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PAIN MEDICINE

Preoperative Oral Rofecoxib Reduces Postoperative Pain and Tramadol Consumption in Patients After Abdominal Hysterectomy

Beyhan Karamanlolu, MD^*, Alparslan Turan, MD^*, Dilek Memi, MD^*, and Mevlüt Türe, PhD Section Editor

Department of *Anesthesiology and Biostatistics, Trakya University, Medical Faculty, Edirne, Turkey

Address correspondence and reprint requests to Doç. Dilek Memi, MD, Trakya Üniversitesi Tp Fakültesi, Anesteziyoloji ve Reanimasyon AD, 22030, Edirne, Turkey. Address e-mail to dilmemis{at}mynet.com

	Abstract

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We designed this study to determine whether the administration of a preoperative dose of rofecoxib to patients undergoing abdominal hysterectomy would decrease patient-controlled analgesia (PCA) tramadol use or enhance analgesia. Sixty patients were randomized to receive either oral placebo or rofecoxib 50 mg 1 h before surgery. All patients received a standard anesthetic protocol. Intraoperative blood loss was determined. At the end of surgery, all patients received tramadol IV via a PCA-device. Pain scores, sedation scores, mean arterial blood pressure, heart rate, and peripheral oxygen saturation were assessed at 1, 2, 4, 6, 8, 12, and 24 h after surgery. Total and incremental tramadol consumption at the same times was recorded from the PCA-device. Antiemetic requirements and adverse effects were noted during the first postoperative 24 h. Duration of hospital stay was also recorded. The pain scores were significantly lower in the rofecoxib group compared with the placebo group at 6 times during the first 12 postoperative h (P < 0.05). The total consumption of tramadol (627 ± 69 mg versus 535 ± 45 mg; P < 0.05) and the incremental doses at 1, 2, 4, 6, 8, and 12 h after surgery were significantly more in the placebo group than in the rofecoxib group. There were no differences between groups in intraoperative blood loss, sedation scores, hemodynamic variables, peripheral oxygen saturation, antiemetic requirements, or adverse effects after surgery. The length of hospital stay was also similar in the groups. We conclude that the preoperative administration of oral rofecoxib provided a significant analgesic benefit and decreased the opioid requirements in patients undergoing abdominal hysterectomy.

IMPLICATIONS: This study was designed to determine whether the administration of a preoperative dose of rofecoxib to patients undergoing abdominal hysterectomy would decrease patient-controlled analgesia tramadol use or enhance analgesia. We conclude that the preoperative administration of oral rofecoxib provided a significant analgesic benefit and decreased the opioid requirements in patients undergoing abdominal hysterectomy.

	Introduction

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Current therapeutic strategies for the management of acute pain are largely dependent on opioid analgesics and nonsteroidal antiinflammatory drugs (NSAIDs). Opioids, although highly effective in managing pain, have a range of side effects such as respiratory depression, central nervous system depression/sedation, nausea, and vomiting (1). These side effects are common and can limit the use of opioids in postoperative analgesia despite their analgesic efficacy. Multimodal therapy is recommended in postoperative surgical patients to reduce opioid consumption by coadministering non-opioid analgesics such as NSAIDs. The opioid-sparing effect of NSAIDs is clinically relevant because it may improve pain relief while reducing opioid-related side effects (2,3). At therapeutic doses, conventional NSAIDs nonspecifically inhibit both cyclooxygenase (COX)-1 and COX-2. The antiinflammatory and analgesic effects are produced by COX-2 inhibition, whereas gastrointestinal toxicity and platelet dysfunction are caused by COX-1 inhibition (4).

