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The use of topical anesthesia in diagnostic hysteroscopy and endometrial biopsy
Topical Anesthesiain DiagnosticHysteroscopyand EndomelrialBiopsy Zupi et al
The Use of Topical Anesthesia in Diagnostic Hysteroscopy and Endometrial Biopsy Errico Zupi, M.D., Anthony A. Luciano, M.D., Daniela Marconi, M.D., Edoardo Valli, M.D., Gianfranco Patrizi, M.D., and Carlo Romanini, M.D. Abstract Study Objective. To determine whether the pain and discomfort of routine hysteroscopy with endometrial biopsy to diagnose infertility and endometrial pathology can be minimized by topical application of mepivacaine. Design. Prospective, randomized, double-blind study. Setting. The Department of Obstetrics and Gynecology at a teaching hospital in Rome, Italy. Patients. Eighteen women undergoing diagnostic hysteroscopy. Interventions. Hysteroscopy and endometrial biopsy were performed after transcervical injection of 5 ml 2% mepivacaine or 5 ml saline solution into the uterine cavity. Measurements and Main Results. Difficulty introducing the hysteroscope was rated by the operator on a scale of 1 to 3. An observer scored visible signs of each woman's distress using a three-point scale. The patients reported their pain 15, 30, 60, and 120 minutes after the procedure on a visual analog scale. Mepivacaine was more effective than placebo according to all measurements. Conclusions. Topical mepivacaine reduced the pain experienced during and after hysteroscopy and endometrial biopsy. H y s t e r o s c o p y is b e c o m i n g a routine o u t p a t i e n t procedure in the diagnosis of infertility and e n d o m e trial pathology. One limitation to its widespread use is its invasiveness, with discomfort and pain, especially if an endometrial biopsy is p e r f o r m e d or cervical stenosis exists. T h e local anesthesia in this procedure has b e e n limited to p a r a c e r v i c a l infiltration, but this is also
t r a u m a t i c , and is a s s o c i a t e d with p a i n and risk of anesthetic intravasation. 1 Topical endometrial anest h e s i a was p r o p o s e d f o r h y s t e r o s a l p i n g o g r a p h y ( H S G ) and e n d o m e t r i a l b i o p s y ? We c o m p a r e d the efficacy and safety of topical endometrial anesthesia v e r s u s p l a c e b o f o r d i a g n o s t i c h y s t e r o s c o p y with endometrial biopsy.
Drs. Zupi, Marconi, Valli, Patrizi, and Romanini are members of the Department of Obstetrics and Gynecology, "Tor Vergata," University of Rome, Italy. Dr. Luciano is affiliated with the Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Connecticut Health Center, Farmington, Connecticut. Address reprint requests to Errico Zupi, M.D., 12 Viale Parioli, 00197 Rome, Italy. Presented at the 22nd annual meeting of the American Association of Gynecologic Laparoscopists, San Francisco.
249
Vol. 1, No. 3, May 1994
The Journal of the American Association of Gynecologic Laparoscopists
TABLE 1. Patient Characteristics
Materials and Methods Eighteen women undergoing diagnostic hysteroscopy (2 for infertility, 16 for abnormal uterine bleeding) at the D e p a r t m e n t of Obstetrics and Gynecology, "Tor Vergata," University of Rome, entered in the study after providing informed consent. All women with uterine bleeding were excluded owing to the risk of anesthetic intravasation. Before the procedure each woman filled out a 20cm visual analog affective experience rating form to indicate the amount of pain she expected to experience. Blood pressure and pulse rate were measured immediately before and after the procedure. The women were prospectively randomized in a doubleblind fashion to receive topical intrauterine instillation of anesthetic (group A) or placebo (group B). A small catheter (endocyte 3 mm) was inserted into the uterine cavity through which women in the first group were given 5 ml 2% mepivacaine, and those in the second group 5 ml saline solution. Hysteroscopy was performed by the same operator with a Hamou 1 diagnostic hysteroscope with carbon dioxide distention of the uterine cavity. The difficulty encountered while introducing the hysteroscope was rated by the operator on an arbitrary scale of 0 = none, 1 = moderate, 2 = severe. Endometrial biopsy was performed both when hysteroscopic examination revealed endometrial anomalies and for functional evaluation. 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 using a three-point scale where 0 -- no response, 1 = mild response, and 2 -- severe response. Each patient reported her pain experience 15, 30, 60, and 120 minutes after the procedure on the 20-cm visual analog scale. The pain experienced and its correlation with the difficulty to introduce the instrument were recorded. Student's t test for unpaired data, Mann-Whitney sum rank test, and Spearman's rank correlation were used for statistical analysis.
