Association Between Pediatric Delirium and Quality of Life After Discharge.

OBJECTIVE: Delirium occurs frequently in critically ill children, with highest rates reported in children under 5 years old. The objective of this study was to measure the residual effect of delirium on quality of life at 1 and 3 months after hospital discharge. DESIGN: Prospective observational cohort study. SETTING: Urban academic PICU. PATIENTS: Children younger than five years of age at time of admission to the PICU. INTERVENTIONS: All children were screened for delirium (using the Cornell Assessment for Pediatric Delirium) throughout their stay in the PICU. Quality of life was measured using the Infant-Toddler Quality of Life questionnaire at three time points: baseline, 1 month, and 3 months after hospital discharge. Infant-Toddler Quality of Life scores were compared between children who did and did not develop delirium. MEASUREMENTS AND MAIN RESULTS: Two hundred seven children were enrolled. One hundred twenty-two completed the 1-month follow-up, and 117 completed the 3-month follow-up. Fifty-six children (27%) developed delirium during their PICU stay. At follow-up, Infant-Toddler Quality of Life scores for the PICU cohort overall were consistently lower than age-related norms. When analyzed by delirium status, children who had experienced delirium scored lower in every quality of life domain when compared with children who did not experience delirium. Even after controlling for severity of illness, delirious patients demonstrated an average 11-point lower general health score than nondelirious patients (p = 0.029). CONCLUSION: This pilot study shows an independent association between delirium and decreased quality of life after hospital discharge in young children.

Delirium and Developmental Disability: Improving Specificity of a Pediatric Delirium Screen.

OBJECTIVES: Children with developmental disabilities are at high risk for developing delirium when critically ill. However, existing pediatric delirium screening tools were designed for children with typical development. The objective of this study was to improve the specificity of the Cornell Assessment for Pediatric Delirium, to allow for accurate detection of delirium in developmentally delayed children admitted to the PICU. We hypothesized that the Cornell Assessment for Pediatric Delirium, when combined with fluctuation in level of awareness as measured by the Richmond Agitation-Sedation Scale, would be valid and reliable for the diagnosis of delirium in developmentally delayed children. DESIGN: Prospective observational double-blind cohort study. SETTING: Tertiary care academic PICU. PATIENTS: Children with moderate to severe developmental delay. INTERVENTIONS: Each child was evaluated by the bedside nurse with the Cornell Assessment for Pediatric Delirium once every 12 hours and the Richmond Agitation-Sedation Scale every 4 hours. Cornell Assessment for Pediatric Delirium (score ≥ 9) + Richmond Agitation-Sedation Scale fluctuation (change in Richmond Agitation-Sedation Scale score of at least 2 points during a 24-hr period) was compared with the criterion standard psychiatric evaluation for diagnosis of delirium. MEASUREMENTS AND MAIN RESULTS: Forty children participated; 94 independent paired assessments were completed. The psychiatrists' diagnostic evaluations were compared with the detection of delirium by the Cornell Assessment for Pediatric Delirium and Richmond Agitation-Sedation Scale. Specificity of the Cornell Assessment for Pediatric Delirium + Richmond Agitation-Sedation Scale fluctuation was 97% (CI, 90-100%), positive predictive value of Cornell Assessment for Pediatric Delirium + Richmond Agitation-Sedation Scale fluctuation was 89% (CI, 65-99%); and negative predictive value remained acceptable at 87% (95% CI, 77-94%). In addition, to confirm interrater reliability of the criterion standard, 11 assessments were performed by two or more psychiatrists in a blinded fashion. There was perfect agreement (κ = 1), indicating reliability in psychiatric diagnosis of delirium in developmentally delayed children. CONCLUSION: When used in conjunction with Richmond Agitation-Sedation Scale score fluctuation, the Cornell Assessment for Pediatric Delirium is a sensitive and specific tool for the detection of delirium in children with developmental delay. This allows for reliable delirium screening in this hard-to-assess population.

The Validity and Reliability of the Japanese Version of the Cornell Assessment of Pediatric Delirium.

