Evaluation of Automated Propofol Delivery in Patients Undergoing Thoracic Surgery

June 29, 2019 updated by: Dr Nitin Sethi

Evaluation of Automated Delivery of Propofol Using Closed-Loop Anaesthesia Delivery System in Patients Undergoing Thoracic Surgery: A Randomised Controlled Study

Automated delivery of propofol using computer-controlled closed loop anaesthesia device delivers propofol based on patient's frontal cortex electrical activity as determined by bi-spectral index (BIS). Evaluation of anaesthesia delivery by these systems has shown that they deliver propofol and maintain depth of anaesthesia with far more precision as compared to manual administration.

By automatically controlling anaesthesia depth consistency they provide time to the anaesthesiologist to focus on other aspects of patient care such as managing intra-operative hemodynamics and ventilation perturbations during major surgeries.

Closed loop anaesthesia delivery system (CLADS) is an indigenously developed continuous automated intravenous infusion system which delivers propofol based on patients EEG profile (BIS) feedback. Although a few studies have already evaluated these automated systems in patients undergoing thoracic surgery, but suffered from significant limitations (small number of patients, not dedicated to thoracic surgery cohort). Currently, there is no data available regarding CLADS performance vis a vis adequacy of GA and haemodynamic profile in patients undergoing thoracic surgery.

We contend that propofol as delivered by CLADS will proffer greater consistency to anaesthesia depth, intra-operative hemodynamic stability, and rapid recovery upon anaesthesia discontinuation than manual means of delivering propofol TIVA. This randomised controlled study aims to compare the efficiency of CLADS-driven propofol TIVA versus manually controlled propofol TIVA in patients undergoing thoracic surgery.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

After Ethics Committee approval and written informed consent, thirty-participants (30 per group) aged 18-65 years, ASA physical status I-III, of either sex, and undergoing unilateral open thoracic surgery or unilateral video-assisted thoracic surgery (VATS) will be included in this single centre (Sir Ganga Ram Hospital, New Delhi-110060, India) prospective, single-blinded, two-arm, randomised controlled study.

The patients who qualify inclusion criteria and consent for recruitment will be randomly divided into one of the two groups:

Group-1 [CLADS Group, n=15, Study group]: Anaesthesia will be induced and maintained with propofol administered using the automated CLADS.

Group-2 [Manual Group, n=15, Control group]: Anaesthesia will be induced and maintained with propofol administered using manually controlled infusion pumps titrated to BIS scores.

Sample-size Estimation In a previous multi-centre study, the percentage of time the BIS was within 10 percentage of the target BIS was 81.4 percent in the CLADS group versus 55.34 percent in the manual group. Based on the above, to detect 20 percent difference in the two groups, a sample size of 12 patients per group to provide 90 percent power with a bilateral alpha risk value of 0.05 will be required. We plan to recruit a total of 30 patients to cover up for unanticipated losses after the recruitment.

Randomisation, Allocation Concealment The patients will be randomly allocated to one of the two groups based on a computer-generated random number table. Randomisation sequence concealment will include opaque-sealed envelopes with alphabetic codes whose distribution will be in control of an independent analyst. The envelopes will be opened; patient's data-slip will be pasted on them, and will be sent back to the control analyst.

Blinding Strategy Inside the OR, the attending anaesthesiologist will not be blinded to the technique utilised to administer GA and the recovery parameters immediately after extubation. However, the postoperative patient recovery profile will be evaluated by an independent assessor blinded to the GA technique and periextubation profile.

Management of Anesthesia Two peripheral venous lines (18G/20G catheter) will be secured. Invasive vascular access (arterial line for direct continuous blood pressure assessment, central venous catheter) will be secured as per the requirement of surgery. Standard monitoring (EKG, NIBP, pulse oximeter, EtCO2) will be applied. A BIS sensor (Covidien IIc, Mansfield, USA) will be applied over the patient's forehead according to manufacturer's instructions (Model DSC-XP, Aspect medical system, USA) prior to induction of anaesthesia for continuous monitoring of depth-of-anaesthesia.

