Heidi Smith

Diagnosing delirium in critically ill children: Validity and reliability of the Pediatric Confusion Assessment Method for the Intensive Care Unit*

Objective:To validate a diagnostic instrument for pediatric delirium in critically ill children, both ventilated and nonventilated, that uses standardized, developmentally appropriate measurements. Design and Setting:A prospective observational cohort study investigating the Pediatric Confusion Assessment Method for Intensive Care Unit (pCAM-ICU) patients in the pediatric medical, surgical, and cardiac intensive care unit of a university-based medical center. Patients:A total of 68 pediatric critically ill patients, at least 5 years of age, were enrolled from July 1, 2008, to March 30, 2009. Interventions:None. Measurements:Criterion validity including sensitivity and specificity and interrater reliability were determined using daily delirium assessments with the pCAM-ICU by two critical care clinicians compared with delirium diagnosis by pediatric psychiatrists using Diagnostic and Statistical Manual, 4th Edition, Text Revision criteria. Results:A total of 146 paired assessments were completed among 68 enrolled patients with a mean age of 12.2 yrs. Compared with the reference standard for diagnosing delirium, the pCAM-ICU demonstrated a sensitivity of 83% (95% confidence interval, 66–93%), a specificity of 99% (95% confidence interval, 95–100%), and a high interrater reliability (&kgr; = 0.96; 95% confidence interval, 0.74–1.0). Conclusions:The pCAM-ICU is a highly valid reliable instrument for the diagnosis of pediatric delirium in critically ill children chronologically and developmentally at least 5 yrs of age. Use of the pCAM-ICU may expedite diagnosis and consultation with neuropsychiatry specialists for treatment of pediatric delirium. In addition, the pCAM-ICU may provide a means for delirium monitoring in future epidemiologic and interventional studies in critically ill children.

l-Citrulline ameliorates chronic hypoxia-induced pulmonary hypertension in newborn piglets

Newborn piglets develop pulmonary hypertension and have diminished pulmonary vascular nitric oxide (NO) production when exposed to chronic hypoxia. NO is produced by endothelial NO synthase (eNOS) in the pulmonary vascular endothelium using l-arginine as a substrate and producing l-citrulline as a byproduct. l-Citrulline is metabolized to l-arginine by two enzymes that are colocated with eNOS in pulmonary vascular endothelial cells. The purpose of this study was to determine whether oral supplementation with l-citrulline during exposure of newborn piglets to 10 days of chronic hypoxia would prevent the development of pulmonary hypertension and increase pulmonary NO production. A total of 17 hypoxic and 17 normoxic control piglets were studied. Six of the 17 hypoxic piglets were supplemented with oral l-citrulline starting on the first day of hypoxia. l-Citrulline supplementation was provided orally twice a day. After 10 days of hypoxia or normoxia, the animals were anesthetized, hemodynamic measurements were performed, and the lungs were perfused in situ. Pulmonary arterial pressure and pulmonary vascular resistance were significantly lower in hypoxic animals treated with l-citrulline compared with untreated hypoxic animals (P < 0.001). In vivo exhaled NO production (P = 0.03) and nitrite/nitrate accumulation in the perfusate of isolated lungs (P = 0.04) were significantly higher in l-citrulline-treated hypoxic animals compared with untreated hypoxic animals. l-Citrulline supplementation ameliorated the development of pulmonary hypertension and increased NO production in piglets exposed to chronic hypoxia. We speculate that l-citrulline may benefit neonates exposed to prolonged periods of hypoxia from cardiac or pulmonary causes.

The Preschool Confusion Assessment Method for the ICU: Valid and Reliable Delirium Monitoring for Critically Ill Infants and Children.

Objectives:Delirium assessments in critically ill infants and young children pose unique challenges due to evolution of cognitive and language skills. The objectives of this study were to determine the validity and reliability of a fundamentally objective and developmentally appropriate delirium assessment tool for critically ill infants and preschool-aged children and to determine delirium prevalence. Design and Setting:Prospective, observational cohort validation study of the PreSchool Confusion Assessment Method for the ICU in a tertiary medical center PICU. Patients:Participants aged 6 months to 5 years and admitted to the PICU regardless of admission diagnosis were enrolled. Measurements and Main Results:An interdisciplinary team created the PreSchool Confusion Assessment Method for the ICU for pediatric delirium monitoring. To assess validity, patients were independently assessed for delirium daily by the research team using the PreSchool Confusion Assessment Method for the ICU and by a child psychiatrist using the Diagnostic and Statistical Manual of Mental Disorders criteria. Reliability was assessed using blinded, concurrent PreSchool Confusion Assessment Method for the ICU evaluations by research staff. A total of 530-paired delirium assessments were completed among 300 patients, with a median age of 20 months (interquartile range, 11–37) and 43% requiring mechanical ventilation. The PreSchool Confusion Assessment Method for the ICU demonstrated a specificity of 91% (95% CI, 90–93), sensitivity of 75% (95% CI, 72–78), negative predictive value of 86% (95% CI, 84–88), positive predictive value of 84% (95% CI, 81–87), and a reliability &kgr;–statistic of 0.79 (0.76–0.83). Delirium prevalence was 44% using the PreSchool Confusion Assessment Method for the ICU and 47% by the reference rater. The rates of delirium were 53% versus 56% in patients younger than 2 years old and 33% versus 35% in patients 2–5 years old using the PreSchool Confusion Assessment Method for the ICU and reference rater, respectively. The short-form PreSchool Confusion Assessment Method for the ICU maintained a high specificity (87%) and sensitivity (78%) in post hoc analysis. Conclusions:The PreSchool Confusion Assessment Method for the ICU is a highly valid and reliable delirium instrument for critically ill infants and preschool-aged children, in whom delirium is extremely prevalent.

