Analgesic Effect of Intraoperative Intravenous S-Ketamine During Total Knee Arthroplasty Surgery

Analgesic Effect of Intraoperative Intravenous S-Ketamine During Total Knee Arthroplasty Surgery:A Randomized Controlled Clinical Trial

Severe acute pain after total knee arthroplasty surgery has multiple implications for hospitals and patients, monopolising resources and affecting the quality of life. S-ketamine inhibits N-methyl-d-aspartate (NMDA) receptor activation and attenuates central sensitization associated with hyperalgesia, opioid tolerance.Therefore, the primary aim of this trial was to investigate whether s-ketamine decreases pain and opioid consumption postoperatively in adult individuals undergoing total knee arthroplasty surgery.

Study Overview

• Status: Recruiting
• Conditions: Postoperative Pain, Acute; Anaesthetic
• Intervention / Treatment: Drug: sodium chloride (NaCl; 0.9%); Drug: S-ketamine

Detailed Description

Total knee arthroplasty surgery is considered a cost-effective therapy for end-stage knee osteoarthritis (KOA). With an ageing population and rising rates of obesity in the world, knee joint replacements are estimated to escalate. While joint replacement is a cost effective intervention,approximately 20% of people experience persist pain postoperatively. The surgical injury triggers a myriad of responses in the pain matrix, from sensitization of peripheral and central pain pathways to feelings of fear, anxiety and frustration.

Opioids are effective for acute postoperative pain but have numerous adverse effects. In addition, postoperative opioid treatment may pose a risk of opioid addiction.

Numerous publications state that adjuvant s-ketamine reduces pain and opioid consumption postoperatively . Whether intraoperative intravenous s-ketamine alleviates postoperative acute pain after total knee arthroplasty surgery still unclear . Therefore, a randomized, controlled, clinical study was designed to observed analgesic effect intraoperative intravenous a lower doses of s-ketamine(0.3mg/kg/h) with patients after total knee arthroplasty surgery .

• Study Type: Interventional
• Enrollment (Anticipated): 144
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Shiyuan Deng, master; Phone Number: 13791127650; Email: 13791127650@163.com
• Study Contact Backup: Name: Ling Dong, Ph.D; Phone Number: 18866862815; Email: dongling1668@163.com

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250000
      • Recruiting
      • Qianfoshan Hospital, The First Hospital affiliated of Shandong First Medical University
      • Contact: Ling Dong, Ph.D; Phone Number: 18866862815; Email: dongling1668@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 90 years (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. ASA physical statusI-III;
2. Patients understood the study in detail and voluntarily signed the informed consent before the study;
3. Patients to be treated with total knee arthroplasty Surgery under General anesthesia;
4. Elderly patients(≥65y),regardless of gender;
5. Patients can communicate normally;
6. Patients who have no contraindications to drugs such as midazolam,fentanyl,s-ketamine.

7.18 kg/m2 ≤BMI≤30 kg/m2;

Exclusion Criteria:

