Therapeutic hypothermia is recommended for comatose adults after witnessed out-of-hospital cardiac arrest, but data about this intervention in children are limited. We conducted this trial of two targeted temperature interventions at 38 children's 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. 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. 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.)

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 exp...

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. In a trial conducted at 37 children’s 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. 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. 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.)

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. Secondary analysis of a prospective observational study of 98 pediatric patients after cardiopulmonary bypass at a tertiary care, academic, PICU. None. 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). 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.

Objectives To describe the magnitude of off-label drug use, to identify drugs most commonly used off-label, and to identify factors associated with off-label drug use in children hospitalized in the United States. Design Retrospective cohort study. Setting Administrative database containing inpatient resource utilization data from January 1 to December 31, 2004, from 31 tertiary care pediatric hospitals in the United States. Participants Hospitalized patients 18 years or younger. Main Exposures Institution and patient characteristics. Main Outcome Measures Off-label drug use was defined as use of a specific drug in a patient younger than the Food and Drug Administration–approved age range for any indication of that drug. Results At least 1 drug was used off-label in 297 592 (78.7%) of 355 409 patients discharged during the study. Off-label use accounted for $270 275 849 (40.5%) of the total dollars spent on these medications. Medications classified as central or autonomic nervous system agents or as fluids or nutrients, or gastrointestinal tract agents were most commonly used off-label, whereas antineoplastic agents were rarely used off-label. Factors associated with off-label use in multivariate analysis were as follows: undergoing a surgical procedure, age older than 28 days, greater severity of illness, and all-cause in-hospital mortality. Conclusions Most patients hospitalized at tertiary care pediatric institutions receive at least 1 medication outside the terms of the Food and Drug Administration product license. Substantial variation in the frequency of off-label use was observed across diagnostic categories and drug classes. Despite the frequent off-label use of drugs, using an administrative database, we cannot determine which of these treatments are unsafe or ineffective and which treatments result in substantial benefit to the patient.