Neuronal Inertia in Propofol Anesthesia (INERTIA)

Loss and recovery of consciousness during propofol anesthesia seem to be mediated by different mechanisms beyond the actual effect-site concentration of anesthetic drug. This eventual difference between dose response curves for loss of consciousness (LOC) and for recovery of consciousness (ROC) beyond hysteresis has received the name of neuronal inertia. We performed a volunteer-study comparing LOC and ROC curves during a slow, steady-sate, stepped target controlled infusion of Propofol. Our hypothesis is that, at steady-state conditions between plasma an effect-site concentration, there is still going to exist a difference between LOC and ROC, demonstrating the existence of neuronal inertia.

Loss and recovery of consciousness during propofol anesthesia seem to be mediated by different mechanisms beyond the actual effect-site concentration of anesthetic drug. This eventual difference between dose response curves for loss of consciousness (LOC) and for recovery of consciousness (ROC) beyond hysteresis has received the name of neuronal inertia. We performed a volunteer-study comparing LOC and ROC curves, during a slow, steady-sate, stepped target controlled infusion of Propofol using Schnider's pharmacologic model. Our hypothesis is that, at steady-state conditions between plasma an effect-site concentration, there is still going to exist a difference between LOC and ROC, demonstrating the existence of neuronal inertia.

General Anesthesia, Propofol Pharmacodynamics, Propofol Target Controlled Infusion, Loss of Consciousness and Recovery of Consciousness, Propofol Plasma Concentration

neuronal inertia, loss of consciousness, propofol pharmacodynamics, Bispectral index, anesthesia, general/pharmacology

(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.

plasma concentration of PROPOFOL (mcg/ml) at other clinically relevant endpoints (amnesia onset, loss of palpebral reflex, etc...) will be determined in order to build a pharmacodynamic curve,

plasma concentration of PROPOFOL (mcg/ml) from venous blood samples will be determinated every 7 minutes, that means at the end of each TCI step. assuming the 7-minute step gave enough time to reach a pseudo-equilibrium state, we consider the results comparable to effect site concentration.

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.

spectral analisis of 32-channel EEG during infusion. a specified time-frame around those two events (i.e.: 14 minutes) will be reconstructed in images and analyzed. cortical areas with enhanced activity and how do this activity changes during loss of consciousness and the recovery of it will be evaluated with a mathematical model in order two determine wether those events correspond with two different processes instead of a bidirectional single one.

Inclusion Criteria: american society of anesthesiologists status I or II age >18 years fasted at least 8 hours BMI<30 Exclusion Criteria: any known adverse reaction to propofol administration soy or egg-protein allergy psychotropic use (illegal of medically indicated)