Heidi R. Flori

Critically ill children during the 2009-2010 influenza pandemic in the United States.

BACKGROUND: The 2009 pandemic influenza A (H1N1) (pH1N1) virus continues to circulate worldwide. Determining the roles of chronic conditions and bacterial coinfection in mortality is difficult because of the limited data for children with pH1N1-related critical illness. METHODS: We identified children (<21 years old) with confirmed or probable pH1N1 admitted to 35 US PICUs from April 15, 2009, through April 15, 2010. We collected data on demographics, baseline health, laboratory results, treatments, and outcomes. RESULTS: Of 838 children with pH1N1 admitted to a PICU, the median age was 6 years, 58% were male, 70% had ≥1 chronic health condition, and 88.2% received oseltamivir (5.8% started before PICU admission). Most patients had respiratory failure with 564 (67.3%) receiving mechanical ventilation; 162 (19.3%) received vasopressors, and 75 (8.9%) died. Overall, 71 (8.5%) of the patients had a presumed diagnosis of early (within 72 hours after PICU admission) Staphylococcus aureus coinfection of the lung with 48% methicillin-resistant S aureus (MRSA). In multivariable analyses, preexisting neurologic conditions or immunosuppression, encephalitis (1.7% of cases), myocarditis (1.4% of cases), early presumed MRSA lung coinfection, and female gender were mortality risk factors. Among 251 previously healthy children, only early presumed MRSA coinfection of the lung (relative risk: 8 [95% confidence interval: 3.1–20.6]; P < .0001) remained a mortality risk factor. CONCLUSIONS: Children with preexisting neurologic conditions and immune compromise were at increased risk of pH1N1-associated death after PICU admission. Secondary complications of pH1N1, including myocarditis, encephalitis, and clinical diagnosis of early presumed MRSA coinfection of the lung, were mortality risk factors.

Pediatric Acute Respiratory Distress Syndrome: Consensus Recommendations From the Pediatric Acute Lung Injury Consensus Conference

OBJECTIVE To describe the final recommendations of the Pediatric Acute Lung Injury Consensus Conference. DESIGN Consensus conference of experts in pediatric acute lung injury. SETTING Not applicable. SUBJECTS PICU patients with evidence of acute lung injury or acute respiratory distress syndrome. INTERVENTIONS None. METHODS A panel of 27 experts met over the course of 2 years to develop a taxonomy to define pediatric acute respiratory distress syndrome and to make recommendations regarding treatment and research priorities. When published, data were lacking a modified Delphi approach emphasizing strong professional agreement was used. MEASUREMENTS AND MAIN RESULTS A panel of 27 experts met over the course of 2 years to develop a taxonomy to define pediatric acute respiratory distress syndrome and to make recommendations regarding treatment and research priorities. When published data were lacking a modified Delphi approach emphasizing strong professional agreement was used. The Pediatric Acute Lung Injury Consensus Conference experts developed and voted on a total of 151 recommendations addressing the following topics related to pediatric acute respiratory distress syndrome: 1) Definition, prevalence, and epidemiology; 2) Pathophysiology, comorbidities, and severity; 3) Ventilatory support; 4) Pulmonary-specific ancillary treatment; 5) Nonpulmonary treatment; 6) Monitoring; 7) Noninvasive support and ventilation; 8) Extracorporeal support; and 9) Morbidity and long-term outcomes. There were 132 recommendations with strong agreement and 19 recommendations with weak agreement. Once restated, the final iteration of the recommendations had none with equipoise or disagreement. CONCLUSIONS The Consensus Conference developed pediatric-specific definitions for acute respiratory distress syndrome and recommendations regarding treatment and future research priorities. These are intended to promote optimization and consistency of care for children with pediatric acute respiratory distress syndrome and identify areas of uncertainty requiring further investigation.

A Prospective Study of Ventilator-Associated Pneumonia in Children

OBJECTIVE. We conducted a prospective, observational study in a tertiary care pediatric center to determine risk factors for the development of and outcomes from ventilator-associated pneumonia. METHODS. From November 2004 to June 2005, all NICU and PICU patients mechanically ventilated for >24 hours were eligible for enrollment after parental consent. The primary outcome measure was the development of ventilator-associated pneumonia, which was defined by both Centers for Disease Control and Prevention/National Nosocomial Infections Surveillance criteria and clinician diagnosis. Secondary outcome measures were length of mechanical ventilation, hospital and ICU length of stay, hospital cost, and death. RESULTS. Fifty-eight patients were enrolled. The median age was 6 months, and 57% were boys. The most common ventilator-associated pneumonia organisms identified were Gram-negative bacteria (42%), Staphylococcus aureus (22%), and Haemophilus influenzae (11%). On multivariate analysis, female gender, postsurgical admission diagnosis, presence of enteral feeds, and use of narcotic medications were associated with ventilator-associated pneumonia. Patients with ventilator-associated pneumonia had greater need for mechanical ventilation (12 vs 22 median ventilator-free days), longer ICU length of stay (6 vs 13 median ICU-free days), higher total median hospital costs (

