Physiological Modeling of Hemodynamic Responses to Sodium Nitroprusside

Background: Computational modeling of physiology has become a routine element in the development, evaluation, and safety testing of many types of medical devices. Members of the Food and Drug Administration have recently published a manuscript detailing the development, validation, and sensitivity testing of a computational model for blood volume, cardiac stroke volume, and blood pressure, noting that such a model might be useful in the development of closed-loop fluid administration systems. In the present study, we have expanded on this model to include the pharmacologic effect of sodium nitroprusside and calibrated the model against our previous experimental animal model data. Methods: Beginning with the model elements in the original publication, we added six new parameters to control the effect of sodium nitroprusside: two for the onset time and clearance rates, two for the stroke volume effect (which includes venodilation as a “hidden” element), and two for the direct effect on arterial blood pressure. Using this new model, we then calibrated the predictive performance against previously collected animal study data using nitroprusside infusions to simulate shock with the primary emphasis on MAP. Root-mean-squared error (RMSE) was calculated, and the performance was compared to the performance of the model in the original study. Results: RMSE of model-predicted MAP to actual MAP was lower than that reported in the original model, but higher for SV and CO. The individually fit models showed lower RMSE than using the population average values for parameters, suggesting the fitting process was effective in identifying improved parameters. Use of partially fit models after removal of the lowest variance population parameters showed a very minor decrement in improvement over the fully fit models. Conclusion: The new model added the clinical effects of SNP and was successfully calibrated against experimental data with an RMSE of <10% for mean arterial pressure. Model-predicted MAP showed an error similar to that seen in the original base model when using fluid shifts, heart rate, and drug dose as model inputs.