S-ketamine Prevents Postoperative Pain and Cognitive Dysfunction After Tibial Fracture

August 7, 2021 updated by: Guolin Wang, Tianjin Medical University General Hospital

S-ketamine Prevents Tibial Fracture-associated Postoperative Pain and Cognitive Dysfunction After Orthopedic Surgery in Patients: a Randomized Double-blind Controlled Trial

Purpose:

To explore effects of S-ketamine on postoperative pain and cognitive dysfunction after tibial fracture and orthopedic surgery.

To evaluate and examine the incidence of adverse effects with the purpose of selecting the optimum dose.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

With the increase in human life span, orthopedic injuries and subsequent repair surgery have become a major health problem which impairs the life quality of patients and burdens healthcare systems worldwide. Poor post-surgical pain control is a leading factor that hinders the physical rehabilitation and musculoskeletal functional recovery, and causes acute cognitive impairment and chronic pain syndrome. Also, existing treatments of opioids and non-steroidal anti-inflammatory drugs have potential drawbacks, which may in turn interfere with bone healing. Therefore, prophylaxis of fracture-associated pain is indispensable to postoperative comfort and satisfaction.

There is no denying the fact that pathologic pain is related to central glutaminergic system and N-methyl-d-aspartate (NMDA) receptor activation induced central sensitization. Also, we previously reported that neuroinflammation is associated with pain development and cognitive dysfunction. Ketamine, a NMDA receptor antagonist, is effective in reversing NMDA receptor activation underlying pain states. But the side effects of ketamine limit its clinical application, such as Delirium, gibberish and agitation. It is clarified that S-ketamine has lower side effects than ketamine and that antinociception of S-ketamine is stronger than ketamine. The following study is carried out to evaluate whether S-ketamine can prevent postoperative pain and cognitive impairment after tibial fracture and orthopedic surgery in patients.

Study Type

Interventional

Enrollment (Anticipated)

120

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Tianjin, China, 300052
        • Recruiting
        • Tianjin Medical University General Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

65 years to 85 years (OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Subject is scheduled to undergo tibial fracture with orthopedic surgery under a short general anesthesia of less than 2 hours
  2. Subject's American Society of Anesthesiologists physical status is I-II.
  3. The subject's parent/legally authorized guardian has given written informed consent to participate.

Exclusion Criteria:

  1. Subject has a diagnosis of bronchial asthma, coronary heart disease, severe hypertension, renal failure or liver failure.
  2. Subject has a diagnosis of Insulin dependent diabetes.
  3. Subject is allergy and contraindication to S-ketamine.
  4. Subject has a history of chronic pain, a history of alcohol or opioid abuse, pre- existing therapy with opioids.
  5. Subject has any contraindication for the use of patient-controlled analgesia (PCA).
  6. Subject is pregnant or breast-feeding.
  7. Subject is obese (body mass index >30kg/m^2).
  8. Subject is incapacity to comprehend pain assessment and cognitive assessment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
PLACEBO_COMPARATOR: Normal saline in patients
After the induction of anesthesia, normal saline is intravenously injected in a volume of 2ml, and then a continuous infusion of 20 ml/h normal saline until starting skin suture.
Drug: Normal saline
After the induction of anesthesia, normal saline is intravenously injected in a volume of 2ml, and then a continuous infusion of 20ml/h normal saline until starting skin suture.
Other Names:
  • 0. 9% Sodium Chloride Injection
ACTIVE_COMPARATOR: S-ketamine at low dose in patients
After the induction of anesthesia, S-ketamine is intravenously injected at 0.2mg/kg, and then a continuous infusion of 0.2mg/kg/h S-ketamine until starting skin suture.
Drug: S-ketamine (low-dose)
After the induction of anesthesia, S-ketamine is intravenously injected at 0.2mg/kg, and then a continuous infusion of 0.2mg/kg/h S-ketamine until starting skin suture.
Other Names:
  • Esketamine Hydrochloride Injection
ACTIVE_COMPARATOR: S-ketamine at high dose in patients
After the induction of anesthesia, S-ketamine is intravenously injected at 0.4mg/kg, and then a continuous infusion of 0.4mg/kg/h S-ketamine until starting skin suture.
Drug: S-ketamine (high-dose)
After the induction of anesthesia, S-ketamine is intravenously injected at 0.4mg/kg, and then a continuous infusion of 0.4mg/kg/h S-ketamine until starting skin suture.
Other Names:
  • Esketamine Hydrochloride Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mechanical hyperalgesia threshold on the palms of feet
Time Frame: 48 hours after surgery
The mechanical hyperalgesia threshold was defined as the lowest force (g) necessary to bend a Von Frey filament, which was perceived to be painful by the patient and measured by Von Frey filament.
48 hours after surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Occurrence of Side Effects
Time Frame: 48 hours after surgery
Occurrence of side effects: nausea, vomiting, dizziness, headache, shivering, pruritus
48 hours after surgery
Time of First Postoperative Analgesic Requirement
Time Frame: 1 hour after surgery
First postoperative pain (NRS≥5) is initially controlled by titration of sufentanyl.
1 hour after surgery
Total Dose of First Postoperative Analgesic Requirement
Time Frame: 1 hour after surgery
First postoperative pain (NRS≥5) is initially controlled by titration of sufentanyl.
1 hour after surgery
Pain Score (NRS)
Time Frame: 48 hours after surgery
The pain score at rest or after movement was evaluated by pain 11-point numerical rating scale (NRS): 0 = no pain, 10 = greatest imaginable pain.
48 hours after surgery
Mechanical Hyperalgesia Threshold on the Dominant Inner Forearm
Time Frame: 48 hours after surgery
The mechanical hyperalgesia threshold was defined as the lowest force (g) necessary to bend a Von Frey filament, which was perceived to be painful by the patient and measured by Von Frey filament
48 hours after surgery
Cumulative Sufentanyl Consumption
Time Frame: 48 hours after surgery
Each patient was administered analgesics using a PCA (Patient-controlled analgesia) pump containing sufentanil (100μg) in normal saline at a total volume of 100 ml after leaving PACU (Postanesthesia care unit). This device was set to deliver a basal infusion of 2 ml/h and bolus doses of 0.5 ml with a 15-min lockout period. Sufentanyl cumulative consumption is recorded 48 hours postoperatively
48 hours after surgery
Mini-Mental State Examination (MMSE)
Time Frame: 48 hours after surgery
Cognitive performance was assessed with Mini-Mental State Examination (MMSE).
48 hours after surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tianjin Medical University General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

December 15, 2020

Primary Completion (ANTICIPATED)

November 15, 2021

Study Completion (ANTICIPATED)

December 15, 2021

Study Registration Dates

First Submitted

November 17, 2020

First Submitted That Met QC Criteria

November 22, 2020

First Posted (ACTUAL)

November 24, 2020

Study Record Updates

Last Update Posted (ACTUAL)

August 13, 2021

Last Update Submitted That Met QC Criteria

August 7, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GWang011

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

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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