OBJECTIVES: To examine validity and reliability of the Japanese version of the Cornell Assessment of Pediatric Delirium. DESIGN: Prospective double-blinded observational cohort study. SETTING: Eight-bed mixed PICU (post-surgical and internal medicine) from May 2017 to June 2018. PATIENTS: All children between the ages of 0-13 years who were admitted to the PICU for at least 24 hours were eligible for inclusion, as long as the child was arousable to verbal stimulation. INTERVENTIONS: Two nurses simultaneously and independently assessed each patient for pediatric delirium with the Japanese version of the Cornell Assessment of Pediatric Delirium; this was compared to the gold standard of psychiatric diagnosis based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition standards. MEASUREMENTS AND MAIN RESULTS: Forty-one children were enrolled and 92 assessments (ranging from one to four per subject) were completed. Congenital heart disease patients accounted for 73 enrollees (79%). Forty-three percent of observations were performed in children on invasive mechanical ventilation. Pediatric delirium prevalence (as determined by psychiatric diagnosis) was 53%. The Japanese version of the Cornell Assessment of Pediatric Delirium demonstrated an optimal scoring cutpoint of 9. Overall, area under the curve was 92%, sensitivity 90% (95% CI, 79-97%), specificity 88% (95% CI, 75-96%), positive predictive value of 90% (95% CI, 79-97%), negative predictive value of 91% (95% CI, 80-97%), and a Cohen's κ of 0.89 (95% CI, 0.8-0.98). In children on invasive mechanical ventilation, the Japanese version of the Cornell Assessment of Pediatric Delirium maintained an area under the curve 87%, sensitivity 97%, and specificity 64%. CONCLUSIONS: The Japanese version of the Cornell Assessment of Pediatric Delirium is a valid and reliable tool for use in Japanese PICUs. This will allow for detection of delirium in real-time and may lead to better identification of the population and risk factors for appropriate management and therapeutic and preventative interventions.

A systematic approach to family engagement: Feasibility pilot of a pediatric delirium management and prevention toolkit.

OBJECTIVE: Delirium is a frequent and severe complication of serious pediatric illness. Development of a nonpharmacologic approach to prevent pediatric delirium may improve short- and long-term outcomes in children and their families. In this brief report, we describe the development of a quality improvement project designed to methodically promote the family member's engagement, comforting, and orienting activities with their critically ill child to decrease delirium rates. METHOD: We created a developmentally specific Delirium Prevention Toolkit for families. In a feasibility pilot, March through June 2016, we offered the kit to 15 patients and their families. On discharge, families were asked to describe use of the toolkit and whether or not it was helpful for them. RESULTS: Twelve of 15 patients and families used various elements of the toolkit, particularly the headphones, music, and games; no one regularly used the blank journal. All reported that it was easy and helpful to have as support for their stay in the pediatric intensive care unit.Significance of resultsThis pilot demonstrated practicality of a nonpharmacologic delirium prevention toolkit in the pediatric intensive care unit, and satisfaction from patients and families.

Cornell Assessment of Pediatric Delirium: Italian cultural validation and preliminary testing.

INTRODUCTION: Paediatric delirium is associated with a longer duration of hospitalization in paediatric intensive care units, the emergence of post-traumatic symptoms and possible neurocognitive dysfunction after discharge. In preschool children, the diagnosis of delirium appears rather challenging: their pre-verbal status and the presence of cognitive skills still in development make accurate diagnosis difficult. Recently, a pediatric delirium screening tool suitable for critical preschool children has also been developed and identified in international literature, with excellent results also in critical infants under 2 years of age: the Cornell Assessment of Pediatric Delirium (CAPD). The CAPD, using a Likert scale, bases the assessment of paediatric delirium within the context of child development. This scale follows the development of the infant by comparing the detection of specific items on the scale as the anchor points that characterize the development of infants by age groups. OBJECTIVE: Culturally and linguistically validation in Italian language and prior testing of the Cornell Assessment of Pediatric Delirium. METHOD: Translation and Cultural Validation of the Cornell Assessment of Pediatric Delirium (CAPD) for the Evaluation/Diagnosis of Pediatric Delirium within Pediatric Intensive Care. The translation and adaptation of this instrument followed the phases of the model proposed by the World Health Organization. Prior testings, such as item descriptive analysis, item-total correlation and Cronbach's alpha, were conducted. RESULTS: All phases of the cultural-linguistic validation process were carried out in a satisfactory manner. For the prior testing, the scale was administered to a sample of 42 children, with age ranged 0-5 years old (66.6%), with a higher prevalence of the male gender. All items were normally distributed and there was no excessive Skeweness and Kurtosis. Each item contributed to the scale fairly well and all coefficients of item total correlation (rjx) were higher than the recommended level of 0.30. The composite reliability index was 0.94 and Cronbach's alpha was 0.96. CONCLUSIONS: The process has meticulously followed the recommendations in international literature. The final version was approved by the authors of the original instrument.

