Cerebral Oximetry During Pediatric In-Hospital Cardiac Arrest: A Multicenter Study of Survival and Neurologic Outcome.

OBJECTIVES: To determine if near-infrared spectroscopy measuring cerebral regional oxygen saturation (crS o2 ) during cardiopulmonary resuscitation is associated with return of spontaneous circulation (ROSC) and survival to hospital discharge (SHD) in children. DESIGN: Multicenter, observational study. SETTING: Three hospitals in the pediatric Resuscitation Quality (pediRES-Q) collaborative from 2015 to 2022. PATIENTS: Children younger than 18 years, gestational age 37 weeks old or older with in-hospital cardiac arrest (IHCA) receiving cardiopulmonary resuscitation greater than or equal to 1 minute and intra-arrest crS o2 monitoring. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome was ROSC greater than or equal to 20 minutes without extracorporeal membrane oxygenation. Secondary outcomes included SHD and favorable neurologic outcome (FNO) (Pediatric Cerebral Performance Category 1-2 or no change from prearrest). Among 3212 IHCA events (index and nonindex), 123 met inclusion criteria in 93 patients. Median age was 0.3 years (0.1-1.4 yr) and 31% (38/123) of the cardiopulmonary resuscitation events occurred in patients with cyanotic heart disease. Median cardiopulmonary resuscitation duration was 8 minutes (3-28 min) and ROSC was achieved in 65% (80/123). For index events, SHD was achieved in 59% (54/91) and FNO in 41% (37/91). We determined the association of median intra-arrest crS o2 and percent of crS o2 values above a priori thresholds during the: 1) entire cardiopulmonary resuscitation event, 2) first 5 minutes, and 3) last 5 minutes with ROSC, SHD, and FNO. Higher crS o2 for the entire cardiopulmonary resuscitation event, first 5 minutes, and last 5 minutes were associated with higher likelihood of ROSC, SHD, and FNO. In multivariable analysis of the infant group (age < 1 yr), higher crS o2 was associated with ROSC (odds ratio [OR], 1.06; 95% CI, 1.03-1.10), SHD (OR, 1.04; 95% CI, 1.01-1.07), and FNO (OR, 1.05; 95% CI, 1.02-1.08) after adjusting for presence of cyanotic heart disease. CONCLUSIONS: Higher crS o2 during pediatric IHCA was associated with increased rate of ROSC, SHD, and FNO. Intra-arrest crS o2 may have a role as a real-time, noninvasive predictor of ROSC.

Development and Validation of a Model for Endotracheal Intubation and Mechanical Ventilation Prediction in PICU Patients.

OBJECTIVES: To develop and externally validate an intubation prediction model for children admitted to a PICU using objective and routinely available data from the electronic medical records (EMRs). DESIGN: Retrospective observational cohort study. SETTING: Two PICUs within the same healthcare system: an academic, quaternary care center (36 beds) and a community, tertiary care center (56 beds). PATIENTS: Children younger than 18 years old admitted to a PICU between 2010 and 2022. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical data was extracted from the EMR. PICU stays with at least one mechanical ventilation event (≥ 24 hr) occurring within a window of 1-7 days after hospital admission were included in the study. Of 13,208 PICU stays in the derivation PICU cohort, 1,175 (8.90%) had an intubation event. In the validation cohort, there were 1,165 of 17,841 stays (6.53%) with an intubation event. We trained a Categorical Boosting (CatBoost) model using vital signs, laboratory tests, demographic data, medications, organ dysfunction scores, and other patient characteristics to predict the need of intubation and mechanical ventilation using a 24-hour window of data within their hospital stay. We compared the CatBoost model to an extreme gradient boost, random forest, and a logistic regression model. The area under the receiving operating characteristic curve for the derivation cohort and the validation cohort was 0.88 (95% CI, 0.88-0.89) and 0.92 (95% CI, 0.91-0.92), respectively. CONCLUSIONS: We developed and externally validated an interpretable machine learning prediction model that improves on conventional clinical criteria to predict the need for intubation in children hospitalized in a PICU using information readily available in the EMR. Implementation of our model may help clinicians optimize the timing of endotracheal intubation and better allocate respiratory and nursing staff to care for mechanically ventilated children.

Leveraging Clinical Informatics and Data Science to Improve Care and Facilitate Research in Pediatric Acute Respiratory Distress Syndrome: From the Second Pediatric Acute Lung Injury Consensus Conference.

