Background/Objectives: Vancomycin dosing in neonates is challenging due to high pharmacokinetic variability and immature renal function. This study evaluated current therapeutic drug monitoring (TDM) practices, the association between vancomycin concentration and clinical outcomes, and the predictive performance of a locally developed population pharmacokinetic (popPK) model compared to the published models. Methods: This was a retrospective cohort study of neonates admitted to a tertiary neonatal intensive care unit (NICU). We assessed the persistent positive culture, infection recurrence, mortality and acute kidney injury (AKI) stratified by initial vancomycin trough concentrations (<10 mg/L, 10-15 mg/L, >15 mg/L). The locally developed popPK model was externally validated and compared with 32 other published neonatal vancomycin popPK models (with a total of 33 models evaluated). Results: A total of 366 neonates were included (mean postmenstrual age of 28.9 ± 3.81 weeks; 191 received at least 5 days of vancomycin). Only 28% of neonates achieved initial vancomycin trough concentrations within the 10-15 mg/L using standard vancomycin dosing. Higher vancomycin trough concentrations (>15 mg/L) were not associated with improved efficacy but were significantly associated with a higher incidence of AKI. The locally derived popPK model demonstrated superior predictive accuracy, meeting all predefined performance criteria, whereas none of the 32 other published models met all the criteria. Conclusions: Current vancomycin dosing strategies often result in suboptimal exposure and increased nephrotoxicity without added efficacy. Model-informed precision dosing using the locally developed popPK model may offer a safer, more effective approach for neonatal vancomycin therapy.

Background Delirium is a common complication of critical care admissions. In pediatrics, the introduction of antipsychotics for delirium management has not yet been established. Objectives We aimed to assess the effectiveness and short-term safety of quetiapine for delirium in critically ill patients younger than 2 years of age. Methods A single-center descriptive study included 78 patients less than 2 years old who were prescribed quetiapine in the intensive care units (ICU) from July 2018 to November 2023. Quetiapine dosing regimens, efficacy, and short-term safety parameters were assessed. Results Quetiapine use was more frequent in the cardiac critical care unit (n = 62 [79.5%]) compared to the pediatric intensive care unit (n = 16 [20.5%]). The median quetiapine course duration was 6 days (interquartile range [IQR], 2-23 days). Although Cornell Assessment of Pediatric Delirium (CAPD) scores during quetiapine use (median, 9.1 [IQR, 6-11.5]) were lower than scores before quetiapine use (median, 13.0 [IQR, 10-16]), they were still indicative of delirium (P = 0.4). Median opioid use did not differ during quetiapine use (P = 0.6), whereas benzodiazepine exposure decreased (P < 0.01). Changes in alpha-agonist use showed a transition from intravenous to oral agents (P < 0.01). Half of the patients had improvements in their mechanical ventilation requirements (P < 0.01). No adverse effects associated with quetiapine were observed. Conclusions Patients receiving quetiapine for ICU delirium had a statistically significant decrease in benzodiazepine exposure and mechanical ventilation requirements (P < 0.01). No statistically significant changes in CAPD scores (P = 0.4) or opioid exposure (P = 0.6) were observed. Quetiapine use appeared to be safe. Future research is required to standardize the duration and weaning of quetiapine in this patient population and evaluate which pediatric ICU subpopulations would most benefit from quetiapine for delirium management.

Background:National consensus-based clinical pharmacy key performance indicators (cpKPIs) are health quality indicators representing processes of care associated with an impact on meaningful patient outcomes. Canadian hospitals are measuring cpKPIs at the local level. However, variations exist regarding which cpKPIs are measured and the associated cpKPI practice profiles. At the time this study was undertaken, a national registry did not exist to capture real-world cpKPI patient data and to track pooled national progress. Objectives:To develop a national cpKPI patient registry, to characterize cpKPI-related care delivered, and to generate pooled national summary cpKPI reports to inform the advancement of pharmacy practice and improve patient outcomes. Methods:In this national, retrospective, observational quality improvement study, hospitals measuring at least one cpKPI in at least one inpatient area were enrolled and submitted aggregated, de-identified cpKPI patient data for the calendar year 2018 (January to December). Patient-proportion cpKPI data for individual hospitals were summarized, and pooled national reports were generated. Results:Overall, 32 Canadian health care organizations were enrolled, capturing 275 896 patient visits. The core analysis focused on 25 acute care institutions that were continuously measuring cpKPIs. The most commonly delivered cpKPI processes of care were development of a pharmaceutical care plan (59% of patients), resolution of drug therapy problems (37% of patients), and participation in interprofessional patient care rounds (36% of patients). The least commonly delivered cpKPI care services were patient medication education during the hospital stay (7% of patients), medication reconciliation at discharge (15% of patients), and patient medication education at discharge (17% of patients). Conclusions:The first national registry for capturing clinical pharmacy health quality indicators was established and used to characterize real-world cpKPI-related patient care delivery. The findings from this registry could facilitate hospital-level cpKPI benchmarking and could support national sharing of best practices to advance pharmacy practice and improve patient outcomes.

