No abstract

A growing number of patients with an indication for stroke prevention in atrial fibrillation have kidney-, age-, or weight-related alterations in pharmacokinetics that affect dosing of direct oral anticoagulants. Because these patients were excluded from or comprised a small number of patients in clinical trials, there is a lack of evidence to guide clinicians. As a consequence, many patients do not receive oral anticoagulation despite a high risk for atrial fibrillation-related stroke. Here, we present a review of direct oral anticoagulant pharmacokinetics and a review of the available clinical evidence in patients with weight-, kidney-, and age-related disease.

In patients with ischemic stroke who receive systemic recombinant tissue plasminogen activator (rt-PA), the risk of secondary hemorrhage is 1-7%. Fibrinogen supplementation with cryoprecipitate is recommended in patients with rt-PA-associated symptomatic hemorrhage. We examined whether fibrinogen concentrate can be used safely in this setting. A single-center retrospective case series was performed in patients who received fibrinogen concentrate for post-rt-PA hemorrhage between January-2012 and December-2017. The primary outcome was the incidence of in-hospital thromboembolic events and infusion reactions. Secondary outcomes included incidence of clinically significant ICH expansion within 24-hours and patient serum fibrinogen response to fibrinogen concentrate therapy. Thromboembolic events occurred in 3 (12.5%) of 24 patients included in the analysis. No patients experienced infusion-related reactions. Five of 22 patients with ICH experienced clinically significant hemorrhage expansion. Hypofibrinogenemia was corrected in 87.5%(7/8) of patients with baseline hypofibrinogenemia, with a median increase in serum fibrinogen 166 mg/dL. Median fibrinogen increase in patients without baseline hypofibrinogenemia was 18 mg/dL. Fibrinogen concentrate is a safe potential therapeutic option to restore fibrinogen levels in acute ischemic stroke patients with thrombolysis-associated hemorrhage.

INTRODUCTION: Iatrogenic withdrawal syndrome (IWS) is associated with large doses and prolonged use of opioidssedatives. This study aimed to determine current utilization patterns of opioids-sedatives in adult ICUs that may be associated with IWS. We hypothesized that cumulative doses would increase with prolonged ICU stay. METHODS:We conducted an international, observational, point prevalence study on a single date between June 1 and September 30, 2021 for adult ICU patients (≥ 18 years). Demographic data, medication exposures in the preceding 24 hours, and outcomes were collected following institutional ethics approval. The primary outcome was the proportion of patients receiving continuous parenteral opioids-sedatives for ≥ 72 hours. We defined continuous use as continuous IV infusion, scheduled intermittent injections, or as needed parenteral doses with at least half of the possible doses administered in 24 hours. Outcomes were compared between patients receiving opioids-sedatives < 72 and ≥ 72 hours. Parametric and nonparametric statistical analyses were performed using IBM SPSS Statistics version 28.0.0 (Armonk, New York) according to level of measurement, data distribution and assumptions. The a priori alpha was 5%.RESULTS: There were 1506 patients who received parenteral opioids-sedatives in 229 ICUs at 87 hospitals in 11 countries. Median ICU stay was 6 (IQR; 12) days, 31% had ARDS, and 71% were invasively mechanically ventilated. Continuous opioids were administered to 50% (647/1305), sedatives to 52% (600/1151), and both to 37% (561/1506) of patients ≥ 72-hr, with 84% receiving continuous IV infusion opioids and 98% sedatives ≥ 72-hr (p< 0.001). All median 24-hr total opioid-sedative doses were significantly greater when used ≥ 72 hr. There was no difference in opioid-sedative dose reduction in the previous 24-hr, but significantly more patients on opioids-sedatives < 72-hr received > 50% dose reductions (61% vs. 38%; p< 0.001) and had enteral opioids-sedatives initiated in the previous 24-hr (24% vs. 15%; p< 0.001). Three of 9 patients assessed had IWS, all of whom received opioids-sedatives ≥ 72-hr. CONCLUSIONS:Half of adult ICU patients receive continuous parenteral opioids-sedatives for ≥ 72-hr at higher doses than earlier in admission, which may increase the risk of IWS.