Barry P. Markovitz

Anemia, Blood Loss, and Blood Transfusions in North American Children in the Intensive Care Unit

RATIONALE Minimizing exposure of children to blood products is desirable. OBJECTIVES We aimed to understand anemia development, blood loss, and red blood cell (RBC) transfusions in the pediatric intensive care unit (PICU). METHODS Prospective, multicenter, 6-month observational study in 30 PICUs. Data were collected on consecutive children (<18 yr old) in the PICU for 48 hours or more. MEASUREMENTS AND MAIN RESULTS Anemia development, blood loss, and RBC transfusions were measured. A total of 977 children were enrolled. Most (74%) children were anemic in the PICU (33% on admission, 41% developed anemia). Blood draws accounted for 73% of daily blood loss; median loss was 5.0 ml/day. Forty-nine percent of children received transfusions; 74% of first transfusions were on Days 1-2. After adjusting for age and illness severity, compared with nontransfused children, children who underwent transfusion had significantly longer days of mechanical ventilation (2.1 d, P < 0.001) and PICU stay (1.8 d, P = 0.03), and had increased mortality (odds ratio [OR], 11.6; 95% confidence interval [CI], 1.43-90.9; P = 0.02), nosocomial infections (OR, 1.9; 95% CI, 1.2-3.0; P = 0.004), and cardiorespiratory dysfunction (OR, 2.1; 95% CI, 1.5-3.0; P < 0.001). High blood loss per kilogram body weight from blood draws (OR, 1.11; 95% CI, 1.03-1.2; P = 0.01) was associated with RBC transfusion more than 48 hours after admission. The most common indication for transfusion was low hemoglobin (42%). Pretransfusion hemoglobin values varied greatly (mean, 9.7 +/- 2.7 g/dl). CONCLUSIONS Critically ill children are at significant risk for developing anemia and receiving blood transfusions. Transfusion in the PICU was associated with worse outcomes. It is imperative to minimize blood loss from blood draws and to set clear transfusion thresholds.

A retrospective cohort study of prognostic factors associated with outcome in pediatric severe sepsis: What is the role of steroids?*

Objective: Systemic corticosteroids remain controversial in the treatment of pediatric patients with severe sepsis. Recent studies in septic adults have shown decreased mortality with the use of hydrocortisone in patients with relative adrenal insufficiency. We conducted this large retrospective cohort study to further characterize severe sepsis in infants and children and correlates of outcome, including the use of steroids. Design: Retrospective cohort study. Setting: The Pediatric Health Information System (PHIS), an administrative database of the Child Health Corporation of America (CHCA), was queried for inpatients 0–17 yrs of age with severe sepsis (defined here as an International Classification of Disease 9th edition code for infection with use of simultaneous mechanical ventilation and vasoactive infusions) from 2001 to 2002. In addition to demographic information, use of systemic corticosteroids (hydrocortisone, methylprednisolone, or dexamethasone) concurrent with the ventilatory and vasoactive support was collected. Subjects: Data from PHIS. Interventions: None. Measurements and Main Results: Patients (n = 6693) were identified at 27 PHIS-participating CHCA member hospitals. Overall mortality was 24%; univariate predictors of death included use of steroids (odds ratio [OR], 1.9; 95% confidence interval (CI), 1.7, 2.2), older age (e.g., 13–17 yrs vs. neonates; OR, 1.6; 95% CI, 1.3, 2.0), a hematologic-oncologic diagnosis (OR, 5.87; 95% CI, 4.19, 8.23), and moderate vs. high case volume (OR, 1.25; 95% CI, 1.09, 1.44). Age, hematologic-oncologic diagnosis, case volume, and use of steroids remained independent predictors of mortality in multivariable analysis. Conclusions: From this administrative database analysis, there is no evidence that steroids are associated with improved outcome in critically ill infants and children with sepsis. Although steroids may be given preferentially to more severely ill children, their use was associated with increased mortality. Clinicians should maintain equipoise on this topic pending prospective randomized clinical trials.