Objectives:To describe the epidemiology of nine medications with pharmacogenetic guidance (targeted medications) and frequency of pharmacogenetic testing; and to develop a retrospective machine learning (ML) model to predict prescription of targeted medications within 3 and 6 months of admission. Methods and Analysis:For the epidemiology aim, the cohort included patients prescribed at least one targeted medication. Pharmacogenetic testing rates were determined before and after first targeted medication prescription. For the ML aim, the cohort included all inpatient admissions. Outcome was receipt of a targeted medication within 3 or 6 months. Models were trained using L2-regularised logistic regression and two gradient boosting machine frameworks (LightGBM and XGBoost). Data were temporally split into training (80%), validation (10%) and test (10%) sets. Results:For the epidemiology cohort, 4520 patients were prescribed at least one targeted medication. Only 4.3% (n=194) had pharmacogenetic testing performed at any point, and only 1.0% (n=44) completed testing before the first prescription. For the ML cohort, 57 368 admissions were included. LightGBM was the best-performing ML model. For the prediction of prescription of a targeted medication at 3 and 6 months, area under the receiver operating characteristic curves was 0.926 (95% CI 0.911 to 0.939) and 0.922 (95% CI 0.911 to 0.932), respectively. Area under the precision recall curves was 0.477 (95% CI 0.462 to 0.495) and 0.450 (95% CI 0.411 to 0.494), respectively. Conclusion:Only 1% of patients receiving a targeted medication had pharmacogenetic testing before the medication order. We developed an ML model with acceptable performance to predict targeted medication administration with the goal of facilitating earlier pharmacogenomic testing.

BACKGROUND:Bloodstream infections (BSIs) are associated with significant mortality and morbidity, including multiple organ dysfunction. We explored if delayed adequate antimicrobial treatment for children with BSIs is associated with change in organ dysfunction as measured by PELOD-2 scores. METHODS:We conducted a multicenter, retrospective cohort study of critically ill children <18 years old with BSIs. The primary outcome was change in PELOD-2 score between days 1 (index blood culture) and 5. The exposure variable was delayed administration of adequate antimicrobial therapy by ≥3 h from blood culture collection. We compared PELOD-2 score changes between those who received early and delayed treatment. RESULTS:Among 202 children, the median (interquartile range) time to adequate antimicrobial therapy was 7 (0.8-20.1) hours; 124 (61%) received delayed antimicrobial therapy. Patients who received early and delayed treatment had similar baseline characteristics. There was no significant difference in PELOD-2 score changes from days 1 and 5 between groups (PELOD-2 score difference -0.07, 95% CI -0.92 to 0.79, p = 0.88). CONCLUSIONS:We did not find an association between delayed adequate antimicrobial therapy and PELOD-2 score changes between days 1 and 5 from detection of BSI. PELOD-2 score was not sensitive for clinical effects of delayed antimicrobial treatment. IMPACT:In critically ill children with bloodstream infections, there was no significant change in organ dysfunction as measured by PELOD-2 scores between patients who received adequate antimicrobial therapy within 3 h of their initial positive blood culture and those who started after 3 h. Higher PELOD-2 scores on day 1 were associated with larger differences in PELOD-2 scores between days 1 and 5 from index positive blood cultures. Further study is required to determine if PELOD-2 or alternative measures of organ dysfunction could be used as primary outcome measures in trials of antimicrobial interventions in pediatric critical care research.