In recent years, the development of COX-2-selective inhibitors, which inhibit COX-2 but not COX-1 at therapeutic doses, has provided new advances in the management of acute pain. COX-2-selective inhibitors provide efficacy equivalent to conventional NSAIDs without causing serious platelet and gastrointestinal side effects. Thus, COX-2-selective inhibitors provide an alternative therapeutic option with an improved safety profile in the management of inflammation and pain (5). Rofecoxib, an oral COX-2-selective inhibitor, has been approved for the treatment of acute pain. Previous studies with rofecoxib have shown it to be an effective analgesic after dental surgery (6), postspinal fusion surgery (7), abdominal hysterectomy, and laparoscopic gastric banding (8). However, rofecoxib was not effective in preventing postoperative pain or reducing morphine consumption in patients after prostate surgery (9). We therefore evaluated, in a randomized, double-blinded, placebo-controlled study, the analgesic efficacy of preoperative rofecoxib in patients undergoing abdominal hysterectomy involving a lower abdominal incision (Pfannenstiel technique).

	Methods

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After obtaining approval from the local ethics committee and written informed consent, we studied 60 ASA physical status I–II women undergoing elective total abdominal hysterectomy. Exclusion criteria included a known allergy, sensitivity, or contraindications to tramadol or any NSAID, renal insufficiency, a history of peptic ulcer, a history of a bleeding diathesis, pregnancy, and inability to use the patient-controlled analgesia (PCA) device.

The patients were randomly divided into 2 groups with 30 patients in each. The study design was randomized and double-blinded. Patients were randomly allocated according to computer-generated randomization list. For premedication, midazolam 0.07 mg/kg and atropine 0.01 mg/kg were administered IM 45 min before the surgical procedure. In the operating room, a crystalloid infusion was started, and mean arterial blood pressure (MAP), heart rate (HR), and peripheral oxygen saturation (SpO₂) were monitored (Cato PM 8040; Dräger, Lübeck, Germany). Patients in the placebo group received a placebo tablet, and those in the rofecoxib group received rofecoxib 50 mg (Vioxx®, Merck Sharp & Dohme Pty Ltd, South Granville, Australia) orally, 1 h before surgery. The study drugs were prepared by the pharmacy, and an appropriate code number was assigned. They were given to the patients by a trained nurse who was not involved in the study in the postanesthesia care unit (PACU).

After the administration of oxygen, anesthesia was induced with IV propofol (2 mg/kg), fentanyl (2 µg/kg), and rocuronium (0.6 mg/kg). Anesthesia was maintained by 1.5%–2.5% sevoflurane in nitrous oxide and oxygen (ratio 2:1). The lungs of the patients were mechanically ventilated (Cato; Dräger, Lübeck, Germany), and ventilation was adjusted to maintain end-expiratory CO₂ between 34–36 mm Hg. Surgery was performed via a Pfannenstiel incision. Intraoperative blood loss was determined by combining the blood collected in the suction canister as well as by estimating the blood present in the surgical sponges (7).

After tracheal extubation, patients were transferred to the PACU. Postoperative pain was assessed using a visual analog scale (VAS; 0 = "no pain" and 10 = "worst pain imaginable"). Postoperative analgesia was provided by IV PCA tramadol. The PCA technique and the VAS were explained to the patients during the preoperative visit. Patients were connected to the PCA-device (Abbott Pain Management Provider, North Chicago, IL) on arrival in the PACU. The PCA solution contained tramadol 3 mg/mL. The administration variables were as follows: initial dose, 50 mg; demand dose, 20 mg; lockout interval, 5 min; 4-h limit, 300 mg; and no basal infusion. The demand dose was increased to 30 mg if analgesia was inadequate after 1 h. Degree of sedation was determined according to a sedation score ranging from 0 to 2 (0 = alert, 1 = drowsy but rousable to voice, and 2 = very drowsy, but rousable to shaking). The VAS scores, MAP, HR, SpO₂, and sedation scores were assessed at 1, 2, 4, 6, 8, 12, and 24 h after surgery. Total and incremental tramadol consumption at these times was also recorded from the PCA-device. On patient’s request, or if nausea and vomiting occurred, 8 mg of ondansetron IV was given. The number of patients receiving antiemetics and doses in patients receiving antiemetics were noted. Patients were questioned about the occurrence of any adverse effects during the first 24 h. Every 24 h after the operation, patients were assessed as ready or not ready for discharge from hospital by 4 discharge criteria: (a) normal defecation and no urinary retention; (b) able to mobilize and dress; (c) need for opioid; and (d) surgical complication requiring patient hospitalization. When the patient scored yes on the two former and no on the latter questions, they were assessed ready for discharge from hospital (10). All measurements were recorded by the same anesthesia resident who was blinded to the study drugs administered.

