Denise M. Goodman

Therapeutic Hypothermia after Out-of-Hospital Cardiac Arrest in Children

BACKGROUND Therapeutic hypothermia is recommended for comatose adults after witnessed out-of-hospital cardiac arrest, but data about this intervention in children are limited. METHODS We conducted this trial of two targeted temperature interventions at 38 childrens hospitals involving children who remained unconscious after out-of-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose patients who were older than 2 days and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a Vineland Adaptive Behavior Scales, second edition (VABS-II), score of 70 or higher (on a scale from 20 to 160, with higher scores indicating better function), was evaluated among patients with a VABS-II score of at least 70 before cardiac arrest. RESULTS A total of 295 patients underwent randomization. Among the 260 patients with data that could be evaluated and who had a VABS-II score of at least 70 before cardiac arrest, there was no significant difference in the primary outcome between the hypothermia group and the normothermia group (20% vs. 12%; relative likelihood, 1.54; 95% confidence interval [CI], 0.86 to 2.76; P=0.14). Among all the patients with data that could be evaluated, the change in the VABS-II score from baseline to 12 months was not significantly different (P=0.13) and 1-year survival was similar (38% in the hypothermia group vs. 29% in the normothermia group; relative likelihood, 1.29; 95% CI, 0.93 to 1.79; P=0.13). The groups had similar incidences of infection and serious arrhythmias, as well as similar use of blood products and 28-day mortality. CONCLUSIONS In comatose children who survived out-of-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a good functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute and others; THAPCA-OH ClinicalTrials.gov number, NCT00878644.).

How Well Can Hospital Readmission Be Predicted in a Cohort of Hospitalized Children? A Retrospective, Multicenter Study

BACKGROUND. Children with complex chronic conditions depend on both their families and systems of pediatric health care, social services, and financing. Investigations into the workings of this ecology of care would be advanced by more accurate methods of population-level predictions of the likelihood for future hospitalization. METHODS. This was a retrospective cohort study. Hospital administrative data were collected from 38 childrens hospitals in the United States for the years 2003–2005. Participants included patients between 2 and 18 years of age discharged from an index hospitalization during 2004. Patient characteristics documented during the index hospitalization or any previous hospitalization during the preceding 365 days were included. The main outcome measure was readmission to the hospital during the 365 days after discharge from the index admission. RESULTS. Among the cohort composed of 186856 patients discharged from the participating hospitals during 2004, the mean age was 9.2 years, with 54.4% male and 52.9% identified as non-Hispanic white. A total of 17.4% were admitted during the previous 365 days, and among those discharged alive (0.6% died during the admission), 16.7% were readmitted during the ensuing 365 days. The final readmission model exhibited a c statistic of 0.81 across all hospitals, with a range from 0.76 to 0.84 for each hospital. Bootstrap-based assessments demonstrated the stability of the final model. CONCLUSIONS. Accurate population-level prediction of hospital readmissions is possible, and the resulting predicted probability of hospital readmission may prove useful for health services research and planning.

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.

Early postoperative fluid overload precedes acute kidney injury and is associated with higher morbidity in pediatric cardiac surgery patients.

Objective: Fluid overload has been independently associated with increased morbidity and mortality in pediatric patients with renal failure, acute lung injury, and sepsis. Pediatric patients who undergo cardiopulmonary bypass are at risk for poor cardiac, pulmonary, and renal outcomes. They are also at risk of fluid overload from cardiopulmonary bypass, which stimulates inflammation, release of antidiuretic hormone, and capillary leak. This study tested the hypothesis that patients with fluid overload in the early postcardiopulmonary bypass period have worse outcomes than those without fluid overload. We also examined the timing of the association between postcardiopulmonary bypass acute kidney injury and fluid overload. Design, Setting, and Patients: Secondary analysis of a prospective observational study of 98 pediatric patients after cardiopulmonary bypass at a tertiary care, academic, PICU. Interventions: None. Measurements and Main Results: Early postoperative fluid overload, defined as a fluid balance 5% above body weight by the end of postoperative day 1, occurred in 30 patients (31%). Patients with early fluid overload spent 3.5 days longer in the hospital, spent 2 more days on inotropes, and were more likely to require prolonged mechanical ventilation than those without early fluid overload (all p < 0.001). Fluid overload was associated with the development of acute kidney injury and more often preceded it than followed it. Conversely, acute kidney injury was not associated with more fluid accumulation. Patients with fluid overload were administered higher fluid volume over the study period, 395.4 ± 150 mL/kg vs. 193.2 ± 109.1 mL/kg (p < 0.001), and had poor urinary response to diuretics. Cumulative fluid administered was an excellent predictor of pediatric-modified Risk, Injury, Failure, Loss, and End-stage “Failure” (area under the receiver-operating characteristic curve, 0.963; 95% CI, 0.916–1.000; p = 0.002). Conclusions: Early postoperative fluid overload is independently associated with worse outcomes in pediatric cardiac surgery patients who are 2 weeks to 18 years old. Patients with fluid overload have higher rates of postcardiopulmonary bypass acute kidney injury, and the occurrence of fluid overload precedes acute kidney injury. However, acute kidney injury is not consistently associated with fluid overload.

