Slow Stepwise Propofol TCI Induction for Titration Anesthesia Maintenance ((TITINDUC))

February 15, 2020 updated by: Hernan Boveri, Hospital Italiano de Buenos Aires
The purpose of this study is to determine if a slow stepwise propofol TCI induction with Marsh model (Ke0 0.26), allows for an accurate estimation of the effect site concentration required for maintenance of the general anesthesia, with propofol and remifentanil, in adult populations older and younger than 65 years of age.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Introduction: Currently, propofol is the most widely used intravenous anesthetic drug that is able to provide a safe general anesthesia. Propofol can be administered by using different techniques including target controlled infusion (TCI). The ability to maintain the pharmacological conditions after achieving a predetermined clinical effect is one of the major advantages of this technique. Although the use of TCI devices has increased in common clinical practice, whether or not all patients are suitable for TCI remains unclear. Pharmacological models were created based on information from healthy volunteers which may not apply for specific clinical conditions resulting either in over- or sub-dosed when using certain drugs.

It is not only individual variability in the pharmacokinetic (PK) parameters of the anesthetic that is a clinical problem, but it is also the pharmacodynamic variability. A previous study showed up to 6 times the inter-individual difference among young volunteers in loss of consciousness (LOC) and return of consciousness (ROC). In addition, greater differences may be found in the elderly.

Inaccurate general models require the anesthetic team to manually tailor medication requirements for each individual based on the desired therapeutic effect.

The purpose of this study is to evaluate if a slow stepwise propofol TCI induction with Marsh model (Ke0 0.26), assessed by clinical and electroencephalographic parameters, allows for an accurate estimation of the effect concentration required for hypnosis titration and maintenance of the general anesthesia, in adult populations older and younger than 65 years of age.

General Objective

• To establish whether a guided slow stepwise guided propofol induction with TCI represents a good correlation between the calculated Effect-Site Concentration (Ce) for the loss of consciousness and the required Ce to maintain a bispectral index (BIS) value between 45 and 65 during anesthesia maintenance in both age populations

Specific Objectives

  • To determine the BIS value achieved with every propofol infusion based on the calculated Ce for the time of loss of consciousness (TLOC)
  • To compare the drug infused per time unit required for the loss of consciousness in both groups
  • To compare the time and Ce required to achieve loss of consciousness in both groups
  • To evaluate the impact of remifentanil during hypnosis by using the BIS index

Hypothesis

During a slow stepwise anesthetic induction with TCI using the Marsh Model 4.0, the calculated Ce for the TLOC is comparable to the Ce required for the maintenance of the hypnosis during the general anesthesia, overcoming the inter-individual variability.

Methods

Experimental study, prospective clinical trial, phase 4. Each subject will be assigned to the propofol induction modality as described in the "intervention" section.

Once consciousness has been lost and maintenance target concentration has been established, manual ventilation will be initiated. Remifentanil TCI 6 ng/ml and a neuromuscular relaxant will be administered afterwards in order to perform endotracheal intubation. An infusion of phenylephrine between 0,1 and 0,4 mcg/kg/min will be initiated in order to maintain blood pressure values within 20% of the baseline value.

Continuous monitoring of BIS will be maintained after remifentanil infusion and intubation. Three minutes after endotracheal intubation, surgery will be prepared following standard procedures. BIS, spectrogram, and hemodynamics will be registered every 15 seconds, continuously, and every 3 minutes during 10 minutes respectively.

Subsequently, propofol Ce at TLOC will be established (if any modifications were necessary after TLOC) and it will be observed for another 30 minutes.

Study Type

Interventional

Enrollment (Anticipated)

60

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • ASA 1 or 2.
  • Age over 20 years old.
  • Scheduled to undergo elective surgery of minor or medium complexity under general anesthesia.
  • Regarding cognitive function: subjects will be considered with enough cognitive function if they are able to read and understand the medical history form by properly answering medical questions during the preoperative anesthesia assessment and being also able to sign the informed consent form.

Exclusion Criteria:

  • Pregnancy.
  • Obesity (BMI >30).
  • Patients taking benzodiazepines or other central nervous system action drugs.
  • Subjects with psychiatric disorders with or without treatment.
  • Allergies or any adverse reaction to propofol or any of its components (egg lecithin).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group 1
Patients < 65 years old Propofol 1% TCI induction using plasma concentration, Marsh model (Ke0=0.26 min-1) at 1 mcg/ml, increasing the target concentration by 0.5 mcg/ml every minute until LOC. Remifentanil TCI 6 ng/ml and a neuromuscular relaxant will be administered afterwards in order to perform endotracheal intubation. CeLOC propofol concentration will be established and it will be observed for another 30 minutes. If BIS <40 or >65 propofol target concentration will be modified by 0,3 mcg/ml.
Drug: Propofol
Propofol intravenously by a stepwise TCI titration with Marsh pharmacokinetic model
Other Names:
  • Fresofol
Drug: Remifentanil Hydrochloride
Remifentanil intravenously 6 ng/ml by TCI effect site, 3 min prior to intubation and maintained at that concentration throughout the study. If clinical signs of inadequate analgesia are present, remifentanil target concentration will be increased by 1 ng/ml.
Experimental: Group 2
Patients ≥ 65 years old Propofol 1% TCI induction using plasma concentration, Marsh model (Ke0=0.26 min-1) at 1 mcg/ml, increasing the target concentration by 0.5 mcg/ml every minute until LOC. Remifentanil TCI 6 ng/ml and a neuromuscular relaxant will be administered afterwards in order to perform endotracheal intubation. CeLOC propofol concentration will be established and it will be observed for another 30 minutes. If BIS <40 or >65 propofol target concentration will be modified by 0,3 mcg/ml.
Drug: Propofol
Propofol intravenously by a stepwise TCI titration with Marsh pharmacokinetic model
Other Names:
  • Fresofol
Drug: Remifentanil Hydrochloride
Remifentanil intravenously 6 ng/ml by TCI effect site, 3 min prior to intubation and maintained at that concentration throughout the study. If clinical signs of inadequate analgesia are present, remifentanil target concentration will be increased by 1 ng/ml.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time that BIS range remains within 45 and 65 after a stepwise TCI titration
Time Frame: A 30-minute period, starting 10 minutes after Remifentanil infusion (when propofol and remifentanil plasma-effect compartment equilibration has been reached)
TCI Effect Site Concentration achieved at LOC, depth of anesthesia will be recorded with BIS bilateral sensor
A 30-minute period, starting 10 minutes after Remifentanil infusion (when propofol and remifentanil plasma-effect compartment equilibration has been reached)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time for loss of consciousness
Time Frame: Up to First 10 minutes, from start of propofol infusion at time 0 until loss of verbal response
In seconds, using TCI induction with Marsh 4.0 pharmacokinetic model
Up to First 10 minutes, from start of propofol infusion at time 0 until loss of verbal response
Effect Site Concentration required for loss of consciousness
Time Frame: Up to first 10 minutes. It will be considered the propofol effect site concentration displayed at the moment loss of consciousness is achieved.
In mcg/ml, using Marsh Pharmacokinetic Model, Ke0 0.26 min-1
Up to first 10 minutes. It will be considered the propofol effect site concentration displayed at the moment loss of consciousness is achieved.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital Italiano de Buenos Aires

Investigators

  • Principal Investigator: Hernán Boveri, MD, Hospital Italiano de Buenos Aires

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2016

Primary Completion (Anticipated)

December 1, 2020

Study Completion (Anticipated)

March 1, 2021

Study Registration Dates

First Submitted

December 8, 2016

First Submitted That Met QC Criteria

December 16, 2016

First Posted (Estimate)

December 21, 2016

Study Record Updates

Last Update Posted (Actual)

February 18, 2020

Last Update Submitted That Met QC Criteria

February 15, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2884

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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