title: Local identifiability and sensitivity analysis of neuromuscular blockade and depth of hypnosis models.
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.
authors.affiliation: Departamento de Matemática, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre, 4169-007 Porto, Portugal; Division of Systems and Control, Department of Information Technology, Uppsala University, Box 337, SE-751 05 Uppsala, Sweden; Center for Research and Development in Mathematics and Applications (CIDMA), Universidade de Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal. Electronic address: margarida.silva@fc.up.pt.
authors.forename: M M
authors.initials: MM
authors.lastname: Silva
authors.forename: J M
authors.initials: JM
authors.lastname: Lemos
authors.forename: A
authors.initials: A
authors.lastname: Coito
authors.forename: B A
authors.initials: BA
authors.lastname: Costa
authors.forename: T
authors.initials: T
authors.lastname: Wigren
authors.forename: T
authors.initials: T
authors.lastname: Mendonça
mesh_terms: D000768:Anesthesia, General; D006801:Humans; D006990:Hypnosis; D008954:Models, Biological; D019148:Neuromuscular Blockade; D010599:Pharmacokinetics
keywords: Anesthesia; BIS; DoH; EEG; Identifiability; MPP; Minimally parameterized models; NMB; PD; PEM; PK; PK/PD models; Sensitivity; TOF; Wiener models; bispectral index; depth of hypnosis; electroencephalogram; minimally parameterized parsimonious; neuromuscular blockade; pharmacodynamics; pharmacokinetics; prediction error method; train-of-four