Impact of Intravenous Fat Emulsion Choice on Candida Biofilm, Hyphal Growth, and Catheter-Related Bloodstream Infections in Pediatric Patients.

BACKGROUND: Use of mixed-oil (MO) intravenous fat emulsion (IFE) was shown to inhibit Candida albicans biofilm formation and overall rate of catheter-related bloodstream infections (CR-BSIs) compared with soybean-oil (SO) IFE). We aimed to delineate this inhibitory mechanism and impact of IFE choice on distribution of fungal CR-BSIs. METHODS: Transcriptional profiling was conducted on C. albicans grown in SO-IFE, MO-IFE, or SO-IFE with capric acid. Overexpression strains of shared down-regulated genes were constructed using a tetracycline-off system to assess hypha and biofilm formation in IFEs. A 5-year retrospective multicenter cohort study was performed to assess differences in CR-BSIs caused by Candida species based on the IFE formulation received in pediatric patients. RESULTS: Genes significantly down-regulated in MO-IFE and SO-IFE with capric acid included CDC11, HGC1, and UME6. Overexpression of HGC1 or UME6 enabled filamentation in capric acid and MO-IFE. Interestingly, only overexpression of UME6 was sufficient to rescue biofilm growth in MO-IFE. MO-IFE administration was associated with a higher proportion of non-albicans Candida versus C. albicans CR-BSIs (42% vs 33%; odds ratio, 1.22 [95% confidence interval, .46-3.26]). CONCLUSIONS: MO-IFE affects C. albicans biofilm formation and hyphal growth via a UME6-dependent mechanism. A numerical but not statistically significant difference in distribution of Candida spp. among CR-BSIs was observed.

Delivery of carbohydrates, amino acids, and lipids via intravenous catheters is necessary for some patients to supply daily caloric needs. These nutrient-dense parenteral solutions can promote microbial biofilm growth on the catheter surface, which may seed subsequent catheter-related bloodstream infection (CR-BSI). In fact, receipt of parenteral nutrition is an established risk factor for CR-BSI caused by the polymorphic fungal pathogen Candida albicans. New intravenous fat emulsions (IFEs) have gained market share and IFEs containing capric acid (mixed-oil [MO] IFE) compared with those without (soybean-oil [SO] IFE) impair the C. albicans yeast-to-hypha switch­a trait strongly associated with pathogenicity and biofilm formation. In this study, we found that MO-IFE and capric acid reduced expression of a transcriptional regulator involved in hyphal extension (UME6) and down-regulated genes involved in cell partitioning (HGC1). Overexpression of these genes enabled hyphal growth in MO-IFE. Secondly, we sought to determine whether the type of IFE administered was associated with the clinical incidence of CR-BSIs caused by C. albicans or other common non-albicans Candida species. There was a nonsignificant numerical reduction in C. albicans infections in patients administered MO-IFE compared with SO-IFE. Collectively, this work shows that IFEs differentially affect Candida biology with potential infectious consequences for the patient.

Delirium Assessment Treatment Strategies in Critically Ill Pediatric Patients: A Pediatric Pharmacy Association Practice-Based Research Network Survey Study.

OBJECTIVES: The purpose of this study was to describe overall screening, prevention, and treatments for pediatric delirium at various neonatal intensive care units (NICUs), cardiac intensive care units (CICUs), and pediatric intensive care units (PICUs) from the Pediatric Pharmacy Association (PPA) membership. The primary objective was to identify the number of respondents that had a defined delirium-based protocol. The secondary objectives included identification of delirium assessment tools used, first- and second-line delirium treatment options, and monitoring practices for antipsychotics for delirium management. METHODS: A cross-sectional questionnaire was distributed to PPA members from February 8, 2022, to March, 25, 2022. Comparisons between the NICUs, PICUs, and CICUs were conducted by using chi-square tests, with a priori p value of <0.05. RESULTS: The questionnaire was completed by 84 respondents at 62 institutions; respondents practiced in the PICU or mixed PICU (n = 48; 57.1%), CICU (n = 13; 15.5%), and NICU (n = 23; 27.4%). Sixty-one respondents (72.6%) noted their units routinely screen for delirium, and there was a significant difference between the respondents of different units that use a delirium scoring tool (p < 0.01). Only 33 respondents (39.3%) had a defined delirium protocol, and there was no difference between units (p = 0.31). The most common agents used for delirium treatment were quetiapine and risperidone. There was variability in the monitoring used between respondents, but the majority (n = 74; 88%) monitor electrocardiograms to assess the corrected QT interval, but practice variability existed. CONCLUSIONS: Most respondents did not have a defined delirium protocol. Variations were noted in the treatment options and monitoring for critically ill pediatric patients with delirium.

