Piperacillin pharmacokinetics and pharmacodynamics in paediatric patients who received high frequency intra-operative piperacillin/tazobactam dosing.

Piperacillin/tazobactam (PTZ) is a broad-spectrum antibiotic, typically dosed every six hours (q6h). Guidelines recommend dosing PTZ every 2 hours (q2h) intra-operatively for complex abdominal surgery, including liver transplant. The data supporting the guidelines for intra-operative dosing are sparse and the pharmacokinetics/pharmacodynamics (PK/PD) of q2h dosing has not been studied by simulation or in humans. In this study, PK/PD parameters of high-frequency intra-operative dosing and q6h post-operative dosing were compared in critically ill children. Paediatric patients who received PTZ during complex abdominal surgery or transplant and who had intra-operative and post-operative opportunistic samples were included. Using a published PK model and observed concentrations, individual piperacillin PK/PD parameters were estimated using Bayesian estimation. Alternative post-operative dosing strategies were simulated using the patients with the highest and lowest estimated piperacillin clearance. Thirteen patients were included (median age: 3.1 years, 85% liver transplant recipients). PK parameters in the intra-operative and post-operative phases were not significantly different (clearance: 15.8 ± 7.2 vs. 12.6 ± 6.3 L/h/70 kg, P=0.070; central volume: 13.4 [13.1, 13.8] vs. 15.2 [12.2, 16.0] L/70 kg, P=0.22). At an individual level, intra-operative clearance values were -35% to 139% of the post-operative values, whereas central volume intra-operative values were -40% to 77% of the post-operative values. Intra-operative piperacillin exposure was higher during high-frequency dosing compared with the post-operative period (AUC/h: 109 [93.4, 127] vs. 62.8 [41.6, 78.3] mg/L, P=0.002). Simulations showed great variation in optimal dosing strategies that would minimise toxicity and maximise efficacy, indicating a role for individualised dosing in paediatric surgical populations.

Implementation of CYP2D6-guided opioid therapy at Cincinnati Children's Hospital Medical Center.

PURPOSE: We describe the implementation of CYP2D6-focused pharmacogenetic testing to guide opioid prescribing in a quaternary care, nonprofit pediatric academic medical center. SUMMARY: Children are often prescribed oral opioids after surgeries, for cancer pain, and occasionally for chronic pain. In 2004, Cincinnati Children's Hospital Medical Center implemented pharmacogenetic testing for CYP2D6 metabolism phenotype to inform codeine prescribing. The test and reports were updated to align with changes over time in the testing platform, the interpretation of genotype to phenotype, the electronic health record, and Food and Drug Administration (FDA) guidance. The use of the test increased when a research project required testing and decreased as prescribing of oxycodone increased due to FDA warnings about codeine. Education about the opioid-focused pharmacogenetic test was provided to prescribers (eg, the pain and sickle cell teams) as well as patients and families. Education and electronic health record capability increased provider compliance with genotype-guided postsurgical prescribing of oxycodone, although there was a perceived lack of utility for oxycodone prescribing. CONCLUSION: The implementation of pharmacogenetic testing to inform opioid prescribing for children has evolved with accumulating evidence and guidelines, requiring changes in reporting of results and recommendations.

Polypharmacy among medicaid-insured children with and without documented obesity.

