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Previous latent class analysis of adults with acute respiratory distress syndrome (ARDS) identified two phenotypes, distinguished by the degree of inflammation. We aimed to identify phenotypes in children with ARDS in whom developmental differences might be important, using a latent class analysis approach similar to that used in adults.This study was a secondary analysis of data aggregated from the Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) clinical trial and the Genetic Variation and Biomarkers in Children with Acute Lung Injury (BALI) ancillary study. We used latent class analysis, which included demographic, clinical, and plasma biomarker variables, to identify paediatric ARDS (PARDS) phenotypes within a cohort of children included in the RESTORE and BALI studies. The association of phenotypes with clinically relevant outcomes and the performance of paediatric data in adult ARDS classification algorithms were also assessed.304 children with PARDS were included in this secondary analysis. Using latent class analysis, a two-class model was a better fit for the cohort than a one-class model (p0·001). Latent class analysis identified two classes: class 1 (181 [60%] of 304 patients with PARDS) and class 2 (123 [40%] of 304 patients with PARDS), referred to as phenotype 1 and 2 hereafter. Phenotype 2 was characterised by higher concentrations of inflammatory biomarkers, a higher incidence of vasopressor use, and more frequent diagnosis of sepsis, consistent with the adult hyperinflammatory phenotype. All levels of severity of PARDS were observed across both phenotypes. Children with the hyperinflammatory phenotype (phenotype 2) had worse clinical outcomes than those with the hypoinflammatory phenotype (phenotype 1), with a longer duration of mechanical ventilation (median 10·0 days [IQR 6·3-21·0] for phenotype 2 vs 6·6 days [4·1-10·8] for phenotype 1, p0·0001), and higher incidence of mortality (17 [13·8%] of 123 patients vs four [2·2%] of 181 patients, p=0·0001). When using adult phenotype classification algorithms in children, the soluble tumour necrosis factor receptor-1 (sTNFr1), vasopressor use, and interleukin (IL)-6 variables gave an area under the curve (AUC) of 0·956, and the sTNFr1, vasopressor use, and IL-8 variables gave an AUC of 0·954, compared with the gold standard of latent class analysis.Latent class analysis identified two phenotypes in children with ARDS with characteristics similar to those in adults, including worse outcomes among patients with the hyperinflammatory phenotype. PARDS phenotypes should be considered in design and analysis of future clinical trials in children.US National Institutes of Health.

Rationale: Racial disparities in pain management have been previously reported for children receiving emergency care. Objectives: To determine whether patient race or ethnicity is associated with the broader goal of pain management and sedation among pediatric patients mechanically ventilated for acute respiratory failure. Methods: Planned secondary analysis of RESTORE (Randomized Evaluation of Sedation Titration for Respiratory Failure). RESTORE, a cluster-randomized clinical trial conducted in 31 U.S. pediatric intensive care units, compared protocolized sedation management (intervention arm) with usual care (control arm). Participants included 2,271 children identified as non-Hispanic white (white, n = 1,233), non-Hispanic Black (Black, n = 502), or Hispanic of any race (Hispanic, n = 536). Results: Within each treatment arm, neither opioid nor benzodiazepine selection, nor cumulative dosing, differed significantly among race and ethnicity groups. Black patients experienced fewer days with an episode of pain (compared with white patients in the control arm and with Hispanic patients in the intervention arm) and experienced less iatrogenic withdrawal syndrome (compared with white patients in either arm or with Hispanic patients in the intervention arm). The percentage of days awake and calm while intubated was not significantly different in pairwise comparisons by race and ethnicity groups in either the control arm (median: white, 75%; Black, 71%; Hispanic, 75%) or the intervention arm (white, 86%; Black, 88%; Hispanic, 85%). Conclusions: Across multiple measures, our study found scattered differences in sedation management among critically ill Black, Hispanic, and white children that did not consistently favor any group. However, racial disparities related to implicit bias cannot be completely ruled out. Clinical trial registered with clinicaltrials.gov (NCT 00814099).

