Prevalence of acute kidney injury in pediatric patients receiving vancomycin before and after transitioning from trough to area under the curve monitoring. Gustavo R. Alvira-Arill, Kelley R. Lee. Jeremy S. Stultz. Department of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN. Department of Pharmacy, Le Bonheur Children's Hospital, Memphis, TN. galviraa@uthsc.edu; 407-319-9927
Introduction: Originally, guidelines for the management of complicated methicillin-resistant S. aureus (MRSA) infections with vancomycin recommended maintaining serum trough concentrations of 15–20 mg/L as a surrogate to area under the curve (AUC) as the primary pharmacodynamic predictor of vancomycin activity. Recent evidence in adult and pediatric patients demonstrates poor correlation of trough concentrations to AUC, so these monitoring guidelines were revised to recommend an individualized target for AUC/MIC of 400–600 mg*h/L. Despite the lack of evidence for efficacy in pediatric patients, several pediatric institutions have transitioned to AUC-based monitoring or avoiding serum trough concentrations > 15 mg/L to minimize acute kidney injury (AKI) risk. Thus, the purpose of this study was to compare the prevalence of AKI in pediatric patients that received vancomycin before and after transitioning from trough to AUC-based monitoring.
Methods: A retrospective study using the Pediatric Health Information System (PHIS) database of patients that received vancomycin courses for 4–42 days within the first 3 days of admission from January 2015 to December 2021 was performed. Medication administration and diagnosis coding data was combined with survey responses provided by pediatric infectious diseases pharmacists identifying monitoring strategies used at their respective institutions contributing to PHIS. Courses were categorized to trough or AUC-based monitoring depending on the date of exposure, documented ICD-9/10 diagnosis codes indicating serious infection (such as bacteremia, infective endocarditis, meningitis, pneumonia, or sepsis) and/or MRSA involvement, and survey responses. As diagnosis codes apply to each admission and multiple courses of vancomycin may have been administered, only first courses per admission were reviewed for analysis. AKIs were similarly identified with corresponding ICD diagnosis codes and procedural codes indicating dialysis receipt. Generalized logistic mixed effects modeling was performed to assess AKI prevalence between the two monitoring strategies while adjusting for other factors including critical illness and concomitant nephrotoxin exposure.
Results: 20,316 vancomycin courses from 22 institutions contributing to PHIS were included. Based on received survey responses, exposure dates, and corresponding diagnostic coding; 564 and 19,752 courses were categorized to AUC and trough-based monitoring, respectively. 49 (8.7%) AUC and 2267 (11.5%) trough monitored courses had a documented AKI during their respective encounters (adjusted OR 1.14; 95% CI, 0.80–1.62, p = 0.475). Covariates/factors independently associated with AKI included longer durations of therapy, receipt of concomitant nephrotoxins, and ICU admission.
Conclusions: Reported use of AUC or trough-based monitoring for vancomycin therapy among pediatric institutions contributing to PHIS did not demonstrate a difference in prevalence of AKI. Study limitations include lack of laboratory data to confirm AKI and limiting assessment to first courses within admissions. These findings suggest that the type of monitoring strategy used may not provide a significant safety benefit with regards to prevention of AKI.
Use of ketamine as an adjunct infusion in the neonatal intensive care unit. Steven Astrachan, PharmD; Nicole Palazzolo, PharmD, BCPPS, UVA Children's, Charlottesville, VA. Ghu6zk@uvahealth.org
Introduction: Management of critically ill late preterm and term infants requiring prolonged invasive mechanical ventilation can be challenging. With limited data to guide specific sedative and analgesic selections, a multimodal approach is often utilized to minimize the risk of adverse effects and maximize the benefits from each respective drug class. Opioids and benzodiazepines have been used most traditionally but with well-studied consequences, an increasing incorporation of alpha-2 receptor agonists such as dexmedetomidine into sedation protocols has resulted. However, for the complex infant with refractory needs, the remaining options are limited. Ketamine, an NMDA antagonist and dissociative anesthetic, is more typically used in a bolus fashion for procedural pain and sedation management, but presents an interesting alternative. At the UVA Children's Hospital Neonatal Intensive Care Unit, a continuous infusion of ketamine has increasingly been incorporated as the fourth-line option for the patient who remains refractory to the aforementioned traditional therapies.
Methods: At UVA Children's Hospital, medical records were reviewed for NICU patients who were initiated on continuous ketamine infusions during their admission occurring from 10/6/2018 through 10/6/2022. Data regarding GA, birth weight, diagnosis, indication, concurrent infusions, age at initiation, prescribing team, duration of infusion, weans, and outcomes were recorded for analysis.
Results: Over a four year time period, 21 individual neonates were treated with 25 ketamine infusions with 19 recommended by the palliative care team. The average GA was 33 and 2/7 weeks and the average birthweight was 2.39 kg. The average PMA at initiation was 49 and 1/7 weeks and mean weight at initiation was 5.05 kg. The most common indications for use of ketamine were transition to end of life care (11/25), 3rd–4th agent for sedation or agitation management (10/25), and as an aid for sedative or paralytic weans (3/25). One patient was initiated on ketamine by the cardiology team to raise systemic vascular resistance. The most common starting dose utilized was 5 mcg/kg/min (23/25) with the average peak dose being 18.6 mcg/kg/min and the maximum dose of 60 mcg/kg/min (n=1). Five patients had reported increased secretions most commonly treated with sublingual atropine. Of the nine patients who were weaned off of ketamine infusions, one patient had reported difficulty with the wean process. 6/21 neonates survived to discharge.
Conclusions: In this retrospective chart review, neonates were initiated on ketamine primarily for end of life care and as adjunct for sedation control in refractory patients. Higher doses did not typically have adverse effects causing withdrawal or requiring treatment, and when weans did occur, they were generally well tolerated. While more data is required to conclude more formal guidance on indications and dosing for future use of ketamine, this review serves as anecdotal evidence from a large academic medical center.
INCIDENCE OF ACUTE KIDNEY INJURY IN PEDIATRIC INTENSIVE CARE UNIT PATIENTS EXPOSED TO ANTIBIOTICS. Delaney Bryant, Cheryl Sargel. Nationwide Children's Hospital, Columbus, OH. Delaney.Bryant@nationwidechildrens.org
Introduction: Patients admitted to the pediatric intensive care unit (PICU) often require intravenous (IV) antibiotics such as vancomycin, piperacillin/tazobactam (PTZ) or cefepime (CPE). Recent evidence suggests higher rates of acute kidney injury (AKI) associated with the combination of vancomycin and PTZ compared to CPE, when using serum creatinine as a marker of AKI. PTZ is known to inhibit tubular secretion of creatinine, causing elevation in serum creatinine concentrations, and may represent a pseudonephrotoxicity. This project aimed to evaluate the incidence of AKI among PICU patients who received PTZ, CPE alone or in combination with vancomycin using renal biomarkers.
Methods: This is a single-center retrospective electronic medical record review of patients > 28 days to 18 years old admitted to the PICU, between April 1 2022 and September 30 2022, who received IV PTZ, CPE with or without IV vancomycin for at least 48 hours. Changes in serum creatinine, NGAL, and cystatin C were compared from baseline to 24 hours after completion of therapy, and need for dialysis 30 days after completion of antibiotic therapy was recorded. Patients were excluded if they received monotherapy with vancomycin before transitioning to combination therapy, received both PTZ and CPE within seven days or each other, had chronic kidney disease or need for dialysis prior to admission, required extracorporeal membrane oxygenation, or were missing baseline serum creatinine values. Data analysis was performed using descriptive statistics.
Results: 73 patient were reviewed and 36 met inclusion criteria. There were 13 patients treated with CPE (36%), 14 with PTZ (39%), 5 with CPE-vancomycin (14%), and 4 with PTZ-vancomycin (11%). Overall, 15% of patients who received CPE, 7% who received PTZ, 40% who received CPE-vancomycin, and 0% who received PTZ-vancomycin had at least a 50% increase in serum creatinine after starting antibiotics. Nine patients had a urine NGAL recorded, and 7 were indicative of a high AKI risk. Seven patients had a cystatin C recorded, 5 of which were elevated for age. Dialysis was initiated in 7% of patients who received PTZ, 15% who received CPE, and 20% who received CPE-vancomycin. While patients treated with CPE had larger increases in serum creatinine after starting antibiotics, mean baseline and follow up serum creatinine values were highest in the PTZ monotherapy treatment group.
Conclusions: The combination of vancomycin and PTZ compared to CPE did not appear to increase the risk of AKI in the 36 PICU patients included in this study, when using serum creatinine as a marker of AKI. No patients who received vancomycin and PTZ had a significant enough increase in serum creatinine from baseline to follow-up to be classified as an AKI.
HIT ME WITH YOUR BEST SHOT: USE OF BEST PRACTICE ALERTS IN THE ELECTRONIC MEDICAL RECORD TO REDUCE TIME TO IMMUNIZATION ADMINISTRATION IN THE NICU CARE UNIT. Jordan Burdine, Shayda Ebrahimi, Maria Franco Fuenmayor. UTMB Health Department of Pediatrics, Division of Neonatology, Galveston, TX. jlburdin@utmb.edu
Introduction: Studies evaluating children discharged from the neonatal intensive care unit (NICU) have shown some infants experience delays in receipt of routine childhood immunization, whether it be due their low birthweight and prematurity or critical condition. This places already at-risk patients at greater risk of contracting preventable diseases. Improving the timeliness and completion of vaccination is the key to reducing the number patients who are either unvaccinated or behind due to a prolonged catch-up schedule. A quality improvement initiative was designed to assess the adherence of a new best practice alert (BPA) notifying prescribers of patients needing immunizations. This BPA was implemented in the electronic medical record (EMR) in a Level IV NICU with a goal to decrease the days to immunization administration by 20% after one year.
Methods: An electronic BPA was developed by a multidisciplinary team to alert prescribers upon chart entry of the need for immunizations on designated dates based on the date of birth and immunization schedule for every neonate admitted to the NICU. An immunization panel was built to accompany the alert and direct the prescriber to the necessary immunization, which were grouped by age using the Centers for Disease Control and Prevention (CDC) recommended vaccine schedule. The BPA and panel were approved by the neonatology division at UTMB Health in June 2021 and placed in production within the EMR in July 2021. A six-month pre-implementation retrospective chart review for time of immunization administration was performed to obtain baseline time to immunization. A post-implementation chart review to assess time to administration was performed for July 2021 thru July 2022. BPA firing data was also evaluated for this period. Descriptive statistics and student's t-test were performed to evaluate data.
Results: Patients were evaluated between January 2021 and June 2021 (n=22) to establish a baseline time to immunization. All patients in which the BPA fired between July 2021 and July 2022 (n=59) were evaluated in the post-intervention group. The mean length of time between patients qualifying for 2-month immunizations to the time of administration was reduced from 18.7 + 28.6 days to 0.32 + 1.40 days (p = 0.0001). Furthermore, the mean length of time between patients qualifying for 4- and 6-month immunizations to the time of administration was reduced from 25.6 + 56 days to 0 days (p = 0.0007), and 14.2 + 16.9 days to 0 days (p = 0.0001), respectively.
Conclusions: Use of BPAs linked with order panels to notify prescribers of patients due to receive immunizations aided in the timely prescribing of vaccines and result in a 98.3% reduction in time to administration. There was a statistically significant reduction in the time to immunization for 2-, 4-, and 6-month immunizations. Timely administration of immunizations while in the NICU aids in protection against preventable diseases in these high-risk patients, as well as improves transitions of care by ensuring patients are up to date on vaccines prior to discharge.
Antithrombin III replacement in the neonatal intensive care unit (NICU) in the absence of extracorporeal membrane oxygenation (ECMO). Eva Byerley, Teresa Puthoff, Jacqueline Magers. Nationwide Children's Hospital, Columbus, OH. byerleyeva@gmail.com
Introduction: Some infants may require higher than usual doses of unfractionated heparin or low molecular weight heparin (LMWH) to achieve therapeutic anticoagulation. These infants are often deficient in antithrombin III (ATIII) and benefit from replacement. There are varying practices at Nationwide Children's Hospital (NCH) and across the country for calculating a replacement ATIII dose, including desired ATIII level and whether to use a correction factor (CF). The objective of this study is to determine the efficacy of chosen ATIII dose calculation on ability to achieve therapeutic anti-Xa for infants in the absence of extracorporeal membrane oxygenation (ECMO) and assess frequency of safety events.
Methods: This retrospective chart review analyzed ATIII administrations in infants at the NCH main campus neonatal intensive care unit (NICU) between 7/1/2012 and 6/30/2022. Patients were included if they were less than one year of age, received at least one dose of ATIII, and were on concurrent unfractionated heparin or LMWH monitored by anti-Xa levels. Infants were excluded if they were on ECMO at the time of ATIII replacement or had suspected or confirmed ATIII mutation or hereditary deficiency.
