Intraoperative Ketamine Versus Saline in Depressed Patients Undergoing Anesthesia for Non-cardiac Surgery

Study Overview
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Brief Summary
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This study evaluates whether ketamine, given as part of an anesthetic, improves depression symptoms in depressed patients undergoing non-cardiac surgery. Half of participants will receive a ketamine infusion during surgery, while the other half will receive a placebo (normal saline) during surgery.

Detailed Description
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Major Depressive Disorder (MDD) is widely prevalent among patients preparing to have surgery, and is a known risk factor for complications after surgery, including wound infection, myocardial infarction and opioid use disorder. Ketamine has emerged as an effective, rapid-acting antidepressant therapy for patients with MDD, and may be a useful tool to prevent MDD-related morbidity in the perioperative period. Ketamine has been well studied for MDD in outpatient clinics where it is given as an infusion (0.5 mg/kg over 40 minutes) in awake patients. Ketamine is often used as part of an anesthetic cocktail in sedated or anesthetized patients, but it is unknown whether ketamine has an antidepressant effect in this context. The investigators will determine whether a ketamine infusion, compared to placebo (normal saline infusion), has an antidepressant effect when given during surgical anesthesia. If ketamine is an effective antidepressant in this population under anesthesia, its use could be incorporated into a set of interventions to minimize the perioperative complications associated with MDD.

Official Title
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Double-blind Trial of Intraoperative Ketamine Versus Saline in Depressed Patients Undergoing Anesthesia for Non-cardiac Surgery

Conditions
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Major Depressive Disorder, Surgery, Orthopedic Disorder

Intervention / Treatment
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* Drug: Ketamine
* Drug: Normal saline (placebo)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient presenting for non-cardiac, non-intracranial surgery Major Depressive Disorder Exclusion Criteria: Pregnant of breastfeeding women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open label ketamine<br>Patients will receive an intravenous ketamine infusion during surgery. | Drug: Ketamine<br>* 0.5 mg/kg over 40 minutes, intravenous.<br>* Other names: Ketalar.;|
| Experimental: Double blind ketamine<br>Patients will receive an intravenous ketamine infusion during surgery. | Drug: Ketamine<br>* 0.5 mg/kg over 40 minutes, intravenous.<br>* Other names: Ketalar.;|
| Placebo Comparator: Double blind placebo<br>Participants will receive placebo (normal saline infusion) during surgery. | Drug: Normal saline (placebo)<br>* Normal saline infusion over 40 minutes, equivalent volume to ketamine infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montgomery-Asberg Depression Rating Scale (MADRS) Score | The MADRS is a 10-item scale for the evaluation of depressive symptoms (Montgomery et al 1979). Each MADRS item is rated on a 0 to 6 scale. Total score range from 0-60, where lower MADRS scores indicate lower levels of depressive symptoms. The assessment for this outcome will be taken once daily on days 1, 2 and 3 post procedure. A mixed model for repeated measures (MMRM) was used to analyze the difference in postoperative MADRS score between ketamine and placebo groups.. | Post-intervention days 1, 2 and 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinical Response | Clinical response defined as >=50% reduction in MADRS score from baseline. MADRS score range: 0 to 60, a lower score indicates lower severity of symptoms. | Post-intervention days 1, 2 and 3 | 
| Number of Participants With Remission | Remission defined as a MADRS score of <=12 on day 14. MADRS score range: 0 to 60, a lower score indicates lower severity of symptoms. | Post-intervention day 14 | 
| Hospital Anxiety and Depression Scale (HADS) Scale Score | This outcome measures self-reported symptoms of anxiety and depression on a scale that ranges from 0 to 42. A lower score indicates lower severity of symptoms. | Post-intervention days 1, 2, 3, 5, 7 and 14 | 
| Cumulative Opioid Use | This outcome measures how many cumulative morphine-equivalents milligrams of opioid pain medication the patient has taken as an inpatient and after discharge from hospital | Post-intervention days 1, 2, 3, 5, 7 and 14 | 
| Hospital Length of Stay | Number of days from admission (day of surgery) through discharge after surgery. | Average approximately 3 days post-intervention | 
| Brief Pain Inventory Pain Intensity Scale Score | Average pain intensity in the past 24 hours, rated on a numerical scale from 0 to 10 (with 0 representing No pain and 10 representing Pain as bad as you can imagine). | Post-intervention days 1, 2, 3, 5, 7 and 14 | 
| Brief Pain Inventory Pain Interference Scale Score | Pain interference in the past 24 hours, rated on a numerical scale from 0 to 10 (with 0 representing Does not interfere and 10 representing Completely interferes). | Post-intervention days 1, 2, 3, 5, 7 and 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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depression, ketamine, anesthesia, total joint arthroplasty