Neuronal Inertia in Propofol Anesthesia

General Anesthesia Clinical Trial

— INERTIA  

Official title:

Neuronal Inertia´s Effect on Pharmacological Behavior Representation of Propofol

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01962285
• Other study ID #: INERTIA
• Status: Completed
• Phase: Phase 4
• First received: October 9, 2013
• Last updated: October 11, 2013
• Start date: August 2013
• Est. completion date: October 2013

Study information

• Verified date: October 2013
• Source: Universidad del Desarrollo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: October 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

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

Intervention

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

Locations

Country	Name	City	State
Chile	Clinica Alemana de Santiago	Santiago	Region Metropolitana

Sponsors (1)

Lead Sponsor	Collaborator
Universidad del Desarrollo

Country where clinical trial is conducted

Chile, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	performance of Schnider´s pharmacokinetic parameters in a slow infusion	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.	2 hours
Other	Electroencephalographic behavior at LOC and ROC 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.	2 hours (during propofol infusion)
Primary	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	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
Secondary	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
Secondary	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