Altered Mental Status and Delirium in Pediatric Patients.

Mental status is the collection of an individual's consciousness, perception, emotion, memory, and cognition at a particular point in time, which is inferred by the clinician through careful observation and interaction. The pediatric mental status assessment must be approached with an understanding of cognitive, language, and psychosocial development. Alterations must then be comprehensively and clearly described. Delirium is a phenotypic diagnosis with a specific set of criteria in the DSM and is a serious neurocognitive disorder caused by physiologic changes due to illness, injury, toxins, medications, and/or substances. Recognition of delirium in children is improved by monitoring of predisposing risks and precipitating factors, as well as the regular use of validated pediatric screening tools. Management of delirium is focused on treatment of the underlying etiology, prevention of iatrogenic deliriogenic factors, and patient safety.

Sedation Research in Critically Ill Pediatric Patients: Proposals for Future Study Design From the Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research IV Workshop.

OBJECTIVES: Sedation and analgesia for infants and children requiring mechanical ventilation in the PICU is uniquely challenging due to the wide spectrum of ages, developmental stages, and pathophysiological processes encountered. Studies evaluating the safety and efficacy of sedative and analgesic management in pediatric patients have used heterogeneous methodologies. The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research (SCEPTER) IV hosted a series of multidisciplinary meetings to establish consensus statements for future clinical study design and implementation as a guide for investigators studying PICU sedation and analgesia. DESIGN: Twenty-five key elements framed as consensus statements were developed in five domains: study design, enrollment, protocol, outcomes and measurement instruments, and future directions. SETTING: A virtual meeting was held on March 2-3, 2022, followed by an in-person meeting in Washington, DC, on June 15-16, 2022. Subsequent iterative online meetings were held to achieve consensus. SUBJECTS: Fifty-one multidisciplinary, international participants from academia, industry, the U.S. Food and Drug Administration, and family members of PICU patients attended the virtual and in-person meetings. Participants were invited based on their background and experience. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Common themes throughout the SCEPTER IV consensus statements included using coordinated multidisciplinary and interprofessional teams to ensure culturally appropriate study design and diverse patient enrollment, obtaining input from PICU survivors and their families, engaging community members, and using developmentally appropriate and validated instruments for assessments of sedation, pain, iatrogenic withdrawal, and ICU delirium. CONCLUSIONS: These SCEPTER IV consensus statements are comprehensive and may assist investigators in the design, enrollment, implementation, and dissemination of studies involving sedation and analgesia of PICU patients requiring mechanical ventilation. Implementation may strengthen the rigor and reproducibility of research studies on PICU sedation and analgesia and facilitate the synthesis of evidence across studies to improve the safety and quality of care for PICU patients.

Caring for Critically Ill Children With the ICU Liberation Bundle (ABCDEF): Results of the Pediatric Collaborative.

OBJECTIVES: Assess clinical outcomes following PICU Liberation ABCDEF Bundle utilization. DESIGN: Prospective, multicenter, cohort study. SETTING: Eight academic PICUs. PATIENTS: Children greater than 2 months with expected PICU stay greater than 2 days and need for mechanical ventilation (MV). INTERVENTIONS: ABCDEF Bundle implementation. MEASUREMENT AND MAIN RESULTS: Over an 11-month period (3-mo baseline, 8-mo implementation), Bundle utilization was measured for 622 patients totaling 5,017 PICU days. Risk of mortality was quantified for 532 patients (4,275 PICU days) for correlation between Bundle utilization and MV duration, PICU length of stay (LOS), delirium incidence, and mortality. Utilization was analyzed as subject-specific (entire PICU stay) and day-specific (single PICU day). Median overall subject-specific utilization increased from 50% during the 3-month baseline to 63.9% during the last four implementation months ( p < 0.001). Subject-specific utilization for elements A and C did not change; utilization improved for B (0-12.5%; p = 0.007), D (22.2-61.1%; p < 0.001), E (17.7-50%; p = 0.003), and F (50-79.2%; p = 0.001). We observed no association between Bundle utilization and MV duration, PICU LOS, or delirium incidence. In contrast, on adjusted analysis, every 10% increase in subject-specific utilization correlated with mortality odds ratio (OR) reduction of 34%, p < 0.001; every 10% increase in day-specific utilization correlated with a mortality OR reduction of 1.4% ( p = 0.006). CONCLUSIONS: ABCDEF Bundle is applicable to children. Although enhanced Bundle utilization correlated with decreased mortality, increased utilization did not correlate with duration of MV, PICU LOS, or delirium incidence. Additional research in the domains of comparative effectiveness, implementation science, and human factors engineering is required to understand this clinical inconsistency and optimize PICU Liberation concept integration into clinical practice.

