Clinical trial NCT04731480: Comparison of TIVA by Closed Loop Anaesthesia Delivery System Versus Target Controlled Infusion Device
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Anesthesia
Lead sponsor: Sir Ganga Ram Hospital
Sponsor class: OTHER
First posted: 2021-02-01
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: One hundred sixty-participants (40/group) aged 18-65 years, ASA physical status I-II, of either sex, and undergoing elective non-cardiac surgery of minimum 60-minutes duration recruitment will be randomly divided into one of the four groups:

Group-1 \[CLADS group, n= 40, study group\], Group-2 \[Marsh model (MM) group, n= 40, study group\], Group-3 \[Schneider Model (SM) Group, n= 40, study group\], and Group-4 \[Manual (M) Group, n= 40, Control group\].
Primary purpose: OTHER

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).

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

Primary outcomes:
measure: Anaesthesia depth consistency
timeFrame: From end of surgery till 8 hours intraoperatively
Secondary outcomes:
measure: Performance characteristic of propofol delivery system
timeFrame: From end of surgery till 10-hours intraoperatively
measure: Performance characteristic of propofol delivery system
timeFrame: From end of surgery till 10-hours intraoperatively
measure: Performance characteristic of propofol delivery system
timeFrame: From end of surgery till 10-hours intraoperatively
measure: Performance characteristic of propofol delivery system
timeFrame: From end of surgery till 10-hours intraoperatively
measure: Propofol induction dose (mg/kg)
timeFrame: From start of propofol injection till 2-minutes intraoperatively
measure: Propofol maintenance dose (mg/kg/hr)
timeFrame: From 2-minutes intraoperatively till 10-hours intraoperatively
measure: Intra-operative heart Rate (beats per minute)
timeFrame: From beginning of anaesthesia till 10 hours intraoperatively
measure: Intra-operative systolic , diastolic, and mean blood pressure (mmHg)
timeFrame: From beginning of anaesthesia till 10 hours intraoperatively
measure: Early recovery from anaesthesia
timeFrame: From end of anaesthesia till 20-minutes postoperatively
measure: Early recovery from anaesthesia
timeFrame: From end of anaesthesia till 20-minutes postoperatively
measure: Postoperative sedation
timeFrame: From end of anaesthesia till 24-hours postoperatively
measure: Induction Time
timeFrame: From beginning of anesthesia till 5-minutes intraoperatively
Other outcomes:
Locations:
city: New Delhi
country: India
facility: Nitin Sethi
state: Delhi
city: New Delhi
country: India
facility: Sir Ganga Ram Hospital
state: Delhi
Study officials:
affiliation: Sir Ganga Ram Hospital, New Delhi, INDIA
name: Jayashree Sood, MBBS, MD, FFRCA, PGDHHM, FICA
role: STUDY_CHAIR
affiliation: Postgraduate Institute for Medical Education & Research, Chandigarh, India
name: Goverdhan D Puri, MBBS, MD, PhD
role: STUDY_DIRECTOR
affiliation: Sir Ganga Ram Hospital, New Delhi, INDIA
name: Nitin Sethi, MBBS, DNB
role: PRINCIPAL_INVESTIGATOR
affiliation: Sir Ganga Ram Hospital, New Delhi, INDIA
name: Amitabh Dutta, MBBS, MD, PGDHR
role: PRINCIPAL_INVESTIGATOR
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