Intraoperative S-ketamine to Prevent Postoperative Hyperalgesia in Patients Undergoing Video-assisted Thoracic Surgery

Second Affiliated Hospital Zhejiang University School of Medicine

Postoperative hyperalgesia (POH) is a paradoxical clinical state of increased sensation of pain or increased sensitivity to non-painful stimuli at the site of surgery or at a surrounding area that was not directly injured. Opioid-induced hyperalgesia (OIH) and nociceptive-induced hyperalgesia (NIH) are the two main causes of POH.N-methyl-D-aspartate receptor (NMDAR) activation plays a central role in the development of POH.S-ketamine，which is a NMDA-receptor antagonist,has been on the market in china since 2019.The aim of this study is to evaluate the effects of S-ketamine on POH and chronic postoperative pain after video-assisted thoracic surgery.

Study Overview

• Status: Recruiting
• Conditions: Postoperative Hyperalgesia
• Intervention / Treatment: Drug: S-ketamine; Drug: saline

• Study Type: Interventional
• Enrollment (Anticipated): 92
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: LiNa Yu, doctor; Phone Number: 13958033387; Email: zryulina@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Recruiting
      • Second affiliated Hospital School of Medicine,Zhejiang University
      • Contact: lina Yu, doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• American Society of Anesthesiologists (ASA) physical status class I-III.
• elective single-port video-assisted thoracic surgery under general

Exclusion Criteria:

• a history of thoracic surgery
• a history of chronic pain
• ongoing pain treatment
• opioid drug or alcohol abuse
• a history of allergy to anesthetics
• obesity (body mass index [BMI] >30 kg/m2 )
• pregnancy
• psychiatric disorders
• neurological disease
• severe diabetes
• renal or hepatic insufficiency
• uncontrolled hypertension, or arrhythmia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: S-ketamine; a 0.25 mg/kg bolus and 0.125 mg/kg/h via intravenous infusion during surgery	Drug: S-ketamine; S-ketamine is used for preventing postoperative hyperalgesia,thus reducing the patient's acute postoperative pain; Other Names: esketamine
Placebo Comparator: Saline; a 0.25 mg/kg bolus and 0.125 mg/kg/h via intravenous infusion during surgery	Drug: saline; saline is used for control; Other Names: 0.9%saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the mechanical pain threshold around the incision	the mechanical pain threshold was assessed by using 10 calibrated (4-300 g mm-2 ) hand-held Von Frey filaments (North Coast Medical Inc.USA)around the skin incision.The per pain threshold was defined as the smallest force (g mm-2 ) necessary to bend a von Frey hair, and perceived by the patient as three consecutive painful stimuli with approximately 10 s elapsing between two successive stimuli. The mechanical pain threshold was recorded as the mean of 6 measurements at 2 cm vertically above and below the middle and bilateral edges of the incision.	Day1 after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the mechanical pain threshold on the forearm	the mechanical pain threshold was assessed by using 10 calibrated (4-300 g mm-2 )hand-held Von Frey filaments (North Coast Medical Inc. USA)on the nondominant inner forearm The per pain threshold was defined as the smallest force (g mm-2 ) necessary to bend a von Frey hair, and perceived by the patient as three consecutive painful stimuli with approximately 10 s elapsing between two successive stimuli. The mechanical pain threshold was recorded as the mean of 3 measurements at 3, 6, and 9 cm distal to the middle of the antecubital crease	the day before surgery
the mechanical pain threshold	the mechanical pain threshold was assessed by using 10 calibrated (4-300 g mm-2 )hand-held Von Frey filaments (North Coast Medical Inc.USA)on the nondominant inner forearm The per pain threshold was defined as the smallest force (g mm-2 ) necessary to bend a von Frey hair, and perceived by the patient as three consecutive painful stimuli with approximately 10 s elapsing between two successive stimuli. The mechanical pain threshold was recorded as the mean of 3 measurements at 3, 6, and 9 cm distal to the middle of the antecubital crease .	Day1 after surgery
the mechanical pain threshold	the mechanical pain threshold was assessed by using 10 calibrated (4-300 g mm-2 )hand-held Von Frey filaments (North Coast Medical Inc.USA)on the nondominant inner forearm The per pain threshold was defined as the smallest force (g mm-2 ) necessary to bend a von Frey hair, and perceived by the patient as three consecutive painful stimuli with approximately 10 s elapsing between two successive stimuli. The mechanical pain threshold was recorded as the mean of 3 measurements at 3, 6, and 9 cm distal to the middle of the antecubital crease .	Day2 after surgery
the mechanical pain threshold around the incision	the mechanical pain threshold was assessed by using 10 calibrated (4-300 g mm-2 ) hand-held Von Frey filaments (North Coast Medical Inc. USA)around the skin incision.The per pain threshold was defined as the smallest force (g mm-2 ) necessary to bend a von Frey hair, and perceived by the patient as three consecutive painful stimuli with approximately 10 s elapsing between two successive stimuli. The mechanical pain threshold was recorded as the mean of 6 measurements at 2 cm vertically above and below the middle and bilateral edges of the incision.	Day2 after surgery
postoperative pain scores	postoperative pain scores was assessed by using numeric rating scales(0-10,0 means"better ',10 means "worst") at 6 time points:1 hours,3 hours,6 hours, 12 hours,24 hours, and 48 hours after the operation. The worst pain score during each interval was recorded.	up to day2 after surgery
Anxiety scale scores	Anxiety scale scores was assessed by Hamilton Anxiety Scale at three time points:the day before surgery, day1 after surgery and day2 after surgery. If the total score exceeds 29 points, it may be severe anxiety. If the score exceeds 21 points, there must be obvious anxiety. If the score exceeds 14, there must be anxiety. If it exceeds 7 points, there may be anxiety. If it is less than 6, the patient has no anxiety symptoms.	up to day2 after surgery
Depression scale scores	Depression scale scores was assessed by Hamilton Depression Scale at three time points:the day before surgery, day1 after surgery and day2 after surgery. The total score is less than 7 points, normal; 7-17 points, there may be depression. 17-24 points, there must be depression, more than 24 points, severe depression.	up to day2 after surgery
The hyperalgesic area around the incision	The hyperalgesic area around the surgical incision was measured by the von Frey filament that in postoperative pain threshold testing evoked pain on the opposite side. Stimulation was started far from the surgical incision and moved toward the incision in 0.5 cm steps until the patient reported a distinct change in pain perception. The first point at which the patient reported a more painful, sore or sharp feeling was marked, and the distance to the incision was measured . Finally, we calculated the incidence and extension of peri-incisional mechanical hyperalgesia	up to day2 after surgery

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2021
• Primary Completion (Anticipated): December 30, 2021
• Study Completion (Anticipated): April 30, 2022

Study Registration Dates

• First Submitted: August 9, 2021
• First Submitted That Met QC Criteria: August 15, 2021
• First Posted (Actual): August 23, 2021

Study Record Updates

• Last Update Posted (Actual): September 29, 2021
• Last Update Submitted That Met QC Criteria: September 27, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Sensation Disorders; Somatosensory Disorders; Hyperalgesia; 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: 2021-0442

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