(healthy volunteers, non invasive monitoring and O2 supply via nasal cannula) Target controlled infusion of propofol using Schnider´s pharmacokinetic parameters in a slow, stepped fashion. beginning at Cp 0.5 mcg/ml and increasing in 0.5 mcg/ml every 7 minutes until LOC occurred, then a prolonged step of 14 minutes (2 samples), increase 2 steps further and then decrease in 0.5 mcg/ml steps until ROC and a 7 minute registry after ROC.

Blood sampling for propofol plasma level every 7 minutes (at the end of each step, allowing for pseudo-equilibrium condition.

32 channel-EEg and BIS continuous monitoring

slow stepped propofol target controlled infusion using Schinider´s pharmacokinetic parameters seriated venous blood sampling

determination of plasma concentration of PROPOFOL at the time of Loss of Consciousness and the time of recovery of consciousness during the 7-minute step infusion.

Provided it is a slow increasing infusion we assume a pseudo-equilibrium state between plasma and effect site.

the existence of a difference between these two values will support the hypothesis of neuronal inertia

we measured the BISPECTRAL INDEX all through the protocol: from previous to start the infusion until 7 minutes after recovery of consciousness. values of BIS at LOC and ROC will be compared.

a potential difference found between those two values supports the theory thas LOC and ROC reflects different neuronal processes Other clinically relevant endpoints (loss of palpebral reflex, onset of amnesia) will be registered in order to build the pharmacodynamic loop.

to compare plasma (and effect site) Propofol concentration predicted by the model with measured values thus evaluating model´s performance. Median performance error (MDPE) and median absolute performance error (MDAPE), divergence and other often reported parameters will be determinated.