Immunocompromised-Associated Pediatric Acute Respiratory Distress Syndrome: Experience From the 2016/2017 Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology Prospective Cohort Study.

OBJECTIVES: To characterize immunocompromised-associated pediatric acute respiratory distress syndrome (I-PARDS) and contrast it to PARDS. DESIGN: This is a secondary analysis of the 2016-2017 PARDS incidence and epidemiology (PARDIE) study, a prospective observational, cross-sectional study of children with PARDS. SETTING: Dataset of 145 PICUs across 27 countries. PATIENTS: During 10 nonconsecutive weeks (from May 2016 to June 2017), data about immunocompromising conditions (ICCs, defined as malignancy, congenital/acquired immunodeficiency, posttransplantation, or diseases requiring immunosuppression) were collected. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 708 subjects, 105 (14.8%) had ICC. Before the development of I-PARDS, those with ICC were more likely to be hospitalized (70% vs. 35%, p < 0.001), have more at-risk for PARDS ( p = 0.046), and spent more hours at-risk (20 [interquartile range, IQR: 8-46] vs. 11 [IQR: 4-33], [ p = 0.002]). Noninvasive ventilation (NIV) use was more common in those with ICC ( p < 0.001). Of those diagnosed with PARDS on NIV ( n = 161), children with ICC were more likely to be subsequently intubated ( n = 28/40 [70%] vs n = 53/121 [44%], p = 0.004). Severe PARDS was more common (32% vs 23%, p < 0.001) in I-PARDS. Oxygenation indices were higher at diagnosis and had less improvement over the first 3 days of PARDS ( p < 0.001). Children with I-PARDS had greater nonpulmonary organ dysfunction. Adjusting for Pediatric Risk of Mortality IV and oxygenation index, children with I-PARDS had a higher severity of illness-adjusted PICU mortality (adjusted hazard ratio: 3.0 [95% CI, 1.9-4.7] p < 0.001) and were less likely to be extubated alive within 28 days (subdistribution hazard ratio: 0.47 [95% CI, 0.31-0.71] p < 0.001). CONCLUSIONS: I-PARDS is a unique subtype of PARDS associated with hospitalization before diagnosis and increased: time at-risk for PARDS, NIV use, hypoxia, nonpulmonary organ dysfunction, and mortality. The opportunity for early detection and intervention seems to exist. Dedicated study in these patients is imperative to determine if targeted interventions will benefit these unique patients with the ultimate goal of improving outcomes.

A risk-stratified assessment of biomarker-based acute kidney injury phenotypes in children.

BACKGROUND: The functional acute kidney injury (AKI) diagnostic tests serum creatinine (SCr) and urine output are imprecise and make management challenging. Combining tubular injury biomarkers with functional markers reveal AKI phenotypes that may facilitate personalized care. However, when and in whom to obtain injury biomarkers remains unclear. METHODS: This was a prospective, observational study of patients admitted to a pediatric intensive care unit (PICU). Using the Renal Angina Index (RAI), subjects were screened for the presence (RAI+) or absence (RAI-) of renal angina 12 h post-admission and assigned an AKI phenotype using urinary NGAL (NGAL+: ≥150 ng/ml) and SCr (SCr+: ≥KDIGO Stage 1). Outcomes for each AKI phenotype were assessed and compared by RAI status. RESULTS: In all, 200/247 (81%) subjects were RAI+. RAI+ subjects who were NGAL+ had higher risk of Day 3 AKI, renal replacement therapy use, and mortality and fewer ventilator- and PICU-free days, compared to NGAL-, irrespective of Day 0 SCr. Similar findings were not demonstrated in RAI- subjects, though NGAL+/SCr+ was associated with fewer ventilator- and PICU-free days compared to NGAL-/SCr+. CONCLUSIONS: NGAL- and SCr-based AKI phenotypes provide improved prognostic information in children with renal angina (RAI+) and/or with SCr elevation. These populations may be appropriate for targeted biomarker testing. IMPACT: New consensus recommendations encourage the integration of kidney tubular injury biomarkers such as urinary NGAL with serum creatinine for diagnosis and staging of acute kidney injury; however, no structured testing framework exists guiding when to test and in whom. Urinary NGAL- and serum creatinine-based acute kidney injury phenotypes increase diagnostic precision in critically ill children experiencing renal angina (RAI+) or serum creatinine-defined acute kidney injury. These data provide preliminary evidence for a proposed framework for directed urinary NGAL assessment in the pediatric intensive care unit.

Complement blockade for TA-TMA: lessons learned from a large pediatric cohort treated with eculizumab.

Overactivated complement is a high-risk feature in hematopoietic stem cell transplant (HSCT) recipients with transplant-associated thrombotic microangiopathy (TA-TMA), and untreated patients have dismal outcomes. We present our experience with 64 pediatric HSCT recipients who had high-risk TA-TMA (hrTA-TMA) and multiorgan injury treated with the complement blocker eculizumab. We demonstrate significant improvement to 66% in 1-year post-HSCT survival in treated patients from our previously reported untreated cohort with same hrTA-TMA features that had 1-year post-HSCT survival of 16.7%. Responding patients benefited from a brief but intensive course of eculizumab using pharmacokinetic/pharmacodynamic-guided dosing, requiring a median of 11 doses of eculizumab (interquartile range [IQR] 7-20). Treatment was discontinued because TA-TMA resolved at a median of 66 days (IQR 41-110). Subjects with higher complement activation measured by elevated blood sC5b-9 at the start of treatment were less likely to respond (odds ratio, 0.15; P = .0014) and required more doses of eculizumab (r = 0.43; P = .0004). Patients with intestinal bleeding had the fastest eculizumab clearance, required the highest number of eculizumab doses (20 vs 9; P = .0015), and had lower 1-year survival (44% vs 78%; P = .01). Over 70% of survivors had proteinuria on long-term follow-up. The best glomerular filtration rate (GFR) recovery in survivors was a median 20% lower (IQR, 7.3%-40.3%) than their pre-HSCT GFR. In summary, complement blockade with eculizumab is an effective therapeutic strategy for hrTA-TMA, but some patients with severe disease lacked a complete response, prompting us to propose early intervention and search for additional targetable endothelial injury pathways.

Assessment of a Situation Awareness Quality Improvement Intervention to Reduce Cardiac Arrests in the PICU.

OBJECTIVES: To use improved situation awareness to decrease cardiopulmonary resuscitation events by 25% over 18 months and demonstrate process and outcome sustainability. DESIGN: Structured quality improvement initiative. SETTING: Single-center, 35-bed quaternary-care PICU. PATIENTS: All patients admitted to the PICU from February 1, 2017, to December 31, 2020. INTERVENTIONS: Interventions targeted situation awareness and included bid safety huddles, bedside mitigation signs and huddles, smaller pod-based huddles, and an automated clinical decision support tool to identify high-risk patients. MEASUREMENTS AND MAIN RESULTS: The primary outcome metric, cardiopulmonary resuscitation event rate per 1,000 patient-days, decreased from a baseline of 3.1-1.5 cardiopulmonary resuscitation events per 1,000 patient-days or by 52%. The secondary outcome metric, mortality rate, decreased from a baseline of 6.6 deaths per 1,000 patient-days to 3.6 deaths per 1,000 patient-days. Process metrics included percent of clinical deterioration events predicted, which increased from 40% to 67%, and percent of high-risk patients with shared situation awareness, which increased from 43% to 71%. Balancing metrics included time spent in daily safety huddle, median 0.4 minutes per patient (interquartile range, 0.3-0.5), and a number needed to alert of 16 (95% CI, 14-25). Neither unit acuity as measured by Pediatric Risk of Mortality III scores nor the percent of deaths in patients with do-not-attempt resuscitation orders or electing withdrawal of life-sustaining technologies changed over time. CONCLUSIONS: Interprofessional teams using shared situation awareness may reduce cardiopulmonary resuscitation events and, thereby, improve outcomes.

Efficacy of Early Prophylaxis Against Catheter-Associated Thrombosis in Critically Ill Children: A Bayesian Phase 2b Randomized Clinical Trial.

OBJECTIVES: We obtained preliminary evidence on the efficacy of early prophylaxis on the risk of central venous catheter-associated deep venous thrombosis and its effect on thrombin generation in critically ill children. DESIGN: Bayesian phase 2b randomized clinical trial. SETTING: Seven PICUs. PATIENTS: Children less than 18 years old with a newly inserted central venous catheter and at low risk of bleeding. INTERVENTION: Enoxaparin adjusted to anti-Xa level of 0.2-0.5 international units/mL started at less than 24 hours after insertion of central venous catheter (enoxaparin arm) versus usual care without placebo (usual care arm). MEASUREMENTS AND MAIN RESULTS: At the interim analysis, the proportion of central venous catheter-associated deep venous thrombosis on ultrasonography in the usual care arm, which was 54.2% of 24 children, was significantly higher than that previously reported. This resulted in misspecification of the preapproved Bayesian analysis, reversal of direction of treatment effect, and early termination of the randomized clinical trial. Nevertheless, with 30.4% of 23 children with central venous catheter-associated deep venous thrombosis on ultrasonography in the enoxaparin arm, risk ratio of central venous catheter-associated deep venous thrombosis was 0.55 (95% credible interval, 0.24-1.11). Including children without ultrasonography, clinically relevant central venous catheter-associated deep venous thrombosis developed in one of 27 children (3.7%) in the enoxaparin arm and seven of 24 (29.2%) in the usual care arm (p = 0.02). Clinically relevant bleeding developed in one child randomized to the enoxaparin arm. Response profile of endogenous thrombin potential, a measure of thrombin generation, was not statistically different between trial arms. CONCLUSIONS: These findings suggest the efficacy and safety of early prophylaxis that should be validated in a pivotal randomized clinical trial.

