…perché i ciliegi tornassero in fiore”
(Fabrizio de André, Un medico)
TABLE OF CONTENTS
Abstract/Riassunto pag. 6 Abbreviations pag. 7 Chapter 1: Introduction pag. 8 Chapter 2: Propofol pag. 102.1 Historical background: the use of propofol in human and veterinary anaesthesia
pag. 10
2.2 Chemistry pag. 12
2.3 Metabolism pag. 13
2.4 Clinical use of propofol in dogs pag. 14
2.4.1 Propofol induction dose and effect of premedication on
induction doses and infusion rates pag. 15
2.4.2 Respiratory effects of propofol pag. 17
2.4.3 Hemodynamic effects of propofol pag. 18
2.4.4 Recovery pag. 19
2.4.5 The use of propofol in particular patients and procedures pag. 20
2.4.6 Non hypnotic properties pag. 21
2.5 Unwanted effects pag. 21
Chapter 3:
Pharmacokinetics pag. 24
3.1 Introduction pag. 24
3.2 Definitions pag. 24
Exposure-time profile pag. 24 Volume of distribution pag. 26
Absorption pag. 26
Bioavailability pag. 27
Disposition pag. 27
Distribution pag. 27
Blood-brain barrier pag. 28
Protein-binding pag. 29
Elimination pag. 30
Excretion pag. 32
Clearance pag. 32
First-order elimination pag. 34 Zero-order elimination pag. 35 Elimination half-life pag. 36
3.3 Pharmacokinetic models pag. 36
3.4 Compartmental analysis pag. 38
3.4.1 One compartment open model pag. 38
3.4.2 Two compartment open model pag. 39
3.4.3 Three compartment open model pag. 42
3.4.4 Drug hysteresis and effect compartment pag. 46
3.4.5 A critique of pharmacokinetic compartmental analysis pag. 47
3.5 Physiological models pag. 49
3.5.1 Recirculatory PK pag. 49
3.6 Population PK pag. 51
3.7 Pharmacokinetic concepts for TCI anaesthesia pag. 52
3.7.1 Effect-site equilibration time pag. 55
3.7.2 Propofol dosing regimens based on clinical pharmacokinetics pag. 56
3.7.3 Drug concentration decay pag. 58
3.7.4 Context Sensitive Half Time and Context Sensitive Decrement Time pag. 58
3.8 Pharmacokinetics of propofol pag. 61
3.8.1 Pharmacokinetic parameters of propofol in dogs pag. 61
3.8.2 Pharmacokinetic characteristics of propofol in dogs pag. 63
Chapter 4:
Pharmacodynamics pag. 66
4.1 Introduction pag. 66
4.2 Definitions of drug affinity, efficacy and potency pag. 67
4.3 Drug specificity and selectivity pag. 68
4.4 Dose-response and log dose-response curves pag. 69
4.5 Pharmacodynamic characteristics of propofol: mode of action pag. 70
4.6 Pharmacokinetic/ Pharmacodynamic integration pag. 71
4.7 Plasmatic and effect site concentrations for clinical end points pag. 74
Chapter 5:
Clinical application of TIVA and TCI systems pag. 76
5.1 Introduction pag. 76
5.2 Techniques used to administer TIVA pag. 77
5.3 Anaesthetic infusion systems pag. 79
5.4.1 TCI and patients covariates pag. 85
5.5 Propofol TIVA and TCI systems in Veterinary Medicine pag. 86
5.5.1 Review of the literature pag. 86
5.5.2 Development of a target controlled infusion system for
propofol in dogs: determination of pharmacokinetic parameters pag. 88
5.5.3 Determination of an optimum target concentration for the induction
and maintenance of anaesthesia pag. 89
Chapter 6:
CLINICAL STUDY pag. 91
6.1 Introduction pag. 91
6.2 Materials and methods pag. 92
6.2.1 Animals pag. 92
6.2.2 TCI equipment pag. 92
6.2.3 Anaesthetic protocol pag. 93
6.2.4 Data handling and statistic analysis pag. 95
6.3 Results pag. 96
6.3.1 Covariates analysis pag. 98
6.4 Discussion pag. 101
6.5 Conclusions pag. 107
REFERENCES pag. 108
