Local identifiability and sensitivity analysis of neuromuscular blockade and depth of hypnosis models

• Published in: Computer methods and programs in biomedicine Vol. 113; no. 1; pp. 23 - 36
• Main Authors: Silva, M.M, Lemos, J.M, Coito, A, Costa, B.A, Wigren, T, Mendonça, T
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ireland Ltd 01.01.2014; Elsevier
• Subjects: Anesthesia; Anesthesia, General; Biological and medical sciences; General pharmacology; Humans; Hypnosis; Identifiability; Internal Medicine; Medical sciences; Minimally parameterized models; Models, Biological; Neuromuscular Blockade; Other; Pharmacokinetics; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions; Pharmacology. Drug treatments; PK/PD models; Sensitivity; Wiener models; neuromuscular blockade; Minimally parameterized models; NMB; Identifiability; bispectral index; EEG; pharmacodynamics; PK/PD models; Wiener models; TOF; MPP; BIS; electroencephalogram; minimally parameterized parsimonious; prediction error method; Sensitivity; PD; depth of hypnosis; pharmacokinetics; PEM; Anesthesia; PK; DoH; train-of-four; Drug; Input output; Sensitivity analysis; Input signal; Parameterization; Modeling; Standards; Optimization; Pharmacokinetics; Dose; Medical application; Singular value decomposition
• ISSN: 0169-2607; 1872-7565; 1872-7565
• DOI: 10.1016/j.cmpb.2013.07.020

Abstract This paper addresses the local identifiability and sensitivity properties of two classes of Wiener models for the neuromuscular blockade and depth of hypnosis, when drug dose profiles like the ones commonly administered in the clinical practice are used as model inputs. The local parameter identifiability was assessed based on the singular value decomposition of the normalized sensitivity matrix. For the given input signal excitation, the results show an over-parameterization of the standard pharmacokinetic/pharmacodynamic models. The same identifiability assessment was performed on recently proposed minimally parameterized parsimonious models for both the neuromuscular blockade and the depth of hypnosis. The results show that the majority of the model parameters are identifiable from the available input–output data. This indicates that any identification strategy based on the minimally parameterized parsimonious Wiener models for the neuromuscular blockade and for the depth of hypnosis is likely to be more successful than if standard models are used.