Diagnostic performance of single-phase dual-energy CT to differentiate vascular and nonvascular incidental renal lesions on portal venous phase: comparison with CT.

OBJECTIVES: To determine whether single-phase dual-energy CT (DECT) differentiates vascular and nonvascular renal lesions in the portal venous phase (PVP). Optimal iodine threshold was determined and compared to Hounsfield unit (HU) measurements. METHODS: We retrospectively included 250 patients (266 renal lesions) who underwent a clinically indicated PVP abdominopelvic CT on a rapid-kilovoltage-switching single-source DECT (rsDECT) or a dual-source DECT (dsDECT) scanner. Iodine concentration and HU measurements were calculated by four experienced readers. Diagnostic accuracy was determined using biopsy results and follow-up imaging as reference standard. Area under the curve (AUC) was calculated for each DECT scanner to differentiate vascular from nonvascular lesions and vascular lesions from hemorrhagic/proteinaceous cysts. Univariable and multivariable logistic regression analyses evaluated the association between variables and the presence of vascular lesions. RESULTS: A normalized iodine concentration threshold of 0.25 mg/mL yielded high accuracy in differentiating vascular and nonvascular lesions (AUC 0.93, p < 0.001), with comparable performance to HU measurements (AUC 0.93). Both iodine concentration and HU measurements were independently associated with vascular lesions when adjusted for age, gender, body mass index, and lesion size (AUC 0.95 and 0.95, respectively). When combined, diagnostic performance was higher (AUC 0.96). Both absolute and normalized iodine concentrations performed better than HU measurements (AUC 0.92 vs. AUC 0.87) in differentiating vascular lesions from hemorrhagic/proteinaceous cysts. CONCLUSION: A single-phase (PVP) DECT scan yields high accuracy to differentiate vascular from nonvascular renal lesions. Iodine concentration showed a slightly higher performance than HU measurements in differentiating vascular lesions from hemorrhagic/proteinaceous cysts. KEY POINTS: • A single-phase dual-energy CT scan in the portal venous phase differentiates vascular from nonvascular renal lesions with high accuracy (AUC 0.93). • When combined, iodine concentration and HU measurements showed the highest diagnostic performance (AUC 0.96) to differentiate vascular from nonvascular renal lesions. • Compared to HU measurements, iodine concentration showed a slightly higher performance in differentiating vascular lesions from hemorrhagic/proteinaceous cysts.

Health-Related Quality of Life After Community-Acquired Septic Shock in Children With Preexisting Severe Developmental Disabilities.

OBJECTIVES: To serially evaluate health-related quality of life during the first year after community-acquired septic shock in children with preexisting severe developmental disabilities and explore factors associated with health-related quality of life changes in these children. DESIGN: Secondary analysis of the Life after Pediatric Sepsis Evaluation investigation. SETTING: Twelve academic PICU in the United States. PATIENTS: Children greater than or equal to 1 month and less than 18 years old identified by their family caregiver (e.g., parent/guardian) as having severe developmental disability prior to septic shock. INTERVENTIONS: Family caregivers completed the Stein-Jessop Functional Status II-R Short Form as a measure of their child's health-related quality of life at baseline (reflecting preadmission status), day 7, and months 1, 3, 6, and 12 following PICU admission. Stein-Jessop Functional Status II-R Short Form scores were linearly transformed to a 0-100 scale, with higher scores indicating better health-related quality of life. MEASUREMENTS AND MAIN RESULTS: Of 392 Life after Pediatric Sepsis Evaluation participants, 137 were identified by their caregiver as having a severe developmental disability. Sixteen children (11.6%) with severe disability died during the 12 months following septic shock. Among 121 survivors, Stein-Jessop Functional Status II-R Short Form scores declined from preadmission baseline to day 7 (70.7 ± 16.1 vs 55.6 ± 19.2; p < 0.001). Stein-Jessop Functional Status II-R Short Form scores remained below baseline through month 12 (59.1 ± 21.0, p < 0.001 vs baseline). After adjusting for baseline Stein-Jessop Functional Status II-R Short Form, the caregiver being a single parent/guardian was associated with lower month 3 Stein-Jessop Functional Status II-R Short Form scores (p = 0.041). No other baseline child or caregiver characteristic, or critical illness-related factors were significantly associated with month 3 Stein-Jessop Functional Status II-R Short Form scores. CONCLUSIONS: Health-related quality of life among children with severe developmental disability remains, on average, below baseline during the first year following community-acquired septic shock. Children with severe disability and septic shock that are in single parent families are at increased risk. Clinical awareness of the potential for decline in health-related quality of life among disabled children is essential to prevent this adverse outcome from being missed.

Biomarkers for Estimating Risk of Hospital Mortality and Long-Term Quality-of-Life Morbidity After Surviving Pediatric Septic Shock: A Secondary Analysis of the Life After Pediatric Sepsis Evaluation Investigation.

OBJECTIVES: The Life After Pediatric Sepsis Evaluation investigation recently reported that one-third of children who survive sepsis experience significant health-related quality-of-life impairment compared with baseline at 1 year after hospitalization. Pediatric Sepsis Biomarker Risk Model is a multibiomarker tool for estimating baseline risk of mortality among children with septic shock. We determined if the Pediatric Sepsis Biomarker Risk Model biomarkers have predictive capacity for estimating the risk of hospital mortality and long-term health-related quality-of-life morbidity among children with community-acquired septic shock. DESIGN: Secondary analysis. SETTING: Twelve academic PICUs. PATIENTS: A subset of Life After Pediatric Sepsis Evaluation subjects (n = 173) with available blood samples. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three predefined outcomes from the Life After Pediatric Sepsis Evaluation investigation were evaluated: all-cause hospital mortality (n = 173), and the composite outcome of mortality or persistent, serious deterioration of health-related quality of life (> 25% below baseline) among surviving children at 1 month (n = 125) or 3 months (n = 117). Pediatric Sepsis Biomarker Risk Model had an area under the receiver operating characteristic curve of 0.73 (95% CI, 0.59-0.87; p = 0.002) for estimating the risk of hospital mortality and was independently associated with increased odds of hospital mortality. In multivariable analyses, Pediatric Sepsis Biomarker Risk Model was not independently associated with increased odds of the composite outcome of mortality or deterioration of persistent, serious deterioration health-related quality of life greater than 25% below baseline. A new decision tree using the Pediatric Sepsis Biomarker Risk Model biomarkers had an area under the receiver operating characteristic curve of 0.87 (95% CI, 0.80-0.95) for estimating the risk of persistent, serious deterioration health-related quality of life at 3 months among children who survived septic shock. CONCLUSIONS: Pediatric Sepsis Biomarker Risk Model had modest performance for estimating hospital mortality in an external cohort of children with community-acquired septic shock. The Pediatric Sepsis Biomarker Risk Model biomarkers appear to have utility for estimating the risk of persistent, serious deterioration of health-related quality of life up to 3 months after surviving septic shock. These findings suggest an opportunity to develop a clinical tool for early assignment of risk for long-term health-related quality-of-life morbidity among children who survive septic shock.

Early Use of Adjunctive Therapies for Pediatric Acute Respiratory Distress Syndrome: A PARDIE Study.

Rationale: Few data exist to guide early adjunctive therapy use in pediatric acute respiratory distress syndrome (PARDS).Objectives: To describe contemporary use of adjunctive therapies for early PARDS as a framework for future investigations.Methods: This was a preplanned substudy of a prospective, international, cross-sectional observational study of children with PARDS from 100 centers over 10 study weeks.Measurements and Main Results: We investigated six adjunctive therapies for PARDS: continuous neuromuscular blockade, corticosteroids, inhaled nitric oxide (iNO), prone positioning, high-frequency oscillatory ventilation (HFOV), and extracorporeal membrane oxygenation. Almost half (45%) of children with PARDS received at least one therapy. Variability was noted in the median starting oxygenation index of each therapy; corticosteroids started at the lowest oxygenation index (13.0; interquartile range, 7.6-22.0) and HFOV at the highest (25.7; interquartile range, 16.7-37.3). Continuous neuromuscular blockade was the most common, used in 31%, followed by iNO (13%), corticosteroids (10%), prone positioning (10%), HFOV (9%), and extracorporeal membrane oxygenation (3%). Steroids, iNO, and HFOV were associated with comorbidities. Prone positioning and HFOV were more common in middle-income countries and less frequently used in North America. The use of multiple ancillary therapies increased over the first 3 days of PARDS, but there was not an easily identifiable pattern of combination or order of use.Conclusions: The contemporary description of prevalence, combinations of therapies, and oxygenation threshold for which the therapies are applied is important for design of future studies. Region of the world, income, and comorbidities influence adjunctive therapy use and are important variables to include in PARDS investigations.

Critical Illness Factors Associated With Long-Term Mortality and Health-Related Quality of Life Morbidity Following Community-Acquired Pediatric Septic Shock.

OBJECTIVES: A companion article reports the trajectory of long-term mortality and significant health-related quality of life disability among children encountering septic shock. In this article, the investigators examine critical illness factors associated with these adverse outcomes. DESIGN: Prospective, cohort-outcome study, conducted 2013-2017. SETTING: Twelve United States academic PICUs. PATIENTS: Critically ill children, 1 month to 18 years, with community-acquired septic shock requiring vasoactive-inotropic support. INTERVENTIONS: Illness severity, organ dysfunction, and resource utilization data were collected during PICU admission. Change from baseline health-related quality of life at the month 3 follow-up was assessed by parent proxy-report employing the Pediatric Quality of Life Inventory or the Stein-Jessop Functional Status Scale. MEASUREMENTS AND MAIN RESULTS: In univariable modeling, critical illness variables associated with death and/or persistent, serious health-related quality of life deterioration were candidates for multivariable modeling using Bayesian information criterion. The most clinically relevant multivariable models were selected among models with near-optimal statistical fit. Three months following septic shock, 346 of 389 subjects (88.9%) were alive and 43 of 389 had died (11.1%); 203 of 389 (52.2%) had completed paired health-related quality of life surveys. Pediatric Risk of Mortality, cumulative Pediatric Logistic Organ Dysfunction scores, PICU and hospital durations of stay, maximum and cumulative vasoactive-inotropic scores, duration of mechanical ventilation, need for renal replacement therapy, extracorporeal life support or cardiopulmonary resuscitation, and appearance of pathologic neurologic signs were associated with adverse outcomes in univariable models. In multivariable regression analysis (odds ratio [95% CI]), summation of daily Pediatric Logistic Organ Dysfunction scores, 1.01/per point (1.01-1.02), p < 0.001; highest vasoactive-inotropic score, 1.02/per point (1.00-1.04), p = 0.003; and any acute pathologic neurologic sign/event, 5.04 (2.15-12.01), p < 0.001 were independently associated with death or persistent, serious deterioration of health-related quality of life at month 3. CONCLUSIONS AND RELEVANCE: Biologically plausible factors related to sepsis-associated critical illness organ dysfunction and its treatment were associated with poor outcomes at month 3 follow-up among children encountering septic shock.

Trajectory of Mortality and Health-Related Quality of Life Morbidity Following Community-Acquired Pediatric Septic Shock.

OBJECTIVES: In-hospital pediatric sepsis mortality has decreased substantially, but long-term mortality and morbidity among children initially surviving sepsis, is unknown. Accordingly, the Life After Pediatric Sepsis Evaluation investigation was conducted to describe the trajectory of mortality and health-related quality of life morbidity for children encountering community-acquired septic shock. DESIGN: Prospective, cohort-outcome study, conducted 2013-2017. SETTING: Twelve academic PICUs in the United States. PATIENTS: Critically ill children, 1 month to 18 years, with community-acquired septic shock requiring vasoactive-inotropic support. INTERVENTIONS: Demographic, infection, illness severity, organ dysfunction, and resource utilization data were collected daily during PICU admission. Serial parent proxy-report health-related quality of life assessments were obtained at baseline, 7 days, and 1, 3, 6, and 12 months following PICU admission utilizing the Pediatric Quality of Life Inventory or Stein-Jessop Functional Status Scale. MEASUREMENTS AND MAIN RESULTS: Among 389 children enrolled, mean age was 7.4 ± 5.8 years; 46% were female; 18% were immunocompromised; and 51% demonstrated chronic comorbidities. Baseline Pediatric Overall Performance Category was normal in 38%. Median (Q1-Q3) Pediatric Risk of Mortality and Pediatric Logistic Organ Dysfunction scores at PICU admission were 11.0 (6.0-17.0) and 9.0 (6.0-11.0); durations of vasoactive-inotropic and mechanical ventilation support were 3.0 days (2.0-6.0 d) and 8.0 days (5.0-14.0 d); and durations of PICU and hospital stay were 9.4 days (5.6-15.4 d) and 15.7 days (9.2-26.0 d). At 1, 3, 6, and 12 months following PICU admission for the septic shock event, 8%, 11%, 12%, and 13% of patients had died, while 50%, 37%, 30%, and 35% of surviving patients had not regained their baseline health-related quality of life. CONCLUSIONS: This investigation provides the first longitudinal description of long-term mortality and clinically relevant, health-related quality of life morbidity among children encountering community-acquired septic shock. Although in-hospital mortality was 9%, 35% of survivors demonstrated significant, health-related quality of life deterioration from baseline that persisted at least 1 year following hospitalization for septic shock.

Predicting Mortality in Children With Pediatric Acute Respiratory Distress Syndrome: A Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology Study.