OBJECTIVES: The use of electronic algorithms, clinical decision support systems, and other clinical informatics interventions is increasing in critical care. Pediatric acute respiratory distress syndrome (PARDS) is a complex, dynamic condition associated with large amounts of clinical data and frequent decisions at the bedside. Novel data-driven technologies that can help screen, prompt, and support clinician decision-making could have a significant impact on patient outcomes. We sought to identify and summarize relevant evidence related to clinical informatics interventions in both PARDS and adult respiratory distress syndrome (ARDS), for the second Pediatric Acute Lung Injury Consensus Conference. DATA SOURCES: MEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost). STUDY SELECTION: We included studies of pediatric or adult critically ill patients with or at risk of ARDS that examined automated screening tools, electronic algorithms, or clinical decision support systems. DATA EXTRACTION: Title/abstract review, full text review, and data extraction using a standardized data extraction form. DATA SYNTHESIS: The Grading of Recommendations Assessment, Development and Evaluation approach was used to identify and summarize evidence and develop recommendations. Twenty-six studies were identified for full text extraction to address the Patient/Intervention/Comparator/Outcome questions, and 14 were used for the recommendations/statements. Two clinical recommendations were generated, related to the use of electronic screening tools and automated monitoring of compliance with best practice guidelines. Two research statements were generated, related to the development of multicenter data collaborations and the design of generalizable algorithms and electronic tools. One policy statement was generated, related to the provision of material and human resources by healthcare organizations to empower clinicians to develop clinical informatics interventions to improve the care of patients with PARDS. CONCLUSIONS: We present two clinical recommendations and three statements (two research one policy) for the use of electronic algorithms and clinical informatics tools for patients with PARDS based on a systematic review of the literature and expert consensus.

Executive Summary of the Second International Guidelines for the Diagnosis and Management of Pediatric Acute Respiratory Distress Syndrome (PALICC-2).

OBJECTIVES: We sought to update our 2015 work in the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) guidelines for the diagnosis and management of pediatric acute respiratory distress syndrome (PARDS), considering new evidence and topic areas that were not previously addressed. DESIGN: International consensus conference series involving 52 multidisciplinary international content experts in PARDS and four methodology experts from 15 countries, using consensus conference methodology, and implementation science. SETTING: Not applicable. PATIENTS: Patients with or at risk for PARDS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eleven subgroups conducted systematic or scoping reviews addressing 11 topic areas: 1) definition, incidence, and epidemiology; 2) pathobiology, severity, and risk stratification; 3) ventilatory support; 4) pulmonary-specific ancillary treatment; 5) nonpulmonary treatment; 6) monitoring; 7) noninvasive respiratory support; 8) extracorporeal support; 9) morbidity and long-term outcomes; 10) clinical informatics and data science; and 11) resource-limited settings. The search included MEDLINE, EMBASE, and CINAHL Complete (EBSCOhost) and was updated in March 2022. Grading of Recommendations, Assessment, Development, and Evaluation methodology was used to summarize evidence and develop the recommendations, which were discussed and voted on by all PALICC-2 experts. There were 146 recommendations and statements, including: 34 recommendations for clinical practice; 112 consensus-based statements with 18 on PARDS definition, 55 on good practice, seven on policy, and 32 on research. All recommendations and statements had agreement greater than 80%. CONCLUSIONS: PALICC-2 recommendations and consensus-based statements should facilitate the implementation and adherence to the best clinical practice in patients with PARDS. These results will also inform the development of future programs of research that are crucially needed to provide stronger evidence to guide the pediatric critical care teams managing these patients.

Candidacy for Extracorporeal Life Support in Children After Hematopoietic Cell Transplantation: A Position Paper From the Pediatric Acute Lung Injury and Sepsis Investigators Network's Hematopoietic Cell Transplant and Cancer Immunotherapy Subgroup.