1. Increased intracranial or intraocular pressure;
2. severe hypertension;
3. unwillingness the study;
4. severe psychiatric disease and mental system diseases;
5. severe respiratory diseases;
6. hyperthyroidism;
7. liver and kidney dysfunction;
8. alcohol or drug abuse;
9. allergy to midazolam,fentanyl,s-ketamine.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: sodium chloride (NaCl; 0.9%); For patients in the control group,anaesthesia will be maintained with intravenous sodium chloride (NaCl; 0.9%) infusion.while anaesthesia will be maintained with propofol infusion(4-12mg/kg/h),analgesia will be maintained with remifentanil(0.15-0.3ug/kg/min).The sufentanil dose at induction and the rate of intraoperative remifentanil and propofol infusions were at the discretion of the anesthesiologist in charge of the patient. The assessment of the depth of anesthesia was based on clinical evaluation,placebo-controlled infusion will be stopped 15 minutes before the end of surgery.Propofol and remifentanil infusion will be stopped at the end of surgery.	Drug: sodium chloride (NaCl; 0.9%); For patients in the control group,anaesthesia will be maintained with intravenous sodium chloride (NaCl; 0.9%) infusion.while anaesthesia will be maintained with propofol infusion(4-12mg/kg/h),analgesia will be maintained with remifentanil(0.15-0.3ug/kg/min).The sufentanil dose at induction and the rate of intraoperative remifentanil and propofol infusions were at the discretion of the anesthesiologist in charge of the patient.The assessment of the depth of anesthesia was based on clinical evaluation,placebo-controlled infusion will be stopped 15 minutes before the end of surgery.Propofol and remifentanil infusion will be stopped at the end of surgery.
Experimental: S-ketamine; For patients in the s-ketamine group, anaesthesia will be maintained with s-ketamine infusion（0.3mg/kg/h),while anaesthesia will be maintained with propofol infusion(4-12mg/kg/h) ,analgesia will be maintained with remifentanil(0.15-0.3ug/kg/min).The sufentanil dose at induction and the rate of intraoperative remifentanil and propofol infusions were at the discretion of the anesthesiologist in charge of the patient.The assessment of the depth of anesthesia was based on clinical evaluation.S-ketamine infusion will be stopped 15 minutes before the end of surgery.Propofol and remifentanil infusion will be stopped at the end of surgery.	Drug: S-ketamine; For patients in the s-ketamine group,anaesthesia will be maintained with s-ketamine infusion（0.3mg/kg/h),while anaesthesia will be maintained with propofol infusion(4-12mg/kg/h),analgesia will be maintained with remifentanil(0.15-0.3ug/kg/min).The sufentanil dose at induction and the rate of intraoperative remifentanil and propofol infusions were at the discretion of the anesthesiologist in charge of the patient.The assessment of the depth of anesthesia was based on clinical evaluation.S-ketamine infusion will be stopped 15 minutes before the end of surgery.Propofol and remifentanil infusion will be stopped at the end of surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
at rest and movement, evaluated NRS at 24hours after surgery in the surgical ward.	NRS = (numerical rating scale) is widely used to measure pain intensity after surgery.NRS is evaluated on a 11-point NRS (0 = no pain, 10 = worst pain imaginable)	the patient at 24hours after operation.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
at rest and movement, evaluated NRS at 2 hours after surgery in the surgical ward.	NRS = (numerical rating scale) is widely used to measure pain intensity after surgery.NRS is evaluated on a 11-point NRS (0 = no pain, 10 = worst pain imaginable)	the patient at 2 hours after operation.
at rest and movement, evaluated NRS at 48hours after surgery in the surgical ward.	NRS = (numerical rating scale) is widely used to measure pain intensity after surgery.NRS is evaluated on a 11-point NRS (0 = no pain, 10 = worst pain imaginable)	the patient at 48hours after operation
The cumulative Opioids consumption during the first 48h after operation	The cumulative Opioids consumption such as demerol,sufentanil,morphine	Within 48hours after surgery
The number of patients who required additional analgesics during the first 48h after operation	The number of patients who required additional analgesics such as opioids(demerol,sufentanil,morphine)or non-steroid anti-inflammatory drugs(acetaminophen,diclofenac).	Within 48hours after surgery
The Opioids or non-steroid anti-inflammatory drugs total consumption during the first 48h after operation	The opioids (such as demerol,sufentanil,morphine) or non-steroid anti-inflammatory drugs (such as acetaminophen,diclofenac)total consumption.	Within 48hours after surgery
The incidence of PONV and adverse central nervous system (CNS) events.	(Postoperative nausea and vomiting)Nausea is defined as subjective,unpleasant sensation associated with awareness of the urge to vomit. Retching is defined as the laboured, spastic, rhythmic contraction of the respiratory muscles without expulsion of the gastric contents.Vomiting is defined as the forceful expulsion of gastric contents from the mouth.The adverse central nervous system (CNS) events(such as nightmares, hallucinations, dizziness, itchy skin) were recorded (yes/no) at the patient leaves the PACU and at 24, 48hours in the surgical ward.	at2, 24, 48hours after operation.

Collaborators and Investigators

• Sponsor: Ling Dong

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2022
• Primary Completion (Anticipated): September 1, 2024
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: February 26, 2022
• First Submitted That Met QC Criteria: March 18, 2022
• First Posted (Actual): March 21, 2022

Study Record Updates

• Last Update Posted (Estimate): February 28, 2023
• Last Update Submitted That Met QC Criteria: February 25, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Postoperative pain; anaesthetic; total knee arthroplasty surgery; S-ketamine infusion
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Acute Pain; 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; Psychotropic Drugs; Antidepressive Agents; Ketamine; Esketamine
• Other Study ID Numbers: YXLL-KY-2021(077)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No