Effectiveness of the NeuroSENSE for Monitoring the Hypnotic Depth of Anesthesia

A Prospective, Blinded, Clinical Study for Assessing the Effectiveness of the NeuroSENSE for Monitoring the Hypnotic Depth of Anesthesia (DOA)

The objective of this clinical study is to investigate whether the NeuroSENSE is an adequate monitor of hypnotic depth-of-anesthesia (DOA). Therefore, this study will investigate whether the information provided by the NeuroSENSE Monitor can help in assessing the hypnotic effect of anesthetics in adult patients undergoing general anesthesia.

Study Overview

• Status: Completed
• Conditions: Depth of Anesthesia (DOA)
• Intervention / Treatment: Drug: Propofol induction followed by randomized doses of desflurane; Device: Recording of EEG using NeuroSENSE; Other: Data collection; Other: Drug: Emergence by stepping down the desflurane ET

Detailed Description

In particular, the study will focus on the correlation between the WAVcns index, a proprietary quantifier of cortical activity displayed by the NeuroSENSE, with (1) commonly assessed clinical endpoints/variables relating to the DOA, (2) changes in anesthetic drug administration, and (3) the anesthesiologist's assessment of the DOA based on standard of care monitors and his/her own observations of the patient state.

The hypothesis under evaluation is that the WAVcns index is an independent assessor of the progression of the anesthetic state and events of general anesthesia related to hypnotic endpoints.

• Study Type: Observational
• Enrollment (Actual): 76

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • New Westminster, British Columbia, Canada, V3L 3W7
      • Fraser Health: Royal Columbian Hospital
    • Port Moody, British Columbia, Canada, V3H 3W9
      • Fraser Health: Eagle Ridge Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adult patients undergoing general anesthesia procedure in the context of either open or laparoscopic abdominal surgical procedures (e.g. colectomy, hysterectomy, radical retropubic prostatectomy, nephrectomy, pancreatectomy, etc.), breast surgery including reduction, reconstruction and mastectomies, or orthopedic surgeries under general anesthesia, expected to last at least 1 hour.

Description

Inclusion Criteria:

• age 18-75 years
• ASA (American Society of Anesthesiologist) physical status I, II, or III
• ability to read and understand the informed consent form
• undergoing anesthesia procedure requiring intubation
• scheduled to undergo either open or laparoscopic abdominal surgical procedures (e.g. colectomy, hysterectomy, radical retropubic prostatectomy, nephrectomy, pancreatectomy, etc.), breast surgery including reduction, reconstruction and mastectomies, or orthopedic surgeries under general anesthesia, expected to last at least 1 hour.

Exclusion Criteria:

• history of major head injury (possible abnormal EEG)
• acquired scalp or skull abnormalities (e.g. psoriasis, eczema, angioma, scar tissue, burr holes, cranial implants)
• evidence of recent trauma or active neurological disorder, stroke, seizure disorder, intellectual disability, dementia or diagnosis of Alzheimer's disease
• major antipsychotic medications taken within last 7 days (eg. Lithium, risperidone, olanzapine)
• known history of alcohol or drug abuse within last 30 days
• body mass index (weight in kilograms divided by square of height in meters) > 40.0 kg/m2
• uncontrolled hypertension with blood pressure recorded prior to surgery (systolic blood pressure > 200 mmHg or diastolic blood pressure > 110 mmHg)
• systolic blood pressure < 90 mmHg, recorded prior to surgery
• heart rate (HR) < 45 beats/min, recorded prior to surgery
• insulin-dependent diabetes mellitus
• pregnancy
• any serious medical condition that would interfere with cardiovascular response assessment or study results interpretation

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Anesthesia; A single study group undergoing general anesthesia procedure to observe post-hoc the effect on the NeuroSENSE monitor readings. Interventions of interest: Drug: Propofol induction followed by randomized doses of desflurane; Emergence by stepping down the desflurane ET - See intervention descriptions. Device: Recording of EEG using NeuroSENSE (blinded to clinicians) - See intervention descriptions. Other: Data Collection - See intervention descriptions