Descriptive statistics are expressed as mean ± SD unless otherwise stated. All variables were tested for normal distribution by Kolmogorov-Smirnov test. Student’s t-test was used for comparison of the means of weight. Mann-Whitney U-test was used for age, intraoperative blood loss, duration of operation, anesthesia, and hospital stay. Repeated-measures analysis of variance was used for tramadol consumptions, VAS, HR, MAP, SpO₂. Categorical data were analyzed using ² or Fisher’s exact test, as appropriate. A value of P < 0.05 was considered statistically significant. Data were analyzed using MINITAB for windows 13.32 (MINITAB, Inc, State College, PA). In a previous study (7), a single oral dose of rofecoxib 50 mg before surgery resulted in a significant analgesic benefit with regard to postoperative pain relief and decrease in opioid requirement after major surgery. Based on this data, a power analysis indicated that a sample size of 30 patients in each group was sufficient to have an 80% power of detecting a similar difference of postoperative pain scores at the 95% significance level.

	Results

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There were no significant differences between the groups with respect to demographics, surgical data, and postoperative data (Table 1). There were no statistically significant differences in MAP, HR, SpO₂, and sedation scores (Table 2) between the groups at any time during the first 24 h after surgery.

View larger version (13K): [in this window] [in a new window]   Figure 1. Visual analog scale (VAS) pain scores during the first 24-h period after surgery. Values are mean ± SD (* P < 0.05 versus placebo).

	Discussion

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The preoperative use of a COX-2-specific inhibitor with analgesic properties could represent a significant therapeutic advance in the management of acute postoperative pain (13). The recommended dose of rofecoxib in acute pain is 50 mg daily (14), and studies have shown that this dose had a prolonged effect when compared with ibuprofen (6,14) and naproxen (15) for pain relief and produced more effective analgesia than acetaminophen (16).

Previous studies comparing the oral COX-2-selective inhibitors rofecoxib (6) and celecoxib (17) with the classic NSAIDs reported similar analgesic effects when used to manage postdental surgery pain. Reuben and Connelly (7) demonstrated significant opioid-sparing effects with celecoxib and rofecoxib when used in conjunction with PCA morphine after spinal fusion surgery. Other studies have demonstrated that preoperative administration of rofecoxib reduced perioperative opioid consumption after abdominal hysterectomy and laparoscopic gastric banding (8) and postoperative opioid requirements after lumbar disk surgery (18). Turan et al. (19) observed that the preoperative administration of rofecoxib provided a significant analgesic benefit for intraoperative and postoperative pain relief and also reduced intraoperative fentanyl and postoperative diclofenac consumptions in patients undergoing ambulatory ear-nose-throat surgery. In another study, Karamanlioglu et al. (20) showed that the preoperative administration of rofecoxib 50 mg or celecoxib 200 mg provides a significant analgesic benefit with regard to postoperative pain relief and decreases opioid requirement after thyroid surgery. However, Huang et al. (9) found no reduction in pain score or morphine requirements with the preoperative administration of single-dose oral rofecoxib in patients after radical prostate surgery. Both hysterectomy (10) and prostatectomy (21) are performed by lower abdominal incision. The Pfannenstiel incision is associated with less postoperative analgesic consumption when compared with midline infraumbilical incision for retropubic radical prostatectomy (21). The Pfannenstiel incision was the preferred technique in our study. It is not clear which incision was used in the study by Huang et al (9).

