Comparison of TIVA by Closed Loop Anaesthesia Delivery System Versus Target Controlled Infusion Device

Evaluation of Propofol Total Intravenous Anaesthesia Administered by Closed Loop Anaesthesia Delivery System Versus Target Controlled Infusion Device in Adults Undergoing Non-Cardiac Surgery: A Randomised Controlled Study

Total intravenous anaesthesia (TIVA) is now being adopted as a preferred technique for providing GA because of its various inherent advantages like reduced PONV incidence, improved quality of recovery post GA, anti-inflammatory and anti-oxidant action, anti-neoplastic activity, analgesic action, and absence of greenhouse effect. Over the years propofol-TIVA delivery has become more methodical due to the use of target-controlled infusion (TCI) systems. The current TCI technology has evolved with the introduction of the 'open' TCI concept wherein syringes of any configuration can be attached to the TCI-pumps having pre-programmed propofol PK-PD models. The two most commonly use propofol PK-PD models are the Marsh and Schneider models targeting the propofol blood plasma concentration and effect site concentration in the brain respectively. Automated delivery of propofol using computer-controlled closed loop anaesthesia device delivers propofol based on patient's frontal cortex electrical activity as determined by bispectral 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. A recent advance in propofol delivery has been the development of automated closed loop anaesthesia delivery system. These devices deliver propofol based on patient's frontal cortex electrical activity as determined by bispectral index (BIS).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. Currently there is no data available comparing the efficacy of TCI delivered propofol versus automated propofol delivery systems. The investigators hypothesize that automated propofol delivery by CLADS will provide more consistent anaesthesia depth maintenance as compared to TCI delivered propofol. This randomized controlled study aims to compare the efficiency of CLADS-driven propofol TIVA versus TCI administered in patients undergoing non-cardiac surgery with respect to adequacy of anaesthesia depth maintenance, performance characteristic of propofol delivery system hemodynamic stability, recovery from anaesthesia and postoperative sedation.

Study Overview

• Status: Recruiting
• Conditions: Anesthesia
• Intervention / Treatment: Drug: Propofol; Drug: Propofol; Drug: Propofol; Drug: Propofol

Detailed Description

Inhalation anaesthetic were backbone of general anaesthesia (GA) practice till the time an intravenous anaesthetic, propofol was introduced in early 1970's and its commercial availability in 1980's, which led to the resurgence in the practice of total intravenous anaesthesia (TIVA). TIVA is now being adopted as a preferred technique for providing GA because of scores of inherent advantages, like, reduced PONV incidence, improved quality of post-anaesthesia recovery, anti-inflammatory and anti-oxidant action, anti-neoplastic activity, analgesic action, and absence of greenhouse effect among many others.Over the years propofol-TIVA delivery has become more methodical and precise owing to the use of target controlled infusion (TCI) systems. TCI systems use propofol pharmacokinetic (PK) or pharmacodynamics (PD) models which predict either the plasma or the effect-site propofol concentration required for maintenance of GA steady-state during surgery. The 'Diprifusor' TCI-system was the first commercially available propofol TCI-system. The 'Diprifusor' TCI-system was a 'closed' TCI-system which required a special electronically tagged pre-filled propofol syringe to be attached to the TCI-pump. The current TCI technology has evolved with the introduction of the 'open' TCI concept wherein syringes of any configuration can be attached to the TCI-pumps having pre-programmed propofol PK-PD models. Currently, the two most commonly used PK-PD models that drive TCI systems to deliver TIVA are the 'Marsh' and 'Schneider' models. Whereas Marsh model targets blood plasma concentration of propofol for anaesthesia maintenance, the Schneider model targets effect-site concentration in the brain. A recent advance in propofol TIVA delivery has been the development of automated closed loop anaesthesia delivery system. These devices deliver propofol based ascertaining patient's frontal cortex electrical activity as determined by bispectral index (BIS) score and then keeping the values within a pre-assigned range consistent with robust GA depth. Closed loop anaesthesia delivery system (CLADS) is an indigenously developed patented (502/DEL/2003) computer-controlled anaesthesia delivery system. CLADS typically works with feedback loop information elicited by BIS monitoring and delivers propofol TIVA to the patient via a non-TCI automated infusion pump. This basis of CLADS is the control algorithm based on the relationship between diverse rates of propofol infusion and the processed EEG variable. Although propofol delivery by CLADS is based on pharmacokinetic model but for greater precision and efficient administration, its delivery trigger is directly linked with feedback mechanism involving patient's EEG profile as monitored by the BIS scores. In a multicentre study on evaluation of anaesthesia delivery by CLADS, it was shown that CLADS maintains depth of anaesthesia with far more precision as compared to manual administration. Queerly while TCI & CLADS technology evolved over a period of time; there is no data available comparing the efficacy of TCI delivered propofol-TIVA versus automated propofol delivery systems. Based on additional feedback loop incorporated to the PK-PD model the investigators contend that automated propofol TIVA as administered by CLADS is likely to be superior to TCI system in achieving and sustaining anaesthesia depth. This randomized controlled study aims to compare the efficacy of CLADS-driven propofol TIVA versus TCI administered propofol TIVA in adult patients undergoing non-cardiac surgery with respect to: adequacy of anaesthesia depth maintenance (primary objective), performance characteristic of propofol delivery system, propofol requirement, hemodynamic stability, recovery from anaesthesia and postoperative sedation (secondary objectives).