Drug: Propofol induction followed by randomized doses of desflurane; Anesthesia in all patients will be induced with iv propofol 1.5 mg/kg with extra 0.5 mg/kg doses as needed. Anesthesia will be maintained using inhaled desflurane in oxygen/air with the initial desflurane concentration of 1.2 MAC, which will be changed in steps of ±0.4 MAC after reaching the post-intubation steady state. The step changes will be initiated every 7.5 min, as follows: at every level of MAC there is a 1/3 chance in remaining at this level and a 2/3 chance of changing it. The anesthesiologist can accept the change to move to the new level. However, he/she can also reject it to remain at the current level for another 7.5 min. This scheme yields 3 possible desflurane levels: 0.8, 1.2 and 1.6 MAC. The anesthesiologist can also leave the randomization schedule at anytime if clinically indicated, and later re-start it at his/her discretion. All anesthetic doses and their changes fall within conventional dosing.; Other Names: Diprivan; Suprane; Device: Recording of EEG using NeuroSENSE; The NeuroSENSE NS-701 system is a 2-channel device for brain activity monitoring in the operating room, intensive care unit, emergency room and other clinical settings. The system acquires and processes electroencephalograms (EEGs) via noninvasive electrodes placed on a patient's forehead. The acquired raw EEG signals and processed EEG variables are continuously displayed for interpretation by the clinician. The proprietary processed variable, WAVcns, quantifies the patient's brain activity, which is typically affected by anesthetic drugs. The system displays processed variables based on 2 bilateral channels (1 per brain hemisphere) for use as a supplement to the anesthesia standard of care. Note: the indications provided by the NeuroSENSE monitor are not used for anesthesia dosing or patient assessment in this study, and the anesthesia provider is blinded to the monitor readings. The device is used only for acquisition of EEG signals and may be used to log the events of interest.; Other Names: NeuroSENSE Monitoring System, Model NS-701 (approved in Canada and European market (CE Mark)); NeuroFAST Monitoring System, Model NF-202 (US name, the device is not cleared by the FDA); Other: Data collection; Non-invasive blood pressure (BP), heart rate (HR), respiratory rate (RR) and electroencephalogram (EEG) will be recorded during the surgery in all subjects. Also, information about all medically significant events, all study-related events (incl. patient's reactions, responses, observations and assessments) and administered medications (incl. end-tidal (ET) desflurane concentration) will be recorded along with time stamps. The anesthesia and physiological parameters (e.g., BP, HR, RR, ET agent concentration) outputted from the anesthesia monitor will be recorded electronically during the surgery by the anesthesia monitoring system (data-points will be recorded at least every 3 min for BP and every 10 sec for other variables). The EEG signal will be continuously recorded by NeuroSENSE NS-701 Monitor (described under a separate intervention). The CRC will also be present in the Operating Room (OR) to record and manage the recording of all the required information.; Other: Drug: Emergence by stepping down the desflurane ET; Anesthesia will be reduced to facilitate rapid recovery at the discretion of the anesthesiologist, about 20 minutes before the end of surgery. The desflurane ET will be stepped down from 0.8 MAC by steps of 0.2 MAC approximately every 5 min during the Emergence.; Other Names: Suprane

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prediction probability Pk for the WAVcns for consciousness vs unconsciousness	The primary outcome will test the performance of WAVcns index in discriminating between consciousness and unconsciousness during induction of anesthesia. It will be evaluated using Receiver-Operating Characteristic (ROC), and Area Under Curve (AUC) will be calculated. Note that the AUC statistic is equal to the prediction probability Pk for dichotomous responses, such as consciousness and unconsciousness.	During induction of anesthesia, an expected average of 4 min

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prediction probability Pk for the WAVcns for responders vs nonresponders to lidocaine aerosol	This secondary outcome will test if the WAVcns index prior to lidocaine insufflations or intubation is a good predictor of patient response. The aerosolized lidocaine will be used as a standardized stimulus to objectively assess response observed at the larynx and seen in the patient during airway manipulation during induction of anesthesia.	During induction of anesthesia, an expected average of 4 min
Correlation of the WAVcns with primary anesthetic dosing	This secondary outcome will test if the WAVcns index during anesthesia maintenance correlates with primary anesthetic dosing (end tidal agent concentration).	During anesthesia maintenance, an expected average of 2 hrs
Prediction probability for the WAVcns for responders vs nonresponders to verbal command	This secondary outcome will test if the WAVcns index accurately indicates return of consciousness (response to verbal command) during emergence.	During emergence from anesthesia, an expected average of 20 min

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of the WAVcns with burst-suppression ratio	This outcome will study the relationship between the WAVcns index and burst-suppression ratio during maintenance of anesthesia.	During maintenance of anesthesia, an expected average of 2 hrs

Collaborators and Investigators

• Sponsor: NeuroWave Systems Inc.
• Collaborators: Fraser Health; U.S. Army Medical Research Acquisition Activity
• Investigators: Principal Investigator: Richard Merchant, MD FRCPC, Fraser Health

Publications and helpful links

General Publications

• Gorges M, West NC, Cooke EM, Pi S, Brant RF, Dumont GA, Ansermino JM, Merchant RN. Evaluating NeuroSENSE for assessing depth of hypnosis during desflurane anesthesia: an adaptive, randomized-controlled trial. Can J Anaesth. 2020 Mar;67(3):324-335. doi: 10.1007/s12630-019-01522-5. Epub 2019 Nov 5.

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: March 12, 2014
• First Submitted That Met QC Criteria: March 13, 2014
• First Posted (Estimate): March 17, 2014

Study Record Updates

• Last Update Posted (Actual): February 25, 2020
• Last Update Submitted That Met QC Criteria: February 21, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Hypnosis; Propofol; NeuroSENSE; Anesthesia; Desflurane
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Hypnotics and Sedatives; Anesthetics, Inhalation; Propofol; Desflurane
• Other Study ID Numbers: 925-0701-DCI; W81XWH-06-C-0016 (Other Grant/Funding Number: US Army Medical Research Acquisition Activity)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes