Using an Audience Response System Smartphone App to Improve Resident Education in the Pediatric Intensive Care Unit.

In the Pediatric Intensive Care Unit (PICU), most teaching occurs during bedside rounds, but technology now provides new opportunities to enhance education. Specifically, smartphone apps allow rapid communication between instructor and student. We hypothesized that using an audience response system (ARS) app can identify resident knowledge gaps, guide teaching, and enhance education in the PICU. Third-year pediatric residents rotating through the PICU participated in ARS-based education or received traditional teaching. Before rounds, experimental subjects completed an ARS quiz using the Socrative app. Concomitantly, the fellow leading rounds predicted quiz performance. Then, discussion points based on the incorrect answers were used to guide instruction. Scores on the pre-rotation test were similar between groups. On the post-rotation examination, ARS participants did not increase their scores more than controls. The fellow's prediction of performance was poor. Residents felt that the method enhanced their education whereas fellows reported that it improved their teaching efficiency. Although there was no measurable increase in knowledge using the ARS app, it may still be a useful tool to rapidly assess learners and help instructors provide learner-centered education.

Hyperchloremia Is Associated With Complicated Course and Mortality in Pediatric Patients With Septic Shock.

OBJECTIVE: Hyperchloremia is associated with poor outcome among critically ill adults, but it is unknown if a similar association exists among critically ill children. We determined if hyperchloremia is associated with poor outcomes in children with septic shock. DESIGN: Retrospective analysis of a pediatric septic shock database. SETTING: Twenty-nine PICUs in the United States. PATIENTS: Eight hundred ninety children 10 years and younger with septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We considered the minimum, maximum, and mean chloride values during the initial 7 days of septic shock for each study subject as separate hyperchloremia variables. Within each category, we considered hyperchloremia as a dichotomous variable defined as a serum concentration greater than or equal to 110 mmol/L. We used multivariable logistic regression to determine the association between the hyperchloremia variables and outcome, adjusted for illness severity. We considered all cause 28-day mortality and complicated course as the primary outcome variables. Complicated course was defined as mortality by 28 days or persistence of greater than or equal to two organ failures at day 7 of septic shock. Secondarily, we conducted a stratified analysis using a biomarker-based mortality risk stratification tool. There were 226 patients (25%) with a complicated course and 93 mortalities (10%). Seventy patients had a minimum chloride greater than or equal to 110 mmol/L, 179 had a mean chloride greater than or equal to 110 mmol/L, and 514 had a maximum chloride greater than or equal to 110 mmol/L. A minimum chloride greater than or equal to 110 mmol/L was associated with increased odds of complicated course (odds ratio, 1.9; 95% CI, 1.1-3.2; p = 0.023) and mortality (odds ratio, 3.7; 95% CI, 2.0-6.8; p < 0.001). A mean chloride greater than or equal to 110 mmol/L was also associated with increased odds of mortality (odds ratio, 2.1; 95% CI, 1.3-3.5; p = 0.002). The secondary analysis yielded similar results. CONCLUSION: Hyperchloremia is independently associated with poor outcomes among children with septic shock.

Endotype Transitions During the Acute Phase of Pediatric Septic Shock Reflect Changing Risk and Treatment Response.

OBJECTIVE: We previously identified septic shock endotypes A and B based on 100 genes reflecting adaptive immunity and glucocorticoid receptor signaling. The endotypes differ with respect to outcome and corticosteroid responsiveness. We determined whether endotypes change during the initial 3 days of illness, and whether changes are associated with outcomes. DESIGN: Observational cohort study including existing and newly enrolled participants. SETTING: Multiple PICUs. PATIENTS: Children with septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We measured the 100 endotyping genes at day 1 and day 3 of illness in 375 patients. We determined if endotype assignment changes over time, and whether changing endotype is associated with corticosteroid response and outcomes. We used multivariable logistic regression to adjust for illness severity, age, and comorbidity burden. Among the 132 subjects assigned to endotype A on day 1, 56 (42%) transitioned to endotype B by day 3. Among 243 subjects assigned to endotype B on day 1, 77 (32%) transitioned to endotype A by day 3. Assignment to endotype A on day 1 was associated with increased odds of mortality. This risk was modified by the subsequent day 3 endotype assignment. Corticosteroids were associated with increased risk of mortality among subjects who persisted as endotype A. CONCLUSIONS: A substantial proportion of children with septic shock transition endotypes during the acute phase of illness. The risk of poor outcome and the response to corticosteroids change with changes in endotype assignment. Patients persisting as endotype A are at highest risk of poor outcomes.

Improved Risk Stratification in Pediatric Septic Shock Using Both Protein and mRNA Biomarkers. PERSEVERE-XP.

RATIONALE: We previously derived and validated the Pediatric Sepsis Biomarker Risk Model (PERSEVERE) to estimate baseline mortality risk in children with septic shock. The PERSEVERE biomarkers are serum proteins selected from among the proteins directly related to 80 mortality risk assessment genes. The initial approach to selecting the PERSEVERE biomarkers left 68 genes unconsidered. OBJECTIVES: To determine if the 68 previously unconsidered genes can improve upon the performance of PERSEVERE and to provide biological information regarding the pathophysiology of septic shock. METHODS: We reduced the number of variables by determining the biological linkage of the 68 previously unconsidered genes. The genes identified through variable reduction were combined with the PERSEVERE-based mortality probability to derive a risk stratification model for 28-day mortality using classification and regression tree methodology (n = 307). The derived tree, PERSEVERE-XP, was then tested in a separate cohort (n = 77). MEASUREMENTS AND MAIN RESULTS: Variable reduction revealed a network consisting of 18 mortality risk assessment genes related to tumor protein 53 (TP53). In the derivation cohort, PERSEVERE-XP had an area under the receiver operating characteristic curve (AUC) of 0.90 (95% confidence interval, 0.85-0.95) for differentiating between survivors and nonsurvivors. In the test cohort, the AUC was 0.96 (95% confidence interval, 0.91-1.0). The AUC of PERSEVERE-XP was superior to that of PERSEVERE. CONCLUSIONS: PERSEVERE-XP combines protein and mRNA biomarkers to provide mortality risk stratification with possible clinical utility. PERSEVERE-XP significantly improves on PERSEVERE and suggests a role for TP53-related cellular division, repair, and metabolism in the pathophysiology of septic shock.

Glucocorticoid Receptor Polymorphisms and Outcomes in Pediatric Septic Shock.

OBJECTIVE: Polymorphisms of the glucocorticoid receptor gene are associated with outcome and corticosteroid responsiveness among patients with inflammatory disorders. We conducted a candidate gene association study to test the hypothesis that these polymorphisms are associated with outcome and corticosteroid responsiveness among children with septic shock. DESIGN: We genotyped 482 children with septic shock for the presence of two glucocorticoid receptor polymorphisms (rs56149945 and rs41423247) associated with increased sensitivity and one glucocorticoid receptor polymorphism (rs6198) associated with decreased sensitivity to corticosteroids. The primary outcome variable was complicated course, defined as 28-day mortality or the persistence of two or more organ failures 7 days after a septic shock diagnosis. We used logistic regression to test for an association between corticosteroid exposure and outcome, within genotype group, and adjusted for illness severity. SETTING: Multiple PICUs in the United States. INTERVENTIONS: Standard care. MEASUREMENTS AND MAIN RESULTS: There were no differences in outcome when comparing the various genotype groups. Among patients homozygous for the wild-type glucocorticoid receptor allele, corticosteroids were independently associated with increased odds of complicated course (odds ratio, 2.30; 95% CI, 1.01-5.21; p = 0.047). CONCLUSIONS: Based on these glucocorticoid receptor polymorphisms, we could not detect a beneficial effect of corticosteroids among any genotype group. Among children homozygous for the wild-type allele, corticosteroids were independently associated with increased odds of poor outcome.

Role of Inhaled Nitric Oxide in the Management of Severe Acute Respiratory Distress Syndrome.

To date, there have been several systematic reviews with meta-analysis that have shown no reduction in mortality with the use of inhaled nitric oxide (iNO) in patients with acute respiratory distress syndrome (ARDS). Importantly, these reports fail to make a distinction between the pediatric and adult patient. The number of adult patients in these reviews are far greater than the number of pediatric patients, which makes it difficult to interpret the data regarding the role of iNO on the pediatric population. Extrapolating data from the adult population to the pediatric population is complicated as we know that physiology and the body's response to disease can be different between adult and pediatric patients. iNO has been demonstrated to improve outcomes in term and near-term infants with hypoxic respiratory failure associated with pulmonary hypertension. Recently, Bronicki et al. published a prospective randomized control trial investigating the impact of iNO on the pediatric patient population with acute respiratory failure. In this study, a benefit of decreased duration of mechanical ventilation and an increased rate of ECMO-free survival was demonstrated in patients who were randomized to receiving iNO, suggesting that there may be benefit to the use of iNO in pediatric ARDS (PARDS) that has not been demonstrated in adults. iNO has repeatedly been shown to transiently improve oxygenation in all age groups, and yet neonates and pediatric patients have shown improvement in other outcomes that have not been seen in adults. The mechanism that explains improvement with the use of iNO in these patient populations are not well understood but does not appear to be solely a result of sustained improvement in oxygenation. There are physiologic studies that suggest alternative mechanisms for explaining the positive effects of iNO, such as platelet aggregation inhibition and reduction in systemic inflammation. Hence, the role of iNO by various mechanisms and in various age groups warrants further investigation.

Pediatric Sepsis Biomarker Risk Model-II: Redefining the Pediatric Sepsis Biomarker Risk Model With Septic Shock Phenotype.

OBJECTIVE: The Pediatric Sepsis Biomarker Risk Model (PERSEVERE), a pediatric sepsis risk model, uses biomarkers to estimate baseline mortality risk for pediatric septic shock. It is unknown how PERSEVERE performs within distinct septic shock phenotypes. We tested PERSEVERE in children with septic shock and thrombocytopenia-associated multiple organ failure (TAMOF), and in those without new onset thrombocytopenia but with multiple organ failure (MOF). DESIGN: PERSEVERE-based mortality risk was generated for each study subject (n = 660). A priori, we determined that if PERSEVERE did not perform well in both the TAMOF and the MOF cohorts, we would revise PERSEVERE to incorporate admission platelet counts. SETTING: Multiple PICUs in the United States. INTERVENTIONS: Standard care. MEASUREMENTS AND MAIN RESULTS: PERSEVERE performed well in the TAMOF cohort (areas under the receiver operating characteristic curves [AUC], 0.84 [95% CI, 0.77-0.90]), but less well in the MOF cohort (AUC, 0.71 [0.61-0.80]). PERSEVERE was revised using 424 subjects previously reported in the derivation phase. PERSEVERE-II had an AUC of 0.89 (0.85-0.93) and performed equally well across TAMOF and MOF cohorts. PERSEVERE-II performed well when tested in 236 newly enrolled subjects. Sample size calculations for a clinical trial testing the efficacy of plasma exchange for children with septic shock and TAMOF indicated PERSEVERE-II-based stratification could substantially reduce the number of patients necessary, when compared with no stratification. CONCLUSIONS: Testing PERSEVERE in the context of septic shock phenotypes prompted a revision incorporating platelet count. PERSEVERE-II performs well upon testing, independent of TAMOF or MOF status. PERSEVERE-II could potentially serve as a prognostic enrichment tool.

Cardiopulmonary Interactions.

OBJECTIVES: The objectives of this review are to discuss the mechanisms by which respiration impacts cardiovascular function and vice versa, with an emphasis on the impact of these interactions in pediatric cardiac critical care. DATA SOURCE: A search of MEDLINE was conducted using PubMed. CONCLUSIONS: In the presence of underlying cardiac and respiratory disease, the interplay between these two systems is significant and plays a pivotal role in the pathophysiology of acute and chronic phases of a wide spectrum of diseases. An understanding of these relationships is essential to optimizing the care of critically ill patients.

Combining Prognostic and Predictive Enrichment Strategies to Identify Children With Septic Shock Responsive to Corticosteroids.

OBJECTIVES: Prognostic and predictive enrichment strategies are fundamental tools of precision medicine. Identifying children with septic shock who may benefit from corticosteroids remains a challenge. We combined prognostic and predictive strategies to identify a pediatric septic shock subgroup responsive to corticosteroids. DESIGN: We conducted a secondary analysis of 288 previously published pediatric subjects with septic shock. For prognostic enrichment, each study subject was assigned a baseline mortality probability using the pediatric sepsis biomarker risk model. For predictive enrichment, each study subject was allocated to one of two septic shock endotypes, based on a 100-gene signature reflecting adaptive immunity and glucocorticoid receptor signaling. The primary study endpoint was complicated course, defined as the persistence of two or more organ failures at day 7 of septic shock or 28-day mortality. We used logistic regression to test for an association between corticosteroids and complicated course within endotype. MEASUREMENTS AND MAIN RESULTS: Among endotype B subjects at intermediate to high pediatric sepsis biomarker risk model-based risk of mortality, corticosteroids were independently associated with more than a 10-fold reduction in the risk of a complicated course (relative risk, 0.09; 95% CI, 0.01-0.54; p = 0.007). CONCLUSIONS: A combination of prognostic and predictive strategies based on serum protein and messenger RNA biomarkers can identify a subgroup of children with septic shock who may be more likely to benefit from corticosteroids. Prospective validation of these strategies and the existence of this subgroup are warranted.

Differential expression of the Nrf2-linked genes in pediatric septic shock.

INTRODUCTION: Experimental data from animal models of sepsis support a role for a transcription factor, nuclear erythroid-related factor 2 p45-related factor 2 (Nrf2), as a master regulator of antioxidant and detoxifying genes and intermediary metabolism during stress. Prior analysis of a pediatric septic shock transcriptomic database showed that the Nrf2 response is a top 5 upregulated signaling pathway in early pediatric septic shock. METHODS: We conducted a focused analysis of 267 Nrf2-linked genes using a multicenter, genome-wide expression database of 180 children with septic shock 10 years of age or younger and 53 healthy controls. The analysis involved RNA isolated from whole blood within 24 h of pediatric intensive care unit admission for septic shock and a false discovery rate of 5 %. We compared differentially expressed genes from (1) patients with septic shock and healthy controls and (2) across validated gene expression-based subclasses of pediatric septic shock (endotypes A and B) using several bioinformatic methods. RESULTS: We found upregulation of 123 Nrf2-linked genes in children with septic shock. The top gene network represented by these genes contained primarily enzymes with oxidoreductase activity involved in cellular lipid metabolism that were highly connected to the peroxisome proliferator activated receptor and the retinoic acid receptor families. Endotype A, which had higher organ failure burden and mortality, exhibited a greater downregulation of Nrf2-linked genes than endotype B, with 92 genes differentially regulated between endotypes. CONCLUSIONS: Our findings indicate that Nrf2-linked genes may contribute to alterations in oxidative signaling and intermediary metabolism in pediatric septic shock.

A Multibiomarker-Based Model for Estimating the Risk of Septic Acute Kidney Injury.

OBJECTIVE: The development of acute kidney injury in patients with sepsis is associated with worse outcomes. Identifying those at risk for septic acute kidney injury could help to inform clinical decision making. We derived and tested a multibiomarker-based model to estimate the risk of septic acute kidney injury in children with septic shock. DESIGN: Candidate serum protein septic acute kidney injury biomarkers were identified from previous transcriptomic studies. Model derivation involved measuring these biomarkers in serum samples from 241 subjects with septic shock obtained during the first 24 hours of admission and then using a Classification and Regression Tree approach to estimate the probability of septic acute kidney injury 3 days after the onset of septic shock, defined as at least two-fold increase from baseline serum creatinine. The model was then tested in a separate cohort of 200 subjects. SETTING: Multiple PICUs in the United States. INTERVENTIONS: None other than standard care. MEASUREMENTS AND MAIN RESULTS: The decision tree included a first-level decision node based on day 1 septic acute kidney injury status and five subsequent biomarker-based decision nodes. The area under the curve for the tree was 0.95 (CI95, 0.91-0.99), with a sensitivity of 93% and a specificity of 88%. The tree was superior to day 1 septic acute kidney injury status alone for estimating day 3 septic acute kidney injury risk. In the test cohort, the tree had an area under the curve of 0.83 (0.72-0.95), with a sensitivity of 85% and a specificity of 77% and was also superior to day 1 septic acute kidney injury status alone for estimating day 3 septic acute kidney injury risk. CONCLUSIONS: We have derived and tested a model to estimate the risk of septic acute kidney injury on day 3 of septic shock using a novel panel of biomarkers. The model had very good performance in a test cohort and has test characteristics supporting clinical utility and further prospective evaluation.

Multicenter randomized controlled trial of inhaled nitric oxide for pediatric acute respiratory distress syndrome.

OBJECTIVES: To test the hypothesis that inhaled nitric oxide (iNO) would lead to improved oxygenation and a decrease in duration of mechanical ventilation in pediatric patients with acute respiratory distress syndrome. STUDY DESIGN: A total of 55 children with acute respiratory distress syndrome were enrolled from 9 centers. Patients were randomized to iNO or placebo and remained on the study drug until death, they were free of ventilator support, or day 28 after the initiation of therapy. RESULTS: Mean baseline oxygenation indexes (OIs) were 22.0 ± 18.4 and 25.6 ± 14.9 (iNO and placebo groups, respectively, P = .27). There was a trend toward an improved OI in the iNO group compared with the placebo group at 4 hours that became significant at 12 hours. There was no difference in the OI between groups at 24 hours. Days alive and ventilator free at 28 days was greater in the iNO group, 14.2 ± 8.1 and 9.1 ± 9.5 days (iNO and placebo groups, respectively, P = .05). Although overall survival at 28 days failed to reach statistical significance, 92% (22 of 24) in the iNO group and 72% (21 of 29) in the placebo group (P = .07), the rate of extracorporeal membrane oxygenation-free survival was significantly greater in those randomized to iNO 92% (22 of 24) vs 52% (15 of 29) for those receiving placebo (P < .01). CONCLUSION: The use of iNO was associated with a significantly reduced duration of mechanical ventilation and significantly greater rate of extracorporeal membrane oxygenation-free survival.

Prospective Testing and Redesign of a Temporal Biomarker Based Risk Model for Patients With Septic Shock: Implications for Septic Shock Biology.

The temporal version of the pediatric sepsis biomarker risk model (tPERSEVERE) estimates the risk of a complicated course in children with septic shock based on biomarker changes from days 1 to 3 of septic shock. We validated tPERSEVERE performance in a prospective cohort, with an a priori plan to redesign tPERSEVERE if it did not perform well. Biomarkers were measured in the validation cohort (n = 168) and study subjects were classified according to tPERSEVERE. To redesign tPERSEVERE, the validation cohort and the original derivation cohort (n = 299) were combined and randomly allocated to training (n = 374) and test (n = 93) sets. tPERSEVERE was redesigned using the training set and CART methodology. tPERSEVERE performed poorly in the validation cohort, with an area under the curve (AUC) of 0.67 (95% CI: 0.58-0.75). Failure analysis revealed potential confounders related to clinical characteristics. The redesigned tPERSEVERE model had an AUC of 0.83 (0.79-0.87) and a sensitivity of 93% (68-97) for estimating the risk of a complicated course. Similar performance was seen in the test set. The classification tree segregated patients into two broad endotypes of septic shock characterized by either excessive inflammation or immune suppression.

Developing a clinically feasible personalized medicine approach to pediatric septic shock.

RATIONALE: Using microarray data, we previously identified gene expression-based subclasses of septic shock with important phenotypic differences. The subclass-defining genes correspond to adaptive immunity and glucocorticoid receptor signaling. Identifying the subclasses in real time has theranostic implications, given the potential for immune-enhancing therapies and controversies surrounding adjunctive corticosteroids for septic shock. OBJECTIVES: To develop and validate a real-time subclassification method for septic shock. METHODS: Gene expression data for the 100 subclass-defining genes were generated using a multiplex messenger RNA quantification platform (NanoString nCounter) and visualized using gene expression mosaics. Study subjects (n = 168) were allocated to the subclasses using computer-assisted image analysis and microarray-based reference mosaics. A gene expression score was calculated to reduce the gene expression patterns to a single metric. The method was tested prospectively in a separate cohort (n = 132). MEASUREMENTS AND MAIN RESULTS: The NanoString-based data reproduced two septic shock subclasses. As previously, one subclass had decreased expression of the subclass-defining genes. The gene expression score identified this subclass with an area under the curve of 0.98 (95% confidence interval [CI95] = 0.96-0.99). Prospective testing of the subclassification method corroborated these findings. Allocation to this subclass was independently associated with mortality (odds ratio = 2.7; CI95 = 1.2-6.0; P = 0.016), and adjunctive corticosteroids prescribed at physician discretion were independently associated with mortality in this subclass (odds ratio = 4.1; CI95 = 1.4-12.0; P = 0.011). CONCLUSIONS: We developed and tested a gene expression-based classification method for pediatric septic shock that meets the time constraints of the critical care environment, and can potentially inform therapeutic decisions.

Corticosteroids and pediatric septic shock outcomes: a risk stratified analysis.

BACKGROUND: The potential benefits of corticosteroids for septic shock may depend on initial mortality risk. OBJECTIVE: We determined associations between corticosteroids and outcomes in children with septic shock who were stratified by initial mortality risk. METHODS: We conducted a retrospective analysis of an ongoing, multi-center pediatric septic shock clinical and biological database. Using a validated biomarker-based stratification tool (PERSEVERE), 496 subjects were stratified into three initial mortality risk strata (low, intermediate, and high). Subjects receiving corticosteroids during the initial 7 days of admission (n = 252) were compared to subjects who did not receive corticosteroids (n = 244). Logistic regression was used to model the effects of corticosteroids on 28-day mortality and complicated course, defined as death within 28 days or persistence of two or more organ failures at 7 days. RESULTS: Subjects who received corticosteroids had greater organ failure burden, higher illness severity, higher mortality, and a greater requirement for vasoactive medications, compared to subjects who did not receive corticosteroids. PERSEVERE-based mortality risk did not differ between the two groups. For the entire cohort, corticosteroids were associated with increased risk of mortality (OR 2.3, 95% CI 1.3-4.0, p = 0.004) and a complicated course (OR 1.7, 95% CI 1.1-2.5, p = 0.012). Within each PERSEVERE-based stratum, corticosteroid administration was not associated with improved outcomes. Similarly, corticosteroid administration was not associated with improved outcomes among patients with no comorbidities, nor in groups of patients stratified by PRISM. CONCLUSIONS: Risk stratified analysis failed to demonstrate any benefit from corticosteroids in this pediatric septic shock cohort.

