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Trial record 22 of 705 for:    region | Chile

Neuronal Inertia in Propofol Anesthesia (INERTIA)

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ClinicalTrials.gov Identifier: NCT01962285
Recruitment Status : Completed
First Posted : October 14, 2013
Last Update Posted : October 14, 2013
Sponsor:
Information provided by (Responsible Party):
Pablo Sepulveda, 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.

Condition or disease Intervention/treatment Phase
General Anesthesia Propofol Pharmacodynamics Propofol Target Controlled Infusion Loss of Consciousness and Recovery of Consciousness Propofol Plasma Concentration Drug: propofol targel controlled infusion Phase 4

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Neuronal Inertia´s Effect on Pharmacological Behavior Representation of Propofol
Study Start Date : August 2013
Actual Primary Completion Date : September 2013
Actual Study Completion Date : October 2013

Resource links provided by the National Library of Medicine

Drug Information available for: Propofol

Arm Intervention/treatment
Experimental: propofol slow 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

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




Primary Outcome Measures :
  1. plasma-equilibrated effect site concentration of propofol at LOC and ROC (mcg/ml) [ Time Frame: 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 :
  1. Bispectral Index (BIS) al LOC and ROC [ Time Frame: 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.


  2. Pharmacodynamic curve for propofol. [ Time Frame: 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,

  3. PROPOFOL effect site concentration during infusion [ Time Frame: 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 Outcome Measures:
  1. performance of Schnider´s pharmacokinetic parameters in a slow infusion [ Time Frame: 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.

  2. Electroencephalographic behavior at LOC and ROC during Propofol infusion [ Time Frame: 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01962285


Locations
Chile
Clinica Alemana de Santiago
Santiago, Region Metropolitana, Chile
Sponsors and Collaborators
Universidad del Desarrollo
Investigators
Principal Investigator: pablo sepulveda, anesthesiologist Universidad del Desarrollo

Responsible Party: Pablo Sepulveda, Médico Cirujano, Universidad del Desarrollo
ClinicalTrials.gov Identifier: NCT01962285     History of Changes
Other Study ID Numbers: INERTIA
First Posted: October 14, 2013    Key Record Dates
Last Update Posted: October 14, 2013
Last Verified: October 2013

Keywords provided by Pablo Sepulveda, Universidad del Desarrollo:
neuronal inertia
loss of consciousness
propofol pharmacodynamics
Bispectral index
anesthesia, general/pharmacology

Additional relevant MeSH terms:
Unconsciousness
Consciousness Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Propofol
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics