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Purpose Health-related quality of life (HRQL) has been identified as one of the core outcomes most important to assess following pediatric critical care, yet there are no data on the use of HRQL in pediatric critical care research. We aimed to determine the HRQL instruments most commonly used to assess children surviving critical care and describe study methodology, patient populations, and instrument characteristics to identify areas of deficiency and guide investigators conducting HRQL research. Methods We queried PubMed, EMBASE, PsycINFO, Cumulative Index of Nursing and Allied Health Literature, and the Cochrane Registry for studies evaluating pediatric critical care survivors published 1970–2017. We used dual review for article selection and data extraction. Results Of 60,349 citations, 66 articles met inclusion criteria. The majority of studies were observational (89.4%) and assessed HRQL at one post-discharge time-point (86.4%), and only 10.6% of studies included a baseline assessment. Time to the first follow-up assessment ranged from 1 month to 10 years post-hospitalization (median 3 years, IQR 0.5–6). For 26 prospective studies, the median follow-up time was 0.5 years [IQR 0.25–1]. Parent/guardian proxy-reporting was used in 83.3% of studies. Fifteen HRQL instruments were employed, with four used in >5% of articles: the Health Utility Index ( n  = 22 articles), the Pediatric Quality of Life Inventory ( n  = 17), the Child Health Questionnaire ( n  = 16), and the 36-Item Short Form Survey ( n  = 9). Conclusion HRQL assessment in pediatric critical care research has been centered around four instruments, though existing literature is limited by minimal longitudinal follow-up and infrequent assessment of baseline HRQL.

BackgroundPediatric acute kidney injury (AKI) is associated with long-term morbidity and mortality; however, outcomes improve when AKI is detected earlier. Current definitions of AKI use baseline creatinine; community-acquired AKI (CA-AKI) is difficult to define and detect in the pediatric emergency department (ED) when no baseline creatinine is available. Our objective was to compare age- and gender-based creatinine norms to the traditional baseline (lowest creatinine in previous 3 months) to diagnose CA-AKI.MethodsThis was a retrospective cross-sectional study conducted in children 1 month–18 years of age seen in the pediatric ED in whom a creatinine was obtained.ResultsPer the Kidney Disease Improving Global Outcomes AKI definition in encounters with baseline creatinine available, 343/2338 (14.7%) had CA-AKI. When the upper limit of the age- and gender-based creatinine norm was applied as a surrogate baseline creatinine, CA-AKI was diagnosed in 1.5% of encounters (239/15,486). Additionally, CA-AKI was diagnosed in 178 cases using the upper limit of age- and gender-based creatinine norms only, as these cases did not have a baseline creatinine.ConclusionsAge- and gender-based creatinine norms can be applied as a surrogate baseline to detect CA-AKI in all children regardless of whether baseline creatinine is available, potentially detecting it earlier.

Mucosal immunity plays an important role in the control of viral respiratory infections like SARS-CoV-2. While systemic immune responses against the SARS-2-CoV-2 have been studied in children, there is no information on mucosal antibody response, especially in the lower respiratory tract of children coronavirus disease 2019 (COVID-19) and post-infectious multisystem inflammatory syndrome in children (MIS-C) against emerging SARS-CoV-2 variants. Therefore, we evaluated neutralizing antibody responses in paired plasma and endotracheal aspirates of pediatric severe, acute COVID-19 or MIS-C patients against SARS-CoV-2 WA1/2020, as well as against variants of concern (VOCs). Neutralizing antibody responses against the SARS-CoV-2 WA1/2020 strain in pediatric plasma were 2-fold or 35-fold higher compared with the matched endotracheal aspirate in COVID-19 or MIS-C patients, respectively. In contrast to plasma, neutralizing antibody responses against the VOCs and variants of interest (VOIs) in endotracheal aspirates were lower, with only one endotracheal aspirate demonstrating neutralizing titers against the Iota, Kappa, Beta, Gamma, and Omicron variants. In conclusion, our findings suggest that children and adolescents with severe COVID-19 or MIS-C have weak mucosal neutralizing antibodies in the trachea against circulating SARS-CoV-2 Omicron and other VOCs, which may have implications for recovery and for re-infection with emerging SARS-CoV-2 variants.

Study objective: To determine whether adding IV theophylline to an aggressive regimen of inhaled and IV β-agonists, inhaled ipratropium, and IV methylprednisolone would enhance the recovery of children with severe status asthmaticus admitted to the pediatric ICU (PICU). Design: A prospective, randomized, controlled trial. Asthma scoring was performed by investigators not involved in treatment decisions and blinded to group assignment. Setting: The PICU of an urban, university-affiliated, tertiary-care children’s hospital. Patients: Children with a diagnosis of status asthmaticus who were admitted to the PICU for ≤ 2 h and who were in severe distress, as indicated by a modified Wood-Downes clinical asthma score (CAS) of ≥ 5. Interventions: All subjects initially received continuous albuterol nebulizations; intermittent, inhaled ipratropium; and IV methylprednisolone. The theophylline group was also administered infusions of IV theophylline to achieve serum concentrations of 12 to 17 μg/mL. A CAS was tabulated twice daily. Measurements and results: Forty-seven children (median age, 8.3 years; range, 13 months to 17 years) completed the study. Twenty-three children received theophylline. The baseline CASs of both groups were similar and included three subjects receiving mechanical ventilation in each group. All subjects receiving mechanical ventilation and theophylline were intubated before drug infusion. Among the 41 subjects who were not receiving mechanical ventilation, those receiving theophylline achieved a CAS of ≤ 3 sooner than control subjects (18.6 ± 2.7 h vs 31.1 ± 4.5 h; p < 0.05). Theophylline had no effect on the length of PICU stay or the total incidence of side effects. Subjects receiving theophylline had more emesis (p < 0.05), and control patients had more tremor (p < 0.05). Conclusions: Theophylline safely hastened the recovery of children in severe status asthmaticus who were also receiving albuterol, ipratropium, and methylprednisolone. The role of theophylline in the management of asthmatic children in impending respiratory failure should be reexamined.

Background Ongoing measures to improve pediatric continuous kidney replacement therapy (CKRT) have lowered mortality rates, shifting the focus to survivor functional status. While septic acute kidney injury generates new morbidity in pediatric critically ill patients, acquired morbidities and functional status of CKRT population are unknown. We predicted that CKRT survivors are at risk for new morbidity and would have worse functional status at PICU discharge compared to baseline, and aimed to describe associated factors. Methods Retrospective cohort study over 24 months of CKRT patients surviving to PICU discharge in a quaternary children’s hospital. Functional outcome was determined by Functional Status Scale (FSS). Results FSS scores were higher at PICU and hospital discharge compared to baseline. Of 45 CKRT survivors, 31 (69%) had worse FSS score at PICU discharge and 51% had new morbidity (≥3 increase in FSS); majority qualified as moderate to severe disability (FSS ≥10). Four patients (9%) had new tracheostomy, 3 (7%) were ventilator dependent, and 10 (22%) were dialysis dependent. Most (23/45, 51%) required outpatient rehabilitation. Cumulative days on sedation, controlled for illness severity, were independently associated with worse FSS at PICU discharge (aOR 25.18 (3.73, 169.92)). In adjusted analyses, duration of sedation was associated with new morbidity, while neurologic comorbidity, percent fluid overload at CKRT start, and nonrenal comorbidity were associated with moderate to severe disability at PICU discharge when controlled for baseline FSS. Conclusions CKRT survivors, with new morbidity and worse functional outcomes at PICU discharge, are a newly described vulnerable population requiring targeted follow-up. Deliberate decrease of sedation exposure in patients with decreased clearance due to organ dysfunction needs to be studied as a modifiable risk factor.

Abstract Background Coinfection with influenza virus and methicillin-resistant Staphylococcus aureus (MRSA) causes life-threatening necrotizing pneumonia in children. Sporadic incidence precludes evaluation of antimicrobial efficacy. We assessed the clinical characteristics and outcomes of critically ill children with influenza-MRSA pneumonia and evaluated antibiotic use. Methods We enrolled children (<18 years) with influenza infection and respiratory failure across 34 pediatric intensive care units 11/2008-5/2016. We compared baseline characteristics, clinical courses, and therapies in children with MRSA coinfection, non-MRSA bacterial coinfection, and no bacterial coinfection. Results We enrolled 170 children (127 influenza A, 43 influenza B). Children with influenza-MRSA pneumonia (N = 30, 87% previously healthy) were older than those with non-MRSA (N = 61) or no (N = 79) bacterial coinfections. Influenza-MRSA was associated with increased leukopenia, acute lung injury, vasopressor use, extracorporeal life support, and mortality than either group (P ≤ .0001). Influenza-related mortality was 40% with MRSA compared to 4.3% without (relative risk [RR], 9.3; 95% confidence interval [CI], 3.8-22.9). Of 29/30 children with MRSA who received vancomycin within the first 24 hours of hospitalization, mortality was 12.5% (N = 2/16) if treatment also included a second anti-MRSA antibiotic compared to 69.2% (N = 9/13) with vancomycin monotherapy (RR, 5.5; 95% CI, 1.4, 21.3; P = .003). Vancomycin dosing did not influence initial trough levels; 78% were <10 µg/mL. Conclusions Influenza-MRSA coinfection is associated with high fatality in critically ill children. These data support early addition of a second anti-MRSA antibiotic to vancomycin in suspected severe cases. Influenza-methicillin-resistant Staphylococcus aureus (MRSA) coinfection is associated with high fatality in children. In this multicenter study, mortality was lower in critically ill children treated early with a second anti-MRSA antibiotic in addition to vancomycin compared to those who received vancomycin monotherapy.

Hyperosmolar agents are cornerstone therapies for pediatric severe traumatic brain injury. Guideline recommendations for 3% hypertonic saline (HTS) are based on limited numbers of patients, and no study to date has supported a recommendation for mannitol. To characterize current use of hyperosmolar agents in pediatric severe traumatic brain injury and assess whether HTS or mannitol is associated with greater decreases in intracranial pressure (ICP) and/or increases in cerebral perfusion pressure (CPP). In this comparative effectiveness research study, 1018 children were screened and 18 were excluded; 787 children received some form of hyperosmolar therapy during the ICP-directed phase of care, with 521 receiving a bolus. Three of these children were excluded because they had received only bolus administration of both HTS and mannitol in the same hour, leaving 518 children (at 44 clinical sites in 8 countries) for analysis. The study was conducted from February 1, 2014, to September 31, 2017, with follow-up for 1 week after injury. Final analysis was performed July 20, 2021. Boluses of HTS and mannitol were administered. Data on ICP and CPP were collected before and after medication administration. Statistical methods included linear mixed models and corrections for potential confounding variables to compare the 2 treatments. A total of 518 children (mean [SD] age, 7.6 [5.4] years; 336 [64.9%] male; 274 [52.9%] White) were included. Participants' mean (SD) Glasgow Coma Scale score was 5.2 (1.8). Bolus HTS was observed to decrease ICP and increase CPP (mean [SD] ICP, 1.03 [6.77] mm Hg; P < .001; mean [SD] CPP, 1.25 [12.47] mm Hg; P < .001), whereas mannitol was observed to increase CPP (mean [SD] CPP, 1.20 [11.43] mm Hg; P = .009). In the primary outcome, HTS was associated with a greater reduction in ICP compared with mannitol (unadjusted β, -0.85; 95% CI, -1.53 to -0.19), but no association was seen after adjustments (adjusted β, -0.53; 95% CI, -1.32 to 0.25; P = .18). No differences in CPP were observed. When ICP was greater than 20 mm Hg, greater than 25 mm Hg, or greater than 30 mm Hg, HTS outperformed mannitol for each threshold in observed ICP reduction (>20 mm Hg: unadjusted β, -2.51; 95% CI, -3.86 to -1.15, P < .001; >25 mm Hg: unadjusted β, -3.88; 95% CI, -5.69 to -2.06, P < .001; >30 mm Hg: unadjusted β, -4.07; 95% CI, -6.35 to -1.79, P < .001), with results remaining significant for ICP greater than 25 mm Hg in adjusted analysis. In this comparative effectiveness research study, bolus HTS was associated with lower ICP and higher CPP, whereas mannitol was associated only with higher CPP. After adjustment for confounders, both therapies showed no association with ICP and CPP. During ICP crises, HTS was associated with better performance than mannitol.

Background Functional neurologic outcome for children with refractory and super-refractory status epilepticus has not been well defined. Methods Retrospective chart review including children age 0–17 years who received pentobarbital infusion from 2003 to 2016 for status epilepticus. Outcomes were defined in terms of mortality, need for new medical technology assistance at hospital discharge and functional neurologic outcome determined by pediatric cerebral performance category score (PCPC). Potential patient characteristics associated with functional neurologic outcome including age, sex, ethnicity, etiology of the status epilepticus, and duration of pentobarbital infusion were evaluated. Results Forty children met inclusion criteria. In-hospital mortality was 30% (12/40). Of survivors, 21% (6/28) returned to baseline PCPC while half (14/28) declined in function ≥ 2 PCPC categories at hospital discharge. 25% (7/28) of survivors required tracheostomy and 27% (7/26) required new gastrostomy. Seizures persisted at discharge for most patients with new onset status epilepticus while the majority of patients with known epilepsy returned to baseline seizure frequency. Etiology ( p  = 0.015), PCPC at admission ( p  = 0.0006), new tracheostomy ( p  = 0.012), and new gastrostomy tube ( p  = 0.012) were associated with increase in PCPC score ≥ 2 categories in univariable analysis. Duration of pentobarbital infusion ( p  = 0.005) and length of hospital stay ( p  = 0.056) were longer in patients who demonstrated significant decline in neurologic function. None of these variables maintained statistical significance when multiple logistic regression model adjusting for PCPC score at admission was applied. At long-term follow-up, 36% (8/22) of children demonstrated improvement in PCPC compared to discharge and 23% (5/22) showed deterioration including three additional deaths. Conclusions Mortality in this population was high. The majority of children experienced some degree of disability at discharge. Despite prolonged pentobarbital infusion, there were cases of survival with good neurologic outcome.

Rare adverse drug reactions (ADRs) are underrecognized and underreported in the electronic medical record (EMR). These events often require clinical review, making systematic identification challenging. The study aim was to develop an approach to prioritize identification and validation of a rare ADR to trimethoprim-sulfamethoxazole causing acute respiratory distress syndrome (TMP-SMX ARDS) across medical institutions. We developed a clinical phenotype based on 2 local TMP-SMX ARDS cases mapped to standardized elements of a national comparative healthcare database (PHIS). We validated identification of TMP-SMX ARDS at scale across medical institutions. A set of scoring criteria was created to prioritize cases and generate a center-specific top 10 list of candidate encounters. External validation at 3 PHIS contributing hospitals with a known TMP-SMX ARDS case was performed by reviewing the top 10 candidate list for the known case. The review period was January 1, 2012-January 1, 2025. EMR data extracted from 2 TMP-SMX ARDS cases included patients that both required extracorporeal membrane oxygenation for > 100 days, experienced air leak early in hospital presentation, required tracheostomy placement, and were hospitalized for > 440 days. Based on the TMP-SMX ARDS phenotype, the local cases ranked 1st and 3rd on the PHIS generated top 10 candidate list for internal validation. For external validation, known cases were identified on their respective hospital top 10 lists, ranking 3rd, 3rd, and 5th. Applying a TMP-SMX ARDS phenotype to a national health care database paired with clinical review of candidate cases may be an effective approach to identify underrecognized ADRs.