OBJECTIVES: The last decade has seen improved outcomes for children requiring extracorporeal life support as well as for children undergoing hematopoietic cell transplantation. Thus, given the historically poor survival of hematopoietic cell transplantation patients using extracorporeal life support, the Pediatric Acute Lung Injury and Sepsis Investigators' hematopoietic cell transplantation and cancer immunotherapy subgroup aimed to characterize the utility of extracorporeal life support in facilitating recovery from critical cardiorespiratory illnesses in pediatric hematopoietic cell transplantation patients. DATA SOURCES: All available published data were identified using a set of PubMed search terms for pediatric extracorporeal life support and hematopoietic cell transplantation. STUDY SELECTION: All articles that provided original reports of pediatric hematopoietic cell transplantation patients who underwent extracorporeal life support were included. Sixty-four manuscripts met search criteria. Twenty-four were included as primary reports of pediatric hematopoietic cell transplantation patients who underwent extracorporeal life support (11 were single case reports, four single institution case series, two multi-institution case series, and seven registry reports from Extracorporeal Life Support Organization, Pediatric Heath Information System, and Virtual Pediatric Systems). DATA EXTRACTION: All 24 articles were reviewed by first and last authors and a spread sheet was constructed including sample size, potential biases, and conclusions. DATA SYNTHESIS: Discussions regarding incorporation of available evidence into our clinical practice were held at biannual meetings, as well as through email and virtual meetings. An expert consensus was determined through these discussions and confirmed through a modified Delphi process. CONCLUSIONS: Extracorporeal life support in hematopoietic cell transplantation patients is being used with increasing frequency and potentially improving survival. The Pediatric Acute Lung Injury and Sepsis Investigators hematopoietic cell transplantation-cancer immunotherapy subgroup has developed a framework to guide physicians in decision-making surrounding extracorporeal life support candidacy in pediatric hematopoietic cell transplantation patients. In addition to standard extracorporeal life support considerations, candidacy in the hematopoietic cell transplantation population should consider the following six factors in order of consensus agreement: 1) patient comorbidities; 2) underlying disease necessitating hematopoietic cell transplantation; 3) hematopoietic cell transplantation toxicities, 4) family and patient desires for goals of care; 5) hematopoietic cell transplantation preparatory regimen; and 6) graft characteristics. Although risk assessment may be individualized, data are currently insufficient to clearly delineate ideal candidacy. Therefore, we urge the onco-critical care community to collaborate and capture data to provide better evidence to guide physicians' decision-making in the future.

Improving Mobilization Times of a Specialized Neonatal and Pediatric Critical Care Transport Team.

OBJECTIVES: The Ground and Air Medical Quality Transport database identifies the average mobilization time (AMT) of the transport team as a metric for benchmarking. Our specific aim was to decrease our AMT to < 25 minutes for our expanded role, ground, nonsimultaneous transports by the end of quarter 4 of 2018. METHODS: Standardization of data collection with awareness building, ambulance vendor involvement, and team-focused interventions were the different phases of project implementation. Documentation of reasons for delay was performed pre- and postimplementation. RESULTS: Our AMT decreased from a baseline of 30.3 minutes to 24.5 minutes after project implementation. Communication delays (19.0%), reason for delay not documented (16.5%), no team available (14.0%), rotor wing vendor delays (12.4%), and ambulance vendor delays (7.4%) were the common reasons for delay on our preimplementation Pareto analysis. Communication and pharmacy delays were the most common reasons during all 3 phases of our project. CONCLUSIONS: Implementation of the project allowed us to achieve our goal of improving our AMT. Understanding the reasons for delay is a crucial consideration, and success depends on careful change management. Further iterations will need to focus on improving communication and the pharmacy medication dispatch process.

Decision-Making in Pediatric Transport Team Dispatch Using Script Concordance Testing.

OBJECTIVES: Our objective was to compare decision-making in dispatching pediatric transport teams by Medical Directors of pediatric transport teams (serving as experts) to that of Pediatric Intensivists and Critical Care fellows who often serve as Medical Control physicians. Understanding decision-making around team composition and dispatch could impact clinical management, cost effectiveness, and educational needs. DESIGN: Survey was developed using Script Concordance Testing guidelines. The survey contained 15 transport case vignettes covering 20 scenarios (45 questions). Eleven scenarios assessed impact of intrinsic patient factors (e.g., procedural needs), whereas nine assessed extrinsic factors (e.g., weather). SETTING: Pediatric Critical Care programs accredited by the Accreditation Council for Graduate Medical Education (the United States). SUBJECTS: Pediatric Intensivists and senior Critical Care fellows at Pediatric Critical Care programs were the target population with Transport Medical Directors serving as the expert panel. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Survey results were scored per Script Concordance Testing guidelines. Concordance within groups was assessed using simple percentage agreement. There was little concordance in decision-making by Transport Medical Directors (median Script Concordance Testing percentage score [interquartile range] of 33.9 [30.4-37.3]). In addition, there was no statistically significant difference between the median Script Concordance Testing scores among the senior fellows and Pediatric Intensivists (31.1 [29.6-33.2] vs 29.7 [28.3-32.3], respectively; p = 0.12). Transport Medical Directors were more concordant on reasoning involving intrinsic patient factors rather than extrinsic factors (10/21 vs 4/24). CONCLUSIONS: Our study demonstrates pediatric transport team dispatch decision-making discordance by pediatric critical care physicians of varying levels of expertise and experience. Script Concordance Testing at a local level may better elucidate standards in medical decision-making within pediatric critical care physicians. The development of a curriculum, which provides education and trains our workforce on the logistics of pediatric transport team dispatch, would help standardize practice and evaluate outcomes based on decision-making.

