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Analgesic Effects of Rofecoxib in Ear-Nose-Throat Surgery

Turan, A.*,; Emet, S.*,; Karamanlioğlu, B.*,; Memiş, D.*,; Turan, N.†,; Pamukcu, Z.*

doi: 10.1097/00000539-200211000-00039

In this study we evaluated the analgesic efficacy and the opioid-sparing effect of rofecoxib in ear-nose-throat surgery patients. Patients undergoing nasal septal or sinus surgery were randomized to receive either oral placebo or rofecoxib 50 mg 1 h before surgery. All patients received propofol 0.8 mg/kg, fentanyl 1 μg/kg, and local anesthesia at the operative site. Sedation was maintained by a continuous infusion of propofol adjusted to maintain sedation at a 2–3 level on the Ramsey scale. Additional fentanyl 0.5–1 μg/kg was administered at the patient’s request or if the verbal rating scale score was >4. Patient sedation and pain scores were obtained at 5, 15, 30 45, and 60 min during surgery and 30 min and 2, 4, 6, 12, and 24 h after completion of the procedure. During the postoperative period, diclofenac 75 mg IM was administered for analgesia at the patient’s request or if the visual analog scale (VAS) rating for pain was more than 4. VAS pain scores, intraoperative fentanyl, and postoperative diclofenac requirements were significantly smaller in the rofecoxib group compared with the placebo group (P < 0.001). The times to first analgesic request were also significantly less in the rofecoxib group. We conclude that the preoperative administration of oral rofecoxib provided a significant analgesic benefit and decreased the need for opioids in patients undergoing nasal septal and nasal sinus surgery.

Departments of *Anaesthesiology and †Biostatistics, Trakya University Medical Faculty, Edirne, Turkey

July 10, 2002.

Address correspondence and reprint requests to Dr. Alparslan Turan, Trakya University Medical Faculty, Department of Anesthesiology and Reanimation, 22030, Edirne, Turkey. Address e-mail to

Sedation and analgesia are the components of monitored anesthesia care. Monitored anesthesia care is especially important in short outpatient surgical procedures, where the main aims are to enhance patient comfort, control pain, decrease patient movement, and maintain hemodynamic stability. In addition to local anesthetics, nonsteroidal antiinflammatory drugs (NSAIDs), acetaminophen, ketamine, adenosine, β-blockers, α2-agonists, and steroids are potentially useful adjuvants for intraoperative and postoperative multimodal analgesic regimens (1,2). The adjunctive use of non-opioid compounds reduces the need for opioid analgesics during painful procedures (3).

Rofecoxib, an oral cyclooxygenase (COX)-2 inhibitor, has been approved for the treatment of acute pain. There are studies evaluating the effect of rofecoxib for postoperative pain after oral surgery (4,5) and for the prevention of postspinal fusion surgery pain, in which rofecoxib was found to be effective (6). However, rofecoxib has not been effective in preventing postoperative pain for prostate surgery (7). Further studies are needed to evaluate the effect of rofecoxib on acute pain with different postoperative pain models. The aim of this study was to determine the analgesic efficacy and opioid-sparing effect of the preoperative administration of a single oral dose of rofecoxib in ear-nose-throat surgery patients.

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After obtaining the approval of the local Ethics Committee and the written consent of patients, 60 patients classified as ASA physical status I–II undergoing elective nasal septal and nasal sinus surgery were studied. Exclusion criteria were known allergy, sensitivity, asthma, contraindications to anesthetics or any NSAID, renal insufficiency, a history of peptic ulcer, a history of a bleeding diathesis, and pregnancy.

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. For premedication, midazolam 0.07 mg/kg and atropine 0.01 mg/kg were administered IM 45 min before the surgical procedure. After the patients had been taken to the surgery room, crystalloid infusion was started through an IV 20-gauge cannula inserted in an appropriate antecubital vein, and the heart rate (HR), mean arterial blood pressure (MAP), and peripheral oxygen saturation (Spo2) were monitored (Cato PM 8040; Dräger, Lübeck, Germany). Control group patients received placebo, and rofecoxib group patients received 50 mg of rofecoxib (Vioxx®, 25-mg tablet; Merck Sharp & Dohme Pty Ltd., South Granville, NSW, Australia), 1 h prior to surgery. The study drugs were prepared by the pharmacy, and an appropriate code number was assigned.

After local anesthesia (lidocaine 2% with epinephrine) performed by the same surgeon, sedation was induced by administering bolus IV 0.8 mg/kg propofol and was maintained by a continuous infusion of propofol adjusted to maintain sedation at a 2–3 level on the Ramsey scale. The propofol infusion was started with 2 mg · kg−1 · h−1 and titrated according to patient needs, and the total propofol consumption was determined. Patients were evaluated during surgery at 5, 15, 30, 45, and 60 min for sedation levels. All patients were administered an IV injection of 1 μg/kg fentanyl. Assessment of intraoperative pain was made on the basis of the verbal rating scale (VRS), and postoperative pain assessment was made on a visual analog scale (VAS; 0 = no pain and 10 = worst pain imaginable). VAS and VRS were explained to the patients during the preoperative visit.

Patients were asked during surgery at 5, 15, 30, 45, and 60 min for pain assessment according to the VRS. If it was >4, or on the patient’s request, 0.5–1 μg/kg of fentanyl was administered. The total fentanyl consumption by each patient was determined and noted. Postoperative pain and sedation scores were recorded by a blinded observer at 30 min and 2, 4, 6, 12, and 24 h after completion of surgery. Additional analgesics needed by each group within 24 h and the time to first analgesic need were determined according to VAS; when VAS values were >4, diclofenac 75 mg IM was administered and noted. The first analgesic need was regarded as the time elapsed between the administration of the study drug and the administration of an additional analgesic.

Patients were questioned for the first 2 h in the postanesthesia care unit (PACU). They were later questioned in the ward every 2 h by an anesthesiology resident not involved in the study about the occurrence of any side effects, such as nausea and vomiting, diarrhea, epigastric discomfort, and so on, and these were recorded if present. On patient request or if nausea and vomiting occurred, ondansetron 8 mg IV was given.

Demographic data, duration of the procedure, and type of operation were analyzed by unpaired Student’s t-test. HR, MAP, Spo2, and sedation scores were evaluated by repeated-measures analysis of variance. Pain scores were analyzed by Wilcoxon’s signed rank test when distribution was not normal. If it was normal, Student’s t-test was performed. Corrections for multiple comparisons were performed by Greenhouse-Geisser. The total dose of diclofenac used was analyzed by nonparametric Wilcoxon’s signed rank test. The times to first analgesia were examined with a Kaplan-Meier survival analysis. Significance was determined at P < 0.05.

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There were no significant differences between the two groups with respect to ASA classification, age, weight, duration of surgery, type of operation, MAP, HR, or Spo2 (Table 1). There were also no differences between the two groups in the total propofol consumption. There were no significant differences with regard to pain scores between the two groups before surgery. However, all subsequent pain scores were significantly lower in the rofecoxib group compared with the placebo group (P < 0.001) (Table 2).

Table 1

Table 1

Table 2

Table 2

Intraoperative fentanyl consumption, the time to first supplemental analgesic requirement, and the total diclofenac requirement were also significantly less in the rofecoxib group (all P < 0.001). Significantly more patients in the placebo group required more than one dose of diclofenac for rescue analgesia (P < 0.001) (Table 3).

Table 3

Table 3

When first analgesic requirement times were compared, the rofecoxib group had significantly prolonged times when compared with the placebo group (P < 0.001) (Table 3). There were no significant differences between the two groups with respect to postoperative side effects.

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NSAIDs are gaining popularity in the management of pain associated with ambulatory surgery. In an effort to minimize bleeding complications and the gastrointestinal and renal damage associated with the classic NSAIDs, the more specific COX-2 inhibitors are increasingly being used as non-opioid adjuvants for minimizing pain during the perioperative period (2). The recommended dosage of rofecoxib in acute pain is 50 mg/d (8), and studies have shown that rofecoxib at this dose had a prolonged effect when compared with ibuprofen and naproxen for pain relief (9) and produced more effective analgesia than acetaminophen (10).

Other recent studies have demonstrated that the selective COX-2 inhibitor rofecoxib has analgesic properties for orthopedic surgery (11), also reducing the time to discharge home (12) and effectively reducing postoperative narcotic consumption after lumbar disk surgery (13). Preoperative administration of rofecoxib reduced postsurgical morphine consumption over a 24-hour period and for effort-dependent pain (14). However, rofecoxib was not effective in postoperative pain in patients undergoing prostate surgery (7), and celecoxib, another drug from selective COX-2 inhibitors, was not more effective than placebo in reducing postoperative pain after otolaryngologic surgery (15).

Ear-nose-throat procedures such as nasal septal or sinus surgery are performed on a day-case surgery basis. In our study, patients were kept for 24 hours, and we had the opportunity to obtain all data without requiring them to keep a diary. In our study we found a single dose of 50 mg of rofecoxib to be effective for 24 hours, and this was safe when compared with placebo. Thirty–40% discharged day-case patients may find relief from moderate to severe pain by using rofecoxib (16). We did not determine any difference in side effects, although opioid consumption was larger in the placebo group; this may be because of the limited number of patients in our study.

Further studies are needed to determine the efficacy of rofecoxib in different pain models, and comparative studies are needed to define the role of COX-2 inhibitors in ambulatory surgery. However, a comparison between conventional NSAIDs and rofecoxib must be made in ear-nose-throat surgery before further conclusions can be made.

In conclusion, the preoperative administration of rofecoxib provided a significant analgesic benefit for intraoperative and postoperative pain relief in patients undergoing ambulatory ear-nose-throat surgery.

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