Evaluation of Closed-loop Titration of the Intravenous Anesthetic Propofol, Sufentanil and Ketamine Guided by BIS Monitor

Recent efforts have focused on the development of new software systems that are able to directly titrate anesthesia based on activity of the brain (EEG) as a feedback mechanism . Brain activity is used to measure the effect of anesthetic medications (anesthetic "depth"), which can vary from person to person despite being given the same amount of medication. There is a potential for new systems to considerably improve anesthetic control by using methods that are able to adapt to the constant input of brain activity. The purpose of this study is to compare a closed -loop intravenous anesthetic (TIVA) using BIS (Bispectral Index) as a feedback loop and a controller based on reinforcement learning to titrate dose and TIVA that is manually controlled or a standard volatile anesthetic agent titrated by the anesthesiologist.

Propofol is the most frequently applied hypnotic-anesthetic IV drug during anesthesia. In "open-loop" controlled propofol administration during anesthesia, initial dosing guidelines are based on the typical subject, without taking into account the large inter-individual variability. To manage this variability, most clinicians will start by giving a standard dose, observes the therapeutic effect and will adapt the dose regimen. Although, "open-loop" drug administration is clinically "standard-of-care", the efficiency of this decision process highly depends on the expertise of the clinician, is very time consuming and might result in a suboptimal therapy.

The study will be using patient with acute cholecystitis scheduled for laparoscopic cholecystectomy surgery and the inclusion/exclusion criteria is described in the appropriate sections. Potential subjects will be identified prior to their surgery based on meeting the inclusion/exclusion criteria. The subject will be approached in the inpatient unit or pre-operative holding area, a private area where curtains can be drawn to maintain privacy. This is a place where patients are routinely examined and consented prior to surgery.. The subject will be informed that participation or a lack of participation in the study does not influence their treatment in any way. The subject will be informed that if they give consent for participation in the study that they may withdraw consent at any time before performance of the study. This withdrawal of consent may be given to the investigator in oral or written form.

The Investigator will explain the study to the potential subject verbally, providing all pertinent information (purpose, procedures, risks, benefits, alternatives to participation, etc.), and allow the potential subject ample opportunity to ask questions. Following this verbal explanation, the potential subject will be provided with a written consent form and given at least one hour to consider whether or not to participate in the research. After allowing the potential subject time to read the consent form, an Investigator listed on the consent form will meet with the potential subject and answer any additional questions she/he may have.

The subject will have been pre randomized to a study arm (Permuted block randomisation via computer generated numbers) and will not be informed which study arm. The three study arms are RL-TIVA (experimental), Manual TIVA, and INH-Sevo.