Faculty Bibliography

BACKGROUND:There are risks associated with excessive intravenous fluid (IVF) administration in critically ill children. Previous efforts have described opportunities to reduce positive cumulative fluid balance (CFB) in this population but have not been widely implemented. In the wake of Hurricane Helene, a national IVF shortage led to the implementation of IVF conservation guidelines. We sought to determine if this was associated with a reduction in IVF use and CFB. METHODS:The present study is a four-site cohort study of critically ill children utilizing a federated data collection framework to extract patient age, sex, weight, and daily fluid intake/output for days 1-4 of all admissions 28 days prior to and 28 days after the implementation of IVF conservation guidelines. Guidelines were individualized per institution. Total fluid intake, total IVF intake, % intake from IVF, and % CFB were compared between pre- and post-IVF conservation groups. RESULTS:All sites had similar conservation recommendations. There were 633 patients admitted pre- and 619 patients admitted post-IVF conservation guideline implementation, with similar age and weight distributions. There was no significant difference in IVF use pre- and post-IVF conservation; 29-35% of patients had > 5% CFB on day 1 pre-IVF conservation while 27-39% did post-conservation, with increasing numbers on day 2. CONCLUSIONS:Even in the setting of a national IVF shortage, simple recommendations without structured change were insufficient to change IVF administration practices. This indicates additional practices will be needed to reduce IVF intake and % CFB in this vulnerable population.

IntroductionFluid overload (FO), a state of pathologic positive cumulative fluid balance (CFB), is common in Pediatric Intensive Care Units (PICU) and associated with morbidity and mortality. Because different PICUs may have unique needs, barriers, and limitations to accurately report fluid balance (FB) and reduce FO, understanding the drivers of positive FB is needed. We hypothesize CFB >5% and >10% is common on ICU days 1 and 2, but that reasons for high %CFB will vary across sites, as will barriers to accurate FB recording and opportunities to improve FB recording/management.MethodsConcurrent mixed methods study utilizing a retrospective observational cohort design and prospective interview and survey design performed at four tertiary pediatric ICUs. FB data were extracted from the electronic health record. A federated data collection framework allowed for rapid data aggregation. The primary outcome was %CFB on ICU days 1 and 2, defined as total intake minus total output divided by ICU admission weight. Chi-square test and Wilcoxon rank sum tests compared results across and within sites.ResultsAmongst 3,071 ICU encounters, day 2 CFB >5% varied from 39% to 54% (p = 0.03) and day 2 CFB >10% varied from 16% to 25% (p = 0.04) across sites. Urine occurrence recordings and patients receiving >100% Holliday-Segar fluids on Day 1 differed across sites (p < 0.001). Sites discussed overall FB and specific FB goals on rounds with differing frequency (42-73% and 19-39%, respectively), but they reported similar barriers to accurate FB reporting and achievable opportunities to improve FB measurements, including patients/families not saving urine/stool, patients not tracking oral intake, and lack of standardized charting of flushes.ConclusionDay 2 CFB >5% and >10% was common among pediatric ICU encounters but proportion of patients varied significantly across ICUs. Individual ICUs have different drivers of FO that must be targeted to improve FB management.

BACKGROUND:Pediatric respiratory syncytial virus (RSV)-related acute lower respiratory tract infection (LRTI) commonly requires hospitalization. The Clinical Progression Scale Pediatrics (CPS-Ped) measures level of respiratory support and degree of hypoxia across a range of disease severity, but it has not been applied in infants hospitalized with severe RSV-LRTI. METHODS:We analyzed data from a prospective surveillance registry of infants hospitalized for RSV-related complications across 39 U.S. PICUs from October through December 2022. We assigned CPS-Ped (0=discharged home at respiratory baseline to 8=death) at admission, days 2-7,10, and 14. We identified predictors of clinical improvement (CPS-Ped≤2 or 3-point decrease) by day 7 using multivariable log-binomial regression models and estimated the sample size (80% power) to detect 15% between-group clinical improvement with CPS-Ped versus hospital length of stay (LOS). RESULTS:Of 585 hospitalized infants, 138 (23.6%) received invasive mechanical ventilation (IMV). Of the 49 (8.4%) infants whose CPS-Ped score worsened by 2 points after admission, one died. Failure to clinically improve by day 7 occurred in 205 (35%) infants and was associated with age <3 months, prematurity, underlying respiratory condition, and IMV in the first 24 hours in the multivariable analysis. The estimated sample size per arm required for detecting a 15% clinical improvement in a potential study was 584 using CPS-Ped clinical improvement versus 2,031 for hospital LOS. CONCLUSIONS:CPS-Ped can be used to capture a range of disease severity and track clinical improvement in infants who develop RSV-related critical illness and could be useful for evaluating therapeutic interventions for RSV.

