PGY2 Critical Care Pharmacy Residency

Anti-Xa Guided Direct Oral Anticoagulant Reversal with Four-Factor Prothrombin Complex Concentrate

Caitlin E. Labay, PharmD; Celia Morton, PharmD; Annette Lista, PharmD; JD Fields, MS; Christina Cisar, BS; Suraj Sulhan, MD; Kevin R. Donahue, PharmD

PURPOSE

Major bleeding in patients taking direct oral anticoagulants (DOACs) is associated with significant cost and increased mortality. DOAC reversal with four-factor prothrombin complex concentrate (4F-PCC) has a hemostatic failure rate of 20%. While use of DOAC anti-Xa levels to guide dosing of 4F-PCC is a theoretical strategy to optimize outcomes, data is lacking.

METHODS

This was a single-center, retrospective study that compared patients with and without rivaroxaban or apixaban DOAC antiXa levels prior to reversal with 4F-PCC. The primary outcome was total cumulative dose of 4F-PCC administered.

RESULTS

A total of 199 patients were included. Fifty-two had a DOAC anti-Xa levels. The most common indication for reversal was major bleeding (90.4% level group vs. 85.7% no-level group). Median cumulative dose of 4F-PCC was not different between groups (39.3 units/kg [IQR 26.450.2] level group vs. 35.6 units/kg [IQR 24.3-49] no-level group; p = 0.3). DOAC anti-Xa levels did not correlate with hemostatic efficacy, however among patients who received DOAC anti-Xa monitoring, the dose of 4F-PCC trended higher in those who achieved hemostasis compared to those who did not both for patients on apixaban (40.2 units/kg effective hemostasis vs. 36.0 units/kg ineffective hemostasis) and rivaroxaban (46.4 units/kg 4F-PCC effective hemostasis vs. 22.2 units/kg ineffective hemostasis).

CONCLUSION

No significant difference was observed in total 4F-PCC dose or clinical outcomes when utilizing DOAC specific anti-Xa levels. Furthermore, DOAC anti-Xa level monitoring did not impede patient care and may result in trends toward more effective hemostasis.

PGY2 CRITICAL CARE PHARMACY RESIDENCY

Caitlin Labay, PharmD

Caitlin received her Doctor of Pharmacy degree from The University of Texas at Austin and completed her PGY1 training at Houston Methodist Hospital. Following the completion of her PGY2 in Critical Care, Caitlin assume the role of a critical care clinical pharmacist at Methodist Hospital in San Antonio, TX. Primary project preceptor: Kevin Donahue, PharmD

Presented at 2021 Virtual Vizient Pharmacy Network and TMC Critical Care Research Forum.

Vancomycin Dosing in High-Intensity Continuous Renal Replacement Therapy: A Retrospective Cohort Study

Nina Srour, PharmD; Chelsea Lopez, PharmD, BCCCP; Luma Succar, PharmD, BCCCP; Peter Nguyen, MD

PURPOSE

An inverse relationship exists between vancomycin serum concentrations and CRRT doses, reflected through the dialysate flow rate (DFR). There remains a lack of evidence to guide initial vancomycin dosing in the setting of high CRRT doses (i.e. DFR >30 mL/kg/h). Improved understanding of the influence of CRRT doses on vancomycin AUC/MIC has the potential to enhance antibiotic dosing and therefore efficacy. The goal of this study is to evaluate current vancomycin dosing strategies and achievement of pharmacokinetic targets in patients on high dose CRRT.

METHODS

This was a single center, retrospective cohort study of adult critically ill patients admitted to Houston Methodist between May 2019 – October 2021 and received vancomycin therapy while on high dose CRRT. High dose CRRT was defined by a DFR that was both ≥3 L/hr and >30 mL/kg/ hr. Depending on the initial vancomycin dosing strategy, patients were stratified into either the traditional (≤15 mg/ kg/day) or enhanced (>15 mg/kg/day) dosing group. The primary outcome was the difference in the rate of AUC:MIC goal (≥ 400 mg*hr/L) attainment between the two groups.

RESULTS

A total of 125 patients were included in the final analysis. The primary endpoint occurred in 74% and 54% of patients in the enhanced and traditional dosing groups, respectively (p=0.029). Therapeutic vancomycin trough levels (10–20 µg/mL) were more commonly achieved in the enhanced dosing group (66.7% vs 45%, p=0.013). As DFR rose, increasingly higher doses of vancomycin, up to 27 mg/kg/ day, were required to achieve the therapeutic targets.

CONCLUSION

This is the first study to evaluate the influence of variable CRRT doses on vancomycin AUC/MIC. Our findings suggest that vancomycin doses ≥ 15 mg/kg/day are needed to achieve early therapeutic targets in patients on high dose CRRT.

PGY2 CRITICAL CARE PHARMACY RESIDENCY

Nina Srour, PharmD

Nina graduated with her Doctorate of Pharmacy degree from the University of Colorado at Denver. She completed her PGY1 Pharmacy Residency at Houston Methodist Hospital. Following completion of her PGY2 residency, Nina has accepted a position as a pediatric critical care pharmacist at Seattle Children’s Hospital. Primary project preceptor: Chelsea Lopez, PharmD, BCCCP

Presented at 2021 Virtual Vizient Pharmacy Network and TMC Critical Care Research Forum.