A randomized, embedded, pragmatic, Bayesian clinical trial examining clinical decision support for high flow nasal cannula management in children with bronchiolitis: design and statistical analysis plan.

BACKGROUND: High flow nasal cannula (HFNC) has been increasingly adopted in the past 2 decades as a mode of respiratory support for children hospitalized with bronchiolitis. The growing use of HFNC despite a paucity of high-quality data regarding the therapy's efficacy has led to concerns about overutilization. We developed an electronic health record (EHR) embedded, quality improvement (QI) oriented clinical trial to determine whether standardized management of HFNC weaning guided by clinical decision support (CDS) results in a reduction in the duration of HFNC compared to usual care for children with bronchiolitis. METHODS: The design and summary of the statistical analysis plan for the REspiratory SupporT for Efficient and cost-Effective Care (REST EEC; "rest easy") trial are presented. The investigators hypothesize that CDS-coupled, standardized HFNC weaning will reduce the duration of HFNC, the trial's primary endpoint, for children with bronchiolitis compared to usual care. Data supporting trial design and eventual analyses are collected from the EHR and other real world data sources using existing informatics infrastructure and QI data sources. The trial workflow, including randomization and deployment of the intervention, is embedded within the EHR of a large children's hospital using existing vendor features. Trial simulations indicate that by assuming a true hazard ratio effect size of 1.27, equivalent to a 6-h reduction in the median duration of HFNC, and enrolling a maximum of 350 children, there will be a > 0.75 probability of declaring superiority (interim analysis posterior probability of intervention effect > 0.99 or final analysis posterior probability of intervention effect > 0.9) and a > 0.85 probability of declaring superiority or the CDS intervention showing promise (final analysis posterior probability of intervention effect > 0.8). Iterative plan-do-study-act cycles are used to monitor the trial and provide targeted education to the workforce. DISCUSSION: Through incorporation of the trial into usual care workflows, relying on QI tools and resources to support trial conduct, and relying on Bayesian inference to determine whether the intervention is superior to usual care, REST EEC is a learning health system intervention that blends health system operations with active evidence generation to optimize the use of HFNC and associated patient outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT05909566. Registered on June 18, 2023.

Mechanical power and normalized mechanical power in pediatric acute respiratory distress syndrome.

Background: Mechanical power (MP) refers to the energy transmitted over time to the respiratory system and serves as a unifying determinant of ventilator-induced lung injury. MP normalization is required to account for developmental changes in children. We sought to examine the relationship between mechanical energy (MEBW), MP normalized to body weight (MPBW), and MP normalized to respiratory compliance (MPCRS) concerning the severity and outcomes of pediatric acute respiratory distress syndrome (pARDS). Method: In this retrospective study, children aged 1 month to 18 years diagnosed with pARDS who underwent pressure-control ventilation for at least 24 h between January 2017 and September 2020 were enrolled. We calculated MP using Becher's equation. Multivariable logistic regression analysis adjusted for age, pediatric organ dysfunction score, and oxygenation index (OI) was performed to determine the independent association of MP and its derivatives 24 h after diagnosing pARDS with 28-day mortality. The association was also studied for 28 ventilator-free days (VFD-28) and the severity of pARDS in terms of OI. Results: Out of 246 admitted with pARDS, 185 were eligible, with an overall mortality of 43.7%. Non-survivors exhibited higher severity of illness, as evidenced by higher values of MP, MPBW, and MEBW. Multivariable logistic regression analysis showed that only MEBW but not MP, MPBW, or MPCRS at 24 h was independently associated with mortality [adjusted OR: 1.072 (1.002-1.147), p = 0.044]. However, after adjusting for the type of pARDS, MEBW was not independently associated with mortality [adjusted OR: 1.061 (0.992-1.136), p = 0.085]. After adjusting for malnutrition, only MP at 24 h was found to be independently associated. Only MPCRS at 1-4 and 24 h but not MP, MPBW, or MEBW at 24 h of diagnosing pARDS was significantly correlated with VFD-28. Conclusions: Normalization of MP is better related to outcomes and severity of pARDS than non-normalized MP. Malnutrition can be a significant confounding factor in resource-limited settings.

Dynamic Airway Driving Pressure and Outcomes in Children With Acute Hypoxemic Respiratory Failure.