BACKGROUND:We aimed to determine if pre-existing immunocompromising conditions (ICCs) were associated with the presentation or outcome of patients with acute coronavirus disease 2019 (COVID-19) admitted for pediatric intensive care. METHODS:Fifty-five hospitals in 30 US states reported cases through the Overcoming COVID-19 public health surveillance registry. Patients <21 years admitted 12 March 2020-30 December 2021 to the pediatric intensive care unit (PICU) or high-acuity unit for acute COVID-19 were included. RESULTS:Of 1274 patients, 105 (8.2%) had an ICC, including 33 (31.4%) hematologic malignancies, 24 (22.9%) primary immunodeficiencies and disorders of hematopoietic cells, 19 (18.1%) nonmalignant organ failure with solid-organ transplantation, 16 (15.2%) solid tumors, and 13 (12.4%) autoimmune disorders. Patients with ICCs were older, had more underlying renal conditions, and had lower white blood cell and platelet counts than those without ICCs, but had similar clinical disease severity upon admission. In-hospital mortality from COVID-19 was higher (11.4% vs 4.6%, P = .005) and hospitalization was longer (P = .01) in patients with ICCs. New major morbidities upon discharge were not different between those with and without ICC (10.5% vs 13.9%, P = .40). In patients with ICCs, bacterial coinfection was more common in those with life-threatening COVID-19. CONCLUSIONS:In this national case series of patients <21 years of age with acute COVID-19 admitted for intensive care, existence of a prior ICCs were associated with worse clinical outcomes. Reassuringly, most patients with ICCs hospitalized in the PICU for severe acute COVID-19 survived and were discharged home without new severe morbidities.

IMPORTANCE/UNASSIGNED:Neurological manifestations during acute SARS-CoV-2-related multisystem inflammatory syndrome in children (MIS-C) are common in hospitalized patients younger than 18 years and may increase risk of new neurocognitive or functional morbidity. OBJECTIVE/UNASSIGNED:To assess the association of severe neurological manifestations during a SARS-CoV-2-related hospital admission with new neurocognitive or functional morbidities at discharge. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This prospective cohort study from 46 centers in 10 countries included patients younger than 18 years who were hospitalized for acute SARS-CoV-2 or MIS-C between January 2, 2020, and July 31, 2021. EXPOSURE/UNASSIGNED:Severe neurological manifestations, which included acute encephalopathy, seizures or status epilepticus, meningitis or encephalitis, sympathetic storming or dysautonomia, cardiac arrest, coma, delirium, and stroke. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcome was new neurocognitive (based on the Pediatric Cerebral Performance Category scale) and/or functional (based on the Functional Status Scale) morbidity at hospital discharge. Multivariable logistic regression analyses were performed to examine the association of severe neurological manifestations with new morbidity in each SARS-CoV-2-related condition. RESULTS/UNASSIGNED:Overall, 3568 patients younger than 18 years (median age, 8 years [IQR, 1-14 years]; 54.3% male) were included in this study. Most (2980 [83.5%]) had acute SARS-CoV-2; the remainder (588 [16.5%]) had MIS-C. Among the patients with acute SARS-CoV-2, 536 (18.0%) had a severe neurological manifestation during hospitalization, as did 146 patients with MIS-C (24.8%). Among survivors with acute SARS-CoV-2, those with severe neurological manifestations were more likely to have new neurocognitive or functional morbidity at hospital discharge compared with those without severe neurological manifestations (27.7% [n = 142] vs 14.6% [n = 356]; P < .001). For survivors with MIS-C, 28.0% (n = 39) with severe neurological manifestations had new neurocognitive and/or functional morbidity at hospital discharge compared with 15.5% (n = 68) of those without severe neurological manifestations (P = .002). When adjusting for risk factors in those with severe neurological manifestations, both patients with acute SARS-CoV-2 (odds ratio, 1.85 [95% CI, 1.27-2.70]; P = .001) and those with MIS-C (odds ratio, 2.18 [95% CI, 1.22-3.89]; P = .009) had higher odds of having new neurocognitive and/or functional morbidity at hospital discharge. CONCLUSIONS AND RELEVANCE/UNASSIGNED:The results of this study suggest that children and adolescents with acute SARS-CoV-2 or MIS-C and severe neurological manifestations may be at high risk for long-term impairment and may benefit from screening and early intervention to assist recovery.

IMPORTANCE:Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections (LRTIs) and infant hospitalization worldwide. OBJECTIVE:To evaluate the characteristics and outcomes of RSV-related critical illness in US infants during peak 2022 RSV transmission. DESIGN, SETTING, AND PARTICIPANTS:This cross-sectional study used a public health prospective surveillance registry in 39 pediatric hospitals across 27 US states. Participants were infants admitted for 24 or more hours between October 17 and December 16, 2022, to a unit providing intensive care due to laboratory-confirmed RSV infection. EXPOSURE:Respiratory syncytial virus. MAIN OUTCOMES AND MEASURES:Data were captured on demographics, clinical characteristics, signs and symptoms, laboratory values, severity measures, and clinical outcomes, including receipt of noninvasive respiratory support, invasive mechanical ventilation, vasopressors or extracorporeal membrane oxygenation, and death. Mixed-effects multivariable log-binomial regression models were used to assess associations between intubation status and demographic factors, gestational age, and underlying conditions, including hospital as a random effect to account for between-site heterogeneity. RESULTS:The first 15 to 20 consecutive eligible infants from each site were included for a target sample size of 600. Among the 600 infants, the median (IQR) age was 2.6 (1.4-6.0) months; 361 (60.2%) were male, 169 (28.9%) were born prematurely, and 487 (81.2%) had no underlying medical conditions. Primary reasons for admission included LRTI (594 infants [99.0%]) and apnea or bradycardia (77 infants [12.8%]). Overall, 143 infants (23.8%) received invasive mechanical ventilation (median [IQR], 6.0 [4.0-10.0] days). The highest level of respiratory support for nonintubated infants was high-flow nasal cannula (243 infants [40.5%]), followed by bilevel positive airway pressure (150 infants [25.0%]) and continuous positive airway pressure (52 infants [8.7%]). Infants younger than 3 months, those born prematurely (gestational age <37 weeks), or those publicly insured were at higher risk for intubation. Four infants (0.7%) received extracorporeal membrane oxygenation, and 2 died. The median (IQR) length of hospitalization for survivors was 5 (4-10) days. CONCLUSIONS AND RELEVANCE:In this cross-sectional study, most US infants who required intensive care for RSV LRTIs were young, healthy, and born at term. These findings highlight the need for RSV preventive interventions targeting all infants to reduce the burden of severe RSV illness.

OBJECTIVES/OBJECTIVE:We aimed to critically evaluate the effectiveness of a designated ECMO team in our ECMO selection process and patient outcomes in the first 3 years of our low-volume pediatric ECMO program. METHODS:We conducted a retrospective chart review of patients who received an ECMO consultation between the start of our program in March 2015 and May 2018. We gathered clinical and demographic information on patients who did and did not receive ECMO, and described our selection process. We reflected on the processes used to initiate our program and our outcomes in the first 3 years. RESULTS:, lactate, and pH between the patients who went on ECMO and who did not. We improved our outcomes from 0% survival to discharge in 2015, to 60% in 2018, with an average of 63% survival to discharge over the first 3 years of our program. CONCLUSIONS:In a low-volume pediatric ECMO center, having a designated team to assist in the patient selection process and management can help provide safe and efficient care to these patients, and improve patient outcomes. Having a strict management protocol and simulation sessions involving all members of the medical team yields comfort for the providers and optimal care for patients. This study describes our novel structure, processes, and outcomes, which we hope will be helpful to others seeking to develop a new pediatric ECMO program.

OBJECTIVES:Extracorporeal membrane oxygenation (ECMO) has been used successfully to support adults with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related cardiac or respiratory failure refractory to conventional therapies. Comprehensive reports of children and adolescents with SARS-CoV-2-related ECMO support for conditions, including multisystem inflammatory syndrome in children (MIS-C) and acute COVID-19, are needed. DESIGN:Case series of patients from the Overcoming COVID-19 public health surveillance registry. SETTING:Sixty-three hospitals in 32 U.S. states reporting to the registry between March 15, 2020, and December 31, 2021. PATIENTS:Patients less than 21 years admitted to the ICU meeting Centers for Disease Control criteria for MIS-C or acute COVID-19. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:The final cohort included 2,733 patients with MIS-C ( n = 1,530; 37 [2.4%] requiring ECMO) or acute COVID-19 ( n = 1,203; 71 [5.9%] requiring ECMO). ECMO patients in both groups were older than those without ECMO support (MIS-C median 15.4 vs 9.9 yr; acute COVID-19 median 15.3 vs 13.6 yr). The body mass index percentile was similar in the MIS-C ECMO versus no ECMO groups (89.9 vs 85.8; p = 0.22) but higher in the COVID-19 ECMO versus no ECMO groups (98.3 vs 96.5; p = 0.03). Patients on ECMO with MIS-C versus COVID-19 were supported more often with venoarterial ECMO (92% vs 41%) for primary cardiac indications (87% vs 23%), had ECMO initiated earlier (median 1 vs 5 d from hospitalization), shorter ECMO courses (median 3.9 vs 14 d), shorter hospital length of stay (median 20 vs 52 d), lower in-hospital mortality (27% vs 37%), and less major morbidity at discharge in survivors (new tracheostomy, oxygen or mechanical ventilation need or neurologic deficit; 0% vs 11%, 0% vs 20%, and 8% vs 15%, respectively). Most patients with MIS-C requiring ECMO support (87%) were admitted during the pre-Delta (variant B.1.617.2) period, while most patients with acute COVID-19 requiring ECMO support (70%) were admitted during the Delta variant period. CONCLUSIONS:ECMO support for SARS-CoV-2-related critical illness was uncommon, but type, initiation, and duration of ECMO use in MIS-C and acute COVID-19 were markedly different. Like pre-pandemic pediatric ECMO cohorts, most patients survived to hospital discharge.

IMPORTANCE/UNASSIGNED:There is limited evidence for therapeutic options for pediatric COVID-19 outside of multisystem inflammatory syndrome in children (MIS-C). OBJECTIVE/UNASSIGNED:To determine whether the use of steroids within 2 days of admission for non-MIS-C COVID-19 in children is associated with hospital length of stay (LOS). The secondary objective was to determine their association with intensive care unit (ICU) LOS, inflammation, and fever defervescence. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cohort study analyzed data retrospectively for children (<18 years) who required hospitalization for non-MIS-C COVID-19. Data from March 2020 through September 2021 were provided by 58 hospitals in 7 countries who participate in the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) COVID-19 registry. EXPOSURE/UNASSIGNED:Administration of steroids within 2 days of admission. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Length of stay in the hospital and ICU. Adjustment for confounders was done by mixed linear regression and propensity score matching. RESULTS/UNASSIGNED:A total of 1163 patients met inclusion criteria and had a median (IQR) age of 7 years (0.9-14.3). Almost half of all patients (601/1163, 51.7%) were male, 33.8% (392/1163) were non-Hispanic White, and 27.9% (324/1163) were Hispanic. Of the study population, 184 patients (15.8%) received steroids within 2 days of admission, and 979 (84.2%) did not receive steroids within the first 2 days. Among 1163 patients, 658 (56.5%) required respiratory support during hospitalization. Overall, patients in the steroids group were older and had greater severity of illness, and a larger proportion required respiratory and vasoactive support. On multivariable linear regression, after controlling for treatment with remdesivir within 2 days, country, race and ethnicity, obesity and comorbidity, number of abnormal inflammatory mediators, age, bacterial or viral coinfection, and disease severity according to ICU admission within first 2 days or World Health Organization ordinal scale of 4 or higher on admission, with a random intercept for the site, early steroid treatment was not significantly associated with hospital LOS (exponentiated coefficient, 0.94; 95% CI, 0.81-1.09; P = .42). Separate analyses for patients with an LOS of 2 days or longer (n = 729), those receiving respiratory support at admission (n = 286), and propensity score-matched patients also showed no significant association between steroids and LOS. Early steroid treatment was not associated with ICU LOS, fever defervescence by day 3, or normalization of inflammatory mediators. CONCLUSIONS AND RELEVANCE/UNASSIGNED:Steroid treatment within 2 days of hospital admission in a heterogeneous cohort of pediatric patients hospitalized for COVID-19 without MIS-C did not have a statistically significant association with hospital LOS.

BACKGROUND:Describe the incidence and associated outcomes of gastrointestinal (GI) manifestations of acute coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in hospitalized children (MIS-C). METHODS:Retrospective review of the Viral Infection and Respiratory Illness Universal Study registry, a prospective observational, multicenter international cohort study of hospitalized children with acute COVID-19 or MIS-C from March 2020 to November 2020. The primary outcome measure was critical COVID-19 illness. Multivariable models were performed to assess for associations of GI involvement with the primary composite outcome in the entire cohort and a subpopulation of patients with MIS-C. Secondary outcomes included prolonged hospital length of stay defined as being >75th percentile and mortality. RESULTS:Of the 789 patients, GI involvement was present in 500 (63.3%). Critical illness occurred in 392 (49.6%), and 18 (2.3%) died. Those with GI involvement were older (median age of 8 yr), and 18.2% had an underlying GI comorbidity. GI symptoms and liver derangements were more common among patients with MIS-C. In the adjusted multivariable models, acute COVID-19 was no associated with the primary or secondary outcomes. Similarly, despite the preponderance of GI involvement in patients with MIS-C, it was also not associated with the primary or secondary outcomes. CONCLUSIONS:GI involvement is common in hospitalized children with acute COVID-19 and MIS-C. GI involvement is not associated with critical illness, hospital length of stay or mortality in acute COVID-19 or MIS-C.