Elevated surfactant protein D (SP-D) is a relatively specific indicator of lung injury and is associated with both acute and chronic lung disease in adults and respiratory distress syndrome in premature infants. The relationship between plasma SP-D and lung injury in children with acute respiratory failure is unclear.Is plasma SP-D associated with lung injury or outcome in children with acute respiratory failure?This was a prospective cohort study in children 2 weeks to 17 years of age with acute respiratory failure who participated in the BALI multi-center study. Analyses were done using SP-D levels in plasma from the first sample taken on either the day of intubation or one of the following 2 days. SP-D level was measured by enzyme-linked immunosorbent assay.Plasma samples from 350 patients were used in the analysis; 233 had pediatric ARDS (PARDS). SP-D levels varied across primary diagnoses (P .001). Elevated SP-D levels were associated with severe PARDS after adjusting for age, pediatric risk of mortality III (PRISM-III), and primary diagnosis (OR = 1.02; CI = 1.01-1.04; P = .011). Multivariable analyses also indicated that elevated SP-D levels were associated with death (OR = 1.02; CI = 1.01-1.04; P = .004), duration of mechanical ventilation (P = .012), PICU length of stay (P = .019), and highest oxygenation index (P = .040). SP-D levels also correlated with age (rElevated plasma SP-D levels are associated with severe PARDS and poor outcomes in children with acute respiratory failure. Future studies will determine whether SP-D can be used to predict the degree of lung injury or response to treatment and whether SP-D is useful in identifying PARDS endotypes.

To compare current analgesia and sedation management practices between critically ill children with pre-existing cognitive impairment and critically ill neurotypical children, including possible indicators of therapeutic efficacy.This study used secondary analysis of prospective data from the RESTORE clinical trial, with 2449 children admitted to the pediatric intensive care unit and receiving mechanical ventilation for acute respiratory failure. Subjects with a baseline Pediatric Cerebral Performance Category ≥3 were defined as subjects with cognitive impairment, and differences between groups were explored using regression methods accounting for pediatric intensive care unit as a cluster variable.This study identified 412 subjects (17%) with cognitive impairment. Compared with neurotypical subjects, subjects with cognitive impairment were older (median, years, 6.2 vs 1.4; P .001) with more severe pediatric acute respiratory distress syndrome (40% vs 33%; P = .009). They received significantly lower cumulative doses of opioids (median, mg/kg, 14.2 vs 16.2; P .001) and benzodiazepines (10.6 vs 14.4; P .001). Three nonverbal subjects with cognitive impairment received no analgesia or sedation. Subjects with cognitive impairment were assessed as having more study days awake and calm and fewer study days with an episode of pain. They were less likely to be assessed as having inadequate pain/sedation management or unplanned endotracheal/invasive tube removal. Subjects with cognitive impairment had more documented iatrogenic withdrawal symptoms than neurotypical subjects.Subjects with cognitive impairment in this study received less medication, but it is unclear whether they have authentically lower analgesic and/or sedative requirements or are vulnerable to inadequate assessment of discomfort because of the lack of validated assessment tools. We recommend the development of pain and sedation assessment tools specific to this patient population.

Purpose This paper describes the methodology of a clinical trial of prone positioning in pediatric patients with acute lung injury (ALI). Nonrandomized studies suggest that prone positioning improves oxygenation in patients with ALI/acute respiratory distress syndrome without the risk of serious iatrogenic injury. It is not known if these improvements in oxygenation result in improvements in clinical outcomes. A clinical trial was needed to answer this question. Materials and Methods The pediatric prone study is a multicenter, randomized, noncrossover, controlled clinical trial. The trial is designed to test the hypothesis that at the end of 28 days, children with ALI treated with prone positioning will have more ventilator-free days than children treated with supine positioning. Secondary end points include the time to recovery of lung injury, organ failure–free days, functional outcome, adverse events, and mortality from all causes. Pediatric patients, 42 weeks postconceptual age to 18 years of age, are enrolled within 48 hours of meeting ALI criteria. Patients randomized to the prone group are positioned prone within 4 hours of randomization and remain prone for 20 hours each day during the acute phase of their illness for a maximum of 7 days. Both groups are managed according to ventilator protocol, extubation readiness testing, and sedation protocols and hemodynamic, nutrition, and skin care guidelines. Conclusions This paper describes the process, multidisciplinary input, and procedures used to support the design of the clinical trial, as well as the challenges faced by the clinical scientists during the conduct of the clinical trial.

