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Objectives: To develop evidence-based recommendations for clinicians caring for children (including infants, school-aged children, and adolescents) with septic shock and other sepsis-associated organ dysfunction., Design: A panel of 49 international experts, representing 12 international organizations, as well as three methodologists and three public members was convened. Panel members assembled at key international meetings (for those panel members attending the conference), and a stand-alone meeting was held for all panel members in November 2018. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. Teleconferences and electronic-based discussion among the chairs, co-chairs, methodologists, and group heads, as well as within subgroups, served as an integral part of the guideline development process., Methods: The panel consisted of six subgroups: recognition and management of infection, hemodynamics and resuscitation, ventilation, endocrine and metabolic therapies, adjunctive therapies, and research priorities. We conducted a systematic review for each Population, Intervention, Control, and Outcomes question to identify the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak, or as a best practice statement. In addition, "in our practice" statements were included when evidence was inconclusive to issue a recommendation, but the panel felt that some guidance based on practice patterns may be appropriate., Results: The panel provided 77 statements on the management and resuscitation of children with septic shock and other sepsis-associated organ dysfunction. Overall, six were strong recommendations, 49 were weak recommendations, and nine were best-practice statements. For 13 questions, no recommendations could be made; but, for 10 of these, "in our practice" statements were provided. In addition, 52 research priorities were identified., Conclusions: A large cohort of international experts was able to achieve consensus regarding many recommendations for the best care of children with sepsis, acknowledging that most aspects of care had relatively low quality of evidence resulting in the frequent issuance of weak recommendations. Despite this challenge, these recommendations regarding the management of children with septic shock and other sepsis-associated organ dysfunction provide a foundation for consistent care to improve outcomes and inform future research.

Rationale: The ARDS Network (ARDSNet) used a positive end-expiratory pressure (PEEP)/Fi O 2 model in many studies. In general, pediatric intensivists use less PEEP and higher Fi O 2 than this model., Objectives: To evaluate whether children managed with PEEP lower than recommended by the ARDSNet PEEP/Fi O 2 model had higher mortality., Methods: This was a multicenter, retrospective analysis of patients with pediatric acute respiratory distress syndrome (PARDS) managed without a formal PEEP/Fi O 2 protocol. Four distinct datasets were combined for analysis. We extracted time-matched PEEP/Fi O 2 values, calculating the difference between PEEP level and the ARDSNet-recommended PEEP level for a given Fi O 2 . We analyzed the median difference over the first 24 hours of PARDS diagnosis against ICU mortality and adjusted for confounding variables, effect modifiers, or factors that may have affected the propensity to use lower PEEP., Measurements and Main Results: Of the 1,134 patients with PARDS, 26.6% were managed with lower PEEP relative to the amount of Fi O 2 recommended by the ARDSNet protocol. Patients managed with lower PEEP experienced higher mortality than those who were managed with PEEP levels in line with or higher than recommended by the protocol (P < 0.001). After adjustment for hypoxemia, inotropes, comorbidities, severity of illness, ventilator settings, nitric oxide, and dataset, PEEP lower than recommended by the protocol remained independently associated with higher mortality (odds ratio, 2.05; 95% confidence interval, 1.32-3.17). Findings were similar after propensity-based covariate adjustment (odds ratio, 2.00; 95% confidence interval, 1.24-3.22)., Conclusions: Patients with PARDS managed with lower PEEP relative to Fi O 2 than recommended by the ARDSNet model had higher mortality. Clinical trials targeting PEEP management in PARDS are needed.

Objectives: To examine the feasibility of deploying a virtual web service for sharing data within a research network, and to evaluate the impact on data consistency and quality., Material and Methods: Virtual machines (VMs) encapsulated an open-source, semantically and syntactically interoperable secure web service infrastructure along with a shadow database. The VMs were deployed to 8 Collaborative Pediatric Critical Care Research Network Clinical Centers., Results: Virtual web services could be deployed in hours. The interoperability of the web services reduced format misalignment from 56% to 1% and demonstrated that 99% of the data consistently transferred using the data dictionary and 1% needed human curation., Conclusions: Use of virtualized open-source secure web service technology could enable direct electronic abstraction of data from hospital databases for research purposes., (© The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Importance: Functional status assessment methods are important as outcome measures for pediatric critical care studies., Objective: To investigate the relationships between the 2 functional status assessment methods appropriate for large-sample studies, the Functional Status Scale (FSS) and the Pediatric Overall Performance Category and Pediatric Cerebral Performance Category (POPC/PCPC) scales., Design, Setting, and Participants: Prospective cohort study with random patient selection at 7 sites and 8 children's hospitals with general/medical and cardiac/cardiovascular pediatric intensive care units (PICUs) in the Collaborative Pediatric Critical Care Research Network. Participants included all PICU patients younger than 18 years., Main Outcomes and Measures: Functional Status Scale and POPC/PCPC scores determined at PICU admission (baseline) and PICU discharge. We investigated the association between the baseline and PICU discharge POPC/PCPC scores and the baseline and PICU discharge FSS scores, the dispersion of FSS scores within each of the POPC/PCPC ratings, and the relationship between the FSS neurologic components (FSS-CNS) and the PCPC., Results: We included 5017 patients. We found a significant (P < .001) difference between FSS scores in each POPC or PCPC interval, with an FSS score increase with each worsening POPC/PCPC rating. The FSS scores for the good and mild disability POPC/PCPC ratings were similar and increased by 2 to 3 points for the POPC/PCPC change from mild to moderate disability, 5 to 6 points for moderate to severe disability, and 8 to 9 points for severe disability to vegetative state or coma. The dispersion of FSS scores within each POPC and PCPC rating was substantial and increased with worsening POPC and PCPC scores. We also found a significant (P < .001) difference between the FSS-CNS scores between each of the PCPC ratings with increases in the FSS-CNS score for each higher PCPC rating., Conclusions and Relevance: The FSS and POPC/PCPC system are closely associated. Increases in FSS scores occur with each higher POPC and PCPC rating and with greater magnitudes of change as the dysfunction severity increases. However, the dispersion of the FSS scores indicated a lack of precision in the POPC/PCPC system when compared with the more objective and granular FSS. The relationship between the PCPC and the FSS-CNS paralleled the relationship between the FSS and POPC/PCPC system.