BACKGROUND:Neonatal sepsis is commonly treated with vancomycin in the neonatal intensive care unit. Therapeutic drug monitoring of vancomycin is routinely used to personalise dosing to optimise effectiveness and avoid toxicity. OBJECTIVES:This study aimed to define a target range by evaluating associations between vancomycin trough concentrations or area under the concentration time curve over 24 hours (AUC24h) and clinical outcomes in neonates. METHODS:Neonates, who were admitted to the neonatal intensive care unit and received intravenous vancomycin, were included in this retrospective cohort study. For evaluating effectiveness, patients who received vancomycin for < 5 days were excluded. The AUC24h was estimated based on a study-derived population pharmacokinetic model. Primary outcomes were persistent/recurrent infections and mortality within 30 days. Secondary outcomes, including acute kidney injury (AKI), were also assessed. Logistic regression and classification and regression tree analyses were performed. RESULTS:A total of 448 patients (123 patients for effectiveness analysis) were included. A vancomycin trough > 10 mg/L was associated with 70% lower odds of persistent/recurrent infections (adjusted OR 0.30, 95% CI 0.09-0.86; P = 0.023). Patients who took more than a day to reach target range had 1.4 times higher odds of persistent/recurrent infections or death (P = 0.04). A vancomycin trough > 15 mg/L was associated with a three times higher risk of AKI (P = 0.003). An AUC24h of 420-650 mg*h/L was also associated with the lowest risk of composite outcomes (adjusted OR 0.29, 95% CI 0.08-0.86; P = 0.025). CONCLUSION:A vancomycin trough target range of 10-15 mg/L and achievement of this target within a day of treatment initiation were associated with the most optimal clinical outcomes in treating neonatal sepsis.

Introduction: Vancomycin dosing tailored for newborns is challenging due to the significant influence of maturation and organ function on pharmacokinetics. Population pharmacokinetic (popPK) models can be used to improve target attainment in neonates.Objectives: The primary objective was to derive and evaluate a popPK model of intravenous vancomycin for neonates. Second, the predictive performance of this popPK model was compared with published popPK models.Methods: This is a retrospective cohort study of neonates admitted to the neonatal intensive care unit receiving intravenous vancomycin. A popPK model was derived with 70% of the dataset using a nonlinear mixed effects modeling method. The predictive performance of the current popPK model was validated and compared with 22 published popPK models using the remaining 30% of the dataset. Monte Carlo simulations (MCS) were performed to derive optimal dosing regimens to treat neonatal sepsis caused by coagulase-negative staphylococci (CoNS).Results: Among 655 vancomycin courses from 448 neonates, 78% of vancomycin trough concentrations were outside target range (10-15 mg/L) for central nervous system infections and 43% were outside target range (5-12 mg/L) for other infections using the institution's vancomycin dosing. A one-compartment model best described the observed data with a mean clearance of 0.11 +/- 0.03 L/kg/h and volume of distribution (V) of 1.02 +/- 0.08 L/kg. Body weight (WT), postmenstrual age (PMA), and serum creatinine (SCr) were significant covariates associated with clearance (p < 0.001) and body WT was a significant covariate associated with V (p = 0.009). Our study's popPK model has similar or better accuracy and precision than other published models. MCS-derived vancomycin doses from the validated model achieved >90% target attainment for a steady state through target range of 10-15 mg/L in the majority of PMA and SCr categories (78%) to treat CoNS sepsis.Conclusion: A vancomycin dosing guideline derived from a validated popPK model in neonates with CoNS sepsis is recommended to improve target attainment.

