Clinical trial NCT05725135: Effect of Gender on Propofol Requirement
Official title: Gender Differences in Propofol Requirements During Total Intravenous Anaesthesia Administered by Closed-loop Anaesthesia Delivery System: An Observational Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Anesthesia
Keywords: propofol
male
female
Lead sponsor: Sir Ganga Ram Hospital
Sponsor class: OTHER
First posted: 2023-02-13
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients undergoing elective surgery requiring general anesthesia

Brief summary: Total intravenous anaesthesia (TIVA) has emerged as a viable alternative to inhalational general anaesthesia (GA). Propofol is the preferred drug for providing TIVA due to its favorable pharmacokinetic profile, such as, rapid onset of action and a short context sensitivity half -life. There is suggestion that consumption of Propofol required during TIVA is influenced by gender with females requiring higher dose due to higher volume of distribution of drug. The evidence on gender differences in Propofol requirement for TIVA is largely based on studies done using subjective (manual titration of infusions)/semi-objective (target-controlled infusions) methods of drug administration, whose initial setting and ongoing control may be affected by attending anesthesiologist discretion and action. A recent advance in Propofol TIVA delivery is development of objective automated anaesthesia delivery systems. These systems administer Propofol titrated to patients' electroencephalogram (EEG) response reflected by processed EEG monitoring, namely the Bispectral index (BIS). One such indigenously developed automated anaesthesia delivery system is the closed-loop anaesthesia delivery system (CLADS). CLADS is a more precise and robust system to facilitate administration of Propofol TIVA, which automatically regulates the dose of medication based on feedback from patient's BIS data. The present study proposes to explore if there can be any gender differences in Propofol requirements during total intravenous anaesthesia administered by CLADS. All patients undergoing elective surgery under Propofol TIVA using CLADS will be screened, and those eligible will be enrolled. Enrolled patients will receive automated Propofol TIVA using CLADS. Demographic and clinical details including gender of patient will be noted. Cumulative dose of Propofol use will be computed through algorithm executed and monitored by software built into the CLADS. The findings will then be compared between male and female gender. Other intraoperative and post- operative outcomes such as time-to-loss of consciousness, time-to-induction of anaesthesia, anaesthesia depth consistency, performance characteristic of CLADS, hemodynamic profile (heart rate, mean arterial blood pressure), time-to-early recovery from anaesthesia, and postoperative sedation scale (modified observers' assessment of alertness/sedation scale \[MOAA/S\]); will be noted and compared between males and females. We expect to enroll 80 patients in our study.

Detailed description: Total intravenous anaesthesia (TIVA) has emerged as a viable alternative to inhalational general anaesthesia (GA). Progress into TIVA is much desirable for continued development of precision GA. To this effect, Propofol is a key intravenous agent because of its favorable pharmacokinetic (PK) and pharmacodynamic (PD) profile and broad administration applicability with different methods of delivery: manual and target-controlled infusion \[TCI\].

The evidence on gender differences during manual/TCI Propofol TIVA suggests that females as compared to males have increased requirement of Propofol and yet have a faster time to recovery from anaesthesia. A 5-10% excess body fat and 15-20% decreased water content in females as compared to males' results in an increase in volume of distribution (Vd) of lipophilic drugs (e.g., Propofol), which consequently necessitates a higher rate of delivery of the Propofol infusion to achieve the same plasma concentration (as males) for clinically acceptable depth-of-anaesthesia. Whereas an increased Propofol sensitivity results in early awakening from anaesthesia.

The studies on gender differences in Propofol requirements and recovery from anaesthesia are largely based on semi-objective methods of Propofol TIVA administration (manual/TCI). The human element in titration and control of manual/TCI delivery of Propofol TIVA in above studies may be a limiting and a confounding factor in interpretating the actual difference induced by the 'gender' context. Whilst processed electroencephalogram (EEG) monitoring (Bispectral index \[BIS\], entropy, Narcotrend®) facilitates control of Propofol TIVA; it may still be imprecise due to subjective differences in understanding and execution of Propofol TIVA.

