Heart Rate Characteristics Monitoring Research Articles

Cost-effectiveness analysis of heart rate characteristics monitoring to improve survival for very low birth weight infants.

Over 50,000 very low birth weight (VLBW) infants are born each year in the United States. Despite advances in care, these premature babies are subjected to long stays in a neonatal intensive care unit (NICU), and experience high rates of morbidity and mortality. In a large randomized controlled trial (RCT), heart rate characteristics (HRC) monitoring in addition to standard monitoring decreased all-cause mortality among VLBW infants by 22%. We sought to understand the cost-effectiveness of HRC monitoring to improve survival among VLBW infants. We performed a secondary analysis of cost-effectiveness of heart rate characteristics (HRC) monitoring to improve survival from birth to NICU discharge, up to 120 days using data and outcomes from an RCT of 3,003 VLBW patients. We estimated each patient's cost from a third-party perspective in 2021 USD using the resource utilization data gathered during the RCT (NCT00307333) during their initial stay in the NICU and applied to specific per diem rates. We computed the incremental cost-effectiveness ratio and used non-parametric boot-strapping to evaluate uncertainty. The incremental cost-effectiveness ratio of HRC-monitoring was $34,720 per life saved. The 95th percentile of cost to save one additional life through HRC-monitoring was $449,291. HRC-monitoring appears cost-effective for increasing survival among VLBW infants.

Monitoring of heart rate characteristics to detect neonatal sepsis.

Monitoring of heart rate characteristics (HRC) index may improve outcomes of late-onset neonatal sepsis (LOS) through early detection. We aimed at describing the association between LOS and elevated HRC index. This single-center retrospective case-control study included neonates who presented with blood culture-proven hospital-acquired LOS. Controls were matched to cases (ratio 1:2) based on gestational age, postnatal age, and birthweight. We compared the highest HRC indexes in the 48 h preceding blood culture sampling in LOS cases to the highest HRC indexes at the same postnatal days in controls. In 59 LOS cases and 123 controls, an HRC index > 2 was associated with LOS (OR 7.1, 95% CI 2.6-19.0). Sensitivity and specificity of an HRC index > 2 to predict LOS were 53% (32/59) and 79% (98/123). Sensitivity increased from 25% in infants born > 32 weeks to 76% in infants born < 28 weeks. Specificity decreased from 97% in infants > 32 weeks to 63% in those born < 28 weeks. An increase of HRC index > 2 has a significant association with the diagnosis of LOS, supporting the use of HRC monitoring to assist early detection of LOS. Clinicians using HRC monitoring should be aware of its diagnostic accuracy and limitations in different gestational age groups. There is a paucity of data regarding the predictive value of heart rate characteristics (HRC) monitoring for early diagnosis of late-onset neonatal sepsis (LOS) in daily clinical practice. Monitoring of heart rate characteristics provides valuable information to assist the early diagnosis of LOS across all gestational age groups. However, the strong influence of gestational age on positive and negative predictive values adds complexity to the interpretation of HRC indexes.

Urinary tract infections in very low birthweight infants: A two-center analysis of microbiology, imaging and heart rate characteristics.

Increased understanding of characteristics of urinary tract infection (UTI) among very low birthweight infants (VLBW) might lead to improvement in detection and treatment. Continuous monitoring for abnormal heart rate characteristics (HRC) could provide early warning of UTIs. Describe the characteristics of UTI, including HRC, in VLBW infants. We reviewed records of VLBW infants admitted from 2005-2010 at two academic centers participating in a randomized clinical trial of HRC monitoring. Results of all urine cultures, renal ultrasounds (RUS), and voiding cystourethrograms (VCUG) were assessed. Change in the HRC index was analyzed before and after UTI. Of 823 VLBW infants (27.7±2.9 weeks GA, 53% male), 378 had > / = 1 urine culture obtained. A UTI (≥10,000 CFU and >five days of antibiotics) was diagnosed in 80 infants, (10% prevalence, mean GA 25.8±2.0 weeks, 76% male). Prophylactic antibiotics were administered to 29 (36%) infants after UTI, of whom four (14%) had another UTI. Recurrent UTI also occurred in 7/51 (14%) of infants not on uroprophylaxis after their first UTI. RUS was performed after UTI in 78%, and hydronephrosis and other major anomalies were found in 19%. A VCUG was performed in 48% of infants and 18% demonstrated vesicoureteral reflux (VUR). The mean HRC rose and fell significantly in the two days before and after diagnosis of UTI. UTI was diagnosed in 10% of VLBW infants, and the HRC index increased prior to diagnosis, suggesting that continuous HRC monitoring in the NICU might allow earlier diagnosis and treatment of UTI.

Mortality and Neurodevelopmental Outcomes in the Heart Rate Characteristics Monitoring Randomized Controlled Trial

To test whether the composite outcome of death or neurodevelopmental impairment (NDI) at 18-22months corrected age for infants ≤1000g at birth is decreased by continuous monitoring of heart rate characteristics during neonatal intensive care. We studied a subset of participants enrolled in a multicenter randomized trial of heart rate characteristics monitoring. Survivors were evaluated at 18-22months corrected age with a standardized neurologic examination and the Bayley Scales of Infant Development-III (BSID-III). NDI was defined as Gross Motor Function Classification System of >2 (moderate or severe cerebral palsy), BSID-III language or cognitive scores of <70, severe bilateral hearing impairment, and/or bilateral blindness. The composite outcome, death or NDI, was obtained for 628 of 884 study infants (72%). The prevalence of this outcome was 44.4% (136/306) among controls (infants randomized to heart rate characteristics monitored but not displayed) and 38.9% (125/322) among infants randomized to heart rate characteristics monitoring displayed (relative risk, 0.87; 95% CI, 0.73-1.05; P=.17). Mortality was reduced from 32.0% (99/307) among controls to 24.8% (81/326) among monitoring displayed infants (relative risk, 0.75; 95% CI, 0.59 to 0.97; P=.028). The composite outcomes of death or severe CP and death or mildly low Bayley cognitive score occurred less frequently in the displayed group (P<.05). We found no difference in the composite outcome of death or NDI for extremely preterm infants whose heart rate characteristics were and were not displayed during neonatal intensive care. Two outcomes that included mortality or a specific NDI were less frequent in the displayed group.

Heart Rate Characteristic Index Monitoring for Early Detection of Infections in Very Low Birth Weight Infants

The aim of this study is 1) to determine the sensitivity and specificity of continuous heart rate characteristics (HRC) monitoring in detection of infections and 2) to evaluate whether HRC monitoring detects infections prior to onset of clinical symptoms in very low birth weight (VLBW) infants. A retrospective cohort study was conducted analyzing HRC scores and episodes of infection for VLBW infants in the Neonatal Intensive Care Unit (NICU) at Cincinnati Children’s Hospital Medical Center from January 2015 through May 2016. HRC scores were acquired using the HRC monitor system and entered into the electronic medical record by bedside staff. Culture-positive and culture-negative clinical infections were recorded. Positive HRC scores were defined as an increase 1 point above the baseline or the first rise above 2. HRC scores within 24 hours and also within the 5-day period before the start of antibiotics for infections were analyzed for sensitivity, specificity, positive predictive value and negative predictive value for detection of neonatal infection. The HRC score increase 1 point above the baseline or the first rise above 2 in the 24 hours before the start of antibiotics for infectious events had a sensitivity of 68.0%, a specificity of 10.8%. Positive predictive value (PPV) and negative predictive value (NPV) were 34.0% and 33.3%, respectively. The PPV and NPV were modestly higher for elevated HRC scores during the 5-day period before infections, 41.1% and 66.7%, respectively. In our single-center retrospective study, elevated HRC scores had limited ability to detect infection. More than half of the positive monitor events were not related to infection. The potential clinical impact of the monitor to detect infection before the onset of clinical symptoms was limited and the risk for unnecessary evaluation and treatment was high.

Neonatal Intensive Care Unit Length of Stay Reduction by Heart Rate Characteristics Monitoring

To examine the effect of heart rate characteristics (HRC) monitoring on length of stay among very low birth weight (VLBW; <1500 g birth weight) neonates in the HeRO randomized controlled trial (RCT). We performed a retrospective analysis of length of stay metrics among 3 subpopulations (all patients, all survivors, and survivors with positive blood or urine cultures) enrolled in a multicenter, RCT of HRC monitoring. Among all patients in the RCT, infants randomized to receive HRC monitoring were more likely than controls to be discharged alive and prior to day 120 (83.6% vs 80.1%, P = .014). The postmenstrual age at discharge for survivors with positive blood or urine cultures was 3.2 days lower among infants randomized to receive HRC monitoring when compared with controls (P = .026). Although there were trends in other metrics toward reduced length of stay in HRC-monitored patients, none reached statistical significance. HRC monitoring is associated with reduced mortality in VLBW patients and a reduction in length of stay among infected surviving VLBW infants. ClinicalTrials.gov: NCT00307333.

Infection and Other Clinical Correlates of Abnormal Heart Rate Characteristics in Preterm Infants

To identify clinical conditions associated with a large increase (spike) in the heart rate characteristics index in very low birth weight (VLBW) infants. Retrospective medical record review within a day of all large heart rate characteristics index spikes (increase of ≥3 from the previous 5-day average) in VLBW infants at a single center enrolled from 2007 to 2010 in a multicenter trial of heart rate characteristics monitoring. In the trial, infants were randomized to having their heart rate characteristics index displayed to clinicians or not displayed. Of 274 eligible infants, 224 large heart rate characteristics spikes occurred in 105 infants. Thirty-three spikes were associated with surgery or procedures requiring anesthetic or anticholinergic medications, and infection-related conditions were the most common clinical association with the other spikes. Of the first spikes in 47 infants randomized to conventional monitoring (heart rate characteristics index not displayed to clinicians), 53% were associated with suspected or proven infection. Respiratory deterioration without suspected infection occurred with 34%, and no association was identified in 13%. Infants randomized to having their heart rate characteristics index displayed were more likely to have antibiotics initiated around the time of a large heart rate characteristics index spike. Sepsis, other infectious or systemic inflammatory conditions, respiratory deterioration, and surgical procedures are the most common clinical associations with a large increase in the heart rate characteristics index in VLBW infants. This information may improve use of heart rate characteristics monitors in patients in the neonatal intensive care unit.

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

BackgroundAbnormal 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.MethodsThis 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.ResultsLOS 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.ConclusionsContinuous HRC monitoring is associated with a lower septicemia-associated mortality in VLBW infants, possibly due to diagnosis earlier in the course of illness.

Abnormal heart rate characteristics before clinical diagnosis of necrotizing enterocolitis

ObjectiveEarlier diagnosis and treatment of necrotizing enterocolitis (NEC) in preterm infants, prior to clinical deterioration, might improve outcomes. A monitor that measures abnormal heart rate characteristics (HRC) of decreased variability and repetitive decelerations was developed as an early warning system for sepsis. Since NEC shares pathophysiologic features with sepsis, we tested the hypothesis that abnormal HRC occur prior to clinical diagnosis of NEC.Study DesignRetrospective review of Bells stage II to III NEC cases among infants <34 weeks gestation enrolled in a prospective randomized clinical trial of HRC monitoring at 3 neonatal intensive care units.ResultsOf 97 infants with NEC and HRC data, 33 underwent surgical intervention within one week of diagnosis. The baseline HRC index from 1 to 3 days before diagnosis was higher in patients who developed surgical versus medical NEC (2.06 ± 1.98 vs. 1.22 ± 1.10, p=0.009). The HRC index increased significantly 16 hours prior to the clinical diagnosis of surgical NEC and 6 hours prior to medical NEC. At the time of clinical diagnosis, the HRC index was higher in patients with surgical versus medical NEC (3.3 ± 2.2 vs 1.9 ± 1.7, p<0.001).ConclusionsAbnormal HRC occur before clinical diagnosis of NEC, suggesting that continuous HRC monitoring may facilitate earlier detection and treatment.

Predictive monitoring for early detection of sepsis in neonatal ICU patients.

Predictive monitoring is an exciting new field involving analysis of physiologic data to detect abnormal patterns associated with critical illness. The first example of predictive monitoring being taken from inception (proof of concept) to reality (demonstration of improved outcomes) is the use of heart rate characteristics (HRC) monitoring to detect sepsis in infants in the neonatal ICU. The commercially available 'HeRO' monitor analyzes electrocardiogram data from existing bedside monitors for decreased HR variability and transient decelerations associated with sepsis, and converts these changes into a score (the HRC index or HeRO score). This score is the fold increase in probability that a patient will have a clinical deterioration from sepsis within 24 h. This review focuses on HRC monitoring and discusses future directions in predictive monitoring of ICU patients. In a randomized trial of 3003 very low birthweight infants, display of the HeRO score reduced mortality more than 20%. Ongoing research aims to combine respiratory and HR analysis to optimize care of ICU patients. Predictive monitoring has recently been shown to save lives. Harnessing and analyzing the vast amounts of physiologic data constantly displayed in ICU patients will lead to improved algorithms for early detection, prognosis, and therapy of critical illnesses.

