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The use of topical anesthesia in diagnostic hysteroscopy and endometrial biopsy*
FERTILITY AND STERILITY
Vol. 63, No.2, February 1995
Printed on acid-free paper in U. S. A.
Copyright c 1995 American Society for Reproductive Medicine
The use of topical anesthesia in diagnostic hysteroscopy and endometrial biopsy*
Errico Zupi, M.D.t:!: Anthony A. Luciano, M.D.§ Edoardo Valli, M.D.t
Daniela Marconi, M.D.t Francesco Maneschi, M.D.II Carlo Romanini, M.D.t
Universitci di Roma Tor Vergata, and Universitci Cattolica del Sacro Cuore Roma, Rome, Italy, and New Britain General Hospital, New Britain, Connecticut
Objective: To show that intrauterine anesthesia is a reliable method for reducing pain associated with endocavitary procedures. Design: A prospective, randomized, double-blind study. Setting: The Department of Obstetrics and Gynecology, Tor Vergata University of Rome, Rome, Italy. Patients: Forty-five patients undergoing diagnostic hysteroscopy (n = 27) or hysteroscopy and endometrial biopsy (n = 18). Interventions: Five milliliters of 2% mepivacaine or saline solution were injected transcervically into the uterine cavity before performing the procedures. Main Outcome Measures: Evaluation of pain reduction on a visual analogue scale. Results: Pain expectation and pain reported were reduced during and after the procedures. Conclusion: Topical anesthesia effectively reduces pain during hysteroscopy and endometrial biopsy. Fertil SterilI995;63:414-6 Key Words: Anesthesia, hysteroscopy, endometrial biopsy
Hysteroscopy today is becoming a routine outpatient diagnostic procedure for infertility and endometrial pathology. One limitation to the widespread use of this examination is represented by its invasiveness, with discomfort and pain, especially if an endometrial biopsy is performed or a cervical
Received February 28, 1994; revised and accepted August 26, 1994. * Presented at the 22nd Annual Meeting of the American Association of Gynecologic Laparoscopists, San Francisco, California, November 10 to 14, 1993. t Department of Obstetrics and Gynecology, Universita di Roma Tor Vergata. :j: Reprint requests: Errico Zupi, M.D., Department of Obstetrics and Gynecology, Universita di Roma Tor Vergata, 12 Viale Parioli, Rome 00197, Italy (FAX: 39-6-8070857). § Division of Reproductive Endocrinolgy and Infertility, New Britain General Hospital. II Department of Obstetrics and Gynecology, Universita Cattolica del Sacro Cuore Roma.
414
Zupi et al.
Communications-in-brief
stenosis exists. The use of local anesthesia in this procedure up to now has been limited to paracervical infiltration, but this is also a traumatic method that causes pain and risk of anesthetic intravasation (1). Jacobs et al. (Jacobs SL, Luciano AA, Raphael D, Litt M, abstract) have proposed recently topical endometrial anesthesia for hysterosalpingography (HSG) and endometrial biopsy. This study compares the efficacy and safety of topical endometrial anesthesia versus placebo for diagnostic hysteroscopy with or without endometrial biopsy. MATERIALS AND METHODS
Forty-five women undergoing diagnostic hysteroscopy for infertility (n = 9) or for abnormal uterine bleeding (n = 36) at the Department of Obstetrics and Gynecology "Tor Vergata" University of Rome entered in the study after informed consent. PaFertility and Sterility
tients with metrorrhagia at the time of examination were excluded because of the risk of anesthetic intravasation. Before the procedure, each woman filled out an "affective experience rating" form to evaluate her pain expectation and its correlation with the pain experienced. The form contained a 20-cm visual analogue scale for the patient to record her responses as follows: 0 cm, no pain; 5 cm, low pain; 10 cm, moderate pain; 15 cm, severe pain; and 20 cm, excruciating pain. The patient was told to report her pain experience during the procedure (TO) and 15, 30, 60, and 120 minutes (TI5, T30, T60, T120) after it, putting a mark on the 20-cm visual analogue scale. Blood pressure and pulse rate were measured immediately before and after the procedure. The women were randomized prospectively double blind into two groups: topical intrauterine instillation of anesthetic versus placebo. A 3-mm catheter (endocyte; Laboratoire CCD, Paris, France) was inserted into the uterine cavity, and women of the first group were given 5 mL of 2% mepivacaine (Carbocaine; Pierrel Spa, Milano, Italy under ASTRA Pharmaceutic license Sweden), whereas women of the second group received 5 mL of 0.9% saline solution. Hysteroscopy was performed 3 minutes after the instillation with Hamou 1 diagnostic hysteroscope (Karl Storz GMBH, Tuttlingen, Germany) by CO 2 distention of the uterine cavity. The difficulty encountered during introduction of the hysteroscope was rated by the operator on the following arbitrary scale: 