Benzodiazepines and Development of Delirium in Critically Ill Children: Estimating the Causal Effect.

OBJECTIVES: Benzodiazepine use may be associated with delirium in critically ill children. However, benzodiazepines remain the first-line sedative choice in PICUs. Objectives were to determine the temporal relationship between administration of benzodiazepines and delirium development, control for time-varying covariates such as mechanical ventilation and opiates, and evaluate the association between dosage of benzodiazepines and subsequent delirium. DESIGN: Retrospective observational study. SETTING: Academic tertiary care PICU. PATIENTS: All consecutive admissions from January 2015 to June 2015. INTERVENTIONS: Retrospective assessment of benzodiazepine exposure in a population that had been prospectively screened for delirium. MEASUREMENTS AND MAIN RESULTS: All subjects were prospectively screened for delirium throughout their stay, using the Cornell Assessment for Pediatric Delirium, with daily cognitive status assigned as follows: delirium, coma, or normal. Multivariable mixed effects modeling determined predictors of delirium overall, followed by subgroup analysis to assess effect of benzodiazepines on subsequent development of delirium. Marginal structural modeling was used to create a pseudorandomized sample and control for time-dependent variables, obtaining an unbiased estimate of the relationship between benzodiazepines and next day delirium. The cumulative daily dosage of benzodiazepines was calculated to test for a dose-response relationship. Benzodiazepines were strongly associated with transition from normal cognitive status to delirium, more than quadrupling delirium rates (odds ratio, 4.4; CI, 1.7-11.1; p < 0.002). Marginal structural modeling demonstrated odds ratio 3.3 (CI, 1.4-7.8), after controlling for time-dependent confounding of cognitive status, mechanical ventilation, and opiates. With every one log increase in benzodiazepine dosage administered, there was a 43% increase in risk for delirium development. CONCLUSIONS: Benzodiazepines are an independent and modifiable risk factor for development of delirium in critically ill children, even after carefully controlling for time-dependent covariates, with a dose-response effect. This temporal relationship suggests causality between benzodiazepine exposure and pediatric delirium and supports limiting the use of benzodiazepines in critically ill children.

Delirium is a Common and Early Finding in Patients in the Pediatric Cardiac Intensive Care Unit.

OBJECTIVE: To determine incidence, associated risk factors, and characteristics of delirium in a pediatric cardiac intensive care unit (CICU). Delirium is a frequent and serious complication in adults after cardiac surgery, but there is limited understanding of its impact in children with critical cardiac disease. STUDY DESIGN: Single-center prospective observational study of CICU patients ≤21 years old. All were screened for delirium using the Cornell Assessment for Pediatric Delirium each 12-hour shift. RESULTS: Ninety-nine patients were included. Incidence of delirium was 57%. Median time to development of delirium was 1 day (95% CI 0, 1 days). Children with delirium were younger (geometric mean age 4 vs 46 months; P < .001), had longer periods of mechanical ventilation (mean 35.9 vs 8.8 hours; P = .002) and had longer cardiopulmonary bypass times (geometric mean 126 vs 81 minutes; P = .001). Delirious patients had longer length of CICU stay than those without delirium (median 3 (IQR 2, 12.5) vs 1 (IQR1, 2) days; P < .0001). A multivariable generalized linear mixed model showed a significant association between delirium and younger age (OR 0.35 for each additional month, 95% CI 0.19, 0.64), need for mechanical ventilation (OR 4.1, 95% CI 1.7, 9.89), and receipt of benzodiazepines (OR 3.78, 95% CI 1.46, 9.79). CONCLUSIONS: Delirium is common in patients in the pediatric CICU and is associated with longer length of stay. There may be opportunities for prevention of delirium by targeting modifiable risk factors, such as use of benzodiazepines.

