It’s easy to use and makes dosing easier. The graphing of the pharmacokinetics, based on actual or predicted values, helps us make better dosing decisions.
Opportunity
The antibiotic vancomycin is widely used in inpatient settings to treat and prevent bacterial infections—but is difficult to administer precisely. Supra-therapeutic levels of vancomycin caused by overdosing can lead to acute kidney injury (AKI) and longer inpatient stays. Conventional methods of selecting vancomycin dosage are based solely on weight, or rely on manual data entry into spreadsheets or other offline calculators.
Solution
Until April 2019, Covenant HealthCare was manually calculating vancomycin dosing using spreadsheet calculations developed in-house. These calculations were based on measuring trough levels rather than area under the curve (AUC) dosing. After the benefits of using AUC dosing were documented in multiple studies, the health system sought a Bayesian software solution that would enable them to quickly and accurately calculate AUC. They initially rolled out the InsightRX Nova platform to four of its 11 hospitals: Mackinaw, Cooper, Harrison, and Hamilton. Because of the ease of use of the InsightRX platform, staff at Covenant were able to self-onboard.
What I like about InsightRX is how all relevant information was available on one screen—that was a definite benefit. We can see what’s happening with drug kinetics, what’s currently happening with patients, and what we can expect to happen based on the present clinical situation.
Impact
Covenant launched the InsightRX platform in early 2019. In the first four months of the platform’s launch (April 23, 2019, to August 23, 2019), InsightRX was used to select vancomycin doses for a cohort of 301 patients at Covenant (the “post- InsightRX cohort”). Compared to the pre-InsightRX cohort of 307 patients, the percent of patients with on-target vancomycin levels in the first 24 hours increased from 24% to 59%. The incidence of severe AKI was reduced by 54%, from 15.8% to 7.2%. Based on recent estimates of length of stay (LOS) and costs for patients with and without severe AKI, the use of InsightRX reduced LOS by 68 patient-days in this cohort, with an estimated cost reduction of $203,716 as derived from the literature.1 Extrapolating the results for this cohort to a full year leads to an estimated annual cost reduction of $611,147.
Results
Using InsightRX increases AUC24 on-target rate in the first 24 hours from 24% to 59%
The recent consensus guidelines recommend achieving an AUC24 of 400-600 mg*h/L within the first 24-48 hours.2
In the post-InsightRX cohort, 59% of patients achieved an AUC24 of 400-600 mg*h/L within the first 24 hours, compared to 24% in the pre- InsightRX cohort. In part, this was likely due to more optimal initial dosing, including increased use of loading doses by Covenant pharmacists, who were able to use InsightRX to see predicted exposures prior to giving empiric doses. At 48 hours and after, 50% of patients in the post- InsightRX cohort were on-target, compared to 40% in the pre-InsightRX cohort.
Figure 1 shows the average AUC24 over an encounter and the proportion of patients in each AUC24 category during the first day (first 24 hours), the second day (hours 24 through 48), and the third day onwards (48 hours plus) over the course of treatment.
Using InsightRX reduces the rate of stage 2 or 3 AKIs from 15.8% to 7.2%
AKI class was calculated based on serum creatinine (SCr) values over time using the Kidney Disease: Improving Global Outcomes (KDIGO) method. According to guidelines published by the KDIGO working group3, AKI can be diagnosed if any of the following conditions is present:
- an increase in SCr of at least 0.3 mg/dl
- an increase in SCr to 1.5 times the baseline SCr (defined here as the patient’s first SCr measurement, taken prior to vancomycin administration), or
- urine volume 0.5 ml/kg-h over 6 hours.
AKI can be further separated, with stage 2 describing patients with an increase in SCr over baseline of 0.5 mg/dl or by a factor of 2, and with stage 3 describing patients with an increase in SCr over baseline by a factor of 3 or SCr greater than 4.0 mg/dl. (Urinary output was not considered in staging in this analysis.)
Severe AKI events (stage 2 or 3) occurred in 7.2% of patients in the post-InsightRX cohort, compared to 15.8% in the pre-InsightRX cohort, a reduction of 54%.
Figure 2 shows the proportion of patients in each cohort by AKI class.
Using InsightRX reduces AUC24 variation from 45% to 28%
AUC describes patient exposure to the drug. A daily AUC (AUC24) of at least 400 mg*h/L is typically targeted, and an AUC24 above 700 mg*h/L is associated with significantly increased incidence of nephrotoxicity.4,5
The coefficient of variation (CV) decreased from 32.3% in the pre-InsightRX cohort to 22.0% in the post-InsightRX cohort, a reduction of 32%.
Figure 3 shows the average AUC24 over an encounter, with the shaded region indicating a target AUC24 range of 400-600 mg*h/L
Conclusions
The positive results for Covenant HealthCare — and the impact on patient safety — are clear. Beyond the intrinsic value of precision dosing, InsightRX’s ability to measure and report on metrics can help groups like Covenant further improve clinical and financial outcomes. This experience has also stimulated the development of InsightRX’s analytics and reporting platform, Apollo. As additional data are collected, Covenant envisions building on these initial precision dosing successes.