Understanding clinical and biological heterogeneity to advance precision medicine in paediatric acute respiratory distress syndrome.

Paediatric acute respiratory distress syndrome (PARDS) is a heterogeneous clinical syndrome that is associated with high rates of mortality and long-term morbidity. Factors that distinguish PARDS from adult acute respiratory distress syndrome (ARDS) include changes in developmental stage and lung maturation with age, precipitating factors, and comorbidities. No specific treatment is available for PARDS and management is largely supportive, but methods to identify patients who would benefit from specific ventilation strategies or ancillary treatments, such as prone positioning, are needed. Understanding of the clinical and biological heterogeneity of PARDS, and of differences in clinical features and clinical course, pathobiology, response to treatment, and outcomes between PARDS and adult ARDS, will be key to the development of novel preventive and therapeutic strategies and a precision medicine approach to care. Studies in which clinical, biomarker, and transcriptomic data, as well as informatics, are used to unpack the biological and phenotypic heterogeneity of PARDS, and implementation of methods to better identify patients with PARDS, including methods to rapidly identify subphenotypes and endotypes at the point of care, will drive progress on the path to precision medicine.

Nutrition practices and outcomes in patients with pediatric acute respiratory distress syndrome.

BACKGROUND: Pediatric acute respiratory distress syndrome (PARDS) remains a significant cause of morbidity and mortality. Evidence suggests enteral nutrition (EN) may be protective in critically ill children. METHODS: This is a retrospective cohort study comparing intubated patients with PARDS who received EEN and those who did not. We included patients aged 2 weeks to 18 years who could receive full nutrition enterally prior to their disease and excluded patients with cyanotic heart disease. Disease severity was captured with oxygenation index (OI), oxygen saturation index (OSI), and pediatric logistic organ dysfunction (PELOD-2). EEN was defined as having received ≥25% of the calculated energy goal enterally within the first 48 h of PARDS diagnosis. RESULTS: We included 151 patients. Adjusted for age, OI, and OSI, the EEN group had a lower PICU mortality rate (adjusted odds ratio [aOR] = 0.071; 95% CI, 0.009-0.542; P = 0.011), had a higher likelihood of PICU discharge (adjusted risk ratio = 1.79; 95% CI, 1.25-2.55; P = 0.001), and was more likely to have at least one ventilator-free day (aOR = 3.96; 95% CI, 1.28-12.22; P = 0.017). Adjusted for age and PELOD-2, a statistically significant association between the EEN group and lower PICU mortality (P = 0.033), shorter PICU LOS (P < 0.001), and more ventilator-free days (P = 0.037) persisted. CONCLUSION: Our study found that EEN was associated with superior mortality rates, PICU LOS, and ventilator-free days in patients with PARDS.

Development of a Standardized Clinical Assessment and Management Plan for Pediatric Acute Respiratory Distress Syndrome.

Pediatric acute respiratory distress syndrome (PARDS) is one of the most challenging patient populations for a clinician to manage with mortality between 8 and 31%. The project was designed to identify patients with PARDS, implement management guidelines with the goal of standardizing practice. Our objectives were to describe the development and implementation of a protocolized approach to identify patients with PARDS and institute ventilator management guidelines. Patients who met criteria for moderate or severe PARDS as per the Pediatric Acute Lung Injury Consensus Conference (PALICC) definitions were identified using the best practice alert (BPA) in the electronic health record (EHR). Patients who did not meet exclusion criteria qualified for management using the Standardized Clinical Assessment and Management Plan (SCAMP), a quality improvement (QI) methodology with iterative cycles. The creation of a BPA enabled identification of patients with PARDS. With our second cycle, the number of false BPA alerts due to incorrect data decreased from 66.7 (68/102) to 29.2% (19/65; p < 0.001) and enrollment increased from 48.3 (14/29) to 73.2% (30/41; p = 0.03). Evaluation of our statistical process control chart (SPC) demonstrated a shift in the adherence with the tidal volume guideline. Overall, we found that SCAMP methodology, when used in the development of institutional PARDS management guidelines, allows for development of a process to aid identification of patients and monitor adherence to management guidelines. This should eventually allow assessment of impact of deviations from clinical practice guidelines.