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nitin Sethi, MBBS, DNB; Phone Number: 00911142252523; Email: nitinsethi77@yahoo.co.in
• Study Contact Backup: Name: Amitabh Dutta, MBBS, MD, PGDHR; Phone Number: 00911142252523; Email: duttaamitabh@yahoo.com

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110060
      • Recruiting
      • Sir Ganga Ram Hospital
      • Contact: Nitin Sethi, DNB; Phone Number: +911142252523; Email: nitinsethi77@yahoo.co.in
      • Contact: Amitabh Dutta, MD; Phone Number: +911142252523; Email: duttaamiatbh@yahoo.co.in
      • Sub-Investigator: Prabhat Choudhary, MD
      • Sub-Investigator: Manish Gupta, MD
      • Sub-Investigator: Savitar Malhotra, MD
      • Sub-Investigator: Bhuwan C Panday, MD
    • New Delhi, Delhi, India, 110060
      • Recruiting
      • Nitin Sethi
      • Contact: Nitin Sethi, DNB; Phone Number: 009142252523; Email: nitinsethi77@yahoo.co.in

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• aged 18-65 years
• ASA physical status I-II
• undergoing elective non-cardiac surgery of minimum 60-minutes duration

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

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: CLADS group; Propofol administration rate will be controlled by a feedback loop facilitated by BIS monitoring using the closed-loop anaesthesia delivery system (CLADS). A BIS value of 50 will be used as the target point for induction and maintenance of anesthesia.	Drug: Propofol; Propofol administration rate will be controlled by a feedback loop facilitated by BIS monitoring using the closed loop anaesthesia delivery system (CLADS). A BIS value of 50 will be used as the target point for induction and maintenance of anaesthesia.; Drug: Propofol; The target controlled infusion (TCI) pump will be programmed to marsh model with the target plasma site concentration of 3-µg/ml. The plasma concentration will be altered to maintain a target BIS of 50 during induction and maintenance of anesthesia; Drug: Propofol; The target controlled infusion (TCI) pump will be programmed to Schneider model with the target effect site concentration of 3-µg/ml. The effect-site concentration will be altered to maintain a target BIS of 50 during induction and maintenance of anesthesia; Drug: Propofol; Manual propofol administration will be done using an intravenous infusion pump to maintain a target BIS of 50 during induction and maintenance of anesthesia.
Active Comparator: Marsh model group; The target-controlled infusion (TCI) pump will be programmed to marsh model with the target plasma site concentration of 3-µg/ml. The plasma concentration will be altered to maintain a target BIS of 50 during induction and maintenance of anesthesia	Drug: Propofol; Propofol administration rate will be controlled by a feedback loop facilitated by BIS monitoring using the closed loop anaesthesia delivery system (CLADS). A BIS value of 50 will be used as the target point for induction and maintenance of anaesthesia.; Drug: Propofol; The target controlled infusion (TCI) pump will be programmed to marsh model with the target plasma site concentration of 3-µg/ml. The plasma concentration will be altered to maintain a target BIS of 50 during induction and maintenance of anesthesia; Drug: Propofol; The target controlled infusion (TCI) pump will be programmed to Schneider model with the target effect site concentration of 3-µg/ml. The effect-site concentration will be altered to maintain a target BIS of 50 during induction and maintenance of anesthesia; Drug: Propofol; Manual propofol administration will be done using an intravenous infusion pump to maintain a target BIS of 50 during induction and maintenance of anesthesia.
Active Comparator: Schnider model group; The TCI-pump will be programmed to will be programmed to Schnider model with the target effect site concentration of 3-µg/ml. The effect-site concentration will be altered to maintain a target BIS of 50 during induction and maintenance of anesthesia.	Drug: Propofol; Propofol administration rate will be controlled by a feedback loop facilitated by BIS monitoring using the closed loop anaesthesia delivery system (CLADS). A BIS value of 50 will be used as the target point for induction and maintenance of anaesthesia.; Drug: Propofol; The target controlled infusion (TCI) pump will be programmed to marsh model with the target plasma site concentration of 3-µg/ml. The plasma concentration will be altered to maintain a target BIS of 50 during induction and maintenance of anesthesia; Drug: Propofol; The target controlled infusion (TCI) pump will be programmed to Schneider model with the target effect site concentration of 3-µg/ml. The effect-site concentration will be altered to maintain a target BIS of 50 during induction and maintenance of anesthesia; Drug: Propofol; Manual propofol administration will be done using an intravenous infusion pump to maintain a target BIS of 50 during induction and maintenance of anesthesia.