Differential expression of the nuclear-encoded mitochondrial transcriptome in pediatric septic shock.

INTRODUCTION: Increasing evidence supports a role for mitochondrial dysfunction in organ injury and immune dysregulation in sepsis. Although differential expression of mitochondrial genes in blood cells has been reported for several diseases in which bioenergetic failure is a postulated mechanism, there are no data about the blood cell mitochondrial transcriptome in pediatric sepsis. METHODS: We conducted a focused analysis using a multicenter genome-wide expression database of 180 children ≤ 10 years of age with septic shock and 53 healthy controls. Using total RNA isolated from whole blood within 24 hours of PICU admission for septic shock, we evaluated 296 nuclear-encoded mitochondrial genes using a false discovery rate of 1%. A series of bioinformatic approaches were applied to compare differentially expressed genes across previously validated gene expression-based subclasses (groups A, B, and C) of pediatric septic shock. RESULTS: In total, 118 genes were differentially regulated in subjects with septic shock compared to healthy controls, including 48 genes that were upregulated and 70 that were downregulated. The top scoring canonical pathway was oxidative phosphorylation, with general downregulation of the 51 genes corresponding to the electron transport system (ETS). The top two gene networks were composed primarily of mitochondrial ribosomal proteins highly connected to ETS complex I, and genes encoding for ETS complexes I, II, and IV that were highly connected to the peroxisome proliferator activated receptor (PPAR) family. There were 162 mitochondrial genes differentially regulated between groups A, B, and C. Group A, which had the highest maximum number of organ failures and mortality, exhibited a greater downregulation of mitochondrial genes compared to groups B and C. CONCLUSIONS: Based on a focused analysis of a pediatric septic shock transcriptomic database, nuclear-encoded mitochondrial genes were differentially regulated early in pediatric septic shock compared to healthy controls, as well as across genotypic and phenotypic distinct pediatric septic shock subclasses. The nuclear genome may be an important mechanism contributing to alterations in mitochondrial bioenergetic function and outcomes in pediatric sepsis.

Development of learning objectives and a validated testing tool for management of pediatric mechanical ventilation*.

OBJECTIVES: Graduate medical education is shifting toward an outcome-based paradigm, where physicians are evaluated for competency using well-defined criteria. Our aim was to learning objectives and a testing tool to assess competency in the management of mechanical ventilation for infants, children, and adolescents and to verify that the test was reliable and valid. DESIGN: Prospective reliability and validity study. SETTING: Large, university-affiliated academic hospital. SUBJECTS: Sixty-one total subjects from five different academic centers divided into three groups of varying experience. The groups were second- and third-year pediatric residents (Novice), second- and third-year pediatric critical care fellows (Advanced), and pediatric critical care faculty (Expert). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Ten learning objectives considered important for the management of pediatric mechanical ventilation were developed from expert opinion and current evidence. Based on these objectives, a 35-question multiple choice, knowledge- and case-based test was created. Content validity was achieved by consensus of three experts in pediatric critical care medicine evaluating whether the questions reflected the learning objectives and the responses were consistent with current practice and evidence-based medicine. The test was then administered to the three groups to establish construct validity. The "Novice" group scored a mean of 34.6% (95% CI, 28-41%), the "Advanced" group a mean of 59.4% (95% CI, 53-65%), and the "Expert" group a mean of 74.8% (95% CI, 69-80%), with p less than 0.01 for all comparisons. As determined by Hoyt's analysis, the reliability coefficient was 0.89, reflecting excellent reliability. CONCLUSIONS: This is the first description of specific learning objectives for management of pediatric mechanical ventilation and the first validated and reliable testing tool for assessing knowledge. This tool could be used by fellowship programs to assess fellow competency and identify knowledge gaps in this area prior to completion of training. Further work must be done to determine the criteria for determination of competency.