The Pediatric Data Science and Analytics Subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators Network: Use of Supervised Machine Learning Applications in Pediatric Critical Care Medicine Research.

OBJECTIVE: Perform a scoping review of supervised machine learning in pediatric critical care to identify published applications, methodologies, and implementation frequency to inform best practices for the development, validation, and reporting of predictive models in pediatric critical care. DESIGN: Scoping review and expert opinion. SETTING: We queried CINAHL Plus with Full Text (EBSCO), Cochrane Library (Wiley), Embase (Elsevier), Ovid Medline, and PubMed for articles published between 2000 and 2022 related to machine learning concepts and pediatric critical illness. Articles were excluded if the majority of patients were adults or neonates, if unsupervised machine learning was the primary methodology, or if information related to the development, validation, and/or implementation of the model was not reported. Article selection and data extraction were performed using dual review in the Covidence tool, with discrepancies resolved by consensus. SUBJECTS: Articles reporting on the development, validation, or implementation of supervised machine learning models in the field of pediatric critical care medicine. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 5075 identified studies, 141 articles were included. Studies were primarily (57%) performed at a single site. The majority took place in the United States (70%). Most were retrospective observational cohort studies. More than three-quarters of the articles were published between 2018 and 2022. The most common algorithms included logistic regression and random forest. Predicted events were most commonly death, transfer to ICU, and sepsis. Only 14% of articles reported external validation, and only a single model was implemented at publication. Reporting of validation methods, performance assessments, and implementation varied widely. Follow-up with authors suggests that implementation remains uncommon after model publication. CONCLUSIONS: Publication of supervised machine learning models to address clinical challenges in pediatric critical care medicine has increased dramatically in the last 5 years. While these approaches have the potential to benefit children with critical illness, the literature demonstrates incomplete reporting, absence of external validation, and infrequent clinical implementation.

Pediatric Cardiac Intensive Care Distribution, Service Delivery, and Staffing in the United States in 2018.

OBJECTIVES: To assess the distribution, service delivery, and staffing of pediatric cardiac intensive care in the United States. DESIGN: Based on a 2016 national PICU survey, and verified through online searching and clinician networking, medical centers were identified with a separate cardiac ICU or mixed ICU. These centers were sent a structured web-based survey up to four times, with follow-up by mail and phone for nonresponders. SETTING: Cardiac ICUs were defined as specialized units, specifically for the treatment of children with life-threatening primary cardiac conditions. Mixed ICUs were defined as separate units, specifically for the treatment of children with life-threatening conditions, including primary cardiac disease. PARTICIPANTS: Cardiac ICU or mixed ICU physician medical directors or designees. MEASUREMENTS AND MAIN RESULTS: One-hundred twenty ICUs were identified: 61 (51%) were mixed ICUs and 59 (49%) were cardiac ICUs. Seventy five percent of institutions at least sometimes used a neonatal ICU prior to surgery. The most common temporary cardiac support beyond extracorporeal membrane oxygenation was a centrifugal pump such as Centrimag. Durable cardiac support devices were far more common in separate cardiac ICUs (84% vs 20%; p < 0.0001). Significantly less availability of electrophysiology, heart failure, and cardiac anesthesia consultation was available in mixed ICUs (p = 0.0003, p < 0.0001, p = 0.042 respectively). ICU attending physicians were in-house day and night 98% of the time in mixed ICUs and 87% of the time in cardiac ICUs. Nurse practitioners were consistent front-line providers in the ICUs caring for children with primary cardiac disease staffing 88% of cardiac ICUs and 56% of mixed ICUs. Mixed ICUs were more commonly staffed with pediatric residents, and critical care fellows were found in more cardiac ICUs (83% vs 77%; p < 0.0001). CONCLUSIONS: Mixed ICUs and cardiac ICUs have statistically different staffing models and available services. More evaluation is needed to understand how this may impact patient outcomes and training programs of physicians and nurses.

Risk Factors for Mortality and Pre-ICU Fluid Balance Among Critically Ill Hematopoietic Stem Cell Transplant Patients.

