Intra-operative low-dose ketamine versus dexmedetomidine for attenuation of acute postoperative pain following laparoscopic cholecystectomy: a randomized clinical trial
DOI:
https://doi.org/10.18203/2320-6012.ijrms20260617Keywords:
Ketamine, Dexmedetomedine, Cholecystectomy, Post-op analgesiaAbstract
Background: Ketamine and dexmedetomidine are opioid-sparing agents with distinct analgesic properties. Ketamine is valued for its ability to prevent central sensitization and hyperalgesia without causing respiratory depression. Dexmedetomidine exhibits sedative, anxiolytic, analgesic, anaesthetic, and sympatholytic effects. This study hypothesized that a low-dose combination of ketamine and dexmedetomidine would offer superior analgesia compared to either agent alone when used as an adjuvant during balanced general anaesthesia.
Methods: Sixty patients scheduled for elective laparoscopic cholecystectomy under general anaesthesia were randomized into four groups group D: dexmedetomidine 0.25 μg/kg i.v., group K: ketamine 0.25 mg/kg i.v., group DK: combination of dexmedetomidine and ketamine at the same doses, group S: normal saline. All drugs were diluted to 5 ml and administered intravenously 20 minutes before anticipated skin closure. Postoperative VAS scores and sedation were assessed. The time to first rescue analgesia and total diclofenac consumption over 24 hours were documented.
Results: Postoperatively, group DK demonstrated significantly lower VAS scores at rest and during movement across multiple time points compared to the other groups (p<0.05). The combination group also had the longest time to first rescue analgesia and the lowest total diclofenac requirement. No significant adverse effects were reported in any of the groups.
Conclusions: A low-dose combination of ketamine and dexmedetomidine administered prior to skin closure in laparoscopic cholecystectomy significantly improves postoperative analgesia without increasing side effects. This combination appears to be a safe and effective strategy for enhancing pain control following laparoscopic cholecystectomy.
Metrics
References
Rawal N. Current issues in postoperative pain management. Eur J Anesthesiol. 2016;33(3):160-71. DOI: https://doi.org/10.1097/EJA.0000000000000366
Gan TJ. Poorly controlled postoperative pain: prevalence, consequences, and prevention. J Pain Res. 2017;10:2287-98. DOI: https://doi.org/10.2147/JPR.S144066
Khademi H, Kamangar F, Brennan P, Malekzadeh R. Opioid therapy and its side effects: a review. Arch Iran Med. 2016;19(12):870-6.
Chia YY, Liu K, Wang JJ, Kuo MC, Ho ST. Intraoperative high-dose fentanyl induces postoperative fentanyl tolerance. Can J Anaesth. 1999;46(9):872-7. DOI: https://doi.org/10.1007/BF03012978
Chang G, Chen L, Mao J. Opioid tolerance and hyperalgesia. Med Clin North Am. 2007;91(2):199-211. DOI: https://doi.org/10.1016/j.mcna.2006.10.003
Helander EM, Menard BL, Harmon CM, Homra BK, Allain AV, Bordelon GJ, et al. Multimodal analgesia, current concepts, and acute pain considerations. Curr Pain Headache Rep. 2017;21(1):3. DOI: https://doi.org/10.1007/s11916-017-0607-y
Kim SH, Kim SI, Ok SY, Park SY, Kim MG, Lee SJ, et al. Opioid sparing effect of low dose ketamine in patients with intravenous patient-controlled analgesia using fentanyl after lumbar spinal fusion surgery. Korean J Anesthesiol. 2013;64(6):524-8. DOI: https://doi.org/10.4097/kjae.2013.64.6.524
Gupta N, Rath GP, Prabhakar H, Dash HH. Effect of intraoperative dexmedetomidine on postoperative recovery profile of children undergoing surgery for spinal dysraphism. J Neurosurg Anesthesiol. 2013;25(3):271-8. DOI: https://doi.org/10.1097/ANA.0b013e31828cb6c0
Imani F, Varrassi G. Ketamine as adjuvant for acute pain management. Anesth Pain Med. 2019;9(6):e100178. DOI: https://doi.org/10.5812/aapm.100178
Ebert T, Maze M. Dexmedetomidine: another arrow for the clinician's quiver. Anesthesiology. 2004;101(3):568-70. DOI: https://doi.org/10.1097/00000542-200409000-00003
Mitra R, Prabhakar H, Rath GP, Bithal PK, Khandelwal A. A comparative study between intraoperative low-dose ketamine and dexmedetomidine, as an anesthetic adjuvant in lumbar spine instrumentation surgery for the post-operative analgesic requirement. J Neuroanesthesiol Crit Care. 2017;4:91-8.