Objectives We used modified contingent valuation methodology to determine how noninferiority margin sizes influence clinicians’ willingness to accept clinical trial results that compare mortality in critically ill children. Methods We surveyed pediatric infectious diseases and critical care clinicians in Canada, Australia, and New Zealand and randomized respondents to review 1 of 9 mock abstracts describing a noninferiority trial of bacteremic critically ill children assigned to 7 or 14 d of antibiotics. Each scenario showed higher mortality in the 7-d group but met noninferiority criterion. We explored how noninferiority margins and baseline mortality rates influenced respondent acceptance of results. Results There were 106 survey respondents: 65 (61%) critical care clinicians, 28 (26%) infectious diseases physicians, and 13 (12%) pharmacists. When noninferiority margins were 5% and 10%, 73% (24/33) and 79% (27/33) respondents would accept shorter treatment, compared with 44% (17/39) when the margin was 20% ( P = 0.003). Logistic regression adjusted for baseline mortality showed 5% and 10% noninferiority margins were more likely to be associated with acceptance of shorter treatment compared with 20% margins (odds ratio [OR] 3.5, 95% confidence interval [CI]: 1.3–9.6, P = 0.013; OR 5.1, 95% CI: 1.8–14.6, P = 0.002). Baseline mortality was not a significant predictor of acceptance of shorter treatment. Conclusions Clinicians are more likely to accept shorter treatment when noninferiority margins are ≤10%. However, nearly half of respondents who reviewed abstracts with 20% margins were still willing to accept shorter treatment. This is a novel application of contingent valuation methodology to elicit acceptance of research results among end users of the medical literature. Highlights Clinicians are more likely to accept shorter treatment durations based on noninferior mortality results when the noninferiority margin is 5% or 10% than if the margin is 20%. However, nearly half of clinicians would still accept shorter-duration treatment as noninferior with margins of 20%. Baseline mortality does not independently predict acceptance of shorter-duration treatment. Contingent valuation is a novel approach to elicit the acceptance of research design parameters from the perspective of endusers of the medical literature.

Gray, S.1; Silver, S.2; Seto, W.3; Pong, S.3; Theissen, A.3; Chan, P.4; Carey, S.4; Chmietewski, A.4; Gilfoyle, E.1; Jessa, K.2; Mckinnon, N. K.1 Author Information

OBJECTIVE:To describe antibiotic treatment durations that pediatric infectious diseases (ID) and critical care clinicians usually recommend for bloodstream infections in critically ill children.DESIGN:Anonymous, online practice survey using five common pediatric-based case scenarios of bloodstream infections.SETTING:Pediatric intensive care units in Canada, Australia and New Zealand.PARTICIPANTS:Pediatric intensivists, nurse practitioners, ID physicians and pharmacists.MAIN OUTCOME MEASURES:Recommended treatment durations for common infectious syndromes associated with bloodstream infections and willingness to enrol patients into a trial to study treatment duration.RESULTS:Among 136 survey respondents, most recommended at least 10 days antibiotics for bloodstream infections associated with: pneumonia (65%), skin/soft tissue (74%), urinary tract (64%) and intra-abdominal infections (drained: 90%; undrained: 99%). For central vascular catheter-associated infections without catheter removal, over 90% clinicians recommended at least 10 days antibiotics, except for infections caused by coagulase negative staphylococci (79%). Recommendations for at least 10 days antibiotics were less common with catheter removal. In multivariable linear regression analyses, lack of source control was significantly associated with longer treatment durations (+5.2 days [95% CI: 4.4-6.1 days] for intra-abdominal infections and +4.1 days [95% CI: 3.8-4.4 days] for central vascular catheter-associated infections). Most clinicians (73-95%, depending on the source of bloodstream infection) would be willing to enrol patients into a trial of shorter versus longer antibiotic treatment duration.CONCLUSIONS:The majority of clinicians currently recommend at least 10 days of antibiotics for most scenarios of bloodstream infections in critically ill children. There is practice heterogeneity in self-reported treatment duration recommendations among clinicians. Treatment durations were similar across different infectious syndromes. Under appropriate clinical conditions, most clinicians would be willing to enrol patients into a trial of shorter versus longer treatment for common syndromes associated with bloodstream infections.

Background Bloodstream infections (BSIs) cause significant morbidity and mortality in critically ill children but treatment duration is understudied. We describe the durations of antimicrobial treatment that critically ill children receive and explore factors associated with treatment duration. Methods We conducted a retrospective observational cohort study in six pediatric intensive care units (PICUs) across Canada. Associations between treatment duration and patient-, infection- and pathogen-related characteristics were explored using multivariable regression analyses. Results Among 187 critically ill children with BSIs, the median duration of antimicrobial treatment was 15 (IQR 11–25) days. Median treatment durations were longer than two weeks for all subjects with known sources of infection: catheter-related 16 (IQR 11–24), respiratory 15 (IQR 11–26), intra-abdominal 20 (IQR 14–26), skin/soft tissue 17 (IQR 15–33), urinary 17 (IQR 15–35), central nervous system 33 (IQR 15–46) and other sources 29.5 (IQR 15–55) days. When sources of infection were unclear, the median duration was 13 (IQR 10–16) days. Treatment durations varied widely within and across PICUs. In multivariable linear regression, longer treatment durations were associated with severity of illness (+ 0.4 days longer [95% confidence interval (CI), 0.1 to 0.7, p = 0.007] per unit increase in PRISM-IV) and central nervous system infection (+ 17 days [95% CI, 6.7 to 27.4], p = 0.001). Age and pathogen type were not associated with treatment duration. Conclusions Most critically ill children with BSIs received at least two weeks of antimicrobial treatment. Further study is needed to determine whether shorter duration therapy would be effective for selected critically ill children.

Abstract Objectives An eight-bed adult coronavirus (COVID-19) critical care (CC) unit was established within our pediatric CC unit (PCCU) when SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) variants increased the CC bed demand. Our objective was to rapidly implement electronic order sets (OSs) to facilitate computerized provider order entry (CPOE) for adult patients admitted within a children's hospital. Methods OS development began from the assessment of OSs from seven adult CC units. Using a pre-existing PCCU admission template, we created two OSs: adult COVID-19 admission and ongoing care. We tested the prototypes in a multidisciplinary onsite–virtual hybrid tabletop simulation to evaluate usability within established workflows. Participants utilized role-specific profiles within the electronic health record (EHR) training environment which paralleled their computer interface, permitting charting and documentation. EHR analysts were present to gather change requests. Following implementation, we performed twice-daily huddles with end users to identify issues. Results A total of 13 multidisciplinary bedside providers participated in simulation testing of the prototypes. Two safety issues were addressed before implementation. The electronic OSs were developed, tested, and implemented within 8 days. The postimplementation huddles identified one medication addition, and no deletions were necessary. Conclusion Caring for adult COVID-19 patients within a freestanding children's hospital presents challenges and has the potential to introduce latent safety threats. Rapid development and implementation of electronic OSs within 8 days to facilitate CPOE and reduce health care provider cognitive burden relied on leveraging functionality within the EMR system, performing iterative testing with a tabletop simulation, integration into previously established workflows, and gathering post-implementation feedback for continuous improvement.

BACKGROUND AND OBJECTIVES Discharge prescription practices may contribute to medication overuse and polypharmacy. We aimed to estimate changes in the number and types of medications reported at inpatient discharge (versus admission) at a tertiary care pediatric hospital. METHODS Electronic medication reconciliation data were extracted for inpatient admissions at The Hospital for Sick Children from January 1, 2016, to December 31, 2017 (n = 22 058). Relative changes in the number of medications and relative risks (RRs) of specific types and subclasses of medications at discharge (versus admission) were estimated overall and stratified by the following: sex, age group, diagnosis of a complex chronic condition, surgery, or ICU (PICU) admission. Micronutrient supplements, nonopioid analgesics, cathartics, laxatives, and antibiotics were excluded in primary analyses. RESULTS Medication counts at discharge were 1.27-fold (95% confidence interval [CI]: 1.25-1.29) greater than admission. The change in medications at discharge (versus admission) was increased by younger age, absence of a complex chronic condition, surgery, PICU admission, and discharge from a surgical service. The most common drug subclasses at discharge were opioids (22% of discharges), proton pump inhibitors (18%), bronchodilators (10%), antiemetics (9%), and corticosteroids (9%). Postsurgical patients had higher RRs of opioid prescriptions at discharge (versus admission; RR: 13.3 [95% CI: 11.5-15.3]) compared with nonsurgical patients (RR: 2.38 [95% CI: 2.22-2.56]). CONCLUSIONS Pediatric inpatients were discharged from the hospital with more medications than admission, frequently with drugs that may be discretionary rather than essential. The high frequency of opioid prescriptions in postsurgical patients is a priority target for educational and clinical decision support interventions.

Introduction Vancomycin is a common antibiotic used to treat hemodialysis (HD) or hemodiafiltration (HDF)-related infections in pediatric patients, but optimal dosing remains unknown. This is the first observational study to characterize the pharmacokinetics and evaluate dosing of vancomycin in this population. Methods Eligible patients received IV vancomycin 10 mg/kg per dose postdialysis followed by a series of serum vancomycin concentrations collected before, immediately after, 1 hour after, and 4 hours after dialysis. The pharmacokinetic parameters were estimated using 1- and 2-compartment models and a nonlinear least-squares algorithm. Results Among 42 vancomycin courses in 16 patients, 1 compartment model had the best fit for observed data. The net drug removal was 43 ± 13% (39% for HD and 50% for HDF) from an average 3-hour HD/HDF session. The mean elimination constant was 0.28 h−1 (standard deviation [SD], 0.11 h−1) during the intradialytic period compared with 0.0049 h−1 (SD, 0.004 h−1) when off dialysis. The mean volume of distribution was 0.65 (SD, 0.19) L/kg. Duration of dialysis session and mode of dialysis (HD vs. HDF) were significant predictors of vancomycin pharmacokinetic parameters. Half-life was shorter for HDF compared with HD (2.1 vs. 3.5 hours). Conclusions Based on the simulations, an initial vancomycin dose of 10 mg/kg per dose and redosing postdialysis was optimal to achieve a vancomycin concentration range of 5 to 12 mg/L at 4 hours postdialysis and 24-hour area under the curve over minimum inhibitory concentration of ≥400 hours. Therapeutic drug monitoring is necessary to account for residual variability in vancomycin elimination in pediatric patients receiving HD/HDF.

Objective To describe the size and variability of non-inferiority margins used in non-inferiority trials of medications with primary outcomes involving mortality, and to examine the association between trial characteristics and non-inferiority margin size. Design Systematic review. Data sources Medline, Medline In Process, Medline Epub Ahead of Print and Embase Classic+Embase databases from January 1989 to December 2019. Eligibility criteria Prospective non-inferiority randomised controlled trials comparing pharmacological therapies, with primary analyses for non-inferiority and primary outcomes involving mortality alone or as part of a composite outcome. Trials had to prespecify non-inferiority margins as absolute risk differences or relative to risks of outcome and provide a baseline risk of primary outcome in the control intervention. Results 3992 records were screened, 195 articles were selected for full text review and 111 articles were included for analyses. 82% of trials were conducted in thrombosis, infectious diseases or oncology. Mortality was the sole primary outcome in 23 (21%) trials, and part of a composite primary outcome in 88 (79%) trials. The overall median non-inferiority margin was an absolute risk difference of 9% (IQR 4.2%–10%). When non-inferiority margins were expressed relative to the baseline risk of primary outcome in control groups, the median relative non-inferiority margin was 1.5 (IQR 1.3–1.7). In multivariable regression analyses examining the association between trial characteristics (medical specialty, inclusion of paediatric patients, mortality as a sole or part of a composite primary outcome, presence of industry funding) and non-inferiority margin size, only medical specialty was significantly associated with non-inferiority margin size. Conclusion Absolute and relative non-inferiority margins used in published trials comparing medications are large, allowing conclusions of non-inferiority in the context of large differences in mortality. Accepting the potential for large increases in outcomes involving mortality while declaring non-inferiority is a challenging methodological issue in the conduct of non-inferiority trials.

Objectives: Despite the ubiquitous role of pharmacotherapy in the care of critically ill children, descriptions of the extent of pharmacotherapy in critical illness are limited. Greater understanding of drug therapy can help identify clinically important associations and assist in the prioritization of efforts to address knowledge gaps. The objectives of this study were to describe the diversity, volume, and patterns of pharmacotherapy in critically ill children. Design: A retrospective cohort study was performed with patient admissions to the ICU between July 31, 2006, and July 31, 2015. Setting: The study took place at a single, free-standing, pediatric, quaternary center. Patients: Eligible patient admissions were admitted to the ICU for more than 6 hours and received one or more drug administration. There were a total 17,482 patient-admissions and after exclusion of 283 admissions (2%) with no documented enteral or parenteral drug administration, 17,199 eligible admissions were studied. Interventions: None. Measurements and Main Results: The 17,199 eligible admissions were admitted to the ICU for 2,208,475 hours and received 515 different drugs. The 1,954,171 administrations were 894,709 (45%) enteral administrations, 998,490 (51%) IV injections and 60,972 (3%) infusions. Infusions were administered for 4,476,538 hours. Twelve-thousand two-hundred seventy-three patients (71%) were administered five or more different drugs on 80,943 of patient days (75%). The 10 most commonly administered drugs comprised of 834,441 administrations (43%). Conclusions: Drug administration in the ICU is complex, involves many medications, and the potential for drug interaction and reaction is compounded by the volume and diversity of therapies routinely provided in ICU. Further evaluation of polytherapy could be used to improve outcomes and enhance the safety of pharmacotherapy in critically ill children.