Incidence of Intracranial Hemorrhage in Patients Younger Than 2 Months Receiving Sodium Bicarbonate 4.2% vs 8.4.

OBJECTIVE: To assess the incidence of intracranial hemorrhage (ICH), including intraventricular hemorrhage, in infants receiving 4.2% or 8.4% sodium bicarbonate. METHODS: This is a single-center retrospective chart review of neonates and infants with a gestational age (GA) >32 weeks and a postnatal age <2 months who received sodium bicarbonate in an intensive care unit at an academic tertiary children's hospital. The primary outcome was the incidence of ICH in patients with baseline and follow-up head imaging. The secondary outcome was the incidence of ICH on follow-up head imaging, with or without baseline head imaging. RESULTS: There were 351 patients screened, with 135 meeting inclusion criteria. Of these, 84% were born ≥37 weeks GA. Forty-two met the criteria for the primary outcome. Study participants were further subdivided into 3 groups based on the concentration of sodium bicarbonate received: only 4.2%, only 8.4%, or a mixed group that received at least 1 dose each of 4.2% and 8.4%. Intracranial hemorrhage was noted in 1 patient in each group: 8.3%, 5.6%, and 8.3%, respectively (p = 1.00). For the secondary outcome, 11 ICHs were seen on head imaging: 11.3%, 3.8%, and 10%, respectively. There was no statistically significant difference in the incidence of ICH (p = 0.325). CONCLUSIONS: The incidence of ICH in term neonates and infants was not significantly different in those receiving 4.2% vs 8.4% sodium bicarbonate. Although additional studies are needed, this study suggests it may be possible to safely expand the use of 8.4% in neonates/infants ≥37 weeks GA. These results should not be applied to preterm neonates (<37 weeks GA and/or <1500 g) or neonates with additional ICH risk factors.

Implementation Strategies for Baby NINJA (Nephrotoxic Injury Negated by Just-in-Time Action) to Prevent Neonatal Medication-Induced Kidney Injury.

Acute kidney injury (AKI) is a common complication among patients admitted to the neonatal intensive care unit. Nephrotoxic medications (NTMs) are known to increase the incidence of AKI, but the use of these -medications is often unavoidable. Baby NINJA (Nephrotoxic Injury Negated by Just-in-Time Action) is a -quality improvement (QI) project that may be implemented at individual institutions and aims to systematically identify AKI in neonates and infants receiving NTMs. The purpose of this review is to describe nephrotoxic AKI in the neonatal population, introduce the Baby NINJA QI project and its potential to reduce neonatal AKI, and outline strategies for effective implementation of Baby NINJA.

Evaluation of Parenteral Potassium Supplementation in Pediatric Patients.

OBJECTIVE: The primary objective was to evaluate the effect of parenteral potassium chloride (KCl) supplementation on potassium (K+) concentrations in a non-cardiac pediatric population. Secondary outcomes were to identify variables that may influence response to KCl supplementation (i.e., change in K+ concentration after KCl administration) and assess the incidence of hyperkalemia. METHODS: This single-center, retrospective study evaluated infants and children who received parenteral KCl supplementation of 0.5 or 1 mEq/kg between January 2017 and December 2019. RESULTS: The study included 102 patients with a median age of 1 year (IQR, 0.4-3.9) and weight of 9.1 kg (IQR, 4.9-14.2) who received 288 parenteral KCl administrations. One hundred seventy-three administrations were in the 1 mEq/kg group, and 115 administrations were in the 0.5 mEq/kg group. The median changes in K+ were 0.8 and 0.5 mEq/L in the 1 mEq/kg and 0.5 mEq/kg groups, respectively. Patients who had a repeat K+ concentration within 4 hours of the end of a 1 to 2-hour infusion had a higher median change in K+ compared with those who had a concentration drawn after this time frame (0.8 vs 0.6 mEq/L; p < 0.01). CONCLUSIONS: There is a paucity of data on the correlation between parenteral KCl supplementation and change in K+ concentrations in pediatric patients. Our study demonstrated an association between KCl supplementation doses of 1 and 0.5 mEq/kg and changes in K+ of 0.8 and 0.5 mEq/L, respectively, in non-cardiac pediatric patients, with low observed incidence of hyperkalemia.

