Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.736
5-Year Impact Factor – 2.135
Index Copernicus  – 168.52
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

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Advances in Clinical and Experimental Medicine

2018, vol. 27, nr 4, April, p. 487–491

doi: 10.17219/acem/68630

Publication type: original article

Language: English

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Does preemptive gabapentin modulate cytokine response in total knee arthroplasty? A placebo controlled study

Ezgi Erkılıç1,A,B,C, Elvin Kesimci1,A,B,C,D,E,F, Duygu Sahin2,B, Bülent Bektaşer3,B, Nadir Yalçın3,A,B, Süleyman Ellik1,B, Aylin Sepici-Dinçel4,A,B,C

1 Clinic of Anesthesiology and Reanimation, Atatürk Training and Research Hospital, Ankara, Turkey

2 Department of Biochemistry, Faculty of Medicine, Baskent University, Ankara, Turkey

3 Department of Orthopedics and Traumatology, Atatürk Training and Research Hospital, Ankara, Turkey

4 Department of Medical Biochemistry, Faculty of Medicine, Gazi University, Ankara, Turkey

Abstract

Background. Gabapentin, as a structural analogue of γ-aminobutyric acid, has been investigated to provide pain relief in the early postoperative period following various surgical interventions.
Objectives. The objective of this study was to investigate whether preemptive oral administration of gabapentin 800 mg can reduce postoperative pain and modulate the inflammatory cytokine response in comparison to placebo in patients undergoing total knee arthroplasty under general anesthesia.
Material and Methods. Fifty-two patients were randomly divided into 2 groups before surgery, either to receive peroral gabapentin 800 mg or placebo drug, 1 h before surgery. All patients had general anesthesia with endotracheal intubation, in a standardized fashion, by the same anesthetist. Thirty min before completion of surgery, intramuscular diclofenac sodium 75 mg was administered. Following extubation, visual analogue pain scale (VAS) scores and additional analgesic requirements were recorded at 15 min at post-anesthesia care unit (PACU), and at 4th and 24th h postoperatively. Plasma levels of interleukin 6 (IL-6), and tumor necrosis factor R (TNF-R) were measured at predetermined time points (T0 1 h before administration of gabapentin, T1 at postoperative the 4th h mark, and T2 at postoperative at the 24th h mark).
Results. The VAS scores at postoperative 4th h were significantly higher in placebo and gabapentin groups compared with VAS scores at PACU and at 24th h. The groups did not differ in terms of additional analgesic requirements. In gabapentin group, IL-6 levels at T1 and T2 were significantly lower in comparison to values measured in placebo group at the same time points. This difference was not significant in TNF-R levels between the groups.
Conclusion. Though preemptive oral gabapentin administration did not reduce postoperative pain and analgesic requirements in total knee arthroplasty surgery, it attenuated IL-6 production on the first postoperative day.

Key words

preemptive, gabapentin, postoperative analgesia, serum IL-6, serum TNF

References (31)

