The Effect of Intraperitoneal Bupivacaine Versus Bupivacaine With Neostigmine on Pain in Laparoscopic Cholecystectomy

Study Overview
=================
Brief Summary
-----------------
Injection of intraperitoneal bupivacaine revealed an analgesic effect whether injected alone or in combination with other adjuvants, which increase duration of analgesia and decrease the dose of administered bupivacaine thus minimizing its side effects e.g. Opioids, Corticosteroids and Magnesium sulphate. Neostigmine, a cholinesterase inhibitor that produces muscarinic receptor-mediated analgesia, increased postoperative analgesia when combined with local anaesthetics. Peripheral afferent nerve fibres contain muscarinic receptors, these could be a good target for pain suppression.

Detailed Description
-----------------
The use of neostigmine as adjuvant to intraperitoneal bupivacaine was not previously investigated. In this study the investigators will compare the analgesic effect of bupivacaine alone and bupivacaine in combination with neostigmine when injected intraperitoneal in patients undergoing laparoscopic cholecystectomy.

Official Title
-----------------
The Evaluation of the Analgesic Effect of Intraperitoneal Bupivacaine Versus Bupivacaine With Neostigmine on Postoperative Pain in Laparoscopic Cholecystectomy:A Prospective, Randomized, Comparative, Double-blind Study.

Conditions
-----------------
Pain, Postoperative

Intervention / Treatment
-----------------
* Drug: Bupivacaine Hydrochloride
* Drug: Neostigmine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: • American Society of Anaesthesiologist (ASA) I-II. Age 18 - 60 years. Elective laparoscopic cholecystectomy. Body Mass Index (BMI) <35 (kg/m2). Exclusion Criteria: • Anaphylaxis to local anaesthetics. Anaphylaxis to Neostigmine. American Society of Anaesthesiologist (ASA) III-IV. Chronic pain diseases. Acute cholecystitis. Psychological or nervous system diseases

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Group 1 (Bupivacaine group= B group) will receive a 50 mL solution of bupivacaine 0.25% intraperitoneal instilled solution. Group 2 (Bupivacaine neostigmine group=BN group) will receive 500 μg neostigmine mixed with bupivacaine 0.25% with a total volume of 50 mL intraperitoneal instilled solution.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: B group<br>-Group 1 (Bupivacaine group= B group) will receive a 50 mL solution of bupivacaine 0.25% intraperitoneal instilled solution. | Drug: Bupivacaine Hydrochloride<br>* after induction of general anesthesia and before the start of surgery, after inflating the pneumoperitoneum and before any surgical manipulation, the surgeon infuse 50 mL of blinded solution (bupivacaine or bupivacaine neostigmine) intraperitoneally to the sub-diaphragmatic space and gall bladder area guided by the camera and the patients are kept in Trendelenburg position for 5-10 minutes. Thereafter all patients will be positioned in the anti-Trendelenburg position to start the surgery and the laparoscopic procedure will be carried out in a standard fashion.<br>* Other names: Marcaine;|
| Active Comparator: BN group<br>Group 2 (Bupivacaine neostigmine group=BN group) will receive 500 μg neostigmine mixed with bupivacaine 0.25% with a total volume of 50 mL intraperitoneal instilled solution. | Drug: Bupivacaine Hydrochloride<br>* after induction of general anesthesia and before the start of surgery, after inflating the pneumoperitoneum and before any surgical manipulation, the surgeon infuse 50 mL of blinded solution (bupivacaine or bupivacaine neostigmine) intraperitoneally to the sub-diaphragmatic space and gall bladder area guided by the camera and the patients are kept in Trendelenburg position for 5-10 minutes. Thereafter all patients will be positioned in the anti-Trendelenburg position to start the surgery and the laparoscopic procedure will be carried out in a standard fashion.<br>* Other names: Marcaine;Drug: Neostigmine<br>* after induction of general anesthesia and before the start of surgery, after inflating the pneumoperitoneum and before any surgical manipulation, the surgeon infuse 50 mL of blinded solution (bupivacaine or bupivacaine neostigmine) intraperitoneally to the sub-diaphragmatic space and gall bladder area guided by the camera and the patients are kept in Trendelenburg position for 5-10 minutes. Thereafter all patients will be positioned in the anti-Trendelenburg position to start the surgery and the laparoscopic procedure will be carried out in a standard fashion.<br>* Other names: prostigmin;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time of first analgesic requirements (in hours) after extubation | hours | 24 Hours post-operatively. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| • Total dose of intravenous pethidine (mg/24 hours). | milligram | 24 hours | 
| • The use of intra-operative rescue analgesia. | milligram | intraoperative period | 
| • The severity of post-operative shoulder pain assessed by visual analogue scale | segmented numeric version of the visual analog scale (VAS) in which a respondent selects a whole number (0-10 integers) that best reflects the intensity of their pain 0 (no pain), 10(worst pain). The common format is a horizontal bar or line | 24 Hours post-operatively. | 
| • The severity of post-operative abdominal pain assessed by visual analogue scale | segmented numeric version of the visual analog scale (VAS) in which a respondent selects a whole number (0-10 integers) that best reflects the intensity of their pain 0 (no pain), 10(worst pain). The common format is a horizontal bar or line | 24 hours posoperatively | 
| • Post-operative nausea and vomiting assessed by postoperative nausea and vomiting score | A simplified risk score for predicting postoperative nausea and vomiting female gender, history of PONV and/or motion sickness, non-smoking status, and postoperative use of opioids. When 0, 1, 2, 3, or 4 factors are present, the risk of postoperative nausea and vomiting is 10%, 20%, 40%, 60%, or 80%, respectively | 24 hours postoperatively |