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

Study Overview
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Brief Summary
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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.

Official Title
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Second Affiliated Hospital Zhejiang University School of Medicine

Conditions
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Postoperative Hyperalgesia

Intervention / Treatment
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* Drug: S-ketamine
* Drug: saline


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 meansbetter ',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 |