Active Comparator: Manual group; Propofol administration will be controlled manually using an intravenous infusion pump to maintain a target BIS of 50 during induction and maintenance of anesthesia.	Drug: Propofol; Propofol administration rate will be controlled by a feedback loop facilitated by BIS monitoring using the closed loop anaesthesia delivery system (CLADS). A BIS value of 50 will be used as the target point for induction and maintenance of anaesthesia.; Drug: Propofol; The target controlled infusion (TCI) pump will be programmed to marsh model with the target plasma site concentration of 3-µg/ml. The plasma concentration will be altered to maintain a target BIS of 50 during induction and maintenance of anesthesia; Drug: Propofol; The target controlled infusion (TCI) pump will be programmed to Schneider model with the target effect site concentration of 3-µg/ml. The effect-site concentration will be altered to maintain a target BIS of 50 during induction and maintenance of anesthesia; Drug: Propofol; Manual propofol administration will be done using an intravenous infusion pump to maintain a target BIS of 50 during induction and maintenance of anesthesia.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anaesthesia depth consistency	It will be determined by the percentage of the anaesthesia time during which the BIS remained +/- 10 of the target BIS of 50	From end of surgery till 8 hours intraoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intra-operative heart Rate (beats per minute)	Comparison of intra-operative heart rate between the study arms will be done	From beginning of anaesthesia till 10 hours intraoperatively
Intra-operative systolic , diastolic, and mean blood pressure (mmHg)	Comparison of intra-operative blood pressure- systolic, diastolic, and mean blood pressure between the study arms will be done	From beginning of anaesthesia till 10 hours intraoperatively
Postoperative sedation	Will be assessed using Modified Observer's assessment of alertness/sedation scale. The scale has a maximum value of '5', which refers to a fully awake patient and a minimum value of '0' which refers to a deeply sedated patient.	From end of anaesthesia till 24-hours postoperatively
Performance characteristic of propofol delivery system	It will be determined using the Varvel criteria parameter :median performance error (MDPE). This parameter is calculated by the computer software which analyses the intraoperative BIS data. This parameter have no unit of measurement. Its just a abstract number.	From end of surgery till 10-hours intraoperatively
Performance characteristic of propofol delivery system	It will be determined using the Varvel criteria parameter: median absolute performance error (MDAPE).This parameter is calculated by the computer software which analyses the intraoperative BIS data. This parameter have no unit of measurement. Its just a abstract number.	From end of surgery till 10-hours intraoperatively
Performance characteristic of propofol delivery system	It will be determined using the Varvel criteria parameter: wobble. This parameter is calculated by the computer software which analyses the intraoperative BIS data. This parameter have no unit of measurement. Its just a abstract number..	From end of surgery till 10-hours intraoperatively
Performance characteristic of propofol delivery system	It will be determined using the Varvel criteria parameter: global score. It is calculated using the formula Median absolute performance error + wobble / percentage of the anesthesia time during which the BIS remained +/- 10 of the target BIS of 50. This parameter have no unit of measurement. Its just a abstract number..	From end of surgery till 10-hours intraoperatively
Propofol induction dose (mg/kg)	Dose of propofol required for induction of anaesthesia	From start of propofol injection till 2-minutes intraoperatively
Propofol maintenance dose (mg/kg/hr)	Dose of propofol required for maintenance of anaesthesia	From 2-minutes intraoperatively till 10-hours intraoperatively
Early recovery from anaesthesia	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
Early recovery from anaesthesia	Time taken for tracheal extubation after discontinuation of anaesthesia will be noted	From end of anaesthesia till 20-minutes postoperatively
Induction Time	Time taken for for induction of anesthesia i.e. time taken from starting propofol infusion till a target BIS value of 50 is achieved	From beginning of anesthesia till 5-minutes intraoperatively

Collaborators and Investigators

• Sponsor: Sir Ganga Ram Hospital
• Investigators: Study Chair: Jayashree Sood, MBBS, MD, FFRCA, PGDHHM, FICA, Sir Ganga Ram Hospital, New Delhi, INDIA; Study Director: Goverdhan D Puri, MBBS, MD, PhD, Postgraduate Institute for Medical Education & Research, Chandigarh, India; Principal Investigator: Nitin Sethi, MBBS, DNB, Sir Ganga Ram Hospital, New Delhi, INDIA; Principal Investigator: Amitabh Dutta, MBBS, MD, PGDHR, Sir Ganga Ram Hospital, New Delhi, INDIA

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2021
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): February 1, 2025

Study Registration Dates

• First Submitted: January 25, 2021
• First Submitted That Met QC Criteria: January 28, 2021
• First Posted (Actual): February 1, 2021

Study Record Updates

• Last Update Posted (Actual): January 23, 2024
• Last Update Submitted That Met QC Criteria: January 22, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Hypnotics and Sedatives; Propofol
• Other Study ID Numbers: EC/12/20/1787

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