Objective
To test the hypothesis that heart rate characteristics (HRC) monitoring improves neonatal outcomes.
Study design
Two-group, parallel, individually randomized controlled clinical trial of 3003 very low birth weight infants in 9 NICUs. In one group, HRC monitoring was displayed; in the other, it was masked. The primary outcome was number of days alive and ventilator-free in the 120 days after randomization. Secondary outcomes were mortality, number of ventilator days, NICU stay and antibiotic use.
Results
Mortality was reduced in infants whose HRC monitoring was displayed, from 10.2% to 8.1% (HR = 0.78, 95% CI = 0.61 to 0.99, P = 0.04, number needed to monitor 48), and there was a trend toward increased days alive and ventilator-free (95.9 of 120 days compared to 93.6 in controls, P = 0.08). Mortality benefit was concentrated in infants with birth weight <1000g (HR=0.74, 95% CI 0.57 to 0.95, P=0.02, number needed to monitor 23). There were no significant differences in the other outcomes.
Conclusion
Heart rate characteristics monitoring can reduce mortality in very low birth weight infants.
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 2989 VLBW infants enrolled in a randomized controlled trial of HRC monitoring in 9 NICUs from 2004–2010.
Results
LOS was diagnosed 974 times in 700 patients, and the incidence and distribution of organisms were similar in HRC display and non-display groups. Mortality within 30 days of LOS was lower in the HRC display compared to the non-display group (11.8% vs 19.6%, RR 0.61, 95% CI 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.
Conclusions
Continuous HRC monitoring is associated with a lower septicemia-associated mortality in VLBW infants, possibly due to diagnosis earlier in the course of illness.
Neutrophils contribute to ischemic brain injury in adult animals. The role of neutrophils in perinatal hypoxic-ischemic (HI) brain injury is unknown. Allopurinol reduces neutrophil accumulation after tissue ischemia and is protective against HI brain injury. This study was designed to investigate how neutrophils contribute to perinatal hypoxic ischemic brain injury and how neutropenia compared with allopurinol in its neuroprotective effects. A HI insult was produced in the right cerebral hemisphere of 7-d-old rats by right common carotid artery ligation and systemic hypoxia. Half the rats were rendered neutropenic with an anti-neutrophil serum (ANS). At 15 min of recovery from hypoxia, half the neutropenic and nonneutropenic rats received allopurinol (135 mg/kg, s.c.). The protective effect of the four treatment combinations was determined on brain swelling at 42 h of recovery. Neutropenia reduced brain swelling by about 70%, p < 0.01. Allopurinol alone produced similar protection so that the relatively small number of animals studied did not permit assessment of an additive effect. Neutrophil accumulation in cerebral hemispheres was measured by myeloperoxidase (MPO) activity assay and by neutrophil counts in 6-microm sections stained by MPO and ANS immunostaining. MPO activity peaked between 4 and 8 h of recovery in both hemispheres. Hemispheric neutrophil counts peaked at the end of the HI insult and again at 18 h of recovery. Neutrophils were stained within blood vessels and did not infiltrate the injured brain before infarction had occurred. We conclude that neutrophils contribute to HI brain injury in the neonate and that neutrophil depletion before the insult is neuroprotective.
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