In-silico analysis of closed-loop vasopressor control of phenylephrine versus norepinephrine

We have previously demonstrated in in-silico, pre-clinical animal models, and finally human clinical studies the ability of a novel closed-loop vasopressor titration system to manage norepinephrine infusion rates to keep mean arterial blood pressure in a very tight range, reduce hypotension time and severity, and reduce overtreatment. We hypothesized that the same controller could, with modification for pharmacologic differences, suitably titrate a lower-potency longer duration of action agent like phenylephrine. Using the same physiologic simulation model as was used previously for in-silico testing of our controller for norepinephrine, we first updated the model to include a new vasopressor agent modeled after phenylephrine. A series of simulation tests patterned after our previous norepinephrine study was then conducted, this time using phenylephrine for management, in order to both test the system with the new agent and allow for comparisons between the two. Hundreds of simulation trials were conducted across a range of patient and environmental variances. The controller performance was characterized based on time in target, time above and below target, coefficient of variation, and using Varvel's criteria. The controller kept the simulated patients' MAP in target for 94% of management time in the simple scenarios and more than 85% of time in the most challenging scenarios. Varvel criteria were all under 1% error for expected pharmacologic responses and were consistent with those established for norepinephrine in our previous studies. The controller was able to acceptably titrate phenylephrine in this simulated patient model consistent with performance previously seen for norepinephrine after adjusting for the anticipated differences between the two agents.