2022 Society of Critical Care Medicine Clinical Practice Guidelines on Prevention and Management of Pain, Agitation, Neuromuscular Blockade, and Delirium in Critically Ill Pediatric Patients With Consideration of the ICU Environment and Early Mobility.

RATIONALE: A guideline that both evaluates current practice and provides recommendations to address sedation, pain, and delirium management with regard for neuromuscular blockade and withdrawal is not currently available. OBJECTIVE: To develop comprehensive clinical practice guidelines for critically ill infants and children, with specific attention to seven domains of care including pain, sedation/agitation, iatrogenic withdrawal, neuromuscular blockade, delirium, PICU environment, and early mobility. DESIGN: The Society of Critical Care Medicine Pediatric Pain, Agitation, Neuromuscular Blockade, and Delirium in critically ill pediatric patients with consideration of the PICU Environment and Early Mobility Guideline Taskforce was comprised of 29 national experts who collaborated from 2009 to 2021 via teleconference and/or e-mail at least monthly for planning, literature review, and guideline development, revision, and approval. The full taskforce gathered annually in-person during the Society of Critical Care Medicine Congress for progress reports and further strategizing with the final face-to-face meeting occurring in February 2020. Throughout this process, the Society of Critical Care Medicine standard operating procedures Manual for Guidelines development was adhered to. METHODS: Taskforce content experts separated into subgroups addressing pain/analgesia, sedation, tolerance/iatrogenic withdrawal, neuromuscular blockade, delirium, PICU environment (family presence and sleep hygiene), and early mobility. Subgroups created descriptive and actionable Population, Intervention, Comparison, and Outcome questions. An experienced medical information specialist developed search strategies to identify relevant literature between January 1990 and January 2020. Subgroups reviewed literature, determined quality of evidence, and formulated recommendations classified as "strong" with "we recommend" or "conditional" with "we suggest." Good practice statements were used when indirect evidence supported benefit with no or minimal risk. Evidence gaps were noted. Initial recommendations were reviewed by each subgroup and revised as deemed necessary prior to being disseminated for voting by the full taskforce. Individuals who had an overt or potential conflict of interest abstained from relevant votes. Expert opinion alone was not used in substitution for a lack of evidence. RESULTS: The Pediatric Pain, Agitation, Neuromuscular Blockade, and Delirium in critically ill pediatric patients with consideration of the PICU Environment and Early Mobility taskforce issued 44 recommendations (14 strong and 30 conditional) and five good practice statements. CONCLUSIONS: The current guidelines represent a comprehensive list of practical clinical recommendations for the assessment, prevention, and management of key aspects for the comprehensive critical care of infants and children. Main areas of focus included 1) need for the routine monitoring of pain, agitation, withdrawal, and delirium using validated tools, 2) enhanced use of protocolized sedation and analgesia, and 3) recognition of the importance of nonpharmacologic interventions for enhancing patient comfort and comprehensive care provision.

Prospective Validation of the Preschool Confusion Assessment Method for the ICU to Screen for Delirium in Infants Less Than 6 Months Old.