0, no; 1, moderate; 2, severe. Endometrial biopsy was performed both when hysteroscopic examination revealed endometrial anomalies and for functional evaluation by Kevorkian curette (Martin, Tuttlingen, Germany). An observer who was unaware of whether saline or mepivacaine was injected recorded and scored visible signs of the women's distress during the procedure (moaning, body movement, grabbing the table), using a three-point observer scale for each of the three parameters where 0 is no response, 1 is mild response, and 2 is severe response. The pain experienced and its correlation with the difficulty to introduce the instrument were recorded. Patients who subsequently underwent endometrial biopsy were analyzed separately; thus, the following four subgroups were considered for evaluating the long-term anesthetic effect: patients who underwent hysteroscopy with (group A [n = 14]) or without mepivacaine (group B [n = 13]) and patients who underwent hysteroscopy and endometrial biopsy with (group C [n = 9]) or without mepivacaine (group D [n = 9]). Vol. 63, No.2, February 1995
Student's t-test for unpaired data, Mann-Whithey sum rank test, and Spearman's rank correlation were used for statistical analysis. RESULTS
The four groups of women were homogeneous in age, parity, and pain expectation. The mean of the levels of pain experienced by the patients during the procedure and after scored on the analogue scale is shown in Figure 1. The use of anesthetic reduced the pain experienced during the hysteroscopy with or without endometrial biopsy but not significantly with Mann-Whitney sum rank test (r = not significant [NS]). The effect of mepivacaine lasted up to 30 minutes after the procedure. Pain rated by the observer was significantly lower in the anesthetic groups (A and C versus Band D, P = 0.01 and P < 0.01). A significant correlation was observed between the rate of difficulty and the pain experienced by the patient during the hysteroscopy in patients who received placebo (r = 758; P < 0.05) but not in patients treated with mepivacaine (r = NS). Vital signs were not influenced by the procedure or by the use of anesthetic. There was no correlation between pain expectation and pain experienced (r = NS). Regarding side effects, two mild vagal reactions occurred in the placebo groups. The examination of the uterine cavity and endometrium was not hindered either by the presence of the liquid or minimal bleeding caused, in some cases, by insertion of the catheter. The insertion of the catheter originates only a mild discomfort, and the instillation of the liquid was painless for the patient. DISCUSSION
This is the first double-blind report in gynecological literature about the use of local anesthetic versus placebo in diagnostic hysteroscopy and endometrial biopsy. Topical anesthesia has already been studied and used in other tissues such as oral, bladder, and rectal mucosae (2, 3). In gynecological procedures, topical anesthesia has been used for the vagina and cervix (1), for endocervical procedures (4), and for tubal anesthesia in laparoscopic sterilization (5). The first study of topical endometrial anesthesia was reported by Jacobs et al. (Jacobs SL, Luciano AA, Raphael D, Litt M, abstract) for HSG and endometrial biopsy. Their results showed that topical anesthesia was as effective as paracervical block in reducing pain for HSG, with fewer side effects, and it also reduces the pain for endometrial Zupi et al.
Communications-in-brief
415
12
10
8
•
Group A
D
Group B
III
Group C
•
Group D
6
4
2
o TO
T15
T30
biopsy without any statistical difference. In our study we chose to use mepivacaine for its more prolonged effect on the assumption that it could reduce the pain reported after the procedure. In addition, we used 5 mL at 2% because we decided to introduce only a small volume of liquid into the uterine cavity to ensure a good hysteroscopic examination. Our results show that instillation of the anesthetic into the uterine cavity reduces pain by blocking the nerve ending at the internal uterine os and especially the pain caused by uterine contractions that are responsible for the pain reported during and after hysteroscopy and endometrial biopsy. This allows better compliance of the woman during the examination and also reduces her anxiety about any other hysteroscopies. We must emphasize also the absence of side effects with the anesthetic, whereas there were two vagal reactions in the placebo group. Thus we deduce that topical anesthesia could reduce the incidence of vagal reaction by blocking the nerve ending at the internal uterine os. In conclusion, in this report we show that intrauterine anesthesia is a reliable method for reducing pain associated with endocavitary procedures and that it could be used in selected patients when a cervical stenosis is suspected, when the patient reports a
416
Zupi et a1.
Communications-in-brief
T60
T120
Figure 1 The results of reported pain experienced for hysteroscopy (HYS) (group A, anesthetic group [n = 14]; group B, placebo group [n = 13]) and hysteroscopy with endometrial biopsy (HYS - EBX) (group C, anesthetic [n = 9]; group D, placebo [n = 9]) are based on a 20-cm visual analogue scale marked by the patient during (TO) and 15 (TI5), 30 (T30), 60 (T60), and 120 (T120) minutes after the procedure (r = NS).
high degree of pain in previous intrauterine procedures, and in very anxious patients to prevent a vagal reaction. Other studies will be necessary to select the best anesthetic, its concentration, and the lowest effective quantity needed to obtain a significant reduction of pain and whether it is preferable to inject the anesthetic into the uterine cavity at the internal os or both.
REFERENCES 1. Rylander E, Sjoberg I, Lillieborg S, Stockman O. Local anesthesia of the genital mucosa with a lidocaine/prilocaine cream (EMLA) for laser treatment of condylomata acuminata: a placebo-controlled study. Obstet Gynecol 1990;75: 3027. 2. Lorino C, Prough S, Aksel S, Abuzeid M, Alexander S, Wiebe R. Pain relief in hysterosalpingography. A comparison of analgesics. J Reprod Med 1990;35:533 6. 3. Adriani J, Zepernik R. Clinical effectiveness of drugs for topical anesthesia. JAMA 1963;188:711 6. 4. Rabin JM, Spitzer M, Dwyer AT, Kaiser IH. Topical anesthesia for gynecologic procedures. Obstet Gynecol 1989; 73:10404. 5. Koetswang S, Srisupandit S, Apimas JS, Champion CB. A comparative study of topical anesthesia for laparoscopy sterilization with the use of tubal ring. Am J Obstet Gynecol 1984;150:931 3.
Fertility and Sterility
Vol. 63, No.2, February 1995
Printed on acid-free paper in U. S. A.
Copyright c 1995 American Society for Reproductive Medicine
The use of topical anesthesia in diagnostic hysteroscopy and endometrial biopsy*
Errico Zupi, M.D.t:!: Anthony A. Luciano, M.D.§ Edoardo Valli, M.D.t
Daniela Marconi, M.D.t Francesco Maneschi, M.D.II Carlo Romanini, M.D.t
Universitci di Roma Tor Vergata, and Universitci Cattolica del Sacro Cuore Roma, Rome, Italy, and New Britain General Hospital, New Britain, Connecticut
Objective: To show that intrauterine anesthesia is a reliable method for reducing pain associated with endocavitary procedures. Design: A prospective, randomized, double-blind study. Setting: The Department of Obstetrics and Gynecology, Tor Vergata University of Rome, Rome, Italy. Patients: Forty-five patients undergoing diagnostic hysteroscopy (n = 27) or hysteroscopy and endometrial biopsy (n = 18). Interventions: Five milliliters of 2% mepivacaine or saline solution were injected transcervically into the uterine cavity before performing the procedures. Main Outcome Measures: Evaluation of pain reduction on a visual analogue scale. Results: Pain expectation and pain reported were reduced during and after the procedures. Conclusion: Topical anesthesia effectively reduces pain during hysteroscopy and endometrial biopsy. Fertil SterilI995;63:414-6 Key Words: Anesthesia, hysteroscopy, endometrial biopsy
Hysteroscopy today is becoming a routine outpatient diagnostic procedure for infertility and endometrial pathology. One limitation to the widespread use of this examination is represented by its invasiveness, with discomfort and pain, especially if an endometrial biopsy is performed or a cervical
Received February 28, 1994; revised and accepted August 26, 1994. * Presented at the 22nd Annual Meeting of the American Association of Gynecologic Laparoscopists, San Francisco, California, November 10 to 14, 1993. t Department of Obstetrics and Gynecology, Universita di Roma Tor Vergata. :j: Reprint requests: Errico Zupi, M.D., Department of Obstetrics and Gynecology, Universita di Roma Tor Vergata, 12 Viale Parioli, Rome 00197, Italy (FAX: 39-6-8070857). § Division of Reproductive Endocrinolgy and Infertility, New Britain General Hospital. II Department of Obstetrics and Gynecology, Universita Cattolica del Sacro Cuore Roma.
414
Zupi et al.
Communications-in-brief
stenosis exists. The use of local anesthesia in this procedure up to now has been limited to paracervical infiltration, but this is also a traumatic method that causes pain and risk of anesthetic intravasation (1). Jacobs et al. (Jacobs SL, Luciano AA, Raphael D, Litt M, abstract) have proposed recently topical endometrial anesthesia for hysterosalpingography (HSG) and endometrial biopsy. This study compares the efficacy and safety of topical endometrial anesthesia versus placebo for diagnostic hysteroscopy with or without endometrial biopsy. MATERIALS AND METHODS
Forty-five women undergoing diagnostic hysteroscopy for infertility (n = 9) or for abnormal uterine bleeding (n = 36) at the Department of Obstetrics and Gynecology "Tor Vergata" University of Rome entered in the study after informed consent. PaFertility and Sterility
tients with metrorrhagia at the time of examination were excluded because of the risk of anesthetic intravasation. Before the procedure, each woman filled out an "affective experience rating" form to evaluate her pain expectation and its correlation with the pain experienced. The form contained a 20-cm visual analogue scale for the patient to record her responses as follows: 0 cm, no pain; 5 cm, low pain; 10 cm, moderate pain; 15 cm, severe pain; and 20 cm, excruciating pain. The patient was told to report her pain experience during the procedure (TO) and 15, 30, 60, and 120 minutes (TI5, T30, T60, T120) after it, putting a mark on the 20-cm visual analogue scale. Blood pressure and pulse rate were measured immediately before and after the procedure. The women were randomized prospectively double blind into two groups: topical intrauterine instillation of anesthetic versus placebo. A 3-mm catheter (endocyte; Laboratoire CCD, Paris, France) was inserted into the uterine cavity, and women of the first group were given 5 mL of 2% mepivacaine (Carbocaine; Pierrel Spa, Milano, Italy under ASTRA Pharmaceutic license Sweden), whereas women of the second group received 5 mL of 0.9% saline solution. Hysteroscopy was performed 3 minutes after the instillation with Hamou 1 diagnostic hysteroscope (Karl Storz GMBH, Tuttlingen, Germany) by CO 2 distention of the uterine cavity. The difficulty encountered during introduction of the hysteroscope was rated by the operator on the following arbitrary scale: 0, no; 1, moderate; 2, severe. Endometrial biopsy was performed both when hysteroscopic examination revealed endometrial anomalies and for functional evaluation by Kevorkian curette (Martin, Tuttlingen, Germany). An observer who was unaware of whether saline or mepivacaine was injected recorded and scored visible signs of the women's distress during the procedure (moaning, body movement, grabbing the table), using a three-point observer scale for each of the three parameters where 0 is no response, 1 is mild response, and 2 is severe response. The pain experienced and its correlation with the difficulty to introduce the instrument were recorded. Patients who subsequently underwent endometrial biopsy were analyzed separately; thus, the following four subgroups were considered for evaluating the long-term anesthetic effect: patients who underwent hysteroscopy with (group A [n = 14]) or without mepivacaine (group B [n = 13]) and patients who underwent hysteroscopy and endometrial biopsy with (group C [n = 9]) or without mepivacaine (group D [n = 9]). Vol. 63, No.2, February 1995
Student's t-test for unpaired data, Mann-Whithey sum rank test, and Spearman's rank correlation were used for statistical analysis. RESULTS
The four groups of women were homogeneous in age, parity, and pain expectation. The mean of the levels of pain experienced by the patients during the procedure and after scored on the analogue scale is shown in Figure 1. The use of anesthetic reduced the pain experienced during the hysteroscopy with or without endometrial biopsy but not significantly with Mann-Whitney sum rank test (r = not significant [NS]). The effect of mepivacaine lasted up to 30 minutes after the procedure. Pain rated by the observer was significantly lower in the anesthetic groups (A and C versus Band D, P = 0.01 and P < 0.01). A significant correlation was observed between the rate of difficulty and the pain experienced by the patient during the hysteroscopy in patients who received placebo (r = 758; P < 0.05) but not in patients treated with mepivacaine (r = NS). Vital signs were not influenced by the procedure or by the use of anesthetic. There was no correlation between pain expectation and pain experienced (r = NS). Regarding side effects, two mild vagal reactions occurred in the placebo groups. The examination of the uterine cavity and endometrium was not hindered either by the presence of the liquid or minimal bleeding caused, in some cases, by insertion of the catheter. The insertion of the catheter originates only a mild discomfort, and the instillation of the liquid was painless for the patient. DISCUSSION
This is the first double-blind report in gynecological literature about the use of local anesthetic versus placebo in diagnostic hysteroscopy and endometrial biopsy. Topical anesthesia has already been studied and used in other tissues such as oral, bladder, and rectal mucosae (2, 3). In gynecological procedures, topical anesthesia has been used for the vagina and cervix (1), for endocervical procedures (4), and for tubal anesthesia in laparoscopic sterilization (5). The first study of topical endometrial anesthesia was reported by Jacobs et al. (Jacobs SL, Luciano AA, Raphael D, Litt M, abstract) for HSG and endometrial biopsy. Their results showed that topical anesthesia was as effective as paracervical block in reducing pain for HSG, with fewer side effects, and it also reduces the pain for endometrial Zupi et al.