Risk Factors for the Development of Postoperative Delirium in Pediatric Intensive Care Patients.

OBJECTIVES: To determine and quantify risk factors for postoperative pediatric delirium. DESIGN: Single-center prospective cohort study. SETTING: Twenty-two bed PICU in a tertiary care academic medical center in Germany. PATIENTS: All children admitted after major elective surgery (n = 93; 0-17 yr). INTERVENTIONS: After awakening, children were screened for delirium using the Cornell Assessment of Pediatric Delirium bid over a period of 5 days. Demographic and clinical data were collected from the initiation of general anesthesia. MEASUREMENTS AND MAIN RESULTS: A total of 61 patients (66%) were delirious. Younger children developed delirium more frequently, and the symptoms were more pronounced. The number of preceding operations did not influence the risk of delirium. Total IV anesthesia had a lower risk than inhalational anesthesia (p < 0.05). Duration of anesthesia was similar in all groups. Patients with delirium had a longer duration of mechanical ventilation in the PICU (p < 0.001). Significant differences in cumulative doses of various medications (e.g., sedatives, analgesics, and anticholinergics) were noted between groups; these differences were independent of disease severity. Invasive catheters and respiratory devices (p < 0.01) as well as infections (p < 0.001) increased risk of delirium. CONCLUSIONS: A high prevalence of delirium was noted in the PICU, and several perioperative risk factors were identified. Our data may be a base for development of strategies to prevent and treat postoperative delirium in children.

Provider Beliefs Regarding Early Mobilization in the Pediatric Intensive Care Unit.

PURPOSE: Critically ill patients are at risk for short and long term morbidity. Early mobilization (EM) of critically ill adults is safe and feasible, with improvement in outcomes. There are limited studies evaluating EM in pediatric critical care patients. Provider beliefs and concerns must be evaluated prior to EM implementation in the pediatric intensive care unit (PICU). DESIGN AND METHODS: A survey was distributed to PICU providers assessing beliefs and concerns with regards to EM of PICU patients. RESULTS: Seventy-one providers responded. Most staff believed EM would be beneficial. The largest perceived benefits were decreased length of both stay and mechanical ventilation. The largest perceived concerns were risk of both endotracheal tube and central venous catheter dislodgement. Surveyed clinicians felt significantly more comfortable mobilizing the oldest as compared to the youngest patients (p<0.0001). Clinicians also felt significantly more comfortable mobilizing patients receiving invasive mechanical ventilation in the oldest as compared to the youngest patients (p<0.0001). CONCLUSION: There is clear benefit to the EM of adult ICU patients, with evidence supporting its safety and feasibility. As pediatric patients pose different challenges, it is imperative to understand provider concerns prior to the implementation of EM. Our research demonstrates similar concerns between adult and pediatric programs, with the addition of significant concern surrounding EM in very young children. PRACTICE IMPLICATIONS: Understanding pediatric specific concerns with regards to EM will allow for the proper development and implementation of pediatric EM programs, allowing us to assess safety, feasibility, and ultimately outcomes.

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.

Delirium in Critically Ill Children: An International Point Prevalence Study.

OBJECTIVES: To determine prevalence of delirium in critically ill children and explore associated risk factors. DESIGN: Multi-institutional point prevalence study. SETTING: Twenty-five pediatric critical care units in the United States, the Netherlands, New Zealand, Australia, and Saudi Arabia. PATIENTS: All children admitted to the pediatric critical care units on designated study days (n = 994). INTERVENTION: Children were screened for delirium using the Cornell Assessment of Pediatric Delirium by the bedside nurse. Demographic and treatment-related variables were collected. MEASUREMENTS AND MAIN RESULTS: Primary study outcome measure was prevalence of delirium. In 159 children, a final determination of mental status could not be ascertained. Of the 835 remaining subjects, 25% screened positive for delirium, 13% were classified as comatose, and 62% were delirium-free and coma-free. Delirium prevalence rates varied significantly with reason for ICU admission, with highest delirium rates found in children admitted with an infectious or inflammatory disorder. For children who were in the PICU for 6 or more days, delirium prevalence rate was 38%. In a multivariate model, risk factors independently associated with development of delirium included age less than 2 years, mechanical ventilation, benzodiazepines, narcotics, use of physical restraints, and exposure to vasopressors and antiepileptics. CONCLUSIONS: Delirium is a prevalent complication of critical illness in children, with identifiable risk factors. Further multi-institutional, longitudinal studies are required to investigate effect of delirium on long-term outcomes and possible preventive and treatment measures. Universal delirium screening is practical and can be implemented in pediatric critical care units.

Delirium in Hospitalized Children with Cancer: Incidence and Associated Risk Factors.

OBJECTIVE: To assess the incidence of delirium and its risk factors in hospitalized children with cancer. STUDY DESIGN: In this cohort study, all consecutive admissions to a pediatric cancer service over a 3-month period were prospectively screened for delirium twice daily throughout their hospitalization. Demographic and treatment-related data were collected from the medical record after discharge. RESULTS: A total of 319 consecutive admissions, including 186 patients and 2731 hospital days, were included. Delirium was diagnosed in 35 patients, for an incidence of 18.8%. Risk factors independently associated with the development of delirium included age <5 years (OR = 2.6, P = .026), brain tumor (OR = 4.7, P = .026); postoperative status (OR = 3.3, P = .014), and receipt of benzodiazepines (OR = 3.7,P < .001). Delirium was associated with increased hospital length of stay, with median length of stay for delirious patients of 10 days compared with 5 days for patients who were not delirious during their hospitalization (P < .001). CONCLUSIONS: In this cohort, delirium was a frequent complication during admissions for childhood cancer, and was associated with increased hospital length of stay. Multi-institutional prospective studies are warranted to further characterize delirium in this high-risk population and identify modifiable risk factors to improve the care provided to hospitalized children with cancer.

Development of the Vanderbilt Assessment for Delirium in Infants and Children to Standardize Pediatric Delirium Assessment By Psychiatrists.

BACKGROUND: Pediatric delirium assessment is complicated by variations in baseline language and cognitive skills, impairment during illness, and absence of pediatric-specific modifiers within the Diagnostic and Statistical Manual of Mental Disorders delirium criterion. OBJECTIVE: To develop a standardized approach to pediatric delirium assessment by psychiatrists. METHODS: A multidisciplinary group of clinicians used Diagnostic and Statistical Manual criterion as the foundation for the Vanderbilt Assessment for Delirium in Infants and Children (VADIC). Pediatric-specific modifiers were integrated into the delirium criterion, including key developmental and assessment variations for children. The VADIC was used in clinical practice to prospectively assess critically ill infants and children. The VADIC was assessed for content validity by the American Academy of Child and Adolescent Psychiatry Delirium Special Interest Group. RESULTS: The American Academy of Child and Adolescent Psychiatry-Delirium Special Interest Group determined that the VADIC demonstrated high content validity. The VADIC (1) preserved the core Diagnostic and Statistical Manual delirium criterion, (2) appropriately paired interactive assessments with key criterion based on development, and (3) addressed confounders for delirium. A cohort of 300 patients with a median age of 20 months was assessed for delirium using the VADIC. Delirium prevalence was 47%. CONCLUSION: The VADIC provides a comprehensive framework to standardize pediatric delirium assessment by psychiatrists. The need for consistency in both delirium education and diagnosis is highlighted given the high prevalence of pediatric delirium.

Patterns of Postoperative Delirium in Children.

