Septicemia mortality reduction in neonates in a heart rate characteristics monitoring trial

Abstract

Background: Abnormal heart rate characteristics (HRC) wax and wane in early stages of culture-positive, late-onset septicemia (LOS) in patients in the neonatal intensive care unit (NICU). Continuously monitoring an HRC index leads to a reduction in mortality among very low birth weight (VLBW) infants. We hypothesized that the reduction in mortality was due to a decrease in septicemia-associated mortality.

Methods: This is a secondary analysis of clinical and HRC data from 2,989 VLBW infants enrolled in a randomized clinical trial of HRC monitoring in nine NICUs from 2004 to 2010.

Results: LOS was diagnosed 974 times in 700 patients, and the incidence and distribution of organisms were similar in HRC display and nondisplay groups. Mortality within 30 d of LOS was lower in the HRC display as compared with the nondisplay group (11.8 vs. 19.6%; relative risk: 0.61; 95% confidence interval: 0.43, 0.87; P < 0.01), but mortality reduction was not statistically significant for patients without LOS. There were fewer large, abrupt increases in the HRC index in the days leading up to LOS diagnosis in infants whose HRC index was displayed.

Conclusion: Continuous HRC monitoring is associated with a lower septicemia-associated mortality in VLBW infants, possibly due to diagnosis earlier in the course of illness.

Conflict of interest statement

DISCLOSURES: J.R.M. and D.E.L. have consulting agreements and equity shares in Medical Predictive Science Corporation, Charlottesville, VA. The other authors declare no conflicts of interest.

Figures

Figure 1

Late-onset septicemia in a randomized clinical trial of heart rate characteristics (HRC) monitoring in very low birth weight infants. 2989 VLBW infants at 9 neonatal intensive care units had HRC monitoring and were randomized to having their HRC index displayed to clinicians or not displayed. Twenty-three percent of infants had LOS (>3 days of age), and the organism distribution is shown for infants randomized to HRC display (left) or non-display (right). Black=coagulase-negative staphylococcus, white=other Gram-positive, grey=Gram-negative, striped=fungus.

Figure 2

Organism-specific mortality based on heart rate characteristics (HRC) monitor display. Survival is shown within 30 days of diagnosis of late-onset septicemia with CONS (A), other Gram-positive bacteria (B), Gram-negative bacteria (C), and fungi (D). Survival was higher in each organism group in infants with HRC displayed (solid line) compared with those with HRC not displayed (dashed line).

Figure 3

Heart rate characteristics index and risk factor–based probability in cases of late onset septicemia A) Average HRC index (solid line) in the 2-week period around the diagnosis of LOS at day 0, compared to the risk-factor based probability of sepsis (dotted line) based on gestational and postmenstrual age, birth weight, and mechanical ventilation. B) Average HRC index around the diagnosis of LOS in infants randomized to HRC display (solid line) or non-display (dashed line) (* p

Figure 4

Heart rate characteristics index monitor screen shots illustrating normal HRC and large HRC index spikes. A) HRC monitor individual patient display shows the 5-day HRC index trend (orange), the latest 30 minutes of heart rate in beats per minute (green), and the current HRC index (0.42). In this infant, the HRC index has been low (<1) for at least 5 days, indicating normal heart rate characteristics and low probability of sepsis in the next 24 hours. B) HRC monitor display for an infant with a large HRC index spike at the time of septicemia diagnosis (orange arrow, HeRO score 4.80) and no large spikes in the days before. C) Large HRC index spike at the time of septicemia diagnosis (orange arrow, HeRO score 4.99) and a large HRC index spike two days before sepsis diagnosis (yellow arrow, HeRO score 3.89).