Anaesthesia Technique

All the patients will receive pre-induction fentanyl-citrate 2 mcg/kg and anesthesia will be induced with propofol. In the CLADS group, propofol administration rate will be controlled by a feedback loop facilitated by BIS monitoring. A BIS value of 50 will be used as the target point for induction and maintenance of anesthesia. The Manual group would comprise manual propofol administration by an intravenous infusion pump to maintain a target BIS of 50 during induction and maintenance of anesthesia.

After induction of anesthesia, atracurium besylate 0.05mg/kg will be given to facilitate tracheal intubation. In order to facilitate one lung ventilation (OLV) patients trachea will be intubated using appropriate-sized double-lumen tube in all the patients. Oxygen-air mixture (FiO2 0.50) will be used for intraoperative ventilation in both the groups. In addition, starting the period after tracheal intubation, all the patients will receive 1 mcg/kg/hr fentanyl infusion for intraoperative analgesia. Intraoperative muscle relaxation will be maintained using atracurium infusion controlled by train-of-four response on peripheral neuromuscular monitor (Infinity TridentNMT Smartpod, Draeger Medical Systems, Inc Telford, USA).

In all patients undergoing open thoracic surgery, a thoracic epidural catheter will be placed in the indicated intervertebral space for facilitating postoperative analgesia.

Thirty minutes before the end of surgery, non-opioid analgesics, such as paracetamol 1-gm, tramadol 100 mg and/or diclofenac 75 mg will be administered to all the patients. Propofol delivery will be stopped at the point of completion of skin closure. Residual neuromuscular blockade (assessed with train-of-four response) will be reversed with neostigmine (50 µg/kg) and glycopyrrolate (20 µg/kg). Tracheal extubation will be undertaken if planned post-extubation ventilation is not instituted and the patients are wide awake and obeying commands.

Assessment Parameters Intraoperative

  1. Adequacy of anaesthesia depth will be determined by the percentage of the valid CLADS time during which the BIS remained within 10% of the target BIS (50), median absolute performance error (MDAPE), wobble and global score (Varvel criteria)
  2. Haemodynamic parameters such a heart rate, non-invasive blood pressure will be recorded
  3. Early recovery from anaesthesia profile which includes time to eye opening and time to extubation after discontinuation of anesthesia will be noted

Postoperative

  1. Sedation will be assessed using Modified Observer's assessment of alertness/sedation scale.
  2. Incidence of awareness will be determined using Modified Brice Questionnaire.

After discontinuation of anaesthesia delivery (0-time point) the time to eye opening and time to extubation will be determined. After tracheal extubation, the patients will be shifted to postoperative recovery room adjoining OT suites and will be closely observed for oxygenation and ventilation status, pain (numeric rating score) and sedation. Patients with epidural catheter in-situ will be started with PCEA pump for pain relief. Patients will be analysed for intra-operative awareness using Modified Brice Questionnaire (24 hours, 48 hours postoperatively).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • India
    • Delhi
      • New Delhi, Delhi, India, 110060
        • Sir Ganga Ram Hospital

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • ASA physical status I-III
  • undergoing unilateral open thoracic surgery or unilateral video-assisted thoracic surgery (VATS) Exclusion Criteria:

Exclusion Criteria:

  • Uncompensated cardiovascular disease (e.g. uncontrolled hypertension, atrio-ventricular block, sinus bradycardia, congenital heart disease, reduced LV compliance, diastolic dysfunction)
  • Hepato-renal insufficiency
  • Uncontrolled endocrinology disease (e.g. diabetes mellitus, hypothyroidism)
  • Known allergy/hypersensitivity to the study drug
  • Drug dependence/substance abuse
  • Requirement of postoperative ventilation
  • Refusal to informed consent

