Delirium Screening in Critically Ill Children: Secondary Analysis of the Multicenter PICU Up! Pilot Trial Dataset, 2019-2020.

OBJECTIVES: To determine the patient-level factors associated with performing daily delirium screening in PICUs with established delirium screening practices. DESIGN: A secondary analysis of 2019-2020 prospective data from the baseline phase of the PICU Up! pilot stepped-wedge multicenter trial (NCT03860168). SETTING: Six PICUs in the United States. PATIENTS: One thousand sixty-four patients who were admitted to a PICU for 3 or more days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 1064 patients, 74% (95% CI, 71-76%) underwent delirium screening at least once during their PICU stay. On 57% of the 8965 eligible patient days, screening was conducted. The overall prevalence of delirium was 46% across all screened days, and 64% of screened patients experienced delirium at some point during their PICU stay. Factors associated with greater adjusted odds ratio (aOR) of increased daily delirium screening included PICU stay longer than 15 days compared with 1-3 days (aOR 3.36 [95% CI, 2.62-4.30]), invasive mechanical ventilation as opposed to room air (aOR 1.67 [95% CI, 1.32-2.12]), dexmedetomidine infusions (aOR 1.23 [95% CI, 1.04-1.44]) and propofol infusions (aOR 1.55 [95% CI, 1.08-2.23]). Conversely, decreased aOR of daily delirium screening was associated with female gender (aOR 0.78 [95% CI, 0.63-0.96]), and the administration of continuous infusions of opioids (aOR 0.75 [95% CI, 0.63-0.90]) or ketamine (aOR 0.48 [95% CI, 0.29-0.79]). Neither patient age, the presence of family or physical restraints, or benzodiazepine infusions were associated with daily delirium screening rates. CONCLUSIONS: In the 2019-2020 PICU UP! cohort, across six PICUs, delirium screening occurred on only 57% of days, despite the presence of established practices. Female gender, patients in the early stages of their PICU stay, and patients not receiving mechanical ventilation were associated with lower odds of daily delirium screening. Our results highlight the need for structured quality improvement processes to both standardize and increase the frequency of delirium screening.

Effect of a Sepsis Screening Algorithm on Care of Children with False-Positive Sepsis Alerts.

OBJECTIVES: To determine if implementation of an automated sepsis screening algorithm with low positive predictive value led to inappropriate resource utilization in emergency department (ED) patients as evidenced by an increased proportion of children with false-positive sepsis screens receiving intravenous (IV) antibiotics. STUDY DESIGN: Retrospective cohort study comparing children <18 years of age presenting to an ED who triggered a false-positive sepsis alert during 2 different 5-month time periods: a silent alert period when alerts were generated but not visible to clinicians and an active alert period when alerts were visible. Primary outcome was the proportion of patients who received IV antibiotics. Secondary outcomes included proportion receiving IV fluid boluses, proportion admitted to the hospital, and ED length of stay (LOS). RESULTS: Of 1457 patients, 1277 triggered a false-positive sepsis alert in the silent and active alert periods, respectively. In multivariable models, there were no changes in the proportion administered IV antibiotics (27.0% vs 27.6%, aOR 1.1 [0.9,1.3]) or IV fluid boluses (29.7% vs 29.1%, aOR 1.0 [0.8,1.2]). Differences in ED LOS and proportion admitted to the hospital were not significant when controlling for similar changes seen across all ED encounters. CONCLUSIONS: An automated sepsis screening algorithm did not lead to changes in the proportion receiving IV antibiotics or IV fluid boluses, department LOS, or the proportion admitted to the hospital for patients with false-positive sepsis alerts.

Outcomes of Patients with Sepsis in a Pediatric Emergency Department after Automated Sepsis Screening.