OBJECTIVES: Pediatric acute respiratory distress syndrome is heterogeneous, with a paucity of risk stratification tools to assist with trial design. We aimed to develop and validate mortality prediction models for patients with pediatric acute respiratory distress syndrome. DESIGN: Leveraging additional data collection from a preplanned ancillary study (Version 1) of the multinational Pediatric Acute Respiratory Distress syndrome Incidence and Epidemiology study, we identified predictors of mortality. Separate models were built for the entire Version 1 cohort, for the cohort excluding neurologic deaths, for intubated subjects, and for intubated subjects excluding neurologic deaths. Models were externally validated in a cohort of intubated pediatric acute respiratory distress syndrome patients from the Children's Hospital of Philadelphia. SETTING: The derivation cohort represented 100 centers worldwide; the validation cohort was from Children's Hospital of Philadelphia. PATIENTS: There were 624 and 640 subjects in the derivation and validation cohorts, respectively. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The model for the full cohort included immunocompromised status, Pediatric Logistic Organ Dysfunction 2 score, day 0 vasopressor-inotrope score and fluid balance, and PaO2/FIO2 6 hours after pediatric acute respiratory distress syndrome onset. This model had good discrimination (area under the receiver operating characteristic curve 0.82), calibration, and internal validation. Models excluding neurologic deaths, for intubated subjects, and for intubated subjects excluding neurologic deaths also demonstrated good discrimination (all area under the receiver operating characteristic curve ≥ 0.84) and calibration. In the validation cohort, models for intubated pediatric acute respiratory distress syndrome (including and excluding neurologic deaths) had excellent discrimination (both area under the receiver operating characteristic curve ≥ 0.85), but poor calibration. After revision, the model for all intubated subjects remained miscalibrated, whereas the model excluding neurologic deaths showed perfect calibration. Mortality models also stratified ventilator-free days at 28 days in both derivation and validation cohorts. CONCLUSIONS: We describe predictive models for mortality in pediatric acute respiratory distress syndrome using readily available variables from day 0 of pediatric acute respiratory distress syndrome which outperform severity of illness scores and which demonstrate utility for composite outcomes such as ventilator-free days. Models can assist with risk stratification for clinical trials.

Severe Acute Kidney Injury Is Associated With Increased Risk of Death and New Morbidity After Pediatric Septic Shock.

OBJECTIVES: Acute kidney injury is common in critically ill children; however, the frequency of septic shock-associated acute kidney injury and impact on functional status are unknown. We evaluated functional outcomes of children with septic shock-associated acute kidney injury. DESIGN: Secondary analysis of patients with septic shock from the prospective Life after Pediatric Sepsis Evaluation study. We defined acute kidney injury using Kidney Disease Improving Global Outcomes criteria, comparing patients with absent/Stage 1 acute kidney injury to those with Stage 2/3 acute kidney injury (severe acute kidney injury). Our primary outcome was a composite of mortality or new functional morbidity at day 28 of hospitalization or discharge. We also assessed poor long-term outcome, defined as mortality or a persistent, serious deterioration in health-related quality of life at 3 months. SETTING: Twelve academic PICUs in the United States. PATIENTS: Critically ill children, 1 month to 18 years, with community-acquired septic shock requiring vasoactive-inotropic support. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: More than 50% of patients (176/348) developed severe acute kidney injury; of those, 21.6% (38/176) required renal replacement therapy. Twice as many patients with severe acute kidney injury died or developed new substantive functional morbidity (38.6 vs 16.3%; p < 0.001). After adjustment for age, malignancy, and initial illness severity, severe acute kidney injury was independently associated with mortality or new substantive morbidity (adjusted odds ratio, 2.78; 95% CI, 1.63-4.81; p < 0.001). Children with severe acute kidney injury had poorer health-related quality of life at 3 months (adjusted effect size 2.46; 95% CI, 1.44-4.20; p = 0.002). Children with severe acute kidney injury required longer duration of mechanical ventilation (11.0 vs 7.0 d; p < 0.001) and PICU stay (11.7 vs 7.1 d; p < 0.001). CONCLUSIONS: Among children with septic shock, severe acute kidney injury was independently associated with increased risk of death or new substantive functional morbidity. Survivors of sepsis with severe acute kidney injury were more likely to have persistent, serious health-related quality of life deterioration at 3 months.

Longitudinal Trajectories of Caregiver Distress and Family Functioning After Community-Acquired Pediatric Septic Shock.

OBJECTIVES: To identify trajectories and correlates of caregiver distress and family functioning in families of children who survived community-acquired septic shock. We hypothesized that: 1) a substantial subset of families would demonstrate trajectories of persistent elevated caregiver distress and impaired family functioning 12 months after hospitalization and 2) sociodemographic and clinical risk factors would be associated with trajectories of persistent distress and family dysfunction. DESIGN: Prospective cohort. SETTING: Fourteen PICUs in the United States. PATIENTS: Caregivers of 260 children who survived community-acquired septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Caregivers completed ratings of distress on the Brief Symptom Inventory and of family functioning on the Family Assessment Device at baseline, 1, 3, 6, and 12 months after hospitalization. Results from group-based trajectory modeling indicated that 67% of the current sample was characterized by persistent low caregiver distress, 26% by persistent moderate to high distress that remained stable across 12 months (high-risk caregiver distress group), and 8% by initial high distress followed by gradual recovery. Forty percent of the sample was characterized by stable high family functioning, 15% by persistent high dysfunction across 12 months (high-risk family functioning group), 12% by gradually improving functioning, and 32% by deteriorating function over time. Independently of age, child race was associated with membership in the high-risk caregiver distress group (non-white/Hispanic; effect size, -0.12; p = 0.010). There were no significant sociodemographic or clinical correlates of the high-risk family functioning group in multivariable analyses. CONCLUSIONS: Although the majority of families whose children survived community-acquired septic shock were characterized by resilience, a subgroup demonstrated trajectories of persistently elevated distress and family dysfunction during the 12 months after hospitalization. Results suggest a need for family-based psychosocial screening after pediatric septic shock to identify and support at-risk families.

Trajectories and Risk Factors for Altered Physical and Psychosocial Health-Related Quality of Life After Pediatric Community-Acquired Septic Shock.

OBJECTIVES: To evaluate the physical and psychosocial domains of health-related quality of life among children during the first year following community-acquired septic shock, and explore factors associated with poor physical and psychosocial health-related quality of life outcomes. DESIGN: Secondary analysis of the Life After Pediatric Sepsis Evaluation. SETTING: Twelve academic PICUs in the United States. PATIENTS: Children greater than or equal to 1 month and less than 18 years old who were perceived to be without severe developmental disability by their family caregiver at baseline and who survived hospitalization for community-acquired septic shock. INTERVENTIONS: Family caregivers completed the Pediatric Quality of Life Inventory for children 2-18 years old or the Pediatric Quality of Life Inventory Infant Scales for children less than 2 years old at baseline (reflecting preadmission status), day 7, and months 1, 3, 6, and 12 following PICU admission. Higher Pediatric Quality of Life Inventory Physical and Psychosocial Health Summary Scores indicate better health-related quality of life. MEASUREMENTS AND MAIN RESULTS: Of 204 children, 58 (28.2%) had a complex chronic comorbid condition. Children with complex chronic comorbid conditions had lower baseline physical health-related quality of life (62.7 ± 22.6 vs 84.1 ± 19.7; p < 0.001) and psychosocial health-related quality of life (68.4 ± 14.1 vs 81.2 ± 15.3; p < 0.001) than reference norms, whereas children without such conditions had baseline scores similar to reference norms. Children with complex chronic comorbid conditions recovered to their baseline health-related quality of life, whereas children without such conditions did not (physical health-related quality of life 75.3 ± 23.7 vs 83.2 ± 20.1; p = 0.008 and psychosocial health-related quality of life 74.5 ± 18.7 vs 80.5 ± 17.9; p = 0.006). Age less than 2 years was independently associated with higher month 12 physical health-related quality of life, and abnormal neurologic examination and neurologic injury suspected by a healthcare provider during the PICU course were independently associated with lower month 12 physical health-related quality of life. Treatment of increased intracranial pressure and medical device use at month 1 were independently associated with lower month 12 psychosocial health-related quality of life. CONCLUSIONS: Physical and psychosocial health-related quality of life were reduced among children during the first year following community-acquired septic shock compared with reference norms, although many recovered to baseline. Risk factors for poor health-related quality of life included neurologic complications during the hospitalization and dependence on a medical device 1 month postadmission.

In-hospital and 90-day outcomes after total pancreatectomy with islet autotransplantation for pediatric chronic and acute recurrent pancreatitis.

Total pancreatectomy with islet autotransplantation (TPIAT) is used to treat debilitating chronic pancreatitis (CP) and acute recurrent pancreatitis (ARP) that has failed medical and endoscopic therapy. We performed a retrospective review of TPIAT patients at a free-standing children's hospital to evaluate perioperative outcomes. Twenty patients (median age 13, 65% female) underwent TPIAT (2015 through 2017). Of the 20 patients, 95% had CP and 1 patient (5%) had ARP alone. Seventy-five percent of the patients had a pancreatitis-associated genetic mutation; 40% had pancreas divisum. The median surgical time was 757 (IQR 657 to 835) minutes. Median islet equivalents per kg of body weight (IEQ/kg) were 6404 (IQR 5018 to 7554). At 90 days postoperatively vs preoperatively, significantly fewer patients were receiving parenteral nutrition (0% vs 25%, P = .006) and opioids (45% vs 75%, P = .01). Short Form 36-Item Health Survey (SF-36) physical health module scores and total scores improved (34.0 preoperatively vs 54.6 at 90 days, P = .008, and 47.1 vs 65.3, P = .007, respectively); SF-10 physical health scores also improved (13.4 vs 33.1, P = .02). Insulin requirement decreased from 0.5 unit/kg/day to 0.4 unit/kg/day between discharge and 90 days (P = .02). TPIAT is an effective option when debilitating disease persists despite maximal medical and endoscopic therapy. Opioid, parenteral nutrition, and exogenous insulin use can successfully be weaned within 90 days after TPIAT, with gains in health-related quality of life.

Short-Term Adverse Outcomes Associated With Hypoglycemia in Critically Ill Children.