Corticosteroids and Outcome in Children Undergoing Congenital Heart Surgery Analysis of the Pediatric Health Information Systems Database

Background— Children undergoing congenital heart surgery often receive corticosteroids with the aim of reducing the inflammatory response after cardiopulmonary bypass; however, the value of this approach is unclear. Methods and Results— The Pediatric Health Information Systems Database was used to evaluate outcomes associated with corticosteroids in children (0 to 18 years of age) undergoing congenital heart surgery at 38 US centers from 2003 to 2008. Propensity scores were constructed to account for potential confounders: age, sex, race, prematurity, genetic syndrome, type of surgery (Risk Adjustment in Congenital Heart Surgery [RACHS-1] category), center, and center volume. Multivariable analysis, adjusting for propensity score and individual covariates, was performed to evaluate in-hospital mortality, postoperative length of stay, duration of ventilation, infection, and use of insulin. A total of 46 730 children were included; 54% received corticosteroids. In multivariable analysis, there was no difference in mortality among corticosteroid recipients and nonrecipients (odds ratio, 1.13; 95% confidence interval, 0.98 to 1.30). Corticosteroids were associated with longer length of stay (least square mean difference, 2.18 days; 95% confidence interval, 1.62 to 2.74 days), greater infection (odds ratio, 1.27; 95% confidence interval, 1.10 to 1.46), and greater use of insulin (odds ratio, 2.45; 95% confidence interval, 2.24 to 2.67). There was no difference in duration of ventilation. In analysis stratified by RACHS-1 category, no significant benefit was seen in any group, and the association of corticosteroids with increased morbidity was most prominent in RACHS-1 categories 1 through 3. Conclusion— In this observational analysis of children undergoing congenital heart surgery, we were unable to demonstrate a significant benefit associated with corticosteroids and found that corticosteroids may be associated with increased morbidity, particularly in lower-risk patients. # Clinical Perspective {#article-title-43}Background— Children undergoing congenital heart surgery often receive corticosteroids with the aim of reducing the inflammatory response after cardiopulmonary bypass; however, the value of this approach is unclear. Methods and Results— The Pediatric Health Information Systems Database was used to evaluate outcomes associated with corticosteroids in children (0 to 18 years of age) undergoing congenital heart surgery at 38 US centers from 2003 to 2008. Propensity scores were constructed to account for potential confounders: age, sex, race, prematurity, genetic syndrome, type of surgery (Risk Adjustment in Congenital Heart Surgery [RACHS-1] category), center, and center volume. Multivariable analysis, adjusting for propensity score and individual covariates, was performed to evaluate in-hospital mortality, postoperative length of stay, duration of ventilation, infection, and use of insulin. A total of 46 730 children were included; 54% received corticosteroids. In multivariable analysis, there was no difference in mortality among corticosteroid recipients and nonrecipients (odds ratio, 1.13; 95% confidence interval, 0.98 to 1.30). Corticosteroids were associated with longer length of stay (least square mean difference, 2.18 days; 95% confidence interval, 1.62 to 2.74 days), greater infection (odds ratio, 1.27; 95% confidence interval, 1.10 to 1.46), and greater use of insulin (odds ratio, 2.45; 95% confidence interval, 2.24 to 2.67). There was no difference in duration of ventilation. In analysis stratified by RACHS-1 category, no significant benefit was seen in any group, and the association of corticosteroids with increased morbidity was most prominent in RACHS-1 categories 1 through 3. Conclusion— In this observational analysis of children undergoing congenital heart surgery, we were unable to demonstrate a significant benefit associated with corticosteroids and found that corticosteroids may be associated with increased morbidity, particularly in lower-risk patients.