A recent advance in Propofol TIVA delivery is the development of automated anaesthesia delivery systems such as closed loop anaesthesia delivery system (CLADS). These systems administer Propofol actuated, titrated, and controlled by patients' processed electroencephalogram (EEG) response as generated by continuously monitored bispectral index (BIS) score. Current evidence suggests that automated Propofol TIVA delivery systems such as closed loop anaesthesia delivery system (CLADS) facilitate precision administration of Propofol than its TCI/manual counterparts.

Despite a plethora of evidence on effectiveness of Propofol TIVA, gender differences in Propofol PK and PD have not been evaluated while using automated systems of delivery. With the premise that widely researched and precise automated closed-loop anaesthesia delivery system (CLADS) has clear advantages (lower 'operator' dependence and inclusion of 'patient' factor) over manual/TCI mode; it is likely that Propofol TIVA administered by CLADS will lend greater objectivity in qualifying and quantifying the inter-gender differences in Propofol consumption and recovery from anaesthesia. The proposed observational study is planned to explore the gender differences in Propofol consumption and recovery from anaesthesia following CLADS controlled Propofol TIVA.

Eligibility criteria: Inclusion Criteria:

* Age 18-60 years.
* ASA physical status I and II.
* Patients undergoing elective surgeries of minimum 1 hour duration.

Exclusion Criteria:

* Uncompensated cardiovascular disease (e.g., uncontrolled hypertension, systolic and diastolic dysfunction)
* Hepatic dysfunction (liver enzymes \> 2 times the normal range)
* Renal dysfunction (serum creatinine \> 1.4 mg/dl)
* Psychiatric or neurological disorder
* Uncontrolled endocrinology disease (diabetes mellitus, hypothyroidism)
* Known allergy/hypersensitivity to the study drug
* History of recent intake of sedative medication or anti-psychotic medication
* Drug dependence/substance abuse
* Requirement of postoperative ventilation
* Refusal to informed consent

Primary outcomes:
measure: Cumulative Propofol consumption (mg/kg/h) during anaesthesia
timeFrame: From start of Propofol injection 10-hours intraoperatively]
Secondary outcomes:
measure: Time to loss of consciousness
timeFrame: From start of anesthesia till 5- minutes intraoperatively
measure: Time to induction of anaesthesia
timeFrame: From start of anesthesia till 5- minutes intraoperatively
measure: Intra-operative heart rate (beats per minute)
timeFrame: From beginning of anesthesia till 10 hours intraoperatively
measure: Intra-operative systolic , diastolic, and mean blood pressure (mmHg)
timeFrame: From beginning of anesthesia till 10 hours intraoperatively
measure: Anesthesia depth consistency
timeFrame: From beginning of anesthesia till 10 hours intraoperatively
measure: Performance characteristic of Propofol delivery system
timeFrame: From beginning of anesthesia till 10 hours intraoperatively
measure: Performance characteristic of Propofol delivery system
timeFrame: From beginning of anaesthesia till 10 hours intraoperatively
measure: Performance characteristic of Propofol delivery system
timeFrame: From beginning of anaesthesia till 10 hours intraoperatively
measure: Performance characteristic of Propofol delivery system
timeFrame: From beginning of anaesthesia till 10 hours intraoperatively
measure: Early recovery from anesthesia
timeFrame: From end of anaesthesia till 20-minutes postoperatively
measure: Early recovery from anesthesia
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: Sir Ganga Ram Hospital
state: Delhi
Study officials:
affiliation: Sir Ganga Ram Hospital, New Delhi, INDIA
name: Nitin Sethi, DNB
role: PRINCIPAL_INVESTIGATOR
affiliation: Sir Ganga Ram Hospital, New Delhi, INDIA
name: Amitabh Dutta, MD, PGDHR
role: STUDY_DIRECTOR
affiliation: Sir Ganga Ram Hospital, New Delhi, INDIA
name: Jayashree Sood, MD, FFRCA, PGDHHM, FICA
role: STUDY_CHAIR
References: