Physiological Modeling of Concentration-Effect Relationship for Nondepolarizing Neuromuscular Blocking Drugs

This paper reports modeling of physiological processes of neuromuscular transmission considering effects of nondepolarizing neuromuscualr blocking drugs (NDNBs) used during general anesthesia. NDNBs are considered to act by interacting with acetylcohine receptors located at pre- and post-junctional sites. This paper proposes an extension of the standard model of synaptic depression used in the field of neuroscience to describe the pre-junctional effect of NDNBs. The extended model is then combined with a previously proposed model of the post-junctional effect to simulate the whole process of neuromuscular transmission. The derived model can be used to predict pharmacologic relationship between the drug concentration and its actual effect of NDNBs. Specifically, the model firstly enables the estimation of Post-tetanic Count (PTC), a clinically used monitoring measure for deep neuromuscular blockade (NMB). The effectiveness of the derived model is discussed by comparing simulation results with clinical data obtained from a patient undergoing a surgical operation.