Chronic conditions among children admitted to U.S. pediatric intensive care units: Their prevalence and impact on risk for mortality and prolonged length of stay*

Objective:To estimate the prevalence of chronic conditions among children admitted to U.S. pediatric intensive care units and to assess whether patients with complex chronic conditions experience pediatric intensive care unit mortality and prolonged length of stay risk beyond that predicted by commonly used severity-of-illness risk-adjustment models. Design, Setting, and Patients:Retrospective cohort analysis of 52,791 pediatric admissions to 54 U.S. pediatric intensive care units that participated in the Virtual Pediatric Intensive Care Unit Systems database in 2008. Measurements:Hierarchical logistic regression models, clustered by pediatric intensive care unit site, for pediatric intensive care unit mortality and length of stay >15 days. Standardized mortality ratios adjusted for severity-of-illness score alone and with complex chronic conditions. Main Results:Fifty-three percent of pediatric intensive care unit admissions had complex chronic conditions, and 18.5% had noncomplex chronic conditions. The prevalence of these conditions and their organ system subcategories varied considerably across sites. The majority of complex chronic condition subcategories were associated with significantly greater odds of pediatric intensive care unit mortality (odds ratios 1.25–2.9, all p values < .02) compared to having a noncomplex chronic condition or no chronic condition, after controlling for age, gender, trauma, and severity-of-illness. Only respiratory, gastrointestinal, and rheumatologic/orthopedic/psychiatric complex chronic conditions were not associated with increased odds of pediatric intensive care unit mortality. All subcategories were significantly associated with prolonged length of stay. All noncomplex chronic condition subcategories were either not associated or were negatively associated with pediatric intensive care unit mortality, and most were not associated with prolonged length of stay, compared to having no chronic conditions. Among this group of pediatric intensive care units, adding complex chronic conditions to risk-adjustment models led to greater model accuracy but did not substantially change unit-level standardized mortality ratios. Conclusions:Children with complex chronic conditions were at greater risk for pediatric intensive care unit mortality and prolonged length of stay than those with no chronic conditions, but the magnitude of risk varied across subcategories. Inclusion of complex chronic conditions into models of pediatric intensive care unit mortality improved model accuracy but had little impact on standardized mortality ratios.

Socioeconomic factors and adolescent pregnancy outcomes: distinctions between neonatal and post-neonatal deaths?

BackgroundYoung maternal age has long been associated with higher infant mortality rates, but the role of socioeconomic factors in this association has been controversial. We sought to investigate the relationships between infant mortality (distinguishing neonatal from post-neonatal deaths), socioeconomic status and maternal age in a large, retrospective cohort study.MethodsWe conducted a population-based cohort study using linked birth-death certificate data for Missouri residents during 1997–1999. Infant mortality rates for all singleton births to adolescent women (12–17 years, n = 10,131; 18–19 years, n = 18,954) were compared to those for older women (20–35 years, n = 28,899). Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) for all potential associations.ResultsThe risk of infant (OR 1.95, CI 1.54–2.48), neonatal (1.69, 1.24–2.31) and post-neonatal mortality (2.47, 1.70–3.59) were significantly higher for younger adolescent (12–17 years) than older (20–34 years) mothers. After adjusting for race, marital status, age-appropriate education level, parity, smoking status, prenatal care utilization, and poverty status (indicated by participation in WIC, food stamps or Medicaid), the risk of post-neonatal mortality (1.73, 1.14–2.64) but not neonatal mortality (1.43, 0.98–2.08) remained significant for younger adolescent mothers. There were no differences in neonatal or post-neonatal mortality risks for older adolescent (18–19 years) mothers.ConclusionSocioeconomic factors may largely explain the increased neonatal mortality risk among younger adolescent mothers but not the increase in post-neonatal mortality risk.

Management of pediatric trauma

Injury is the number 1 killer of children in the United States. In 2004, injury accounted for 59.5% of all deaths in children younger than 18 years. The financial burden to society of children who survive childhood injury with disability continues to be enormous. The entire process of managing childhood injury is complex and varies by region. Only the comprehensive cooperation of a broadly diverse group of people will have a significant effect on improving the care and outcome of injured children. This statement has been endorsed by the American Association of Critical-Care Nurses, American College of Emergency Physicians, American College of Surgeons, American Pediatric Surgical Association, National Association of Childrens Hospitals and Related Institutions, National Association of State EMS Officials, and Society of Critical Care Medicine.

Day 1 multiple organ dysfunction syndrome is associated with poor functional outcome and mortality in the pediatric intensive care unit.

