Novel approaches to capturing and using continuous cardiorespiratory physiological data in hospitalized children.

Continuous cardiorespiratory physiological monitoring is a cornerstone of care in hospitalized children. The data generated by monitoring devices coupled with machine learning could transform the way we provide care. This scoping review summarizes existing evidence on novel approaches to continuous cardiorespiratory monitoring in hospitalized children. We aimed to identify opportunities for the development of monitoring technology and the use of machine learning to analyze continuous physiological data to improve the outcomes of hospitalized children. We included original research articles published on or after January 1, 2001, involving novel approaches to collect and use continuous cardiorespiratory physiological data in hospitalized children. OVID Medline, PubMed, and Embase databases were searched. We screened 2909 articles and performed full-text extraction of 105 articles. We identified 58 articles describing novel devices or approaches, which were generally small and single-center. In addition, we identified 47 articles that described the use of continuous physiological data in prediction models, but only 7 integrated multidimensional data (e.g., demographics, laboratory results). We identified three areas for development: (1) further validation of promising novel devices; (2) more studies of models integrating multidimensional data with continuous cardiorespiratory data; and (3) further dissemination, implementation, and validation of prediction models using continuous cardiorespiratory data. IMPACT: We performed a comprehensive scoping review of novel approaches to capture and use continuous cardiorespiratory physiological data for monitoring, diagnosis, providing care, and predicting events in hospitalized infants and children, from novel devices to machine learning-based prediction models. We identified three key areas for future development: (1) further validation of promising novel devices; (2) more studies of models integrating multidimensional data with continuous cardiorespiratory data; and (3) further dissemination, implementation, and validation of prediction models using cardiorespiratory data.

Practicing What We Preach: An Effort to Improve Safe Sleep of Hospitalized Infants.

Introduction: To prevent sudden unexpected infant death, pediatric providers recommend the ABCs of infant sleep: Alone, on the Back, and in an empty Crib. This study's objective was to document sleep practices of infants admitted to a large children's hospital, examine adherence to American Academy of Pediatrics safe sleep guidelines, and develop interventions to improve guideline adherence. Methods: We conducted a pre/post quality improvement study at a single quaternary care medical center from 2015 to 2019. Infants 0 to younger than 12 months were observed in their sleeping environment pre- and post-implementation of multiple hospital-wide interventions to improve the sleep safety of hospitalized infants. Results: Only 1.3% of 221 infants observed preintervention met all ABCs of safe sleep; 10.6% of 237 infants met the ABCs of safe sleep postintervention. Significant improvements in the post-intervention cohort included sleeping in a crib (94% versus 80% preintervention; P < 0.001), avoidance of co-sleeping (3% versus 15% preintervention; P < 0.001), absence of supplies in the crib (58% versus 15% preintervention; P < 0.001), and presence of an empty crib (13% versus 2% preintervention; P < 0.001). Conclusions: Most infants hospitalized at our institution do not sleep in a safe environment. However, the implementation of a care bundle led to improvements in the sleep environment in the hospital. Further research is necessary to continue improving in-hospital safe sleep and to assess whether these practices impact the home sleep environment.

Multiple Organ Dysfunction Interactions in Critically Ill Children.

Introduction: Multiple organ dysfunction (MOD) is a common pathway to morbidity and death in critically ill children. Defining organ dysfunction is challenging, as we lack a complete understanding of the complex pathobiology. Current pediatric organ dysfunction criteria assign the same diagnostic value-the same "weight"- to each organ system. While each organ dysfunction in isolation contributes to the outcome, there are likely complex interactions between multiple failing organs that are not simply additive. Objective: Determine whether certain combinations of organ system dysfunctions have a significant interaction associated with higher risk of morbidity or mortality in critically ill children. Methods: We conducted a retrospective observational cohort study of critically ill children at two large academic medical centers from 2010 and 2018. Patients were included in the study if they had at least two organ dysfunctions by day 3 of PICU admission based on the Pediatric Organ Dysfunction Information Update Mandate (PODIUM) criteria. Mortality was described as absolute number of deaths and mortality rate. Combinations of two pediatric organ dysfunctions were analyzed with interaction terms as independent variables and mortality or persistent MOD as the dependent variable in logistic regression models. Results: Overall, 7,897 patients met inclusion criteria and 446 patients (5.6%) died. The organ dysfunction interactions that were significantly associated with the highest absolute number of deaths were cardiovascular + endocrinologic, cardiovascular + neurologic, and cardiovascular + respiratory. Additionally, the interactions associated with the highest mortality rates were liver + cardiovascular, respiratory + hematologic, and respiratory + renal. Among patients with persistent MOD, the most common organ dysfunctions with significant interaction terms were neurologic + respiratory, hematologic + immunologic, and endocrinologic + respiratory. Further analysis using classification and regression trees (CART) demonstrated that the absence of respiratory and liver dysfunction was associated with the lowest likelihood of mortality. Implications and Future Directions: Certain combinations of organ dysfunctions are associated with a higher risk of persistent MOD or death. Notably, the three most common organ dysfunction interactions were associated with 75% of the mortality in our cohort. Critically ill children with MOD presenting with these combinations of organ dysfunctions warrant further study.

