Objective
We sought to investigate the analgesic efficacy of oral dexketoprofen trometamol and intrauterine lidocaine in patients undergoing fractional curettage.
Study Design
A randomized, double-blind, placebo-controlled trial was conducted on 111 women. Subjects were randomly assigned into 4 groups to receive either 25 mg of dexketoprofen or similar-appearing placebo tablets and either 5 mL intrauterine 2% lidocaine or saline. The main outcome measure was the intensity of pain measured by a 10-cm visual analog scale. Pain scoring was performed prior to, during, and 30 minutes after the procedure.
Results
No statistically significant difference was found among the mean pain scores of women during the procedure in the dexketoprofen and saline, placebo and lidocaine, and dexketoprofen and lidocaine groups. The mean pain scores in all 3 groups revealed significant reduction when compared with placebo and saline combination ( P = .001).
Conclusion
Administration of intrauterine lidocaine or oral dexketoprofen appears to be effective in relieving fractional curettage associated pain. However, a combination of them does not work better in further reduction of pain.
Fractional curettage is a common procedure for investigating causes of abnormal uterine bleeding. Patients frequently experience moderate to severe pain during gynecologic procedures that involve the uterine cavity. Therefore, in patients undergoing these operations in outpatient settings, the requirement of an analgesic is inevitable. The analgesic efficacy of various pain-relieving procedures has been tested for women undergoing fractional curettage. The paracervical block with local anesthetics is one of the most common procedures used since 1925. However, it can be associated with adverse effects, which range from mild toxicity such as numbness around the mouth and dizziness to convulsion and respiratory arrest. Five deaths were reported from use of lidocaine to induce paracervical anesthesia. Paracervical block is effective in reducing the sensitivity of cervix but stays ineffective at blocking the innervation to the body and fundus of the uterus. Intrauterine anesthesia is proposed to be an effective method for pain relief in the upper part of the uterus by blocking the nerve endings in the uterine corpus and fundus. Intrauterine instillation of an anesthetic has some advantages over paracervical block, such as painless application, lower risk of bleeding, and intravasation. However, its value remains controversial at the present time since different studies have reported either a positive or null pain-relieving effect during various gynecologic procedures.
The administration of oral nonsteroidal antiinflammatory drugs (NSAIDs) with or without the adjunctive use of paracervical block or intrauterine anesthesia prior to minor gynecologic surgery has been introduced in recent years. Tramadol, naproxen, ibuprofen, and mefenamic acid are the NSAIDs tested and shown to be effective in pain reduction during and following an outpatient curettage.
Dexketoprofen trometamol, the active enantiomer of racemic ketoprofen, is a relatively new NSAID with analgesic and antipyretic properties. When compared with ketoprofen, dexketoprofen possesses the advantages of faster onset of action, increased potency, and fewer gastrointestinal side effects.
Dexketoprofen has widely been used for management of acute and chronic pain in different clinical situations, such as orthopedic, general, and major gynecologic surgical procedures, and found to be at least as effective as other NSAIDs and paracetamol/opioid combinations. Additionally, oral dexketoprofen was found to be effective for treatment of primary dysmenorrhea. However, only 1 study investigating its use in minor gynecologic surgery has been reported, and it was found to produce a satisfactory level of analgesia similar to that achieved with paracervical block during diagnostic hysteroscopy in postmenopausal women.
We conducted a randomized, placebo-controlled trial to investigate the analgesic efficacy of preoperative oral dexketoprofen trometamol and intrauterine lidocaine either alone or in combinations in patients undergoing fractional curettage.
