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

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.

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.

Study Overview

• Status: Completed
• Conditions: Pain, Postoperative
• Intervention / Treatment: Drug: Bupivacaine Hydrochloride; Drug: Neostigmine

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.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 2

Contacts and Locations

Study Locations

• Egypt
  • El Azbakeya
    • Cairo, El Azbakeya, Egypt, 2222
      • Sara Farouk Kassem Habib

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: B group; -Group 1 (Bupivacaine group= B group) will receive a 50 mL solution of bupivacaine 0.25% intraperitoneal instilled solution.	Drug: Bupivacaine Hydrochloride; 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.; Other Names: Marcaine
Active Comparator: BN group; 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; 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.; Other Names: Marcaine; Drug: Neostigmine; 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.; 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

Collaborators and Investigators

• Sponsor: Kasr El Aini Hospital
• Investigators: Principal Investigator: Sara Fa Habib, PhD, Kasr El Aini -Faculty Of Medicine- Cairo University

Publications and helpful links

General Publications

• Khurana S, Garg K, Grewal A, Kaul TK, Bose A. A comparative study on postoperative pain relief in laparoscopic cholecystectomy: Intraperitoneal bupivacaine versus combination of bupivacaine and buprenorphine. Anesth Essays Res. 2016 Jan-Apr;10(1):23-8. doi: 10.4103/0259-1162.164731.
• LAURETTI G. Postoperative analgesia by intra-articular and epidural neostigmine following knee surgery. Reg Anesth Pain Med [Internet]. 1999 Jun;24(3):17.

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2020
• Primary Completion (Actual): July 6, 2020
• Study Completion (Actual): August 6, 2020

Study Registration Dates

• First Submitted: January 21, 2020
• First Submitted That Met QC Criteria: January 27, 2020
• First Posted (Actual): January 28, 2020

Study Record Updates

• Last Update Posted (Actual): September 3, 2020
• Last Update Submitted That Met QC Criteria: September 1, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Enzyme Inhibitors; Sensory System Agents; Anesthetics; Anesthetics, Local; Cholinesterase Inhibitors; Parasympathomimetics; Bupivacaine; Neostigmine
• Other Study ID Numbers: MS-273-2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: results of the study or medical data like vital signs only could be shared
• IPD Sharing Time Frame: 2 months after publication
• IPD Sharing Access Criteria: data concerning results charts will be available by contacting principal investigator
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No