General Anesthesia, Loss of Consciousness and Recovery of Consciousness, Propofol Pharmacodynamics, Propofol Plasma Concentration, Propofol Target Controlled Infusion
Conditions
Keywords
neuronal inertia, loss of consciousness, propofol pharmacodynamics, Bispectral index, anesthesia, general/pharmacology
Brief summary
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
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.
Interventions
DRUGpropofol targel controlled infusion
slow stepped propofol target controlled infusion using Schinider´s pharmacokinetic parameters seriated venous blood sampling
Sponsors
Universidad del Desarrollo
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| plasma-equilibrated effect site concentration of propofol at LOC and ROC (mcg/ml) | 2 hours (during slow steady-state concentration propofol infusion) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bispectral Index (BIS) al LOC and ROC | 2 hours (during slow increasing TCI (Target controlled Infusion) of PROPOFOL | 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. |
| Pharmacodynamic curve for propofol. | 2 hours | 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, |
| PROPOFOL effect site concentration during infusion | 2 hours | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| performance of Schnider´s pharmacokinetic parameters in a slow infusion | 2 hours | 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. |
| Electroencephalographic behavior at LOC and ROC during Propofol infusion | 2 hours (during propofol infusion) | 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. |
Countries
Chile
Outcome results
None listed