M. Eduarda Silva

Statistical analysis of neuromuscular blockade response: contributions to an automatic controller calibration

Muscle relaxant drugs are currently given during surgical operations. The design of controllers for the automatic control of neuromuscular blockade benefits from an individual tuning of the controller to the characteristics of the patient. A novel approach to the characterization of the neuromuscular blockade response induced by an initial bolus at the beginning of anaesthesia is proposed. This approach is based on the statistical analysis of the data using principal components and Walsh-Fourier spectral analysis. These methods provide information about the patients dynamics, allowing the on-line autocalibration of the controller, using multiple linear regression techniques. Observed and simulated data are used to compare different approaches to the characterization of the bolus response.

A Linear Model for Estimating Propofol Individualized Dosage

Abstract In the last decades propofol became established as an intravenous agent for the induction and maintenance of both sedation and general anesthesia procedures. In order to achieve the desired clinical effects appropriate infusion rate strategies must be designed. Moreover, it is important to avoid or minimize side effects which may be associated with adverse cardiorespiratory effects and delayed recovery. Nowadays, to attain these purposes the continuous propofol delivery is usually performed through target-controlled infusion (TCI) systems whose algorithms rely on pharmacokinetic and pharmacodynamic models (Schraag, 2001). This work presents statistical models to estimate both the infusion rate and the bolus administration. The modeling strategy relies on multivariate linear models for panel data (Wooldridge, 2002), based on patient characteristics such as age, height, weight and gender along with the desired target concentration. A clinical database collected with a RugLoopII device on 84 patients undergoing ultrasonographic endoscopy under sedation-analgesia with propofol and remifentanil , (Gambus et al., 2011), is used to estimate the models (training set with 74 cases) and assess their performance (test set with 10 cases). The results obtained in the test set comprising a broad range of characteristics are satisfactory since the models are able to predict bolus and infusion rates comparable to those of TCI.

Online individualized dose estimation

The development of automated individualized drug dosage regimens, namely in general anaesthesia environment, has been a subject of interest in the last decades. The use of continuous intravenous drug administration aims at, accurately, maintaining the system at a desired target effect concentration level. Different methods have been proposed for the design of individualized dosage regimens. In this study individual drug dose design is achieved through the characterization of transient initial response induced by a bolus administration of drug. This approach is based on the statistical analysis of the data using Walsh-Fourier spectral analysis which provides information about patient dynamics, allowing the on-line drug dose design using multiple linear least squares and quantile regression technics. The proposed methodology is illustrated in the case where the effect measured on the patient corresponds to the neuromuscular blockade (NMB) level and the drug to the muscle relaxant atracurium.