Trenton Flanagan

The pharmacokinetic profile of heparin may result in supratherapeutic antifactor-Xa levels using total weight-based protocols for the treatment of venous thromboembolism (VTE) in obese patients. Previous literature has been limited by choice of monitoring assay and inconsistent dosing strategies. The goal of this study was to evaluate safety and efficacy outcomes of an antifactor-Xa based UFH VTE protocol in obese vs. non-obese patients. This was a single center, retrospective study of adult patients with an acute VTE treated with our institution specific UFH VTE protocol. Patients were screened from the preceding 3 years for inclusion into the obese (BMI ≥ 30 kg/m²) or non-obese (BMI < 30 kg/m²) groups. The primary outcome was the weight-based rate of UFH (units/kg/hr) required to attain a therapeutic anti-Xa level. Secondary outcomes included rate required to attain steady state, time to first therapeutic anti-Xa level and steady state, proportion of patients to attain at least one therapeutic anti-Xa level and steady state, number of rate changes required to attain steady state, and proportion of anti-Xa levels being therapeutic, subtherapeutic, or supratherapeutic at the first anti-Xa level drawn, within the first 24 h of treatment, and for the duration of treatment with UFH. Safety outcomes evaluated the incidence of any major or non-major bleeding event, requiring reversal agents, or having additional thrombotic events. The primary outcome of weight-based rate at first therapeutic anti-Xa level was significantly lower in the obese group, and this was consistent for attainment of steady state, as well (14 units/kg/hour vs. 16 units/kg/hour, p < 0.001). Patients in the obese group had significantly more supratherapeutic anti-Xa levels within 24 h (50% vs. 33%, p < 0.0001) and for the total duration of UFH therapy (40% vs. 25%, p < 0.0001) No significant differences in clinically overt bleeding rates were found. Obese patients required a lower weight-based rate of UFH to attain therapeutic anti-Xa levels for the treatment of VTE. Additionally, there appears to be an inverse relationship between weight-based UFH rate and total UFH rate at the first therapeutic anti-Xa and steady state as BMI increases. Future studies should focus on dosing strategies that improve attainment of therapeutic anti-Xa levels in obese patients. Graphical abstract

There is a need to understand contemporary scientific advances as clinical pharmacy evolves. One rapidly expanding area is artificial intelligence (AI), which has grown significantly over the past year because of the public availability of large language models. This commentary reviews published literature describing and evaluating applications of AI to each aspect of the medication use process and forecasts potential future roles for AI in pharmacy practice. Potential challenges in implementation are also described.

Background: Analgesia and sedation are often critical elements of therapy for patients undergoing extracorporeal membrane oxygenation (ECMO). Aside from potential drug-drug interactions, the PK changes associated with ECMO make appropriate analgosedative selection challenging. Ketamine is less lipophilic and has lower protein binding than alternative agents, and may be less impacted by the PK changes during ECMO. Objective: To systematically identify all instances of ketamine use during ECMO support in the literature to elucidate associated efficacy and safety outcomes and prevalence of use, as well as commonly used dosing strategies and pharmacokinetic data. Methods: Web of Science, Cochrane Library, Scopus, Ovid MEDLINE, PubMed, and OVID Embase were searched through 02/2023 using keywords ketamine and ECMO or extracorporal life support (ECLS). Case reports, case series, and studies were included that had (1) original data, (2) included patients that were on ECMO and continuous infusion ketamine, and (3) reported pertinent ketamine related clinical endpoints or prevalence of use. Results: Of the 307 articles screened, 25 were identified as relevant and 11 met our inclusion criteria. Heterogeneity of patient population, ketamine indication, reported outcomes, and reported safety endpoints were identified in the included articles. Commonly reported information includes indications, pharmacokinetics, dosing, adverse effects and use in pediatrics for ketamine, and suspected opioid sparing effect. Conclusion: Our review has found a lack of consistency in reporting and results in adult and pediatric patients. Increased consistency in reporting and larger studies are required to increase our knowledge of ketamine use in both the adult and pediatric patient population.