Duloxetine for Postoperative Analgesia After Modified Radical Mastectomy

Study Overview
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Brief Summary
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The aim of this study is to evaluate the role of duloxetine in controlling pain after radical mastectomy.

Detailed Description
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Inadequate control of postoperative pain is associated with increased length of hospital stay, increased hospital cost, sleep disturbance, depression, functional impairment and affects the quality of life. Modified is one of the commonly performed procedures which is associated with severe postoperative pain. Preemptive analgesia is the analgesic treatment initiated before the surgical procedure to prevent central sensitization from the noxious stimuli. Drugs such as gabapentin, pregabalin, serotonin-norepinephrine reuptake inhibitors, dexamethasone, and cyclooxygenase-2 inhibitors have been used for preemptive analgesia. There are contrary results about the role of duloxetine in mangement of acute postoperative pain. Arecent meta-analysis was done in 2020 that concluded that the currently available evidence does not support the clinical use of duloxetine for the management of acute postoperative pain,so we will discuss that in this study. There are many studies that have shown that perioperative use of duloxetine for a few days has a significant effect on reducing postoperative pain and analgesic requirements. Duloxetine is a dual anti-depressant drug that inhibits the neuronal reuptake of serotonin (5-HT) and norepinephrine (NE) modulating the descending inhibitory pain pathways by increasing the availability of serotonin and norepinephrine. Duloxetine is an approved drug for the treatment of post-traumatic depression, major depression, and generalized anxiety disorder. It is also approved for the treatment of various chronic painful syndromes, including neuropathic pain associated with diabetes, chronic musculoskeletal pain, and fibromyalgia. The mechanisms of action so far described suggest that duloxetine may be useful as an adjunct in the treatment of acute postoperative pain.

Official Title
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Duloxetine for Post Operative Analgesia After Modified Radical Mastectomy:A Randomized Controlled Study

Conditions
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Modified Radical Mastectomy, Postoperative Analgesia

Intervention / Treatment
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* Procedure: Acetaminophen group
* Procedure: Duloxetine group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult female patients aged (18 - 60) years undergoing modified radical mastectomy. American Society of Anesthesiologists Classification I-II-III Exclusion Criteria: Known Allergies to duloxetine. Abnormal liver or renal function tests. Narrow angle glaucoma. Being a chronic opioid abuser (more than 3 months) Being on chronic gabapentin or pregabalin (more than 3 months) Being on Monoamine oxidase inhibitor, tricyclic antidepressant, or fluvoxamine. Pregnant female Patients with psychiatric disorders or seizure disorders.

Ages Eligible for Study
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Minimum Age: 18 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acetaminophen group<br>patients will receive intravenous 500 mg acetaminophen(every 6 hours postoperatively. | Procedure: Acetaminophen group<br>* patients will receive intravenous 500 mg acetaminophen(every 6 hours postoperatively<br>|
| Experimental: Duloxetine group<br>Patients will receive duloxetine 30 mg every 12 hours for 3 days before surgery, 30 mg 2 hours preoperatively and 30 mg 12 hours postoperatively and intravenous 500 mg acetaminophen (every 6 hours postoperatively) | Procedure: Duloxetine group<br>* Patients will receive duloxetine 30 mg every 12 hours for 3 days before surgery, 30 mg 2 hours preoperatively and 30 mg 12 hours postoperatively and intravenous 500 mg acetaminophen every 6 hours postoperatively<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total morphine consumption | Postoperative Total morphine consumption will be recorded | 48 hours postoperatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| First analgesic request | First analgesic request will be recorded | 24 hours postoperatively | 
| Post-operative pain | Post-operative pain will be assessed by visual analogue score (VAS) from 0-10 scale 0 (no pain) to 10 (the worst imaginable pain) at 2,4,6 h then every 6h | 48 hours postoperatively. | 
| Heart rate | Heart rate will be measured every 30 minutes intraoperative and at 0 hour (direct postoperative) at post anesthesia care unit then at 2,4,6 hours at ward then every 6 hours for 48 hours postoperatively | 48 hours postoperatively | 
| Mean arterial blood pressure | Mean arterial blood pressure will be measured every 30 minutes intraoperative and at 0 hour (direct postoperative) at post anesthesia care unit then at 2,4,6 hours at ward then every 6 hours for 48 hours postoperatively | 48 hours postoperatively | 
| Adverse effects | Hypotension, Bradycardia, nausea, dry mouth,diarrhea, constipation,insomnia, somnolence, fatigue, hyperhidrosis and pruritus will be observed and treated accordingly | 48 hours postoperatively |