| Abstract | BACKGROUND AND OBJECTIVE: Abrupt clinical deterioration because of sepsis is a
major cause of morbidity and mortality in neonates, and earlier diagnosis should improve
therapy of this potentially catastrophic illness. In practice, clinical signs and laboratory data
have not been perceived as sensitive or specific for early stages of sepsis. Because heart rate
characteristics (HRC) are abnormal during fetal distress and neonatal illness, we
hypothesized that abnormal HRC might precede the clinical diagnosis of neonatal sepsis,
adding independent information to standard clinical parameters. METHODS: In the neonatal
intensive care unit at the University of Virginia, we prospectively studied infants admitted
from August 1995 to April 1999 who were at risk for developing sepsis. Infants in the sepsis
(culture-positive) and sepsis-like illness (culture-negative) groups had an abrupt clinical
deterioration that raised clinical suspicion of infection and prompted physicians to obtain
blood cultures and start antibiotic therapy. Infants without sepsis raised no clinical suspicion
of illness and had no cultures obtained. We measured novel characteristics-moments and
percentiles-of normalized heart rate (HR) time series for 5 days before and 3 days after
sepsis, sepsis-like illness, or a random time in controls. We also calculated the Score for
Neonatal Acute Physiology (SNAP) and the Neonatal Therapeutic Intervention Scoring
System (NTISS) as clinical scores of the severity of illness. RESULTS: There were 46
episodes of culture-positive sepsis in 40 patients and 27 episodes of culture-negative
sepsis-like illness in 23 patients. We analyzed 29 control periods in 26 patients. Infants with
sepsis and sepsis-like illness had lower birth weights and gestational ages and higher SNAP
and NTISS scores than did infants without sepsis. The most important new finding was that
the infants in the sepsis and sepsis-like illness groups had increasingly abnormal HRC for up
to 24 hours preceding their abrupt clinical deterioration. The abnormal HRC were reduced
baseline variability and short-lived decelerations in HR. These abnormalities led to significant
changes in HRC measures, for example, the third moment (skewness:.59 +/-.10 for sepsis
and.51 +/-. 12 for sepsis-like illness, compared with -.10 +/-.13 for control over the 6 hours
before abrupt deterioration). Culture-positive and culture-negative patients had similar HRC
and clinical scores, including a significant rise in SNAP in the 24 hours before the event.
Multivariable logistic regression analysis showed that HRC and clinical scores independently
added information in distinguishing infants with sepsis and sepsis-like illness from control
patients in the 24 hours before abrupt deterioration. CONCLUSIONS: Newborn infants
who had abrupt clinical deterioration as a result of sepsis and sepsis-like illness had abnormal
HRC and SNAP that worsened over 24 hours before the clinical suspicion of sepsis. A
strategy for monitoring these parameters in infants at risk for sepsis and sepsis-like illness
might lead to earlier diagnosis and more effective therapy. |