137. We obtained all laboratory test results for ratio of immature to total neutrophil count, white blood cell count, glucose, platelet count, HCO3, arterial partial pressure of carbon dioxide, and pH. We tested hypotheses using multivariable logistic regression modeling adjusted for repeated measures.

Results. We found that the HRC index, which was available 92% of the time, was highly significantly associated with sepsis (receiver-operating characteristic [ROC] area: 0.73). The ratio of immature to total neutrophil count, white blood cell count (available 4%–8% of the time, usually around the time of suspected sepsis), and blood glucose and pH (available 28% and 38% of the time) were also significantly associated with sepsis (ROC area: 0.75). HRC and laboratory values added independent information to each other, and a predictive model using all significant variables had ROC area of 0.82.

Conclusions. HRC monitoring adds independent information to laboratory tests in the diagnosis of culture-positive neonatal sepsis.

Key Words: heart rate variability • infant • infection

Abbreviations: VLBW, very low birth weight • NICHD, National Institute of Child Health and Human Development • SIRS, systemic inflammatory response syndrome • HRV, heart rate variability • HR, heart rate • HRC, heart rate characteristics • WBC, white blood cell • I/T ratio, ratio of immature to total neutrophils • PCO2, arterial partial pressure of carbon dioxide • CBC, complete blood count

Accepted Aug 30, 2004.


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