BACKGROUND: Limited adult data suggest that airway driving pressure might better reflect the potential risk for lung injury than tidal volume based on ideal body weight, and the parameter correlates with mortality in ARDS. There is a lack of data about the effect of driving pressure on mortality in pediatric ARDS. This study aimed to evaluate the effect of driving pressure on morbidity and mortality of children with acute hypoxemic respiratory failure. METHODS: This retrospective cohort study was performed in a tertiary level pediatric ICU. Children who received invasive mechanical ventilation for acute hypoxemic respiratory failure (defined as [Formula: see text] < 300 within 24 h after intubation), in a 2-y period were included. The cohort was divided into 2 groups based on the highest dynamic driving pressure (ΔP, calculated as the difference between peak inspiratory pressure and PEEP) in the first 24 h, with a cutoff value of 15 cm H2O. RESULTS: Of the 380 children who were mechanically ventilated during the study period, 101 children who met eligibility criteria were enrolled. Common diagnoses were pneumonia (n = 51), severe sepsis (n = 24), severe dengue (n = 10), and aspiration pneumonia (n = 7). In comparison to the group with high ΔP (ie, ≥ 15 cm H2O), children in the group with low ΔP (ie, < 15 cm H2O) had significantly lower median (interquartile range) duration of ventilation (5 [4-6] d vs 8 [6-11] d, P < .001], ICU length of stay (6 [5-8] d vs 12 [8-15] d, P < .001], and more ventilator-free days at day 28 (23 [20-24] vs 17 [0-22] d, P < .001). Logistic regression analysis also suggested driving pressure as an independent predictor of morbidity after adjusting for confounding variables. However, there was no statistically significant difference in mortality between the 2 groups (17% in low ΔP vs 24% in high ΔP, P = .38). Subgroup analysis of 65 subjects who fulfilled ARDS criteria yielded similar results with respect to mortality and morbidity. CONCLUSIONS: Below a threshold of 15 cm H2O, ΔP was associated with significantly decreased morbidity in children with acute hypoxemic respiratory failure.

Early Hyperoxemia and Outcome Among Critically Ill Children.

OBJECTIVE: To identify whether a high PaO2 (hyperoxemia) at the time of presentation to the PICU is associated with in-hospital mortality. DESIGN: Single-center observational study. SETTING: Quaternary-care PICU. PATIENTS: Encounters admitted between January 1, 2009, and December 31, 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Encounters with a measured PaO2 were included. To account for severity of illness upon presentation, we calculated a modified Pediatric Risk of Mortality IV score excluding PaO2 for each encounter, calibrated for institutional data. Logistic regression was used to determine whether hyperoxemia (PaO2 ≥ 300 torr [39.99 kPa]) in the 12 hours surrounding PICU admission was associated with in-hospital mortality. We reperformed our analysis using a cutoff for hyperoxemia obtained by comparisons of observed versus predicted mortality when encounters were classified by highest PaO2 in 50 torr (6.67 kPa) bins. Results are reported as adjusted odds ratios with 95% CIs. Of 23,719 encounters, 4,093 had a PaO2 recorded in the period -6 to +6 hours after admission. Two hundred seventy-four of 4,093 (6.7%) had in-hospital mortality. The prevalence of hyperoxemia increased with rising modified Pediatric Risk of Mortality IV and was not associated with mortality in multivariable models (adjusted odds ratio, 1.38; 95% CI, 0.98-1.93). When using a higher cutoff of hyperoxemia derived from comparison of observed versus predicted rates of mortality of greater than or equal to 550 torr (73.32 kPa), hyperoxemia was associated with mortality (adjusted odds ratio, 2.78; 95% CI, 2.54-3.05). CONCLUSIONS: A conventional threshold for hyperoxemia at presentation to the PICU was not associated with in-hospital mortality in a model using a calibrated acuity score. Extreme states of hyperoxemia (≥ 73.32 kPa) were significantly associated with in-hospital mortality. Prospective research is required to identify if hyperoxemia before and/or after PICU admission contributes to poor outcomes.

Association of Severe Hyperoxemia Events and Mortality Among Patients Admitted to a Pediatric Intensive Care Unit.

Importance: A high Pao2, termed hyperoxemia, is postulated to have deleterious health outcomes. To date, the association between hyperoxemia during the ongoing management of critical illness and mortality has been incompletely evaluated in children. Objective: To examine whether severe hyperoxemia events are associated with mortality among patients admitted to a pediatric intensive care unit (PICU). Design, Setting, and Participants: A retrospective cohort study was conducted over a 10-year period (January 1, 2009, to December 31, 2018); all 23 719 PICU encounters at a quaternary children's hospital with a documented arterial blood gas measurement were evaluated. Exposures: Severe hyperoxemia, defined as Pao2 level greater than or equal to 300 mm Hg (40 kPa). Main Outcomes and Measures: The highest Pao2 values during hospitalization were dichotomized according to the definition of severe hyperoxemia and assessed for association with in-hospital mortality using logistic regression models incorporating a calibrated measure of multiple organ dysfunction, extracorporeal life support, and the total number of arterial blood gas measurements obtained during an encounter. Results: Of 23 719 PICU encounters during the inclusion period, 6250 patients (13 422 [56.6%] boys; mean [SD] age, 7.5 [6.6] years) had at least 1 measured Pao2 value. Severe hyperoxemia was independently associated with in-hospital mortality (adjusted odds ratio [aOR], 1.78; 95% CI, 1.36-2.33; P < .001). Increasing odds of in-hospital mortality were observed with 1 (aOR, 1.47; 95% CI, 1.05-2.08; P = .03), 2 (aOR, 2.01; 95% CI, 1.27-3.18; P = .002), and 3 or more (aOR, 2.53; 95% CI, 1.62-3.94; P < .001) severely hyperoxemic Pao2 values obtained greater than or equal to 3 hours apart from one another compared with encounters without hyperoxemia. A sensitivity analysis examining the hypothetical outcomes of residual confounding indicated that an unmeasured binary confounder with an aOR of 2 would have to be present in 37% of the encounters with severe hyperoxemia and 0% of the remaining cohort to fail to reject the null hypothesis (aOR of severe hyperoxemia, 1.31; 95% CI, 0.99-1.72). Conclusions and Relevance: Greater numbers of severe hyperoxemia events appeared to be associated with increased mortality in this large, diverse cohort of critically ill children, supporting a possible exposure-response association between severe hyperoxemia and outcome in this population. Although further prospective evaluation appears to be warranted, this study's findings suggest that guidelines for ongoing management of critically ill children should take into consideration the possible detrimental effects of severe hyperoxemia.

Inhaled Pulmonary Vasodilators: Are There Indications Within the Pediatric ICU?

Inhaled nitric oxide (INO) is only FDA-cleared for neonates (> 34 weeks gestation) with hypoxic respiratory failure-associated pulmonary hypertension. Off-label use of INO is common in the pediatric population despite a lack of evidence regarding survival benefit, questioning whether the therapy should be considered outside the neonatal period. A lack of definitive evidence combined with increasing health-care costs has led to the use of less costly inhaled prostacyclin as an alternative to INO, presenting unique patient safety concerns. We evaluate the current evidence and patient safety considerations regarding inhaled pulmonary vasodilators in the pediatric population.

Diastolic Hypotension, Troponin Elevation, and Electrocardiographic Changes Associated With the Management of Moderate to Severe Asthma in Children.

OBJECTIVE: The objective was to determine the occurrence of, and the factors associated with, diastolic hypotension and troponin elevation or electrocardiogram (ECG) ST-segment changes in a convenience sample of children with moderate to severe asthma receiving continuous albuterol nebulization. METHODS: This was a prospective, descriptive study in a pediatric emergency department and an intensive care unit of a tertiary academic center. Fifty children with moderate to severe asthma (clinical asthma score > 8) who received 10 to 15 mg/hour continuous albuterol for >2 hours between June 5, 2007, and February 4, 2008, were approached. Hourly diastolic blood pressures were recorded. Cardiac troponin I (cTnI) and ECG tracings were obtained following the first 2 hours of albuterol and then subsequently every 12 hours while receiving continuous albuterol. Main outcome measures were: 1) incidence of diastolic hypotension, 2) incidence of troponin elevation, and 3) incidence of ECG ST-depression. RESULTS: Fifty patients were enrolled. Thirty-three (66%) patients developed diastolic hypotension during the first 6 hours of continuous albuterol. Diastolic blood pressure declined from baseline at 1-6 hours (p < 0.01 vs. baseline). Twelve patients (24%) had elevated cTnI, 15 patients (30%) had ST-segment change, four patients (8%) had both, and 23 patients (46%, 95% confidence interval [CI] = 32 to 60) had either a cTnI elevation or an ECG ST-segment change. Troponin elevation and diastolic hypotension were not associated (RR = 1.2, 95% CI = 0.6 to 2.3). CONCLUSIONS: In a subset of children with moderate to severe asthma, diastolic hypotension, troponin elevation, and ECG ST-segment change occur during administration of continuous albuterol. Future studies are necessary to determine the clinical significance of these findings.

Reduced glucocorticoid receptor protein expression in children with critical illness.

BACKGROUND/AIMS: The diagnostic criteria for critical illness-related corticoid insufficiency (CIRCI) are not well established, particularly for children. In addition to alterations in adrenal function, cellular resistance to glucocorticoid action could contribute to CIRCI due to alterations in the functioning of the intracellular receptor protein for corticosteroids, the glucocorticoid receptor (GR). METHODS: We have therefore undertaken a pilot, prospective study to assess whether cellular GR activity can be measured in peripheral blood mononuclear cells (PBMCs) from critically ill children. RESULTS: Total and cytoplasmic, but not nuclear GR levels were significantly lower in PBMCs from critically ill children (i.e. sepsis/septic shock and traumatic brain injury) compared to healthy controls . While total cortisol concentrations did not differ between test groups, salivary and serum-free cortisol concentrations were significantly greater in both groups of children with critical illness. Cortisol-binding globulin levels were significantly lower in patients with sepsis/septic shock. CONCLUSIONS: The lower total and cytoplasmic receptor levels in critically ill children suggest that the GR-mediated response to exogenous glucocorticoid therapy may be limited. However, the nuclear transport of GR in critically ill patients suggests that residual receptors in these patients retain functionality and may be accessible to therapeutic treatments that maximize their activity.

Efficacy and predictors of success of noninvasive ventilation for prevention of extubation failure in critically ill children with heart disease.

The study aimed primarily to evaluate the efficacy of noninvasive ventilation (NIV) and to identify possible predictors for success of NIV therapy in preventing extubation failure in critically ill children with heart disease. The secondary objectives of this study were to assess the efficacy of prophylactic NIV therapy initiated immediately after tracheal extubation and to determine the characteristics, outcomes, and complications associated with NIV therapy in pediatric cardiac patients. A retrospective review examined the medical records of all children between the ages 1 day and 18 years who sustained acute respiratory failure (ARF) that required NIV in the cardiovascular intensive care unit (CVICU) at Lucile Packard Children's Hospital between January 2008 and June 2010. Patients were assigned to a prophylactic group if NIV was started directly after extubation and to a nonprophylactic group if NIV was started after signs and symptoms of ARF developed. Patients were designated as responders if they received NIV and did not require reintubation during their CVICU stay and nonresponders if they failed NIV and reintubation was performed. The data collected included demographic data, preexisting conditions, pre-event characteristics, event characteristics, and outcome data. The outcome data evaluated included success or failure of NIV, duration of NIV, CVICU length of stay (LOS), hospital LOS, and hospital mortality. The two complications of NIV assessed in the study included nasal bridge or forehead skin necrosis and pneumothorax. The 221 eligible events during the study period involved 172 responders (77.8 %) and 49 nonresponders (22.2 %). A total of 201 events experienced by the study cohort received continuous positive airway pressure (CPAP), with 156 responders (78 %), whereas 20 events received bilevel positive airway pressure (BiPAP), with 16 responders (80 %). In the study, 58 events (26.3 %) were assigned to the prophylactic group and 163 events (73.7 %) to the nonprophylactic group. Compared with the nonprophylactic group, the prophylactic group experienced significantly shorter CVICU LOS (median, 49 vs 88 days; p = 0.03) and hospital LOS (median, 60 vs 103 days; p = 0.05). The CVICU LOS and hospital LOS did not differ significantly between the responders (p = 0.56) and nonresponders (p = 0.88). Significant variables identifying a responder included a lower risk-adjusted classification for congenital heart surgery (RACHS-1) score (1-3), a good left ventricular ejection fraction, a normal respiratory rate (RR), normal or appropriate oxygen saturation, prophylactic or therapeutic glucocorticoid therapy within 24 h of NIV initiation, presence of atelectasis, fewer than two organ system dysfunctions, fewer days of intubation before extubation, no clinical or microbiologic evidence of sepsis, and no history of reactive airway disease. As a well-tolerated therapy, NIV can be safely and successfully applied in critically ill children with cardiac disease to prevent extubation failure. The independent predictors of NIV success include lower RACHS-1 classification, presence of atelectasis, steroid therapy received within 24 h after NIV, and normal heart rate and oxygen saturations demonstrated within 24 h after initiation of NIV.

