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From the Department of Anesthesiology, Fudan University Cancer Hospital, Shanghai, China.
Address correspondence to: Dr. Zhiming Tan, Department of Anesthesiology, Fudan University Cancer Hospital, No.270 Dongan Road, Shanghai, P. R. China, PC200032. Phone: 86-21-64175590; Fax: 81-21-64174774; E-mail: tan1964zm{at}yahoo.com.cn
Purpose: Flurbiprofen axetil (FA) is a potent non-steroidal anti-inflammatory drug (NSAID). We examined the effects that peri-operative intravenous administration of FA, combined with thoracic epidural anesthesia and postoperative patient-controlled epidural analgesia (PCEA), have on bowel function, postoperative pain, and cytokine release, after open colorectal surgery.
Methods: This was a prospective, randomized, double-blind, placebo-controlled study. Forty patients were randomly assigned to one of two groups (n = 20 in each group). The FA group patients received FA 1 mg·kg–1 iv, 30 min before and six hours after skin incision; whereas the control group patients received an equal volume of intralipid. Blood cytokine levels were measured before FA administration, at the end of surgery, and six hours and 24 hr postoperatively. All patients received postoperative PCEA for pain control. Analgesic efficacy was evaluated for 72 hr postoperatively using visual analogue scale (VAS) pain scores both at rest and during coughing. Gastrointestinal motility was recorded. Temperature and leukocyte count were measured preoperatively, and 24 hr postoperatively.
Results: The times to first bowel movement (87 ± 23 vs 105 ± 19 hr, P = 0.008) and first flatus (63 ± 16 vs 75 ± 11 hr, P = 0.01) were earlier in the FA group compared to the control group. For the first 24 hr, the pain scores in the FA group were also lower during coughing (P < 0.001 compared to control). The plasma concentrations of interleukin (IL)-6 and IL-8 in the FA group were lower, postoperatively (P < 0.01 and P < 0.05, respectively, compared to control). In contrast, the IL-10 levels were significantly increased at six hours, postoperatively, in the FA group (P = 0.009). The total leukocyte count and the incidence of pyrexia were also lower in patients of the FA group (P = 0.001 and P = 0.006, respectively, compared to control).
Conclusion: Flurbiprofen axetil may have an anti-inflammatory effect in major abdominal surgery. The combination of perioperative intravenous FA, intraoperative thoracic epidural anesthesia, and postoperative PCEA facilitated recovery of bowel function, enhanced analgesia, and attenuated the cytokine response.
1 Lavand’homme P, De Kock M, Waterloos H. Intraoperative epidural analgesia combined with ketamine provides effective preventive analgesia in patients undergoing major digestive surgery. Anesthesiology 2005; 103: 813–20.[Medline]
2 Cunha FQ, Lorenzetti BB, Poole S, Ferreira SH. Interleukin-8 as a mediator of sympathetic pain. Br J Pharmacol 1991; 104: 765–7.[Medline]
3 Watkins LR, Milligan ED, Maier SF. Glial proinflammatory cytokines mediate exaggerated pain states: implications for clinical pain. Adv Exp Med Biol 2003; 502: 1–21.
4 Schottelius AJ, Mayo MW, Sartor RB, Baldwin AS Jr. Interleukin-10 signaling blocks inhibitor of kappa B kinase activity and nuclear factor kappa B DNA binding. J Biol Chem 1999; 274: 31868–74.
5 Cruickshank AM, Fraser WD, Burns HJ, Van Damme J, Shenkin A. Response of serum interleukin-6 in patients undergoing elective surgery of varying severity. Clin Sci (Lond) 1990; 79: 161–5.[Medline]
6 Wang W, Smail N, Wang P, Chaudry IH. Increased gut permeability after hemorrhage is associated with upregulation of local and systemic IL-6. J Surg Res 1998; 79: 39–46.[Medline]
7 Kalff JC, Turler A, Schwarz NT, et al. Intra-abdominal activation of a local inflammatory response within the human muscularis externa during laparotomy. Ann Surg 2003; 237: 301–15.[Medline]
8 McCormack K. Non-steroidal anti-inflammatory drugs and spinal nociceptive processing. Pain 1994; 59: 9–43.[Medline]
9 Souter AJ, Fredman B, White PF. Controversies in the perioperative use of nonsteroidal antiinflammatory drugs. Anesth Analg 1994; 79: 1178–90.
10 Kehlet H, Dahl JB. The value of "multimodal" or "balanced analgesia" in postoperative pain treatment. Anesth Analg 1993; 77: 1048–56.
11 Anonymous. Practice guidelines for acute pain management in the perioperative setting. A report by the American Society of Anesthesiologists Task Force on Pain Management, Acute Pain Section. Anesthesiology 1995; 82: 1071–81.[Medline]
12 Mikawa K, Nishina K, Maekawa N, Shiga M, Obara H. Dose-response of flurbiprofen on postoperative pain and emesis after paediatric strabismus surgery. Can J Anaesth 1997; 44: 95–8.
13 Nakayama M, Ichinose H, Yamamoto S, Nakabayashi K, Satoh O, Namiki A. Perioperative intravenous flurbiprofen reduces postoperative pain after abdominal hysterectomy. Can J Anesth 2001; 48: 234–7.