OBJECTIVE: Intensive care delirium is a substantial problem in adults. Intensive care delirium is increasingly recognized in pediatrics in parallel with the development of specific scoring systems for children. However, little is known about the fluctuating course of intensive care delirium in children after surgery and possible implications on diagnostic and therapeutic strategies. DESIGN: Patients that needed treatment in the PICU following elective surgery were screened for intensive care delirium with the Cornell Assessment of Pediatric Delirium. When the patients were awake (Richmond Agitation and Sedation Score > -3), two trained investigators conducted the Cornell Assessment of Pediatric Delirium twice daily for five consecutive days. PATIENTS: Ninety-three patients aged 0 to 17 years. INTERVENTIONS: Eight hundred forty-five assessments completed. MEASUREMENTS AND MAIN RESULTS: Of the 845 scores, 230 were consistent with delirium (27.2%). Sixty-one patients (65.5%) were diagnosed with intensive care delirium. Half of these patients (n = 30; 32.2%) had a short-lasting delirium that resolved within 24 hours, and half (n = 31; 33.3%) had delirium of longer duration. Delirium could be clearly distinguished from sedation by analysis of individual test items of the Cornell Assessment of Pediatric Delirium. Time spent delirious had a measurable effect on outcome variables, including hospital length of stay. CONCLUSION: Most postoperative PICU patients develop intensive care delirium. Some have a short-lasting course, which underlines the need for early screening. Our findings support the view of delirium as a continuum of acute neurocognitive disorder. Further research is needed to investigate prophylactic and treatment approaches for intensive care delirium.

Delirium in Children After Cardiac Bypass Surgery.

OBJECTIVES: To describe the incidence of delirium in pediatric patients after cardiac bypass surgery and explore associated risk factors and effect of delirium on in-hospital outcomes. DESIGN: Prospective observational single-center study. SETTING: Fourteen-bed pediatric cardiothoracic ICU. PATIENTS: One hundred ninety-four consecutive admissions following cardiac bypass surgery, 1 day to 21 years old. INTERVENTIONS: Subjects were screened for delirium daily using the Cornell Assessment of Pediatric Delirium. MEASUREMENTS AND MAIN RESULTS: Incidence of delirium in this sample was 49%. Delirium most often lasted 1-2 days and developed within the first 1-3 days after surgery. Age less than 2 years, developmental delay, higher Risk Adjustment for Congenital Heart Surgery 1 score, cyanotic disease, and albumin less than three were all independently associated with development of delirium in a multivariable model (all p < 0.03). Delirium was an independent predictor of prolonged ICU length of stay, with patients who were ever delirious having a 60% increase in ICU days compared with patients who were never delirious (p < 0.01). CONCLUSIONS: In our institution, delirium is a frequent problem in children after cardiac bypass surgery, with identifiable risk factors. Our study suggests that cardiac bypass surgery significantly increases children's susceptibility to delirium. This highlights the need for heightened, targeted delirium screening in all pediatric cardiothoracic ICUs to potentially improve outcomes in this vulnerable patient population.

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 ($18,832 vs $4,803; p < 0.0001). Costs increased incrementally with number of days spent delirious (median cost of $9,173 for 1 d with delirium, $19,682 for 2-3 d with delirium, and $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.

Adult separation anxiety in treatment nonresponders with anxiety disorders: delineation of the syndrome and exploration of attachment-based psychotherapy and biomarkers.

