Neuronal Inertia in Propofol Anesthesia

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Neuronal Inertia´s Effect on Pharmacological Behavior Representation of Propofol

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

Intervention / Treatment
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* Drug: propofol targel controlled infusion


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: propofol slow infusion<br>(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 | Drug: propofol targel controlled infusion<br>* slow stepped propofol target controlled infusion using Schinider´s pharmacokinetic parameters seriated venous blood sampling<br>* Other names: propofol TCI;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| plasma-equilibrated effect site concentration of propofol at LOC and ROC (mcg/ml) | 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 | 2 hours (during slow steady-state concentration propofol infusion) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bispectral Index (BIS) al LOC and ROC | 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. | 2 hours (during slow increasing TCI (Target controlled Infusion) of PROPOFOL | 
| Pharmacodynamic curve for propofol. | 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, | 2 hours | 
| PROPOFOL effect site concentration during infusion | 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. | 2 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neuronal inertia, loss of consciousness, propofol pharmacodynamics, Bispectral index, anesthesia, general/pharmacology