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This webcast program is based on the webinar from May 24th, 2022
 
Scientific Faculty
Host
Prof. Michel Struys
Universitair Medisch Centrum Groningen, The Netherland
 
Speakers
Prof. Hugo Vereecke
AZ Sint-Jan Brugge-Oostende, Brugge, Belgium 
 
Dr. Laura Hannivoort
University of Groningen, University Medical Center Groningen
 
Dr. Ann Rigby-Jones
University of Plymouth, Plymouth, United Kingdom
 
Target Audience: 
Physician-clinicians and residents in anaesthesia, intensive care and emergency medicine, nurse anaesthetists, intensive care nurses, …
 
Methods to promote adult active learning:
This webinar will include: 
a) Polls: to increase interactivity and engagement. Results from polls will lead to discussions points.  
b) Q&A sessions: to answer questions brought up by the host and submitted by the audience (in real time). Questions will be filtered by support staff to prioritise relevance.
 
Learning Aim 
• Learn how basic pharmacology concepts help to improve the control over the time course of anesthetic effects during induction, maintenance and recovery of anesthesia.
• Learn how to apply the bedside predicted plasma and effect-site concentrations as a diagnostic tool to optimize titration of drugs.
• Learn how in the small and large patient there’s more to drug dosing than simply using a mg/kg dosing basis
• Learn how advanced models can help reduce mental complexity in the extremes of these populations in clinical practice
• To understand the pharmacological characteristics of an ideal sedative-hypnotic agent
• To answer the question: “what is new on the market and how does it improve on existing sedative agents?”
 
After Taking Part 
This webinar will enable the participants to:
• Visualize the time course of administered drug effects better, in concordance with the applied mode of drug administration. (bolus, continuous infusion or target controlled infusion)
• Interpret the effect-site concentration of a drug as a diagnostic aid for better control over drug effect in consecutive patients.
• Appreciate factors contributing to drug dosing other then weight, such as age, different size descriptors, allometric scaling and maturation
• Understand the limitations of current sedative hypnotics, with reference to the mythical ‘ideal agent’. 
• Understand the advantages and limitations of novel sedative agents
 
Key points 
• Time to peak effect, context sensitive halftime and the time course of the effect-site concentration as diagnostic tools for an improved control over anaesthetic drug effect.
• Different size descriptors, allometry, maturation as covariates in PKPD models
• Properties of an ideal sedative-hypnotic  
• Examples of new hypnotic drugs : remimazolam; ciprofol 
 
Learning Objectives 
Knowledge to be acquired after attending to this Webinar
The participant will be able to:
• Refresh the definitions of Time to peak effect, context sensitive half time and the effect-site concentration of a drug.
• Understand how a complex PKPD model can be broken down to PKPD basics and specific covariates that contribute to drug dosing in the very small and very large patients
• Understand the advantages and limitations of novel sedative agents
 
Practical skills to be acquired after attending to this Webinar
This webinar will enable participants to:
• Visualize the timecourse of administered drug effects better
• Be able to understand and use complex PKPD models in TCI in clinical practice, or if TCI is unavailable, use the knowledge about other covariates in drug dosing in extreme populations.
• Consider if or how novel sedative-hypnotics might alter their current clinical practice. 
 
Affective skills acquired after attending to this Webinar
The participant is aware of: 
• The diagnostic value and limitations of the effect-site concentration of a drug.
• The fact that simple weight-based, mg/kg drug dosing is insufficient for adequate drug titration in patients in the extremes of size and weight.
• Sedative-hypnotic agents that are newly licensed and/or in the later stages of drug development. 
 
Recommended reading:
 
• Kuizenga MH, Vereecke HE, Struys MM: Model-based drug administration: current status of target-controlled infusion and closed-loop control. Curr Opin Anaesthesiol 2016; 29:475–81
• Absalom AR, Glen JB, Zwart GJC, Schnider TW, Struys MMRF: Target-Controlled Infusion: A Mature Technology. A&A 2016; 122:pp 70–8
• Berg JP van den, Vereecke HE, Proost JH, Eleveld DJ, Wietasch JK, Absalom AR, Struys MM: Pharmacokinetic and pharmacodynamic interactions in anaesthesia. A review of current knowledge and how it can be used to optimize anaesthetic drug administration. Br J Anaesth 2017; 118:44–57
• Hannivoort LN, Absalom AR, Struys MMRF. The role of pharmacokinetics and pharmacodynamics in clinical anaesthesia practice. Curr Opin Anaesthesiol. 2020 Aug;33(4):483-489
• Eleveld DJ, Colin P, Absalom AR, Struys MMRF. Pharmacokinetic-pharmacodynamic model for propofol for broad application in anaesthesia and sedation. Br J Anaesth. 2018 May;120(5):942-959
• Anderson BJ, Holford NH. Mechanism-based concepts of size and maturity in pharmacokinetics. Annu Rev Pharmacol Toxicol. 2008;48:303-32
• Sneyd JR, Gambus PL, Rigby-Jones AE. Current status of perioperative hypnotics, role of benzodiazepines, and the case for remimazolam: a narrative review. Br J Anaesth. 2021 Jul;127(1):41-55.
• Kilpatrick GJ. Remimazolam: Non-Clinical and Clinical Profile of a New Sedative/Anesthetic Agent. Front Pharmacol. 2021 Jul 20;12:690875. doi: 10.3389/fphar.2021.690875
• Liu Y, Yu X, Zhu D, Zeng J, Lin Q, Zang B, Chen C, Liu N, Liu X, Gao W, Guan X. Safety and efficacy of ciprofol vs propofol for sedation in intensive care unit patients with mechanical ventilation: a multi-center, open label, randomized, phase 2 trial. Chin Med J (Engl). 2021 Dec 16. doi: 10.1097/CM9.0000000000001912.
 
This webinar is supported by MSD. 
All sponsorship goes to ESAIC and no payments were made to the faculty of this webinar. Sponsor was not involved in the selection of the speakers and had no influence on the content of the lectures.
Scientific Summary: 2022-05-24

Pharmacokinetic (P.K.)/pharmacodynamic (P.D.) modelling has contributed to improving the safe and efficient use of sedative-hypnotic agents. However, PK/PD modelling is complex, and both its value and limitation must be understood to properly and safely administer anaesthetic drugs. This webinar, hosted by Prof. Michel Struys of the Universitair Medisch Centrum Groningen, discusses how to utilize PK/PD modelling and looks at newer sedatives-hypnotics on the market. 
 
The webinar begins with Prof. Hugo Vereecke from Brugge, Belgium, discussing pharmacological concepts to improve clinical practice and introducing effect-site concentration. Effect-site concentration is a theoretical drug concentration whereby a drug immediately evokes a clinical effect. It is calculated as a derivative of the plasma concentration predicted by pharmacokinetic models since the effect-site mechanism remains unexplained for many anaesthesiological drugs. As it is not directly measurable, one uses surrogate measures of effect, represented by the effect-site concentration that is mathematically related to the dose. Prof. Vereecke stresses that the clinical relevance of effects-site concentration depends on two aspects. First, it should relate to a single clinical effect, and second, it must control the time relationship between dosing and effect. However, he stresses that the first aspect is only feasible if we look at a population but not at an individual.
 
Prof. Vereecke continues by summarizing former kinetic models of I.V. anaesthetics. The relationship between dose and plasma can be described using a three-compartment model, which is sufficiently accurate for clinical models and demonstrates how theoretical effect-site concentration allows for optimal control of the time course of the effect. Once you understand the meaning of effect-site concentration, one can identify the advantages and disadvantages of different drug administration schemes used in clinical practice and improve titration technique, the timing of bolus doses, and better predict recovery time. 
 
 The second speaker, Dr. Laura Hannivoort from Groningen, Netherlands, expands on the discussion of dosing and how more advanced models will help with the induction of anaesthesia. She points out that among the covariates of dosing that include age, weight and sex, the lean body mass presents a problem with mathematical models. As a patient becomes more obese, the lean body mass will decrease, increasing the difficulty of dosing drugs. She discusses allometric scaling, a method to describe variations in volumes, metabolic rates, and rate constants in different species as well as within-species modelling. Furthermore, advanced PK/PD modelling can utilize different weight scales. However, she notes that it's not one-size-fits-all, and allometry can fix most problems, but not all.
 
The final speaker, Dr. Ann Rigby-Jones from Plymouth, the United Kingdom, discusses new drugs on the market and improvements to existing sedative agents. She Begins by reviewing the pharmacological characteristics of an ideal sedative-hypnotic agent as well as the limitations of existing agents. Although no one drug corresponds to all desirable properties, she points out that the properties one looks for are determined by the intended use and not all properties are equally important. 
 
Dr. Ann Rigby-Jones concludes by reviewing two new drugs, Remimazolam and Ciprofol and refers to numerous studies comparing these drugs to the existing ones on the market, namely propofol and midazolam. 
Scientific Summary: 2022-05-24

Pharmacokinetic (P.K.)/pharmacodynamic (P.D.) modelling has contributed to improving the safe and efficient use of sedative-hypnotic agents. However, PK/PD modelling is complex, and both its value and limitation must be understood to properly and safely administer anaesthetic drugs. This webinar, hosted by Prof. Michel Struys of the Universitair Medisch Centrum Groningen, discusses how to utilize PK/PD modelling and looks at newer sedatives-hypnotics on the market. 
 
The webinar begins with Prof. Hugo Vereecke from Brugge, Belgium, discussing pharmacological concepts to improve clinical practice and introducing effect-site concentration. Effect-site concentration is a theoretical drug concentration whereby a drug immediately evokes a clinical effect. It is calculated as a derivative of the plasma concentration predicted by pharmacokinetic models since the effect-site mechanism remains unexplained for many anaesthesiological drugs. As it is not directly measurable, one uses surrogate measures of effect, represented by the effect-site concentration that is mathematically related to the dose. Prof. Vereecke stresses that the clinical relevance of effects-site concentration depends on two aspects. First, it should relate to a single clinical effect, and second, it must control the time relationship between dosing and effect. However, he stresses that the first aspect is only feasible if we look at a population but not at an individual.
 
Prof. Vereecke continues by summarizing former kinetic models of I.V. anaesthetics. The relationship between dose and plasma can be described using a three-compartment model, which is sufficiently accurate for clinical models and demonstrates how theoretical effect-site concentration allows for optimal control of the time course of the effect. Once you understand the meaning of effect-site concentration, one can identify the advantages and disadvantages of different drug administration schemes used in clinical practice and improve titration technique, the timing of bolus doses, and better predict recovery time. 
 
 The second speaker, Dr. Laura Hannivoort from Groningen, Netherlands, expands on the discussion of dosing and how more advanced models will help with the induction of anaesthesia. She points out that among the covariates of dosing that include age, weight and sex, the lean body mass presents a problem with mathematical models. As a patient becomes more obese, the lean body mass will decrease, increasing the difficulty of dosing drugs. She discusses allometric scaling, a method to describe variations in volumes, metabolic rates, and rate constants in different species as well as within-species modelling. Furthermore, advanced PK/PD modelling can utilize different weight scales. However, she notes that it's not one-size-fits-all, and allometry can fix most problems, but not all.
 
The final speaker, Dr. Ann Rigby-Jones from Plymouth, the United Kingdom, discusses new drugs on the market and improvements to existing sedative agents. She Begins by reviewing the pharmacological characteristics of an ideal sedative-hypnotic agent as well as the limitations of existing agents. Although no one drug corresponds to all desirable properties, she points out that the properties one looks for are determined by the intended use and not all properties are equally important. 
 
Dr. Ann Rigby-Jones concludes by reviewing two new drugs, Remimazolam and Ciprofol and refers to numerous studies comparing these drugs to the existing ones on the market, namely propofol and midazolam. 
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