Chani Traube

Cornell Assessment of Pediatric Delirium: A Valid, Rapid, Observational Tool for Screening Delirium in the PICU*

Objective:To determine validity and reliability of the Cornell Assessment of Pediatric Delirium, a rapid observational screening tool. Design:Double-blinded assessments were performed with the Cornell Assessment of Pediatric Delirium completed by nursing staff in the PICU. These ratings were compared with an assessment by consultation liaison child psychiatrist using the Diagnostic and Statistical Manual IV criteria as the “gold standard” for diagnosis of delirium. An initial series of duplicate Cornell Assessment of Pediatric Delirium assessments were performed in blinded fashion to assess interrater reliability. Nurses recorded the time required to complete the Cornell Assessment of Pediatric Delirium screen. Setting:Twenty-bed general PICU in a major urban academic medical center over a 10-week period, March–May 2012. Patients:One hundred eleven patients stratified over ages ranging from 0 to 21 years and across developmental levels. Intervention:Two hundred forty-eight paired assessments completed. Measurements and Main Results:The Cornell Assessment of Pediatric Delirium had an overall sensitivity of 94.1% (95% CI, 83.8–98.8%) and specificity of 79.2% (95% CI, 73.5–84.9%). Overall Cronbach’s &agr; of 0.90 was observed, with a range of 0.87–0.90 for each of the eight items, indicating good internal consistency. A scoring cut point of 9 demonstrated good interrater reliability of the Cornell Assessment of Pediatric Delirium when comparing results of the screen between nurses (overall &kgr; = 0.94; item range &kgr; = 0.68–0.78). In patients without significant developmental delay, sensitivity was 92.0% (95% CI, 85.7–98.3%) and specificity was 86.5% (95% CI, 75.4–97.6%). In developmentally delayed children, the Cornell Assessment of Pediatric Delirium showed decreased specificity of 51.2% (95% CI, 24.7–77.8%) but sensitivity remained high at 96.2% (95% CI, 86.5–100%). The Cornell Assessment of Pediatric Delirium takes less than 2 minutes to complete. Conclusions:With an overall prevalence rate of 20.6% in our study population, delirium is a common problem in pediatric critical care. The Cornell Assessment of Pediatric Delirium is a valid, rapid, observational nursing screen that is urgently needed for the detection of delirium in PICU settings.

Pediatric delirium and associated risk factors: a single-center prospective observational study.

Objective: To describe a single-institution pilot study regarding prevalence and risk factors for delirium in critically ill children. Design: A prospective observational study, with secondary analysis of data collected during the validation of a pediatric delirium screening tool, the Cornell Assessment of Pediatric Delirium. Setting: This study took place in the PICU at an urban academic medical center. Patients: Ninety-nine consecutive patients, ages newborn to 21 years. Intervention: Subjects underwent a psychiatric evaluation for delirium based on the Diagnostic and Statistical Manual IV criteria. Measurements and Main Results: Prevalence of delirium in this sample was 21%. In multivariate analysis, risk factors associated with the diagnosis of delirium were presence of developmental delay, need for mechanical ventilation, and age 2–5 years. Conclusions: In our institution, pediatric delirium is a prevalent problem, with identifiable risk factors. Further large-scale prospective studies are required to explore multi-institutional prevalence, modifiable risk factors, therapeutic interventions, and effect on long-term outcomes.

Genetic delivery of an anti-RSV antibody to protect against pulmonary infection with RSV

Respiratory syncytial virus (RSV) is a common cause of severe lower respiratory tract infections. Protection against infection with RSV can be achieved by monthly administration of the humanized monoclonal antibody palivizumab. The present study analyzes if genetic delivery of a murine version of palivizumab by single administration would achieve high-level and sustained antibody expression to protect mice against pulmonary infection with RSV. A murine version of the palivizumab antibody was constructed by replacing the human sequences with sequences from the constant region of a murine IgG1 antibody, while preserving the complementarity-determining region. As a proof-of-principle to test the validity of the strategy, the coding sequence for the heavy and light chains were cloned into a replication-defective serotype 5 human adenovirus vector (AdalphaRSV). Antibody expression and specificity for RSV was confirmed by Western analysis. To determine if AdalphaRSV would mediate production of anti-RSV antibodies in vivo, 5x10(10) particle units of AdalphaRSV or a control vector without transgene (AdNull), were administered intravenously to BALB/c mice. RSV neutralizing antibodies were detected in the serum after 4 days in mice receiving AdalphaRSV but not in AdNull-infected or naive mice (p<0.05). The mice that had received AdalphaRSV had at least 5.4-fold lower RSV titers in the lung 4 days following intranasal challenge with RSV compared to the AdNull or naive group (p<0.01). To evaluate long-term protection, the antibody construct was expressed in a non-human primate serotype rh.10 adeno-associated virus vector (AAVrh.10alphaRSV). RSV neutralizing antibodies were detected in serum and bronchoalveolar lavage fluid for up to 21 wk following intrapleural administration of AAVrh.10alphaRSV, but not with a control AAV vector expressing an unrelated transgene (AAVrh.10alpha1AT). Following challenge with RSV at 7 or 21 wk, 14.3-fold and 10.6-fold lower RSV titers were observed after 4 days in the lungs of mice that had received AAVrh.10alphaRSV compared to AAVrh.10alpha1AT (p<0.05). Together these data demonstrate that a gene transfer strategy for delivery of an anti-RSV antibody can generate protective immunity in mice against RSV infection in the respiratory tract and may provide an alternative to the administration of the antibody itself.

Delirium and Mortality in Critically Ill Children: Epidemiology and Outcomes of Pediatric Delirium*

Objectives: Delirium occurs frequently in adults and is an independent predictor of mortality. However, the epidemiology and outcomes of pediatric delirium are not well-characterized. The primary objectives of this study were to describe the frequency of delirium in critically ill children, its duration, associated risk factors, and effect on in-hospital outcomes, including mortality. Secondary objectives included determination of delirium subtype, and effect of delirium on duration of mechanical ventilation, and length of hospital stay. Design: Prospective, longitudinal cohort study. Setting: Urban academic tertiary care PICU. Patients: All consecutive admissions from September 2014 through August 2015. Interventions: Children were screened for delirium twice daily throughout their ICU stay. Measurements and Main Results: Of 1,547 consecutive patients, delirium was diagnosed in 267 (17%) and lasted a median of 2 days (interquartile range, 1–5). Seventy-eight percent of children with delirium developed it within the first 3 PICU days. Most cases of delirium were of the hypoactive (46%) and mixed (45%) subtypes; only 8% of delirium episodes were characterized as hyperactive delirium. In multivariable analysis, independent predictors of delirium included age less than or equal to 2 years old, developmental delay, severity of illness, prior coma, mechanical ventilation, and receipt of benzodiazepines and anticholinergics. PICU length of stay was increased in children with delirium (adjusted relative length of stay, 2.3; CI = 2.1–2.5; p < 0.001), as was duration of mechanical ventilation (median, 4 vs 1 d; p < 0.001). Delirium was a strong and independent predictor of mortality (adjusted odds ratio, 4.39; CI = 1.96–9.99; p < 0.001). Conclusions: Delirium occurs frequently in critically ill children and is independently associated with mortality. Some in-hospital risk factors for delirium development are modifiable. Interventional studies are needed to determine best practices to limit delirium exposure in at-risk children.

Cost Associated With Pediatric Delirium in the ICU.

Objective:To determine the costs associated with delirium in critically ill children. Design:Prospective observational study. Setting:An urban, academic, tertiary-care PICU in New York city. Patients:Four-hundred and sixty-four consecutive PICU admissions between September 2, 2014, and December 12, 2014. Interventions:None. Measurements and Main Results:All children were assessed for delirium daily throughout their PICU stay. Hospital costs were analyzed using cost-to-charge ratios, in 2014 dollars. Median total PICU costs were higher in patients with delirium than in patients who were never delirious (

Evaluation of the Safety of Quetiapine in Treating Delirium in Critically Ill Children: A Retrospective Review

18,832 vs

Neuroblastoma and pediatric delirium: A case series

4,803; p < 0.0001). Costs increased incrementally with number of days spent delirious (median cost of

Delirium in Children After Cardiac Bypass Surgery.

9,173 for 1 d with delirium,

Detection and Management of Delirium in the Neonatal Unit: A Case Series.

19,682 for 2–3 d with delirium, and

Quetiapine as treatment for delirium in critically ill children: A case series

75,833 for > 3 d with delirium; p < 0.0001); this remained highly significant even after adjusting for PICU length of stay (p < 0.0001). After controlling for age, gender, severity of illness, and PICU length of stay, delirium was associated with an 85% increase in PICU costs (p < 0.0001). Conclusions:Pediatric delirium is associated with a major increase in PICU costs. Further research directed at prevention and treatment of pediatric delirium is essential to improve outcomes in this population and could lead to substantial healthcare savings.