Clinical trial NCT05967403: Performance Analysis of Hermetic Closed-loop Anesthesia Delivery System
Official title: Anaesthesia Depth Consistency and System Performance of a Hermetic Closed-loop Anaesthesia Delivery System: A Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Anesthesia
Keywords: propofol
closed-loop
anesthesia
Lead sponsor: Sir Ganga Ram Hospital
Sponsor class: OTHER
First posted: 2023-08-01
Enrollment: 150
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 and fifty participants (75/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 two groups:

Group-1 \[Conventional CLADS (CC) group, n= 75\]: Anaesthesia will be induced and maintained with propofol administered using the automated conventional CLADS.

Group-2 \[Hermetic CLADS (HC) group, n= 75\]: Anaesthesia will be induced and maintained with propofol administered using the hermetic CLADS.
Primary purpose: OTHER

Brief summary: Total intravenous anaesthesia (TIVA) is now a preferred technique for providing general anaesthesia (GA) because of its various inherent advantages like reduced postoperative nausea and vomiting (PONV), improved quality of post-operative recovery, anti-inflammatory and antioxidant action, anti-neoplastic activity, analgesic action, and absence of greenhouse effect. The evolution and advancement in automated anaesthesia delivery systems particularly for propofol have made propofol-TIVA more efficient by removing the human interface for both rate and concentration adjustments. Automated computer-controlled closed loop anaesthesia device adjusts propofol delivery based on patient's frontal cortex electrical activity determined by bispectral index (BIS).

Closed loop anaesthesia delivery system (CLADS) is an indigenously developed patented (Patent no.502/DEL/2003 \& US 9,108,013 B2) computer-controlled anaesthesia delivery system which works with feedback loop information elicited by BIS monitoring and delivers propofol TIVA to the patient via a non-TCI automated infusion pump. It has been an extensively used and validated in patients undergoing both cardiac and non-cardiac surgical procedures.

A new compact and upgraded version of CLADS is now available. This new version incorporates the anesthetic depth monitor, hemodynamic monitor, controller, user interface and actuator syringe pump into a single, compact and user-friendly module.

The investigators aim to conduct a prospective randomized pilot study comparing the new CLADS and older CLADS version with respect to: adequacy of anaesthesia depth maintenance, performance characteristic of propofol delivery system, propofol requirement, haemodynamics stability, recovery from anesthesia and postoperative sedation.

Detailed description: Propofol total intravenous anaesthesia (TIVA) is a preferred technique for providing induction and maintenance of general anaesthesia (GA). As opposed to the conventional inhaled anesthetics for maintaining GA, propofol TIVA has several advantages, such as, lower incidence of postoperative nausea and vomiting (PONV), antinociceptive and anti-inflammatory action, anti-neoplastic activity, and most importantly, its environment disposition (no greenhouse effect); and therefore, has potential to replace inhaled vapors for GA.

The introduction of target-controlled infusion (TCI) pumps has allowed precision control in propofol delivery as compared to the conventional manually operated infusion pumps. In manually operated infusion pumps the clinician regulates the propofol infusion rate to achieve the desired anaesthesia depth, whereas TCI-pumps deliver propofol using inbuilt algorithms based on the pharmacokinetic (PK) and pharmacodynamic (PD) profile of propofol. Two of the most used PK-PD models for propofol delivery are the Marsh model and the Schneider model. Whereas in the Marsh model the user can set the desired target plasma concentration, Schneider model allows the user to set the desired target effect site concentration for achieving adequate depth of GA.

Over the last two decades the evolution and advancement in automated anaesthesia delivery systems, particularly for propofol administration, has made propofol-TIVA delivery more efficient by removing the human interface required for adjusting real-time propofol delivery, both rate and concentration of propofol. Automated anaesthesia delivery systems deliver propofol based on ascertaining frontal cortex electrical activity as determined by the processed electroencephalogram, the bispectral index (BIS) score. These devices regulate propofol delivery based on a feedback loop involving the BIS score (control variable) generated by the patient and the propofol infusion pump (actuator) and attempts to keep the values within a pre-assigned range, consistent with robust GA depth.

Closed loop anaesthesia delivery system (CLADS) is an indigenously developed patented (Patent no.502/DEL/2003 \& US 9,108,013 B2) computer-controlled anaesthesia delivery system which works with feedback loop information elicited by BIS monitoring and delivers propofol TIVA to the patient via a non-TCI automated infusion pump. The basic control algorithm is based on the relationship between the infusion rates of propofol and BIS values, taking into consideration the pharmacokinetic variables, such as, drug distribution and clearance. The system updates the EEG data every 5-seconds and calculates the BIS error, a difference between the target BIS and the actual BIS value using the proportional-integral-derivative (PID) controller. During anaesthesia induction the target concentration is achieved in a stepwise manner with BIS feedback received every 5-seconds. During maintenance phase of anaesthesia, the propofol delivery is modified every 1-epoch of 30-seconds duration. In each epoch an average of initial 3-BIS values (of every 5-seconds) and average of last 3-BIS values (of every 5-seconds) are compared, and a trend assessment is made. If the trend indicates increasing BIS values, then higher propofol rate is delivered by the infusion pump (actuator) and vice-versa. The control algorithm is implemented using a personal computer (PC) with a Pentium 4 processor. The PC controls communication with the infusion pump (Pilot-C, Fresenius, Paris, France) and the vital sign monitor (AS5, Datex Ohmeda Division, GE Healthcare, Singapore) through RS 232 serial ports.

CLADS has been extensively used and validated for administering propofol TIVA in patients undergoing both cardiac and non-cardiac surgical procedures. In a multi-centric 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.

A new compact and upgraded version of CLADS (Clarity Medical Private Ltd., Mohali, Punjab Indiais now available. The new version integrates the anaesthetic depth as well as the hemodynamic monitor, the controller, the user interface and the actuator syringe pump into a single, compact and user-friendly module.

The investigators aim to conduct a prospective randomised pilot to compare the multiple connected-unit conventional CLADS with the hermetically unit-integrated CLADS version, with respect to, the adequacy of anaesthesia depth (primary objective); and, performance characteristic, propofol requirement, haemodynamic stability, recovery from anaesthesia and postoperative sedation of the delivery systems (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.
* Any history of neurological disorder (e.g., epilepsy) or brain trauma
* Uncontrolled endocrine diseases (e.g., diabetes mellitus, hypothyroidism).
* Known allergy/hypersensitivity to the study drug.
* History of any psychiatric disorder and/or drug dependence/substance abuse.
* Requirement of postoperative ventilation.
* Refusal to informed consent.

Primary outcomes:
measure: Anaesthesia depth consistency
timeFrame: From beginning of anaesthesia till 5- minutes post skin closure
Secondary outcomes:
measure: Performance characteristic of propofol delivery system
timeFrame: From beginning of anaesthesia till 5- minutes post skin closure
measure: Performance characteristic of propofol delivery system
timeFrame: From start of anesthesia till 5- minutes post skin closure
measure: Performance characteristic of propofol delivery system
timeFrame: From start of anesthesia till 5- minutes post skin closure
measure: Performance characteristic of propofol delivery system
timeFrame: From start of anesthesia till 5- minutes post skin closure
measure: . Propofol induction dose (mg/kg)
timeFrame: From start of propofol injection till 10-minutes intraoperatively
measure: . Propofol maintenance dose (mg/kg/h)
timeFrame: From start of propofol injection till 5-minutes post skin closure
measure: Time to loss of consciousness (measured in minutes)
timeFrame: From start of propofol injection till 10-minutes intraoperatively
measure: Time to induction of anaesthesia (measured in minutes)
timeFrame: From start of propofol injection till 10-minutes 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 (measured in minutes)
timeFrame: From end of anaesthesia till 20-minutes postoperatively
measure: Early recovery from anaesthesia (measured in minutes)
timeFrame: From end of anaesthesia till 20-minutes postoperatively
measure: Postoperative sedation
timeFrame: From end of anaesthesia till 24-hours postoperatively
Other outcomes:
Locations:
city: New Delhi
country: India
facility: Nitin Sethi
state: Delhi
Study officials:
affiliation: Sir Ganga Ram Hospital, New Delhi, INDIA
name: Nitin Sethi, DNB
role: STUDY_DIRECTOR
affiliation: Sir Ganga Ram Hospital, New Delhi, INDIA
name: Amitabh Dutta, MD, PGDHR
role: PRINCIPAL_INVESTIGATOR
affiliation: Post Graduate Institute of Medical Education & Research, Chandigarh, India
name: Goverdhan D Puri, MD, PhD
role: STUDY_CHAIR
References: