Fraser Free VPA Estimation Equation

Last year, I described how unreliable total VPA concentrations can be in ICU patients. Because of the numerous factors that affect protein binding, free VPA concentrations can be wildly different than expected based on measured total VPA concentrations. Until recently, there was no validated way of estimating free VPA concentrations in ICU patients with any reasonable degree of accuracy. Luckily, this recently changed! The Fraser Equation is the first free VPA estimation equation specifically validated in an ICU population. While not perfect, it provides a decent estimation of what free VPA concentrations will be when only a total VPA concentration is available. 

To make using the equation a little easier, I created a Shiny app to plug in the relevant values and get an estimate. I also added the 95% confidence interval described in the paper and a bell curve to visually represent the probability of the ultimate measured free VPA level. I also provide an interpretation of the predicted free VPA level, using a fairly conservative therapeutic range of 5-15 mg/L.

Disclaimer - the output of this equation is an estimate only. If using in clinical practice, use your clinical discretion when interpreting the estimated free VPA level and, ideally, directly measure a free VPA level when possible. This equation has not been tested in prospective clinical use. 

There are some known limitations, as well. The equation was originally developed with a non-zero intercept, so you may get a negative estimate. This is where the bell curve comes in handy - the true value is (obviously) higher than the estimate, and likely falls somewhere within the upper band of the bell curve. It's also possible for the equation to provide a free VPA estimate that is higher than the total VPA measurement. This is obviously not possible, and so the real free VPA value is likely either nearly equal to the total VPA level or just slightly less. 

This is my first foray into Shiny apps - feel free to try it on its native hosting platform or view the source code/contribute on Github.


  1. I believe albumin units in this calculator should be g/dL.


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