BACKGROUND: The ventilatory ratio (VR) is a dead-space marker associated with mortality in mechanically ventilated adults with ARDS. The end-tidal alveolar dead space fraction (AVDSf) has been associated with mortality in children. However, AVDSf requires capnography measurements, whereas VR does not. We sought to examine the prognostic value of VR, in comparison to AVDSf, in children and young adults with acute hypoxemic respiratory failure. METHODS: We conducted a retrospective study of prospectively collected data from 180 mechanically ventilated children and young adults with acute hypoxemic respiratory failure. VR was calculated as (minute ventilation x PaCO2)/(age-adjusted predicted minute ventilation x 37.5). AVDSf was calculated as (PaCO2 -- PETCO2)/PaCO2. RESULTS: VR and AVDSf had a moderate correlation (rho 0.31, P < .001). VR was similar between survivors at 1.22 (interquartile range [IQR] 1.0-1.52) and nonsurvivors at 1.30 (IQR 0.96-1.95) (P = .2). AVDSf was lower in survivors at 0.12 (IQR 0.03-0.23) than nonsurvivors at 0.24 (IQR 0.13-0.33) (P < .001). In logistic regression and competing risk regression analyses, VR was not associated with mortality or rate of extubation at any given time (competing risk death; all P > .3). An AVDSf in the highest 2 quartiles, in comparison to the lowest quartile (AVDSf < 0.06), was associated with higher mortality after adjustment for oxygenation index and severity of illness (AVDSf ≥ 0.15-0.26: odds ratio 3.58, 95% CI 1.02-12.64, P = .047, and AVDSf ≥ 0.26: odds ratio 3.91 95% CI-1.03-14.83, P = .045). At any given time after intubation, a child with an AVDSf ≥ 0.26 was less likely to be extubated than a child with an AVDSf < 0.06, after adjustment for oxygenation index and severity of illness (AVDSf ≥ 0.26: subdistribution hazard ratio 0.55, 95% CI 0.33-0.94, P = .03). CONCLUSIONS: VR should not be used for prognostic purposes in children and young adults. AVDSf added prognostic information to the severity of oxygenation defect and overall severity of illness in children and young adults, consistent with previous research. [ABSTRACT FROM AUTHOR]

Despite the accepted importance of minimizing time on mechanical ventilation, only limited guidance on weaning and extubation is available from the pediatric literature. A significant proportion of patients being evaluated for weaning are actually ready for extubation, suggesting that weaning is often not considered early enough in the course of ventilation. Indications for extubation are often not clear, although a trial of spontaneous breathing on CPAP without pressure support seems an appropriate prerequisite in many cases. Several indexes have been developed to predict weaning and extubation success, but the available literature suggests they offer little or no improvement over clinical judgment. New techniques for assessing readiness for weaning and predicting extubation success are being developed but are far from general acceptance in pediatric practice. While there have been some excellent physiologic, observational, and even randomized controlled trials on aspects of pediatric ventilator liberation, robust research data are lacking. Given the lack of data in many areas, a determined approach that combines systematic review with consensus opinion of international experts could generate high-quality recommendations and terminology definitions to guide clinical practice and highlight important areas for future research in weaning, extubation readiness, and liberation from mechanical ventilation following pediatric respiratory failure. [ABSTRACT FROM AUTHOR]

Introduction: Our objectives are to (1) describe the pathogens, site, timing and risk factors for acquired infection during neonatal and pediatric ECMO and (2) explore the association between acquired infection and mortality. Methods: Secondary analysis of prospective data collected by the Collaborative Pediatric Critical Care Research Network between December 2012 and September 2014. Clinical factors associated with acquired infection were assessed with multivariable Cox regression. Factors associated with mortality were assessed with logistic regression. Results: Of 481 patients, 247 (51.3%) were neonates and 400 (83.2%) received venoarterial ECMO. Eighty (16.6%) patients acquired one or more infections during ECMO; 60 (12.5%) patients had bacterial, 21 (4.4%) had fungal and 11 (2.3%) had viral infections. The site of infection included respiratory for 53 (11.0%) patients, bloodstream for 21 (4.4%), urine for 20 (4.2%) and other for 7 (1.5%). Candida species were most common. Median time to infection was 5.2 days (IQR 2.3, 9.6). On multivariable analysis, a greater number of procedures for ECMO cannula placement was independently associated with increased risk of acquired infection during ECMO (Hazard Ratio 2.13 (95% CI 1.22, 3.72), p<0.01) and receiving ECMO in a neonatal ICU compared to a pediatric or cardiac ICU was associated with decreased risk (Hazard Ratio pediatric ICU 4.25 (95% CI 2.20, 8.20), cardiac ICU 2.91 (95% CI 1.48, 5.71), neonatal ICU as reference, p<0.001). Acquired infection was not independently associated with mortality. Conclusion: ECMO procedures and location may contribute to acquired infection risk; however, acquired infection did not predict mortality in this study. [ABSTRACT FROM AUTHOR]

Rationale: The ARDS Network (ARDSNet) used a positive end-expiratory pressure (PEEP)/FIO2 model in many studies. In general, pediatric intensivists use less PEEP and higher FIO2 than this model. Objectives: To evaluate whether children managed with PEEP lower than recommended by the ARDSNet PEEP/FIO2 model had higher mortality. Methods: This was a multicenter, retrospective analysis of patients with pediatric acute respiratory distress syndrome (PARDS) managed without a formal PEEP/FIO2 protocol. Four distinct datasets were combined for analysis. We extracted time-matched PEEP/FIO2 values, calculating the difference between PEEP level and the ARDSNet-recommended PEEP level for a given FIO2. We analyzed the median difference over the first 24 hours of PARDS diagnosis against ICU mortality and adjusted for confounding variables, effect modifiers, or factors that may have affected the propensity to use lower PEEP. Measurements and Main Results: Of the 1,134 patients with PARDS, 26.6% were managed with lower PEEP relative to the amount of FIO2 recommended by the ARDSNet protocol. Patients managed with lower PEEP experienced higher mortality than those who were managed with PEEP levels in line with or higher than recommended by the protocol (P, 0.001). After adjustment for hypoxemia, inotropes, comorbidities, severity of illness, ventilator settings, nitric oxide, and dataset, PEEP lower than recommended by the protocol remained independently associated with higher mortality (odds ratio, 2.05; 95% confidence interval, 1.32-3.17). Findings were similar after propensity-based covariate adjustment (odds ratio, 2.00; 95% confidence interval, 1.24-3.22). Conclusions: Patients with PARDS managed with lower PEEP relative to FIO2 than recommended by the ARDSNet model had higher mortality. Clinical trials targeting PEEP management in PARDS are needed. [ABSTRACT FROM AUTHOR]

Background and Aims: The pediatric Critical Illness Stress-induced Immune Suppression (CRISIS) trial compared the effectiveness of 2 nutraceutical supplementation strategies and found no difference in the development of nosocomial infection and sepsis in the overall population. We performed an exploratory post hoc analysis of interaction between nutraceutical treatments and host immune status related to the development of nosocomial infection/sepsis.Methods: Children from the CRISIS trial were analyzed according to 3 admission immune status categories marked by decreasing immune competence: immune competent without lymphopenia, immune competent with lymphopenia, and previously immunocompromised. The comparative effectiveness of the 2 treatments was analyzed for interaction with immune status category.Results: There were 134 immune-competent children without lymphopenia, 79 previously immune-competent children with lymphopenia, and 27 immunocompromised children who received 1 of the 2 treatments. A significant interaction was found between treatment arms and immune status on the time to development of nosocomial infection and sepsis ( P < .05) and on the rate of nosocomial infection and sepsis per 100 patient days ( P < .05). Whey protein treatment protected immune-competent patients without lymphopenia from infection and sepsis, both nutraceutical strategies were equivalent in immune-competent patients with lymphopenia, and zinc, selenium, glutamine, and metoclopramide treatment protected immunocompromised patients from infection and sepsis.Conclusions: The science of immune nutrition is more complex than previously thought. Future trial design should consider immune status at the time of trial entry because differential effects of nutraceuticals may be related to this patient characteristic. [ABSTRACT FROM AUTHOR]

Ready access to physiologic measures, including respiratory mechanics, lung volumes, and ventilation/perfusion inhomogeneity, could optimize the clinical management of the critically ill pediatric or neonatal patient and minimize lung injury. There are many techniques for measuring respiratory function in infants and children but very limited information on the technical ease and applicability of these tests in the pediatric and neonatal intensive care unit (PICU, NICU) environments. This report summarizes the proceedings of a 2011 American Thoracic Society Workshop critically reviewing techniques available for ventilated and spontaneously breathing infants and children in the ICU. It outlines for each test how readily it is performed at the bedside and how it may impact patient management as well as indicating future areas of potential research collaboration. From expert panel discussions and literature reviews, we conclude that many of the techniques can aid in optimizing respiratory support in the PICU and NICU, quantifying the effect of therapeutic interventions, and guiding ventilator weaning and extubation. Most techniques now have commercially available equipment for the PICU and NICU, and many can generate continuous data points to help with ventilator weaning and other interventions. Technical and validation studies in the PICU and NICU are published for the majority of techniques; some have been used as outcome measures in clinical trials, but few have been assessed specifically for their ability to improve clinical outcomes. Although they show considerable promise, these techniques still require further study in the PICU and NICU together with increased availability of commercial equipment before wider incorporation into daily clinical practice. [ABSTRACT FROM AUTHOR]

Rationale: Subglottic edema is the most common cause of pediatric extubation failure, but few studies have confirmed risk factors or prevention strategies. This may be due to subjective assessment of stridor or inability to differentiate supraglottic from subglottic disease.Objectives: Objective 1 was to assess the utility of calibrated respiratory inductance plethysmography (RIP) and esophageal manometry to identify clinically significant post-extubation upper airway obstruction (UAO) and differentiate subglottic from supraglottic UAO. Objective 2 was to identify risk factors for subglottic UAO, stratified by cuffed versus uncuffed endotracheal tubes (ETTs).Methods: We conducted a single-center prospective study of children receiving mechanical ventilation. UAO was defined by inspiratory flow limitation (measured by RIP and esophageal manometry) and classified as subglottic or supraglottic based on airway maneuver response. Clinicians performed simultaneous blinded clinical UAO assessment at the bedside.Measurements and Main Results: A total of 409 children were included, 98 of whom had post-extubation UAO and 49 (12%) of whom were subglottic. The reintubation rate was 34 (8.3%) of 409, with 14 (41%) of these 34 attributable to subglottic UAO. Five minutes after extubation, RIP and esophageal manometry better identified patients who subsequently received UAO treatment than clinical UAO assessment (P < 0.006). Risk factors independently associated with subglottic UAO included low cuff leak volume or high preextubation leak pressure, poor sedation, and preexisting UAO (P < 0.04) for cuffed ETTs; and age (range, 1 mo to 5 yr) for uncuffed ETTs (P < 0.04). For uncuffed ETTs, the presence or absence of preextubation leak was not associated with subglottic UAO.Conclusions: RIP and esophageal manometry can objectively identify subglottic UAO after extubation. Using this technique, preextubation leak pressures or cuff leak volumes predict subglottic UAO in children, but only if the ETT is cuffed. [ABSTRACT FROM AUTHOR]

BACKGROUND: Volumetric capnography dead-space measurements (physiologic dead-space-to-tidal-volume ratio [VD/VT] and alveolar VD/VT) are considered more accurate than the more readily available time-based capnography dead-space measurement (end-tidal alveolar dead-space fraction [AVDSF]). We sought to investigate the correlation between volumetric capnography and time-based capnography dead-space measurements. METHODS: This was a single-center prospective cohort study of 65 mechanically ventilated children with arterial lines. Physiologic VD/VT, alveolar VD/VT, and AVDSF were calculated with each arterial blood gas using capnography data. RESULTS: We analyzed 534 arterial blood gases from 65 children (median age 4.9 y, interquartile range 1.7-12.8). The correlation between physiologic VD/VT and AVDSF (r = 0.66, 95% Cl 0.59-0.72) was weaker than the correlation between alveolar VD/VT and AVDSF (r = 0.8, 95% Cl 0.76-0.85). The correlation between physiologic VD/VT and AVDSF was weaker in children with low ... (< 200 mm Hg), low exhaled VT (< 100 mL), a pulmonary reason for mechanical ventilation, or large airway VD (> 3 mL/kg). All 3 dead-space measurements were highly correlated (r > 0.7) in children without hypoxemia (... > 300 mm Hg), mechanically ventilated for a neurologic or cardiac reason, or on significant inotropes or vasopressors. CONCLUSIONS: In mechanically ventilated children without significant hypoxemia or with cardiac output-related dead-space changes, physiologic VD/VT was highly correlated with AVDSF and alveolar VD/VT. In children with significant hypoxemia, physiologic VD/VT was poorly correlated with AVDSF. Alveolar VD/VT and AVDSF correlated well in most tested circumstances. Therefore, AVDSF may be useful in most children for alveolar dead-space monitoring. [ABSTRACT FROM AUTHOR]

BACKGROUND: Ventilator management for children with hypoxemic respiratory failure may benefit from ventilator protocols, which rely on blood gases. Accurate noninvasive estimates for pH or PaCO2 could allow frequent ventilator changes to optimize lung-protective ventilation strategies. If these models are highly accurate, they can facilitate the development of closed-loop ventilator systems. We sought to develop and test algorithms for estimating pH and PaCO2 from measures of ventilator support, pulse oximetry, and end-tidal carbon dioxide pressure (PETCO2). We also sought to determine whether surrogates for changes in dead space can improve prediction. METHODS: Algorithms were developed and tested using 2 data sets from previously published investigations. A baseline model estimated pH and PaCO2 from PETCO2 using the previously observed relationship between PETCO2 and PaCO2 or pH (using the Henderson-Hasselbalch equation). We developed a multivariate gaussian process (MGP) model incorporating other available noninvasive measurements. RESULTS: The training data set had 2,386 observations from 274 children, and the testing data set had 658 observations from 83 children. The baseline model predicted PaCO2 within ± mm Hg of the observed PaCO2 80% of the time. The MGP model improved this to ± 6 mm Hg. When the MGP model predicted PaCO2 between 35 and 60 mm Hg, the 80% prediction interval narrowed to ± 5 mm Hg. The baseline model predicted pH within 0.07 of the observed pH 80% of the time. The MGP model improved this to ± 0.05. CONCLUSIONS: We have demonstrated a conceptual first step for predictive models that estimate pH and PaCO2 to facilitate clinical decision making for children with lung injury. These models may have some applicability when incorporated in ventilator protocols to encourage practitioners to maintain permissive hypercapnia when using high ventilator support. Refinement with additional data may improve model accuracy. [ABSTRACT FROM AUTHOR]

OBJECTIVE: For children with cyanotic congenital heart disease or acute hypoxemic respiratory failure, providers frequently make decisions based on pulse oximetry, in the absence of an arterial blood gas. The study objective was to measure the accuracy of pulse oximetry in the saturations from pulse oximetry (SpO2) range of 65% to 97%. METHODS: This institutional review board-approved prospective, multicenter observational study in 5 PICUs included 225 mechanically ventilated children with an arterial catheter. With each arterial blood gas sample, SpO2 from pulse oximetry and arterial oxygen saturations from CO-oximetry (SaO2) were simultaneously obtained if the SpO2 was ≤97%. RESULTS: The lowest SpO2 obtained in the study was 65%. In the range of SpO2 65% to 97%, 1980 simultaneous values for SpO2 and SaO2 were obtained. The bias (SpO2 - SaO2) varied through the range of SpO2 values. The bias was greatest in the SpO2 range 81% to 85% (336 samples, median 6%, mean 6.6%, accuracy root mean squared 9.1%). SpO2 measurements were close to SaO2 in the SpO2 range 91% to 97% (901 samples, median 1%, mean 1.5%, accuracy root mean squared 4.2%). CONCLUSIONS: Previous studies on pulse oximeter accuracy in children present a single number for bias. This study identified that the accuracy of pulse oximetry varies significantly as a function of the SpO2 range. Saturations measured by pulse oximetry on average overestimate SaO2 from CO-oximetry in the SpO2 range of 76% to 90%. Better pulse oximetry algorithms are needed for accurate assessment of children with saturations in the hypoxemic range. [ABSTRACT FROM AUTHOR]

Purpose: The purposes of the study are to determine the interobserver variability in the clinical assessment of pediatric upper airway obstruction (UAO) and to explore how variability in assessment of UAO may contribute to risk factors and incidence of postextubation UAO. Materials: This is a prospective trial in 2 tertiary care pediatric intensive care units. Bedside practitioners performed simultaneous, blinded UAO assessments on 112 children after endotracheal extubation. Results: Agreement among respiratory therapists, pediatric intensive care nurses, and pediatric intensive care physicians was poor for cyanosis (κ = 0.01) and hypoxemia at rest (κ = 0.14) and fair for consciousness (κ = 0.27), air entry (κ = 0.32), hypoxemia with agitation (κ = 0.27), and pulsus paradoxus (κ = 0.23). When looking at “stridor” and “retractions,” defined using more than 2 grades of severity from the Westley Croup Score, the interrelater reliability was moderate (κ = 0.43 and κ = 0.47, respectively). This could be improved marginally by dichotomizing the presence or absence of stridor (κ = 0.54) or retractions (κ = 0.53). The overall incidence of UAO after extubation (stridor plus retractions) could range from 7% to 22%, depending on how many providers were required to agree. Conclusions: Physical findings routinely used for UAO have poor interobserver reliability among bedside providers. This variability may contribute to inconsistent findings regarding incidence, risk factors, and therapies for postextubation UAO. [ABSTRACT FROM AUTHOR]

Through discourse analysis of transcribed interviews conducted over the phone with parents whose child died in the Pediatric Intensive Care Unit (PICU) (n = 51), this study uncovers parents' perceptions of clinicians' and their own communicative roles and responsibilities in the context of team-based care. We examine parents' descriptions and narratives of communicative experiences they had with PICU clinicians, focusing on how parents use accounts to evaluate the communicative behaviors they report (n = 47). Findings indicate that parental perceptions of communicative responsibilities are more nuanced than assumed in previous research: Parents identified their own responsibilities as participating as part of the team of care, gathering information, interacting with appropriate affect, and working to understand complex and uncertain medical information. Complementarily, parents identified clinician responsibilities as communicating professionally, providing medical information clearly, managing parents' hope responsibly, and communicating with appropriate affect. Through the accounts they provide, parents evaluate both parental and clinician role-responsibilities as fulfilled and unfulfilled. Clinicians' management of prognostic uncertainty and parents' struggles to understand that uncertainty emerged as key, complementary themes with practical implications for incorporating parents into the PICU care team. The study also highlights insights retrospective interview data bring to the examination of medical communication. [ABSTRACT FROM AUTHOR]

The article examines the difference between pulse oximetric saturation/fraction of oxygen ratio and the Pao2/fraction (PF) of inspired oxygen ratio in children. Methodology-wise, the researchers queried blood gas measurements from tertiary care pediatric intensive care units (PICU). Based on the results, they concluded that saturation/fraction (SF) ration is a reliable nonivasive marker for PF ratio.

Background: Multicenter research has the potential to recruit participants with diverse racial, ethnic, and geographic backgrounds and is essential for understanding heterogeneity in bereavement. The National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network (CPCCRN) is a multicenter network charged with conducting research on the pathophysiology and management of critical illness in childhood. Among its research activities, the CPCCRN has undertaken research in parental bereavement because most childhood deaths in the United States occur in hospitals, primarily in critical care units. Objective: The purpose of this paper is to discuss ethical and logistical issues found by the CPCCRN to be problematic to multicenter research with bereaved parents and to explore research strategies that may be practicably implemented. Results: Ethical and logistical challenges encountered by the CPCCRN included issues of privacy; confidentiality; voluntariness; minimizing risks; working with multiple institutional review boards; researcher qualifications, training and support; and methods of data collection. Strategies to address these challenges included local recruitment of participants; flexibility in consent methods across sites; participant options for methods of data collection; involvement of local bereavement support services; central training of researchers with systematic monitoring and opportunitieas for support; and use of a secure Web-based collaborative workspace. Conclusions: Multicenter parental bereavement research has distinct ethical issues that must be addressed by the logistics of the research plan. Greater attention to the issues identified may facilitate research to reduce adverse mental and physical health outcomes in a diverse population of bereaved individuals. [ABSTRACT FROM AUTHOR]

Objectives: Children with peripheral airways obstruction suffer the negative effects of intrinsic positive end-expiratory pressure: increased work of breathing and difficulty triggering assisted ventilatory support. We examined whether external positive end-expiratory pressure to offset intrinsic positive end-expiratory pressure decreases work of breathing in children with peripheral airways obstruction. The change in work of breathing with incremental pressure support was also tested.Design and Setting: Prospective clinical trial in a pediatric intensive care unit.Patients: Eleven mechanically ventilated, spontaneously breathing children with peripheral airways obstruction.Interventions: Work of breathing (using pressure-rate product as a surrogate) was measured in three tiers: (a) Increasing pressure support over zero end-expiratory pressure. (b) Increasing applied positive end-expiratory pressure and fixed pressure support. The level of applied positive end-expiratory pressure at which pressure-rate product was least determined the compensatory positive end-expiratory pressure. (c) Increasing pressure support over compensatory (fixed) positive end-expiratory pressure.Measurements and Results: Increases in pressure support alone decreased pressure-rate product from mean 724+/-311 to 403+/-192 cmH2O/min. Applied positive end-expiratory pressure alone decreased pressure-rate product from mean 608+/-301 to 250+/-169 cmH2O/min. The lowest pressure-rate product (136+/-128 cmH2O/min) was achieved using compensatory positive end-expiratory pressure (12+/-4 cmH2O) with pressure support 16 cmH2O.Conclusions: For children with peripheral airways obstruction who require assisted ventilation, work of breathing during spontaneous breaths is decreased by the application of either compensatory positive end-expiratory pressure or pressure support. [ABSTRACT FROM AUTHOR]