14 Flath RK, Hicks ML, Dionne RA, Pelleu GB Jr. Pain suppression after pulpectomy with preoperative flurbiprofen. J Endod 1987; 13: 339–47.[Medline]
15 Tanaka S, Sonoda H, Nakabayashi K, Namiki A.Preoperative flurbiprofen provides pain relief after laparoscopic cholecystectomy (Japanese). Masui 1997; 46: 679–83.[Medline]
16 Yamashita K, Fukusaki M, Ando Y, et al. Preoperative administration of intravenous flurbiprofen axetil reduces postoperative pain for spinal fusion surgery. J Anesth 2006; 20: 92–5.[Medline]
17 Huang J, Moochhala SM, Moore PK, Bhatia M. Flurbiprofen and HCT1026 protect mice against acute pancreatitis-associated lung injury. Shock 2005; 24: 182–7.[Medline]
18 Anuar F, Whiteman M, Bhatia M, Moore PKl. Flurbiprofen and its nitric oxide-releasing derivative protect against septic shock in rats. Inflamm Res 2006; 55: 498–503.[Medline]
19 Takada M, Fukusaki M, Terao Y, et al. Preadministration of flurbiprofen suppresses prostaglandin production and postoperative pain in orthopedic patients undergoing tourniquet inflation. J Clin Anesth 2007; 19: 97–100.[Medline]
20 Kehlet H, Dahl JB. Anaesthesia, surgery, and challenges in postoperative recovery. Lancet 2003; 362: 1921–8.[Medline]
21 Rigg JR, Jamrozik K, Myles PS, et al. Epidural anaesthesia and analgesia and outcome of major surgery: a randomised trial. Lancet 2002; 359: 1276–82.[Medline]
22 Kissin I. Preemptive analgesia. Anesthesiology 2000; 93: 1138–43.[Medline]
23 Carli F, Trudel JL, Belliveau P. The effect of intraoperative thoracic epidural anesthesia and postoperative analgesia on bowel function after colorectal surgery: a prospective, randomized trial. Dis Colon Rectum 2001; 44: 1083–9.[Medline]
24 Hong X , Mistraletti G, Zandi S, Stein B, Charlebois P, Carli F. Laparoscopy for colectomy accelerates restoration of bowel function when using patient controlled analgesia. Can J Anesth 2006; 53: 544–50.
25 Liu J, Ding Y, White PF, Feinstein R, Shear JM. Effect of ketorolac on postoperative analgesia and ventilatory function after laparoscopic cholecystectomy. Anesth Analg 1993; 76: 1061–6.
26 Seibert K, Masferrer JL. Role of inducible cyclooxygenase (COX-2) in inflammation. Receptor 1994; 4: 17–23.[Medline]
27 Sinatra RS, Shen QJ, Halaszynski T, Luther MA, Shaheen Y. Preoperative rofecoxib oral suspension as an analgesic adjunct after lower abdominal surgery: the effects on effort-dependent pain and pulmonary function. Anesth Analg 2004; 98: 135–40.
28 Svensson CI, Yaksh TL. The spinal phospholipase- cyclooxygenase-prostanoid cascade in nociceptive processing. Ann Rev Pharmacol Toxicol 2002; 42: 553–83.[Medline]
29 Holzheimer RG, Steinmetz W. Local and systemic concentrations of pro- and anti-inflammatory cytokines in human wounds. Eur J Med Res 2000; 5: 347–55.[Medline]
30 Lin E, Calvano SE, Lowry SF, Goehler LE. Inflammatory cytokines and cell response in surgery. Surgery 2000; 127: 117–26.[Medline]
31 Watkins LR, Maier SF. Immune activation: the role of pro-inflammatory cytokines in inflammation, illness responses and pathological pain states. Pain 1995; 63: 289–302.[Medline]
32 Volk T, Schenk M, Voigt K, Tohtz S, Putzier M, Kox WJ. Postoperative epidural anesthesia preserves lymphocyte, but not monocyte, immune function after major spine surgery. Anesth Analg 2004; 98: 1086–92.
33 Yokoyama M, Itano Y, Katayama H, et al. The effects of continuous epidural anesthesia and analgesia on stress response and immune function in patients undergoing radical esophagectomy. Anesth Analg 2005; 101: 1521–7.
34 Kim MH, Hahm TS. Plasma levels of interleukin-6 and interleukin-10 are affected by ketorolac an an adjunct to patient-controlled morphine after abdominal hysterectomy. Clin J Pain 2001; 17: 72–7.[Medline]
35 Mahdy AM, Galley HF, Abdel-Wahed MA, el-Korny KF, Sheta SA, Webster NR. Differential modulation of interleukin-6 and interleukin-10 by diclofenac in patients undergoing major surgery. Br J Anaesth 2002; 88: 797–802.
36 Gale LM, McColl SR. Chemokines: extracelluar messengers for all occasions? Bioessays 1999; 21: 17–28.[Medline]
37 Giannoudis PV, Smith RM, Perry SL, Windsor AJ, Dickson RA, Bellamy MC. Immediate IL-10 expression following major orthopaedic trauma: relationship to anti-inflammatory response and subsequent development of sepsis. Intensive Care Med 2000; 26: 1076–81.[Medline]
38 Niho Y, Niiro H, Tanaka Y , Nakashima H, Otsuka T. Role of IL-10 in the crossregulation of prostaglandins and cytokines in monocytes. Acta Haematol 1998; 99: 165–70.[Medline]
39 Prasad M, Matthews JB. Deflating postoperative ileus. Gastroenterology 1999; 117: 489–92.[Medline]
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