OBJECTIVES: ICU delirium is a predictor of greater morbidity and higher mortality in the pediatric population. The diagnostic obstacles and validity of delirium monitoring among neonates and young infants have yet to be fully delineated. We sought to validate the Preschool Confusion Assessment Method for the ICU in neonates and young infants and determine delirium prevalence in this young population. DESIGN: Prospective cohort study to validate the Preschool Confusion Assessment Method for the ICU for the assessment of ICU delirium in neonates and young infants compared with the reference standard, Child and Adolescent Psychiatry. SETTING: Tertiary medical center PICU, including medical, surgical, and cardiac patients. PARTICIPANTS: Infants less than 6 months old admitted to the PICU regardless of admission diagnosis. MEASUREMENTS AND MAIN RESULTS: We enrolled 49 patients with a median age of 1.8 months (interquartile range, 0.7-4.1 mo), 82% requiring mechanical ventilation. Enrolled patients were assessed for delirium in blinded-fashion by the research team using the Preschool Confusion Assessment Method for the ICU and independently assessed by the psychiatry reference rater using Diagnostic and Statistical Manual of Mental Disorders-5 criteria. A total of 189 paired assessments were completed, and the Preschool Confusion Assessment Method for the ICU performed with a sensitivity of 95% (95% CI, 89-100%), specificity of 81% (68-90%), "negative and positive predictive values" of 97% (94-100%) and 69% (55-79%), respectively, compared with the reference rater. Delirium prevalence was 47%, with higher rates of 61% observed among neonates (< 1 mo old) and 39% among infants 1-6 months old. CONCLUSIONS: The Preschool Confusion Assessment Method for the ICU is a valid screening tool for delirium monitoring in infants less than 6 months old. Delirium screening was feasible in this population despite evolving neurocognition and arousal architecture. ICU delirium was prevalent among infants. The consequence of acute brain dysfunction during crucial neurocognitive development remains unclear. Future studies are necessary to determine the long-term impact of ICU delirium and strategies to reduce associated harm in critically ill infants.

Validity and Reliability of the Brazilian Portuguese Version of the Pediatric Confusion Assessment Method for the ICU.

OBJECTIVES: To determine the validity and reliability of the Brazilian Portuguese version of the Pediatric Confusion Assessment Method for the ICU for diagnosing delirium in patients with chronological and developmental ages from 5 to 17 years in Brazilian PICUs. DESIGN: Prospective, cross-sectional study. SETTINGS: Eight Brazilian PICUs (seven in Rio de Janeiro and one in São Paulo). PATIENTS: One-hundred sixteen patients, 5-17 years old, without developmental delay, submitted to mechanical ventilation or not. INTERVENTIONS: To assess the inter-observer reliability, two previously trained researchers concomitantly applied the Brazilian Portuguese version of the Pediatric Confusion Assessment Method for the ICU and independently rated the same patient. To assess the criterion validity, a pediatric neurologist or psychiatrist, blinded to the Brazilian Portuguese version of the Pediatric Confusion Assessment Method for the ICU assessments, evaluated the same patient within 30 minutes, using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, considered the reference standard. MEASUREMENTS AND MAIN RESULTS: One-hundred forty-nine paired assessments were included (some patients had more than one). Delirium was diagnosed in 11 of 149 assessments (7%), or eight of 116 patients (7%), using both the Brazilian Portuguese version of the Pediatric Confusion Assessment Method for the ICU and the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. There was one false positive and one false negative diagnosis, which resulted in 90.9% sensitivity (95% CI, 58.7-99.8%) and 99.3% specificity (95% CI, 96-100%) for the Brazilian Portuguese version of the Pediatric Confusion Assessment Method for the ICU. The inter-rater reliability was considered almost perfect (κ = 1.0). CONCLUSIONS: The Brazilian Portuguese version of the Pediatric Confusion Assessment Method for the ICU is a valid and reliable tool for diagnosing delirium in pediatric patients 5-17 years old who are spontaneously breathing and not pharmacologically sedated in Brazilian PICUs. The implementation of this tool may be useful to reduce underdiagnosis, ensure monitoring and earlier intervention, provide a better prognosis, and improve research on delirium in this age group in Brazil. Further studies are necessary to test the psychometric properties of the Brazilian Portuguese version of the Pediatric Confusion Assessment Method for the ICU in sedated and mechanically ventilated children.

