Recirculatory modeling in man using Indocyanine green

Abstract

Titration to effect is the most important action anesthesiologists use to assure adequacy of anesthesia and safeguard their patients from serious side effects. For a proper titration to effect the anesthesiologist takes into consideration the historical response to a given dose to estimate the response to a future dose. During induction of anesthesia the anesthesiologist is still unaware of the dose-response relationship of the patient. Because for many agents the knowledge of the covariates of influence on the induction dose-response relationship is lacking, many patients experience serious side effects during induction of anesthesia, often in the form of hemodynamic depression. In this thesis light is shed on the pharmacology of induction of anesthesia. The front-end kinetics are complex and often flow dependent. The observations in this thesis teach us that the modeling of the dose-concentration-effect relation is insufficiently described by compartmental modeling and improves by applying recirculatory PK-PD modeling. The anesthetic propofol and neuromuscular blocking agent rocuronium are described, using recirculatory modeling. (Non)invasive ICG measurement is used extensively in recirculatory modeling but is less well suited for hemodynamic monitoring. Noninvasive measurement of the ICG plasma disappearance rate proved adequate.