Acute lung injury in children: Therapeutic practice and feasibility of international clinical trials*

308534 vs

Fluid balance in critically ill children with acute lung injury

252652), and increased absolute hospital mortality (10.5% vs 2.4%) than those without ventilator-associated pneumonia. CONCLUSIONS. In mechanically ventilated, critically ill children, those with ventilator-associated pneumonia had a prolonged need for mechanical ventilation, a longer ICU stay, and a higher mortality rate. Female gender, postsurgical diagnosis, the use of narcotics, and the use of enteral feeds were associated with an increased risk of developing ventilator-associated pneumonia in these patients.

Positive Fluid Balance Is Associated with Higher Mortality and Prolonged Mechanical Ventilation in Pediatric Patients with Acute Lung Injury

Objectives: To describe mechanical ventilation strategies in acute lung injury and to estimate the number of eligible patients for clinical trials on mechanical ventilation management. In contrast to adult medicine, there are few clinical trials to guide mechanical ventilation management in children with acute lung injury. Design: A cross-sectional study for six 24-hr periods from June to November 2007. Setting: Fifty-nine pediatric intensive care units in 12 countries in North America and Europe. Patients: We identified children meeting acute lung injury criteria and collected detailed information on illness severity, mechanical ventilatory support, and use of adjunctive therapies. Interventions: None. Measurements and Main Results: Of 3823 patients screened, 414 (10.8%) were diagnosed with acute lung injury by their treating physician, but only 165 (4.3%) patients met prestablished inclusion/exclusion criteria to this trial and, therefore, would have been eligible for a clinical trial. Of these, 124 (75.2%) received conventional mechanical ventilation, 27 (16.4%) received high-frequency oscillatory ventilation, and 14 (8.5%) received noninvasive mechanical ventilation. In the conventional mechanical ventilation group, 43.5% were ventilated in a pressure control mode with a mean tidal volume of 8.3 ± 3.3 mL/kg; and there was no clear relationship between positive end-expiratory pressure and Fio2 delivery in the conventional mechanical ventilation group. Use of adjunctive treatments, including nitric oxide, prone positioning, surfactant, hemofiltration, recruitment maneuvers, steroids, bronchodilators, and fluid restriction, was highly variable. Conclusions: Our study reveals inconsistent mechanical ventilation practice and use of adjunctive therapies in children with acute lung injury. Pediatric clinical trials assessing mechanical ventilation management are needed to generate evidence to optimize outcomes. We estimate that a large number of centers (∼60) are needed to conduct such trials; it is imperative, therefore, to bring about international collaboration.

Early elevation of plasma soluble intercellular adhesion molecule-1 in pediatric acute lung injury identifies patients at increased risk of death and prolonged mechanical ventilation

Objectives: In the Fluid and Catheter Treatment Trial (NCT00281268), adults with acute lung injury randomized to a conservative vs. liberal fluid management protocol had increased days alive and free of mechanical ventilator support (ventilator-free days). Recruiting sufficient children with acute lung injury into a pediatric trial is challenging. A Bayesian statistical approach relies on the adult trial for the a priori effect estimate, requiring fewer patients. Preparing for a Bayesian pediatric trial mirroring the Fluid and Catheter Treatment Trial, we aimed to: 1) identify an inverse association between fluid balance and ventilator-free days; and 2) determine if fluid balance over time is more similar to adults in the Fluid and Catheter Treatment Trial liberal or conservative arms. Design: Multicentered retrospective cohort study. Setting: Five pediatric intensive care units. Patients: Mechanically ventilated children (age ≥1 month to <18 yrs) with acute lung injury admitted in 2007–2010. Interventions: None. Measurements and Main Results: Fluid intake, output, and net fluid balance were collected on days 1–7 in 168 children with acute lung injury (median age 3 yrs, median PaO2/FIO2 138) and weight-adjusted (mL/kg). Using multivariable linear regression to adjust for age, gender, race, admission day illness severity, PaO2/FIO2, and vasopressor use, increasing cumulative fluid balance (mL/kg) on day 3 was associated with fewer ventilator-free days (p = .02). Adjusted for weight, daily fluid balance on days 1–3 and cumulative fluid balance on days 1–7 were higher in these children compared to adults in the Fluid and Catheter Treatment Trial conservative arm (p < .001, each day) and was similar to adults in the liberal arm. Conclusions: Increasing fluid balance on day 3 in children with acute lung injury at these centers is independently associated with fewer ventilator-free days. Our findings and the similarity of fluid balance patterns in our cohort to adults in the Fluid and Catheter Treatment Trial liberal arm demonstrate the need to determine whether a conservative fluid management strategy improves clinical outcomes in children with acute lung injury and support a Bayesian trial mirroring the Fluid and Catheter Treatment Trial.

Zinc homeostasis in pediatric critical illness.

Introduction. We analyzed a database of 320 pediatric patients with acute lung injury (ALI), to test the hypothesis that positive fluid balance is associated with worse clinical outcomes in children with ALI. Methods. This is a post-hoc analysis of previously collected data. Cumulative fluid balance was analyzed in ml per kilogram per day for the first 72 hours after ALI while in the PICU. The primary outcome was mortality; the secondary outcome was ventilator-free days. Results. Positive fluid balance (in increments of 10 mL/kg/24 h) was associated with a significant increase in both mortality and prolonged duration of mechanical ventilation, independent of the presence of multiple organ system failure and the extent of oxygenation defect. These relationships remained unchanged when the subgroup of patients with septic shock (n = 39) were excluded. Conclusions. Persistently positive fluid balance may be deleterious to pediatric patients with ALI. A confirmatory, prospective randomized controlled trial of fluid management in pediatric patients with ALI is warranted.

Transthoracic intracardiac catheters in pediatric patients recovering from congenital heart defect surgery: associated complications and outcomes.

Objective To determine whether soluble intercellular adhesion molecule (sICAM)-1, a biological marker of alveolar epithelial and lung endothelial injury and alveolar macrophage activation, is elevated in the plasma of pediatric patients with acute lung injury and to examine whether elevated plasma sICAM-1 levels correlate with two clinically relevant outcomes, mortality and the duration of mechanical ventilation. Design Prospective cohort study. Setting Pediatric intensive care units at an urban children’s hospital and a tertiary university medical center. Patients Eighty-three pediatric patients with acute lung injury and five intubated controls. Interventions Plasma sICAM-1 levels were measured on days 1 and 2 of acute lung injury in pediatric patients and on day 1 of mechanical ventilation in control patients. Measurements and Main Results Plasma sICAM-1 levels were significantly higher in patients with acute lung injury compared with controls (966 ± 830 vs. 251 ± 168 ng/mL, p < .05). Levels of sICAM-1 were also significantly higher on days 1 and 2 of acute lung injury in nonsurvivors and in patients requiring prolonged duration of mechanical ventilation. Also, plasma sICAM-1 levels >1000 ng/mL had a high specificity for identifying nonsurvivors of acute lung injury. Conclusions Early elevation of sICAM-1 in the plasma of pediatric patients with acute lung injury is associated with increased risk of death or prolonged duration of mechanical ventilation.

American College of Critical Care Medicine Clinical Practice Parameters for Hemodynamic Support of Pediatric and Neonatal Septic Shock

Objective: We explored the hypothesis that marked decline in plasma zinc concentrations among critically ill children is related to shifts in metallothionein expression and inflammation. Design: Prospective pilot study. Setting: Intensive care unit of tertiary care children’s hospital. Patients: All children (<18 yrs) with unadjusted Pediatric Risk of Mortality III score >5 or at least one organ failure admitted to the pediatric intensive care unit from March through August 2006 were eligible for enrollment. Interventions: After consent, blood samples were collected on days 1 and 3 of illness and analyzed for serum chemistries, plasma zinc and copper levels, metallothionein isoform expression, and cytokine levels. Measurements and Main Results: Twenty patients were enrolled, with median age of 2.9 yrs (interquartile range, 0.7–10.1). Male to female ratio was 1.2:1. All patients had low zinc levels (mean, 0.43; range, 0.26–0.66 &mgr;g/dL) on day 1 of pediatric intensive care unit admission, and remained low (mean, 0.51; range, 0.26–0.81 &mgr;g/dL) on day 3, even when corrected for hypoalbuminemia. In comparison, serum copper levels were normal. On day 1, there was a positive correlation between zinc levels and expression of MT-1A (p < 0.01), MT-1G (p = 0.02), and MT-1H (p = 0.03). Plasma zinc levels correlated inversely with C-reactive protein levels (r = −.75, p = 0.01) and interleukin-6 levels (r = −.53, p = 0.04) on day 3. On day 3, patients with two or more organ failures had significantly lower plasma zinc concentrations compared with patients with ≤1 organ failure (p = 0.03). Conclusions: Plasma zinc concentrations are low in critically ill children. Plasma zinc correlated with measures of inflammation (C-reactive protein and interleukin-6) on day 3; low plasma zinc concentrations were associated with the degree of organ failure on day 3. These data serve as the basis for a larger study of shifts in plasma zinc concentrations in critically children to potentially identify patients who might benefit from zinc supplementation.