Vancomycin AUC values estimated with trough-only data: Accuracy in an adult academic medical center population.

PURPOSE: Vancomycin area under the concentration-time curve (AUC) can be calculated using steady-state serum peak and trough concentrations; however, compared to traditional trough-only monitoring, this approach requires an additional blood sample. Recently published data demonstrated vancomycin AUC estimations using trough-only data with a volume of distribution (Vd) model incorporating age and actual body weight were reasonably accurate and precise in a veteran population. This study sought to extend these methods to a Mayo Clinic adult population. METHODS: A retrospective, observational cohort of adult patients with documented steady-state vancomycin peak and trough concentrations was evaluated. Vancomycin AUCs were estimated using trough-only data, and 4 Vd models were assessed for accuracy and precision. Estimated AUCs were compared to AUCs calculated using 1-compartment intermittent infusion equations and steady-state peak and trough ("peak-trough") data. RESULTS: The study population (N = 95) was 46% female, with a median age of 59 years and a median weight of 97 kg. Using the VancoPK equation Vd = 0.29 (age in y) + 0.33 (actual weight in kg) + 11, the mean peak-trough and estimated trough-only AUC were 533 and 534, respectively, with a correlation of 0.936. The root mean square error was 47.7, meaning about 95% of AUCs were within 95 mg · h/L of peak-trough AUCs. CONCLUSIONS: Accuracy and precision of Vancomycin AUC estimations using trough-only data and the described Vd model were demonstrated in a Mayo Clinic cohort. Targeting an estimated AUC of 500 mg · h/L using the VancoPK model would likely result in an actual AUC within 400 to 600 mg · h/L.

Accuracy of vancomycin AUC values estimated with trough-only data in a veteran population.

PURPOSE: The purpose of this study was to evaluate the accuracy and precision of estimating area under the curve (AUC) values using only vancomycin trough concentrations versus both peak and trough values derived from applying 4 different volume of distribution (Vd) models in a veteran population. METHODS: This retrospective, observational study was performed from July 2021 to April 2022 using data from 5 Veterans Affairs hospitals across the US. AUC values for a total of 259 veterans were included in the analysis, with 10 excluded after pooling of data. Trough-only AUC values were calculated with 1-compartment intermittent infusion equations (Sawchuk-Zaske equations) using age- and weight-adjusted Vd values derived from an online calculator (VancoPK) or fixed Vd values specified by 3 comparator models. RESULTS: The mean population peak-trough AUC was 496 (range, 266-886). Of the 4 Vd models evaluated, the VancoPK model was the most accurate and precise, yielding a mean trough-only AUC of 491, with a correlation of 0.925; the root mean square error was 41, meaning that approximately 95% of the trough-only AUCs were within 82 points of values calculated using AUC peak-trough couplets. CONCLUSION: A trough-only AUC estimation approach has many advantages over a peak-trough approach. The equation Vd = 0.29 (age) + 0.33 (actual BW in kg) + 11 provided accurate and precise AUC estimates with trough-only data when applied to pharmacokinetic equations in a veteran population.

Vancomycin area under the curves estimated with pharmacokinetic equations using trough-only data.

WHAT IS KNOWN AND OBJECTIVE: The revised vancomycin monitoring guidelines recommend targeting an area under the curve (AUC) of 400-600 mg*hr/L for serious methicillin-resistant Staphylococcus aureus (MRSA) infections. An AUC can be measured by checking a peak and trough concentration at steady state; however, this requires obtaining an additional blood sample. The most practical way to perform AUC-guided dosing is by estimating an AUC from a steady-state trough. The purpose of this study was to compare AUCs estimated from trough-only data to AUCs calculated from peak and trough concentrations. METHODS: Steady-state peak and trough data were collected from an open-access clinical calculator VancoPK.com. Patients were included who had (1) peaks drawn ≥60 min after the end of infusion, (2) peak and trough levels drawn ≥4 h apart and (3) troughs drawn ≤4 h early or late. The population was randomized and divided into a model group and test group. A population equation for vancomycin volume of distribution (Vd) was derived and compared to other general adult Vd models. Accuracy and precision of estimated AUCs were measured with bias, root mean square error (RMSE) and Lin's concordance correlation. RESULTS AND DISCUSSION: A total of 2,500 adult patients were included in the model group and 1,843 were included in the test group. The derived Vd equation, Vd (L) = 0.29(age) +0.33(total BW in kg) +11, produced accurate and precise AUC estimates from trough-only data. The mean actual AUC and estimated AUC were 504 and 503, respectively, with a correlation of 0.926. The RMSE between estimated and actual AUCs was 47.7, meaning that over 95% of estimated AUCs were within 100 points of actual AUCs with the study's Vd model. Other Vd models performed well for certain types of patients, depending on their body weight and age. WHAT IS NEW AND CONCLUSION: There is limited evidence from large, robust populations regarding how to estimate Vd for general adult patients. Accuracy and precision of estimated AUCs depend on the applied population Vd model. The Vd model from the present study can be used for AUC-guided dosing with trough-only data which requires less blood work than peak-trough monitoring. AUC calculations are practical with the use of open-access websites.

Initiation of direct oral anticoagulants versus warfarin for venous thromboembolism: impact on time to hospital discharge.

The objective of this project was to compare the time from initiation of oral anticoagulation to hospital discharge between warfarin and direct oral anticoagulants (DOACs) for the treatment of acute venous thromboembolism (VTE). This retrospective observational study was done at a single VA medical center. A total of 107 patients were included, with 42 patients (39%) in the DOAC group, which included rivaroxaban, dabigatran, and apixaban, and 65 patients (61%) in the warfarin group. Variables collected through chart review included comorbid conditions, time from initiation of oral anticoagulation to discharge, emergency department (ED) visits and readmission within 30 or 90 days, and bleeding events. The DOAC group had a shorter time to discharge compared to the warfarin group (28 vs. 114 h, p < 0.001). There were similar 30 and 90-day hospital readmission rates and/or ED visits for DOACs (23.8 and 33.3%) compared to warfarin (18.5 and 30.8%), including those related to bleeding of any severity (11.9% for DOACs vs. 9.2% for warfarin; p = 0.75). There was one major bleeding event in the DOAC group and two in the warfarin group. The use of DOACs for the treatment of acute VTE in hospitalized patients was associated with shorter time to hospital discharge when compared to warfarin.

A Comparison Between Dabigatran and Warfarin on Time to Elective Cardioversion.

OBJECTIVE: To evaluate the use of dabigatran versus warfarin on time to elective direct current cardioversion (DCCV). METHODOLOGY: This retrospective observational study was conducted at a single Veterans Affairs hospital in the Southwestern region of the U.S. Patients with atrial fibrillation or atrial flutter who were initiated on either warfarin or dabigatran prior to DCCV were reviewed. The time to cardioversion was compared between warfarin and dabigatran, as well as costs of therapy, rescheduling rates, and adverse events. RESULTS: Out of 258 patients reviewed, a total of 68 patients were included in the study. All patients were male with an average age of 68 years (SD=8.6). A total of 38 patients (56%) received dabigatran and 30 patients (44%) received warfarin. Patients in both groups had a median CHADS2 and HASBLED score of 2. The median number of days to cardioversion was 34.5 (range=22-148) for dabigatran compared to 66.5 (range=32-183) for warfarin (p<0.01). Total costs of anticoagulation for warfarin averaged $183.50 (SD=95.02) from initiation of anticoagulation to the end of the required four week period following cardioversion, whereas dabigatran costs averaged $193.20 (SD=59.38). Three patients (10%) in the warfarin group had DCCV rescheduled compared to none in the dabigatran group. There was one bleeding event in the warfarin group and no thromboembolic events in either group. CONCLUSION: The use of dabigatran prior to elective DCCV results in a significant decrease in number of days from initiation of anticoagulation to cardioversion as compared to warfarin, with a minor increase in total costs.

Evaluation of initial heparin infusion rates for a high-dose protocol.

Unfractionated heparin is widely used as anticoagulant therapy for thrombotic disease. However, determining appropriate dosing by intravenous infusion is highly variable in practice. Multiple standardized protocols have been adopted, including a weight-based nomogram entailing a loading dose of 80 U/kg, followed by an initial infusion rate of 18 U/kg/h. In some instances, 18 U/kg/h has resulted in supratherapeutic activated partial thromboplastin time (aPTT). This study aimed to determine if an initial heparin infusion rate of 14 U/kg/h per a high-dose protocol achieved therapeutic anticoagulation more rapidly than 18 U/kg/h. A retrospective chart review performed at a Veterans Health Administration facility located in the southwestern U.S. identified 129 patients hospitalized from January 2009 to August 2011 receiving a high-dose protocol for heparin with an initial infusion rate of 14 or 18 U/kg/h. The proportion of patients achieving subtherapeutic, at goal, or supratherapeutic aPTT on two subsequent mornings was determined. Time to reach therapeutic aPTT was assessed with a multivariable generalized linear model. Patients provided 18 U/kg/h for heparin anticoagulation therapy experienced elevated aPTT values initially. Also, these patients generally took 1.41 times longer to reach therapeutic aPTT than patients receiving 14 U/kg/h [estimate = 0.34, 95% CI 0.11, 0.57; p < 0.01]. Larger body mass index led to increased time to reach therapeutic anticoagulation. This study's results suggest that patients may benefit from receiving an initial heparin infusion rate of 14 U/kg/h over 18 U/kg/h. Decreasing the time to therapeutic aPTT may further help reduce workload from monitoring and dose titrations.