Intraoperative Ketamine for Patients Undergoing Total Joint Arthroplasty

Randomized Blinded, Placebo Controlled Trial of Intrapoperative Ketamine for Patients Undergoing Total Joint

Prospective randomized double blinded, placebo controlled study that will evaluate the effect of intra-operative ketamine administration on post-operative analgesic requirements and self-reported pain in patients undergoing total hip and total knee arthroplasty who demonstrate high levels of pain catastrophizing.

Study Overview

• Status: Completed
• Conditions: Pain, Postoperative; Arthroplasty Complications
• Intervention / Treatment: Drug: Ketamine

Detailed Description

Pain management can be one of the most challenging aspects of care for total joint arthroplasty patients. Poor post-operative pain control can lead to poor patient satisfaction and functional outcomes. Moreover, prolonged post-operative opioid utilization for post-operative pain is associated with substantial adverse sequelae. Identifying patients at high risk for poor post-operative pain control, and implementing strategies to improve pain management in this population is of utmost importance. One patient feature that has been shown to reliably predict poor post-operative pain management is pain catastrophizing. Currently available self-reported metrics such as the pain catastrophizing scale allow for pre-operative identification of patients who exhibit high levels of pain catastrophizing. Furthermore, there currently exist strategies which may effectively improve post-operative pain management in this population. One such strategy is "pre-emptive" analgesia utilizing ketamine administered at the time of surgery. Ketamine is commonly utilized in the treatment of both acute and chronic pain, and is believed to reduce pain intensity through a complex mechanism involving opioid receptors and excitatory neurotransmitters. It has been utilized in a variety of surgical procedures and has consistently been shown to reduce acute post-operative pain and analgesic consumption as long as 6 months after surgery, without a significant incidence of medication related side effects. To date, no study has evaluated the use of ketamine for total joint arthroplasty patients who demonstrate high levels of pain catastrophizing. We aim to study the effect of intra-operative ketamine administration on post-operative analgesic requirements and self-reported pain in patients undergoing total hip and total knee arthroplasty who demonstrate high levels of pain catastrophizing.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03766
      • Dartmouth-Hitchcock

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adults, 18 years and older, undergoing primary total hip arthroplasty or total knee arthroplasty

Exclusion Criteria:

• History of intolerance or allergy to ketamine, either documented or self-reported.
• History of increased intra-ocular pressure, uncontrolled hypertension, increased intra-cranial pressure, psychosis.
• Unable to provide consent.
• Current incarceration.
• Pregnant or breast feeding

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Racemic Ketamine; ketamine 0.5mg/kg bolus on induction of anesthesia and 10mcg/kg/min infusion initiated prior to incision and terminated at the completion of wound closure. Maximum ketamine dose will not exceed 500mg	Drug: Ketamine; Ketamine versus saline placebo will be compared in order to evaluate the effects of Ketamine on patients that are pain catastrophizers
Placebo Comparator: Saline; saline in the same volume as the study drug, administered in the exact same format.	Drug: Ketamine; Ketamine versus saline placebo will be compared in order to evaluate the effects of Ketamine on patients that are pain catastrophizers

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Morphine consumption during the first 48 hours post surgery	Morphine consumption will be measured in a pain diary for 6- weeks post-surgical procedure. Decreased is morphine consumption will indicate effectiveness of ketamine administration	Daily for six weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hip Disability and Osteoarthritis Outcome Score for Joint Replacement (HOOS, JR.)	six question questionnaire measuring joint specific pain and physical function, scored by summing the raw response (range 0-24) and then converting it to an interval score using the table provided below. The interval score ranges from 0 to 100 where 0 represents total hip disability and 100 represents perfect hip health.	Pre-operation, post-operation at 6 weeks, 12 weeks, and 6 months
Knee Disability and Osteoarthritis Outcome Score for Joint Replacement (KOOS, JR.)	Seven question questionnaire measuring joint specific pain and physical functionscored by summing the raw response (range 0-28) and then converting it to an interval score using the table provided below. The interval score ranges from 0 to 100 where 0 represents total knee disability and 100 represents perfect knee health.	Pre-operation, post-operation at 6 weeks, 12 weeks, and 6 months
Patient-Reported Outcomes Measurement Information System (PROMIS-10)	patient-reported questionnaire in which the response options are presented as 5-point (as well as a single 11-point) rating scales. The results of the questions are used to calculate two summary scores: a Global Physical Health Score and a Global Mental Health score. The higher the score the healthier the subject is compared to the general population.	Pre-operation, post-operation at 6 weeks, 12 weeks, and 6 months
Pain Catastrophizing Scale (PCS)	The PCS is a 13 item scale, with each item rated on a 5-point scale: 0 (Not at all) to 4 (all the time). The PCS is broken into three subscales being magnification, rumination, and helplessness. The higher the score, the more catastrophizing thoughts are present.	post-operation at 6 weeks, 12 weeks, and 6 months

Collaborators and Investigators

• Sponsor: Dartmouth-Hitchcock Medical Center
• Investigators: Principal Investigator: Wayne E Moschetti, MD, MS, Dartmouth-Hitchcock Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2020
• Primary Completion (Actual): April 5, 2024
• Study Completion (Actual): June 1, 2024

Study Registration Dates

• First Submitted: June 16, 2020
• First Submitted That Met QC Criteria: June 16, 2020
• First Posted (Actual): June 18, 2020

Study Record Updates

• Last Update Posted (Actual): September 27, 2024
• Last Update Submitted That Met QC Criteria: September 26, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Ketamine; Pain Catastrophizing; Total Knee Replacement; Total Hip Replacement
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; 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: D20116; STUDY02000376 (Other Identifier: Dartmouth-Hitchcock)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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