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

NeuroWave Systems

Status and phase: Completed; Phase 1

Conditions: Anesthesia

Treatments: Other: Placebo; Drug: Ketamine Injectable Solution

Study type: Interventional

Funder types: Other; Industry; Other U.S. Federal agency

Identifiers

NCT03009409

925-0702-DCI

Details and patient eligibility

About

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.

Full 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).

Enrollment: 60 patients

Sex: All

Ages: 19 to 54 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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60 participants in 2 patient groups, including a placebo group

Ketamine Group

Active Comparator group

Description:

Participants randomized to the ketamine group will receive a 0.25 mg/kg loading dose of intravenous ketamine immediately before induction of anesthesia, followed by a continuous 5 mcg/kg/min infusion throughout maintenance of anesthesia, for approximately 45 minutes, up to a maximum cumulative dose of 100 mg. This dose is in accordance with the guidelines from the recently published Clinical Practice Guidelines for the management of post-operative pain. The attending anesthesiologist will confirm whether the use of ketamine is appropriate for each patient prior to enrolling the patient in the study.

Treatment:

Drug: Ketamine Injectable Solution

Control Group

Placebo Comparator group

Description:

Participants in the control group will receive an equivalent volume bolus and infusion of normal saline to mimic the ketamine infusion.

Treatment:

Other: Placebo