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

NCT ID: NCT04731480

Last Updated: 2025-08-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-02
• Study Completion Date: 2025-06-17

Brief Summary

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.

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).

Conditions

Anesthesia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Propofol

Intervention Type: DRUG

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.

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

Group Type: ACTIVE_COMPARATOR

Propofol

Intervention Type: DRUG

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

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.

Group Type: ACTIVE_COMPARATOR

Propofol

Intervention Type: DRUG

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

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.

Group Type: ACTIVE_COMPARATOR

Propofol

Intervention Type: DRUG

Manual propofol administration will be done using an intravenous infusion pump to maintain a target BIS of 50 during induction and maintenance of anesthesia.

Interventions

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.

Intervention Type: 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

Intervention Type: 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

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sir Ganga Ram Hospital

OTHER

Sponsor Role: lead

Responsible Party

Nitin Sethi, DNB

Senior Consultant

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jayashree Sood, MBBS, MD, FFRCA, PGDHHM, FICA

Role: STUDY_CHAIR

Sir Ganga Ram Hospital, New Delhi, INDIA

Goverdhan D Puri, MBBS, MD, PhD

Role: STUDY_DIRECTOR

Postgraduate Institute for Medical Education & Research, Chandigarh, India

Nitin Sethi, MBBS, DNB

Role: PRINCIPAL_INVESTIGATOR

Sir Ganga Ram Hospital, New Delhi, INDIA

Amitabh Dutta, MBBS, MD, PGDHR

Role: PRINCIPAL_INVESTIGATOR

Sir Ganga Ram Hospital, New Delhi, INDIA

Locations

Nitin Sethi

New Delhi, National Capital Territory of Delhi, India

Sir Ganga Ram Hospital

New Delhi, National Capital Territory of Delhi, India

Countries

India

Other Identifiers

EC/12/20/1787

Identifier Type: -

Identifier Source: org_study_id