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Evidence of hysteresis in propofol pharmacodynamics.

Authors
  • Sepúlveda, P O 5th1
  • Carrasco, E1
  • Tapia, L F1
  • Ramos, M1
  • Cruz, F1
  • Conget, P2
  • Olivares, Q F B3
  • Cortínez, I4
  • 1 Servicio de Anestesia, Clínica Alemana Universidad del Desarrollo, Santiago de Chile, Chile. , (Chile)
  • 2 Centro de Química Médica, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Santiago de Chile, Chile. , (Chile)
  • 3 Centro de Medicina Regenerativa, Facultad de Medicina Clínica Alemana Universidad del Desarrollo, Santiago de Chile, Chile. , (Chile)
  • 4 División de Anestesiología, Pontificia Universidad Católica de Chile, Santiago de Chile, Chile. , (Chile)
Type
Published Article
Journal
Anaesthesia
Publisher
Wiley (Blackwell Publishing)
Publication Date
Sep 05, 2017
Identifiers
DOI: 10.1111/anae.14009
PMID: 28872658
Source
Medline
Keywords
License
Unknown

Abstract

It is commonly assumed that loss of responsiveness and recovery of responsiveness occur at similar concentrations of propofol. However, the 'conscious' and 'anaesthetised' conditions produced by general anaesthetics may behave as two bistable states. We hypothesised that loss of responsiveness and recovery of responsiveness occur at different propofol concentrations. Propofol was administered to 19 healthy volunteers by effect-site target-controlled infusion using increasing and decreasing stable concentration steps of 7 min. Propofol serum concentrations were measured from venous blood samples at the end of each 7-min step. A long step of 14 min was performed at loss of responsiveness. At this step, propofol concentrations were measured at 7 and 14 min. Propofol concentrations measured at loss of responsiveness and recovery of responsiveness were 2.6 (1.2-4.7) μg.ml-1 and 1.6 (0.6-3.3) μg.ml-1 , respectively (p < 0.001). Propofol plasma concentration and the corresponding bispectral index values measured at minute 7 and minute 14 of the long step performed at loss of responsiveness were 2.6 (1.2-4.7) vs. 2.6 (1.3-4.3) at recovery of responsiveness, (p = 0.96) and 61.2 (49.0-77.0) vs. 58.4 (45.0-74.0), (p = 0.058), respectively. Loss of responsiveness and recovery of responsiveness appear to occur at different propofol concentrations. However, it is possible that, if equilibration was not achieved between plasma and effect-sites at the end of each 7-min step, the higher concentrations found at loss of responsiveness compared with those observed during recovery of responsiveness could be explained by a possible bias in estimations of the effect-site concentrations of propofol by the Schnider model, rather than neural inertia.

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