Hi I am new to using the pulse engine. I am trying to test the limits and extremes of the engine by giving 10mg boluses of epinephrine or 500 mg boluses of fentanyl expecting large responses but when I give them it only changes the variables by 20% and then quickly returns to normal. I’m using the pre created substances that come with the engine and even when I change the scalar values to 1 it does the same. Thank you in advance
Good Timing! Yes, we have been evaluating the drug model and its deficits in recent weeks. There are a couple of problems that I have found:
- We were overriding some respiratory effects based on a sedation level. These caused an all or nothing response for any drug with a sedation effect.
- I believe our EC50 values are too high in the substance files, which is causing the drugs to have a strong effect initially (when the bolus first occurs) then it fades rapidly as the drug disperses through the body.
My conclusion now is that the PK (plasma concentration and diffusion behavior) is well-validated and correct. However, the PD effects model is too simplistic. When we validated PD, we did it with the expected dose and got a good response; however, the model is not robust enough to handle a wide range of doses.
It should also be noted that we do not have an intoxication model. Giving an overdose just moves to the ceiling effect listed in the drug file, but will not cause cardiac arrest, respiratory distress, etc that may be expected during an overdose.
I have been working on fixing #1 on the above list. You can find the changes on the drug_sedation branch if you are interested. It is early days and I have not tested this extensively. You can also try to reduce the EC50 values and see if that provides a better response.
We hope to make some significant improvements to the PD model in the fall of this year.
I am happy to discuss further.