Pediatric delirium: monitoring and management in the pediatric intensive care unit.

This review article updates the pediatric medical community on the current literature regarding diagnosis and treatment of delirium in critically ill children. This information will be of value to pediatricians, intensivists, and anesthesiologists in developing delirium monitoring and management protocols in their pediatric critical care units.

Delirium: An Emerging Frontier in the Management of Critically Ill Children

Delirium is a syndrome of acute brain dysfunction that commonly occurs in critically ill adults and most certainly is prevalent in critically ill children all over the world. The dearth of information about the incidence, prevalence, and severity of pediatric delirium stems from the simple fact that there have not been well-validated instruments for routine delirium diagnosis at the bedside. This article reviewed the emerging solutions to this problem, including description of a new pediatric tool called the pCAM-ICU. In adults, delirium is responsible for significant increases in both morbidity and mortality in critically ill patients. The advent of new tools for use in critically ill children will allow the epidemiology of this form of acute brain dysfunction to be studied adequately, will allow clinical management algorithms to be developed and implemented following testing, and will present the necessary incorporation of delirium as an outcome measure for future clinical trials in pediatric critical care medicine.

Meeting the Challenges of Delirium Assessment Across the Aging Spectrum

Critical Care Medicine www.ccmjournal.org 1775 Delirium is anything but simplistic. The ability for medical personnel to monitor for delirium across the continuum of human life requires consideration of the intricate neurobehavioral changes from infancy to late adulthood to the end of life. Acute brain dysfunction in these settings of ongoing physiologic and anatomic changes is a manifestation of the elaborate spectrum of neuroscience. It thus is remarkable that despite these challenges, valid and reliable tools have been developed and successfully used for delirium monitoring. In fact, by any standards, many of these tools represent some of the most efficient and accurate tools in clinical practice. This accuracy has been accomplished by thoughtful researchers recognizing that delirium assessment requires a neurodevelopmental and behavioral approach to assess key delirium features within different populations. In other words, one tool does not fit all patients. Both adult and pediatric delirium screening tools, whether largely observational or interactive, have led to the successful monitoring of delirium in our most fragile patients and have laid the foundation for further study of delirium epidemiology. Despite the significant accomplishment of researchers in creating developmentally unique delirium tools for use in these varied populations, the question of whether a singular approach to all of delirium monitoring has been proposed in this issue of Critical Care Medicine. Schieveld and Zwieten (1) recommend a unified approach to delirium screening across the entire age span (i.e., using the same tool for infants, adolescents, adults, and the aged). Their rationale is based upon the “idea hypothesis” that there is a “common underlying mechanism of delirium,” and the current Diagnostic and Statistical Manual of Mental Disorders (DSM) and International Classification of Diseases criteria for delirium are “identical across ages.” They assume that delirium has essentially the same symptomatology and pathophysiology from infants up to the elderly. First, although delirium epidemiology is well established in older and critically ill patients, there remains a dearth of information regarding the epidemiology of pediatric delirium. Only recently has the extremely high prevalence of delirium among critically ill infants and children been demonstrated (2). Furthermore, pediatric specific risk factors and outcomes associated with delirium have not been well delineated, although a recent study reveals that patient factors such as developmental delay, duration of mechanical ventilation, and age are associated with delirium during critical illness (3). Similarly, the underlying mechanism of pediatric delirium has yet to be fully realized and therefore many aspects of delirium management remain in the exploratory phase. These very important but undefined areas of delirium within the very young also remain poorly described in the elderly, particularly in patients with delirium superimposed on dementia. Second, delirium “phenomenology” and the disparities in delirium manifestations between pediatric and adult patients have been previously illustrated. In fact, the limitations of DSM criterion not addressing these important variations in development and age differences, within patient populations such as pediatrics and elderly with dementia, have been considered as a disadvantage to core criterion by Schieveld et al (4). Sleep-wake cycle disturbances, impaired psychomotor Copyright

Diagnosing delirium in critically ill children: Spanish translation and cultural adaptation of the Pediatric Confusion Assessment Method for the Intensive Care Unit.

To the Editor: Smith et al recently developed the Pediatric Confusion Assessment Method for the Intensive Care Unit (pCAM-ICU), which is a highly reliable and valid bedside tool conducted by the caregiver that assesses four cardinal features of the diagnosis of delirium in critically ill children 5 yrs of age. The characteristics of the pCAM-ICU, including the pocket card, worksheet, and daily guide, are amply explained in a report published in Critical Care Medicine (1). Given the absence of this kind of instrument in the Spanish language, we translated and adapted the original tool to the pCAM-ICU–Spanish (pCAM-ICU-S). Principles of good practice for translation and cultural adaptation were followed (2). The ten steps of the translation and adaptation process are described subsequently. 1) Preparation: We formed an international interdisciplinary team of native Spanish speakers from Colombia and Spain (JGF, CR, JFM, JdeP) and members of the original instrument development group (PB, EWE, HABS). The team members’ expertise included pediatric consultation–liaison psychiatry, pediatric neuropsychology, pediatric critical care, and delirium research; 2) forward translation: three independent forward-translated versions were developed (JGF, CR, JFM); 3) reconciliation: divergences in the interpretation of concepts in the three versions were resolved by consensus of the three translators, and a merged Spanish version was obtained; 4) back translation: an independent, highly qualified, native English-speaking medical translator back translated the merged Spanish version into English to provide quality control; 5) back translation review: the back-translated version was reviewed against the English source language (PB, EWE, HABS) to ensure its conceptual equivalence. Comments from this review were returned to the forward translators; 6) harmonization: the merged Spanish version was modified, taking into account the comments from the back translation reviewers; 7) cognitive debriefing: one expert on delirium from Spain (JdeP) evaluated the merged and modified, Spanish version to highlight and correct potentially confusing issues. All team members were informed of any changes; 8) approval and finalization: the Spanish tool was approved by all international team members; 9) proofreading: an independent, Spanish-speaking proofreader checked the Spanish tool for remaining spelling errors; and 10) publication: the pCAM-ICU-S was published on the Web site (http://www.icudelirium.org). The most relevant potentially confusing aspects that were resolved in steps 3 through 8 were related to the use of the word “delirium.” Although some clinicians in Spain use the word delirio when referring to the brain dysfunction evaluated by the pCAM-ICU-S, the word “delirium” was preferred for this tool, which was developed for use in Spain and Latin America. The Spanish word delirio also means “delusion” and is a source of interdisciplinary communication difficulties. The acute brain dysfunction evaluated by the pCAM-ICU-S is called “delirium” in the Spanish version of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Revised. It is recommended that the term “delirium” be used across languages and medical disciplines (3, 4). Another cultural adaptation issue that deserves mention is that a backslash (/) was used in a few cases to include different words when cultural differences could hinder comprehension of the items (for example, “alligator” was translated as “caimán/cocodrilo/lagarto”). Validity and reliability studies of the pCAM-ICU-S in diverse clinical settings are needed. Dr. Ely is supported by the National Institutes of Health (AG001023), Modifying the Impact of ICU-associated Neurological Dysfunction-USA (MIND-USA) Study (1R01AG035117-01A1), and the Veterans Affairs Tennessee Valley Geriatric Research, Education and Clinical Center (GRECC). Dr. Ely also consulted for Cumberland, Masimo, received honoraria/speaking fees form Hospira, and received grant support from Lilly. The remaining authors have not disclosed any potential conflicts of interest. José G. Franco, MD, MSci, PhD, Hospital Universitari Psiquiàtric Institut Pere Mata, IISPV, Universitat Rovira I Virgili, Tarragona, Spain; and Faculty of Medicine, Universidad Pontificia Bolivariana, Medellín, Colombia; Carmenza Ricardo, MD, Faculty of Medicine, Universidad Pontificia Bolivariana, Medellín, Colombia; Juan F. Muñoz, MD, Instituto Neurológico de Antioquia, Medellín, Colombia; Joan de Pablo, MD, PhD, Hospital Universitari Psiquiàtric Institut Pere Mata, IISPV, Universitat Rovira I Virgili, Tarragona, Spain; Pamela Berry, RN, Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN; and Department of Pediatrics, Division of Pediatric Critical Care, Monroe Carrell Jr Children’s Hospital at Vanderbilt, Nashville, NC; E. Wesley Ely, MD, MPH, Department of Internal Medicine, Center for Health Services Research and Division of Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN; and Tennessee Valley VA Geriatric Research, Education and Clinical Center, Nashville, TN, Heidi A. B. Smith, MD, MSci, Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN

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.

128: PEDIATRIC DELIRIUM PREVALENCE AND MOTORIC SUBTYPES IN CRITICALLY ILL INFANTS AND YOUNG CHILDREN

IN-HOSPITAL ARRESTS, ANOXIC/HYPOXIC ISCHEMIC ENCEPHALOPATHY, AND G TUBE/TRACHEOSTOMY ESTIMATES. Veerajalandhar Allareddy1, Sankeerth Rampa2, Romesh Nalliah3, Karen Lidsky4, Veerasathpurush Allareddy5, Alexandre Rotta1; 1Rainbow Babies & Children’s Hospital, Cleveland, OH, 2University of Nebraska Medical University, College of Public Health, Omaha, NE, 3Dental Medicine, Harvard University, Boston, MA, 4Rainbow Babies & Children’s Hosp., Cleveland, OH, 5College of Dentistry, University of Iowa, Iowa City, IA