Group A
Group B
p
Mean (range) age (yrs)
45 (62-30)
46 (63-34)
NS
Mean parity
1.9
1.7
NS
Indication for surgery Infertility Abnormal uterine bleeding
1 (11.1%) 8 (88.8%)
1 (11.1%) 8 (88.8%)
NS NS
Expectation of pain
10.5 + 1
12.6 + 1.2
NS
(mean _+ SEM)
Results The two groups of women were similar with respect to age, parity, indication for surgery, and expectation of pain (Table 1). The level of the pain experienced during the procedure and scored on the analog scale is shown in Figure 1. Vital signs were not influenced by the procedure or by the use of anesthetic (Table 2). A significant correlation was observed between the rate of difficulty inserting the instrument and the pain experienced by patients who received placebo (R = 758; p <0.05), but not in those treated with mepivacaine (R = NS). There was no correlation between pain expected and pain experienced (R = NS). Pain rated by the observer was significantly lower in the anesthetic group than in the placebo group (Figure Hysteroscopy
and Endometrial
Biopsy
9 8 7
g6 ~ 5 e
4
g.a 2 1 0
TO
T15
T30
T60
T120
FIGURE 1. Results of patients' pain experienced during hysteroscopy-endometrial biopsy (group A anesthetic, group B placebo) are based on a 20-cm visual analog scale filled out 0, 15, 30, 60, and 120 minutes after the procedure.
250
Topical Anesthesiain Diagnostic Hysteroscopyand Endometrial Biopsy Zupi et al
TABLE 2. Vital Signs (mean ± SEM) Before and After Hysteroscopy and Endometrial Biopsy
Blood Pressure Before After
biopsy, although topical anesthesia has been studied and used in other tissues such as oral, bladder, and rectal mucosa. 3,4 In gynecologic procedures, topical anesthesia has been applied to the vagina and cervix) for endocervical procedures, s and for tubal anesthesia in laparoscopic sterilization.6 The first study of topical endometrial anesthesia compared 10 ml 1% lidocaine injected into the uterine cavity versus paracervical block for HSG, and topical lidocaine versus placebo for endometrial biopsy.2 Topical anesthesia was as effective as paracervical block in reducing pain associated with HSG and caused fewer side effects, and also reduced the pain of endometrial biopsy, without any statistical difference. We chose to use mepivacaine for its more prolonged effect, on the assumption that it could reduce pain after the procedure. In addition, we used 5 ml at 2% because we decided to introduce only a small volume of fluid into the uterine cavity to ensure a good hysteroscopic examination. We found that instillation of the anesthetic into the uterine cavity significantly reduced pain during insertion of the instrument, presumably by blocking the nerve endings at the internal uterine os. It also reduced uterine contractions, which are responsible for pain reported during and after hysteroscopy and endometrial biopsy. Such pain reduction ensures better patient compliance during the examination. We must also emphasize the absence of side effects with the anesthetic, whereas two vagal reactions occurred in the placebo group. Thus we deduce that topical anesthesia could reduce the frequency of vagal reaction by blocking the nerve endings at the internal uterine orifice.
Pulse Before
After
GroupA
145+3/ 83+2
145+10/ 76+3
73.0+3.2
70.2+2.3
Group B
148+8/ 82+4
142+6/ 78+3
78.4+4.6
71.2+3.5
2). The effect of mepivacaine lasted up to 30 minutes after the procedure. Two mild vagal reactions in the placebo group were the only adverse effects. Examination of the uterine cavity and endometrium was not hindered either by the presence of fluid or by occasional minor bleeding in the cervical canal caused by insertion of the catheter. Neither the anesthetic nor the saline solution affected the histologic quality of specimens. Discussion
This is the first report in the gynecologic literature on a double-blind trial of local anesthetic versus placebo for diagnostic hysteroscopy with endometrial Observer
pain
rating
5 4.5 4 3.5 3
Conclusions
2.5
Intrauterine anesthesia is reliable for reducing the pain associated with endocavitary procedures, and it may be used in selected patients in whom cervical stenosis is suspected, in women who report a high degree of pain with 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 dose to obtain a significant reduction of pain, and to determine whether it is preferable to inject the anesthetic into the uterine cavity or at the internal os, or both.
2 1.5 1 0.5 0
Group A
Group B
FIGURE 2. Results of observer pain rating. The pain rated
by the observer was significantly lower (p <0.01) in the anesthetic group than in the placebo group.
251
Vol. 1, No. 3, May 1994
TheJournal of the American Association of Gynecologic Laparoscopists
References
1. Rylander E, Sjoberg I, LiUieborg S, et al: Local anesthesia of the genital mucosa with a lidocaine/prilocaine cream (EMLA) for laser treatment of condylomata acuminata: A placebo-controlled study. Obstet Gynecol 75:302-307,1990
4. Adriani J, Zepernik R: Clinical effectiveness of drugs for topical anesthesia. JAMA 188:711-716, 1963 5. Rabin JM, Spitzer M, Dwyer AT, et al: Topical anesthesia for gynecologic procedures. O b s t e t Gynecol 73(6):1040-1044, 1989
2. Jacobs SL, Luciano AA, Raphael D, et al: The use of topical endometrial lidocaine in hysterosalpingograms and endometerial biopsies. Presented in part as an award semifinalist at the 46th annual meeting of the American Fertility Society, Washington, DC, October 13-18, 1990
6. Koetswang S, Srisupandit S, Apimas JS, et al: A comparative study of topical anesthesia for laparoscopy sterilization with the use of tubal ring. Am J Obstet Gynecol 150(8):931-933, 1984
3. Lorino C, Prough S, Aksel S, et al: Pain relief in hysterosalpingography. A comparison of analgesics. J Reprod Med 35(5):533-536, 1990
7. Owens OM, Schiff I, Kaul AF, et al: Reduction of pain following hysterosalpingogram by prior analgesic administration. Fertil Steri143(1):146-148, 1984
252
The Use of Topical Anesthesia in Diagnostic Hysteroscopy and Endometrial Biopsy Errico Zupi, M.D., Anthony A. Luciano, M.D., Daniela Marconi, M.D., Edoardo Valli, M.D., Gianfranco Patrizi, M.D., and Carlo Romanini, M.D. Abstract Study Objective. To determine whether the pain and discomfort of routine hysteroscopy with endometrial biopsy to diagnose infertility and endometrial pathology can be minimized by topical application of mepivacaine. Design. Prospective, randomized, double-blind study. Setting. The Department of Obstetrics and Gynecology at a teaching hospital in Rome, Italy. Patients. Eighteen women undergoing diagnostic hysteroscopy. Interventions. Hysteroscopy and endometrial biopsy were performed after transcervical injection of 5 ml 2% mepivacaine or 5 ml saline solution into the uterine cavity. Measurements and Main Results. Difficulty introducing the hysteroscope was rated by the operator on a scale of 1 to 3. An observer scored visible signs of each woman's distress using a three-point scale. The patients reported their pain 15, 30, 60, and 120 minutes after the procedure on a visual analog scale. Mepivacaine was more effective than placebo according to all measurements. Conclusions. Topical mepivacaine reduced the pain experienced during and after hysteroscopy and endometrial biopsy. H y s t e r o s c o p y is b e c o m i n g a routine o u t p a t i e n t procedure in the diagnosis of infertility and e n d o m e trial pathology. One limitation to its widespread use is its invasiveness, with discomfort and pain, especially if an endometrial biopsy is p e r f o r m e d or cervical stenosis exists. T h e local anesthesia in this procedure has b e e n limited to p a r a c e r v i c a l infiltration, but this is also
t r a u m a t i c , and is a s s o c i a t e d with p a i n and risk of anesthetic intravasation. 1 Topical endometrial anest h e s i a was p r o p o s e d f o r h y s t e r o s a l p i n g o g r a p h y ( H S G ) and e n d o m e t r i a l b i o p s y ? We c o m p a r e d the efficacy and safety of topical endometrial anesthesia v e r s u s p l a c e b o f o r d i a g n o s t i c h y s t e r o s c o p y with endometrial biopsy.
Drs. Zupi, Marconi, Valli, Patrizi, and Romanini are members of the Department of Obstetrics and Gynecology, "Tor Vergata," University of Rome, Italy. Dr. Luciano is affiliated with the Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Connecticut Health Center, Farmington, Connecticut. Address reprint requests to Errico Zupi, M.D., 12 Viale Parioli, 00197 Rome, Italy. Presented at the 22nd annual meeting of the American Association of Gynecologic Laparoscopists, San Francisco.
249
Vol. 1, No. 3, May 1994
The Journal of the American Association of Gynecologic Laparoscopists
TABLE 1. Patient Characteristics
Materials and Methods Eighteen women undergoing diagnostic hysteroscopy (2 for infertility, 16 for abnormal uterine bleeding) at the D e p a r t m e n t of Obstetrics and Gynecology, "Tor Vergata," University of Rome, entered in the study after providing informed consent. All women with uterine bleeding were excluded owing to the risk of anesthetic intravasation. Before the procedure each woman filled out a 20cm visual analog affective experience rating form to indicate the amount of pain she expected to experience. Blood pressure and pulse rate were measured immediately before and after the procedure. The women were prospectively randomized in a doubleblind fashion to receive topical intrauterine instillation of anesthetic (group A) or placebo (group B). A small catheter (endocyte 3 mm) was inserted into the uterine cavity through which women in the first group were given 5 ml 2% mepivacaine, and those in the second group 5 ml saline solution. Hysteroscopy was performed by the same operator with a Hamou 1 diagnostic hysteroscope with carbon dioxide distention of the uterine cavity. The difficulty encountered while introducing the hysteroscope was rated by the operator on an arbitrary scale of 0 = none, 1 = moderate, 2 = severe. Endometrial biopsy was performed both when hysteroscopic examination revealed endometrial anomalies and for functional evaluation. 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 using a three-point scale where 0 -- no response, 1 = mild response, and 2 -- severe response. Each patient reported her pain experience 15, 30, 60, and 120 minutes after the procedure on the 20-cm visual analog scale. The pain experienced and its correlation with the difficulty to introduce the instrument were recorded. Student's t test for unpaired data, Mann-Whitney sum rank test, and Spearman's rank correlation were used for statistical analysis.
Group A
Group B
p
Mean (range) age (yrs)
45 (62-30)
46 (63-34)
NS
Mean parity
1.9
1.7
NS
Indication for surgery Infertility Abnormal uterine bleeding
1 (11.1%) 8 (88.8%)
1 (11.1%) 8 (88.8%)
NS NS
Expectation of pain
10.5 + 1
12.6 + 1.2
NS
(mean _+ SEM)
Results The two groups of women were similar with respect to age, parity, indication for surgery, and expectation of pain (Table 1). The level of the pain experienced during the procedure and scored on the analog scale is shown in Figure 1. Vital signs were not influenced by the procedure or by the use of anesthetic (Table 2). A significant correlation was observed between the rate of difficulty inserting the instrument and the pain experienced by patients who received placebo (R = 758; p <0.05), but not in those treated with mepivacaine (R = NS). There was no correlation between pain expected and pain experienced (R = NS). Pain rated by the observer was significantly lower in the anesthetic group than in the placebo group (Figure Hysteroscopy
and Endometrial
Biopsy
9 8 7
g6 ~ 5 e
4
g.a 2 1 0
TO
T15
T30
T60
T120
FIGURE 1. Results of patients' pain experienced during hysteroscopy-endometrial biopsy (group A anesthetic, group B placebo) are based on a 20-cm visual analog scale filled out 0, 15, 30, 60, and 120 minutes after the procedure.