Results: Eighteen patients and 30 ATIII doses were included. Eighty-three percent (25/30) of administrations were calculated with a desired ATIII level greater than or equal to 80%. Fifty-seven percent (17/30) of administrations were calculated using a CF. Anti-Xa levels were sub-therapeutic with 18 administrations, therapeutic with 11 administrations, and supra-therapeutic with 1 administration. Therapeutic anti-Xa levels occurred in 44% (11/25) of administrations calculated to a desired ATIII level greater than or equal to 80%. Of these 11 ATIII administrations, 8 (73%) were calculated using a CF. Minor bleeding events, defined as a drop in hemoglobin greater than or equal to 3 g/dL in one week, coincided with 8 ATIII administrations, although 7 of these bleeding events occurred at sub-therapeutic anti-Xa levels. One of four infants (25%) who experienced a major bleeding event achieved a therapeutic anti-Xa level. This ATIII administration was calculated with a desired ATIII level greater than or equal to 80% and used a CF. Major bleeding events were intracranial hemorrhage confirmed by head ultrasound and bleeding events leading to discontinuation of anticoagulation.
Conclusions: Therapeutic anti-Xa levels occurred most frequently and with minimal safety events in infants who received ATIII doses with a desired ATIII goal greater than or equal to 80% and using a CF. ATIII replacement may not always achieve therapeutic anticoagulation. Drug cost, patient selection and risk-benefit of ATIII replacement should be considered.
EFFICACY AND SAFETY OF INTRAVENOUS ACETAMINOPHEN FOR THE TREATMENT OF THE PERSISTENT PATENT DUCTUS ARTERIOSUS IN NEONATES WITH CONCOMITANT CRITICAL CONGENITAL HEART DISEASE. Maria Chacon MD, Bronwyn Crandall and Bao Nguyen Puente MD. Children's National Hospital, Washington D.C. bcrandall@childrensnational.org
Introduction: Persistent patent ductus arteriosus (PDA), in patients with concomitant critical congenital heart disease (CHD) such as defects with left to right shunt, is associated with worsening heart failure, and may accelerate the timing of surgery. Acetaminophen can be efficacious in closing PDA in very premature neonates. This case series assesses the efficacy and safety of acetaminophen treatment for PDA closure in patients with concomitant critical CHD.
Methods: This is a retrospective, single center study. Neonates with persistent PDA and concomitant critical CHD who underwent acetaminophen therapy for ductal closure were selected. Acetaminophen efficacy was assessed based on ductal constriction on echocardiogram. Markers of hepatic, renal, and respiratory function were evaluated pre- and post-therapy.
Results: 7 neonates met criteria for inclusion. 2 were term, 3 late preterm and 2 very preterm. Mean age at time of treatment was 7.5 days. All except for one, the PDAs were moderate to large at the initiation of treatment. Acetaminophen was given intravenously at 15mg/kg every 6 hours. The mean duration of treatment was 4 days. At time of treatment completion, the PDA was closed in 2 patients, trivial in 2 and small in 3 patients. 5 out of 7 patients had complete PDA closure one week after treatment completion, with resultant decrease in diuretics and/or respiratory support. No adverse effects were identified.
Conclusions: Acetaminophen was efficacious and safe in closing persistent PDA in this small sample of patients with critical concomitant CHD. Further studies on the use of acetaminophen for PDA closure in this patient population is warranted.
SUCCESSFUL IMPLMENTATION OF STANDARDIZE 4 SAFETY (S4S) PEDIATRIC CONTINUOUS INFUSION STANDARDS AT A STAND-ALONE PEDIATRIC HEALTH CARE SYSTEM. Jason M. Evans, Dani Ball, Rhonda Carlton, Jorden Seamands, Stephanie Tupper, Mary Kay Weiss. Cook Children's Health Care System, Fort Worth, TX. jason.evans@cookchildrens.org
Introduction: An important component of ASHP's Standardize 4 Safety (S4S) initiative is the standardization of pediatric-specific continuous medication infusions, as supported by FDA, ISMP, and PPA. Our institution wished to align our infusion concentrations with S4S where possible. However, changing infusion concentrations is a difficult endeavor, growing exponentially harder with more complex electronic health records (EHR), interconnected hardware/software (e.g. infusion pumps), and multi-site health care systems. We chose a multiphase implementation schedule over 3 years with separate Go-Live dates for 3 batches spaced approximately 12 months apart.
Methods: Standard and fluid restricted (FR) infusion concentrations were compared to S4S standards. A multi-disciplinary task force was created to analyze the findings with key stakeholders including pharmacy, pharmacy informatics, information services (IS), safety, nursing, transport, biomed, ICU providers, anesthesiology, and hospital administration. Several focus-groups were held with these stake holders to share vision, gain insight and obtain recommendations on specific concentrations. A finalized list of standard and FR concentrations was agreed upon by all, with any deviations from S4S clearly documented with operational or clinical rationale. Implementation was driven via an IS Project, chartered and led by an IS Project Manager. A three phase approach was utilized with ~12 months between each phase. Twice-monthly project meetings were held, with weekly meetings approaching each go-live date. Very detailed timelines and action items were created and followed closely via project-tracking software. Each Go-Live date consisted of an ~1 hour EHR migration and a multi-faceted manual reboot/update of over 700 smart infusion pumps of multiple brands at different sites. Go-Live ground-level teams of pharmacy, nursing, and anesthesia were formed a few days prior to identify and triage any affected patients or other problematic clinical situations. Pharmacy and nursing increased staff where able. Desktop Alerts and Daily Safety Call announcements were utilized at Go-Lives to drive communication across the system. An open-call conversation was maintained during go-live to report updates and issues to the taskforce. Post go-live debriefs were held to improve the next phase.
Results: 40 medications available at our institution for continuous infusion are S4S applicable. Pre-implementation, 30/40 medications had a non-recommended concentration in use. Specifically, 23 medications had a non-recommended standard concentration. Post implementation, only 13/40 medications had a non-recommended concentration, with only 5 medications having a non-recommended standard concentration.
Conclusions: Successful adoption of the majority of S4S standards was achieved over a 3 year period with a multidisciplinary approach. An IS Project Manager, with specific and detailed goals and timelines kept the project on pace. Early and continuous communication with nursing leadership regarding Go-Live events allowed for no reported adverse events or patient harm. Our continuous infusions were simplified and streamlined, thus increasing patient safety, optimizing workflow and decreasing waste.
NATIONAL SURVEY ON VERY LOW BIRTH WEIGHT STARTER PARENTERAL NUTRITION. Ju Eun Jun, Christine A. Robinson, Rachel S. Meyers, Anita Siu, Pooja Shah, Molly Siver. Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ; Morristown Medical Center, Morristown, NJ; Cooperman Barnabas Medical Center, Livingston, NJ; Hackensack Meridian Jersey Shore Medical Center, Neptune Township, NJ; Hackensack University Medical Center, Hackensack, NJ. jj561@pharmacy.rutgers.edu
Introduction: Parenteral nutrition (PN) is initiated as early as possible in very low birth weight (VLBW) neonates to prevent protein catabolism. Each institution takes a different approach to assure that appropriate nutrition is administered as soon as possible after birth. While there are general recommendations on the initial amounts of dextrose, amino acids, and electrolytes in VLBW PNs, clinical practice varies. The objective of this study is to describe the initial nutritional management for VLBW infants in various neonatal intensive care units.
Methods: This is an Institutional Review Board approved survey study. A Qualtrics™ link for a 16-question electronic survey was distributed to Pediatric Pharmacy Association (PPA) members via the Neonatology, Critical Care and Garden State PPA list-serv from November 11, 2022 to January 31, 2023. The survey had 6 sections: institution characteristics, method of supplying starter PN, PN contents and their concentrations, practice of fat emulsions, various content maximums in peripheral PN, and cysteine-to-amino acid ratio. Duplicate responses from the same institution were excluded and incomplete responses and outliers were analyzed for interpretation or removal. The primary outcome was to identify the most common macronutrients and micronutrients in starter PN and their concentrations. Secondary outcomes were starting concentrations of electrolytes of the VLBW starter PN, starting dose, start time and type of fat emulsion, maximum osmolarity, and dextrose and calcium concentration permitted in peripheral PN.
Results: Of 81 survey responses, 5 incomplete and 6 duplicate responses were excluded. Of the 70 responses included, 64 institutions (91%) stocked at least one standardized starter PN and 6 institutions (9%) custom-compounded starter PN. Six institutions with standardized starter PNs also custom-compounded. Of the 102 standardized starter PNs, the most common contents were amino acids (100%), dextrose (100%), calcium gluconate (73%) and heparin (74%). The reported concentrations in mean (range), were 3.4% (1.8–6%), 8.9% (5–12.5%), 14.6 mEq/L (2.4–38 mEq/L), and 0.5 units/mL (0.2–1 units/mL), respectively. Of the 12 custom-made starter PNs, the most common contents were amino acids (100%), dextrose (100%), calcium gluconate (75%), and heparin (92%). Mean concentrations were 3.5% (2–6%), 8.9% (5–12.5%), 13.3 mEq/L (2.4–38 mEq/L), and 0.46 units/mL (0.25–0.5 units/mL), respectively. Sodium phosphate (8%), potassium acetate (8%), potassium phosphate (17%), and magnesium sulfate (33%) were also reported in custom PNs. The mean initial lipid dose was 1.2 g/kg/day (0.5–3 g/kg/day) and the mean maximum peripheral osmolarity was 1018 mOsm/L (900–1250 mOsm/L).
Conclusions: This study indicates that while there are common contents reported in VLBW starter PNs, there is a wide variation in their concentrations. There is also a variation in the various electrolytes in custom-made starter PNs. Future research on nutritional needs of VLBW may provide an opportunity to develop standardized starter TPNs.
MEDICATION DOSE ADJUSTMENTS IN PEDIATRIC PATIENTS WITH ACUTE KIDNEY INJURY. Amy L. Kiskaddon, Marla Tanski. Johns Hopkins All Children's Hospital, St. Petersburg, FL. akiskad1@jhmi.edu
Introduction: Pediatric patients with renal impairment have altered pharmacokinetics, resulting in variable responses to pharmacotherapy. Numerous drugs and their metabolites, including many with narrow therapeutic indices, have extensive renal elimination. Appropriate dose adjustments are vital to avoid toxicity. An increased risk of adverse drug events (ADE) is associated with drug dosing errors in pediatric patients with renal impairment, which can result in increased costs, lengths of stay, and hospital readmissions. It is difficult to ensure compliance with appropriate dose adjustment of renally eliminated drugs.
Methods: A single center retrospective study from October 2022 to December 2022 (inclusive). Patients ≥42 weeks gestational age (GA) and <18 years of age, acute kidney injury (AKI), and receiving nephrotoxic medication(s) were eligible for inclusion. AKI was defined as an increase in serum creatinine (SCr) by ≥50% above baseline or ≥0.3 mg/dL in the last 48 hours. Patients in the emergency center (EC) or on observation status were excluded. The primary outcome of this study was to quantify the number of medications requiring dose adjustment in pediatric patients with AKI. Secondary outcomes included identifying medications that were commonly requiring dose adjustment and evaluating whether proper dose adjustments were made, when appropriate.
Results: A total of 21 patients, accounting for 43 AKI encounters, met eligibility criteria and were included in the study. Fifteen (71.4%) of patents were female. The median (range) age and weight were: 10 (0–17) years and 26 (2.65–74.3) kg, respectively. A total of 13 (61.9%), 3 (14.3%), and 5 (23.8%) patients were admitted in the ICUs, hematology/oncology, medical/surgical pediatric units, respectively. The median (range) baseline SCr was 0.25 (0.2–3.2) mg/dL and SCr associated with AKI was 0.64 (0.4–8.02) mg/dL. The median (range) medications requiring dose adjustments were 3 (2–7) medications per AKI encounter. The most common medications (n, %) were antimicrobials (90, 62%) and gastrointestinal (22, 15.2%) medications. Of note, a total of 28.3% of medications requiring dose adjustment for AKI were not adjusted.
Conclusions: Pediatric patients with renal impairment often require dose adjustments to their current medication regimens. Future studies evaluating pharmacist driven involvement in such processes would be beneficial.
STANDARDIZED NEONATAL ADDITIVE PROJECT (SNAP): A CLINICAL PROCESS IMPROVEMENT PROJECT TO ACCELERATE DELIVERY OF INTRAVENOUS FLUIDS FOR NEONATES IN A PEDIATRIC UNIT. Cassmain Low1, Simran Mahtani2, Joanne Tan2, Serena Chang2, Kelvin Xu1, 1. Pharmacy Department, KK Women's and Children's Hospital, Singapore. 2. Department of Paediatric Medicine, KK Women's and Children's Hospital, Singapore. kelvin.xu.sr@kkh.com.sg
Introduction: Term neonates required a unique combination of dextrose, sodium and potassium in intravenous fluids due to their unique developmental physiology. In general, 2 mMol/kg of sodium with or without 1 mMol/kg of potassium are added to base solution of dextrose 10% which can cause a great variability based on a patient's weight and daily fluid requirements. As high dextrose and, low sodium and potassium combination infusion fluids were not available as commercial preparations, providers were required to prescribe customised infusion fluids meeting those requirements, requiring pharmacy to compound and deliver to the patient's bedside. Each part of the process had potential issues that led to either inappropriate infusion fluids being administered or a delay in administration. There was also a need to reduce wastage in amounts of infusions compounded and time needed to correct orders or do ad hoc compounding. A clinical process improvement project was initiated to reduce inappropriate prescribing of customised infusion fluids as well as reduce preparation and administration time for intravenous fluids for neonates admitted in the pediatric setting.