Communications-in-brief
415
12
10
8
•
Group A
D
Group B
III
Group C
•
Group D
6
4
2
o TO
T15
T30
biopsy without any statistical difference. In our study we chose to use mepivacaine for its more prolonged effect on the assumption that it could reduce the pain reported after the procedure. In addition, we used 5 mL at 2% because we decided to introduce only a small volume of liquid into the uterine cavity to ensure a good hysteroscopic examination. Our results show that instillation of the anesthetic into the uterine cavity reduces pain by blocking the nerve ending at the internal uterine os and especially the pain caused by uterine contractions that are responsible for the pain reported during and after hysteroscopy and endometrial biopsy. This allows better compliance of the woman during the examination and also reduces her anxiety about any other hysteroscopies. We must emphasize also the absence of side effects with the anesthetic, whereas there were two vagal reactions in the placebo group. Thus we deduce that topical anesthesia could reduce the incidence of vagal reaction by blocking the nerve ending at the internal uterine os. In conclusion, in this report we show that intrauterine anesthesia is a reliable method for reducing pain associated with endocavitary procedures and that it could be used in selected patients when a cervical stenosis is suspected, when the patient reports a
416
Zupi et a1.
Communications-in-brief
T60
T120
Figure 1 The results of reported pain experienced for hysteroscopy (HYS) (group A, anesthetic group [n = 14]; group B, placebo group [n = 13]) and hysteroscopy with endometrial biopsy (HYS - EBX) (group C, anesthetic [n = 9]; group D, placebo [n = 9]) are based on a 20-cm visual analogue scale marked by the patient during (TO) and 15 (TI5), 30 (T30), 60 (T60), and 120 (T120) minutes after the procedure (r = NS).
high degree of pain in previous intrauterine procedures, and in very anxious patients to prevent a vagal reaction. Other studies will be necessary to select the best anesthetic, its concentration, and the lowest effective quantity needed to obtain a significant reduction of pain and whether it is preferable to inject the anesthetic into the uterine cavity at the internal os or both.
REFERENCES 1. Rylander E, Sjoberg I, Lillieborg S, Stockman O. Local anesthesia of the genital mucosa with a lidocaine/prilocaine cream (EMLA) for laser treatment of condylomata acuminata: a placebo-controlled study. Obstet Gynecol 1990;75: 3027. 2. Lorino C, Prough S, Aksel S, Abuzeid M, Alexander S, Wiebe R. Pain relief in hysterosalpingography. A comparison of analgesics. J Reprod Med 1990;35:533 6. 3. Adriani J, Zepernik R. Clinical effectiveness of drugs for topical anesthesia. JAMA 1963;188:711 6. 4. Rabin JM, Spitzer M, Dwyer AT, Kaiser IH. Topical anesthesia for gynecologic procedures. Obstet Gynecol 1989; 73:10404. 5. Koetswang S, Srisupandit S, Apimas JS, Champion CB. A comparative study of topical anesthesia for laparoscopy sterilization with the use of tubal ring. Am J Obstet Gynecol 1984;150:931 3.
Fertility and Sterility