Browsing by Subject "Drug monitoring"

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    A Novel Perioperative Multidose Methadone-Based Multimodal Analgesic Strategy in Children Achieved Safe and Low Analgesic Blood Methadone Levels Enabling Opioid-Sparing Sustained Analgesia With Minimal Adverse Effects
    (Wolters Kluwer, 2021) Sadhasivam, Senthilkumar; Aruldhas, Blessed W.; Packiasabapathy, Senthil; Overholser, Brian R.; Zhang, Pengyue; Zang, Yong; Renschler, Janelle S.; Fitzgerald, Ryan E.; Quinney, Sara K.; Anesthesia, School of Medicine
    Background: Intraoperative methadone, a long-acting opioid, is increasingly used for postoperative analgesia, although the optimal methadone dosing strategy in children is still unknown. The use of a single large dose of intraoperative methadone is controversial due to inconsistent reductions in total opioid use in children and adverse effects. We recently demonstrated that small, repeated doses of methadone intraoperatively and postoperatively provided sustained analgesia and reduced opioid use without respiratory depression. The aim of this study was to characterize pharmacokinetics, efficacy, and safety of a multiple small-dose methadone strategy. Methods: Adolescents undergoing posterior spinal fusion (PSF) for idiopathic scoliosis or pectus excavatum (PE) repair received methadone intraoperatively (0.1 mg/kg, maximum 5 mg) and postoperatively every 12 hours for 3-5 doses in a multimodal analgesic protocol. Blood samples were collected up to 72 hours postoperatively and analyzed for R-methadone and S-methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidene (EDDP) metabolites, and alpha-1 acid glycoprotein (AAG), the primary methadone-binding protein. Peak and trough concentrations of enantiomers, total methadone, and AAG levels were correlated with clinical outcomes including pain scores, postoperative nausea and vomiting (PONV), respiratory depression, and QT interval prolongation. Results: The study population included 38 children (10.8-17.9 years): 25 PSF and 13 PE patients. Median total methadone peak plasma concentration was 24.7 (interquartile range [IQR], 19.2-40.8) ng/mL and the median trough was 4.09 (IQR, 2.74-6.4) ng/mL. AAG concentration almost doubled at 48 hours after surgery (median = 193.9, IQR = 86.3-279.5 µg/mL) from intraoperative levels (median = 87.4, IQR = 70.6-115.8 µg/mL; P < .001), and change of AAG from intraoperative period to 48 hours postoperatively correlated with R-EDDP (P < .001) levels, S-EDDP (P < .001) levels, and pain scores (P = .008). Median opioid usage was minimal, 0.66 (IQR, 0.59-0.75) mg/kg morphine equivalents/d. No respiratory depression (95% Wilson binomial confidence, 0-0.09) or clinically significant QT prolongation (median = 9, IQR = -10 to 28 milliseconds) occurred. PONV occurred in 12 patients and was correlated with morphine equivalent dose (P = .005). Conclusions: Novel multiple small perioperative methadone doses resulted in safe and lower blood methadone levels, <100 ng/mL, a threshold previously associated with respiratory depression. This methadone dosing in a multimodal regimen resulted in lower blood methadone analgesia concentrations than the historically described minimum analgesic concentrations of methadone from an era before multimodal postoperative analgesia without postoperative respiratory depression and prolonged corrected QT (QTc). Larger studies are needed to further study the safety and efficacy of this methadone dosing strategy.
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    Analyzing the Clinical Outcomes of a Rapid Mass Conversion From Rosuvastatin to Atorvastatin in a VA Medical Center Outpatient Setting
    (SAGE, 2017-10) Naville-Cook, Chad; Rhea, Leroy; Triboletti, Mark; White, Christina; Pharmacology and Toxicology, School of Medicine
    Background: Medication conversions occur frequently within the Veterans Health Administration. This manual process involves several pharmacists over an extended period of time. Macros can automate the process of converting a list of patients from one medication to a therapeutic alternative. Objectives: To develop a macro that would convert active rosuvastatin prescriptions to atorvastatin and to create an electronic dashboard to evaluate clinical outcomes. Methods: A conversion protocol was approved by the Pharmacy & Therapeutics Committee. A macro was developed using Microsoft Visual Basic. Outpatients with active prescriptions for rosuvastatin were reviewed and excluded if they had a documented allergy to atorvastatin or a significant drug-drug interaction. An electronic dashboard was created to compare safety and efficacy endpoints pre- and postconversion. Primary endpoints included low-density lipoprotein (LDL), creatine phosphokinase (CPK), aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase. Secondary endpoints evaluated cardiovascular events, including the incidences of myocardial infarction, stroke, and stent placement. Results: The macro was used to convert 1520 patients from rosuvastatin to atorvastatin over a period of 20 hours saving $5760 in pharmacist labor. There were no significant changes in LDL, AST, ALT, or secondary endpoints (P > .05). There was a significant increase in alkaline phosphatase (P = .0035). Conclusions: A rapid mass medication conversion from rosuvastatin to atorvastatin saved time and money and resulted in no clinically significant changes in safety or efficacy endpoints. Macros and clinical dashboards can be applied to any Veterans Health Administration facility.