OBJECTIVE: Polypharmacy increases the risk of drug-drug interactions and adverse drug events. As obesity and rates of obesity-associated comorbid chronic conditions continue to rise, an improved understanding of whether children with obesity experience higher risk of polypharmacy is needed. This study aimed to compare chronic medication polypharmacy prevalence among children with and without a diagnosis of obesity. METHODS: We performed a cross-sectional examination of prescription data for children aged 2-18 years prescribed ≥1 chronic medication using the 2019 Marketscan Medicaid database. Children with documented obesity were identified using medical visit diagnosis codes. Chronic medications included any ≥30-day prescription with ≥2 dispensed refills. Polypharmacy was defined as the prescription of ≥2 chronic medications for ≥1 overlapping days. Chi-squared tests compared polypharmacy prevalence and the distribution of chronic medication classes between children with and without obesity. Logistic regression determined the adjusted odds ratio (aOR) of polypharmacy for children with obesity, adjusting for relevant demographic and clinical differences. RESULTS: Of 634,671 included children, 12.2% had documented obesity. More than one-half (52.7%) of children with obesity experienced polypharmacy compared with 47.6% of children without obesity (aOR 1.06 [95% confidence interval 1.04-1.08]). Chronic medication prescriptions, particularly for psychiatric and asthma medications, were more commonly prescribed among children with obesity than those without obesity. CONCLUSIONS: Children with documented obesity have higher polypharmacy prevalence than children without obesity. Clinicians must be aware of this risk and minimize inappropriate polypharmacy whenever possible. Future work should examine the consequences of polypharmacy, including drug-drug interactions and adverse drug events in children with obesity.

Perspectives from the Society for Pediatric Research: pharmacogenetics for pediatricians.

This review evaluates the pediatric evidence for pharmacogenetic associations for drugs that are commonly prescribed by or encountered by pediatric clinicians across multiple subspecialties, organized from most to least pediatric evidence. We begin with the pharmacogenetic research that led to the warning of increased risk of death in certain pediatric populations ("ultrarapid metabolizers") who are prescribed codeine after tonsillectomy or adenoidectomy. We review the evidence for genetic testing for thiopurine metabolism, which has become routine in multiple pediatric subspecialties. We discuss the pharmacogenetic research in proton pump inhibitors, for which clinical guidelines have recently been made available. With an increase in the prevalence of behavioral health disorders including attention deficit hyperactivity disorder (ADHD), we review the pharmacogenetic literature on selective serotonin reuptake inhibitors, selective norepinephrine reuptake inhibitors, and ADHD medications. We will conclude this section on the current pharmacogenetic data on ondansetron. We also provide our perspective on how to integrate the current research on pharmacogenetics into clinical care and what further research is needed. We discuss how institutions are managing pharmacogenetic test results and implementing them clinically, and how the electronic health record can be leveraged to ensure testing results are available and taken into consideration when prescribing medications. IMPACT: While many reviews of pharmacogenetics literature are available, there are few focused on pediatrics. Pediatricians across subspecialties will become more comfortable with pharmacogenetics terminology, know resources they can use to help inform their prescribing habits for drugs with known pharmacogenetic associations, and understand the limitations of testing and where further research is needed.

Reducing Electrolyte Testing in Hospitalized Children by Using Quality Improvement Methods.

BACKGROUND AND OBJECTIVES: Despite studies indicating a high rate of overuse, electrolyte testing remains common in pediatric inpatient care. Frequently repeated electrolyte tests often return normal results and can lead to patient harm and increased cost. We aimed to reduce electrolyte testing within a hospital medicine service by >25% within 6 months. METHODS: We conducted an improvement project in which we targeted 6 hospital medicine teams at a large academic children's hospital system by using the Model for Improvement. Interventions included standardizing communication about the electrolyte testing plan and education about the costs and risks associated with overuse of electrolyte testing. Our primary outcome measure was the number of electrolyte tests per patient day. Secondary measures included testing charges and usage rates of specific high-charge panels. We tracked medical emergency team calls and readmission rates as balancing measures. RESULTS: The mean baseline rate of electrolyte testing was 2.0 laboratory draws per 10 patient days, and this rate decreased by 35% after 1 month of initial educational interventions to 1.3 electrolyte laboratory draws per 10 patient days. This change has been sustained for 9 months and could save an estimated $292 000 in patient-level charges over the course of a year. Use of our highest-charge electrolyte panel decreased from 67% to 22% of testing. No change in rates of medical emergency team calls or readmission were found. CONCLUSIONS: Our improvement intervention was associated with significant and rapid reduction in electrolyte testing and has not been associated with unintended adverse events.