Objective: To compare the pressure-rate products and phase angles of children during minimal support ventilation and after extubation.Design and Setting: Prospective, randomized single-center trial in a pediatric intensive care unit in a tertiary children's hospital.Methods: Seventeen endotracheally intubated, mechanically ventilated children were placed on T-piece, T-piece with heliox, continuous positive airway pressure, and pressure support in random order. Esophageal pressure swings, phase angles, respiratory mechanics, and physiological parameters were measured on these modes and after extubation.Measurements and Results: Pressure-rate product postextubation was significantly higher than on support modes. For each mode and after extubation they were: pressure support 198+/-31, continuous positive airway pressure 237+/-30, T-piece 323+/-47, T-piece/heliox 308+/-61, and extubation 378+/-43 cmH2O/min. Phase angles were significantly higher during T-piece ventilation than pressure support but not did not differ significantly from postextubation.Conclusions: Assessment of effort of breathing during even minimal mechanical ventilation may underestimate postextubation effort in children. Postextubation pressure-rate product and hence "effort of breathing" in children is best approximated by T-piece ventilation. [ABSTRACT FROM AUTHOR]

A response from the authors of an article about pressure support during pediatric extubation readiness testing is presented.

BACKGROUND AND OBJECTIVES: Childhood obesity is epidemic and may be associated with PICU mortality. Using a large multicenter PICU database, we investigated the association between obesity and PICU mortality, adjusting for initial severity of illness. We further investigated whether height- and weight-based classifications of obesity compared with a weight-based classification alone alter the mortality distribution. METHODS: This retrospective analysis used prospectively collected data from the Virtual PICU Systems database. Height, weight, age, and gender were used to calculate z score groups based on Centers for Disease Control and Prevention and World Health Organization growth curves. A random effects mixed logistic regression model was used to evaluate the association between obesity and PICU mortality, controlling for hospital, initial severity of illness, and comorbidities. RESULTS: A total of 127 607 patients were included; the mortality rate was 2.48%. Being overweight was independently associated with increased PICU mortality after controlling for severity of illness with the Pediatric Index of Mortality 2 score and preexisting comorbidities. Mortality had a U-shaped distribution when classified according to weight-for-age or weight-for-height/BMI. When classifying patients using weight-for-age without respect to height, the nadir of the mortality curve was shifted, potentially falsely implying a benefit to mild obesity. CONCLUSIONS: Risk-adjusted PICU mortality significantly increases as weight-for-height/BMI increases into the overweight and obese ranges. We believe that height data are necessary to correctly classify body habitus; without such information, a protective benefit from mild obesity may be incorrectly concluded. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the association between inhaled nitric oxide treatment and ICU mortality and 28-day ventilator-free days in pediatric acute respiratory distress syndrome.Design: Retrospective cohort study. A propensity score for inhaled nitric oxide treatment was developed and used in the analysis.Setting: Two quaternary care PICUs.Patients: Children with pediatric acute respiratory distress syndrome.Interventions: None.Measurements and Main Results: There were 499 children enrolled in this study with 143 (28.7%) receiving inhaled nitric oxide treatment. Children treated with inhaled nitric oxide were more likely to have a primary diagnosis of pneumonia (72% vs 54.8%; p < 0.001), had a higher initial oxygenation index (median 16.9 [interquartile range, 10.1-27.3] vs 8.5 [interquartile range, 5.8-12.2]; p < 0.001), and had a higher 72-hour maximal Vasoactive-Inotrope Score (median 15 [interquartile range, 6-25] vs 8 [interquartile range, 0-17.8]; p < 0.001) than those not receiving inhaled nitric oxide. Mortality was higher in the inhaled nitric oxide treatment group (25.2% vs 16.3%; p = 0.02), and children in this group had fewer 28-day ventilator-free days (10 d [interquartile range, 0-18 d] vs 17 d (interquartile range 5.5-22 d]; p < 0.0001). We matched 176 children based on propensity score for inhaled nitric oxide treatment. In the matched cohort, inhaled nitric oxide treatment was not associated with mortality (odds ratio, 1.3 [95% CI, 0.56-3.0]) or 28-day ventilator-free days (incidence rate ratio, 0.91 [95% CI, 0.80-1.04]). These results remained consistent in the entire study cohort when the propensity score for inhaled nitric oxide treatment was used for either inverse probability weighting or stratification in regression modeling with the exception that subjects treated with inhaled nitric oxide were more likely to have 0 ventilator-free days (p ≤ 0.02). In secondary analysis stratified by oxygenation response, inhaled nitric oxide treatment was not associated with mortality or 28-day ventilator-free days in children with a positive oxygenation response (all p > 0.2) CONCLUSIONS:: Treatment with inhaled nitric oxide in pediatric acute respiratory distress syndrome is not associated with improvement in either mortality or ventilator-free days and may be associated with harm. Further prospective trials are required to define the role of inhaled nitric oxide treatment in pediatric acute respiratory distress syndrome. [ABSTRACT FROM AUTHOR]

Background: Early identification of children at risk for cardiac arrest would allow for skill training associated with improved outcomes and provides a prevention opportunity.Objective: Develop and assess a predictive model for cardiopulmonary arrest using data available in the first 4 h.Methods: Data from PICU patients from 8 institutions included descriptive, severity of illness, cardiac arrest, and outcomes.Results: Of the 10074 patients, 120 satisfying inclusion criteria sustained a cardiac arrest and 67 (55.9%) died. In univariate analysis, patients with cardiac arrest prior to admission were over 6 times and those with cardiac arrests during the first 4 h were over 50 times more likely to have a subsequent arrest. The multivariate logistic regression model performance was excellent (area under the ROC curve = 0.85 and Hosmer-Lemeshow statistic, p = 0.35). The variables with the highest odds ratio's for sustaining a cardiac arrest in the multivariable model were admission from an inpatient unit (8.23 (CI: 4.35-15.54)), and cardiac arrest in the first 4 h (6.48 (CI: 2.07-20.36). The average risk predicted by the model was highest (11.6%) among children sustaining an arrest during hours >4-12 and continued to be high even for days after the risk assessment period; the average predicted risk was 9.5% for arrests that occurred after 8 PICU days.Conclusions: Patients at high risk of cardiac arrest can be identified with routinely available data after 4 h. The cardiac arrest may occur relatively close to the risk assessment period or days later. [ABSTRACT FROM AUTHOR]

Objective: Respiratory muscle weakness frequently develops during mechanical ventilation, although in children there are limited data about its prevalence and whether it is associated with extubation outcomes. We sought to identify risk factors for pediatric extubation failure, with specific attention to respiratory muscle strength.Design: Secondary analysis of prospectively collected data.Setting: Tertiary care PICU.Patients: Four hundred nine mechanically ventilated children.Interventions: Respiratory measurements using esophageal manometry and respiratory inductance plethysmography were made preextubation during airway occlusion and on continuous positive airway pressure of 5 and pressure support of 10 above positive end-expiratory pressure 5 cm H2O, as well as 5 and 60 minutes postextubation.Measurements and Main Results: Thirty-four patients (8.3%) were reintubated within 48 hours of extubation. Reintubation risk factors included lower maximum airway pressure during airway occlusion (aPiMax) preextubation, longer length of ventilation, postextubation upper airway obstruction, high respiratory effort postextubation (pressure rate product, pressure time product, tension time index), and high postextubation phase angle. Nearly 35% of children had diminished respiratory muscle strength (aPiMax ≤ 30 cm H2O) at the time of extubation, and were nearly three times more likely to be reintubated than those with preserved strength (aPiMax > 30 cm H2O; 14% vs 5.5%; p = 0.006). Reintubation rates exceeded 20% when children with low aPiMax had moderately elevated effort after extubation (pressure rate product > 500), whereas children with preserved aPiMax had reintubation rates greater than 20% only when postextubation effort was very high (pressure rate product > 1,000). When children developed postextubation upper airway obstruction, reintubation rates were 47.4% for those with low aPiMax compared to 15.4% for those with preserved aPiMax (p = 0.02). Multivariable risk factors for reintubation included acute neurologic disease, lower aPiMax, postextubation upper airway obstruction, higher preextubation positive end-expiratory pressure, higher postextubation pressure rate product, and lower height.Conclusions: Neuromuscular weakness at the time of extubation was common in children and was independently associated with reintubation, particularly when postextubation effort was high. [ABSTRACT FROM AUTHOR]

Objectives: To determine the incidence of cardiopulmonary resuscitation in PICUs and subsequent outcomes.Design, Setting, and Patients: Multicenter prospective observational study of children younger than 18 years old randomly selected and intensively followed from PICU admission to hospital discharge in the Collaborative Pediatric Critical Care Research Network December 2011 to April 2013.Results: Among 10,078 children enrolled, 139 (1.4%) received cardiopulmonary resuscitation for more than or equal to 1 minute and/or defibrillation. Of these children, 78% attained return of circulation, 45% survived to hospital discharge, and 89% of survivors had favorable neurologic outcomes. The relative incidence of cardiopulmonary resuscitation events was higher for cardiac patients compared with non-cardiac patients (3.4% vs 0.8%, p <0.001), but survival rate to hospital discharge with favorable neurologic outcome was not statistically different (41% vs 39%, respectively). Shorter duration of cardiopulmonary resuscitation was associated with higher survival rates: 66% (29/44) survived to hospital discharge after 1-3 minutes of cardiopulmonary resuscitation versus 28% (9/32) after more than 30 minutes (p < 0.001). Among survivors, 90% (26/29) had a favorable neurologic outcome after 1-3 minutes versus 89% (8/9) after more than 30 minutes of cardiopulmonary resuscitation.Conclusions: These data establish that contemporary PICU cardiopulmonary resuscitation, including long durations of cardiopulmonary resuscitation, results in high rates of survival-to-hospital discharge (45%) and favorable neurologic outcomes among survivors (89%). Rates of survival with favorable neurologic outcomes were similar among cardiac and noncardiac patients. The rigorous prospective, observational study design avoided the limitations of missing data and potential selection biases inherent in registry and administrative data. [ABSTRACT FROM AUTHOR]

Objective: Elevated dead space has been consistently associated with increased mortality in adults with respiratory failure. In children, the evidence for this association is more limited. We sought to investigate the association between dead space and mortality in mechanically ventilated children.Design: Single-center retrospective review.Setting: Tertiary care pediatric critical care unit.Patients: Seven hundred twelve mechanically ventilated children with an arterial catheter.Interventions: None.Measurements and Main Results: The end-tidal alveolar dead space fraction ((PaCO2-PETCO2)/PaCO2), a dead space marker, was calculated with each arterial blood gas. The initial end-tidal alveolar dead space fraction (first arterial blood gas after intubation) (per 0.1 unit increase: odds ratio, 1.59; 95% CI, 1.40-1.81) and day 1 mean end-tidal alveolar dead space fraction (odds ratio, 1.95; 95% CI, 1.66-2.30) were associated with mortality. The relationship between both initial and day 1 mean end-tidal alveolar dead space fraction and mortality held in multivariate modeling after controlling for any of the following individually: PaO2/FIO2, oxygenation index, 24-hour maximal inotrope score, and Pediatric Risk of Mortality III (all p<0.01), although end-tidal alveolar dead space fraction was no longer significant after controlling for the combination of oxygenation index, 24-hour maximal inotrope score, and Pediatric Risk of Mortality III. In 217 children with acute hypoxemic respiratory failure, initial end-tidal alveolar dead space fraction (per 0.1 unit increase odds ratio, 1.38; 95% CI, 1.14-1.67) and day 1 mean end-tidal alveolar dead space fraction (per 0.1 unit increase odds ratio, 1.60; 95% CI, 1.27-2.0) were associated with mortality. Day 1 mean end-tidal alveolar dead space fraction remained associated with mortality after controlling individually for any of the following in multivariate models: PaO2/FIO2, oxygenation index, and 24-hour maximal inotrope score (p≤0.02), although end-tidal alveolar dead space fraction was no longer significant after controlling for the combination of oxygenation index, 24-hour maximal inotrope score, and Pediatric Risk of Mortality III.Conclusions: Increased dead space is associated with higher mortality in critically ill children, although it is no longer independently associated with mortality after controlling for severity of oxygenation defect, inotrope use, and severity of illness. However, because end-tidal alveolar dead space fraction is easy to calculate at the bedside, it may be useful for risk stratification and severity-of-illness scores. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Assessments of care including quality assessments adjusted for physiological status should include the development of new morbidities as well as mortalities. We hypothesized that morbidity, like mortality, is associated with physiological dysfunction and could be predicted simultaneously with mortality. DESIGN: Prospective cohort study from December 4, 2011, to April 7, 2013. SETTING: General and cardiac/cardiovascular PICUs at seven sites. PATIENTS: Randomly selected PICU patients from their first PICU admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 10,078 admissions, the unadjusted morbidity rates (measured with the Functional Status Scale and defined as an increase of >= 3 from preillness to hospital discharge) were 4.6% (site range, 2.6-7.7%) and unadjusted mortality rates were 2.7% (site range, 1.3-5.0%). Morbidity and mortality were significantly (p < 0.001) associated with physiological instability (measured with the Pediatric Risk of Mortality III score) in dichotomous (survival and death) and trichotomous (survival without new morbidity, survival with new morbidity, and death) models without covariate adjustments. Morbidity risk increased with increasing Pediatric Risk of Mortality III scores and then decreased at the highest Pediatric Risk of Mortality III values as potential morbidities became mortalities. The trichotomous model with covariate adjustments included age, admission source, diagnostic factors, baseline Functional Status Scale, and the Pediatric Risk of Mortality III score. The three-level goodness-of-fit test indicated satisfactory performance for the derivation and validation sets (p > 0.20). Predictive ability assessed with the volume under the surface was 0.50 ± 0.019 (derivation) and 0.50 ± 0.034 (validation) (vs chance performance = 0.17). Site-level standardized morbidity ratios were more variable than standardized mortality ratios. CONCLUSIONS: New morbidities were associated with physiological status and can be modeled simultaneously with mortality. Trichotomous outcome models including both morbidity and mortality based on physiological status are suitable for research studies and quality and other outcome assessments. This approach may be applicable to other assessments presently based only on mortality. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the feasibility and perceived benefits of conducting physician-parent follow-up meetings after a child's death in the PICU according to a framework developed by the Collaborative Pediatric Critical Care Research Network. Design: Prospective observational study. Setting: Seven Collaborative Pediatric Critical Care Research Network-affiliated children's hospitals. Subjects: Critical care attending physicians, bereaved parents, and meeting guests (i.e., parent support persons, other health professionals). Interventions: Physician-parent follow-up meetings using the Collaborative Pediatric Critical Care Research Network framework. Measurements and Main Results: Forty-six critical care physicians were trained to conduct follow-up meetings using the framework. All meetings were video recorded. Videos were evaluated for the presence or absence of physician behaviors consistent with the framework. Present behaviors were evaluated for performance quality using a 5-point scale (1 = low, 5 = high). Participants completed meeting evaluation surveys. Parents of 194 deceased children were mailed an invitation to a follow-up meeting. Of these, one or both parents from 39 families (20%) agreed to participate, 80 (41%) refused, and 75 (39%) could not be contacted. Of 39 who initially agreed, three meetings were canceled due to conflicting schedules. Thirty-six meetings were conducted including 54 bereaved parents, 17 parent support persons, 23 critical care physicians, and 47 other health professionals. Physician adherence to the framework was high; 79% of behaviors consistent with the framework were rated as present with a quality score of 4.3 ±0.2. Of 50 evaluation surveys completed by parents, 46 (92%) agreed or strongly agreed the meeting was helpful to them and 40 (89%) to others they brought with them. Of 36 evaluation surveys completed by critical care physicians (i.e., one per meeting), 33 (92%) agreed or strongly agreed the meeting was beneficial to parents and 31 (89%) to them. Conclusions: Follow-up meetings using the Collaborative Pediatric Critical Care Research Network framework are feasible and viewed as beneficial by meeting participants. Future research should evaluate the effects of follow-up meetings on bereaved parents' health outcomes. [ABSTRACT FROM AUTHOR]

The article discusses a study which validated the comparability of SpO2F102 to PaO2F102 and oxygen saturation index to oxygenation index in children with acute lung injury. The study concluded that lung injury severity markers are adequate surrogate markers for PaO2 in children with respiratory failure.