Methods: A multidisciplinary team was formed and a root cause analysis was conducted. Root causes identified included inappropriate order selection, inappropriate type and amounts of electrolytes added, time taken for orders to be calculated and checked, time for compounding, time for order correction as well as changes in orders where the previously compounded infusion fluids cannot be used and therefore wasted.
Different amounts of electrolyte additives were simulated for term neonates of different weights and fluid volume requirements and two standardised preparations were identified – one with potassium and one without. The standardised preparations of dextrose 10% contain 20.4 mMol/L of sodium chloride with or without 10 mMol/L of potassium chloride. When administered in doses of 100 to 170 mL/kg/DAY, the infusion fluids will deliver a glucose infusion rate of 6.9 to 11.8 mg/kg/min, sodium of 2 to 3.5 mMol/kg/DAY and potassium (if added) 1 to 1.7 mMol/kg/DAY. We adopted the following inclusion criteria for safety reasons during the pilot phase - Gestational age of more than 37 weeks, postnatal age of more than 48 hours of life to 1 month of age, starting fluid requirements between 100 to 170ml/kg/DAY with normal sodium requirement of 2 to 4 Mmol/kg/DAY and normal Potassium requirement of 1 to 2 mMol/kg/DAY. We excluded patients who were younger than 48 hours of life, required total fluids of less than 100 mL/kg/DAY, requiring electrolytes other than sodium and potassium and patient with abnormal baseline sodium and potassium levels as well as those with renal impairment or abnormal serum creatinine levels. Computerised physician order entry ordersets were created for the 2 standardised infusion fluids along with workflows for compounding and supply of the mentioned fluids. A pilot was conducted in a pediatric ward which admits patients from 0 to 3 years of age. Plan-Do-Study-Act (PDSA) cycles were conducted with time taken to compounding and time taken from ordering to administration were collected and analysed alongside manpower cost savings. Adverse events and, sodium and potassium levels done as part of routine care were collected for safety purposes.
Results: Average time taken for compounding customised infusion was 49 minutes compared with 2.5 minutes for customised drips made in batches. Average time taken from ordering to administration dropped from an initial mean of 221.2 minutes to 124.9 minutes and to eventually 9.5 minutes after 2 PDSA cycles. Estimated annal savings based on pharmacy manpower costs for batch making standardised neonatal infusion fluids compared to compounding customised infusion fluids was about 370 manhours a year. No adverse events were reported. There were no significant differences in levels of sodium and potassium noted between patients on the traditional customised intravenous fluids compared to the new standardised neonatal premix.
Conclusions: The use of standardised neonatal intravenous fluids reduced the time between ordering to administration greatly and this was facilitated by the reduced complexity of ordering customised intravenous infusion fluids and time required for compounding. Inappropriate orders for neonatal intravenous infusion fluids were also greatly reduced. Pharmacy manpower costs were also greatly reduced due to batch compounding instead of compounding of individualised intravenous fluids.
INNOVATIVE DEVELOPMENT OF SCHEDULING SYSTEM FOR IMPROVED EMPLOYEE SATISFACTION. Sarah Scar-pace Lucas, PharmD, BCPS, BCPPS, Leigh Ann Witherspoon, PharmD, BCPPS, Allyson Thrall, PharmD, BCPPS, Ethel Odiakosa, PharmD, Rebecca Deoras, PharmD, BCPPS, Joshua Robinson, PharmD, APh, BCCCP. University of California San Francisco Benioff Children's Hospital, San Francisco, CA. sarah.lucas@ucsf.edu
Introduction: We developed a proposal to improve employee satisfaction in scheduling through the development of a POD-based team approach. Our tactics included the development of 5 scheduling PODs for employee self-scheduling of weekday shifts, a self-signup process for weekend shifts, and a site-specific scheduling workgroup for continuous process improvement. Staff were divided into five different PODs based on service line (Critical Care, Ambulatory Care/Transitions of Care, Heme-Onc/BMT, Acute Care, Operations) and each POD had a lead scheduler that was responsible for scheduling their team as well as a certain number of operational shifts determined by POD size.
Methods: It was proposed that the new self-scheduled PODs would be able to make specific % improvements in the following areas as primary endpoints: 50% decrease in shift trades, 50% improved ability to schedule team members in the clinical evening shift, 20% improved consistency through a reduction in double-backing and an improvement in precepting consistency through a goal for 70% in learner rotation time with < 3 preceptors. Secondary endpoints of staff satisfaction were measured through quarterly staff engagement surveys based on Gallup methodology which looked at improvement in three areas: opportunity to do best, opportunities to learn and grow, and opinions seem to count.
Results: The new scheduling approach was started in August 2022 and by six months the new scheduling approach was able to meet metric goals for three of four of the primary endpoints (double backing, trade reduction, and consistency in precepting) and trending toward meeting goals in the ability to schedule clinical evening shifts however limited likely due to multiple vacancies. For secondary goals, the new scheduling workgroup has been able to meet two of three staff engagement goals of +0.2 for Gallup survey significance (opinions count, opportunity to do best) and were trending toward meeting the third goal of learning and growing.
Conclusions: Overall implementing this innovative approach to scheduling was able to successfully improve multiple endpoints that led to improved employee satisfaction, consistency as well as learner consistency in the scheduling process.
EVALUATION OF VANCOMYCIN AREA UNDER THE CURVE THERAPEUTIC DRUG MONITORING IN PEDIATRIC PATIENTS. Meighan Marlo, PharmD, Zach Thompson, PharmD, MPH, BCPPS, Pavel Prusakov, PharmD, BCPPS, BCIDP, Jacqueline Magers, PharmD, BCPS. Nationwide Children's Hospital, Columbus, OH. Meighan.Marlo@nationwidechildrens.org.
Introduction: In 2020, a revised consensus guideline, endorsed by Pediatric Infectious Disease Society, recommended monitoring vancomycin's area under the curve to minimum inhibitory concentration ratio (AUC/MIC) over surrogate parameter (i.e. trough). Studies in neonatal and pediatric populations are limited to retrospective chart reviews with and without pharmacokinetic modeling. There continues to be a paucity of pediatric efficacy and toxicity data associated with vancomycin therapy when targeting AUC/MIC of 400–600. The purpose of this study was to evaluate the proportion of patients attaining AUC/MIC of 400–600 with institutional empiric vancomycin dosing regimens.
Methods: This study was a one year retrospective chart review at a free standing children's hospital and affiliated neonatal intensive care units (NICU) in Columbus, OH. Patients were included if they had received at least two doses of empiric institutionally dosed vancomycin and had vancomycin AUC/MIC therapeutic drug monitoring obtained during the course of therapy. Patients were excluded if there was a trough level obtained resulting in vancomycin therapy adjustment prior to AUC/MIC assessment or if there was incomplete data surrounding vancomycin dosing, levels, time of administration, weight, urine output, or serum creatinine for time points evaluated. Pertinent demographic and clinical data were obtained from electronic health records.