Elbadawy AM, Salama AK, Mohammad MM. Comparative study of intra-articular dexmedetomidine versus ketamine as adjuvant analgesics after knee arthroscopy. Egypt J Anaesth. 2015;31:309-14. DOI: https://doi.org/10.1016/j.egja.2015.05.003
Karasu D, Yilmaz C, Ozgunay SE, Yalcin D, Ozkaya G. Ultrasound-guided transversus abdominis plane block for postoperative analgesia in laparoscopic cholecystectomy: a retrospective study. North Clin Istanb. 2020;8(1):88-94. DOI: https://doi.org/10.14744/nci.2020.84665
Ragupathy R, Prabhu SCG, Thiyagarajan D, Anto V. Opioid-free anesthesia for laparoscopic surgeries- a prospective non-randomized study in a tertiary care hospital. Indian J Anaesth. 2022;66(3):207-12. DOI: https://doi.org/10.4103/ija.ija_785_21
Pandya MJ, Shah A. Comparative evaluation of dexmedetomidine and ketamine for epidural analgesia in lower limb orthopedic surgeries. Indian J Clin Anaesth. 2020;7(1):166-71. DOI: https://doi.org/10.18231/j.ijca.2020.029
Mohmed AH, Mansour HS, Hassanein AA, Ahmed MA. Ketamine versus dexmedetomidine as an adjuvant in ultrasound-guided supraclavicular brachial plexus block: a double-blind randomized clinical trial. Res Opin Anesth Intens Care. 2021;8:137-46. DOI: https://doi.org/10.4103/roaic.roaic_22_21
Garg N, Panda NB, Gandhi KA, Bhagat H, Batra YK, Grover VK, et al. Comparison of small dose ketamine and dexmedetomidine infusion for postoperative analgesia in spine surgery- a prospective randomized double-blind placebo-controlled study. J Neurosurg Anesthesiol. 2016;28(1):27-31. DOI: https://doi.org/10.1097/ANA.0000000000000193
Mena GE, Zorrilla-Vaca A, Vaporciyan A, Mehran R, Lasala JD, Williams W, et al. Intraoperative dexmedetomidine and ketamine infusions in an enhanced recovery after thoracic surgery program: a propensity score matched analysis. J Cardiothorac Vasc Anesth. 2022;36(4):1064-72. DOI: https://doi.org/10.1053/j.jvca.2021.09.038
Gupta BK, Mhaske VR, Pai VK, Mishra LD. A comparative study of sedo analgesic effect of dexmedetomidine and dexmedetomidine with ketamine in postoperative mechanically ventilated patients. J Anesthesiol Clin Pharmacol 2022;38:68-72. DOI: https://doi.org/10.4103/joacp.JOACP_234_19
Singh A, Iyer KV, Maitra S, Khanna P, Sarkar S, Ahuja V, et al. Ketamine and dexmedetomidine (Keto-dex) or ketamine and propofol (Keto-fol) for procedural sedation during endoscopic retrograde cholangiopancreatography: Which is safer? A randomized clinical trial. Indian J Gastroenterol. 2022;41(6):583-90. DOI: https://doi.org/10.1007/s12664-022-01291-y
Jain S, Nazir N, Mustafi SM. Preemptive low-dose intravenous ketamine in the management of acute and chronic postoperative pain following laparoscopic cholecystectomy: a prospective randomized control study. Med Gas Res. 2022;12(4):141-5. DOI: https://doi.org/10.4103/2045-9912.337995
Thappa P, Singh N, Luthra A, Deshpande P, Chauhan R, Meena SC, et al. Comparison of intraoperative low-dose ketodex and fentanyl infusion for postoperative analgesia in spine surgery: a prospective randomized double-blind study. Asian Spine J. 2023;17(5):894-903. DOI: https://doi.org/10.31616/asj.2022.0439
Gurbet A, Basagan-Mogol E, Turker G, Ugun F, Kaya FN, Ozcan B. Intraoperative infusion of dexmedetomidine reduces perioperative analgesic requirements. Can J Anesth. 2006;53(7):646-52. DOI: https://doi.org/10.1007/BF03021622
Efe Mercanoglu E, Girgin Kelebek N, Turker G, Aksu H, Ozgur M, Karakuzu Z, et al. Comparison of the effect of ketamine and dexmedetomidine combined with total intravenous anesthesia in laparoscopic cholecystectomy procedures: a prospective randomized controlled study. Int J Clin Pract. 2022;2022:1878705. DOI: https://doi.org/10.1155/2022/1878705
Vishnuraj KR, Singh K, Sahay N, Sinha C, Kumar A, Kumar N. Opioid-free anesthesia using a combination of ketamine and dexmedetomidine in patients undergoing laparoscopic cholecystectomy: a randomized controlled trial. Anesth Pain Med. 2024;19(2):109-16. DOI: https://doi.org/10.17085/apm.23097
Málek J, Marecek F, Hess L, Kurzová A, Ocadlík M, Votava M. A combination of dexmedetomidine with ketamine and opioids results in significant inhibition of hemodynamic changes associated with laparoscopic cholecystectomy and in prolongation of postoperative analgesia. Rozhl Chir. 2010;89(5):275-81.
Create a blocked randomization list. England: Sealed Envelope Ltd; c2001-24. Available from: https://www.sealedenvelope.com/simple-randomiser/v1/lists. Accessed on 9 November 2022.
Daabiss M. American Society of Anaesthesiologists physical status classification. Indian J Anaesth. 2011;55(2):111-5. DOI: https://doi.org/10.4103/0019-5049.79879
Ramsay MA, Savege TM, Simpson BR, Goodwin R. Controlled sedation with alphaxalone-alphadolone. Br Med J. 1974;2(5920):656-9. DOI: https://doi.org/10.1136/bmj.2.5920.656
Collins SL, Moore RA, McQuay HJ. The visual analogue pain intensity scale: what is moderate pain in millimetres? Pain. 1997;72(1):95-7. DOI: https://doi.org/10.1016/S0304-3959(97)00005-5