Pulmonary embolism (PE) is a life-threatening condition and a leading cause of morbidity and mortality. There have been many advances in the field of PE in the last few years, requiring a careful assessment of their impact on patient care. However, variations
Current guidelines recommend 4-factor prothrombin complex concentrate (4PCC) for emergent reversal of bleeding secondary to warfarin. While current research has demonstrated superiority of 4PCC over plasma, direct comparisons with 3-factor PCC (3PCC) are lacking. The purpose of this study is to compare the efficacy and safety of 3PCC and 4PCC. We conducted a retrospective analysis of patients who received PCC at one of four medical centers. All patients in the 3PCC group were treated at one center that utilizes a fixed, weight-based dosing protocol. After evaluation of all patients meeting inclusion criteria, propensity-score matching was used to adjust for differences in treatment characteristics. There was no difference in the primary outcome of INR ≤ 1.4 between 3PCC and 4PCC in both the unmatched (85.7 vs. 90.6 %; p = 0.37) and matched (84.2 vs. 92.1 %; p = 0.48) analyses. There was a significant difference in goal INR achieved favoring 4PCC (56.3 vs 90.0 %; p < 0.02) when baseline INR > 4.0. A total of three thrombotic events were documented, all in the 4PCC group. We found no difference in the rate of INR reversal in those treated with 3PCC and 4PCC. However, those with a baseline INR > 4.0 may experience more successful INR reversal with 4PCC.
Purpose
We present the case of a 56-year-old man with stage IV sarcoidosis on veno-venous extracorporeal membrane oxygenation (VV-ECMO) support for the management of respiratory failure receiving treatment with isavuconazole for invasive aspergillosis.
Summary
VV-ECMO is an increasingly utilized life support therapy for patients with cardiac and/or respiratory failure, but its impact on medication dosing is poorly understood. In our patient with invasive Aspergillus infection receiving VV-ECMO, because of difficulty achieving therapeutic serum concentrations of voriconazole, we administered isavuconazole 372 mg intravenously (IV) every 8 hours for 6 doses followed by 372 mg IV once daily. Isavuconazole has a favorable pharmacokinetic and safety profile compared to other azole antifungal agents, but its high protein binding and lipophilicity raise concerns about drug sequestration in the VV-ECMO circuit. To optimize the efficacy and safety of this treatment, the isavuconazole trough concentration was measured at days 5 and 17, at which time it was 1.7 and 0.7 μg/mL, respectively. The dose was subsequently increased to 744 mg IV once daily, and serum trough concentrations were measured 5 and 8 days after dose adjustment, corresponding to 3.7 and 2.9 μg/mL, respectively. To our knowledge, this is the third report to describe inadequate isavuconazole trough concentrations during VV-ECMO support when utilizing standard doses.
Conclusion
In the case described here, standard-dose isavuconazole (372 mg every 8 hours for 6 doses followed by 372 mg daily) did not achieve target trough concentrations in a patient receiving concomitant ECMO support.
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