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

Sponsor

Qianfoshan Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT05289050

Collaborator

(none)

144

Enrollment

Location

Arms

Anticipated Duration (Months)

5.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Postoperative Pain, Acute Anaesthetic	Drug: sodium chloride (NaCl; 0.9%) Drug: S-ketamine	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

144 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Other

Official Title:

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

Actual Study Start Date :

Jan 1, 2022

Anticipated Primary Completion Date :

Sep 1, 2023

Anticipated Study Completion Date :

Mar 1, 2024

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

at rest and movement, evaluated NRS at 24hours after surgery in the surgical ward. [the patient at 24hours after operation.]
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)

Secondary Outcome Measures

at rest and movement, evaluated NRS at 2 hours after surgery in the surgical ward. [the patient at 2 hours after operation.]
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)
at rest and movement, evaluated NRS at 48hours after surgery in the surgical ward. [the patient at 48hours after operation]
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 cumulative Opioids consumption during the first 48h after operation [Within 48hours after surgery]
The cumulative Opioids consumption such as demerol,sufentanil,morphine
The number of patients who required additional analgesics during the first 48h after operation [Within 48hours after surgery]
The number of patients who required additional analgesics such as opioids(demerol,sufentanil,morphine)or non-steroid anti-inflammatory drugs(acetaminophen,diclofenac).
The Opioids or non-steroid anti-inflammatory drugs total consumption during the first 48h after operation [Within 48hours after surgery]
The opioids (such as demerol,sufentanil,morphine) or non-steroid anti-inflammatory drugs (such as acetaminophen,diclofenac)total consumption.
The incidence of PONV and adverse central nervous system (CNS) events. [the patient leaves the PACU and at 24, 48hours after operation.]
(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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

65 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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