OBJECTIVE: To examine if fluid balance surrounding pediatric intensive care unit (PICU) admission in hematopoietic stem cell transplant (HSCT) patients was associated with mortality, ventilator-free days, and intensive care unit (ICU)-free days. To explore other population-specific factors associated with poor outcome. MATERIALS AND METHODS: Retrospective review of HSCT patients admitted to 2 quaternary PICUs, Children's Hospital Los Angeles and University of California San Francisco Benioff Children's Hospital from January 2009 to December 2014. RESULTS: Of 144 patients, 92 were identified with complete fluid balance data available. No difference in fluid balance between survivors and nonsurvivors in the 24 hours preceding PICU admission (P = .81) or when the first 24 hours of PICU stay were taken into account (P = .48) was identified. There was no difference in ventilator-free or ICU-free days. Comparing Pediatric Index of Mortality (PIM)-2, Pediatric Risk of Mortality (PRISM)-3, and a multivariable model using independent risk factors identified through multivariable analysis, the receiver operating characteristic plot for the multivariable model (area under the curve = 0.844 [95% confidence interval: 0.77-0.92]) was superior to both PIM-2 and PRISM-3 in discriminating mortality. CONCLUSIONS: Fluid balance immediately preceding and early in the course of admission was not associated with mortality in PICU HSCT patients. A subset of variables was identified which better discriminated mortality in this cohort than accepted PICU severity of illness scores.

Safety, Efficacy, and Timeliness of Intravenous Potassium Chloride Replacement Protocols in a Pediatric Cardiothoracic Intensive Care Unit.

OBJECTIVE: Hypokalemia in children following cardiac surgery occurs frequently, placing them at risk of life-threatening arrhythmias. However, renal insufficiency after cardiopulmonary bypass warrants careful administration of potassium (K+). Two different nurse-driven protocols (high dose and tiered dosing) were implemented to identify an optimal K+ replacement regimen, compared to an historical low-dose protocol. Our objective was to evaluate the safety, efficacy, and timeliness of these protocols. DESIGN: A retrospective cohort review of pediatric patients placed on intravenous K+ replacement protocols over 1 year was used to determine efficacy and safety of the protocols. A prospective single-blinded review of K+ repletion was used to determine timeliness. PATIENTS: Pediatric patients with congenital or acquired cardiac disease. SETTING: Twenty-four-bed cardiothoracic intensive care unit in a tertiary children's hospital. INTERVENTIONS: Efficacy was defined as fewer supplemental potassium chloride (KCl) doses, as well as a higher protocol to total doses ratio per patient. Safety was defined as a lower percentage of serum K+ levels ≥4.8 mEq/L after a dose of KCl. Between-group differences were assessed by nonparametric univariate analysis. RESULTS: There were 138 patients with a median age of 3.0 (interquartile range: 0.23-10.0) months. The incidence of K+ levels ≥4.8 mEq/L after a protocol dose was higher in the high-dose protocol versus the tiered-dosing protocol but not different between the low-dose and tiered-dosing protocols (high dose = 2.2% vs tiered dosing = 0.5%, P = .05). The ratio of protocol doses to total doses per patient was lower in the low-dose protocol compared to the tiered-dosing protocol (P < .05). Protocol doses were administered 45 minutes faster (P < .001). CONCLUSION: The tiered-dosed, nurse-driven K+ replacement protocol was associated with decreased supplemental K+ doses without increased risk of hyperkalemia, administering doses faster than individually ordered doses; the protocol was effective, safe, and timely in the treatment of hypokalemia in pediatric patients after cardiac surgery.

Growth and Changing Characteristics of Pediatric Intensive Care 2001-2016.

OBJECTIVES: We assessed the growth, distribution, and characteristics of pediatric intensive care in 2016. DESIGN: Hospitals with PICUs were identified from prior surveys, databases, online searching, and clinician networking. A structured web-based survey was distributed in 2016 and compared with responses in a 2001 survey. SETTING: PICUs were defined as a separate unit, specifically for the treatment of children with life-threatening conditions. PICU hospitals contained greater than or equal to 1 PICU. SUBJECTS: Physician medical directors and nurse managers. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: PICU beds per pediatric population (< 18 yr), PICU bed distribution by state and region, and PICU characteristics and their relationship with PICU beds were measured. Between 2001 and 2016, the U.S. pediatric population grew 1.9% to greater than 73.6 million children, and PICU hospitals decreased 0.9% from 347 to 344 (58 closed, 55 opened). In contrast, PICU bed numbers increased 43% (4,135 to 5,908 beds); the median PICU beds per PICU hospital rose from 9 to 12 (interquartile range 8, 20 beds). PICU hospitals with greater than or equal to 15 beds in 2001 had significant bed growth by 2016, whereas PICU hospitals with less than 15 beds experienced little average growth. In 2016, there were eight PICU beds per 100,000 U.S. children (5.7 in 2001), with U.S. census region differences in bed availability (6.8 to 8.8 beds/100,000 children). Sixty-three PICU hospitals (18%) accounted for 47% of PICU beds. Specialized PICUs were available in 59 hospitals (17.2%), 48 were cardiac (129% growth). Academic affiliation, extracorporeal membrane oxygenation availability, and 24-hour in-hospital intensivist staffing increased with PICU beds per hospital. CONCLUSIONS: U.S. PICU bed growth exceeded pediatric population growth over 15 years with a relatively small percentage of PICU hospitals containing almost half of all PICU beds. PICU bed availability is variable across U.S. states and regions, potentially influencing access to care and emergency preparedness.

Association of 24/7 In-House Intensive Care Unit Attending Physician Coverage With Outcomes in Children Undergoing Heart Operations.

BACKGROUND: Multicenter data regarding the around-the-clock (24/7) presence of an in-house critical care attending physician with outcomes in children undergoing cardiac operations are limited. METHODS: Patients younger than 18 years of age who underwent operations (with or without cardiopulmonary bypass [CPB]) for congenital heart disease at 1 of the participating intensive care units (ICUs) in the Virtual PICU Systems (VPS, LLC) database were included (2009-2014). The study population was divided into 2 groups: the 24/7 group (14,737 patients; 32 hospitals), and the No 24/7 group (10,422 patients; 22 hospitals). Propensity-score matching was performed to match patients 1:1 in the 24/7 group and in the No 24/7 group. RESULTS: Overall, 25,159 patients from 54 hospitals qualified for inclusion. By propensity matching, 9,072 patients (4,536 patient pairs) from 51 hospitals were matched 1:1 in the 2 groups. After matching, mortality at ICU discharge was lower among the patients treated in hospitals with 24/7 coverage (24/7 versus No 24/7, 2.8% versus 4.0%; p = 0.002). The use of extracorporeal membrane oxygenation (ECMO), the incidence of cardiac arrest, extubation within 48 hours after operation, the rate of reintubation, and the duration of arterial line and central venous line use after operation were significantly improved in the 24/7 group. When stratified by surgical complexity, survival benefits of 24/7 coverage persisted among patients undergoing both high-complexity and low-complexity operations. CONCLUSIONS: The presence of 24-hour in-ICU attending physician coverage in children undergoing cardiac operations is associated with improved outcomes, including ICU mortality. It is possible that 24-hour in-ICU attending physician coverage may be a surrogate for other factors that may bias the results. Further study is warranted.

Comparison of Pediatric Severe Sepsis Managed in U.S. and European ICUs.

OBJECTIVES: Pediatric severe sepsis remains a significant global health problem without new therapies despite many multicenter clinical trials. We compared children managed with severe sepsis in European and U.S. PICUs to identify geographic variation, which may improve the design of future international studies. DESIGN: We conducted a secondary analysis of the Sepsis PRevalence, OUtcomes, and Therapies study. Data about PICU characteristics, patient demographics, therapies, and outcomes were compared. Multivariable regression models were used to determine adjusted differences in morbidity and mortality. SETTING: European and U.S. PICUs. PATIENTS: Children with severe sepsis managed in European and U.S. PICUs enrolled in the Sepsis PRevalence, OUtcomes, and Therapies study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: European PICUs had fewer beds (median, 11 vs 24; p < 0.001). European patients were younger (median, 1 vs 6 yr; p < 0.001), had higher severity of illness (median Pediatric Index of Mortality-3, 5.0 vs 3.8; p = 0.02), and were more often admitted from the ward (37% vs 24%). Invasive mechanical ventilation, central venous access, and vasoactive infusions were used more frequently in European patients (85% vs 68%, p = 0.002; 91% vs 82%, p = 0.05; and 71% vs 50%; p < 0.001, respectively). Raw morbidity and mortality outcomes were worse for European compared with U.S. patients, but after adjusting for patient characteristics, there were no significant differences in mortality, multiple organ dysfunction, disability at discharge, length of stay, or ventilator/vasoactive-free days. CONCLUSIONS: Children with severe sepsis admitted to European PICUs have higher severity of illness, are more likely to be admitted from hospital wards, and receive more intensive care therapies than in the United States. The lack of significant differences in morbidity and mortality after adjusting for patient characteristics suggests that the approach to care between regions, perhaps related to PICU bed availability, needs to be considered in the design of future international clinical trials in pediatric severe sepsis.

Impact of Timing of ECMO Initiation on Outcomes After Pediatric Heart Surgery: A Multi-Institutional Analysis.

Little is known about the relationship of timing of extracorporeal membrane oxygenation (ECMO) initiation on patient outcomes after pediatric heart surgery. We hypothesized that increasing timing of ECMO initiation after heart surgery will be associated with worsening study outcomes. Patients aged ≤18 years receiving ECMO after pediatric cardiac surgery at a Pediatric Health Information System-participating hospital (2004-2013) were included. Outcomes evaluated included in-hospital mortality, composite poor outcome, prolonged length of ECMO, prolonged length of mechanical ventilation, prolonged length of ICU stay, and prolonged length of hospital stay. Multivariable logistic regression models were fitted to study the probability of study outcomes as a function of timing from cardiac surgery to ECMO initiation. A total of 2908 patients from 42 hospitals qualified for inclusion. The median timing of ECMO initiation after cardiac surgery was 0 days (IQR 0-1 day; range 0-294 days). After adjusting for patient and center characteristics, increasing duration of time from surgery to ECMO initiation was not associated with higher mortality or worsening composite poor outcome. However, increasing duration of time from surgery to ECMO initiation was associated with prolonged length of ECMO, prolonged length of ventilation, prolonged length of ICU stay, and prolonged length of hospital stay. Although this relationship was statistically significant, the odds for prolonged length of ECMO, prolonged length of ventilation, prolonged length of ICU stay, and prolonged length of hospital stay increased by only 1-3 % for every 1-day increase in ECMO that may be clinically insignificant. We did not demonstrate any relationship between timing of ECMO initiation and mortality among the patients of varying age groups, and patients undergoing cardiac surgery of varying complexity. We concluded that increasing duration of time from surgery to ECMO initiation is not associated with worsening mortality. Our results suggest that ECMO is initiated at the appropriate time when dictated by clinical situation among patients of all age groups, and among patients undergoing heart operations of varying complexity.

PICU Volume and Outcome: A Severity-Adjusted Analysis.

OBJECTIVES: To determine the relationship between PICU volume and severity-adjusted mortality in a large, national dataset. DESIGN: Retrospective cohort study. SETTING: The VPS database (VPS, LLC, Los Angeles, CA), a national multicenter clinical PICU database. PATIENTS: All patients with discharge dates between September 2009 and March 2012 and valid Pediatric Index of Mortality 2 and Pediatric Risk of Mortality III scores, who were not transferred to another ICU and were seen in an ICU that collected at least three quarters of data. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Anonymized data received included ICU mortality, hospital and patient demographics, and Pediatric Index of Mortality 2 and Pediatric Risk of Mortality III scores. PICU volume/quarter was determined (VPS sites submit data quarterly) per PICU and was divided by 100 to assess the impact per 100 discharges per quarter (volume). A mixed-effects logistic regression model accounting for repeated measures of patients within ICUs was performed to assess the association of volume on severity-adjusted mortality, adjusting for patient and unit characteristics. Multiplicative interactions between volume and severity of illness were also modeled. We analyzed 186,643 patients from 92 PICUs, with an overall ICU mortality rate of 2.6%. Volume ranged from 0.24 to 8.89 per ICU per quarter; the mean volume was 2.61. The mixed-effects logistic regression model found a small but nonlinear relationship between volume and mortality that varied based on the severity of illness. When severity of illness is low, there is no clear relationship between volume and mortality up to a Pediatric Index of Mortality 2 risk of mortality of 10%; for patients with a higher severity of illness, severity of illness-adjusted mortality is directly proportional to a unit's volume. CONCLUSIONS: For patients with low severity of illness, ICU volume is not associated with mortality. As patient severity of illness rises, higher volume units have higher severity of illness-adjusted mortality. This may be related to differences in quality of care, issues with unmeasured confounding, or calibration of existing severity of illness scores.

Association of house staff training with mortality in children with critical illness.

AIM: To evaluate the association of house staff training with mortality in children with critical illness. METHODS: Patients <18 years of age in the Virtual PICU Systems (VPS, LLC) Database (2009-2013) were included. The study population was divided in two study groups: hospitals with residency programme only and hospitals with both residency and fellowship programme. Control group constituted hospitals with no residency or fellowship programme. The primary study outcome was mortality before intensive care unit (ICU) discharge. Multivariable logistic regression models were fitted to evaluate association of training programmes with ICU mortality. RESULTS: A total of 336 335 patients from 108 centres were included. Case-mix of patients among the hospitals with training programmes was complex; patients cared for in the hospitals with training programmes had greater severity of illness, had higher resource utilisation and had higher overall admission risk of death compared to patients cared for in the control hospitals. Despite caring for more complex and sicker patients, the hospitals with training programmes were associated with lower odds of ICU mortality. CONCLUSION: Our study establishes that ICU care provided in hospitals with training programmes is associated with improved adjusted survival rates among the Virtual PICU database hospitals in the United States.