OBJECTIVE: To determine the effect of an automated sepsis screening tool on treatment and outcomes of severe sepsis in a pediatric emergency department (ED). STUDY DESIGN: Retrospective cohort study of encounters of patients with severe sepsis in a pediatric ED with a high volume of pediatric sepsis cases over a 2-year period. The automated sepsis screening algorithm replaced a manual screen 1 year into the study. The primary outcome was the proportion of patients treated for sepsis while in the ED. Secondary outcomes were time from ED arrival to first intravenous (IV) antibiotic and first IV fluid bolus, volume of fluid administered in the ED, 30-day mortality, intensive care unit-free days, and hospital-free days. RESULTS: In year 1 of the study, 8910 of 61 026 (14.6%) of encounters had a manual sepsis screen; 137 patients met criteria for severe sepsis. In year 2, 100% of 61 195 encounters had an automated sepsis screen and there were 136 cases of severe sepsis. There was a higher proportion of patients with severe sepsis who had an active malignancy and indwelling central venous catheter in year 2. There were no differences in the proportion of patients treated for sepsis in the ED, time to first IV antibiotic or first IV fluid bolus, fluid volume delivered in the ED, hospital-free days, intensive care unit-free days, or 30-day mortality after implementation of the automated screening algorithm. CONCLUSIONS: An automated sepsis screening algorithm introduced into an academic pediatric ED with a high volume of sepsis cases did not lead to improvements in treatment or outcomes of severe sepsis in this study.

Implementation of an Analgesia-Sedation Protocol Is Associated With Reduction in Midazolam Usage in the PICU.

OBJECTIVES: Examine the association of a revised analgesia-sedation protocol with midazolam usage in the PICU. DESIGN: A single-center nonrandomized before-after study. SETTING: PICU at a quaternary pediatric hospital (Boston Children's Hospital, Boston, MA). PATIENTS: Children admitted to the PICU who were mechanically ventilated for greater than 24 hours. The preimplementation cohort included 190 eligible patients admitted between July 29, 2017, and February 28, 2018, and the postimplementation cohort included 144 patients admitted between July 29, 2019, and February 28, 2020. INTERVENTIONS: Implementation of a revised analgesia-sedation protocol. MEASUREMENTS AND MAIN RESULTS: Our primary outcome, total dose of IV midazolam administered in mechanically ventilated patients up to day 14 of ventilation, decreased by 72% (95% CI [61-80%]; p < 0.001) in the postimplementation cohort. Dexmedetomidine usage increased 230% (95% CI [145-344%]) in the postimplementation cohort. Opioid usage, our balancing metric, was not significantly different between the two cohorts. There were no significant differences in ventilator-free days, PICU length of stay, rate of unplanned extubations, failed extubations, cardiorespiratory arrest events, and 24-hour readmissions to the PICU. CONCLUSIONS: We successfully implemented an analgesia-sedation protocol that primarily uses dexmedetomidine and intermittent opioids, and it was associated with significant decrease in overall midazolam usage in mechanically ventilated patients in the PICU. The intervention was not associated with changes in opioid usage or prevalence of adverse events.

Association Between Anticholinergic Drug Burden and Adequacy of Enteral Nutrition in Critically Ill, Mechanically Ventilated Pediatric Patients.

OBJECTIVES: Enteral nutrition delivery is limited by intolerance and interruptions in critically ill children. Anticholinergic properties of frequently administered medications may contribute to altered gastric motility and enteral nutrition intolerance in this population. We examined the association between the anticholinergic burden of administered medications using the Anticholinergic Drug Scale and adequacy of enteral nutrition delivery. DESIGN: Secondary analysis of data from a previously characterized PICU cohort. SETTING: Multidisciplinary PICU in a quaternary academic medical center. PATIENTS: Younger than or equal to 18 years, on mechanical ventilation and received enteral nutrition within the first 3 days of PICU admission. MEASUREMENTS AND MAIN RESULTS: Daily Anticholinergic Drug Scale score, demographic data, and clinical data were obtained from the primary study. Percent enteral energy adequacy ([kcal delivered ÷ kcal prescribed] × 100) during the first 3 days of PICU admission was calculated. Forty-two patients received enteral nutrition, with median age (interquartile range) 5 years (1.09-12.54 yr), and 62% were male. Median Anticholinergic Drug Scale score was inversely correlated with energy adequacy, with a median 9% decline in energy adequacy per 1-point increase in Anticholinergic Drug Scale score (coefficient, -9.3; 95% CI, -13.43 to -5.27; R2 = 0.35; p < 0.0001). Median hours of enteral nutrition interruptions directly correlated with Anticholinergic Drug Scale score (coefficient, 1.5; 95% CI, 0.531-2.54; R2 = 0.19; p = 0.004). Severity score was greater in patients with less than or equal to 25% enteral energy adequacy and directly correlated with median Anticholinergic Drug Scale score. CONCLUSIONS: Anticholinergic burden from medications administered in the PICU is a potentially modifiable factor for suboptimal enteral nutrition delivery.

Performance of an Automated Screening Algorithm for Early Detection of Pediatric Severe Sepsis.

OBJECTIVES: To create and evaluate a continuous automated alert system embedded in the electronic health record for the detection of severe sepsis among pediatric inpatient and emergency department patients. DESIGN: Retrospective cohort study. The main outcome was the algorithm's appropriate detection of severe sepsis. Episodes of severe sepsis were identified by chart review of encounters with clinical interventions consistent with sepsis treatment, use of a diagnosis code for sepsis, or deaths. The algorithm was initially tested based upon criteria of the International Pediatric Sepsis Consensus Conference; we present iterative changes which were made to increase the positive predictive value and generate an improved algorithm for clinical use. SETTING: A quaternary care, freestanding children's hospital with 404 inpatient beds, 70 ICU beds, and approximately 60,000 emergency department visits per year PATIENTS:: All patients less than 18 years presenting to the emergency department or admitted to an inpatient floor or ICU (excluding neonatal intensive care) between August 1, 2016, and December 28, 2016. INTERVENTION: Creation of a pediatric sepsis screening algorithm. MEASUREMENTS AND MAIN RESULTS: There were 288 (1.0%) episodes of severe sepsis among 29,010 encounters. The final version of the algorithm alerted in 9.0% (CI, 8.7-9.3%) of the encounters with sensitivity 72% (CI, 67-77%) for an episode of severe sepsis; specificity 91.8% (CI, 91.5-92.1%); positive predictive value 8.1% (CI, 7.0-9.2%); negative predictive value 99.7% (CI, 99.6-99.8%). Positive predictive value was highest in the ICUs (10.4%) and emergency department (9.6%). CONCLUSIONS: A continuous, automated electronic health record-based sepsis screening algorithm identified severe sepsis among children in the inpatient and emergency department settings and can be deployed to support early detection, although performance varied significantly by hospital location.

Anticholinergic Medication Burden in Pediatric Prolonged Critical Illness: A Potentially Modifiable Risk Factor for Delirium.

OBJECTIVES: It is important to describe and understand the prevalence and risk factors for the syndrome of delirium in critical illness. Since anticholinergic medication may contribute to the development of delirium in the PICU, we have sought to quantify anticholinergic medication exposure in patients with prolonged admission. We have used Anticholinergic Drug Scale scores to quantify the magnitude or extent of this burden. DESIGN: Retrospective cohort study, January 2011 to December 2015. SETTING: Single academic medical center PICU. PATIENTS: Children under 18 years old with a PICU admission of 15 days or longer, requiring mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Daily Anticholinergic Drug Scale scores for the first 15 days of admission, in each of 88 subjects (total of 1,320 PICU days), were collected and assessed in relation to demographic data, severity of illness, and medication use. Median (interquartile range) of daily Anticholinergic Drug Scale score was 5 (interquartile range, 3-7). Anticholinergic Drug Scale score was not associated with age, sex, medical history, presenting Severity of Illness score, PICU length of stay, ventilator hours, or hospital mortality. Medications most frequently associated with high Anticholinergic Drug Scale score were low potency anticholinergic drugs such as morphine, midazolam, vancomycin, steroids, and furosemide, with the exception of ranitidine (Anticholinergic Drug Scale score 2). Patients receiving high doses of midazolam infusion had significantly higher Anticholinergic Drug Scale scores compared with those receiving lower or no midazolam dosing. CONCLUSIONS: A high number of medications with anticholinergic effects are administered to PICU patients receiving prolonged mechanical ventilation. These exposures are much higher than those reported in adult intensive care patients. Since anticholinergic drug exposure is associated with delirium, further study of this exposure in PICU patients is needed.

