Downloaded from http://journals.lww.com/jlgtd by BhDMf5ePHKbH4TTImqenVG1FEF7qxsIE6BBwP/HM+77OoaL7WmoFjsOwmI0QFdEy on 06/02/2020 Role of Oral Tramadol 50 mg in Reducing Pain During Colposcopy-Directed Cervical Biopsy: A Randomized Controlled Trial Fatma Faisal Darweesh, MD, 1 Ahmed Samy, MD, 1 Abdalla Mohamed Mousa, MD, 1 Ahmed Tarek Abdelbar, MD, 1 Mostafa Mahmoud, MD, 1 Ahmed Mohamed Abdelhakim, 2 and Ahmed A. Metwally, MD 1 Objective: The aim of the study was to assess safety and efficacy of 50-mg tramadol in reducing patient-perceived pain during colposcopy. Material and Methods: We conducted a randomized double-blind placebo-controlled trial in the colposcopy unit of a tertiary referral hospital, Cairo, Egypt, from April 2018 to October 2018. Our primary outcome was pain during colposcopy-guided ectocervical punch biopsy. Our secondary outcomes were pain during speculum insertion, acetic acid application, Lugol iodine application, endocervical curettage (ECC), endocervical brushing, 10-minute postprocedure, and additional analgesia requirement. Pain was assessed using 10-cm visual analog scale. Results: One hundred fifty women were randomized into 2 groups: tram- adol group (n = 75) received oral 50-mg tramadol tablets, and control group (n = 75) received placebo tablets. Both groups showed no significant dif- ference in anticipated pain score (p = .56), pain scores during speculum in- sertion (p = .70), application of acetic acid (p = .40), and Lugol iodine (p = .79). However, the mean pain scores were significantly lower in tram- adol group compared with placebo at ectocervical biopsy (p = .001), ECC (p = .001), endocervical brushing (p = .001), and 10 minutes after colpos- copy (p = .001). Need for additional analgesia was significantly lower in tramadol group (p = .03). Conclusions: Oral tramadol 50 mg significantly reduces pain perception during colposcopy-guided ectocervical biopsy, ECC, endocervical brushing, and 10 minutes after colposcopy with tolerable adverse effects. Key Words: tramadol, colposcopic biopsy, pain, cervical biopsy, colposcopy (J Low Genit Tract Dis 2020;24: 206–210) C olposcopy is used for diagnosis and follow-up in patients with cervical cytologic abnormalities. 1 Cervical punch bi- opsy is a common ambulatory procedure performed routinely dur- ing colposcopy for evaluation of abnormal Pap test or complaints suggestive of cervical dysplasia or malignancy. 2 Colposcopy is frequently associated with pain, discomfort, and stress that espe- cially increases with colposcopy-directed biopsy. 3 The literature has focused on pain relief during colposcopy- guided biopsy, and several pharmacological and nonpharmacological methods have been investigated. 4–8 Church et al. 9 showed topical benzocaine gel and oral ibuprofen and provided no benefits over placebo in decreasing colposcopy pain. Local anesthesia injec- tions are effective in alleviating procedure associated pain but pose several disadvantages as risk of allergy, pain from injection itself, longer procedure time, and higher costs. 10,11 Local anesthe- sia with vasoconstrictor is considered the best analgesic option as reported by a recent Cochrane study. 12 However, the fear of injec- tions prevents many women from receiving local anesthesia to al- leviate pain from cervical biopsy. 7 Tramadol is an opioid analgesic, which produces its central action through serotonin release and inhibition of neural uptake of noradrenaline. The drug's analgesic effect usually starts within 1 hour after administration, reaching a peak at 2 hours, and lasting nearly 4 to 8 hours. 13 Tramadol has a lower incidence of respi- ratory depression, cardiac depression, adverse effects on smooth muscle, and abuse potential as compared with typical opioid agents. 14,15 Tramadol has been investigated in many gynecologi- cal procedures to relieve pain and showed promising results 16–20 as in hysterectomy, 21 hysterosalpingography (HSG), 22 and diag- nostic outpatient hysteroscopy. 14 Therefore, we aimed to evaluate the safety and efficacy of oral 50-mg tramadol in reducing pain during colposcopic directed biopsy. MATERIALS AND METHODS We conducted a prospective single-center, randomized, double-blind, and placebo-controlled trial at the colposcopy unit of a tertiary referral hospital, Cairo, Egypt, from April 2018 to October 2018. The study was prospectively registered at clinical trials.gov (NCT03532841), and an institutional review board approval was obtained (March 2018, IRB: 08233). We recruited patients referred to the colposcopy unit to undergo a colposcopy- directed cervical punch biopsy. We included women aged 18 to 55 years, possessing abnor- mal cervical cytology making them candidates for colposcopy and biopsy. We excluded participants with the following criteria: pregnant patients or patients taking psychotropic or anticoagulant medications or analgesics in the previous 24 hours, or a mono- amine oxidase inhibitor antidepressant in the last 14 days. Patients who had cervical and vaginal infection, or histories of bleeding disorders or bleeding ulcers, or who had allergy or contraindica- tions to tramadol as severe asthma, severe renal, or hepatic impair- ment were also excluded. An experienced investigator in the colposcopy unit interviewed the eligible patients, invited them to participate in the study, explained clearly the objective of the study, study methodology, obtained their written informed consent, and inquired about the patients' anticipated pain score for the colposcopy procedure. We randomized women into 2 groups using a 1:1 allocation ra- tio and a computer-generated random numbers table. A statistician, not directly involved in the study, generated the computerized ran- domization list and kept the key for group allocation concealed from investigators until completion of the study. The first group 1 Department of Obstetrics and Gynecology, Faculty of Medicine, Cairo Univer- sity, Cairo, Egypt; and 2 Kasr Al-Ainy Faculty of Medicine, Cairo University, Cairo, Egypt Reprint requests to: Ahmed Mohamed Abdelhakim, Kasr Al-Ainy Faculty of Medicine, Cairo University, 395 Portsaid St, Bab el-kalq, Cairo, Egypt (Postal code: 11638). E-mail: ahmed.m.rohei@students.kasralainy.edu.eg The authors have declared they have no conflicts of interest. F.F.D. and A.S. did the study design and concept. All authors did the material preparation and the data collection and analysis. All authors drafted the manuscript. All authors revised, read, and approved the final manuscript. The study was prospectively registered at clinical trials.gov (NCT03532841), and an institutional review board approval was obtained (March 2018, IRB: 08233). Informed consent was obtained from the patients for study participation. © 2020, ASCCP DOI: 10.1097/LGT.0000000000000522 ORIGINAL RESEARCH ARTICLE:CERVIX AND HPV 206 Journal of Lower Genital Tract Disease • Volume 24, Number 2, April 2020 Copyright © 2020 ASCCP. Unauthorized reproduction of this article is prohibited.