Results: Forty-two patients were included in the final evaluation. There were 6 infants in the NICU group (median gestational age 26 weeks (IQR, 24–30), median birth weight 688 grams (IQR, 570–794). Vancomycin was initiated at a median postnatal age of 88 days (IQR, 51–124), starting dose was 15 mg/kg for all patients with frequencies ranging from every 6–12 hours. Four of the six neonates were started at every 8 hour dosing. The non-NICU group included 36 children with a median age of 1 year (IQR, 0.5–2.5). Starting dose of vancomycin was 20 mg/kg (IQR, 15–20) with most common frequency of every 6 hours in 28 (78%) of children. Twenty-three (55%) of 42 children evaluated did not achieve AUC/MIC goals, with 15 children needing a dose or frequency increase. There were no incidences of vancomycin-induced acute kidney injury (AKI). Out of all patients, 10 were on vancomycin to treat bacteremia. In 7 of those children, microbiological clearance was attained within 24 hours after vancomycin initiation and within 48 hours for 2 others. The last patient had an initial AUC/MIC of 266 with microbiological clearance taking 5 days to achieve. There were no recurrent infections.
Conclusions: More than half of total patients did not achieve AUC/MIC goals with institutional empiric dosing. The most common reason for missing the goal target was inadequate dosing. Since there were no incidences of AKI in patients with high AUC/MICs, higher empiric dosing should be evaluated in future studies.
PHARMACIST PRESCRIBING OF NIRMATRELVIR AND RITONAVIR AT A FREE-STANDING CHILDREN'S HOSPITAL. Kimberly J. Novak, PharmD, BCPS, BCPPS, FPPA; R. Zach Thompson, PharmD, MPH, BCPPS; Jill Blind, PharmD, CCRP; Meighan Marlo, PharmD; Whitney Jones, PharmD Candidate; Joshua Watson, MD. Nationwide Children's Hospital; Columbus, OH. Kimberly.Novak@NationwideChildrens.org
Introduction: Nirmatrelvir and ritonavir (Paxlovid) was approved on December 22, 2021 for emergency use authorization (EUA) to prevent the progression of mild to moderate COVID-19 in patients 12 years and older, weighing 40 kilograms or more, with known risk factors for disease progression. Therapy should be initiated as early as possible and within 5 days of symptom onset. Tablets may not be split or crushed which may limit feasibility in some pediatric patients or adult patients with swallow impairment. Dose adjustment is indicated with an estimated GFR (eGFR) of 30–59 mL/min, and use is contraindicated with an eGFR of < 30 mL/min or in the setting of severe liver disease (Child-Pugh class C). Additionally, many drug interactions exist with nirmatrelvir and ritonavir, most notably due to strong CYP3A4 inhibition by ritonavir, which necessitate dose reduction or temporary interruption of other therapies. When drug interactions cannot be reasonably managed, nirmatrelvir and ritonavir use may be contraindicated. Due to the complexity of prescribing criteria and drug interaction assessment, we sought to centralize nirmatrelvir and ritonavir prescribing as a service to our health-system's patients as well as community prescribers for pediatric patients receiving care outside our health-system.
Methods: In January 2022, stakeholders from Clinical Pharmacy, Investigational Drugs Services (IDS), and Infectious Diseases (ID) collaborated to develop a nirmatrelvir and ritonavir prescribing and IDS dispensing workflow utilizing an institutional Collaborative Practice Agreement (CPA). Clinical pharmacists developed an internal drug interaction management guide, standardized assessment tool, patient/caregiver encounter script, and standardized electronic medical record (EMR) documentation template for evaluating and prescribing nirmatrelvir and ritonavir. The nirmatrelvir and ritonavir prescribing workflow was implemented in February 2022. Prescribers within our health system, as well as community prescribers, were educated to call the physician/provider consult-transfer center and ask to speak with an ID specialist to make a referral. An ID physician would evaluate the patient's reported symptoms and basic demographics to determine initial eligibility for nirmatrelvir and ritonavir or an intravenous therapy alternative (monoclonal antibody or remdesivir). Patients approved for nirmatrelvir and ritonavir would be referred to the COVID-19 Oral Therapies pool in the EMR. A clinical pharmacist would contact the patient/caregiver by telephone to conduct a full medication reconciliation, perform drug interaction analysis, review for renal and liver dysfunction, and determine final eligibility based on patient-specific factors. The pharmacist would prescribe nirmatrelvir and ritonavir and adjust any medications for drug interactions using the CPA, or if a contraindication was noted, the pharmacist would refer the patient for an intravenous therapy alternative. Education regarding nirmatrelvir and ritonavir side effects, drug interactions and associated medication dose changes, and EUA status was provided by telephone. Initially, nirmatrelvir and ritonavir was only prescribed through IDS and delivery coordinated with a courier service or patient pick-up at our outpatient pharmacy. When nirmatrelvir and ritonavir supply became more widespread, dispensing was transitioned to a community pharmacy of the patient/caregiver's choice. When anecdotally noted that nirmatrelvir and ritonavir could be prescribed bypassing the consult and prescribe workflow, EMR functionality was implemented to require pharmacist verification before electronic transmission of the prescription. Pharmacists would provide the same review as provided through the referral process. An IRB-approved retrospective chart review of pediatric patients prescribed nirmatrelvir and ritonavir from March 1, 2022, through July 31, 2022 was conducted to evaluate outcomes in pediatric patients. A quality improvement audit was performed to evaluate pharmacist referrals for intravenous therapy alternatives as well as nirmatrelvir and ritonavir prescribing for adult patients within the same time period.
Results: Eighty-five patients were prescribed nirmatrelvir and ritonavir within our institution during the specified timeframe, with 37 (44 %) being pediatric patients 12–17 years of age. Over 60% of pediatric patients were male, and the median age was 15 years. There were no hospitalizations for progression or death from COVID-19 among the patients evaluated. The most common risk factors for COVID-19 progression were receipt immunosuppressive therapy (n=17, 40%) and obesity (n=14, 33%). On average, patients sought therapy 2 days after symptoms first appeared. There was documentation of pharmacist review for 80% of prescriptions, and dose modification interventions were made for nine patients (20 %) who were taking interacting medications. One pediatric patient initially prescribed nirmatrelvir and ritonavir was unable to swallow tablets and was referred for intravenous therapy. Nirmatrelvir and ritonavir was prescribed to 47 adult patients (55%) 18 years of age or older during this time period, with 31 patients (65 %) having documented pharmacist review and 18 (58%) of these patients with dose modification interventions. Of the 16 adult patients without pharmacist review, 9 (56%) had actionable drug interactions with only 2 of these patients having prescriber-documented dose adjustment. An additional 7 adult patients referred for nirmatrelvir and ritonavir were subsequently referred for intravenous therapy due to either contraindicated medications (n=6) or inability to swallow tablets (n=1).
Conclusions: Due to the large number of potential drug interactions with nirmatrelvir and ritonavir, the pharmacist is critical to help ensure patient safety and the safety and effectiveness of all medications being taken by the patient. Ongoing prospective pharmacist evaluation and prescribing of nirmatrelvir and ritonavir via a consult service is warranted. Audit data support the decision to implement EMR functionality requiring pharmacist verification before electronic transmission nirmatrelvir and ritonavir prescriptions. An institutional Collaborative Practice Agreement for nirmatrelvir and ritonavir prescribing and associated dose modification interventions is an effective and efficient way to operationalize pharmacist prescribing.
TADALAFIL USE IN NEONATES AND INFANTS LESS THAN THREE MONTHS OF AGE WITH PULMONARY HYPERTENSION. Katy Stephens1, Peter Johnson2, Jamie Miller2, Ashley Benedict2, Madison Casten2, Andrew Cave3. Oklahoma Children's Hospital at OU Health, University of Oklahoma College of Pharmacy, University of Oklahoma College of Medicine; Oklahoma City, OK. katy.stephens2@ouhealth.com
Introduction: Neonates and infants can develop pulmonary hypertension due to multiple etiologies. Currently, limited data exists for pharmacotherapy options for the management of pulmonary hypertension in this population. More recently, tadalafil, a phosphodiesterase-5 inhibitor, has been explored due to its favorable once daily dosing compared to sildenafil. However, there is a paucity of data for tadalafil use in pediatrics, especially neonates and young infants. The purpose of this study was to evaluate tadalafil dosing in neonates and infants less than three months of age.
Methods: This was a descriptive, retrospective review of patients less than three months of age who were admitted to the neonatal intensive care unit (NICU), cardiac intensive care unit (CICU), or pediatric intensive care unit (PICU) and received tadalafil between January 1, 2019 and November 30, 2022. Patients were excluded if they received tadalafil prior to admission or if they received less than 48 hours of tadalafil during their admission. Data collection included patient demographics, pulmonary hypertension etiology, tadalafil dosing regimens, sildenafil use prior to tadalafil, tadalafil continuation at discharge, concomitant pulmonary hypertension therapies, echocardiogram findings, vital signs and respiratory requirements, hospital length of stay, and noted tadalafil-associated adverse effects. The primary objective was to identify the median tadalafil dose (mg/kg) administered. Secondary objectives were to identify the indications for tadalafil and adverse effects related to tadalafil administration. Descriptive statistics were performed for data analyses.
Results: Seventy-four patients were included. Thirty-nine (52.7 percent) were male, and the median weight at the time of tadalafil initiation was 3.52 kg [interquartile range (IQR) 3.17–3.99 kg]. The median gestational age was 38, 1/7 weeks (IQR 36, 4/7–39, 1/7 weeks), and at the time of tadalafil initiation the median postnatal age was 43 days (IQR 15–62.8 days). Indications for pulmonary hypertension were congenital heart disease (n=52; 70.3 percent), idiopathic (n=7; 9.5 percent), persistent pulmonary hypertension of the newborn (n=6; 8.1 percent), congenital diaphragmatic hernia (n=5; 6.8 percent), meconium aspiration (n=3; 4.1 percent), and bronchopulmonary dysplasia (n=1; 1.4 percent). Twenty-three patients (31.1 percent) were transitioned from sildenafil to tadalafil for ease of administration. The median initial tadalafil dose was 1 mg/kg (IQR 1–1.05 mg/kg) administered once daily. The dose was increased in 26 patients (35 percent) to a maximum median dose of 1.5 mg/kg. Fifty-four patients (73 percent) were discharged on tadalafil. For adverse events, two patients (2.7 percent) were noted to have hyperemia following tadalafil initiation
Conclusions: Tadalafil dosing in neonates and infants less than three months was found to be comparable to published dosing of older infants and children. Only two patients were noted to have adverse events in the study. Overall, more exploration of tadalafil use in this population is needed.
VANCOMYCIN KINETICS NAVIGATOR IS INTENDED FOR ADULTS, BUT COULD IT WORK FOR ADOLESCENT PATIENTS FOR INITIAL DOSING RECOMMENDATIONS? A QUALITY IMPROVEMENT ANALYSIS. A. Jill Thompson, Katherine Malloy. Medical University of South Carolina Shawn Jenkins Children's Hospital, Charleston, SC. thompsam@musc.edu.
Introduction: A calculation tool within our electronic medical record, the vancomycin kinetics navigator, became available at our institution in September 2021. It was intended only for adult patients, but due to cross-coverage among adult and pediatric areas, it was used occasionally for adolescent patients. The initial vancomycin dosing recommendations the navigator generated were based on equations validated only in adults. We aimed to assess whether the navigator performed well when generating initial dosing recommendations for adolescents.
Methods: All vancomycin serum concentrations from October 1, 2021 through November 18, 2022 in patients ages 12 through 17 years were accessed using a report. Patients' actual pharmacokinetic parameters were compared to navigator-predicted pharmacokinetic parameters and then used to evaluate the potential performance of navigator-recommended dosing regimens. The dataset including patients' actual pharmacokinetic parameters was then used to design empiric adolescent vancomycin regimens.
Results: There were 265 vancomycin concentrations in 93 patient encounters. After excluding patients for duplicate concentrations in same patient (181), impaired kidney function (25), patients for whom no pharmacokinetic parameters could be calculated (5), and pregnancy (1), 53 concentrations (patients) were evaluated. Median age was 15 years (interquartile range 14–16 years) and median weight was 60 kg (interquartile range 48–74 kg). The navigator consistently underpredicted vancomycin clearance compared to the actual calculated values derived from measured serum concentrations (median predicted versus actual clearance, 3.844 L/h versus 6.583 L/h). As a result, the navigator overpredicted area under the curve (AUC) values, (median predicted versus actual AUC 500 versus 327 mg per h/L), resulting in the potential for suboptimal vancomycin regimens early in therapy if the navigator-recommended dosing regimen had been used. No correlation appeared evident between clearance and either age, serum creatinine, or creatinine clearance (using Bedside Schwartz glomerular filtration rate calculation). Utilizing the pharmacokinetic parameters from this dataset, the following initial vancomycin dosing recommendations in adolescents with normal kidney function were provided to staff as an alternative to relying on the navigator: standard dosing targeting AUC 400–600 mg per h/L, 40–60 mg/kg/day divided every 6–8 hours, maximum initial regimen 4500 mg/day; central nervous system (CNS) infection dosing targeting trough 15–20 mg/L, 60–70 mg/kg/day divided every 6–8 hours, maximum initial regimen 4500–6000 mg/day, with concentration monitoring early (day 1–2) and often (every 3–5 days). The every-6-hour dosing interval is more likely to be needed in critically ill patients or in ages 12–15 years.