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.

Differentiating Delirium From Sedative/Hypnotic-Related Iatrogenic Withdrawal Syndrome: Lack of Specificity in Pediatric Critical Care Assessment Tools.

OBJECTIVES: To identify available assessment tools for sedative/hypnotic iatrogenic withdrawal syndrome and delirium in PICU patients, the evidence supporting their use, and describe areas of overlap between the components of these tools and the symptoms of anticholinergic burden in children. DATA SOURCES: Studies were identified using PubMed and EMBASE from the earliest available date until July 3, 2016, using a combination of MeSH terms "delirium," "substance withdrawal syndrome," and key words "opioids," "benzodiazepines," "critical illness," "ICU," and "intensive care." Review article references were also searched. STUDY SELECTION: Human studies reporting assessment of delirium or iatrogenic withdrawal syndrome in children 0-18 years undergoing critical care. Non-English language, exclusively adult, and neonatal intensive care studies were excluded. DATA EXTRACTION: References cataloged by study type, population, and screening process. DATA SYNTHESIS: Iatrogenic withdrawal syndrome and delirium are both prevalent in the PICU population. Commonly used scales for delirium and iatrogenic withdrawal syndrome assess signs and symptoms in the motor, behavior, and state domains, and exhibit considerable overlap. In addition, signs and symptoms of an anticholinergic toxidrome (a risk associated with some common PICU medications) overlap with components of these scales, specifically in motor, cardiovascular, and psychiatric domains. CONCLUSIONS: Although important studies have demonstrated apparent high prevalence of iatrogenic withdrawal syndrome and delirium in the PICU population, the overlap in these scoring systems presents potential difficulty in distinguishing syndromes, both clinically and for research purposes.

Mannose-Binding Lectin Levels in Critically Ill Children With Severe Infections.

OBJECTIVES: Low mannose-binding lectin levels and haplotypes associated with low mannose-binding lectin production have been associated with infection and severe sepsis. We tested the hypothesis that mannose-binding lectin levels would be associated with severe infection in a large cohort of critically ill children. DESIGN: Prospective cohort study. SETTING: Medical and Surgical PICUs, Boston Children's Hospital. PATIENTS: Children less than 21 years old admitted to the ICUs from November 2009 to November 2010. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We measured mannose-binding lectin levels in 479 of 520 consecutively admitted children (92%) with severe or life-threatening illness. We genotyped 213 Caucasian children for mannose-binding lectin haplotype tagging variants and assigned haplotypes. In the univariate analyses of mannose-binding lectin levels with preadmission characteristics, levels were higher in patients with preexisting renal disease. Patients who received greater than 100 mL/kg of fluids in the first 24 hours after admission had markedly lower mannose-binding lectin, as did patients who underwent spinal fusion surgery. Mannose-binding lectin levels had no association with infection status at admission, or with progression from systemic inflammatory response syndrome to sepsis or septic shock. Although mannose-binding lectin haplotypes strongly influenced mannose-binding lectin levels in the predicted relationship, low mannose-binding lectin-producing haplotypes were not associated with increased risk of infection. CONCLUSIONS: Mannose-binding lectin levels are largely genetically determined. This relationship was preserved in children during critical illness, despite the effect of large-volume fluid administration on mannose-binding lectin levels. Previous literature evaluating an association between mannose-binding lectin levels and severe infection is inconsistent; we found no relationship in our PICU cohort. We found that mannose-binding lectin levels were lower after aggressive fluid resuscitation and suggest that studies of mannose-binding lectin in critically ill patients should assess mannose-binding lectin haplotypes to reflect preillness levels.

The Effects of Pointe Shoes on Ballet Dancers' Biomechanics, Muscle Activity, Movement and Symptoms: A Scoping Review.

Introduction: Dancing en pointe requires ballet dancers to stand on the tips of their toes while wearing a structured pointe shoe. Understanding the effect of pointe shoes on ballet dancers' biomechanics, function, symptoms and skin health is essential to guide shoe development and ultimately improve dancer performance. Therefore, the purpose of this scoping review was to map the evidence and identify knowledge gaps related to the effect of wearing pointe shoes on professional and recreational ballet dancers. Method: A scoping review was conducted by searching 6 electronic databases and the International Association for Dance Medicine and Science Bibliography. Results: Thirty-five studies were grouped into 5 categories: pointe shoe factors (eg, toe box and shank, pointe shoe status; 9 studies), shoe types (eg, flat shoes vs demi pointe vs pointe; 10 studies), ballet movements (11 studies), symptoms (5 studies), and intrinsic dancer factors (eg, foot type/toe length; 7 studies). Studies were published between 1979 and 2023, with 72% (n = 23) published between 2006 and 2020. Most (86%) of the studies were cross-sectional. Most studies explored biomechanical outcomes and the most common data collection device was force plates (19 studies). Overall, there was an insufficient volume of evidence for specific research aims. Significant gaps in knowledge exist regarding functional and performance-based outcomes, injury outcomes including exploration of factors such as shoe age/usage, and pointe shoe treatment factors. Conclusions: Currently the field of research suffers from threats to ecological validity, with many study methods not reflecting ballet-specific demands or environments. The impact of pointe shoes on ballet dancers is a developing research area, and this scoping review can help guide future research decisions. Studies need to target the knowledge gaps and employ rigorous ecologically valid study designs and ensure that findings inform shoe design and dancer education to minimize injury and maximize comfort and performance.

Antipsychotic Drug Prescription in Pediatric Intensive Care Units: A 10-Year U.S. Retrospective Database Study.

Delirium recognition during pediatric critical illness may result in the prescription of antipsychotic medication. These medications have unclear efficacy and safety. We sought to describe antipsychotic medication use in pediatric intensive care units (PICUs) contributing to a U.S. national database. This study is an analysis of the Pediatric Health Information System Database between 2008 and 2018, including children admitted to a PICU aged 0 to 18 years, without prior psychiatric diagnoses. Antipsychotics were given in 16,465 (2.3%) of 706,635 PICU admissions at 30 hospitals. Risperidone (39.6%), quetiapine (22.1%), and haloperidol (20.8%) were the most commonly used medications. Median duration of prescription was 4 days (interquartile range: 2-11 days) for atypical antipsychotics, and haloperidol was used a median of 1 day (1-3 days). Trend analysis showed quetiapine use increased over the study period, whereas use of haloperidol and chlorpromazine (typical antipsychotics) decreased ( p < 0.001). Compared with no antipsychotic administration, use of antipsychotics was associated with comorbidities (81 vs. 65%), mechanical ventilation (57 vs. 36%), longer PICU stay (6 vs. 3 days), and higher mortality (5.7 vs. 2.8%) in univariate analyses. In the multivariable model including demographic and clinical factors, antipsychotic prescription was associated with mortality (odds ratio [OR] = 1.09, 95% confidence interval [CI]: 1.02-1.18). Use of atypical antipsychotics increased over the 10-year period, possibly reflecting increased comfort with their use in pediatric patients. Antipsychotics were more common in patients with comorbidities, mechanical ventilation, and longer PICU stay, and associated with higher mortality in an adjusted model which warrants further study.