Scott D. Nei

Levetiracetam Pharmacokinetics in a Patient Receiving Continuous Venovenous Hemofiltration and Venoarterial Extracorporeal Membrane Oxygenation

Levetiracetam is a first‐line therapy for seizures in critically ill patients because of its clinical efficacy, minimal drug interactions, and wide therapeutic window. The primary mechanism of levetiracetam clearance is renal, and the drug has a low molecular weight. It is hydrophilic and exhibits minimal protein binding. Thus it is expected that levetiracetam will be removed by continuous venovenous hemofiltration (CVVH), with limited clearance by venoarterial extracorporeal membrane oxygenation (ECMO). We describe the case of a 67‐year‐old man who was admitted to the cardiovascular surgery intensive care unit after cardiac arrest and initiation of venoarterial ECMO. His course was complicated by multiorgan dysfunction including acute renal failure requiring CVVH. On hospital day 6, intravenous levetiracetam, at a loading dose of 2000 mg followed by a maintenance dose of 1000 mg every 12 hours, was initiated for new‐onset seizures. The volume of distribution was 0.65 L/kg, and clearance was measured with peak (ranging from 26.5–39.8 μg/ml) and trough (ranging from 13.9–18.2 μg/ml) concentrations. Elimination half‐life ranged from 8.7–10.1 hours. Renal dysfunction reduces levetiracetam clearance, and dosage reductions are recommended to prevent accumulation. Current CVVH dosing recommendations are based on predicted removal without clinical data. The volume of distribution and clearance in this case were similar to those of a normal healthy patient. Based on these results, we recommend considering an initial levetiracetam dose of 1000 mg every 12 hours for patients receiving CVVH, with dosage adjustments based on therapeutic drug monitoring.

Comparison of In-Hospital Bleeding and Cardiovascular Events with High-Dose Bolus Tirofiban and Shortened Infusion to Short-Duration Eptifibatide as Adjunctive Therapy for Percutaneous Coronary Intervention

Potent platelet inhibition is one of the most important medical interventions to prevent ischemic complications during and after percutaneous coronary intervention (PCI). Practice has evolved with the introduction of potent oral P2Y12 inhibitors that provide quick, effective platelet inhibition, and the need for routine glycoprotein IIb/IIIa inhibitors (GPIs) has decreased. Additionally, a shorter duration of GPI infusion has been shown to be safe with adequate oral antiplatelet loading, but clinical outcome data are limited to eptifibatide. This single-center, retrospective cohort study analyzed in-hospital outcomes for patients who received adjunctive GPI therapy for PCI before and after an institution-wide switch to high-dose bolus tirofiban with shortened infusion from short-duration eptifibatide. The primary end point was a composite in-hospital outcome of major and minor bleeding and cardiovascular events (death, myocardial infarction, coronary artery bypass grafting, ischemic stroke, and target vessel revascularization). Secondary end points included bleeding and cardiovascular event types. A total of 357 and 446 patients received eptifibatide and tirofiban, respectively, from February 1, 2014 through September 30, 2017. Thirty five eptifibatide and 46 tirofiban patients experienced an in-hospital composite event (9.8% vs 10.3%, p = 0.81). There was no difference found between in-hospital bleeding (6.4% vs 5.4%, p = 0.52) or cardiovascular events (5.6% vs 6.5%, p = 0.60) with the use of eptifibatide or tirofiban, respectively. Multivariable analysis showed that patients with transradial access or an indication of unstable angina were less likely to experience an in-hospital composite event (OR 0.30 and 0.19, respectively, p <0.001 for both). In conclusion, the use of high-dose bolus tirofiban with shortened infusion versus short-duration eptifibatide was not associated with an increase of in-hospital bleeding or cardiovascular events.