Materials and Methods
A randomized, double-blind, placebo-controlled trial was designed at our outpatient clinics. The study protocol was approved by the local ethics committee. The participants consisted of women who were scheduled for fractional curettage with the indications of abnormal uterine bleeding, such as postmenopausal bleeding, myoma uteri causing menometrorrhagia, cervical polyp, tamoxifen treatment for breast cancer, and adnexal mass. Exclusion criteria were pregnancy, suspected pelvic infection, known cervical stenosis, significantly impaired respiratory or cardiac conduction functions, active liver disease, previous adverse reaction to any of the drugs used in the study, and inability to understand how to score a 10-cm visual analog scale (VAS) pain score. A total of 119 patients were evaluated for eligibility and 8 patients were excluded, of which 1 refused to participate in the study and 7 did not meet the inclusion criteria (5 cervical stenosis, 1 acute cervicitis, and 1 peptic ulcer). The final study group was composed of 111 subjects.
On the basis of previously published studies assessing pain scores during minor gynecologic surgical procedures, we accepted that at least a 1.5-cm difference between the pain scores could be accepted as a clinically significant difference. It was estimated that at least 25 subjects were required in each arm to detect a difference between the 4 groups of at least 1.5 cm on a 10-cm VAS scale when assuming a power of 80% at a type I error of 0.05 and SD of 2.2 cm.
After providing their informed consent, the subjects were randomly assigned into 1 of 4 study groups to receive 25 mg of oral dexketoprofen trometamol or similar-appearing placebo tablets and either 5 mL of intrauterine 2% lidocaine or saline by using a computer-generated random number chart (SPSS, version 11.0 for Windows; SPSS, Inc, Chicago, IL) before the study. As shown in Figure 1 , the first treatment arm consisted of women receiving dexketoprofen and lidocaine (DL) (n = 28) and the second treatment arm consisted of women receiving placebo and lidocaine (PL) (n = 25), whereas the third group consisted of women receiving dexketoprofen and saline (DS) (n = 32) and the fourth group consisted of women receiving placebo and saline (PS) (n = 26). In all, 111 consecutive patient numbers were written on envelopes, while the assignment codes were written on separate papers that were put into the consecutively numbered opaque envelopes, which were then sealed. When the woman was admitted to the outpatient clinics and met the inclusion criteria, she was informed about the study protocol and, if she agreed, she signed the informed consent form and was given her consecutive participation number. At the time of the fractional curettage, the envelope with the participation number on its cover was opened to reveal the randomization by the responsible nurse and she prepared the trial medications accordingly. The patients and the gynecologist performing the procedure were blinded to the contents of the oral and the intrauterine medications. Each patient received both oral and intrauterine medications together. The oral medications were administered 30 minutes before the fractional curettage with respect to the pharmacokinetic properties of dexketoprofen, since it is known to possess a very rapid onset of action (within 30 minutes of administration) with a long-lasting effect (at least for 6 hours). The fractional curettage was performed by the same gynecologist (B.E.) to maintain consistency and limit confounding variables. Since the frequency of the adverse effects related to intrauterine instillation of lidocaine was among the secondary outcomes, we did not perform paracervical block in any of the patients. The fractional curettage and intrauterine anesthesia were performed under the aseptic technique as described in the following: a sterile bivalve speculum was introduced into the vagina for visualization of the cervix. The cervix and vagina were washed with antiseptic solution. The cervix was grasped with single-toothed tenaculum to straighten the uterine axis, and 5 mL of unlabeled test solution was instilled through the endocervix into the uterine cavity with an 18-gauge angiocatheter. The angiocatheter was left in place for 3 minutes before it was withdrawn to limit backflow and to allow the anesthetic to take effect. The fractional curettage was accomplished through the following steps: the endocervical curettage was performed using a Sims curette no. 00 (5 mm in the greatest diameter); the cervix was dilated to Hegar no. 5 (Aesculap, Ag and Co. GK, Tuttlingen, Germany) if necessary; the uterine depth was measured using a Sims uterine sound device (Aesculap, Ag and Co.); and then the uterine curettage was performed using a Sims curette no. 0.