Conclusions: The adult-based vancomycin kinetics navigator should not be used to generate initial vancomycin dosing recommendations for adolescent patients. Weight-based initial vancomycin regimen suggestions are provided based on targets (standard versus CNS dosing).
Pharmacogenomics in Patients with Acute Lymphoblastic Leukemia (ALL) to Characterize Vincristine and Triazoles Metabolism. M. Tuan Tran, Antonio Arrieta, Negar Ashouri, Jaime Frediani, Fiona Lam, Carol Lin. Children's Health of Orange County (CHOC), Children's Hospital, Orange, CA. mtran@choc.org
Introduction: Vincristine (VCR) is commonly used in acute lymphoblastic leukemia (ALL), and neurotoxicity associated with increased exposure to VCR is broadly recognized. VCR has been reported to preferentially metabolized via cytochrome P450 (CYP) 3A5 over 3A4 isoform by 14-fold. Substantial diversity in CYP enzymes expression have been reported, reflecting wide interpatient variability in VCR pharmacokinetics and exposures. Triazole antifungals are commonly used in immunocompromised patients for management of invasive Candida and mold infections. Triazoles are known inhibitors of CYP leading to significant potential for drug interactions with VCR. Voriconazole is both a substrate and inhibitor of 2C19 and 3A4; adverse events from drug interactions with voriconazole are unpredictable due to the high genetic polymorphism associated with CYP2C19. While VCR-associated toxicity has been widely reported with concomitant use of triazoles, there is no clear guidance to assist clinicians. Our pilot study aims to characterize and determine frequency of CYP polymorphisms associated with impaired VCR metabolism.
Methods: Signed informed consent/assent obtained for patients aged 1 – 26 years old, diagnosed with ALL or lymphoma and received VCR. Patients allergic to triazole or have history of liver transplant were excluded. Specimen obtained with buccal swab collection kit and sent to Mayo Clinic Laboratory for cytochrome P450 genotyping.
Results: Forty patients were enrolled from May – October 2022, mean age was 9.6 years (range 1.3 – 22.5), 27 (67.5%) males, all were diagnosed with ALL. Mean weight, height was 37 kg (range 11.7 – 132) and 130.3 cm (78 – 188) respectively. Fifteen (37.5%) patients identified as Hispanic race, 11 (27.5%) White, 8 (20%) patients identified as both Hispanic/White, 4 (10%) Asian and 2 patients declined to state. Nineteen (47.5%) patients received a triazole, primarily as prophylaxis during induction 12 (63.2%). The most common triazole was fluconazole (17, 89.5%), and one each voriconazole or isavuconazole. Five (12.5%) patients were carrier for a reduced function 3A4*22 allele, including one with 3A4*22/*22 genotype. Twenty-five (62.5%) patients were homozygous for nonfunctional 3A5*3 and are considered poor metabolizer, another 11 (27.5%) were carrier for one nonfunctional allele. Only 4 (10%) patients were carrier for two functional genotype, 3A5*1/*1. CYP3A5 nonexpresser was common in both Hispanic, 13 (86.7%) and White 10 (90.9%) patients. Seventeen (42.5%) patients expressed a nonfunctional 2C19*2 allele, including 3 (7.5%) poor metabolizers with nonfunctional 2C19*2/*2; 10 (25%) patients were rapid metabolizer, carrier for 2C19*17, 6 (60%) of whom are Hispanics. Of the 10 (25%) patients who experienced VCR-associated neuropathy, 6 (60%) were homozygous 3A5*3/*3 and 3 (30%) patients were carrier for one nonfunctional allele 3A5*3.
Conclusions: CYP3A5 nonexpresser is common in Hispanics and White patients, potentially leading to decreased VCR metabolism and increased risk for toxicity. CYP2C19 expression varied, close therapeutic monitoring for voriconazole is warranted.
ECHO CHANGES WITH ONE VS. TWO-DAY DOSING REGIMENS OF DOXORUBICIN. Megan Wright, Sarah Timaeus, Laura Hall. Vanderbilt University Medical Center Department of Pharmaceutical Services, Nashville, TN. megan.wright@vumc.org
Introduction: Doxorubicin is utilized in a variety of chemotherapy regimens and is heavily associated with cardiotoxicity. Current standard of care for sarcoma patients uses a two-day dosing scheme to limit cardiotoxicity. A one-day dosing scheme has been proposed in adolescents to decrease the length of hospital stay or healthcare utilization. At this large academic children's hospital, to monitor for cardiotoxicity, echocardiograms (ECHO) are obtained at baseline, after 150 mg/m2 of cumulative doxorubicin, after 300 mg/m2, then every cycle thereafter. This study aims to describe ECHO changes and subsequent interventions made for patients receiving doxorubicin as a one-day or two-day dosing scheme.
Methods: This is a single center, retrospective chart review of patients who received doxorubicin for sarcoma treatment at a large academic children's hospital. In addition to general demographic information, the date of ECHO, cumulative dose of doxorubicin at time of ECHO, ejection fraction (EF), fraction shortening (FS), and any interventions made were collected for each ECHO. A clinically significant ECHO change was defined as EF<50% or FS <27%. Possible interventions included referral to cardio-oncology, completion of a cardiac MRI, initiation of cardiac medications, and adjustment in chemotherapy timing.
Results: From April 2017 to November 2022, 68 patients received upfront therapy for Ewing's sarcoma or Osteosarcoma. Fifty-five patients were analyzed, and 49 patients received doxorubicin over two days. Prior to therapy initiation, no patients had cardiac dysfunction with a median EF of 62.1% and FS of 37.4%. Most patients received their full doxorubicin course for their respective disease state. During the active treatment period, 1 patient (16%) in the one-day group had a clinically significant ECHO change compared to 3 patients (6%) in the two-day dosing scheme. The most common intervention for these 4 patients was adjustment in chemotherapy timing. No patients were switched from a one-day regimen to a two-day regimen. Despite 27% of patients being lost to follow up, there was limited evidence of long-term toxicity in either group based on post-treatment ECHOs. During the entire study period, 71% of patients received a referral to cardio-oncology, with most of the referrals occurring at the end of therapy.
Conclusions: A robust comparison between the one-day and two-day dosing schemes is difficult given limited utilization of the one-day dosing scheme. Regardless of dosing scheme, 89% of patients experienced no clinically significant ECHO changes. The large number of patients lost to follow-up is thought to have occurred due to the COVID-19 pandemic and concerns for healthcare exposure. Moving forward, providers can consider utilizing a one-day dosing scheme to limit the burden of hospitalization, but there is no conclusive data surrounding effects on long term toxicity.