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: BASIC_SCIENCE
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
ACTIVE_COMPARATOR: CLADS group
Anaesthesia will be induced and maintained with Propofol administered by CLADS. Its administration rate will be controlled by a feedback loop facilitated by BIS monitoring. A BIS value of 50 will be used as the target point for induction and maintenance of anaesthesia.
Drug: Propofol
Propofol delivery will be controlled using automated closed loop anaesthesia delivery system which will control propofol delivery rate to consistent anaesthetic depth (BIS-50) feedback from the patient (CLADS group)
Drug: Propofol
Propofol delivery will be controlled using infusion pumps which will be manually controlled to deliver propofol to maintain consistent anaesthetic depth (BIS-50). (Manual group)
ACTIVE_COMPARATOR: Manual group
Anaesthesia will be induced and maintained with propofol administration by an intravenous infusion pump. Its administration rate will be controlled manually to maintain a target BIS of 50 during induction and maintenance of anaesthesia.
Drug: Propofol
Propofol delivery will be controlled using automated closed loop anaesthesia delivery system which will control propofol delivery rate to consistent anaesthetic depth (BIS-50) feedback from the patient (CLADS group)
Drug: Propofol
Propofol delivery will be controlled using infusion pumps which will be manually controlled to deliver propofol to maintain consistent anaesthetic depth (BIS-50). (Manual group)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Anaesthesia depth consistency using BIS scores
Time Frame: From beginning of anaesthesia (0-hours, baseline) till 10 hours intraoperatively
Determined by the percentage of the total anaesthesia time in which the BIS scores remain within a score of 10% of the target BIS (i.e. BIS-50) in both the study arms.
From beginning of anaesthesia (0-hours, baseline) till 10 hours intraoperatively

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Intra-operative systolic , diastolic, and mean (mmHg)
Time Frame: From beginning of anaesthesia (0-hours, baseline) till 10 hours intraoperatively
Comparison of intra-operative blood pressure- systolic, diastolic, and mean between both the arms will be done
From beginning of anaesthesia (0-hours, baseline) till 10 hours intraoperatively
Propofol maintenance dose (mg/kg/hr)
Time Frame: From 2-minutes intraoperatively till 10-hours intraoperatively
Dose of propofol required for maintenance of anaesthesia
From 2-minutes intraoperatively till 10-hours intraoperatively
Performance Characteristic of propofol anaesthesia delivery system
Time Frame: From beginning of anaesthesia (0-hours, baseline) till 10 hours intraoperatively
Determined by using Varvel criteria parameters; median performance error (MDP), median absolute performance error (MDAPE), wobble and global score in both the study arms
From beginning of anaesthesia (0-hours, baseline) till 10 hours intraoperatively
Change in Intra-operative heart Rate (beats per minute)
Time Frame: From beginning of anaesthesia (0-hours, baseline) till 10 hours intraoperatively
Comparison of intra-operative heart rate between both the arms will be done
From beginning of anaesthesia (0-hours, baseline) till 10 hours intraoperatively
Recovery from anesthesia
Time Frame: From end of anaesthesia till 20-minutes postoperatively]
Time taken by the patient to open his/her eyes after discontinuation of anaesthesia will be noted
From end of anaesthesia till 20-minutes postoperatively]
Recovery from anesthesia
Time Frame: From end of anaesthesia till 20-minutes postoperatively]
Time taken for tracheal extubation after discontinuation of anaesthesia will be noted
From end of anaesthesia till 20-minutes postoperatively]
Intra-operative awareness
Time Frame: From the end of anaesthesia till 48-hours postoperatively
Will be assessed using modified brice questionnaire
From the end of anaesthesia till 48-hours postoperatively
Propofol induction dose (mg)
Time Frame: From start of propofol injection till 2- minutes intraoperatively
Dose of propofol required for induction of anaesthesia
From start of propofol injection till 2- minutes intraoperatively

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Dr Nitin Sethi

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 (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 31, 2017

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 25, 2019

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 25, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 6, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 10, 2017

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 11, 2017

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 2, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 29, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • EC/09/17/1254

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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.

Clinical Trials on Surgery

Clinical Trials on Propofol

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings