The Effect of Low Dose Intra-operative Ketamine on Closed-loop Controlled General Anesthesia
Condition: Anesthesia
Study type: Interventional
Phase: Phase 1

Summary: 
      Closed-loop control of anesthesia involves using feedback from a measure of clinical effect
      to continuously adjust drug infusion rates. As a result, anesthetic drugs are delivered at a
      variable rate that is frequently personalized to each individual patient. The aim is to
      provide greater stability at an optimal depth of anesthesia, reducing the occurrence of
      under- or overdosing, with the goal of ultimately improving patient outcomes.

      The purpose of this randomized, controlled equivalence trial is to compare controller
      performance during closed-loop controlled induction and maintenance of total intravenous
      anesthesia, using iControl system, with the addition of a low (analgesic) dose of ketamine
      versus saline control.
    

Detailed description: 
      For the primary outcome measure, the investigators hypothesize that controller performance
      with low-dose ketamine will be equivalent to the controller performance without low-dose
      ketamine. The primary outcome measure, controller performance, is the percentage of time
      during the maintenance phase when the depth-of-hypnosis (DOH) measure is within +-10 points
      of the set point in patients receiving low dose ketamine versus those receiving saline
      control.

      This study will consider other clinical data of interest from both intra- and post-operative
      contexts in order to establish a broader understanding of the potential implications of the
      use of a low dose of ketamine during closed-loop controlled anesthesia. In the OR, the
      investigators will record other indications of anesthetic quality, such as vital signs and
      the occurrence of any unwanted intra-operative events. Propofol and remifentanil consumption
      will be quantified, and the requirement of any other interventions will be recorded. The
      investigators will also record post-operative patient outcomes that have previously been
      associated with ketamine administration, such as acute post-operative pain intensity, opioid
      requirements, the occurrence of PONV, and shivering occurring in the post-anesthesia care
      unit (PACU).
    

Intervention name(s): Ketamine Injectable Solution; Placebo
Intervention type(s): Drug; Other
Intervention description(s): Once IV access has been obtained and a facemask has been applied for pre-oxygenation, the loading dose (0.25 mg/kg) of the study drug will be given over 60 seconds and the fixed infusion (5 mcg/kg/min to a maximum of 60 mg/hour) will be initiated by the anesthetist through the pump interface.
The study drug will be infused at a constant rate of 5 mcg/kg/min throughout the maintenance phase, until the end of the procedure (last suture), up to a maximum cumulative dose of 100 mg. If at any point the anesthesiologist feels that it is clinically necessary to reduce the amount of study drug infusion rate, they may opt to reduce the infusion rate by 50% (to 2.5 mcg/kg/min), or stop the infusion entirely.; Participants in the control group will receive an equivalent volume bolus and infusion of normal saline to mimic the ketamine infusion in the ketamine group.
Intervention MeSH terms: Ketamine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Other