Comparison of Remifentanil-induced Postoperative Hyperalgesia Between Patients From Plain Area and Plateau Area

Study Overview
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Brief Summary
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Purpose: To compare the incidence of postoperative hyperalgesia induced by remifentanil in patients undergoing gynecological laparoscopic surgery in plateau and plain areas To compare the peri-operative analgesic requirements of patients in plain and plateau areas

Detailed Description
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Our research group has been committed to the research of remifentanil-induced hyperalgesia for a long time. In the previous study, it was found that intraoperative infusion of remifentanil (0.3ug/kg•min) >1h can lead to remifentanil-induced hyperalgesia and the incidence rate is relative high in the plain area. Due to the long-term low pressure and hypoxia of people living in plateau areas, a series of changes will occur in the respiratory and circulatory systems, and their anesthesia management needs to be adjusted accordingly. However, there is no relevant research on whether or not hyperalgesia occurs in people in plateau areas (altitude level >3000 meters). Therefore, this study hopes to compare the incidence and degree of remifentanil-induced hyperalgesia after gynecological laparoscopic surgery in plain areas and plateau areas.

Official Title
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Comparison of Remifentanil-induced Postoperative Hyperalgesia After Gynecological Laparoscopic Surgery Between Patients From the Plain Area and the Plateau Area

Conditions
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Pain, Postoperative, Anesthesia

Intervention / Treatment
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* Drug: Sufentanil injection
* Drug: Remifentanil Hydrochloride
* Other: plain areas
* Other: plateau areas


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is scheduled to undergo gynecological laparoscopic surgery under a short general anesthesia of less than 2 hours Subject's American Society of Anesthesiologists physical status is I-II. The subject's parent/legally authorized guardian has given written informed consent to participate. Patients in plateau areas are long staying residents in above 3000 meters above sea level for enrollment, while patients in plain areas are long staying residents below 1000 meters above sea level. Exclusion Criteria: Subject has a diagnosis of renal or liver failure. Subject has a diagnosis of Insulin dependent diabetes. Subject is allergy and contraindication to any drugs used during general anesthesia. Subject has a history of chronic pain, a history of alcohol or opioid abuse, pre-existing therapy with opioids, intake of any analgesic drug within 48 hours before surgery. Subject has any contraindication for the use of patient-controlled analgesia (PCA). Subject is pregnant or breast-feeding. Subject is obese (body mass index >30kg/m2).

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sufentanil-analgesia in plain area patients<br>Sufentanil 0.3 μg/kg is intravenously administrated to maintain intraoperative analgesia in plain area patients. | Drug: Sufentanil injection<br>* Sufentanil 0.3 μg/kg is intravenously administrated to maintain intraoperative analgesia<br>* Other names: Sufentanil;Other: plain areas<br>* Patients should be long staying residents in plain areas (altitude level below 1,000 meters above sea level)<br>|
| Remifentanil-analgesia in plain area patients<br>Remifentanil 0.3ug/kg/min is intravenously administrated to maintain intraoperative analgesia in plain area patients. | Drug: Remifentanil Hydrochloride<br>* Remifentanil 0.3ug/kg/min is intravenously administrated to maintain intraoperative analgesia<br>* Other names: Remifentanil;Other: plain areas<br>* Patients should be long staying residents in plain areas (altitude level below 1,000 meters above sea level)<br>|
| Sufentanil-analgesia in plateau area patients<br>Sufentanil 0.3 μg/kg is intravenously administrated to maintain intraoperative analgesia in plateau area patients. | Drug: Sufentanil injection<br>* Sufentanil 0.3 μg/kg is intravenously administrated to maintain intraoperative analgesia<br>* Other names: Sufentanil;Other: plateau areas<br>* Patients should be long staying residents in plateau areas (altitude level>3000 meters above sea level)<br>|
| Remifentanil-analgesia in plateau area patients<br>Remifentanil 0.3ug/kg/min is intravenously administrated to maintain intraoperative analgesia in plateau area patients. | Drug: Remifentanil Hydrochloride<br>* Remifentanil 0.3ug/kg/min is intravenously administrated to maintain intraoperative analgesia<br>* Other names: Remifentanil;Other: plateau areas<br>* Patients should be long staying residents in plateau areas (altitude level>3000 meters above sea level)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mechanical Hyperalgesia Threshold on the Dominant Inner Forearm | 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 after surgery | 48 hours after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Score (NRS) | 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 | 
| Normalized Area of Hyperalgesia Around the Incision | The skin around the incision is stimulated in steps of 5 mm at intervals of 1 s starting outside of the hyperalgesic area in the direction of the incision. The distance from the incision to the first point where a'painful', 'sore' or 'sharper' feeling occurred is measured and noted. This measurement is repeated at predefined radial lines around the incision. To eliminate the variable length of incision, this length is subtracted from the longer diameter leaving four radial distances from the end and from the middle of the incision. The normalized area of hyperalgesia is calculated by summing up the areas of the remaining four triangles measured by and Von Frey filament. | 48 hours after surgery | 
| Mechanical hyperalgesia threshold around the incision | 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 | 
| Time of First Postoperative Analgesic Requirement | First postoperative pain (NRS≥5) is initially controlled by titration of Hydromorphone. | 1 hour after surgery | 
| Total Dose of First Postoperative Analgesic Requirement | First postoperative pain (NRS≥5) is initially controlled by titration of Hydromorphone. | 1 hour after surgery | 
| Cumulative Hydromorphone Consumption | Each patient was administered analgesics using a PCA (Patient-controlled analgesia) pump containing Hydromorphone (200μg) 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. Hydromorphone cumulative consumption is recorded 48 hours postoperatively | 48 hours after surgery | 
| Occurrence of Side Effects | Occurrence of side effects: nausea, vomiting, dizziness, headache, shivering, pruritus | 48 hours after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Remifentanil, Opioid-induced hyperalgesia, Postoperative pain, pain intensity