Maintenance of Drug-eluting Stent Patency through Use of a Cangrelor Infusion in the Clinical Setting of Massive Pulmonary Hemorrhage and Venoarterial Extracorporeal Membrane Oxygenation

We report ultra-short–acting parenteral P2Y12 inhibitor, cangrelor, for maintenance of fresh drug-eluting stent patency concurrent pulmonary hemorrhage and cardiogenic shock requiring central venoarterial extracorporeal membrane oxygenation. In the setting of stent placement after acute coronary syndrome, standard of care includes indefinite aspirin use plus 12 months of P2Y12 inhibitor to avoid in-stent thrombosis. Cangrelor therapy, with its downregulation of platelet activation and aggregation, was initiated at one-half the recommended percutaneous coronary intervention dosing (2 mcg/kg/min) and maintained patency during central venoarterial extracorporeal membrane oxygenation.

Therapeutic drug monitoring of mexiletine at a large academic medical center

Introduction: The therapeutic trough range for mexiletine (0.8–2 mcg/mL) was largely established in the setting of arrhythmia prophylaxis following myocardial infarction. Objective: Describe the usage patterns of serum mexiletine concentrations and the impact of these concentrations on mexiletine dosing in modern practice for ventricular arrhythmia treatment. Methods: A single-center, retrospective analysis was conducted using the electronic medical record to identify serum mexiletine concentrations drawn between December 2004 and December 2014. The primary endpoint was the incidence of mexiletine concentrations drawn as troughs. Secondary outcomes included the incidence of mexiletine concentrations that prompted a dose change, association between adverse events and elevated concentrations, and association between baseline characteristics and mexiletine concentrations. Results: A total of 237 individual concentrations were included for analysis with 109 (46.0%) drawn appropriately as trough concentrations. Only 31 (13.1%) of the 237 concentrations drawn prompted a dose change. Mexiletine was primarily used for the treatment of ventricular arrhythmias (96.2%), and 108 (45.6%) concentrations were drawn in an effort to assess efficacy. The median concentration was statistically different between patients with and without an adverse event (0.8 vs 0.7 mcg/mL, respectively; p = 0.017), but may not represent a clinical significance. Patients with hepatic dysfunction had higher median concentrations compared to those without hepatic dysfunction (1.30 vs 1.07 mcg/mL; p = 0.01). Conclusion: Mexiletine concentrations are often drawn at inappropriate times and seldom influence a dose change. This study suggests that routine monitoring of mexiletine concentrations may not be necessary; however, therapeutic drug monitoring may be considered in patients with hepatic dysfunction or to confirm mexiletine absorption in patients where this represents a concern.

Effect of a Shortened-Duration Eptifibatide Infusion (75 mg) as Adjunctive Therapy for Percutaneous Coronary Intervention on Inhospital Cardiovascular Outcomes and Bleeding

A retrospective cohort analysis was conducted on patients who underwent percutaneous coronary intervention (PCI) before and after a practice change which reduced the infusion duration of eptifibatide from 18 hours to the time required for completion of a single vial of 75 mg initiated during PCI. Primary end points were inhospital cardiovascular events, target vessel revascularization, and major or minor bleeding. The secondary end point was drug cost. A total of 1,647 patients received the standard-duration infusion (18 hours), and 1,237 received the short-duration infusion. The median infusion times were 18.1 hours (interquartile range 17.7 to 18.7) and 6.6 hours (interquartile range 5.6 to 11.3) in the standard- and short-duration groups, respectively. No differences were found for the rate of inhospital cardiovascular events (2.0% vs 1.9%, respectively; p = 0.78) or inhospital revascularization (0.2% vs 0.3%, respectively; p = 0.68). Also, no statistically significant difference was observed in major bleeding (standard 4.3% vs short 4.4%; p = 0.94) or minor bleeding (standard 3.3% vs short 2.3%; p = 0.09). In conclusion, using a shortened infusion reduced eptifibatide use by an average of 1.6 vials at cost savings of

Levetiracetam Pharmacokinetics During Continuous Venovenous Hemofiltration and Acute Liver Dysfunction

823 per patient and resulted in no difference in inhospital cardiovascular events, revascularization, or bleeding.