Oral Pregabalin Premedication for Postoperative Pain Relief

Study Overview
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Brief Summary
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Pain management after gynecological surgeries is essential for early mobilization of the patient, decrease postoperative complication and hospital stay. The use of opioids is associated with adverse effects such as nausea, vomiting, ileus, pruritus, sedation and respiratory depression. Previous studies stated that pregabalin has been used to reduce pre-operative anxiety, acute postoperative pain, postoperative opioid requirements, postoperative nausea, vomiting and postoperative delirium. The most effective dose of pregabalin to relief postoperative pain with least side effect is still under trial. In this study we will compare between two different doses of pregabalin when given as oral premedication in patients undergoing gynecological surgeries under spinal anesthesia regarding postoperative pain in order to reduce opioids consumption and subsequently avoid opioid-related adverse effects.

Detailed Description
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Postoperative pain, nausea and vomiting continue to be one of the most common and unpleasant complications after surgery. The traditional pain treatment with opioids alone is not adequate any more. To optimize pain treatment and postoperative outcome, new analgesics and new combination of already existing analgesics are searched for. Pain after gynecological surgery usually severe. Uncontrolled acute post-operative pain is associated with dissatisfaction, post-operative complications and considered as a strong risk factor for development of chronic pain. An enhanced recovery pathway for gynecological surgery must include a strategy to effectively control post-operative pain and allow attainment of other Enhanced Recovery After Surgery (ERAS) targets such as early mobilization and return to oral diet whilst reducing the need for opiates. Beyond increasing the risk of developing opioid use disorder, perioperative opioid consumption may produce undesirable side effects such as nausea, vomiting, constipation, ileus, pruritus, altered mental status, urinary retention, respiratory complications and increased length of hospital stay. While many of these side effects are frustrating to patient in the immediate postoperative period, the most dangerous effects are those that affect the respiratory system such as opioid-induced respiratory depression (ORD) which consider as a significant cause of brain damage and death in the postoperative period. Opioid reduction strategies prove useful for decreasing total opioid dose and, in turn, their associated adverse effects. Such strategies may include adjuvant non opioid analgesics such as α-2 agonists, gabapentinoids and N-methyl-D-aspartate receptor agonists as well as local, regional or neuraxial anesthesia and modification of surgical technique where possible for operative patients. Pregabalin is a new synthetic molecule and a structural derivative of the inhibitory neurotransmitter gamma-amino butyric acid. It is a α2-δ ligand that has analgesic, anticonvulsant, anxiolytic and sleep-modulating activities. Pregabalin binds potently to the α2-δ subunit of calcium channels, resulting in a reduction in the release of several neurotransmitters including glutamate, noradrenaline, serotonin, dopamine and substance P. Pregabalin could reduce the hyperexcitability of dorsal horn neurons induced by tissue damage; therefore it may be useful in the postsurgical pain prevention. In 2015, a meta-analysis published in British Medical Journal (BMJ) suggested that pregabalin could improve postoperative analgesia and opioid-related adverse effects namely, vomiting and visual disturbances after surgery. However, the use of the pregabalin for acute postoperative pain is still under trial though widely reported.

Official Title
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Effect of Two Different Doses of Oral Pregabalin Premedication for Postoperative Pain Relief After Gynecological Surgeries

Conditions
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Gynecologic Disease

Intervention / Treatment
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* Drug: placebo capsule (vitamin c)
* Drug: Group pregabalin 150
* Drug: Group pregabalin 300


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Physical status: ASA I-II BMI ≥ 20kg/m2 & ≤ 35kg/m2, Written informed consent from the patient. Exclusion Criteria: Patients with known history of allergy to study drugs, Patients on ACE inhibitors, anticonvulsant therapy or any drug interacting with pregabalin, Patients on chronic alcohol, opioid, tranquilizer or sedative use, Patient with renal impairment or heart failure, Pregnant females, Psychological, mental disorders or depression, Patients receiving anticoagulants therapy or suspected coagulopathy, Patients already on pregbalin or gabapentin therapy.

Ages Eligible for Study
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Minimum Age: 21 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The patients will be allocated randomly using computer generated randomization table into three equal groups
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: control group<br>the patient will receive one placebo capsule (vitamin c) once one hour before the operation. | Drug: placebo capsule (vitamin c)<br>* the patient will receive one placebo capsule (vitamin c) once one hour before the operation<br>|
| Active Comparator: Group Pregabalin 150<br>the patient will receive one capsule of pregabalin 150 mg once one hour before the operation | Drug: Group pregabalin 150<br>* the patient will receive one capsule of pregabalin 150 mg once one hour before the operation<br>* Other names: p150;|
| Active Comparator: Group Pregabalin 300<br>the patient will receive one capsule of pregabalin 300 mg once one hour before the operation | Drug: Group pregabalin 300<br>* the patient will receive one capsule of pregabalin 300 mg once one hour before the operation<br>* Other names: p300;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in Postoperative pain | will be assessed by visual analogue scale (VAS), On a scale of 0-10, the patient will learn to quantify postoperative pain where 0= No pain and 10= Maximum worst pain. | at 2, 4, 6, 8, 10, 12, 16, 20 and 24 hours postoperatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The level of sedation | using the modified Ramsay Sedation Score: Patient is anxious and agitated or restless, or both. Patient is cooperative, oriented and tranquil. Patient responds to commands only. Patient exhibits brisk response to light glabellar tap or loud auditory stimulus. Patient exhibits sluggish response to light glabellar tap or loud auditory stimulus. Patient exhibits no response. | at 2, 4, 6, 8, 10, 12, 16, 20 and 24 hours postoperatively | 
| Total amount of rescue analgesic | Total amount of rescue analgesic requirement by the patient | in the first 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oral Pregabalin, Postoperative Pain Relief, Gynecological Surgeries