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

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

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.

Study Overview

• Status: Completed
• Conditions: Surgery; Major Depressive Disorder; Orthopedic Disorder
• Intervention / Treatment: Drug: Ketamine; Drug: Normal saline (placebo)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient presenting for non-cardiac, non-intracranial surgery
• Major Depressive Disorder

Exclusion Criteria:

• Pregnant of breastfeeding women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
score on Montgomery-Asberg Depression Rating Scale (MADRS)		Days 5, 7 and 14 days post procedure compared to pre-procedure
score on Hospital Anxiety and Depression Scale (HADS)	This outcome measures self-reported symptoms of anxiety and depression on a scale that ranges from 0-42. A lower score indicates lower severity of symptoms.	1 to 14 days post procedure (up to 5 minutes to complete survey)
Pain at surgical site: scale of 0-10	This outcome measures average pain at the surgical site as reported by the patient on a scale of 0-10, with lower scores corresponding to less pain ("0" = no pain) and higher scores corresponding to more pain.	14 days post procedure (up to 5 minutes to complete survey)
Opioid consumption	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	0 to 14 days post procedure
Hospital length of stay	Number of days from admission (day of surgery) through discharge after surgery.	through study completion, an average of 2 days.
Pain interference score	This self reported outcome measure the extent to which postoperative pain interferes with typical functioning in seven domains, each rated on a scale from 0 (does not interfere) to 10 (completely interferes)	14 days post procedure (up to 5 minutes to complete survey)
Proportion of participants with remission (defined as a MADRS score of <=12 on day 14)		up to 14 days post procedure (up to 20 minutes to complete survey)

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: Boris D Heifets, MD, PhD, Stanford University

Publications and helpful links

General Publications

• Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979 Apr;134:382-9. doi: 10.1192/bjp.134.4.382.

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2019
• Primary Completion (Actual): September 22, 2022
• Study Completion (Actual): September 27, 2022

Study Registration Dates

• First Submitted: March 1, 2019
• First Submitted That Met QC Criteria: March 4, 2019
• First Posted (Actual): March 5, 2019

Study Record Updates

• Last Update Posted (Actual): October 5, 2023
• Last Update Submitted That Met QC Criteria: October 3, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: anesthesia; depression; ketamine; total joint arthroplasty
• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major; Musculoskeletal Diseases; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: 49114

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No current plan to share data.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No