Apnea, Intermittent Hypoxemia, and Bradycardia Events Predict Late-Onset Sepsis in Infants Born Extremely Preterm.

OBJECTIVE: The objective of this study was to examine the association of cardiorespiratory events, including apnea, periodic breathing, intermittent hypoxemia (IH), and bradycardia, with late-onset sepsis for extremely preterm infants (<29 weeks of gestational age) on vs off invasive mechanical ventilation. STUDY DESIGN: This is a retrospective analysis of data from infants enrolled in Pre-Vent (ClinicalTrials.gov identifier NCT03174301), an observational study in 5 level IV neonatal intensive care units. Clinical data were analyzed for 737 infants (mean gestational age: 26.4 weeks, SD 1.71). Monitoring data were available and analyzed for 719 infants (47 512 patient-days); of whom, 109 had 123 sepsis events. Using continuous monitoring data, we quantified apnea, periodic breathing, bradycardia, and IH. We analyzed the relationships between these daily measures and late-onset sepsis (positive blood culture >72 hours after birth and ≥5-day antibiotics). RESULTS: For infants not on a ventilator, apnea, periodic breathing, and bradycardia increased before sepsis diagnosis. During times on a ventilator, increased sepsis risk was associated with longer events with oxygen saturation <80% (IH80) and more bradycardia events before sepsis. IH events were associated with higher sepsis risk but did not dynamically increase before sepsis, regardless of ventilator status. A multivariable model including postmenstrual age, cardiorespiratory variables (apnea, periodic breathing, IH80, and bradycardia), and ventilator status predicted sepsis with an area under the receiver operator characteristic curve of 0.783. CONCLUSION: We identified cardiorespiratory signatures of late-onset sepsis. Longer IH events were associated with increased sepsis risk but did not change temporally near diagnosis. Increases in bradycardia, apnea, and periodic breathing preceded the clinical diagnosis of sepsis.

Clinical correlates of a high cardiorespiratory risk score for very low birth weight infants.

BACKGROUND: A pulse oximetry warning system (POWS) to analyze heart rate and oxygen saturation data and predict risk of sepsis was developed for very low birth weight (VLBW) infants. METHODS: We determined the clinical correlates and positive predictive value (PPV) of a high POWS score in VLBW infants. In a two-NICU retrospective study, we identified times when POWS increased above 6 (POWS spike). We selected an equal number of control times, matched for gestational and chronologic age. We reviewed records for infection and non-infection events around POWS spikes and control times. We calculated the frequencies and PPV of a POWS spike for infection or another significant event. RESULTS: We reviewed 111 POWS spike times and 111 control times. Days near POWS spikes were more likely to have clinical events than control days (77% vs 50%). A POWS spike had 52% PPV for suspected or confirmed infection and 77% for any clinically significant event. Respiratory deterioration occurred near more POWS spike times than control times (34% vs 18%). CONCLUSIONS: In a retrospective cohort, infection and respiratory deterioration were common clinical correlations of a POWS spike. POWS had a high PPV for significant clinical events with or without infection. IMPACT: There are significant gaps in understanding the best approach to implementing continuous sepsis prediction models so that clinicians can best respond to early signals of deterioration. Infection and respiratory deterioration were common clinical events identified at the time of a high predictive model score. Understanding the clinical correlates of a high-risk early warning score will inform future implementation efforts.

Impact of pharmacologic patent ductus arteriosus treatment on acute respiratory and oxygenation metrics in very low birth weight infants.

BACKGROUND: Hypoxemia and respiratory compromise occur in very low birthweight (VLBW, <1500 grams) infants and may be associated with shunting across a patent ductus arteriosus (PDA). The impact of pharmacologic PDA treatment on acute hypoxemia and respiratory metrics is unclear. OBJECTIVE: To determine whether pharmacologic PDA treatment is associated with acute improvement in hypoxemia and respiratory metrics in VLBW infants. STUDY DESIGN: At a single center (2012-2022), all VLBW infants with echocardiographic evidence of a PDA and without exclusions were classified as having received or not received pharmacologic PDA treatment (PDA-T, PDA-NT). Mean daily FiO2 and Respiratory Acuity Score (RAS, PMID 30374050) were compared at baseline (day 0) and 3 days after treatment start. For PDA-T infants with archived 0.5Hz (every-2-second) SpO2 data, mean daily SpO2 and the percentage of time with severe hypoxemia (SpO2 <80%) were compared before and after treatment. Severe hypoxemia was further analyzed after stratification by clinical variables (sex, medication, gestational age, postnatal age). RESULTS: We analyzed 125 VLBW infants with a PDA, of whom 66 received pharmacologic PDA treatment. We analyzed a subgroup of 43 PDA-T infants with every-2-second SpO2 data available. PDA-T infants had higher baseline FiO2 and RAS and lower SpO2 than PDA-NT infants (p<0.05). Compared to baseline, RAS decreased from median 258 (IQR 171, 348) to 254 (IQR 174, 419) three days after the start of treatment (p=0.012), but median FiO2 increased from 37% (IQR 28, 46) to 40% (IQR 29, 52) (p=0.008). SpO2 and the percent time with severe hypoxemia were unchanged. CONCLUSIONS: In this 10-year retrospective single-center analysis, pharmacologic PDA treatment in VLBW infants was not associated with a major improvement in acute measures of oxygenation or level of respiratory support.

Heart Rate Variability as a Prognostic Tool for Gastroschisis Infants in the Neonatal Intensive Critical Unit.

OBJECTIVE: Gastroschisis is the most common congenital abdominal wall defect, with an increasing incidence. It results in extrusion of abdominal contents with associated delayed intestinal motility. Abnormal heart rate characteristics (HRCs) such as decreased variability occur due to the inflammatory response to sepsis in preterm infants. This study aimed to test the hypothesis that infants with gastroschisis have decreased heart rate variability (HRV) after birth and that this physiomarker may predict outcomes. STUDY DESIGN: We analyzed heart rate data from and clinical variables for all infants admitted with gastroschisis from 2009 to 2020. RESULTS: Forty-seven infants were admitted during the study period and had available data. Complex gastroschisis infants had reduced HRV after birth. For those with sepsis and necrotizing enterocolitis, abnormal HRCs occurred early in the course of illness. CONCLUSION: Decreased HRV was associated with complex gastroschisis. Infants in this group experienced complications that prolonged time to full enteral feeding and time on total parenteral nutrition. KEY POINTS: · Infants with gastroschisis can be classified into two subcategories, simple and complex disease.. · Those with complex disease often require prolonged stays in the neonatal intensive care unit and costly hospitalizations. We hypothesized that infants with complex gastroschisis are more likely to have abnormal HRC due to intestinal inflammation.. · In this study, we identified associations between abnormal HRV, heart rate characteristicHRC, and the development of gastroschisis complications. Additionally, we described differences in clinical characteristics between infants with complex versus simple gastroschisis..

Artificial and human intelligence for early identification of neonatal sepsis.

Artificial intelligence may have a role in the early detection of sepsis in neonates. Machine learning can identify patterns that predict high or increasing risk for clinical deterioration from a sepsis-like illness. In developing this potential addition to NICU care, careful consideration should be given to the data and methods used to develop, validate, and evaluate prediction models. When an AI system alerts clinicians to a change in a patient's condition that warrants a bedside evaluation, human intelligence and experience come into play to determine an appropriate course of action: evaluate and treat or wait and watch closely. With intelligently developed, validated, and implemented AI sepsis systems, both clinicians and patients stand to benefit. IMPACT: This narrative review highlights the application of AI in neonatal sepsis prediction. It describes issues in clinical prediction model development specific to this population. This article reviews the methods, considerations, and literature on neonatal sepsis model development and validation. Challenges of AI technology and potential barriers to using sepsis AI systems in the NICU are discussed.

Cardiorespiratory signature of neonatal sepsis: development and validation of prediction models in 3 NICUs.

BACKGROUND: Heart rate characteristics aid early detection of late-onset sepsis (LOS), but respiratory data contain additional signatures of illness due to infection. Predictive models using cardiorespiratory data may improve early sepsis detection. We hypothesized that heart rate (HR) and oxygenation (SpO2) data contain signatures that improve sepsis risk prediction over HR or demographics alone. METHODS: We analyzed cardiorespiratory data from very low birth weight (VLBW, <1500 g) infants admitted to three NICUs. We developed and externally validated four machine learning models to predict LOS using features calculated every 10 m: mean, standard deviation, skewness, kurtosis of HR and SpO2, and cross-correlation. We compared feature importance, discrimination, calibration, and dynamic prediction across models and cohorts. We built models of demographics and HR or SpO2 features alone for comparison with HR-SpO2 models. RESULTS: Performance, feature importance, and calibration were similar among modeling methods. All models had favorable external validation performance. The HR-SpO2 model performed better than models using either HR or SpO2 alone. Demographics improved the discrimination of all physiologic data models but dampened dynamic performance. CONCLUSIONS: Cardiorespiratory signatures detect LOS in VLBW infants at 3 NICUs. Demographics risk-stratify, but predictive modeling with both HR and SpO2 features provides the best dynamic risk prediction. IMPACT: Heart rate characteristics aid early detection of late-onset sepsis, but respiratory data contain signatures of illness due to infection. Predictive models using both heart rate and respiratory data may improve early sepsis detection. A cardiorespiratory early warning score, analyzing heart rate from electrocardiogram or pulse oximetry with SpO2, predicts late-onset sepsis within 24 h across multiple NICUs and detects sepsis better than heart rate characteristics or demographics alone. Demographics risk-stratify, but predictive modeling with both HR and SpO2 features provides the best dynamic risk prediction. The results increase understanding of physiologic signatures of neonatal sepsis.

Inflammatory biomarkers and physiomarkers of late-onset sepsis and necrotizing enterocolitis in premature infants.

Background: Early diagnosis of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) in very low birth weight (VLBW, <1,500 g) infants is challenging due to non-specific clinical signs. Inflammatory biomarkers increase in response to infection, but non-infectious conditions also cause inflammation. Cardiorespiratory data contain physiological biomarkers, or physiomarkers, of sepsis that may be useful in combination with inflammatory hematologic biomarkers for sepsis diagnosis. Objectives: To determine whether inflammatory biomarkers measured at the time of LOS or NEC diagnosis differ from times without infection and whether biomarkers correlate with cardiorespiratory sepsis physiomarkers in VLBW infants. Methods: Remnant plasma sample collection from VLBW infants occurred with blood draws for routine laboratory testing and suspected sepsis. We analyzed 11 inflammatory biomarkers and a pulse oximetry sepsis warning score (POWS). We compared biomarker levels obtained at the time of gram-negative (GN) bacteremia or NEC, gram-positive (GP) bacteremia, negative blood cultures, and no suspected infection. Results: We analyzed 188 samples in 54 VLBW infants. Several biomarkers were increased at the time of GN LOS or NEC diagnosis compared with all other samples. POWS was higher in patients with LOS and correlated with five biomarkers. IL-6 had 78% specificity at 100% sensitivity to detect GN LOS or NEC and added information to POWS. Conclusions: Inflammatory plasma biomarkers discriminate sepsis due to GN bacteremia or NEC and correlate with cardiorespiratory physiomarkers.

Apnea, Intermittent Hypoxemia, and Bradycardia Events Predict Late-Onset Sepsis in Extremely Preterm Infants.

Objectives: Detection of changes in cardiorespiratory events, including apnea, periodic breathing, intermittent hypoxemia (IH), and bradycardia, may facilitate earlier detection of sepsis. Our objective was to examine the association of cardiorespiratory events with late-onset sepsis for extremely preterm infants (<29 weeks' gestational age (GA)) on versus off invasive mechanical ventilation. Study Design: Retrospective analysis of data from infants enrolled in Pre-Vent (ClinicalTrials.gov identifier NCT03174301), an observational study in five level IV neonatal intensive care units. Clinical data were analyzed for 737 infants (mean GA 26.4w, SD 1.71). Monitoring data were available and analyzed for 719 infants (47,512 patient-days), of whom 109 had 123 sepsis events. Using continuous monitoring data, we quantified apnea, periodic breathing, bradycardia, and IH. We analyzed the relationships between these daily measures and late-onset sepsis (positive blood culture >72h after birth and ≥5d antibiotics). Results: For infants not on a ventilator, apnea, periodic breathing, and bradycardia increased before sepsis diagnosis. During times on a ventilator, increased sepsis risk was associated with longer IH80 events and more bradycardia events before sepsis. IH events were associated with higher sepsis risk, but did not dynamically increase before sepsis, regardless of ventilator status. A multivariable model predicted sepsis with an AUC of 0.783. Conclusion: We identified cardiorespiratory signatures of late-onset sepsis. Longer IH events were associated with increased sepsis risk but did not change temporally near diagnosis. Increases in bradycardia, apnea, and periodic breathing preceded the clinical diagnosis of sepsis.

Data Science and Precision Oncology Nursing: Creating an Analytic Ecosystem to Support Personalized Supportive Care across the Trajectory of Illness.

OBJECTIVES: The authors' objective is to present an overarching framework of an analytic ecosystem using diverse data domains and data science approaches that can be used and implemented across the cancer continuum. Analytic ecosystems can improve quality practices and offer enhanced anticipatory guidance in the era of precision oncology nursing. DATA SOURCES: Published scientific articles supporting the development of a novel framework with a case exemplar to provide applied examples of current barriers in data integration and use. CONCLUSION: The combination of diverse data sets and data science analytic approaches has the potential to extend precision oncology nursing research and practice. Integration of this framework can be implemented within a learning health system where models can update as new data become available across the continuum of the cancer care trajectory. To date, data science approaches have been underused in extending personalized toxicity assessments, precision supportive care, and enhancing end-of-life care practices. IMPLICATIONS FOR NURSING PRACTICE: Nurses and nurse scientists have a unique role in the convergence of data science applications to support precision oncology across the trajectory of illness. Nurses also have specific expertise in supportive care needs that have been dramatically underrepresented in existing data science approaches thus far. They also have a role in centering the patient and family perspectives and needs as these frameworks and analytic capabilities evolve.

Individual illness dynamics: An analysis of children with sepsis admitted to the pediatric intensive care unit.

Illness dynamics and patterns of recovery may be essential features in understanding the critical illness course. We propose a method to characterize individual illness dynamics in patients who experienced sepsis in the pediatric intensive care unit. We defined illness states based on illness severity scores generated from a multi-variable prediction model. For each patient, we calculated transition probabilities to characterize movement among illness states. We calculated the Shannon entropy of the transition probabilities. Using the entropy parameter, we determined phenotypes of illness dynamics based on hierarchical clustering. We also examined the association between individual entropy scores and a composite variable of negative outcomes. Entropy-based clustering identified four illness dynamic phenotypes in a cohort of 164 intensive care unit admissions where at least one sepsis event occurred. Compared to the low-risk phenotype, the high-risk phenotype was defined by the highest entropy values and had the most ill patients as defined by a composite variable of negative outcomes. Entropy was significantly associated with the negative outcome composite variable in a regression analysis. Information-theoretical approaches to characterize illness trajectories offer a novel way of assessing the complexity of a course of illness. Characterizing illness dynamics with entropy offers additional information in conjunction with static assessments of illness severity. Additional attention is needed to test and incorporate novel measures representing the dynamics of illness.

Physiological machine learning models for prediction of sepsis in hospitalized adults: An integrative review.

BACKGROUND: Diagnosing sepsis remains challenging. Data compiled from continuous monitoring and electronic health records allow for new opportunities to compute predictions based on machine learning techniques. There has been a lack of consensus identifying best practices for model development and validation towards early identification of sepsis. OBJECTIVE: To evaluate the modeling approach and statistical methodology of machine learning prediction models for sepsis in the adult hospital population. METHODS: PubMed, CINAHL, and Cochrane databases were searched with the Preferred Reporting Items for Systematic Reviews guided protocol development. We evaluated studies that developed or validated physiologic sepsis prediction models or implemented a model in the hospital environment. RESULTS: Fourteen studies met the inclusion criteria, and the AUROC of the prediction models ranged from 0.61 to 0.96. We found a variety of sepsis definitions, methods used for event adjudication, model parameters used, and modeling methods. Two studies tested models in clinical settings; the results suggested that patient outcomes were improved with implementation of machine learning models. CONCLUSION: Nurses have a unique perspective to offer in the development and implementation of machine learning models detecting patients at risk for sepsis. More work is needed in developing model harmonization standards and testing in clinical settings.

Dynamic Transitions of Pediatric Sepsis: A Markov Chain Analysis.

Pediatric sepsis is a heterogeneous disease with varying physiological dynamics associated with recovery, disability, and mortality. Using risk scores generated from a sepsis prediction model to define illness states, we used Markov chain modeling to describe disease dynamics over time by describing how children transition among illness states. We analyzed 18,666 illness state transitions over 157 pediatric intensive care unit admissions in the 3 days following blood cultures for suspected sepsis. We used Shannon entropy to quantify the differences in transition matrices stratified by clinical characteristics. The population-based transition matrix based on the sepsis illness severity scores in the days following a sepsis diagnosis can describe a sepsis illness trajectory. Using the entropy based on Markov chain transition matrices, we found a different structure of dynamic transitions based on ventilator use but not age group. Stochastic modeling of transitions in sepsis illness severity scores can be useful in describing the variation in transitions made by patient and clinical characteristics.