Efficacy of Perioperative Duloxetine as a Part of Multimodal Analgesia in Laparoscopic Colorectal Cancer Surgery

Study Overview
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Brief Summary
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Our aim will be to evaluate the efficacy of perioperative Duloxetine in decreasing acute postoperative pain after laparoscopic colorectal cancer surgery and its role in reducing postoperative morphine requirements

Detailed Description
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Abdominal surgery is usually associated with severe; wide spread post-operative pain. The greater propensity for pain and opioid-related side effects are likely contributing factors for poor postsurgical recovery, and it often results in significant pain and slow recovery. Although Opioids are considered the analgesics of choice to treat moderate to severe pain, their use carries the risk of side effects and hyperalgesia. Multimodal analgesia is advocated for perioperative pain management to reduce opioid use and its associated adverse effects. Multimodal analgesia can be achieved by combining different analgesics and different methods of administration, to provide better analgesia synergistically compared with conventional analgesia.Therefore, lower doses for each drug can be provided with fewer overall side-effects obtained from individual compounds.Serotonin and norepinephrine are involved in the modulation of endogenous analgesic mechanisms via descending inhibitory pain pathways in the brain and spinal cord. An increase in serotonin and norepinephrine may increase inhibition of nociceptive input and improve pain relief. Duloxetine is a serotonin-norepinephrine reuptake inhibitor commonly prescribed for the treatment of major depression and anxiety. Duloxetine also has been used in the treatment of chronic pain conditions. There several reasons why duloxetine might improve postsurgical quality of recovery. First, systemic Duloxetine seems to have perioperative analgesic effects. In addition, as a serotonin-norepinephrine reuptake inhibitor, it is possible that the drug may prevent transient emotional problems that are common during the perioperative period. Lastly, the combination of less pain and better emotional status can result in better physical independence scores after surgery. The main objective of the current study is to examine the effect of perioperative Duloxetine on postoperative pain after laparoscopic colorectal surgery.

Official Title
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Efficacy of Perioperative Duloxetine as a Part of Multimodal Analgesia in Laparoscopic Colorectal Cancer Surgery

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: Duloxetine
* Drug: Placebo oral tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ASA I-III aged 18-65 years and scheduled for laparoscopic colorectal surgery for cancer colon Exclusion Criteria: unable to express their pain or patient refusal. allergy to the study drug an abnormal liver or renal function tests a chronic opioid abuser(> 3 mo), being on chronic gabapentin or pregabalin(> 3 mo) antidepressant drugs, patients with psychiatric disorders Pregnant females

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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Accepts Healthy Volunteers

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group (I) (D) : (Duloxetine group)<br> | Drug: Duloxetine<br>* Each Patient will receive oral Duloxetine capsule 60mg at the night before operation(12hrs before surgery), the 2nd dose 60 mg Duloxetine capsule 1hr before operation and 3rd dose 60mg capsule after 24hrs postoperative<br>|
| Placebo Comparator: Group (II) (P): (placebo group)<br> | Drug: Placebo oral tablet<br>* Each patient will receive a similar looking placebo capsule in the same time schedule. The placebo capsule will be prepared by hospital pharmacy to insure that active Duloxetine capsules will be indistinguishable from the placebo capsules contained starch<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| morphine consumption | total morphine consumption(mg) in 48 hours if VAS score( Visual Analog Scale ) more than 3. score from 0 to 10 where 0 = no pain and 10 = the worst pain imaginable | 48 hours postoperative | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pain scores | - pain scores ( theVAS score ).evaluation the pain using VAS ( Visual Analog Scale ) scored from 0 to 10 where 0 = no pain and 10 = the worst pain imaginable | 48 hours postoperative | 
| first request of analgesia | - the time of first request of analgesia (morphine) requirement postoperative | 48 hours postoperative | 
| Postoperative sedation | Postoperative sedation will be assessed using a modified observers. Assessment of alterness /sedation scale where 6= agitated to 0 = doesn't respond to deep stimulus. | 48 hours postoperative | 
| Postoperative patient satisfaction | Postoperative patient satisfaction will be measured using a numerical score of 1-4 (1= poor, 2= fair, 3= good, 4= very good) . | 48 hours postoperative |