Missed Opportunities: Healthcare Encounters Prior to Sudden Unexpected Infant Death.

Introduction: Sudden unexpected infant death (SUID) is the leading cause of death in children 28 days to 1 year of age. The study aim was to identify opportunities for healthcare professionals to provide families with education on sleep and prevention of SUID. Methods: We performed a retrospective chart review of SUID infants over 10 years (12/2010-12/2020). The study included patients 0-12 months who presented to single institution with SUID (including asphyxia, suffocation, and SIDS). Baseline descriptive characteristics, sleep patterns (location, position, co-sleeping, presence of pillows/blankets), and prior healthcare encounters (type, duration, frequency, timing) were described. Results: Thirty-five infants met inclusion criteria. Twenty-three percent of families routinely practiced unsafe sleep, while 63% practiced unsafe sleep at the time of SUID. All unsafe sleep behaviors increased during the SUID event compared to routine, including inappropriate location (60%), co-sleeping (46%), and inappropriate position (37%) at the time of SUID. There were 54 total healthcare encounters (mean 1.5 per patient +/- 2.1) prior to SUID. Primary care physicians (57%) and NICU (29%) were the most frequent prior healthcare encounters, however visits spanned multiple specialties. Twenty-six percent had a healthcare encounter within 7 days of their death. Discussion: We demonstrated the frequency and variability in healthcare encounters among SUID infants prior to their death. Majority of infants had prior healthcare encounters, with 26% seen by healthcare professionals within 7 days of their death. These results highlight the important role healthcare professionals across all specialties have the potential to play in educating families about safe sleep and SUID.

Virtual Reality in the Pediatric Intensive Care Unit: Patient Emotional and Physiologic Responses.

Context: Patients in the Pediatric Intensive Care Unit (PICU) are limited in their ability to engage in developmentally typical activity. Long-term hospitalization, especially with minimal interpersonal engagement, is associated with risk for delirium and delayed recovery. Virtual reality (VR) has growing evidence as a safe, efficacious, and acceptable intervention for pain and distress management in the context of uncomfortable healthcare procedures, and for enhancing engagement in, and improving outcomes of rehabilitation therapy. Hypothesis: Critically ill children may experience high levels of engagement and physiologic effects while engaging with VR. Methods and Models: This cross-sectional study of 3-17-year-old children admitted to a PICU used a VR headset to deliver 360-degree immersive experiences. This study had a mixed-method approach, including standardized behavioral coding, participant and parent surveys, and participant physiologic responses. Investigators noted comments the child made about VR, observed emotional responses, and documented an engagement score. To determine physiologic response to VR, integer heart rate variability (HRVi) was collected 30 min before, during, and 30 min after VR. Results: One hundred fifteen participants were enrolled from 6/18 to 10/19, and they interacted with VR for a median of 10 min (interquartile range 7-17). Most children enjoyed the experience; 83% of participants smiled and 36% laughed while using VR. Seventy-two percent made positive comments while using VR. The strongest age-related pattern regarding comments was that the youngest children were more likely to share the experience with others. Seventy-nine percent of participants were highly engaged with VR. Ninety-two percent of parents reported that VR calmed their child, and 78% of participants felt that VR was calming. HRVi Minimum scores were significantly higher during VR than pre- (p < 0.001) or post-VR (p < 0.001). There was no significant difference between pre-and post-VR (p = 0.387); therefore, children returned to their pre-intervention state following VR. Interpretations and Conclusions: Children admitted to the PICU are highly engaged with and consistently enjoyed using VR. Both participants and parents found VR to be calming, consistent with intra-intervention physiologic improvements in HRVi. VR is an immersive tool that can augment the hospital environment for children.

Association Between Heart Rate Variability and Inflammatory Biomarkers in Critically Ill Children.

OBJECTIVES: The autonomic nervous system (ANS) can both modulate and be modulated by the inflammatory response during critical illness. We aimed to determine whether heart rate variability (HRV), a measure of ANS function, is associated with proinflammatory biomarker levels in critically ill children. DESIGN: Two cohorts were analyzed. The first was a prospective observational cohort from August 2018 to August 2020 who had plasma proinflammatory cytokine measurements within 72 hours of admission, including tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, and IL-8. The second was a retrospective cohort from June 2012 to August 2020 who had at least one C-reactive protein (CRP) measurement within 72 hours of admission. SETTING: Forty-six-bed PICU. PATIENTS: Critically ill children in either cohort who had continuous heart rate data available from the bedside monitors. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sixty-two patients were included in the prospective cohort and 599 patients in the retrospective cohort. HRV was measured using the age-adjusted integer heart rate variability (HRVi), which is the sd of the heart rate sampled every 1 second over 5 consecutive minutes. The median HRVi was measured in the 12-hour period ending 30 minutes prior to inflammatory biomarker collection. HRVi was inversely correlated with IL-6, IL-8, and CRP levels (p ≤ 0.02); correlation with IL-8 and CRP persisted after adjusting for Pediatric Risk of Mortality III and age, and median HR and age (p < 0.001). CONCLUSIONS: HRVi is inversely correlated with IL-6, IL-8, and CRP. Further studies are needed to validate this measure as a proxy for a proinflammatory state.

Vitamin therapy in sepsis.

Vitamins are essential micronutrients with key roles in many biological pathways relevant to sepsis. Some of these relevant biological mechanisms include antioxidant and anti-inflammatory effects, protein and hormone synthesis, energy generation, and regulation of gene transcription. Moreover, relative vitamin deficiencies in plasma are common during sepsis and vitamin therapy has been associated with improved outcomes in some adult and pediatric studies. High-dose intravenous vitamin C has been the vitamin therapy most extensively studied in adult patients with sepsis and septic shock. This includes three randomized control trials (RCTs) as monotherapy with a total of 219 patients showing significant reduction in organ dysfunction and lower mortality when compared to placebo, and five RCTs as a combination therapy with thiamine and hydrocortisone with a total of 1134 patients showing no difference in clinical outcomes. Likewise, the evidence for the role of other vitamins in sepsis remains mixed. In this narrative review, we present the preclinical, clinical, and safety evidence of the most studied vitamins in sepsis, including vitamin C, thiamine (i.e., vitamin B1), and vitamin D. We also present the relevant evidence of the other vitamins that have been studied in sepsis and critical illness in both children and adults, including vitamins A, B2, B6, B12, and E. IMPACT: Vitamins are key effectors in many biological processes relevant to sepsis. We present the preclinical, clinical, and safety evidence of the most studied vitamins in pediatric sepsis. Designing response-adaptive platform trials may help fill in knowledge gaps regarding vitamin use for critical illness and association with clinical outcomes.

Development of a Heart Rate Variability Risk Score to Predict Organ Dysfunction and Death in Critically Ill Children.

OBJECTIVES: Determine whether the Heart Rate Variability Dysfunction score, a novel age-normalized measure of autonomic nervous system dysregulation, is associated with the development of new or progressive multiple organ dysfunction syndrome or death in critically ill children. DESIGN, SETTING, AND PATIENTS: This was a retrospective, observational cohort study from 2012 to 2018. Patients admitted to the PICU with at least 12 hours of continuous heart rate data available from bedside monitors during the first 24 hours of admission were included in the analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Heart rate variability was measured using the integer heart rate variability, which is the sd of the heart rate sampled every 1 second over 5 consecutive minutes. The Heart Rate Variability Dysfunction score was derived from age-normalized values of integer heart rate variability and transformed, so that higher scores were indicative of lower integer heart rate variability and a proxy for worsening autonomic nervous system dysregulation. Heart Rate Variability Dysfunction score performance as a predictor of new or progressive multiple organ dysfunction syndrome and 28-day mortality were determined using the area under the receiver operating characteristic curve. Of the 7,223 patients who met inclusion criteria, 346 patients (4.8%) developed new or progressive multiple organ dysfunction syndrome, and 103 (1.4%) died by day 28. For every one-point increase in the median Heart Rate Variability Dysfunction score in the first 24 hours of admission, there was a 25% increase in the odds of new or progressive multiple organ dysfunction syndrome and a 51% increase in the odds of mortality. The median Heart Rate Variability Dysfunction score in the first 24 hours had an area under the receiver operating characteristic curve to discriminate new or progressive multiple organ dysfunction syndrome of 0.67 and to discriminate mortality of 0.80. These results were reproducible in a temporal validation cohort. CONCLUSIONS: The Heart Rate Variability Dysfunction score, an age-adjusted proxy for autonomic nervous system dysregulation derived from bedside monitor data is independently associated with new or progressive multiple organ dysfunction syndrome and mortality in PICU patients. The Heart Rate Variability Dysfunction score could potentially be used as a single continuous physiologic biomarker or as part of a multivariable prediction model to increase awareness of at-risk patients and augment clinical decision-making.

Autonomic Nervous System Dysfunction Is Associated With Re-hospitalization in Pediatric Septic Shock Survivors.

Objective: Re-hospitalization after sepsis can lead to impaired quality of life. Predictors of re-hospitalization could help identify sepsis survivors who may benefit from targeted interventions. Our goal was to determine whether low heart rate variability (HRV), a measure of autonomic nervous system dysfunction, is associated with re-hospitalization in pediatric septic shock survivors. Materials and Methods: This was a retrospective, observational cohort study of patients admitted between 6/2012 and 10/2020 at a single institution. Patients admitted to the pediatric intensive care unit with septic shock who had continuous heart rate data available from the bedside monitors and survived their hospitalization were included. HRV was measured using age-normalized z-scores of the integer HRV (HRVi), which is the standard deviation of the heart rate sampled every 1 s over 5 consecutive minutes. The 24-h median HRVi was assessed on two different days: the last 24 h of PICU admission ("last HRVi") and the 24-h period with the lowest median HRVi ("lowest HRVi"). The change between the lowest and last HRVi was termed "delta HRVi." The primary outcome was re-hospitalization within 1 year of discharge, including both emergency department encounters and hospital readmission, with sensitivity analyses at 30 and 90 days. Kruskal-Wallis, logistic regression, and Poisson regression evaluated the association between HRVi and re-hospitalizations and adjusted for potential confounders. Results: Of the 463 patients who met inclusion criteria, 306 (66%) were re-hospitalized, including 270 readmissions (58%). The last HRVi was significantly lower among re-hospitalized patients compared to those who were not (p = 0.02). There was no difference in the lowest HRVi, but patients who were re-hospitalized showed a smaller recovery in their delta HRVi compared to those who were not re-hospitalized (p = 0.02). This association remained significant after adjusting for potential confounders. In the sensitivity analysis, a smaller recovery in delta HRVi was consistently associated with a higher likelihood of re-hospitalization. Conclusion: In pediatric septic shock survivors, a smaller recovery in HRV during the index admission is significantly associated with re-hospitalization. This continuous physiologic measure could potentially be used as a predictor of patients at risk for re-hospitalization and lower health-related quality of life.

Dexmedetomidine leading to profound bradycardia in a pediatric liver transplant recipient.

Dexmedetomidine, an α2 -agonist, is used in the PICU for its sedative properties as it minimally affects respiratory status. However, hemodynamic instability is one of its known side effects. There is limited published experience with its use in pediatric liver transplant. We present a case of a 9-month-old infant who received a deceased donor liver transplantation for biliary atresia and received an IV dexmedetomidine infusion for sedation starting at 20 hours post-operatively. The patient received an IV bolus of 0.08 mcg/kg followed by an increase to 1 mcg/kg/hour. She was also receiving a fentanyl infusion for sedation at the time of dexmedetomidine initiation. Approximately 3 hours after initiation, she developed bradycardia as low as 30 beats-per-minute with an associated sinus pause of 7 seconds. She was given chest compressions by the bedside nurse briefly before arousing and becoming agitated. Evaluation of other etiologies for the patient's bradycardia was unrevealing. Thus, bradycardia was attributed to dexmedetomidine therapy which was discontinued without recurrence. Hemodynamic instability, specifically bradycardia, is known to occur with dexmedetomidine administration. As this medication is primarily metabolized by the liver, its use immediately after transplantation, when liver function is still recovering, may be associated with an increased risk of side effects. Understanding risk factors for bradycardia and hemodynamic instability early after liver transplantation, particularly with dexmedetomidine, is critical to allow clinicians to identify the patients for higher risk for dexmedetomidine side effects.

Impact of an untrained CPR Coach in simulated pediatric cardiopulmonary arrest: A pilot study.

AIM: To determine if an untrained cardiopulmonary resuscitation (CPR) Coach, with no access to real-time CPR feedback technology, improves CPR quality. METHODS: This was a prospective randomized pilot study at a tertiary care children's hospital that aimed to integrate an untrained CPR Coach into resuscitation teams during simulated pediatric cardiac arrest. Simulation events were randomized to two arms: control (no CPR Coach) or intervention (CPR Coach). Simulations were run by pediatric intensive care unit (PICU) providers and video recorded. Scenarios focused on full cardiopulmonary arrest; neither team had access to real-time CPR feedback technology. The primary outcome was CPR quality. Secondary outcomes included workload assessments of the team leader and CPR Coach using the NASA Task Load Index and perceptions of CPR quality. RESULTS: Thirteen simulations were performed; 5 were randomized to include a CPR Coach. There was a significantly shorter duration to backboard placement in the intervention group (median 20 s [IQR 0-27 s] vs. 52 s [IQR 38-65 s], p = 0.02). There was no self-reported change in the team leader's workload between scenarios using a CPR Coach compared to those without a CPR Coach. There were no significant changes in subjective CPR quality measures. CONCLUSIONS: In this pilot study, inclusion of an untrained CPR Coach during simulated CPR shortened time to backboard placement but did not improve most metrics of CPR quality or significantly affect team leader workload. More research is needed to better assess the value of a CPR Coach and its potential impact in real-world resuscitation.

7 Is the New 8: Improving Adherence to Restrictive PRBC Transfusions in the Pediatric ICU.

Up to 30%-40% of children admitted to the pediatric intensive care unit (PICU) have anemia, and approximately 15% receive packed red blood cell (pRBC) transfusions. Current literature supports a pRBC transfusion threshold of hemoglobin less than or equal to seven for most PICU patients. Our objective was to determine pRBC transfusion rates, assess compliance with transfusion guidelines, understand patient-level variables that affect transfusion practices, and use cross-industry innovation to implement a practice strategy. This was a pre-post study of pediatric patients admitted to our PICU. We collected baseline data on pRBC transfusion practices. Next, we organized an innovation platform, which generated multi-industry ideas and produced an awareness campaign to effect pRBC ordering behavior. Innovative educational interventions were implemented, and postintervention transfusion practices were monitored. Statistical analysis was performed using linear mixed models. A p value < .05 was considered statistically significant. At baseline, 41% of pRBC transfusions met restrictive transfusion guidelines with a pretransfusion hemoglobin less than or equal to 7 g/dl. In the postintervention period, 53% of transfusions met restrictive transfusion guidelines (odds ratio 1.66, 95% confidence interval 1.21-2.28). Implementation of a behavioral campaign using multi-industry innovation led to improved adherence to pRBC transfusion guidelines in a tertiary care PICU.

An Innovative Virtual Reality Experience in the PICU: A Pilot Study.

OBJECTIVES: Patients in the PICU frequently have limitations that impede independent interactions with their environment. Virtual reality is an immersive experience that may improve outcomes in critically ill children. The objective of this study was to assess feasibility and satisfaction with virtual reality. DESIGN: Cross-sectional, single-arm pilot study. SETTING: PICU. PATIENTS: Convenience sample of 3- to 17-year-old patients. INTERVENTIONS: Three-hundred sixty degree immersions were delivered using a simple virtual reality headset and smartphone videos. Each participant was given a choice of developmentally appropriate virtual reality experiences. Following the short (< 15 min) virtual reality experience, participants, and parents completed a brief survey. MEASUREMENTS AND MAIN RESULTS: One-hundred percent of participants enjoyed using virtual reality, and 84% reported preference to use virtual reality for a longer duration. One-hundred percent of parents agreed that their child enjoyed using virtual reality, and 100% enjoyed watching their child use virtual reality. Eighty-two percent of parents reported that virtual reality calmed their child. CONCLUSIONS: Virtual reality is an innovative, easily administered, and enjoyable tool that subjectively calms PICU patients in an otherwise chaotic environment.

Autonomic Nervous System Dysfunction in Pediatric Sepsis.

The autonomic nervous system (ANS) plays a major role in maintaining homeostasis through key adaptive responses to stress, including severe infections and sepsis. The ANS-mediated processes most relevant during sepsis include regulation of cardiac output and vascular tone, control of breathing and airway resistance, inflammation and immune modulation, gastrointestinal motility and digestion, and regulation of body temperature. ANS dysfunction (ANSD) represents an imbalanced or maladaptive response to injury and is prevalent in pediatric sepsis. Most of the evidence on ANSD comes from studies of heart rate variability, which is a marker of ANS function and is inversely correlated with organ dysfunction and mortality. In addition, there is evidence that other measures of ANSD, such as respiratory rate variability, skin thermoregulation, and baroreflex and chemoreflex sensitivity, are associated with outcomes in critical illness. The relevance of understanding ANSD in the context of pediatric sepsis stems from the fact that it might play an important role in the pathophysiology of sepsis, is associated with outcomes, and can be measured continuously and noninvasively. Here we review the physiology and dysfunction of the ANS during critical illness, discuss methods for measuring ANS function in the intensive care unit, and review the diagnostic, prognostic, and therapeutic value of understanding ANSD in pediatric sepsis.