Context-sensitive half-life

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The context-sensitive half-life is a pharmacological term that is used in particular in anesthesiology in connection with the infusion of painkillers and anesthetics . It is defined as the time it takes for the plasma concentration of an active substance to drop by half after continuous infusion of a defined duration (“context”).

background

The concept of the context-sensitive half-life was introduced in 1992 by MA Hughes and, in addition to elimination, also takes into account, in particular, the influence of the redistribution processes that begin with the administration of medication on the decrease in concentration. The authors simulated these processes in two- and three-compartment models.

Almost all anesthetics and opioids are distributed in peripheral compartments (“storage” in tissues and organs). The extent and speed of distribution and redistribution into the central compartment (= plasma), taking into account the duration of the supply, determine the context-sensitive half-life, which is therefore also an indirect measure of the accumulation (accumulation) of an active substance.

The context-sensitive half-life must be differentiated from the elimination half-life , also known as the terminal (plasma) half-life, which is determined from the plasma level-time curve in the elimination phase after the distribution equilibrium has been reached.

meaning

The term plays a role in anesthesiology . Medication is continuously administered during anesthesia . For the class of active substances called opioids that are used in this process, knowledge of the context-sensitive half-lives is important in order to better control the anesthesia. The parameter is a measure of the cumulative potency, controllability of the anesthesia and an estimate of the time to wake up.

A generalization of the concept is the significant decrease in concentration ( relevant decrement time ), in which not only the time to halving the active ingredient concentration as with the context-sensitive half-life, but also other percentage decreases in concentration are described. These are often of greater clinical relevance, for example for waking up from anesthesia.

In anesthesiology, the concept of multi-compartment models using the associated pharmacokinetic model parameters is used in practice with Target Controlled Infusion (TCI), a process for computer-aided infusion using syringe pumps. The therapeutically targeted drug concentrations are achieved by controlling the infusion rate.

Half-lives (half-lives) of some opioids used anesthetically
Active ingredient Context-sensitive half-life (minutes) Note on the context-sensitive HWZ Elimination half-life
Infusion time 120 minutes Infusion time 240 minutes
Fentanyl 120 263 Increasing steadily,
risk of accumulation 		3–12 hours
Alfentanil 45 59 Shorter compared to fentanyl,
longer compared to sufentanil,
stable after 2–3 hours 		1.5–2 hours
Sufentanil 29 34 Shorter compared to fentanyl 11–15 hours
Remifentanil 3-4 3-4 Ultimate short,
stable after 3–4 minutes,
no accumulation 		3–10 minutes

Web links

Individual evidence

  1. ↑ a b c M. Schäfer, C. Zöllner: Opioids in anesthesiology . In: Rossaint et al. (Ed.): The anesthesiology . Springer Reference Medicine. Springer, Berlin, Heidelberg. 2016. pp. 1–24.
  2. ^ MA Hughes, PS Glass, JR Jacobs: Context-sensitive half-time in multicompartment pharmacokinetic models for intravenous anesthetic drugs. In: Anesthesiology. 76 (3), March 1992, pp. 334-341. PMID 1539843 .
  3. ↑ a b Wilhelm, Wolfram (Ed.): Praxis der Anästhesiologie. Springer, Berlin 2018, ISBN 978-3-662-54568-3 , pp. 54 ff .
  4. ↑ G. Geisslinger et al .: Mutschler drug effects . 11th edition. WVG, Stuttgart 2019, p. 32 f.
  5. ↑ a b c T. Heidegger, CF Minto, TW Schnider: Modern concepts of the pharmacokinetics of intravenous anesthetics. In: Anaesthesiologist. 53 (1), Jan 2004, pp. 95-110. PMID 14994741 .
  6. ^ JM Bailey: Context-sensitive half-times and other decrement times of inhaled anesthetics. In: Anesth Analg. 85 (3), Sep 1997, pp. 681-686. PMID 9296431 .
  7. ↑ Wilhelm, Wolfram (Ed.): Practice of anesthesiology. Springer, Berlin 2018, ISBN 978-3-662-54568-3 , pp. 78 f .
  8. ↑ G. Geisslinger et al .: Mutschler drug effects . 11th edition. WVG, Stuttgart 2019, p. 304.
  9. ↑ SL Shafer., JR Varvel: Pharmacokinetics, pharmacodynamics, and rational opioid selection . Anesthesiology, Vol. 74 (1991), pp. 53-63.
  10. ↑ Reinhard Larsen: Anesthesia. 11th edition, Elsevier, Germany, 2018. p. 79.