Clinically significant separation anxiety [SA] has been identified as being common among patients who do not respond to psychiatric interventions, regardless of intervention type (pharmacological or psychotherapeutic), across anxiety and mood disorders. An attachment formation and maintenance domain has been proposed as contributing to anxiety disorders. We therefore directly determined prevalence of SA in a population of adult treatment non-responders suffering from primary anxiety. In these separation anxious nonresponders, we pilot-tested an SA-focused, attachment-based psychotherapy for anxiety, Panic-Focused Psychodynamic Psychotherapy-eXtended Range [PFPP-XR], and assessed whether hypothesized biomarkers of attachment were engaged. We studied separation anxiety [SA] in 46 adults (ages 23-70 [mean 43.9 (14.9)]) with clinically significant anxiety symptoms (Hamilton Anxiety Rating Scale [HARS]≥15), and reporting a history of past non-response to psychotherapy and/or medication treatments. Thirty-seven (80%) had clinically significant symptoms of separation anxiety (Structured Clinical Interview for Separation Anxiety Symptoms [SCI-SAS] score≥8). Five of these subjects completed an open clinical trial of Panic Focused Psychodynamic Psychotherapy eXtended Range [PFPP-XR], a 21-24 session, 12-week manualized attachment-focused anxiolytic psychodynamic psychotherapy for anxiety. Patients improved on "adult threshold" SCI-SAS (current separation anxiety) (p=.016), HARS (p=0.002), and global severity, assessed by the Clinical Global Impression Scale (p=.0006), at treatment termination. Salivary oxytocin levels decreased 67% after treatment (p=.12). There was no significant change in high or low frequency HRV after treatment, but change in high frequency HRV inversely correlated with treatment change in oxytocin (p<.02), and change in low frequency HRV was positively associated with change in oxytocin (p<.02). SA is surprisingly prevalent among non-responders to standard anti-anxiety treatments, and it may represent a novel transdiagnostic target for treatment intervention in this population. Anxiety and global function improved in a small trial of a brief, manualized, attachment-focused psychodynamic psychotherapy, potentially supporting the clinical relevance of attachment dysfunction in this sample. The large decrease in oxytocin levels with treatment, although not statistically significant in this very small sample, suggests the need for further study of oxytocin as a putative biomarker or mediator of SA response. These pilot data generate testable hypotheses supporting an attachment domain underlying treatment-resistant anxiety, and new treatment strategies.

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.

Delirium screening anchored in child development: The Cornell Assessment for Pediatric Delirium.

OBJECTIVE: The recently validated Cornell Assessment for Pediatric Delirium (CAPD) is a new rapid bedside nursing screen for delirium in hospitalized children of all ages. The present manuscript provides a "developmental anchor points" reference chart, which helps ground clinicians' assessment of CAPD symptom domains in a developmental understanding of the presentation of delirium. METHOD: During the development of this CAPD screening tool, it became clear that clinicians need specific guidance and training to help them draw on their expertise in child development and pediatrics to improve the interpretative reliability of the tool and its accuracy in diagnosing delirium. The developmental anchor points chart was formulated and reviewed by a multidisciplinary panel of experts to evaluate content validity and include consideration of sick behaviors within a hospital setting. RESULTS: The CAPD developmental anchor points for the key ages of newborn, 4 weeks, 6 weeks, 8 weeks, 28 weeks, 1 year, and 2 years served as the basis for training bedside nurses in scoring the CAPD for the validation trial and as a multifaceted bedside reference chart to be implemented within a clinical setting. In the current paper, we discuss the lessons learned during implementation, with particular emphasis on the importance of collaboration with the bedside nurse, the challenges of establishing a developmental baseline, and further questions about delirium diagnosis in children. SIGNIFICANCE OF RESULTS: The CAPD with developmental anchor points provides a validated, structured, and developmentally informed approach to screening and assessment of delirium in children. With minimal training on the use of the tool, bedside nurses and other pediatric practitioners can reliably identify children at risk for delirium.

Pediatric delirium: evaluating the gold standard.

OBJECTIVE: Our aim was to evaluate interrater reliability for the diagnosis of pediatric delirium by child psychiatrists. METHOD: Critically ill patients (N = 17), 0-21 years old, including 7 infants, 5 children with developmental delay, and 7 intubated children, were assessed for delirium using the Diagnostic and Statistical Manual-IV (DSM-IV) (comparable to DSM-V) criteria. Delirium assessments were completed by two psychiatrists, each blinded to the other's diagnosis, and interrater reliability was measured using Cohen's κ coefficient along with its 95% confidence interval. RESULTS: Interrater reliability for the psychiatric assessment was high (Cohen's κ = 0.94, CI [0.83, 1.00]). Delirium diagnosis showed excellent interrater reliability regardless of age, developmental delay, or intubation status (Cohen's κ range 0.81-1.00). SIGNIFICANCE OF RESULTS: In our study cohort, the psychiatric interview and exam, long considered the "gold standard" in the diagnosis of delirium, was highly reliable, even in extremely young, critically ill, and developmentally delayed children. A developmental approach to diagnosing delirium in this challenging population is recommended.