Our study demonstrated that, compared with placebo, preoperative oral rofecoxib 50 mg significantly reduced pain scores during the first 12 hours after surgery and PCA-tramadol consumption in the first 24-hours in patients who had undergone abdominal hysterectomy.

The main benefits of selective COX-2 inhibitors are the reduced incidence of gastric ulceration, perforation, and bleeding and no effect on platelets (4,22). Rofecoxib, in doses of 1000 mg/d had no effect on platelet aggregation or bleeding time (6). Our study demonstrated that a single oral dose of rofecoxib 50 mg administered before surgery did not lead to an increase in the incidence of intraoperative bleeding.

IV PCA is effective for individual pain relief in the postoperative period. Tramadol by PCA provides adequate postoperative pain relief after major gynecological surgery (23). It is generally well tolerated, the most common adverse events being nausea and vomiting. In contrast to drugs such as morphine and pethidine, clinically relevant respiratory depression is rare during tramadol administration at equipotent doses (24). Studies have demonstrated that the most common adverse effects of rofecoxib are nausea, vomiting, headache, dizziness, and dry mouth (6,14). In our study, adverse effects were not different between the groups during the first 24 postoperative hours. Many patients experience moderate to severe pain after hysterectomy. Furthermore, hysterectomy is often associated with considerable nausea and vomiting (10,23). The frequent incidence of nausea and vomiting in our study may be related to the use of IV-PCA tramadol in female patients undergoing hysterectomy, which is associated with frequent adverse effects such as nausea and vomiting (24,25). Whereas rofecoxib use was associated with less opioid use, we did not determine a significant decrease in opioid-related side effects. This decrease is statistically insignificant but may be clinically relevant. Combining drugs reduces the use of a single drug, which has the benefit of reducing the extent of potential side effects; however, increasing the drugs prescribed brings the risk of a broader spectrum of side effects (5).

In conclusion, preoperative administration of a single dose of oral rofecoxib was effective in decreasing postoperative pain and PCA-tramadol consumption in patients undergoing abdominal hysterectomy.

	References

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1. Fishman S, Borsook D. Opioids in pain management. In: Benzon H, Raja S, Molloy RE, Strichartz G, eds. Essentials of pain medicine and regional anesthesia. New York: Churchill Livingstone, 1999: 51–4.
2. Kehlet H, Rung GW, Callesen T. Postoperative opioid analgesia: time for a reconsideration? J Clin Anesth 1996; 8: 441–5.[Web of Science][Medline]
3. Kehlet H, Dahl JB. The value of "multimodal" or "balanced analgesia" in postoperative pain treatment. Anesth Analg 1993; 77: 1048–56.[Free Full Text]
4. Kam PCA, Power I. New selective COX-2 inhibitors. Pain Rev 2000; 7: 3–13.
5. Solca M. Acute pain management: unmet needs and new advances in pain management. Eur J Anaesthesiol 2002; 19: 3–10.
6. Ehrich EW, Dallob A, DeLepeleire I, et al. Characterization of rofecoxib as a cyclooxygenase-2 isoform inhibitor and demonstration of analgesia in the dental pain model. Clin Pharmacol Ther 1999; 65: 336–47.[Web of Science][Medline]
7. Reuben SS, Connelly NR. Postoperative analgesic effects of celecoxib or rofecoxib after spinal fusion surgery. Anesth Analg 2000; 91: 1221–5.[Abstract/Free Full Text]
8. Meyer R. Rofecoxib reduces perioperative morphine consumption for abdominal hysterectomy and laparoscopic gastric banding. Anaesth Intensive Care 2002; 30: 389–90.[Web of Science][Medline]
9. Huang JJ, Taguchi A, Hsu H, et al. Preoperative oral rofecoxib does not decrease postoperative pain or morphine consumption in patients after radical prostatectomy: a prospective, randomized, double-blinded, placebo-controlled trial. J Clin Anesth 2001; 13: 94–7.[Web of Science][Medline]
10. Jorgensen H, Fomsgaard JS, Dirks J, et al. Effect of peri- and postoperative epidural anaesthesia on pain and gastrointestinal function after abdominal hysterectomy. Br J Anaesth 2001; 87: 577–83.[Abstract/Free Full Text]
11. Verburg KM, Maziasz TJ, Weiner E, et al. COX-2-specific inhibitors: definition of a new therapeutic concept. Am J Ther 2001; 8: 49–64.[Medline]
12. Scott RM, Jennings PN. Rectal diclofenac analgesia after abdominal hysterectomy. Aust N Z J Obstet Gynaecol 1997; 37: 112–4.[Web of Science][Medline]
13. Tang J, Li S, White PF, et al. Effect of parecoxib, a novel intravenous cyclooxygenase type-2 inhibitor, on the postoperative opioid requirement and quality of pain control. Anesthesiology 2002; 96: 1305–9.[Web of Science][Medline]
14. Malmstrom K, Daniels S, Kotey P, et al. Comparison of rofecoxib and celecoxib, two cyclooxygenase-2 inhibitors, in postoperative dental pain: a randomized, placebo- and active-comparator-controlled clinical trial. Clin Ther 1999; 21: 1653–63.[Web of Science][Medline]
15. Mehlisch DR, Mills S, Sandler M, et al. Ex vivo assay of COX-2 inhibition predicts analgesic efficacy in post-surgical dental pain with MK-966. Clin Pharmacol Ther 1998; 63: 139.
16. Issioui T, Klein KW, White PF, et al. Cost-efficacy of rofecoxib versus acetaminophen for preventing pain after ambulatory surgery. Anesthesiology 2002; 97: 931–7.[Web of Science][Medline]
17. Clemett D, Goa KL. Celecoxib: a review of its use in osteoarthritis, rheumatoid arthritis and acute pain. Drugs 2000; 59: 957–80.[Web of Science][Medline]
18. Bekker A, Cooper PR, Frempong-Boadu A, et al. Evaluation of preoperative administration of the cyclooxygenase-2 inhibitor rofecoxib for the treatment of postoperative pain after lumbar disc surgery. Neurosurgery 2002; 50: 1053–7.[Web of Science][Medline]
19. Turan A, Emet S, Karamanlioglu B, et al. Analgesic effects of rofecoxib in ear-nose-throat surgery. Anesth Analg 2002; 95: 1308–11.[Abstract/Free Full Text]
20. Karamanlioglu B, Arar C, Alagol A, et al. Preoperative oral celecoxib versus preoperative oral rofecoxib for pain relief after thyroid surgery. Eur J Anaesthesiol 2003; 20: 490–5.[Web of Science][Medline]
21. Soulie M, Vazzoler N, Seguin P, et al. Pfannenstiel short horizontal laparotomy in retropubic radical prostatectomy. Prog Urol 2000; 10: 1169–72.[Web of Science][Medline]
22. Van Hecken A, Schwartz JI, Depre M, et al. Comparative inhibitory activity of rofecoxib, meloxicam, diclofenac, ibuprofen, and naproxen on COX-2 versus COX-1 in healthy volunteers. J Clin Pharmacol 2000; 40: 1109–20.[Abstract]
23. Jellinek H, Haumer H, Grubhofer G, et al. Tramadol in postoperative pain therapy: patient-controlled analgesia versus continuous infusion. Anaesthesist 1990; 39: 513–20.[Web of Science][Medline]
24. Lehmann KA. Tramadol in acute pain. Drugs 1997; 53: S25–33.
25. Pang WW, Mok MS, Lin CH, et al. Comparison of patient-controlled analgesia (PCA) with tramadol or morphine. Can J Anaesth 1999; 46: 1030–5.[Web of Science][Medline]

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999