Neuronal Inertia in Propofol Anesthesia

Phase 4

Completed

• Conditions: General Anesthesia; Propofol Pharmacodynamics; Propofol Target Controlled Infusion; Loss of Consciousness and Recovery of Consciousness; Propofol Plasma Concentration
• Interventions: Drug: propofol targel controlled infusion

• Registration Number: NCT01962285
• Lead Sponsor: Universidad del Desarrollo

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.

Study Timeline

• Study Start: 2013-08
• Primary Completion: 2013-09
• Status Verified: 2013-10
• Study Completion: 2013-10
• Study First Submitted: 2013-10-09
• Study First Submitted QC: 2013-10-11
• Last Update Submitted: 2013-10-11
• Study First Posted: 2013-10-14
• Last Update Posted: 2013-10-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 14

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
propofol slow infusion	propofol targel controlled infusion	(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

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

Clinica Alemana de Santiago; 🇨🇱 Santiago, Region Metropolitana, Chile