Objective: The epidemiology and outcomes of multiple organ dysfunction syndrome (MODS) are incompletely characterized in the pediatric population due to small sample size and conflicting diagnoses of organ failure. We sought to describe the epidemiology and outcomes of early MODS in a large clinical database of pediatric intensive care unit (PICU) patients based on consensus definitions of organ failure. Design: Retrospective analysis of a contemporaneously collected clinical PICU database. Setting: Virtual Pediatric Intensive Care Unit Performance System database patient admissions from January 2004 to December 2005 for 35 U.S. children’s hospitals. Patients: We evaluated 63,285 consecutive PICU admissions from January 2004 to December 2005 in the Virtual Pediatric Intensive Care Unit Performance System database. We excluded patients younger than 1 month or older than 18 years of age, and hospitals with >10% missing values for MODS variables. We identified day 1 MODS by International Pediatric Sepsis Consensus Conference criteria with day 1 laboratory and vital sign values. We evaluated functional status using Pediatric Overall Performance Category and Pediatric Cerebral Performance Category scores from PICU admission and discharge. Interventions: Analysis: Student’s t test, chi-square test, Mann-Whitney rank sum, Kruskal-Wallis, and linear and logistic regression. Measurements and Main Results: We analyzed 44,693 admissions from 28 hospitals meeting inclusion criteria. Overall PICU mortality was 2.8%. We identified day 1 MODS in 18.6% of admissions. Patients with day 1 MODS had higher mortality (10.0% vs. 1.2%, p < .001), longer PICU length of stay (3.6 vs. 1.3 days, p < .001), and larger change from baseline Pediatric Overall Performance Category and Pediatric Cerebral Performance Category scores at time of PICU discharge (p < .001). Infants had the highest incidence of day 1 MODS (25.2% vs. 16.5%, p < .001) compared with other age groups. Conclusions: Using the largest clinical dataset to date and consensus definitions for organ failure, we found that children with MODS present on day 1 of intensive care unit admission have worse functional outcomes, higher mortality, and longer PICU length of stay than children who do not have MODS on day 1. Infants are disproportionally affected by MODS.

Characteristics of Children Intubated and Mechanically Ventilated in 16 PICUs

BACKGROUND When designing multicenter clinical trials, it is important to understand the characteristics of children who have received ventilation in PICUs. METHODS This study involved the secondary analysis of an existing data set of all children intubated and mechanically ventilated from 16 US PICUs who were initially screened for a multicenter clinical trial on pediatric acute lung injury (ALI). RESULTS A total of 12,213 children between 2 weeks and 18 years of age who were intubated and mechanically ventilated were included, representing 30% of PICU admissions (center range, 20 to 64%). Of the children who received ventilation, 22% had cyanotic congenital heart disease; 26% had respiratory failure but not bilateral pulmonary infiltrates on chest radiograph; 8% had chronic respiratory disease; 7% had upper airway obstruction; and 5% had reactive airway disease. At least 1,457 patients (15%) with respiratory failure lacked an arterial line. Of these patients, 97% had a positive end-expiratory pressure <or= 8 cm H(2)O, and 80% were supported on an Fio(2) of <or= 0.40. Moreover, 104 of 904 patients (12%) with pulse oximetric saturation (Spo(2)) and Fio(2) measurements available would have met the oxygenation criteria for ALI according to Spo(2)/Fio(2) ratio criteria. CONCLUSIONS At least 30% of children in a cross-section of US PICUs are endotracheally intubated, and 25% of those with respiratory failure do not fulfill the radiographic criteria for ALI. Although few patients without an indwelling arterial line require more than modest ventilator support, many may still meet the oxygenation criteria for ALI. These findings will facilitate sample size calculations and help to determine feasibility for future trials on pediatric mechanical ventilation.

Corticosteroids for the prevention of reintubation and postextubation stridor in pediatric patients: A meta-analysis.