Children With Medical Complexity And Medicaid: Spending And Cost Savings

A small but growing population of children with medical complexity, many of whom are covered by Medicaid, accounts for a high proportion of pediatric health care spending. We first describe the expenditures for children with medical complexity insured by Medicaid across the care continuum. We report the increasingly large amount of spending on hospital care for these children, relative to the small amount of primary care and home care spending. We then present a business case that estimates how cost savings might be achieved for children with medical complexity from potential reductions in hospital and emergency department use and shows how the savings could underwrite investments in outpatient and community care. We conclude by discussing the importance of these findings in the context of Medicaids quality of care and health care reform.

Defining pediatric sepsis by different criteria: Discrepancies in populations and implications for clinical practice

Objective: Pediatric patients with sepsis are identified using related but distinct criteria for clinical, research, and administrative purposes. The overlap between these criteria will affect the validity of extrapolating data across settings. We sought to quantify the extent of agreement among different criteria for pediatric severe sepsis/septic shock and to detect systematic differences between these cohorts. Design: Observational cohort study. Setting: Forty-two bed pediatric intensive care unit at an academic medical center. Patients: A total of 1,729 patients ⩽18 yrs-old. Interventions: None. Measurements and Main Results: All patients were screened for severe sepsis or septic shock using consensus guidelines (research criteria), diagnosis by healthcare professionals (clinical criteria), and International Classification of Diseases, Ninth Revision, Clinical Modification codes (administrative criteria). Cohen’s &kgr; determined the level of agreement among criteria, and patient characteristics were compared between cohorts. Ninety (5.2%) patients were identified by research, 96 (5.6%) by clinical, and 103 (6.0%) by administrative criteria. The &kgr; ± standard error for pair-wise comparisons was 0.67 ± 0.04 for research-clinical, 0.52 ± 0.05 for research-administrative, and 0.55 ± 0.04 for clinical-administrative. Of the patients in the clinical cohort, 67% met research and 58% met administrative criteria. The research cohort exhibited a higher Pediatric Index of Mortality-2 score (median, interquartile range 5.2, 1.6-13.3) than the clinical (3.6, 1.1-6.2) and administrative (3.9, 1.0-6.0) cohorts (p = .005), an increased requirement for vasoactive infusions (74%, 57%, and 45%, p < .001), and a potential bias toward an increased proportion with respiratory dysfunction compared with clinical practice. Conclusions: Although research, clinical, and administrative criteria yielded a similar incidence (5%-6%) for pediatric severe sepsis/septic shock, there was only a moderate level of agreement in the patients identified by different criteria. One third of patients diagnosed clinically with sepsis would not have been included in studies based on consensus guidelines or International Classification of Diseases, Ninth Revision, Clinical Modification codes. Differences in patient selection need to be considered when extrapolating data across settings.

Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children

Background Targeted temperature management is recommended for comatose adults and children after out‐of‐hospital cardiac arrest; however, data on temperature management after in‐hospital cardiac arrest are limited. Methods In a trial conducted at 37 childrens hospitals, we compared two temperature interventions in children who had had in‐hospital cardiac arrest. Within 6 hours after the return of circulation, comatose children older than 48 hours and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a score of 70 or higher on the Vineland Adaptive Behavior Scales, second edition (VABS‐II, on which scores range from 20 to 160, with higher scores indicating better function), was evaluated among patients who had had a VABS‐II score of at least 70 before the cardiac arrest. Results The trial was terminated because of futility after 329 patients had undergone randomization. Among the 257 patients who had a VABS‐II score of at least 70 before cardiac arrest and who could be evaluated, the rate of the primary efficacy outcome did not differ significantly between the hypothermia group and the normothermia group (36% [48 of 133 patients] and 39% [48 of 124 patients], respectively; relative risk, 0.92; 95% confidence interval [CI], 0.67 to 1.27; P=0.63). Among 317 patients who could be evaluated for change in neurobehavioral function, the change in VABS‐II score from baseline to 12 months did not differ significantly between the groups (P=0.70). Among 327 patients who could be evaluated for 1‐year survival, the rate of 1‐year survival did not differ significantly between the hypothermia group and the normothermia group (49% [81 of 166 patients] and 46% [74 of 161 patients], respectively; relative risk, 1.07; 95% CI, 0.85 to 1.34; P=0.56). The incidences of blood‐product use, infection, and serious adverse events, as well as 28‐day mortality, did not differ significantly between groups. Conclusions Among comatose children who survived in‐hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a favorable functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute; THAPCA‐IH ClinicalTrials.gov number, NCT00880087.)

Adults With Chronic Health Conditions Originating in Childhood: Inpatient Experience in Children's Hospitals

OBJECTIVE: To describe the rate of increase of the population of adults seeking care as inpatients in childrens hospitals over time. PATIENTS AND METHODS: We analyzed data from January 1, 1999, to December 31, 2008, from patients hospitalized at 30 academic childrens hospitals, including growth rates according to age group (pediatric: aged <18 years; transitional: aged 18–21 years; or adult: aged >21 years) and disease. RESULTS: There were 3 343 194 hospital discharges for 2 143 696 patients. Transitional patients represented 2.0%, and adults represented 0.8%, totaling 59 974 patients older than 18 years. The number of unique patients, admissions, patient-days, and charges increased in all age groups over the study period and are projected to continue to increase. Resource use was disproportionately higher in the older ages. The growth of transitional patients exceeded that of others, with 6.9% average annual increase in discharges, 7.6% in patient-days, and 15% in charges. Chronic conditions occurred in 87% of adults compared with 48% of pediatric patients. Compared with pediatric patients, the rates of increase of inpatient-days increased significantly for transitional age patients with cystic fibrosis, malignant neoplasms, and epilepsy, and for adults with cerebral palsy. Annual growth rates of charges increased for transitional and adult patients for all diagnoses except cystic fibrosis and sickle cell disease. CONCLUSIONS: The population of adults with diseases originating in childhood who are hospitalized at childrens hospitals is increasing, with varying disease-specific changes over time. Our findings underscore the need for proactive identification of strategies to care for adult survivors of pediatric diseases.

A review of the natriuretic hormone system's diagnostic and therapeutic potential in critically ill children.

Objective: To review the natriuretic hormone system and discuss its diagnostic, prognostic, and therapeutic potential in critically ill children. Data Source: A thorough literature search of MEDLINE was performed using search terms including heart defects, congenital; cardiopulmonary bypass, atrial natriuretic factor; natriuretic peptide, brain; carperitide; nesiritide. Preclinical and clinical investigations and review articles were identified that describe the current understanding of the natriuretic hormone system and its role in the regulation of vascular tone and fluid balance in healthy adults and children and in those with underlying cardiac, pulmonary, and renal disease. Results: A predictable activation of the natriuretic hormone system occurs in children with congenital heart disease and congestive heart failure. Further study is needed to confirm preliminary reports that measurement of natriuretic hormone levels in critically ill children provides diagnostic and prognostic information, as has been demonstrated in adult cardiac populations. Natriuretic hormone infusions provide favorable hemodynamic changes and symptomatic relief when used in adults with decompensated congestive heart failure, and uncontrolled case series suggest that similar benefits may exist in children. The biological activity of the natriuretic hormone system may be decreased following pediatric cardiopulmonary bypass, and additional studies are needed to determine whether natriuretic hormone infusions provide clinical benefit in the postoperative period. Preliminary reports suggest that natriuretic hormone infusions cause physiologic improvements in adults with acute lung injury and asthma but not in those with acute renal failure. Conclusions: Although important perturbations of the natriuretic hormone system occur in critically ill infants and children, further investigation is needed before the measurement of natriuretic peptides and the use of natriuretic hormone infusions are incorporated into routine practice.