The patients were observed thereafter for 30 minutes. No further follow-up was scheduled. Patients were asked to rate their pain level on a continuous 100-mm VAS from 0 (no pain) to 10 (worst pain ever). Pain scoring was performed at 3 different time points: prior to the procedure (t 1 ), during the procedure (immediately following the removal of the speculum from the vagina at the end of the fractional curettage; the patients were asked to score their pain level experienced during the procedure) (t 2 ), and 30 minutes after the procedure (t 3 ). We documented patient demographics: age, parity, weight and height, history of prior fractional curettage/endometrial biopsy, menopause, and indication for biopsy in each patient.
For the statistical analysis, SPSS 13.0 statistical package was used. Normal distribution of the continuous variables was evaluated by Kolmogorov-Smirnov test. Comparisons of the continuous variables among the 4 groups were performed by means of the 1-way analysis of variance test when the distribution of data was similar to Gaussian form and by means of the Kruskal-Wallis test when the Gaussian distribution was violated. Comparisons between the groups were considered statistically significantly different at a P value of < .05. The Tukey honestly significant difference post hoc test was used to identify the source of difference when a statistically significant difference was found among the 4 groups in 1-way analysis of variance test. When a statistically significant difference was detected in Kruskal-Wallis test, Mann-Whitney U test and Bonferroni correction were used in each pair for post hoc analysis.
Due to the differences in the baseline VASt 1 scores of the groups, a 1-way analysis of covariance was also conducted to compare the analgesic efficacy of different treatment modalities using the baseline VASt 1 scores as the covariate. The independent variable was the type of the treatment modality (study groups) and the dependent variable was the VASt 2 scores of the study subjects. Preliminary checks were conducted to ensure that there was no violation of the assumptions of normality, linearity, homogeneity of variances, homogeneity of regression slopes, and reliable measurement of the covariate.
Results
All procedures were successfully completed without any complications, and no serious adverse reaction was noted. The most common indication for fractional curettage among the study participants was dysfunctional uterine bleeding followed by postmenopausal bleeding. There was no statistically significant difference among the 4 study groups in terms of indications, which are listed in Table 1 . There was no evidence of statistical significance in the duration of curettages, which was defined as the time from the beginning of the endocervical curettage until the speculum was removed from the vagina (3 minutes on average). Histologic specimens also were not affected in any of the 111 patients enrolled in this study. There were no clinically significant differences detected among the groups in terms of demographics, as shown in Table 1 .
| Characteristic | DL group (n = 28) | PL group (n = 25) | DS group (n = 32) | PS group (n = 26) | P |
|---|---|---|---|---|---|
| Age, y | 46.07 ± 6.84 | 46.12 ± 9.36 | 47.59 ± 8.22 | 48.34 ± 7.16 | .66 a |
| Nulliparous | 3 (10.7%) | 1 (4%) | 1 (3.1%) | 2 (7.6%) | .62 b |
| Prior curettage | 6 (21.4%) | 10 (40%) | 5 (15.6%) | 10 (38.4%) | .10 b |
| Postmenopause | 12 (42.8%) | 9 (36%) | 7 (21.8%) | 11 (42.3%) | .28 b |
| Indications | .64 b | ||||
| Dysfunctional uterine bleeding | 8 (28.5%) | 13 (52%) | 18 (56%) | 14 (53.8%) | |
| Postmenopausal bleeding | 3 (10.7%) | 4 (16%) | 5 (15.6%) | 6 (23%) | |
| Thickened endometrium | 6 (21.4%) | 1 (4%) | 1 (3.1%) | 4 (15.3%) | |
| Myoma uteri causing menometrorrhagia | 3 (10.7%) | 3 (12%) | 4 (12.5%) | 1 (3.8%) | |
| Cervical polyp | 3 (10.7%) | 3 (12%) | 1 (3.1%) | 4 (15.3%) | |
| Tamoxifen therapy | 4 (14.2%) | 1 (4%) | 2 (6.2%) | 0 | |
| Adnexal mass | 1 (3.5%) | 0 | 1 (3.1%) | 0 | |
| Dysfunctional uterine bleeding | 8 (28.5%) | 13 (52%) | 18 (56%) | 14 (53.8%) |
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