Objective To determine whether corticosteroids are effective in preventing or treating postextubation stridor and in reducing the need for subsequent reintubation of the trachea in critically ill infants and children. Design Meta-analysis of published randomized controlled trials. Data Sources References of each trial from a MEDLINE search were reviewed, and experts in the field were contacted. Study Selection Any randomized controlled trial comparing the administration of corticosteroids with placebo on the prevalence of reintubation or postextubation stridor in infants or children receiving mechanical ventilation via an endotracheal tube in an intensive care unit. Data Extraction Data extraction and methodologic quality assessment were assessed independently by two reviewers. Data Synthesis Six controlled clinical trials met the criteria for inclusion; three trials pertain to neonates and three to children. Five trials examined the use of steroids for the prevention of reintubation (four of these evaluated postextubation stridor specifically); one trial examined the use of steroids to treat existing postextubation stridor in children. There was a nonsignificant trend toward a decreased rate of reintubation in all subjects when prophylactic steroids were used (n = 376, relative risk [RR] = 0.34, 95% confidence interval [CI] = 0.05–2.33). Prophylactic use of steroids reduced postextubation stridor in the pooled studies (n = 325, RR = 0.50, 95% CI = 0.28–0.88). In young children, there were significant reductions of postextubation stridor with preventive treatment (n = 216, RR = 0.53, 95% CI = 0.28–0.97), and a trend toward less stridor was observed in neonates (n = 109, RR = 0.42, 95% CI = 0.07–2.32). There was a nonsignificant trend toward a reduced reintubation rate when steroids were used to treat existing upper airway obstruction requiring reintubation (RR = 0.55, 95% CI = 0.17–1.78). Side effects were seldom reported and could not be evaluated. Conclusions Prophylactic administration of dexamethasone before elective extubation reduces the prevalence of postextubation stridor in neonates and children and may reduce the rate of reintubation.

A Multicenter Collaborative Approach to Reducing Pediatric Codes Outside the ICU

OBJECTIVES: The Child Health Corporation of America formed a multicenter collaborative to decrease the rate of pediatric codes outside the ICU by 50%, double the days between these events, and improve the patient safety culture scores by 5 percentage points. METHODS: A multidisciplinary pediatric advisory panel developed a comprehensive change package of process improvement strategies and measures for tracking progress. Learning sessions, conference calls, and data submission facilitated collaborative group learning and implementation. Twenty Child Health Corporation of America hospitals participated in this 12-month improvement project. Each hospital identified at least 1 noncritical care target unit in which to implement selected elements of the change package. Strategies to improve prevention, detection, and correction of the deteriorating patient ranged from relatively simple, foundational changes to more complex, advanced changes. Each hospital selected a broad range of change package elements for implementation using rapid-cycle methodologies. The primary outcome measure was reduction in codes per 1000 patient days. Secondary outcomes were days between codes and change in patient safety culture scores. RESULTS: Code rate for the collaborative did not decrease significantly (3% decrease). Twelve hospitals reported additional data after the collaborative and saw significant improvement in code rates (24% decrease). Patient safety culture scores improved by 4.5% to 8.5%. CONCLUSIONS: A complex process, such as patient deterioration, requires sufficient time and effort to achieve improved outcomes and create a deeply embedded culture of patient safety. The collaborative model can accelerate improvements achieved by individual institutions.

Lack of insurance coverage and urgent care use for asthma: A retrospective cohort study

BackgroundAsthma is a common chronic disease with profound impacts upon individuals and the US health care system. Inadequate health care coverage has been associated with more frequent and severe exacerbations of the disease. We examined the relationship between adequacy of health care coverage and use of emergent care of adults with asthma.MethodsThe 2001 Behavioral Risk Factor Surveillance System was the source of data on adults with current asthma. Bivariate and multiple logistic regression analysis modeled identifiable factors in predicting urgent or emergent care.ResultsKey variables included demographics and information on self-reported gaps in health care coverage. The primary outcome was emergency room or urgent care visits for worsening of asthma symptoms. Of 16,234 subjects nationally with current asthma, 2,195 from eight states had valid responses to a supplemental module asking about emergency room use or urgent care visits because of asthma. Thirty four percent of these individuals required such care in the previous year. Having an interruption in health care coverage in the past year was associated with an increased risk of needed urgent or emergent care (crude Odds Ratio [OR] 1.48, 95% confidence intervals [CI]1.03, 2.1). The association was not statistically significant in the adjusted multivariate model including race/ethnicity, employment status, gender, age, education and the ability to identify a primary physician (adjusted OR 1.2, 95% CI 0.8, 1.8).ConclusionThis study provides population-level, generalizable evidence of increased risk of exacerbations of asthma in adults and (1) their demographic characteristics, and (2) continuous adequate health care coverage.