Intraperitoneal Ketamine Versus Fentanyl as Adjuvants to Bupivacaine in Laparoscopic Cholecystectomy

Official title

Intraperitoneal Instillation of Ketamine Versus Fentanyl as Adjuvants to Bupivacaine for Postoperative Pain Control in Laparoscopic Cholecystectomy _a Double-blinded Randomized Trial.

Overview

Laparoscopic cholecystectomy is the standard surgical treatment for gallbladder stones; however, the origin of pain after LC is multifactorial and complex in nature. Pain arising from incision sites is parietal pain, whereas pain from the gall bladder bed is mainly visceral in nature, and shoulder pain is mainly referred owing to the residual carbon dioxide irritating the diaphragm. Intraperitoneal administration of local anesthetics has been shown to improve postoperative pain control and reduce the need for systemic analgesics. The addition of adjuvant agents such as fentanyl or ketamine may further enhance analgesic efficacy. This randomized double-blind study aims to compare the effectiveness of intraperitoneal ketamine versus fentanyl as adjuvants to bupivacaine in reducing postoperative pain and analgesic requirements following laparoscopic cholecystectomy.

Detailed description

Laparoscopic cholecystectomy (LC) is widely recognized as the gold standard for the treatment of gallbladder stones due to its significant advantages over the conventional open surgical approach. These benefits include faster postoperative recovery, reduced surgical morbidity, shorter hospital stay, and decreased postoperative pain. Despite these advantages, postoperative pain remains a major concern and is considered one of the primary factors affecting patient comfort and delaying discharge following surgery. Abdominal pain is usually most pronounced during the first 24 hours after the procedure, while shoulder pain commonly develops on the second postoperative day as a consequence of diaphragmatic irritation caused by residual carbon dioxide. Because postoperative pain after laparoscopic surgery is multifactorial in origin, a multimodal analgesic approach is widely recommended . Various strategies have been employed to improve pain control, including the use of local anesthetics administered alone or in combination with intraperitoneal opioid analgesics. Intraperitoneal (I.P.) administration of local anesthetics has become a popular and effective technique for postoperative pain management, as it can reduce the need for systemic analgesics and minimize the adverse effects associated with nonsteroidal anti-inflammatory drugs and opioids. This approach was first investigated in gynecological laparoscopic procedures and has since been extensively studied in patients undergoing LC. Several studies have demonstrated that the addition of adjuvants such as fentanyl, a potent synthetic opioid, and ketamine, an N-methyl-D-aspartate receptor antagonist, may enhance and prolong postoperative analgesia. Consequently, intraperitoneal instillation of local anesthetics with adjuvant agents represents a simple, safe, and effective method for improving postoperative pain control following LC.

Interventions

• Drug Fentanyl
  Fentanyl used as an adjuvant to bupivacaine for intraperitoneal instillation during laparoscopic cholecystectomy, a dose of 1 ug/kg is commonly added to the local anesthetic solution. Bupivacaine: Typically, 0.25% to 0.5% concentration is used for intraperitoneal instillation. A common volume is 20 mL, depending on the clinical protocol.
• Drug Ketamine
  Ketamine used as an adjuvant to bupivacaine for intraperitoneal instillation during laparoscopic cholecystectomy, a dose of 0.25 mg/kg is commonly added to the local anesthetic solution. Bupivacaine: Typically, 0.25% to 0.5% concentration is used for intraperitoneal instillation. A common volume is 20 mL, depending on the clinical protocol.

Primary outcome measures

• Time of first analgesic request. [Time frame: 24 hours]

Secondary outcome measures (2)

• Total analgesia consumption postoperatively. [Time frame: 24 hours]
• Postoperative Numeric Rating Scale of pain [Time frame: 24 hours postoperatively.]

Eligibility criteria

Inclusion criteria

• Patients of age 20-50 years
• Patients of either gender
• Patients planned to undergo elective LC.
• Patients have I-II of the American Society of Anaesthesiologists (ASA)

Exclusion criteria

• Patient's refusal.
• body mass index (BMI) ≥40 kg/m2.
• History of hypersensitivity to the drugs being evaluated
• Inability to comprehend postoperatively the pain assessment scale/neuropsychiatric disorders.
• chronic use of opioids and opioid addiction
• Patients with acute cholecystitis or converted to open surgery.
• Carcinoma of gall bladder
• Pregnant female
• Bleeding disorders

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Mannam R, Sankara Narayanan R, Bansal A, Yanamaladoddi VR, Sarvepalli SS, Vemula SL, Aramadaka S. Laparoscopic Cholecystectomy Versus Open Cholecystectomy in Acute Cholecystitis: A Literature Review. Cureus. 2023 Sep 21;15(9):e45704. doi: 10.7759/cureus.45704. eCollection 2023 Sep. PMID 37868486
• Kuhry E, Jeekel J, Bonjer HJ. Effect of laparoscopy on the immune system. Semin Laparosc Surg. 2004 Mar;11(1):37-44. doi: 10.1177/107155170401100107. PMID 15094977
• Kahokehr A, Sammour T, Soop M, Hill AG. Intraperitoneal use of local anesthetic in laparoscopic cholecystectomy: systematic review and metaanalysis of randomized controlled trials. J Hepatobiliary Pancreat Sci. 2010 Sep;17(5):637-56. doi: 10.1007/s00534-010-0271-7. PMID 20393755
• Khodorova A, Navarro B, Jouaville LS, Murphy JE, Rice FL, Mazurkiewicz JE, Long-Woodward D, Stoffel M, Strichartz GR, Yukhananov R, Davar G. Endothelin-B receptor activation triggers an endogenous analgesic cascade at sites of peripheral injury. Nat Med. 2003 Aug;9(8):1055-61. doi: 10.1038/nm885. Epub 2003 Jun 29. PMID 12847519
• E. E. F. Mohamed, K. M. Hassan, W. A. Aboelwafa, and I. M. Ahmed, "Analgesia for Postoperative Pain in Laparoscopic Surgery: Review Article," Egypt. J. Hosp. Med., vol. 87, no. 1, 2022, doi: 10.21608/ejhm.2022.229353.
• Laisalmi M, Koivusalo AM, Valta P, Tikkanen I, Lindgren L. Clonidine provides opioid-sparing effect, stable hemodynamics, and renal integrity during laparoscopic cholecystectomy. Surg Endosc. 2001 Nov;15(11):1331-5. doi: 10.1007/s004640090126. Epub 2001 Aug 16. PMID 11727145
• Narchi P, Benhamou D, Fernandez H. Intraperitoneal local anaesthetic for shoulder pain after day-case laparoscopy. Lancet. 1991 Dec 21-28;338(8782-8783):1569-70. doi: 10.1016/0140-6736(91)92384-e. PMID 1683981
• Boddy AP, Mehta S, Rhodes M. The effect of intraperitoneal local anesthesia in laparoscopic cholecystectomy: a systematic review and meta-analysis. Anesth Analg. 2006 Sep;103(3):682-8. doi: 10.1213/01.ane.0000226268.06279.5a. PMID 16931681

Identifiers

NCT: NCT07670052 · 04-2026-201752

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