Satisfaction with care and decision making among parents/caregivers in the pediatric intensive care unit: a comparison between English-speaking whites and Latinos.

PURPOSE: Because of previously documented health care disparities, we hypothesized that English-speaking Latino parents/caregivers would be less satisfied with care and decision making than English-speaking non-Latino white (NLW) parents/caregivers. MATERIALS AND METHODS: An intensive care unit (ICU) family satisfaction survey, Family Satisfaction in the Intensive Care Unit Survey (pediatric, 24 question version), was completed by English-speaking parents/caregivers of children in a cardiothoracic ICU at a university-affiliated children's hospital in 2011. English-speaking NLW and Latino parents/caregivers of patients, younger than 18 years, admitted to the ICU were approached to participate on hospital day 3 or 4 if they were at the bedside for greater than or equal to 2 days. Analysis of variance, χ(2), and Student t tests were used. Cronbach αs were calculated. RESULTS: Fifty parents/caregivers completed the survey in each group. Latino parents/caregivers were younger, more often mothers born outside the United States, more likely to have government insurance or no insurance, and had less education and income. There were no differences between the groups' mean overall satisfaction scores (92.6 ± 8.3 and 93.0 ± 7.1, respectively; P = .80). The Family Satisfaction in the Intensive Care Unit Survey (pediatric, 24 question version) showed high internal consistency reliability (α = .95 and .91 for NLW and Latino groups, respectively). CONCLUSIONS: No disparities in ICU satisfaction with care and decision making between English-speaking NLW and Latino parents/caregivers were found.

Existing data analysis in pediatric critical care research.

Our objectives were to review and categorize the existing data sources that are important to pediatric critical care medicine (PCCM) investigators and the types of questions that have been or could be studied with each data source. We conducted a narrative review of the medical literature, categorized the data sources available to PCCM investigators, and created an online data source registry. We found that many data sources are available for research in PCCM. To date, PCCM investigators have most often relied on pediatric critical care registries and treatment- or disease-specific registries. The available data sources vary widely in the level of clinical detail and the types of questions they can reliably answer. Linkage of data sources can expand the types of questions that a data source can be used to study. Careful matching of the scientific question to the best available data source or linked data sources is necessary. In addition, rigorous application of the best available analysis techniques and reporting consistent with observational research standards will maximize the quality of research using existing data in PCCM.

Survey of in-house coverage by pediatric intensivists: characterization of 24/7 in-hospital pediatric critical care faculty coverage*.

OBJECTIVE: To characterize the current state of 24/7 in-hospital pediatric intensivist coverage in academic PICUs, including perceptions of faculty and trainees regarding the advantages and disadvantages of in-hospital coverage. DESIGN: Cross-sectional observational study via web-based survey. SETTING: PICUs at North American academic institutions. SUBJECTS: Pediatric intensivists, pediatric critical care fellows, and pediatric residents. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 1,323 responses were received representing a center response rate of 74% (147 of 200). Ninety percent of respondents stated that in-hospital coverage is good for patient care, and 85% stated that in-hospital coverage provides safer care. Sixty-three percent of intensivists stated that working in in-hospital models limits academic productivity, and 65% stated that in-hospital models interfere with nonclinical responsibilities. When compared with intensivists in home coverage models, intensivists working in in-hospital models generally had more favorable perceptions of the effects of in-hospital on patient care (p < 0.0001) and faculty quality of life. Physician burnout was measured with the abbreviated Maslach Burnout Inventory. Although 57% of intensivists responded that working in in-hospital models increases burnout risk, burnout scores were not different between coverage models. Seventy-nine percent of intensivists currently working at institutions with in-hospital coverage stated that they would prefer to work in an in-hospital coverage model, compared with 31% of those working in a home coverage model (p < 0.0001). CONCLUSIONS: Although concerns exist regarding the effect of 24/7 in-hospital coverage on faculty, the majority of pediatric intensivists and critical care trainees responded that in-hospital coverage by intensivists is good for patient care. The majority of intensivists also state that they would prefer to work at an institution with in-hospital coverage. Further research is needed to objectively delineate the effects of in-hospital coverage on both patients and faculty.