The Effect of Low Dose Intra-operative Ketamine on Closed-loop Controlled General Anesthesia

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.

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).

Eligibility Criteria:
Inclusion Criteria:

* Age 19-54
* ASA I-II
* BMI 15-45
* Elective ACL repair surgery requiring general anesthesia
* Ability to read and understand the informed consent form

Exclusion Criteria:

* Contraindications to ketamine use Those in whom a significant elevation of blood pressure would constitute a serious hazard (e.g. severe cardiovascular disease, pacemaker, pheochromocytoma, malignant hypertension, intraocular pressure pathology, acute globe injury, hyperthyroidism)
* Contraindications to propofol Anaphylactic reaction to eggs, egg products, soybeans or soy products
* Contraindications to remifentanil Hypersensitivity to fentanyl analogues
* Known or suspected neurological disease Tumor, stroke, neurodegenerative disease, major head injury, seizure disorder Abnormality in any previous EEG examination Cognitive deficits (e.g. dementia, developmental delay)
* Acquired scalp or skull abnormalities
* Psychiatric illness Severe depression, PTSD, psychosis Any psychotropic medication taken in the past 7 days
* History of drug misuse/abuse within past 30 days Ketamine, cocaine, heroin, amphetamines, phencyclindine, lysergic acid (LSD), mescaline, psilocybin Chronic alcoholism
* Requirement for pre-operative sedative medication (e.g. midazolam) for anxiolysis
* Anticipated intra-operative or pre-operative use of nitrous oxide, catecholamines (dopamine, epinephrine, norepinephrine) or thyroid hormones
* Pregnant or nursing
* Currently enrolled in any other research study involving drugs or devices