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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Fentanyl | Experimental | 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. |
|
| ketamine | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fentanyl | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Time of first analgesic request. | The primary outcome of the study is comparison of the post-operative analgesic effect regarding the time to first analgesic request of fentanyl versus Ketamine as adjuvants to bupivacaine in patients undergoing laparoscopic cholecystectomy | 24 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Total analgesia consumption postoperatively. | Total Nalphuine consumption in milligrams, in the first 24 hours postoperatively. | 24 hours |
| Postoperative Numeric Rating Scale of pain | Postoperative Numeric Rating Scale of pain.( in post-anaesthesia care unit, half hour, 2, 6, 12, 18, 24 hours postoperatively) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Tarek Mo Essa Tohamy | Contact | +201027342291 | tarekessa970@gmail.com | |
| Eman Ah Ismail, MD | Contact | +20 1060223750 | emanismail@aun.edu.eg |
| Name | Affiliation | Role |
|---|---|---|
| Tarek Mo Essa Tohamy | Assiut University | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37868486 | Background | 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. | |
| 15094977 | Background | 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. |
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| ID | Term |
|---|---|
| D010149 | Pain, Postoperative |
| ID | Term |
|---|---|
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D010146 | Pain |
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| ID | Term |
|---|---|
| D005283 | Fentanyl |
| D007649 | Ketamine |
| ID | Term |
|---|---|
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D003510 | Cyclohexanes |
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Instillation technique Intraperitoneal instillation of study drugs will be done by the operating surgeon through laparoscopic ports guided by surgical camera after the removal of the gall bladder, onto the gall bladder fossa, under the diaphragm, on the liver bed and patient position was changed to 15° 20° Trendelenburg position for 10 min.
Intraperitoneal Instillation: The mixture of bupivacaine and fentanyl or Ketamine is instilled into the peritoneal cavity after securing hemostasis over the gall bladder bed.
Study drug doses:
Bupivacaine: Typically, 0.25% to 0.5% concentration is used for intraperitoneal instillation. A common volume is 20 mL, depending on the clinical protocol.
Fentanyl group (42 patients): When used as an adjuvant to bupivacaine, a dose of 1 ug/kg is commonly added to the local anaesthetic solution.
Ketamine group (42 patients): When used as an adjuvant to bupivacaine, a dose of 0.25 mg/kg is commonly added to the local anesthetic solution.
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An independent anesthesiologist randomly divided the patients into 42 groups of patients each using computer-generated random numbers fentanyl group and ketamine group (Group F and Group K). We discreetly placed the randomization results in envelopes until the end of the study. Both ketamine and fentanyl are colorless liquids, and they were digitally encoded so that the researchers who were responsible for postoperative follow-up and data processing were blinded to the group allocation during the whole study period. All patients were also blinded to the group allocation.
|
| Ketamine | Drug | 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. |
|
| 24 hours postoperatively. |
| 20393755 | Background | 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. |
| 12847519 | Background | 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. |
| Background | 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. |
| 11727145 | Background | 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. |
| 1683981 | Background | 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. |
| 16931681 | Background | 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. |
| Background | Hong E, Jeong DH, Kang HY, Choi JH, Park SW. The effect of preemptive intravenous ketamine on postoperative pain in patients undergoing arthroscopic rotator cuff repair with intra-articular ropivacaine injection Anesth Pain Med. 2003;11:71-75 |
| 30551090 | Background | Glick JL, Christensen T, Park JN, McKenzie M, Green TC, Sherman SG. Stakeholder perspectives on implementing fentanyl drug checking: Results from a multi-site study. Drug Alcohol Depend. 2019 Jan 1;194:527-532. doi: 10.1016/j.drugalcdep.2018.10.017. Epub 2018 Nov 13. |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D003516 |
| Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |