Clinical trial NCT03571945: Incidence of Intraoperative Awareness in Indian Patient Population
Official title: Impact of Bi-spectral Index Guided Inhalation Anaesthesia on the Incidence of Intraoperative Awareness in Indian Patient Population: A Prospective, Randomised, Multi-Centric Study
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: NA
Conditions: Intraoperative Awareness
Lead sponsor: Sir Ganga Ram Hospital
Sponsor class: OTHER
First posted: 2018-06-28
Enrollment: 2000
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: 2000- patients aged 18-65 years scheduled for elective surgery under general anaesthesia will be randomly allocated to one of the following two groups:

Group I \[BIS Guided Group, n=1000\]: GA will be monitored and controlled with Bi-spectral index (BIS).

Group II \[ETAG Guided Group, n=1000\]: GA will be monitored and controlled with end-tidal anaesthesia gas concentration (ETAG).
Primary purpose: PREVENTION

Brief summary: The profiling of bi-spectral index (BIS) monitored facilitation of general anesthesia (GA), including, anesthesia induction and maintenance of GA depth state, emergence characteristics, and postoperative recovery parameters, is now extensively available. However, majority of the data supporting the use of BIS have emanated from western Caucasian patient population. Though research on BIS monitoring have also emerged from Asian subcontinent, the data generated, at the best, is too scattered, random, and non-homogenous to reflect onto how BIS guidance fares in Asians on a population basis. We aim to undertake a multi-centric prospective cohort trial in Asian patient population to analyze as to whether BIS guidance toes the profiling and the evidence in Caucasians.

Detailed description: After Institutional Ethics Committee approval and informed written patient consent, 2000 patients justifying inclusion and exclusion criteria ( will be included in this National, multi-centric, prospective, randomised, double-blind (patients, analyst), 2- arm trial.

All the patients scheduled for elective surgery under general anaesthesia will be randomly (simple computer generated random number table) allocated to one of the following two groups:

Group I \[BIS Guided Group, n=1000\]: GA will be monitored and controlled with Bi-spectral index (BIS).

Group II \[ETAG Guided Group, n=1000\]: GA will be monitored and controlled with end-tidal anaesthesia gas concentration (ETAG).

Sample Size Estimation To detect a difference in incidence of awareness of 0.04 % (a rate based on Mashour et al, Anesthesiology 2012) between the ETAG and BIS-guided group a total of 1800 patients will be required at a power of 80% with a type-II error 0f 0.5. To compensate for possible drop outs 10% additional patients will be recruited for the study. Therefore, the total sample size will include 2000 patients.

Randomization concealment: will be done using opaque sealed envelopes with alphabetic codes. In addition, before opening the envelope patient's data slip will be pasted on the envelopes.

Blinding: Investigator, assessor and the data analyst will be blinded to the method of GA (BIS or ETAG guided) Subgroup Analysis: Subgroup analysis will be specifically performed and reported if the data shows gender equivalence (i.e., at least 40% patients of either sex in each group).

Anaesthesia Technique:

Routine monitoring (EtCO2, pulse oximetery, EKG, NIBP) will be applied during the procedure. Anaesthesia will be induced with fentanyl 2-mcg/kg and propofol 1.5-2.5 mg/kg. Non-depolarizing muscle relaxant (vecuronium/ rocuronium/ atracurium) will be administered to facilitate tracheal intubation. GA will be maintained with inhalation regimen (sevoflurane/desflurane-oxygen-air mixture) to target age-related MAC range of 0.7 to 1.3. Corresponding BIS score and end-tidal agent concentration will be noted at 5-minute interval. While, in the BIS group the anaesthesiologist will be blinded to ETAG and MAC readings, in the ETAG group BIS display will be turned off. However, ETAG and MAC data will both be analyzed once the study is over. Although, the MAC will be titrated to haemodynamic goals (+20% baseline of SBP/MAP/Heart rate), it will be maintained within the prescribed range. On either side of the range of MAC, the haemodynamic depression/ activation will be responded to with vasopressor/vasodilators. At the end of surgery inhalation agent delivery will be stopped. The residual neuromuscular blockade will be reversed with neostigmine and glycopyrrolate.

The patients will be extubated once wide-awake and following commands. ASSESSMENT PARAMETERS Analysis of Intraoperative Awareness Quantitative: The participants will be subjected to modified Brice Interview 20 24-hours after surgery and after one month. The Brice interview at one month will be undertaken through telephonic contact and if awareness is present on any or both the occasions, a three-member independent awareness committee will review the incidence intensively. The awareness will be adjudicated in broad divisions, including, definite, possible, and no awareness. 21 No Awareness: No awareness or a perception of awareness that has a high probability of occurrence in the preoperative and the postoperative period.

Possible Awareness: There is a perception of awareness but the patient is unable to recall any event definitive indicative of awareness.

Definite Awareness: Perception of awareness that has clear recall or has a high likelihood of occurring in the intraoperative period.

Qualitative: After adjudication of a definite awareness by the awareness committee, the participants will be classified on the awareness pattern using the Michigan awareness classification instrument. 21 Class 1 will be defined by isolated auditory perception, Class 2 by tactile perceptions, Class 3 by pain experience, Class 4 by a feeling of paralysis and helplessness to move, and Class 5 by the presence of both paralysis and pain. If the awareness event is associated with distress the class will be modified with a suffix "D".

If definite awareness is present, the participants will be offered counselling sessions to ward off long-term behavioral changes and post-traumatic stress disorder (PTSD) The inter-reviewer observation will be analyzed for agreement using Fleiss's Kappa statistics for blinded assessment.

BIS score and end-tidal inhalation agent concentration: The intraoperative BIS scores and end-tidal inhalation agent concentration will be noted (every 5-minutes).

Time to awakening and tracheal extubation: Time (in minutes) to awakening will be noted after discontinuation of anaesthesia to point of first spontaneous eye opening. The time will be confirmed by the ability of the patient to obey commands. Time (in minutes) to tracheal extubation will comprise of the period after discontinuation of anaesthesia to tracheal extubation.

Statistical Analysis:

Demographic and procedural data will be analyzed with student's t-test, double sided, or the Chi-square test with Yate's correction as appropriate. Analysis of awareness outcome will be performed using Fisher's exact test. Sensitivity and specificity analysis will be undertaken for BIS values vis-à-vis explicit recall or no recall.

Eligibility criteria: Inclusion Criteria:

* Male or female gender
* Aged 18-65 yrs.
* ASA Physical Status I/II
* General Anaesthesia
* Elective Surgery
* Surgery duration \> 30-minutes
* Consenting for follow-up

Exclusion Criteria:

* Uncompensated systemic co-morbidity
* Cardiac and Neurosurgical procedures
* Head \& Neck surgery
* Obstetric surgery
* Emergency surgery
* Anticipated difficult airway
* H/O brain injury, EEG abnormality
* Neuropsychiatry disorders
* Substance abuse (opioids, alcohol, recreational drugs, benzodiazepine)
* Pacemakers \& Electronic implants
* Obesity (BMI\>30kg/m2)
* Adhesive allergy

Primary outcomes:
measure: Incidence of intraoperative awareness
timeFrame: From end of anaesthesia till 30-days postoperatively
Secondary outcomes:
measure: Intraoperative Bi-spectral index (BIS) score
timeFrame: From beginning of anaesthesia (0-hours, baseline) till 8 hours intraoperatively
measure: Intraoperative End-tidal anaesthesia gas (ETAG) concentration
timeFrame: From beginning of anaesthesia (0-hours, baseline) till 8 hours intraoperatively
measure: Intraoperative minimum alveolar concentration (MAC)
timeFrame: From beginning of anesthesia (0-hours, baseline) till 8 hours intraoperatively
measure: Recovery from anaesthesia
timeFrame: From end of anaesthesia till 20-minutes postoperatively
measure: Recovery from anaesthesia
timeFrame: From end of anaesthesia till 20-minutes postoperatively
measure: Changes in intra-operative heart rate (beats per minute)
timeFrame: From beginning of anesthesia (0-hours, baseline) till 8 hours intra-operatively
measure: Change in Intra-operative blood pressure - systolic , diastolic, and mean (mmHg)
timeFrame: From beginning of anaesthesia (0-hours, baseline) till 8 hours intraoperatively]
measure: Postoperative Sedation
timeFrame: From end of anaesthesia till 24-hours postoperatively]
measure: Postoperative Nausea and Vomiting (PONV)
timeFrame: From end of anaesthesia till 24-hours postoperatively]
measure: Postoperative Analgesia
timeFrame: From end of anaesthesia till 24-hours postoperatively
Other outcomes:
Locations:
city: New Delhi
country: India
facility: Sir Ganga Ram Hospital
state: Delhi
city: Chennai
country: India
facility: Prof. L Parthasarathy
state: Tamil Nadu
city: Chandigarh
country: India
facility: Post Graduate Institute For Medical Education & Research
city: Kolkata
country: India
facility: Apollo Gleneagles Hospital
city: Mumbai
country: India
facility: P D Hinduja Hospital & Medical Research Centre
Study officials:
affiliation: Sir Ganga Ram Hospital
name: Amitabh Dutta, MD, PhD
role: STUDY_CHAIR
affiliation: Sir Ganga Ram Hospital
name: Jayashree Sood, MD,FFRCA
role: STUDY_DIRECTOR
affiliation: Sir Ganga Ram Hospital
name: Nitin Sethi, DNB
role: PRINCIPAL_INVESTIGATOR
References: