A Compartmental Modelling Framework for Drug Distribution in Lean and Obese Patients in Long-Term General Anesthesia*

In personalized medicine applications such as general anesthesia, an individualised pharmacokinetic (PK) model requires to move away from the classical assumption of homogeneous drug mixing in various tissue compartments in the body. By default, these model coefficients are pre-surgery initialized from population based models as a function of age, gender, weight, height, lean body mass and do not include at this moment specific drug diffusion patterns in the fat compartment, whereas various types of fat will induce various time constants in non-lean patients. In this work, the pharmacokinetic compartmental model structure is revisited to account for non-uniform distribution of uptake/clearance time constants in patients as a nonlinear function of body mass index. Simulations are confirming expected patterns of drug distribution in the body and can account for post-anesthesia side effects up to 72 hours. The model is a novel advance in providing the control community with yet increasingly realistic patient models for closed loop control of anesthesia.