Performance of Two Different ke0s in the Same Pharmacokinetic Propofol Model
Condition: Unconsciousness
MeSH terms: Unconsciousness
Study type: Observational

Summary: 
      The aim of this study was to assess the clinical performance of two different ke0s (fast and
      slow) in terms of propofol effect-site concentration (Ce) during the loss and recovery of
      consciousness, using Marsh's pharmacokinetic model.The hypothesis to be tested was that the
      Ce of propofol predicted by the slow ke0 in the loss and recovery of consciousness is
      similar, differently from the fast ke0.
    

Detailed description: 
      Introduction: The ke0 can be defined as the proportional variation of the gradient of
      concentration between the plasma and the effect-site in relation to the unit of time.
      Theoretically, the higher the value of the ke0, the faster the drug enters the effect-site.
      Therefore, drugs with short T½ke0 have high ke0s and fast onset of action. The aim of this
      study was to assess the clinical performance of two different ke0s (fast and slow) in terms
      of propofol effect-site concentration (Ce) during the loss and recovery of consciousness,
      using Marsh's pharmacokinetic model. Method: Twenty healthy male adult volunteers
      participated in this study. Propofol was first administered to the individual volunteer using
      Marsh's pharmacokinetic target-controlled infusion model with ke0 of 1.21 min-1 and, on
      another opportunity, with the same pharmacokinetic model but ke0 of 0.26 min-1. Propofol was
      infused in plasma target-concentration of 3.0 µg.mL-1. Loss and recovery of consciousness was
      defined as response of the volunteer to verbal stimulus. The Ce was registered at the moments
      of loss and recovery of consciousness. Results: At loss and recovery of consciousness,
      propofol Ce means predicted by the fast ke0 were different (3.64 ± 0.78 and 1.47 ± 0.29
      µg.mL-1, respectively, p < 0.0001), whereas with the slow ke0 the predicted Ce means were
      similar (2.20 ± 0.70 and 2.13 ± 0.43 µg.mL-1, respectively, p = 0.5425). Conclusion: It can
      be concluded that slow ke0 (0.26 min-1) incorporated into Marsh's pharmacokinetic model
      showed better clinical performance than fast ke0 (1.21 min-1), since the predicted
      effect-site concentrations of propofol at loss and recovery of consciousness were similar.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Twenty healthy male adult volunteers participated in this study. The volunteers appeared at
        the testing location, having refrained from eating and drinking for six hours. All the
        volunteers were monitored with electrocardiogram (DII and V1 derivation), pulse oximetry
        (SpO2), non-invasive average arterial pressure and bispectral index (BIS). Oxygen under 2.0
        L.min-1 nasal catheter was used and the left antecubital vein was punctured and connected
        to the venous catheter filled with propofol (Propovan® - Cristália Laboratório Ltda).
      
Keywords: Intravenous anesthesia; propofol; pharmacokinetic model; Monitoring; bispectral index.