Quetiapine for the Treatment of Pediatric Delirium.

BACKGROUND: Delirium is a common complication of critical illness, with a prevalence of 25% among pediatric intensive care unit (ICU) patients. Pharmacological treatment options for ICU delirium are limited to off-label use of antipsychotics, but their benefit remains uncertain. OBJECTIVE: The purpose of this study was to evaluate quetiapine effectiveness for the treatment of delirium in critically ill pediatric patients and to describe the safety profile of quetiapine. METHODS: A single-center, retrospective review of patients aged ≤ 18 years who screened positive for delirium via the Cornell Assessment of Pediatric Delirium (CAPD ≥ 9) and received ≥ 48 hours of quetiapine therapy was conducted. The relationship between quetiapine and deliriogenic medication doses was evaluated. RESULTS: This study included 37 patients who received quetiapine for the treatment of delirium. The change in sedation requirements before quetiapine initiation to 48 hours after the highest quetiapine dose demonstrated a downward trend; 68% of patients had a decrease in opioid requirements and 43% of patients had a decrease in benzodiazepine requirements. The median CAPD score at baseline was 17 and the median CAPD score at 48 hours after the highest dose was 16. Three patients experienced QTc prolongation (defined as a QTc ≥ 500), although none developed dysrhythmias. CONCLUSION AND RELEVANCE: Quetiapine did not have a statistically significant impact on deliriogenic medication doses. There were minimal changes in QTc and dysrhythmias were not identified. Therefore, quetiapine can be safe to use in our pediatric patients but further studies are needed to find an effective dose.

Integration of the Codonics Safe Label System® and the Omnicell XT® Anesthesia Workstation into Pediatric Anesthesia Practice: Utilizing Technology to Increase Medication Labeling Compliance and Decrease Medication Discrepancies While Maintaining User Acceptability.

Background: Perioperative medication errors are recognized as a source of patient morbidity and mortality. Medication management systems with built-in scanning and label-printing functions that integrate with medication-dispensing cabinets have the potential to decrease medication administration errors by improving compliance with medication labeling. Whether these management systems will also improve periodic automatic replacement (PAR) inventory control and be accepted by users is unknown. We hypothesized that implementation of the Codonics Safe Label System®, an automated labeling system (ALS), would increase compliance with labeling guidelines and improve PAR inventory control by decreasing medication discrepancies while maintaining user acceptability in the OR. Methods: We audited a cohort of anesthesia workstations and electronic anesthesia records for 2 months to compare dispensed and administered medications and establish a discrepancy baseline. We also observed a convenience sample of syringes to evaluate labeling compliance. Post-implementation of the ALS, we repeated the audit. Finally, an anonymous survey was distributed electronically to providers to assess user acceptability. Results: Pre-implementation the average daily medication discrepancy rate was 9.7%, decreasing to 6.1% post-implementation (χ2 1 = 43.9; P < .0001). Pre-implementation 330 of 696 syringes (47.4%) were either missing a label or labeling elements. After implementation, 100% of all syringes received a label with the complete required labeling information (P < .0001). All respondents agreed or strongly agreed that the system was easy to use, accurate, met their needs, printed labels quickly, improved safety and efficiency, and was recommendable. Conclusion: The ALS significantly increased the rate of best-practice-compliant medication labeling while reducing medication inventory discrepancies. The system was highly accepted by providers.

A Multicenter Analysis of Changes in Pediatric Antibiotic Susceptibilities Among Staphylococcus aureus and Pseudomonas aeruginosa Isolates: 2014-2018.