250
Topical Anesthesiain Diagnostic Hysteroscopyand Endometrial Biopsy Zupi et al
TABLE 2. Vital Signs (mean ± SEM) Before and After Hysteroscopy and Endometrial Biopsy
Blood Pressure Before After
biopsy, although topical anesthesia has been studied and used in other tissues such as oral, bladder, and rectal mucosa. 3,4 In gynecologic procedures, topical anesthesia has been applied to the vagina and cervix) for endocervical procedures, s and for tubal anesthesia in laparoscopic sterilization.6 The first study of topical endometrial anesthesia compared 10 ml 1% lidocaine injected into the uterine cavity versus paracervical block for HSG, and topical lidocaine versus placebo for endometrial biopsy.2 Topical anesthesia was as effective as paracervical block in reducing pain associated with HSG and caused fewer side effects, and also reduced the pain of endometrial biopsy, without any statistical difference. We chose to use mepivacaine for its more prolonged effect, on the assumption that it could reduce pain after the procedure. In addition, we used 5 ml at 2% because we decided to introduce only a small volume of fluid into the uterine cavity to ensure a good hysteroscopic examination. We found that instillation of the anesthetic into the uterine cavity significantly reduced pain during insertion of the instrument, presumably by blocking the nerve endings at the internal uterine os. It also reduced uterine contractions, which are responsible for pain reported during and after hysteroscopy and endometrial biopsy. Such pain reduction ensures better patient compliance during the examination. We must also emphasize the absence of side effects with the anesthetic, whereas two vagal reactions occurred in the placebo group. Thus we deduce that topical anesthesia could reduce the frequency of vagal reaction by blocking the nerve endings at the internal uterine orifice.
Pulse Before
After
GroupA
145+3/ 83+2
145+10/ 76+3
73.0+3.2
70.2+2.3
Group B
148+8/ 82+4
142+6/ 78+3
78.4+4.6
71.2+3.5
2). The effect of mepivacaine lasted up to 30 minutes after the procedure. Two mild vagal reactions in the placebo group were the only adverse effects. Examination of the uterine cavity and endometrium was not hindered either by the presence of fluid or by occasional minor bleeding in the cervical canal caused by insertion of the catheter. Neither the anesthetic nor the saline solution affected the histologic quality of specimens. Discussion
This is the first report in the gynecologic literature on a double-blind trial of local anesthetic versus placebo for diagnostic hysteroscopy with endometrial Observer
pain
rating
5 4.5 4 3.5 3
Conclusions
2.5
Intrauterine anesthesia is reliable for reducing the pain associated with endocavitary procedures, and it may be used in selected patients in whom cervical stenosis is suspected, in women who report a high degree of pain with 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 dose to obtain a significant reduction of pain, and to determine whether it is preferable to inject the anesthetic into the uterine cavity or at the internal os, or both.
2 1.5 1 0.5 0
Group A
Group B
FIGURE 2. Results of observer pain rating. The pain rated
by the observer was significantly lower (p <0.01) in the anesthetic group than in the placebo group.
251
Vol. 1, No. 3, May 1994
TheJournal of the American Association of Gynecologic Laparoscopists
References
1. Rylander E, Sjoberg I, LiUieborg S, et al: Local anesthesia of the genital mucosa with a lidocaine/prilocaine cream (EMLA) for laser treatment of condylomata acuminata: A placebo-controlled study. Obstet Gynecol 75:302-307,1990
4. Adriani J, Zepernik R: Clinical effectiveness of drugs for topical anesthesia. JAMA 188:711-716, 1963 5. Rabin JM, Spitzer M, Dwyer AT, et al: Topical anesthesia for gynecologic procedures. O b s t e t Gynecol 73(6):1040-1044, 1989
2. Jacobs SL, Luciano AA, Raphael D, et al: The use of topical endometrial lidocaine in hysterosalpingograms and endometerial biopsies. Presented in part as an award semifinalist at the 46th annual meeting of the American Fertility Society, Washington, DC, October 13-18, 1990
6. Koetswang S, Srisupandit S, Apimas JS, et al: A comparative study of topical anesthesia for laparoscopy sterilization with the use of tubal ring. Am J Obstet Gynecol 150(8):931-933, 1984
3. Lorino C, Prough S, Aksel S, et al: Pain relief in hysterosalpingography. A comparison of analgesics. J Reprod Med 35(5):533-536, 1990
7. Owens OM, Schiff I, Kaul AF, et al: Reduction of pain following hysterosalpingogram by prior analgesic administration. Fertil Steri143(1):146-148, 1984
252