Pharmakokinetische/pharmakodynamische Modelle für Inhalationsanästhetika

Abstract

Pharmacokinetic models can be differentiated into two groups: physiological-based models and empirical models. Traditionally the pharmacokinetics of volatile anaesthetics are described using physiological-based models together with the respective tissue-blood distribution coefficients. The compartments of the empirical model have no anatomical equivalents and are merely the product of the mathematical procedure for parameter estimation. The end expiratory concentration of volatile anaesthetics is approximately equal to the arterial concentration and, therefore, the description of the transition between plasma and effect site for volatile anaesthetics plays a central role. The most important parameter here is the k(e0) value which is a time constant and describes the time delay for the transition from the central compartment to the calculated effect compartment. The k(e0) values for sevoflurane and isoflurane are the same but the concentration balance between the end-tidal concentration and the effect compartment occurs twice as quickly with desflurane. In clinical practice volatile anaesthetics are normally combined with N(2)O and/or opioids. This results in an additive interaction between volatile anaesthetics and N(2)O but a synergistic interaction of volatile anaesthetics with opioids. However, there are relatively few investigations on the interactions between the clinically widely used combination of volatile anaesthetics, N(2)O and opioids.

Brief review: Theory and practice of minimal fresh gas flow anesthesia

“…Multiple studies have shown higher ke0 values for desflurane than for sevoflurane and isoflurane. 42,43 This means that an increase or decrease in Etaa using desflurane will result in a more rapid change in the depth of anesthesia. Bispectral index measurements and ke0 values derived from pharmacokinetic modelling do not provide a full appreciation of inhalational agent equilibration.…”

Perbandingan Nilai SpO2 dan EtCO2 pada Anestesi Umum dengan Teknik Low Flow dan High Flow

“…Untuk mengatasi hal tersebut, aliran gas segar (oksigen) harus dapat mencukupi kebutuhan oksigen basal, tidak ada kebocoran pada sirkuit anestesi, dan alat penyerap CO 2 harus berfungsi baik agar konsentrasi CO 2 dalam udara inspirasi tidak melebihi nilai ambang yang diperkenankan sebesar 0,2%. 9 Teknik low flow anesthesia pada penelitian ini mengikuti guideline yang diberikan oleh Foldes 10 atau Virtue, 11 yaitu pada fase awal selama 10-15 menit digunakan FGF yang tinggi. Foldes 10 telah merekomendasikan pengaturan oksigen 2 L/menit dan N 2 O 3 L/menit selama 10 menit untuk menjamin denitrogenisasi yang adekuat.…”

“…Terakhir, jika flow diturunkan terlalu cepat ke nilai yang sangat rendah, defisiensi volume gas tidak dapat dihindarkan sehingga dapat mengakibatkan ventilasi yang tidak adekuat. 1,9 Sistem rebreathing dapat dipergunakan dengan cara yang berbeda dan jika digunakan FGF yang sama dengan minute volume pasien maka peran rebreathing akan sia-sia. Hampir sepenuhnya udara yang diekspirasikan akan dilepaskan keluar sistem sebagai kelebihan gas melalui katup APL.…”

Two different approaches for pharmacokinetic modeling of exhaled drug concentrations

“…The higher the blood/gas partition coefficient, the more soluble is the anaesthetic in blood compared to air and the more it binds to lipids and proteins in the blood. If an anaesthetic has a high Ostwald coefficient, then a large amount of it will have to be taken up in the body's blood before being passed on to the fatty (lipid) tissues of the brain where it can exert its effect10.…”

“…The blood/gas partition coefficient is widely used for the PK description of volatile anaesthetics10. However, for PK modelling the coefficient could only be used if the partial pressure in both compartments is at equilibrium.…”