OBJECTIVE: To describe antibiotic susceptibilities for Staphylococcus aureus and Pseudomonas aeruginosa among pediatric institutions in 2018. To assess correlations between antibiotic utilization and susceptibilities. METHODS: Institutional antibiograms from 2018 were compiled among 13 institutions via a survey. Resistant pathogens and antibiotic days of therapy/1000 patient days (PD) were collected from 6 institutions over 5 years. Correlations were assessed as pooled data among all institutions and relative changes within individual institutions. RESULTS: All 8552 S aureus isolates in 2018 were vancomycin susceptible and 40.1% were methicillin resistant (MRSA). Among MRSA, 96.3% and 78.8% were susceptible to trimethoprim/sulfamethoxazole and clindamycin, respectively. Pooled yearly MRSA/1000 PD decreased from 2014-2018 and correlated with pooled yearly decreases in vancomycin utilization (R = 0.983, p = 0.003). Institutional relative decreases in vancomycin utilization from 2014-2018 did not correlate with institutional relative decreases in MRSA susceptibility (R = -0.659, p = 0.16). Susceptibility to meropenem was 90.9% among 2315 P aeruginosa isolates in 2018. Antipseudomonal beta-lactam susceptibility ranged from 89.4% to 92.3%. Pooled yearly meropenem-resistant P aeruginosa/1000 PD and meropenem utilization did not significantly decrease over time or correlate (both p > 0.6). Institutional relative change in meropenem utilization from 2013-2017 correlated with the institutional relative change in P aeruginosa susceptibility to meropenem from 2014-2018 (Rs = -0.89, p = 0.019). CONCLUSIONS: Among included institutions, the burden of MRSA decreased over time. Institutional MRSA prevalence did not consistently correlate with institutional vancomycin utilization. Institutional changes in meropenem utilization correlated with P aeruginosa susceptibility the following year. Pooled analyses did not illustrate this correlation, likely owing to variability in utilization between institutions.

Increased Testing and Health Care Costs for Pediatric Cannabis Exposures.

OBJECTIVES: This study aimed to evaluate the process of identifying marijuana exposure in a children's hospital emergency department and compare the cost of diagnostic testing and procedures. METHODS: A retrospective chart review was performed on patients 31 days to 20 years old with a positive marijuana toxicology screen result between November 2009 and December 2014. Primary outcomes included time to provider recognition of marijuana exposure, number of diagnostic tests and procedures performed, and length of hospital stay. Patients were analyzed based on time of exposure recognition (forthcoming compared with not forthcoming of marijuana exposure) and age (children <12 years compared with adolescents >12 years). RESULTS: There were 37 children and 38 adolescents included. Mean time to exposure recognition was 2.3 ± 4.3 hours in children compared with 0.4 ± 0.9 hours in adolescents (P = 0.02). Patients who were not forthcoming of marijuana exposure experienced more than twice as many diagnostic tests or procedures compared with children who were forthcoming of marijuana exposure (mean, 8.91 vs 4 tests, P < 0.0001) and more than a 4-fold higher cost of potentially avoidable diagnostic tests/procedures. Length of hospital stay was significantly longer in children (18.34 ± 2.39 hours) compared with adolescents (4.22 ± 0.52 hours; P ≤ 0.0001). Few parents or guardians were able to disclose characteristics of the marijuana product. CONCLUSION: Delay in recognition of marijuana exposure is associated with high resource utilization, unnecessary medical costs, and prolonged length of stay.

Marijuana Misadventures in Children: Exploration of a Dose-Response Relationship and Summary of Clinical Effects and Outcomes.

OBJECTIVES: This study aimed to explore a dose-response relationship of delta-9-tetrahydrocannabinol (THC) in THC-naïve children after unintentional acute exposure and compare clinical outcomes with non-naïve children. METHODS: A retrospective review was performed on children aged 31 days to 20 years who presented to Children's Hospital Colorado for care related to acute THC toxicity. The children were divided into groups based on exposure: group 1 (THC naïve) and group 2 (THC non-naïve). RESULTS: A total of 38 children (age, 3.5 [3] years) met inclusion for group 1 and an equal number of children (age, 15.1 [3.9] years) met the criteria for comparison in group 2. Eight naïve patients had documentation of estimated THC dose ingested (mean [SD], 7.13 [5.8] mg/kg; range, 2.9-19.5 mg/kg). A direct relationship between estimated oral THC dose, level of medical intervention required, and hospital disposition was observed. Lethargy/somnolence was more common in the naïve group (84% vs. 26%, P < 0.0001) whereas problems in cognition, perception, and behavior were more common in the non-naïve group (4% vs 11%, P = 0.01). The duration of clinical effect and length of hospital stay were longer in the naïve group (19.3 vs 5.0 hours, P < 0.0001) and (0.73 vs 0.19 days, P < 0.0001) respectively. CONCLUSIONS: There seems to be a direct relationship between the estimated oral THC dose (mg/kg), hospital disposition, and level of medical intervention required. Symptoms and duration of effects after THC exposure varied based on the route of exposure, age of patient, and history of previous THC experience.