Nutritional-metabolic factors affecting nitrogen balance and substrate utilization in the critically ill.

To determine clinical, anthropometric, metabolic, and nutritional factors affecting nitrogen balance somatic protein status and substrate utilization in critically ill children measured energy expenditure (MEE) was measured by indirect calorimetry within 24 hr of an acute illness, solid organ transplantation, or cardiovascular surgery. Predicted basal metabolic rate was calculated using the Schofield equation. Somatic protein was estimated by the creatinine-height index. Nitrogen balance (NB) was calculated by subtracting the total nitrogen input from output. The net substrate (fat, carbohydrate, and protein) oxidation rates were calculated using the Weir formula modified by Frayn. Sixty-eight NB studies, indirect calorimetric and anthropometric measurements performed in 37 patients. Nitrogen balance was worse when the MEE/Predicted basal metabolic rate ratio was < 0.9 or > 1.1. The incidence of negative NB was 91% when the caloric intake was less than MEE and 9% when it was equal to or greater than MEE (P < 0.05). On day 1, 27% had mild to moderate somatic protein depletion and 5.4% had severe somatic protein depletion. Only the persistence of stress and co-morbidity were associated with the creatinine-height index (P < 0.001). Without Multiple Organ System Failure (MOSF), there was a trend toward positive nitrogen balance by day 7 while with MOSF, negative nitrogen balance persisted even by day 7 (P < 0.05). When caloric intake was less than MEE, mean substrate utilization was 48.6% from lipid, 37.1% from carbohydrate, and 14.3% from proteins. But, when caloric intake was greater than MEE, mean substrate utilization was 83.3% from carbohydrate and 16.7% from protein. Significant negative nitrogen balance and somatic protein depletion develops in critically ill pediatric patients, especially when they are inadequately fed, develop MOSF, or have previous chronic illness. Caloric intake and MOSF independently affect substrate utilization.

Helium-oxygen therapy for infants with bronchiolitis: a randomized controlled trial.

OBJECTIVE: To compare nebulized racemic epinephrine delivered by 70% helium and 30% oxygen or 100% oxygen followed by helium-oxygen inhalation therapy via high-flow nasal cannula (HFNC) vs oxygen inhalation via HFNC in the treatment of bronchiolitis. DESIGN: Prospective, randomized, controlled, single-blind trial. SETTING: This study was conducted from October 1, 2004, through May 31, 2008, in the emergency department of an urban, tertiary care children's hospital. Patients Infants aged 2 to 12 months with a Modified Wood's Clinical Asthma Score (M-WCAS) of 3 or higher. INTERVENTIONS: Patients initially received nebulized albuterol treatment driven by 100% oxygen. Patients were randomized to the helium-oxygen or oxygen group and received nebulized racemic epinephrine via a face mask. After nebulization, humidified helium-oxygen or oxygen was delivered by HFNC. After 60 minutes of inhalation therapy, patients with an M-WCAS of 2 or higher received a second delivery of nebulized racemic epinephrine followed by helium-oxygen or oxygen delivered by HFNC. Main Outcome Measure Degree of improvement of M-WCAS for 240 minutes or until emergency department discharge. RESULTS: Of 69 infants enrolled, 34 were randomized to the helium-oxygen group and 35 to the oxygen group. The mean change in M-WCAS from baseline to 240 minutes or emergency department discharge was 1.84 for the helium-oxygen group compared with 0.31 for the oxygen group (P < .001). The mean M-WCAS was significantly improved for the helium-oxygen group compared with the oxygen group at 60 minutes (P = .005), 120 minutes (P < .001), 180 minutes (P < .001), and 240 minutes (P < .001). CONCLUSION: Nebulized racemic epinephrine delivered by helium-oxygen followed by helium-oxygen inhalation therapy delivered by HFNC was associated with a greater degree of clinical improvement compared with that delivered by oxygen among infants with bronchiolitis. Trial Registration clinicaltrials.gov Identifier: NCT00116584.

Cytokines and metabolic patterns in pediatric patients with critical illness.

It is not known if cytokines, which are cell-derived mediators released during the host immune response to stress, affect metabolic response to stress during critical illness. The aim of this prospective study was to determine whether the metabolic response to stress is related to the inflammatory interleukin-6 (IL-6), 10 (IL-10), and other stress mediators' responses and to assess their relationships with different feeding patterns, nutritional markers, the severity of illness as assessed by the Multiple Organ System Failure (MOSF), the Pediatric Risk of Mortality Score (PRISM), systemic inflammatory response syndrome (SIRS), and mortality in critically ill children. Patients were classified as hypermetabolic, normometabolic, and hypometabolic when the measured resting energy expenditures (REE) were >110%, 90-110% and, <90% of the predicted basal metabolic rate, respectively. The initial predominance of the hypometabolic pattern (48.6%) declined within 1 week of acute stress (20%), and the hypermetabolic patterns dominated only after 2 weeks (60%). Only oxygen consumption (VO(2)) and carbon dioxide production (VCO(2)) (P < .0001) but none of the cytokines and nutritional markers, were independently associated with a hypometabolic pattern. REE correlated with the IL-10 but not PRISM. In the presence of SIRS or sepsis, CRP, IL-6, IL-10, Prognostic Inflammatory and Nutritional Index (NI), and triglycerides--but not glucose, VO(2), or VCO(2) increased significantly. High IL-10 levels (P = .0000) and low measured REE (P = .0000) were independently associated with mortality (11.7%), which was higher in the hypometabolic compared to other metabolic patterns (P < .005). Our results showed that only VO(2) and VCO(2), but not IL-6 or IL-10, were associated with a hypometabolic pattern which predominated the acute phase of stress, and was associated with increased mortality. Although in SIRS or sepsis, the cytokine response was reliably reflected by increases in NI and triglycerides, it was different from the metabolic (VO(2), VCO(2)) or glucose response.

Weaning and extubation readiness in pediatric patients.

OBJECTIVE: A systematic review of weaning and extubation for pediatric patients on mechanical ventilation. DATA SELECTION: Pediatric and adult literature, English language. STUDY SELECTION: Invited review. DATA SOURCES: Literature review using National Library of Medicine PubMed from January 1972 until April 2008, earlier cross-referenced article citations, the Cochrane Database of Systematic Reviews, and the Internet. CONCLUSIONS: Despite the 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 even less clear, although a trial of spontaneous breathing would seem a prerequisite. Several indices have been developed in an attempt to predict weaning and extubation success but the available literature would suggest they offer no improvement over clinical judgment. Extubation failure rates range from 2% to 20% and bear little relationship to the duration of mechanical ventilation. Upper airway obstruction is the single most common cause of extubation failure. A reliable method of assessing readiness for weaning and predicting extubation success is not evident from the pediatric literature.

A prospective randomized controlled study of two fluid regimens in the initial management of septic shock in the emergency department.

OBJECTIVES: To compare the impact of 40 mL/kg of fluid over 15 minutes followed by dopamine and further titration of therapy to achieve therapeutic goals (study protocol) versus 20 mL/kg over 20 minutes up to a maximum of 60 mL/kg over 1 hour followed by dopamine (control protocol) in septic shock. DESIGN AND SETTING: Prospective randomized controlled study in the emergency department of a public hospital in India. PATIENTS: One hundred forty-seven children older than 1 month presenting with septic shock were enrolled into the study. OUTCOME MEASURES: Hospital mortality (primary outcome), 72-hour survival, achievement of therapeutic goals of shock resolution, incidence of hypoxia, hepatomegaly, intubation at 20, 40, and 60 minutes (secondary outcomes) were compared between the arms. RESULTS: Seventy-four and 73 children were assigned to the study and control group, respectively. Overall mortality was 17.6%, 26 deaths with 13 in each arm. Mortality in the study cohort was lower than our historical mortality of 50% (P<0.0001), 95% confidence interval (CI), 11.9-24.8. Cumulative survival at 72 hours was 72.5% (95% CI, 58.9-86.1) and 77.6% (95% CI, 66.0%-89.2%) in the control and study groups, respectively. Resolution of shock in the emergency department was associated with survival odds ratio (OR) 9.2 (95% CI, 2.1-40.8). Rapidity of achieving therapeutic goals was not significantly different between groups. Intubation rates were also the same (46.5% in the control group versus 55% in the study group; P=0.28). At 20 minutes, 35.6% of the control group and 70% of the study group had hepatomegaly (P<0.01). CONCLUSION: There was no difference in the overall mortality, rapidity of shock resolution, or incidence of complications between the groups. The occurrence of hepatomegaly at 20 minutes following 40 mL/kg is of concern in settings with limited access to post-resuscitation ventilator care.