Long-Term Forecasting of Death in the Neonatal ICU using Heart Rate Characteristics Monitoring and Clinical Data

Background: Early and on-going prediction of in-NICU mortality can aid clinicians and parents who are caring for high-risk preterm infants.We developed heart rate characteristics (HRC) monitoring based on findings of reduced variability and transient decelerations prior to signs of sepsis. The HRC index, or HeRO score, is the fold-increase in risk of sepsis in the next 24 hours. Rising HeRO scores prompt clinicians to evaluate infants not otherwise suspected of illness. In the HeRO trial, we randomized 3000 VLBW infants in 9 US NICUs either to display of HeRO scores or to conventional monitoring. Those whose HeRO score results were displayed had statistically significant mortality reduction in excess of 20%.Aims: In this work, our aim was to test the hypothesis that average HeRO scores and knowledge of sepsis and ventilation can accurately predict NICU mortality from early in the stay.Methods: We modeled 152 deaths in 1489 VLBW infants who received only conventional monitoring in the HeRO trial using multivariable logistic regression.Results: In order of significance, the average HeRO score, presence of ventilator, birth weight, Apgar score at 5 (but not 1) minutes, and sepsis within the past 10 days predicted mortality (p< 0.005 for each). The model had good discrimination, with ROC area near 0.85 starting at 3 hours of monitoring.Conclusions: Heart rate characteristics monitoring and clinical data about ventilation and sepsis predict NICU death beginning at 3 hours. These findings may add to the mortality benefit of HeRO monitoring.

Cardiovascular oscillations at the bedside: early diagnosis of neonatal sepsis using heart rate characteristics monitoring

We have applied principles of statistical signal processing and nonlinear dynamics to analyze heart rate time series from premature newborn infants in order to assist in the early diagnosis of sepsis, a common and potentially deadly bacterial infection of the bloodstream. We began with the observation of reduced variability and transient decelerations in heart rate interval time series for hours up to days prior to clinical signs of illness. We find that measurements of standard deviation, sample asymmetry and sample entropy are highly related to imminent clinical illness. We developed multivariable statistical predictive models, and an interface to display the real-time results to clinicians. Using this approach, we have observed numerous cases in which incipient neonatal sepsis was diagnosed and treated without any clinical illness at all. This review focuses on the mathematical and statistical time series approaches used to detect these abnormal heart rate characteristics and present predictive monitoring information to the clinician.

Mortality Reduction by Heart Rate Characteristic Monitoring in Very Low Birth Weight Neonates: A Randomized Trial

To test the hypothesis that heart rate characteristics (HRC) monitoring improves neonatal outcomes. We conducted a two-group, parallel, individually randomized controlled clinical trial of 3003 very low birth weight infants in 9 neonatal intensive care units. 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, neonatal intensive care unit stay, and antibiotic use. The mortality rate was reduced in infants whose HRC monitoring was displayed, from 10.2% to 8.1% (hazard ratio, 0.78; 95% CI, 0.61-0.99; P = .04; number needed to monitor = 48), and there was a trend toward increased days alive and ventilator-free (95.9 of 120 days compared with 93.6 in control subjects, P = .08). The mortality benefit was concentrated in infants with a birth weight <1000 g (hazard ratio, 0.74; 95% CI, 0.57-0.95; P = .02; number needed to monitor = 23). There were no significant differences in the other outcomes. HRC monitoring can reduce the mortality rate in very low birth weight infants.

Heart Rate Characteristics and Laboratory Tests in Neonatal Sepsis

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

Abnormal heart rate characteristics preceding neonatal sepsis and sepsis-like illness.

Late-onset neonatal sepsis is a significant cause of morbidity and mortality, and early detection could prove beneficial. Previously, we found that abnormal heart rate characteristics (HRC) of reduced variability and transient decelerations occurred early in the course of neonatal sepsis and sepsis-like illness in infants in a single neonatal intensive care unit (NICU). We hypothesized that this finding can be generalized to other NICUs. We prospectively collected clinical data and continuously measured RR intervals in all infants in two NICUs who stayed for >7 d. We defined episodes of sepsis and sepsis-like illness as acute clinical deteriorations that prompted physicians to obtain blood cultures and start antibiotics. A predictive statistical model yielding an HRC index was developed on a derivation cohort of 316 neonates in the University of Virginia NICU and then applied to the validation cohort of 317 neonates in the Wake Forest University NICU. In the derivation cohort, there were 155 episodes of sepsis and sepsis-like illness in 101 infants, and in the validation cohort, there were 118 episodes in 93 infants. In the validation cohort, the HRC index 1) showed highly significant association with impending sepsis and sepsis-like illness (receiver operator characteristic area 0.75, p < 0.001) and 2) added significantly to the demographic information of birth weight, gestational age, and days of postnatal age in predicting sepsis and sepsis-like illness (p < 0.001). Continuous HRC monitoring is a generally valid and potentially useful noninvasive tool in the early diagnosis of neonatal sepsis and sepsis-like illness.