The Effect of Ketamine on the WAVCNS Index During General Anesthesia: A Feasibility Study
Condition: Anesthesia
Study type: Interventional

Summary: 
      Monitoring the brain using electroencephalography (EEG) during general anesthesia provides
      the anesthesiologist with valuable feedback of how deeply anesthetized their patient is,
      reducing the chances of under- or overdosing and potentially improving patient outcomes.
      However, commercial EEG monitors that output processed EEG (pEEG) were developed under
      carefully controlled, simple anesthetic regimes - in contrast to the multimodal "cocktail" of
      drugs often used in clinical practice. Ketamine is one potential adjunct to a standard
      anesthetic, which has a growing body of evidence suggesting that it may improve
      post-operative outcomes. The effects of ketamine on pEEG parameters are poorly understood.
      This randomized, open-label, feasibility study will be undertaken in a sample of 30 adult
      outpatient surgery patients. The primary objective is to observe the intra-operative raw and
      pEEG trends using the NeuroSENSE monitoring system in patients receiving one of two different
      analgesic doses of ketamine, compared to patients not receiving ketamine, during an otherwise
      comparable general anesthetic. Secondarily, we will consider other clinical data of interest
      from both intra- and post-operative contexts in order to establish a broader understanding of
      the potential influence of two analgesic ketamine doses on anesthetic depth and
      post-operative outcomes. Feasibility outcomes will be assessed with the ultimate goal of
      developing a larger-scale clinical trial.
    

Detailed description: 
      Purpose of Study The primary aim of this study is to analyze the effect of two different
      intra-operative ketamine doses, within the low, analgesic range, on raw and processed EEG
      (the WAVCNS) during induction, maintenance, and emergence from general anesthesia compared to
      a no-ketamine control group. These data will be compared against other more traditional
      measures of depth of hypnosis (DoH), such as drug requirements, blood pressure, heart rate,
      and the occurrence of any unwanted intra-operative events. Ultimately, the results of this
      study will be used to assess whether or not it is feasible to rely on the WAVCNS index, as a
      valid measure of anesthetic effect, when either of these doses of ketamine has been added to
      an anesthetic regime. This will inform the feasibility of a larger trial comparing the effect
      of low dose ketamine on the performance of an automated anesthesia system.

      Secondarily, this study aims to observe certain post-operative outcomes that have previously
      been shown to be influenced by ketamine administration, in order to better understand the
      potential for patient benefit associated with these doses of ketamine. Specifically, we will
      record pain intensity, opioid requirements, PONV, dreaming, and shivering occurring in the
      post-anesthesia care unit (PACU).

      Justification for Study The amount of anesthetic required to maintain an adequate DoH varies
      widely between individual patients, and within patients under different conditions. Processed
      EEG-based DoH monitors provide the opportunity to deliver drugs at a dose more appropriate to
      a patient according to dynamic feedback of therapeutic effect. As a result, the quality of an
      anesthetic regimen and patient outcomes may be improved. However, since pEEG values are
      affected differently by different types and doses of drugs, these monitors would be much
      better utilized if the effects of certain drugs on processed values were better defined.
      Accumulating evidence suggests that the use of low dose intra-operative ketamine has the
      potential to be clinically beneficial, especially in terms of reducing post-operative pain,
      which may lead to reduced risk of delirium or chronic pain development. However, conclusive
      evidence on the effect of ketamine on pEEG indices is lacking and in particular, the effect
      of low dose ketamine on the NeuroSENSE monitor's WAVCNS index has not been investigated. This
      study will help to establish whether the WAVCNS index may be used as a reliable measure of
      clinical effect when one of two low doses of ketamine is used during general anesthesia. This
      is a significant step towards the development of a larger randomized controlled clinical
      trial in which the influence of ketamine on pEEG feedback-based anesthesia will be assessed.

      Methods Study Design This randomized, open-label, feasibility study will be undertaken in a
      sample of healthy adult outpatient surgery patients under the direct and immediate
      supervision of an experienced anesthesiologist.

      Intervention

      Patients will undergo general anesthesia, consisting of continuous infusions of propofol (for
      anesthesia) and remifentanil (for analgesia). The study-specific intervention is the addition
      of EEG monitoring with the NeuroSENSE monitor in all three groups, and the addition of one of
      two possible ketamine doses (bolus and infusion) in two groups:

        -  Group 1: Ketamine 0.5 mg/kg loading dose followed by a 10 mcg/kg/min infusion

        -  Group 2: Ketamine 0.25 mg/kg loading dose followed by a 5 mcg/kg/min infusion

        -  Group 3: Control - No ketamine

      Randomization Thirty study participants will be randomly allocated to one of three groups
      based on a randomization code assigned to them after they have provided their informed
      consent. Randomization will be performed in block sizes of six subjects to maintain
      relatively even group sizes throughout the study period.

      Blinding The goal of this study is to integrate the protocol with an otherwise standard
      anesthetic. As a result, the anesthesiologist will be blinded to the NeuroSENSE monitor
      display, as the use of EEG monitoring is not currently part of standard practice. The
      anesthesiologist will instead rely on feedback from the other patient monitors in the OR, as
      they normally would. The NeuroSENSE monitor screen will be covered by an opaque card during
      the entire procedure, except for the displayed signal quality information. Blinding is
      required to avoid influencing the anesthesiologist's decisions based on EEG parameters.
    

Intervention name(s): Ketamine; NeuroSENSE monitor
Intervention type(s): Drug; Device
Intervention description(s): Bolus dose before induction of anesthesia and infusion during maintenance of anesthesia.; NeuroSENSE monitors the brain using electroencephalography (EEG) and produces an index called the WAVCNS. WAVCNS is a measure of depth of hypnosis (DoH).
Other intervention name(s): Ketalar
Intervention MeSH terms: Ketamine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Ketamine; Anesthesia; EEG; NeuroSENSE; Pain