OBJECTIVE To describe nurse decision making and patient responses associated with the administration of analgesics and sedatives in the pediatric cardiac ICU. DESIGN Prospective nonexperimental mixed methods study of pediatric cardiac ICU nursing practice. SETTING Three tertiary academic pediatric heart centers in the United States. SUBJECTS Pediatric cardiac ICU nurses caring for 217 patients completed 1,330 surveys. INTERVENTIONS Four-item open-ended nurse survey completed each time an as needed dose of an analgesic or sedative was administered, an analgesic or sedative infusion/dose was titrated, and/or a new analgesic or sedative was administered. MEASUREMENTS AND MAIN RESULTS Responses to survey questions were entered verbatim and then collapsed using a consensus process. Collapsing of the data continued until there was a working set of "symptoms," "changes," and "clinical situation managed" categories. Nurses identified 28 symptoms managed with analgesia and sedation. The most frequent symptoms included hypertension, tachycardia, crying, pain, and agitation. Nurses identified 20 patient changes that resulted from their interventions. The most prevalent changes included improved hemodynamics, calm state, sleep, comfort, and relaxed state. Nurses identified 22 clinical situations that they were attempting to manage. The most frequent clinical situations included pain, hemodynamics, procedures, hypertension, and agitation. Nurses responded that 22% of their interventions were influenced by others. CONCLUSIONS Pediatric cardiac ICU nurses use many nonspecific indicators to describe patient level of comfort collectively. Decisions for managing patient comfort were influenced by their patients' overall hemodynamic stability.

To compare changes in regional cerebral or flank oxygen saturation measured by near-infrared spectroscopy with changes in central venous oxygen saturation (ScvO2) and to determine clinical variables associated with these changes.Prospective observational cohort study.University tertiary care center, pediatric cardiac intensive care unit.Seventy postoperative congenital cardiac surgical patients (median age 0.3 yrs; interquartile range 0.02-0.46 yrs).None.We measured temporally correlated regional oxygen saturation (rSO2) with hematologic (hematocrit), biochemical (arterial blood gas, ScvO2, and lactate) and physiologic (temperature, heart rate, mean blood pressure, and pulse oximetry) variables in the first postoperative day. Cerebral and flank rSO2 were strongly correlated with ScvO2, in both cyanotic or acyanotic patients and single- or two-ventricle physiology with and without aortic arch obstruction (all p.001). However, individual values had wide limits of agreement on Bland-Altman analysis. The correlations of change in these measurements were weaker but still significant (all p.0001), again with wide limits of agreement. Similar direction of change in cerebral rSO2 and ScvO2 was present 64% (95% confidence interval, 55-73%) of the time. Change in arterial pressure of carbon dioxide (delta PaCO2) was associated with cerebral delta rSO2 (delta PaCO2 beta = 0.35, p.0001) but not flank delta rSO2 or delta ScvO2. A pattern of relative cerebral desaturation (flank rSO2cerebral rSO2) was noted in a majority of patients (81%) with two-site monitoring regardless of bypass method or age.Neither individual values nor changes in rSO2 are interchangeable measures of ScvO2 in postoperative pediatric cardiac patients. The unique relationship between changes in PaCO2 and cerebral rSO2 supports the hypothesis that cerebral near-infrared spectroscopy monitors regional cerebral oxygenation. Clinical application of this monitor must include recognition of the clinical variables that affect regional brain oxygenation.

To describe the effects of prone positioning on airway management, mechanical ventilation, enteral nutrition, pain and sedation management, and staff utilization in infants and children with acute lung injury.Secondary analysis of data collected in a multiple-center, randomized, controlled clinical trial of supine vs. prone positioning.Seven pediatric intensive care units located in the United States.One hundred and two pediatric patients (51 prone and 51 supine) with acute lung injury.Patients randomized to the supine group remained supine. Patients randomized to the prone group were positioned prone per protocol during the acute phase of their illness for a maximum of 7 days. Both groups were managed using ventilator and sedation protocols and nutrition and skin care guidelines.Airway management and mechanical ventilatory variables before and after repositioning, enteral nutrition management, pain and sedation management, staff utilization, and adverse event data were collected for up to 28 days after enrollment. There were a total of 202 supine-prone-supine cycles. There were no differences in the incidence of endotracheal tube leak between the two groups (p = .30). Per protocol, 95% of patients remained connected to the ventilator during repositioning. The inadvertent extubation rate was 0.85 for the prone group and 1.03 for the supine group per 100 ventilator days (p = 1.00). There were no significant differences in the initiation of trophic (p = .24), advancing (p = .82), or full enteral feeds (p = .80) between the prone and supine groups; in the average pain (p = .81) and sedation (p = .18) scores during the acute phase; and in the amount of comfort medications received between the two groups (p = .91). There were no critical events during a turn procedure. While prone, two patients experienced an obstructed endotracheal tube. One patient, supported on high-frequency oscillatory ventilation, experienced persistent hypercapnea when prone and was withdrawn from the study. The occurrence of pressure ulcers was similar between the two groups (p = .71). Compared with the supine group, more staff (p/= .001) and more time were necessary to reposition patients in the prone group.Our data show that prone positioning can be safely performed in critically ill pediatric patients and that these patients can be safely managed while in the prone position for prolonged periods of time.

ContextIn uncontrolled clinical studies, prone positioning appeared to be safe and to improve oxygenation in pediatric patients with acute lung injury. However, the effect of prone positioning on clinical outcomes in children is not known.ObjectiveTo test the hypothesis that at the end of 28 days infants and children with acute lung injury treated with prone positioning would have more ventilator-free days than those treated with supine positioning.Design, Setting, and PatientsMulticenter, randomized, controlled clinical trial conducted from August 28, 2001, to April 23, 2004, of 102 pediatric patients from 7 US pediatric intensive care units aged 2 weeks to 18 years who were treated with supine vs prone positioning. Randomization was concealed and group assignment was not blinded.InterventionPatients were randomized to either supine or prone positioning within 48 hours of meeting acute lung injury criteria, with those patients in the prone group being positioned within 4 hours of randomization and remaining prone for 20 hours each day during the acute phase of their illness for a maximum of 7 days, after which they were positioned supine. Both groups were treated using lung protective ventilator and sedation protocols, extubation readiness testing, and hemodynamic, nutrition, and skin care guidelines.Main Outcome MeasureVentilator-free days to day 28.ResultsThe trial was stopped at the planned interim analysis on the basis of the prespecified futility stopping rule. There were no differences in the number of ventilator-free days between the 2 groups (mean [SD], 15.8 [8.5] supine vs 15.6 [8.6] prone; mean difference, −0.2 days; 95% CI, −3.6 to 3.2; P = .91). After controlling for age, Pediatric Risk of Mortality III score, direct vs indirect acute lung injury, and mode of mechanical ventilation at enrollment, the adjusted difference in ventilator-free days was 0.3 days (95% CI, −3.0 to 3.5; P = .87). There were no differences in the secondary end points, including proportion alive and ventilator-free on day 28 (P = .45), mortality from all causes (P>.99), the time to recovery of lung injury (P = .78), organ-failure−free days (P = .88), and cognitive impairment (P = .16) or overall functional health (P = .12) at hospital discharge or on day 28.ConclusionProne positioning does not significantly reduce ventilator-free days or improve other clinical outcomes in pediatric patients with acute lung injury.