  1. Dighe K, Clarke H, McCartney CJ, Wong CL. Perioperative gabapentin and delirium following total knee arthroplasty: A post-hoc analysis of a double-blind randomized placebo-controlled trial. Can J Anaesth. 2014;61:1136–1137. doi: 10.1007/s12630-014-0235-5
  2. Andres BM, Taub DD, Gurkan I, Wenz JF. Postoperative fever after total knee arthroplasty: The role of cytokines. Clin Orthop Relat Res. 2003;415:221–231.
  3. Hall GM, Peerbhoy D, Shenkin A, Parker CJ, Salmon P. Relationship of the functional recovery after hip arthroplasty to the neuroendocrine and inflammatory responses. Br J Anaesth. 2001;87:537–542.
  4. Szczepanik AM, Scislo L, Scully T, et al. IL-6 serum levels predict postoperative morbidity in gastric cancer patients. Gastric Cancer. 2011;14:266–273. doi: 10.1007/s10120-011-0039-z
  5. Giannoudis PV, Hak D, Sanders D, Donohoe E, Tosounidis T, Bahney C. Inflammation, bone-healing, and anti-inflammatory drugs: An update. J Orthop Trauma. 2015;29:S6–9. doi: 10.1097/BOT.000000 0000000465
  6. Mathiesen O, Møiniche S, Dahl JB. Gabapentin and postoperative pain: A qualitative and quantitative systematic review, with focus on procedure. BMC Anesthesiol. 2007;7:6. doi: 10.1186/1471-2253-7-6
  7. Ménigaux C, Adam F, Guignard B, Sessler DI, Chauvin M. Preoperative gabapentin decreases anxiety and improves early functional recovery from knee surgery. Anesth Analg. 2005;100:1394–1399.
  8. Farzi F, Naderi Nabi B, Mirmansouri A, et al. Postoperative pain after abdominal hysterectomy: A randomized, double-blind, controlled trial comparing the effects of tramadol and gabapentin as premedication. Anesth Pain Med. 2016;6:e32360. doi: 10.5812/aapm.32360
  9. Bang SR, Yu SK, Kim TH. Can gabapentin help reduce postoperative pain in arthroscopic rotator cuff repair? A prospective, randomized, double-blind study. Arthroscopy. 2010;26:S106–111. doi: 10.1016/j.arthro.2009.11.010
  10. Turan A, Karamanlioğlu B, Memiş D, et al. Analgesic effects of gabapentin after spinal surgery. Anesthesiology. 2004;100:935–938.
  11. Montazeri K, Kashefi P, Honarmand A. Pre-emptive gabapentin significantly reduces postoperative pain and morphine demand following lower extremity orthopedic surgery. Singapore Med J. 2007;48: 748–751.
  12. Pandey CK, Navkar DV, Giri PJ, et al. Evaluation of the optimal preemptive dose of gabapentin for postoperative pain relief after lumbar discectomy: A randomized, double-blind, placebo controlled study. J Neurosurg Anesthesiol. 2005;17:65–68.
  13. Short J, Downey K, Bernstein P, Shah V, Carvalho JC. A single preoperative dose of gabapentin does not improve postcesarean delivery pain management: A randomized, double-blind, placebo-controlled dose-finding trial. Anesth Analg. 2012;115:1336–1342. doi: 10.1213/ANE.0b013e31826ac3b9
  14. Clarke H, Pereira S, Kennedy D, et al. Gabapentin decreases morphine consumption and improves functional recovery following total knee arthroplasty. Pain Res Manag. 2009;14:217–222.
  15. Secrist ES, Freedman KB, Ciccotti MG, Mazur DW, Hammoud S. Pain management after outpatient anterior cruciate ligament reconstruction: A systematic review of randomized controlled trials. Am J Sports Med. 2015 Dec 18. pii: 0363546515617737.
  16. Watt DG, Horgan PG, McMillan DC. Routine clinical markers of the magnitude of the systemic inflammatory response after elective operation: A systematic review. Surgery. 2015;157:362–380. doi: 10. 1016/j.surg.2014.09.009
  17. Schäfers M, Geis C, Svensson CI, Luo ZD, Sommer C. Selective increase of tumor necrosis factor-alpha in injured and spared myelinated primary afferents after chronic constrictive injury of rat sciatic nerve. Eur J Neurosci. 2003;17:791–804.
  18. Koch A, Zacharowski K, Boehm O, et al. Nitric oxide and pro-inflammatory cytokines correlate with pain intensity in chronic pain patients. Inflamm Res. 2007;56:32–37.
  19. Davies AL, Hayes KC, Dekaban GA. Clinical correlates of elevated serum concentrations of cytokines and autoantibodies in patients with spinal cord injury. Arch Phys Med Rehabil. 2007;88:1384–1393.
  20. Li S, Yang Y, Yu C, et al. Dexmedetomidine analgesia effects in patients undergoing dental implant surgery and its impact on postoperative inflammatory and oxidative stress. Oxid Med Cell Longev. 2015;2015:186736. doi: 10.1155/2015/186736
  21. Thomas B, Farquhar-Smith P. Extended-release gabapentin in post-herpetic neuralgia. Expert Opin Pharmacother. 2011;12:2565–2571. doi: 10.1517/14656566.2011.622267
  22. Bao YH, Zhou QH, Chen R, et al. Gabapentin enhances the morphine anti-nociceptive effect in neuropathic pain via the interleukin-10-heme oxygenase-1 signalling pathway in rats. J Mol Neurosci. 2014;54:137–146. doi: 10.1007/s12031-014-0262-2
  23. Lee BS, Jun IG, Kim SH, Park JY. Intrathecal gabapentin increases interleukin-10 expression and inhibits pro-inflammatory cytokine in a rat model of neuropathic pain. J Korean Med Sci. 2013;28:308–314. doi: 10.3346/jkms.2013.28.2.308
  24. Pandazi A, Kapota E, Matsota P, Paraskevopoulou P, Dervenis C, Kostopanagiotou G. Preincisional versus postincisional administration of parecoxib in colorectal surgery: Effect on postoperative pain control and cytokine response. A randomized clinical trial. World J Surg. 2010;34:2463–2469.
  25. Feng Y, Ju H, Yang B, An H. Effects of a selective cyclooxygenase-2 inhibitor on postoperative inflammatory reaction and pain after total knee replacement. J Pain. 2008;9:45–52.
  26. Bao Y, Fang J, Peng L, et al. Comparison of preincisional and postincisional parecoxib administration on postoperative pain control and cytokine response after total hip replacement. J Int Med Res. 2012;40:1804–1811.
  27. Catena F, Ansaloni L, Avanzolini A, Di Saverio S, D’Alessandro L, Maldini Casadei M. Systemic cytokine response after emergency and elective surgery for colorectal carcinoma. Int J Colorectal Dis. 2009;24:803–808.
  28. Sachs D, Cunha FQ, Poole S, Ferreira SH. Tumour necrosis factor-α, interleukin-1β and interleukin- 8 induce persistent mechanical nociceptor hypersensitivity. Pain. 2002;96:89–97.
  29. Pirbudak L, Ciçek H, Işik M, Zer Y. The effect of tramadol and tramadol + gabapentin combination in patients with lumbar disc herniation after epidural steroid injection. Turk J Med Sci. 2015;45:1214–1219.
  30. Lu Y, Westlund KN. Gabapentin attenuates nociceptive behaviors in an acute arthritis model in rats. J Pharmacol Exp Ther. 1999;290:214–219.
  31. Field MJ, Holloman EF, McCleary S, Hughes J, Singh L. Evaluation of gabapentin and S-(+)-3-isobutylgaba in a rat model of postoperative pain. J Pharmacol Exp Ther. 1997;282:1242–1246.
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