Delirium and Benzodiazepines Associated With Prolonged ICU Stay in Critically Ill Infants and Young Children.

OBJECTIVES: Delirium is prevalent among critically ill children, yet associated outcomes and modifiable risk factors are not well defined. The objective of this study was to determine associations between pediatric delirium and modifiable risk factors such as benzodiazepine exposure and short-term outcomes. DESIGN: Secondary analysis of collected data from the prospective validation study of the Preschool Confusion Assessment Method for the ICU. SETTING: Tertiary-level PICU. PATIENTS: Critically ill patients 6 months to 5 years old. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Daily delirium assessments were completed using the Preschool Confusion Assessment Method for the ICU. Associations between baseline and in-hospital risk factors were analyzed for likelihood of ICU discharge using Cox proportional hazards regression and delirium duration using negative binomial regression. Multinomial logistic regression was used to determine associations between daily risk factors and delirium presence the following day. Our 300-patient cohort had a median (interquartile range) age of 20 months (11-37 mo), and 44% had delirium for at least 1 day (1-2 d). Delirium was significantly associated with a decreased likelihood of ICU discharge in preschool-aged children (age-specific hazard ratios at 60, 36, and 12 mo old were 0.17 [95% CI, 0.05-0.61], 0.50 [0.32-0.80], and 0.98 [0.68-1.41], respectively). Greater benzodiazepine exposure (75-25th percentile) was significantly associated with a lower likelihood of ICU discharge (hazard ratio, 0.65 [0.42-1.00]; p = 0.01), longer delirium duration (incidence rate ratio, 2.47 [1.36-4.49]; p = 0.005), and increased risk for delirium the following day (odds ratio, 2.83 [1.27-6.59]; p = 0.02). CONCLUSIONS: Delirium is associated with a lower likelihood of ICU discharge in preschool-aged children. Benzodiazepine exposure is associated with the development and longer duration of delirium, and lower likelihood of ICU discharge. These findings advocate for future studies targeting modifiable risk factors, such as reduction in benzodiazepine exposure, to mitigate iatrogenic harm in pediatric patients.

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 κ-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.

Association of Hyperoxia During Cardiopulmonary Bypass and Postoperative Delirium in the Pediatric Cardiac ICU.

OBJECTIVE: ICU delirium commonly complicates critical illness associated with factors such as cardiopulmonary bypass (CPB) time and the requirement of mechanical ventilation (MV). Recent reports associate hyperoxia with poorer outcomes in critically ill children. This study sought to determine whether hyperoxia on CPB in pediatric patients was associated with a higher prevalence of postoperative delirium. DESIGN: Secondary analysis of data obtained from a prospective cohort study. SETTING: Twenty-two-bed pediatric cardiac ICU in a tertiary children's hospital. PATIENTS: All patients (18 yr old or older) admitted post-CPB, with documented delirium assessment scores using the Preschool/Pediatric Confusion Assessment Method for the ICU and who were enrolled in the Precision Medicine in Pediatric Cardiology Cohort from February 2021 to November 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 148 patients, who underwent cardiac surgery, 35 had delirium within the first 72 hours (24%). There was no association between hyperoxia on CPB and postoperative delirium for all definitions of hyperoxia, including hyperoxic area under the curve above 5 predetermined Pao2 levels: 150 mm Hg (odds ratio [95% CI]: 1.176 [0.605-2.286], p = 0.633); 175 mm Hg (OR 1.177 [95% CI, 0.668-2.075], p = 0.572); 200 mm Hg (OR 1.235 [95% CI, 0.752-2.026], p = 0.405); 250 mm Hg (OR 1.204 [95% CI, 0.859-1.688], p = 0.281), 300 mm Hg (OR 1.178 [95% CI, 0.918-1.511], p = 0.199). In an additional exploratory analysis, comparing patients with delirium within 72 hours versus those without, only the z score for weight differed (mean [sd]: 0.09 [1.41] vs. -0.48 [1.82], p < 0.05). When comparing patients who developed delirium at any point during their ICU stay (n = 45, 30%), MV days, severity of illness (Pediatric Index of Mortality 3 Score) score, CPB time, and z score for weight were associated with delirium (p < 0.05). CONCLUSIONS: Postoperative delirium (72 hr from CPB) occurred in 24% of pediatric patients. Hyperoxia, defined in multiple ways, was not associated with delirium. On exploratory analysis, nutritional status (z score for weight) may be a significant factor in delirium risk. Further delineation of risk factors for postoperative delirium versus ICU delirium warrants additional study.

Pediatric critical care perceptions on analgesia, sedation, and delirium.

Critically ill children suffer from pain and anxiety additionally in the face of severe organ dysfunction. The critical care environment challenges pediatric patients' emotional and developmental capabilities. Disease-focused therapy is a priority and usually requires separation of patient from family and completion of invasive procedures. With the lack of familiar surroundings, inability to self-soothe, and deficiency of sleep, critically ill children may benefit from a multidisciplinary approach to care with a specific goal of pain management. Due to the challenges unique to critical care of children, sedatives and hypnotics are heavily relied upon to "protect" children from the intensive care experience. Delirium occurs in at least 30% of critically ill infants and children reported in small prospective studies, without a large-scale protocol for delirium monitoring. Adult studies demonstrate an overwhelming prevalence of delirium in the critically ill, associated with significant morbidity and mortality. Recently, the diagnosis of pediatric delirium has been enhanced by the validation of bedside tools that encourage monitoring within the critical care setting. Though there are likely many similarities in delirium among adults and children, there is much to learn in regard to unique risk factors and outcomes for children. Perhaps, considering the neurodevelopmental and psychosocial capacities of a child, a creative approach to assess and control pain and anxiety, while optimizing disease-related therapies, may ultimately minimize the risk for the development of delirium or other long-term complications of critical illness.

Pediatric Intensive Care Unit Patients: Sedation, Monitoring, and Neurodevelopmental Outcomes.

The design and conduct of pediatric sedation studies in critically ill patients have historically been challenging due to the complexity of the pediatric intensive care unit (PICU) environment and the difficulty of establishing equipoise. Clinical trials, for instance, represent 1 important means of advancing our knowledge in this field, but there is a paucity of such studies in the literature. Accounting for ground-level factors in planning for each trial phase (eg, enrollment, intervention, assessment, and follow-up) and the presence of broader system limitations is of key importance. In addition, there is a need for early planning, coordination, and obtaining buy-in from individual study sites and staff to ensure success, particularly for multicenter studies. This review synthesizes the current state of pediatric sedation research and the myriad of challenges in designing and conducting successful trials in this particular area. The review poses consideration for future research directions, including novel study designs, and discusses electroencephalography monitoring and neurodevelopmental outcomes of PICU survivors.

Improving Delirium Assessments in Vanderbilt Pediatric and Pediatric Cardiovascular Intensive Care Units.

Introduction: Delirium is a disturbance of attention and awareness that represents a change from baseline mental status. Accurate diagnosis of delirium is of paramount importance to improving the management of pediatric delirium in the intensive care unit. Despite ongoing education, inconsistencies in delirium assessments occur. Here, we aimed to determine the extent of the problem and increase compliance with delirium assessments. Methods: We collected preintervention data to assess baseline compliance of delirium assessments in the Pediatric Intensive Care Unit (PICU) and Pediatric Cardiac Intensive Care Unit (PCICU) at Monroe Carell Jr Children's Hospital at Vanderbilt in November 2020. We executed 2 Plan-Do-Study-Act cycles with different interventions and collected data after each and approximately 1 year after the interventions. The first intervention consisted of virtual lectures on delirium assessments for the nursing staff. The second intervention included an educational handout and a new electronic medical record documentation tool. Results: Five hundred five individual nurse-patient encounters were assessed and collected throughout the project. The mean compliance of delirium documentation before the interventions was 52.5%. Target compliance after interventions was 70%. Mean compliance was 70% after cycle 1, 78% after cycle 2, and 86% in March 2022. Conclusions: Using pre- and postintervention data from chart reviews and nurse interviews regarding delirium screenings, we found that interventions targeting nurse education and EMR flowsheet improved compliance with delirium assessment and documentation in the PICU and PCICU. Future work should focus on assessing the clinical implications of this project in diagnosing and treating delirium.

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 (κ = 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.

Translation and cross-cultural adaptation of the Pediatric Confusion Assessment Method for the Intensive Care Unit into Brazilian Portuguese for the detection of delirium in pediatric intensive care units. / Tradução e adaptação transcultural para o Brasil do Pediatric Confusion Assessment Method for the Intensive Care Unit para detecção de delirium em unidades de terapia intensiva pediátrica.

OBJECTIVE: To undertake the translation and cross-cultural adaption into Brazilian Portuguese of the Pediatric Confusion Assessment Method for the Intensive Care Unit for the detection of delirium in pediatric intensive care units, including the algorithm and instructions. METHODS: A universalist approach for the translation and cross-cultural adaptation of health measurement instruments was used. A group of pediatric critical care specialists assessed conceptual and item equivalences. Semantic equivalence was evaluated by means of a translation from English to Portuguese by two independent translators; reconciliation into a single version; back-translation by a native English speaker; and consensus among six experts with respect to language and content understanding by means of Likert scale responses and the Content Validity Index. Finally, operational equivalence was assessed by applying a pre-test to 30 patients. RESULTS: The back-translation was approved by the original authors. The medians of the expert consensus responses varied between good and excellent, except for the feature "acute onset" of the instructions. Items with a low Content Validity Index for the features "acute onset" and "disorganized thinking" were adapted. In the pre-test, the expression "signal with your head" was modified into "nod your head" for better understanding. No further adjustments were necessary, resulting in the final version for Brazilian Portuguese. CONCLUSION: The Brazilian version of the Pediatric Confusion Assessment Method for the Intensive Care Unit was generated in agreement with the international recommendations and can be used in Brazil for the diagnosis of delirium in critically ill children 5 years of age or above and with no developmental cognitive disabilities.

The intensive care delirium research agenda: a multinational, interprofessional perspective.

Delirium, a prevalent organ dysfunction in critically ill patients, is independently associated with increased morbidity. This last decade has witnessed an exponential growth in delirium research in hospitalized patients, including those critically ill, and this research has highlighted that delirium needs to be better understood mechanistically to help foster research that will ultimately lead to its prevention and treatment. In this invited, evidence-based paper, a multinational and interprofessional group of clinicians and researchers from within the fields of critical care medicine, psychiatry, pediatrics, anesthesiology, geriatrics, surgery, neurology, nursing, pharmacy, and the neurosciences sought to address five questions: (1) What is the current standard of care in managing ICU delirium? (2) What have been the major recent advances in delirium research and care? (3) What are the common delirium beliefs that have been challenged by recent trials? (4) What are the remaining areas of uncertainty in delirium research? (5) What are some of the top study areas/trials to be done in the next 10 years? Herein, we briefly review the epidemiology of delirium, the current best practices for management of critically ill patients at risk for delirium or experiencing delirium, identify recent advances in our understanding of delirium as well as gaps in knowledge, and discuss research opportunities and barriers to implementation, with the goal of promoting an integrated research agenda.