Association of Fluid Balance and Survival of Pediatric Patients Treated With Extracorporeal Membrane Oxygenation.

The effect of positive fluid balance (FB) on extracorporeal membrane oxygenation (ECMO) outcomes in pediatric patients remains unknown. We sought to evaluate if positive FB in pediatric intensive care unit (PICU) patients with respiratory and/or cardiac failure necessitating ECMO was associated with increased morbidity or mortality. This was a multicenter retrospective cohort study of data from the deidentified PEDiatric ECMO Outcomes Registry (PEDECOR). Patients entered into the database from 2014 to 2017, who received ECMO support, were included. A total of 168 subjects met the study criteria. Univariate analysis showed no significant difference in total FB on ECMO days 1-5 between survivors and non-survivors [median 90 ml/kg (IQR 18-208.5) for survivors vs. median 139.7 ml/kg (IQR 11.2-300.6) for non-survivors, p = 0.334]. There was also no difference in total FB on ECMO days 1-5 in patients with no change in functional outcome as reflected by the Pediatric Outcome Performance Category (POPC) score vs. those who had worsening in POPC score ≥2 at hospital discharge [median 98 ml/kg (IQR 18-267) vs. median 130 ml/kg (IQR 13-252), p = 0.91]. Subjects that required 50 ml/kg or more of blood products over the initial 5 days of ECMO support had an increased rate of mortality with an odds ratio of 5.8 (95% confidence interval of 2.7-12.3; p = 0.048). Our study showed no association of the noted FB with survival after ECMO cannulation. This FB trend was also not associated with POPC at hospital discharge, MV duration, or ECMO duration. The amount of blood product administered was found to be a significant predictor of mortality.

Tissue Doppler Imaging and Focal, Late-Onset Anthracycline-Induced Cardiovascular Disease in Long Term Survivors of Childhood Cancer: A Research Article.

INTRODUCTION: In anthracycline-induced cardiomyopathy, the onset of diastolic dysfunction occurs before systolic dysfunction. Although, conventional echocardiogram is the standard method to assess cardiac function post anthracycline therapy, Tissue Doppler Imaging (TDI) may detect early onset cardiac diastolic dysfunction among anthracycline-recipient survivors of childhood cancers. There are limited data on the use of TDI in assessing anthracycline-associated cardiotoxicity in children. AIM: To evaluate the role of Tissue Doppler Imaging (TDI) in assessing late-onset cardiotoxicity in survivors of paediatric cancers. MATERIALS AND METHODS: This was a single site, observational, blinded study of 11 long-term survivors of childhood cancer who had been treated with anthracyclines and 22 age-matched controls. The study group and the control group underwent conventional echo and TDI; operators were blind to study group. Conventional echo measurements were obtained. TDI was used to assess systolic and diastolic parameters at the mid-interventricular septum and lateral and medial annuli of the mitral valve; these parameters included: systolic wave (S'), early diastolic wave (E'), late diastolic wave (A'), Isovolemic Contraction Time (ICT), Isovolemic Relaxation Time (IRT) and Ejection Time (ET). Myocardial Performance Index (MPI) was also calculated. RESULTS: Conventional echo measurements were similar in both groups. Using TDI, cases had a lower mean E' velocity (9.7 ± 1.7 cm/s vs. 11.4 ± 1.3 cm/s, p=0.004) and a lower E'/A' (1.8 ± 0.5 vs. 2.2 ± 0.4, p=0.022) at the mid-interventricular septum than controls. The mean E' septum velocity in chemotherapy-recipients who also received chest radiotherapy was 8.5±0.5 cm/s in comparison to 10.2±1.7 cm/s in those that did not receive chest radiotherapy but this not achieve statistical significance. We did not find any additional associations between TDI parameters and patients' gender, age of diagnosis, length of follow-up and dose of anthracycline. CONCLUSION: In long-term survivors of childhood cancer who received anthracyclines, diastolic dysfunction can be detected earlier by using TDI before overt systolic dysfunction. Further large-scale multicenter studies are needed.