OBJECTIVES: Previous studies report worse short-term outcomes with hypoglycemia in critically ill children. These studies relied on intermittent blood glucose measurements, which may have introduced detection bias. We analyzed data from the Heart And Lung Failure-Pediatric INsulin Titration trial to determine the association of hypoglycemia with adverse short-term outcomes in critically ill children. DESIGN: Nested case-control study. SETTING: Thirty-five PICUs. A computerized algorithm that guided the timing of blood glucose measurements and titration of insulin infusion, continuous glucose monitors, and standardized glucose infusion rates were used to minimize hypoglycemia. PATIENTS: Nondiabetic children with cardiovascular and/or respiratory failure and hyperglycemia. Cases were children with any hypoglycemia (blood glucose < 60 mg/dL), whereas controls were children without hypoglycemia. Each case was matched with up to four unique controls according to age group, study day, and severity of illness. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 112 (16.0%) of 698 children who received the Heart And Lung Failure-Pediatric INsulin Titration protocol developed hypoglycemia, including 25 (3.6%) who developed severe hypoglycemia (blood glucose < 40 mg/dL). Of these, 110 cases were matched to 427 controls. Hypoglycemia was associated with fewer ICU-free days (median, 15.3 vs 20.2 d; p = 0.04) and fewer hospital-free days (0 vs 7 d; p = 0.01) through day 28. Ventilator-free days through day 28 and mortality at 28 and 90 days did not differ between groups. More children with insulin-induced versus noninsulin-induced hypoglycemia had zero ICU-free days (35.8% vs 20.9%; p = 0.008). Outcomes did not differ between children with severe versus nonsevere hypoglycemia or those with recurrent versus isolated hypoglycemia. CONCLUSIONS: When a computerized algorithm, continuous glucose monitors and standardized glucose infusion rates were used to manage hyperglycemia in critically ill children with cardiovascular and/or respiratory failure, severe hypoglycemia (blood glucose < 40 mg/dL) was uncommon, but any hypoglycemia (blood glucose < 60 mg/dL) remained common and was associated with worse short-term outcomes.

Use of height-independent baseline creatinine imputation method with renal angina index.

BACKGROUND: The Renal Angina Index (RAI) is a validated screening tool used at 12 h of pediatric intensive care unit (PICU) admission to predict severe acute kidney injury (AKI) on day 3 of PICU stay. A measured or height-imputed baseline serum creatinine (SCr) is required for AKI diagnosis and RAI calculation, yet these are often lacking. We assessed an age-based, height-independent baseline SCr calculation and compared the RAI values employing this method to their historical counterpart. METHODS: An electronic algorithm was implemented to generate RAI score for patients admitted to our PICU. We reviewed 157 consecutive patient records from May 2017, until we cumulated 100 with a valid RAI calculation. We compared RAI scores using the age-based SCr imputation method of Pottel to the historical RAI. Our primary outcome was a difference in the rate of RAI fulfillment (≥ 8) reclassification between methods. RESULTS: Of the first 100 patients, 27 had measured baseline SCr and 73 used height imputation. Only two patients had RAI reclassified with the Pottel method (one in each direction). Being small for age or older were associated with ≥ 25% overestimation of the baseline SCr in 20 patients with the Pottel method compared with height imputation. 15/157 patients had a falsely positive RAI due to lack of measured baseline SCr and height. CONCLUSION: The age-based method to estimate baseline SCr offers a viable height-independent alternative for RAI calculation. While less precise than a height-based approach, this lack of precision rarely leads to reclassification of patient RAI status.

Team-based approach to identify cardiac toxicity in critically ill hematopoietic stem cell transplant recipients.

INTRODUCTION: We observed pulmonary hypertension (PH), pericardial effusions, and left ventricular systolic dysfunction (LVSD) in multiple critically ill hematopoietic stem cell transplant (HSCT) recipients. We implemented routine structured echocardiography screening for HSCT recipients admitted to the pediatric intensive care unit (PICU) using a standardized multidisciplinary process. METHODS: HSCT recipients admitted to the PICU with respiratory distress, hypoxia, shock, and complications related to transplant-associated thrombotic microangiopathy were screened on admission and every 1-2 weeks thereafter. Echocardiography findings requiring intervention and/or further screening included elevated right ventricular pressure, LVSD, and moderate to large pericardial effusions. All echocardiograms were compared to the patient's routine pretransplant echocardiogram. RESULTS: Seventy HSCT recipients required echocardiography screening over a 3-year period. Echo abnormalities requiring intervention and/or further screening were found in 35 (50%) patients. Twenty-four (34%) patients were noted to have elevated right ventricular pressure; 14 (20%) were at risk for PH, while 10 (14%) had PH. All patients with PH were treated with pulmonary vasodilators. LVSD was noted in 22 (31%) patients; 15/22 (68%) received inotropic support. Moderate to large pericardial effusions were present in nine (13%) patients, with six needing pericardial drain placement. DISCUSSION: Echocardiographic abnormalities are common in critically ill HSCT recipients. Utilization of echocardiogram screening may allow for early detection and timely intervention for cardiac complications in this high-risk cohort.