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The effect of an intrauterine application of two percent lignocaine gel on pain perception during Vabra endometrial sampling: a randomised double-blind, placebo-controlled trial
British Journal of Obstetrics and Gynaecology January 2001, Vol. 108, pp. 87±90
The effect of an intrauterine application of two percent lignocaine gel on pain perception during Vabra endometrial sampling: a randomised double-blind, placebo-controlled trial Ezzat Kozman a,*, Peter Collins a, Ann Howard a, Tolu Akanmu a, Alan Gibbs b, Malcolm Frazer a Objective To determine whether two percent lignocaine gel can reduce the perception of pain during Vabra endometrial aspiration. Design Randomised, double-blind placebo-controlled trial. Setting Women's Health Directorate, Warrington Hospital NHS Trust. Population Women were referred to the endometrial sampling clinic for the investigation of pre and postmenopausal vaginal bleeding. Methods Randomisation to either pre-sampling intrauterine two percent lignocaine gel or an inert gel. Patients, recruiters and assessors were blinded to the gel used. Main outcome measures The difference between the study groups in the proportion of women who, after Vabra sampling, recorded a pain score of $6 out of 10 on a visual analogue scale. Results Three hundred and eight women were randomised, 284 (92%) completed a pain scale before and immediately after the procedure. After the procedure, 84 women (30%) recorded a pain score of $6, 38 (26%) received anaesthetic and 46 (33%) an inert gel. The difference in the proportion of women recording a pain score of 6 or above between the two study groups was not signi®cant (relative risk (RR) for the anaesthetic gel 0.79 95% CI, 0.55, 1.14). Conclusions Intrauterine application of 2% lignocaine gel did not signi®cantly reduce the frequency with which women experienced unacceptable levels of pain or anxiety during endometrial aspiration compared with placebo.
INTRODUCTION Some form of endometrial sampling is mandatory in the investigation of irregular premenopausal and postmenopausal vaginal bleeding. The use of high resolution ultrasound scan, although of value in the investigation of women presenting with postmenopausal bleeding, is of no particular bene®t in women with pre- or perimenopausal bleeding, or those with irregular bleeding on hormone replacement therapy 1. Hysteroscopy is another alternative diagnostic tool provided there is not excessive bleeding, but an endometrial sampling may still be required. Over the years many sampling techniques have been described. Common practice in the United
a
Department of Obstetrics and Gynaecology, Warrington Hospital NHS Trust, Warrington, UK b Centre for Cancer Epidemiology, University of Manchester, UK * Correspondence: Mr E.L. Kozman, Department of Obstetrics and Gynaecology, Warrington Hospital NHS Trust, Lovely Lane, Warrington WA5 1QG, UK.
q RCOG 2001 British Journal of Obstetrics and Gynaecology PII: S 0306-545 6(00)00005-X
Kingdom is to perform endometrial sampling without any form of analgesia or anaesthesia. Some samplers, like the Pipelle device (Prodemed, Nevilly-en-Thelle, France), gained popularity mainly because the procedure was well-tolerated and the tissue obtained correlated well with subsequent curettage 2. But the accuracy of the Pipelle device has been questioned by Ferry et al. 3, due to the fact that the Pipelle only samples 4.2% of the endometrial surface area when compared with the Vabra sampler (Berkeley Medevices, Berkeley, California, USA) which samples 41.6% 4. However, the use of more effective endometrial samplers, like Vabra, is not without pain and discomfort. In an effort to reduce discomfort during sampling, we decided to investigate the effect of an intrauterine application of a two percent lignocaine gel on the pain perception during Vabra sampling as suggested by Kitchener 5. A 2% lignocaine gel has also been assessed by Oloto et al. 6 prior to the insertion of intrauterine contraceptive devices in a family planning clinic. We undertook a randomised controlled trial to assess the effectiveness of topical lignocaine gel in reducing pain experienced during endometrial sampling.
www.bjog-elsevier.com
88 E. KOZMAN ET AL.
METHODS Women undergoing endometrial aspiration for investigation of abnormal vaginal bleeding in the Vabra Clinic at Warrington Hospital were randomly allocated to application of an intrauterine topical application of 2% lignocaine gel (Instillagel; CliniMed Ltd), prior to the procedure or to an inert equivalent (Endosgel; CliniMed Ltd,) made of sodium lactate, chlorhexidine digluconate, methyl P-hydroxybenzoate and propyl P-hydroxybenzoate. The study was approved by the local research ethics committee and informed consent obtained. The Instillagel and Endosgel were supplied in pre-loaded, sterile 11 ml syringes that could be connected to an appropriate quill (Instillaquill; CliniMed Ltd). The gels were supplied in identical packaging only identi®ed by a number designated by a predetermined randomisation organised in blocks of four, held by the pharmacy department. Patients, recruiters, operators and outcome assessors remained blind to the nature of the gel. Endometrial aspiration was performed using a standard technique. With the patient in the dorsal lithotomy position, a bimanual vaginal examination was performed to determine the position and the size of the uterus. A bivalve speculum was then inserted and the cervix cleansed using normal saline solution. The 3 mm quill attached to the pre-loaded syringe of gel was inserted into the vagina. One ml of gel was applied to the anterior cervical lip as in some women an application of a Volsellum and occasionally a passage of a uterine sound was considered necessary. The quill was then introduced into the cervical canal beyond the external os, but not through the internal os, and the rest of the gel was then applied. After a delay of 3 minutes, the Vabra aspirator, a 3 mm disposable stainless steel cannula, was inserted into the Table 1. Baseline characteristics of 308 women participating in the trial. Values are given as n (%) or mean {SD} [range]. Lignocain gel No. Age (years) Parity Parous Nulliparous Missing data Currently on HRT Missing data Postmenopausal bleeding Missing data Use of volsellum during procedure Missing data Anxiety at baseline Pain scores before sampling ,6 $6 Missing data
Placebo
157 51 {8.4} [22±76]
151 51 {9.3} [35±82]
151 (96) 6 0 46 (30) 0 54 (35) 0 53 (34)
148 (98) 2 1 52 (34) 2 42 (28) 2 40 (27)
2 47 {13.5} [20±80]
2 45.8 {13.4} [20±80]
153 1 3
141 1 9
uterine cavity. A suction machine producing a negative pressure of 500 to 600 mg of mercury was then activated and the whole endometrial cavity curretted clockwise. The curettage was repeated twice. Women completed a 0±10 visual analogue scale 7,8 and a short version of the Spielberger's State Trait Anxiety Inventory range 20±80, least anxious to morbid anxiety, (females having a mean score of 39.4) 9 immediately before the procedure (in the waiting area) and ®ve minutes following the sampling. A pilot study undertaken in 75 women showed that 32% of women undergoing Vabra aspiration recorded a pain score of $ 6. We estimated that to detect a difference of 15% between the two study groups, we would require 282 women for a study power of 80% at the 5% two sided signi®cance level. Differences between the two groups in the outcomes of interest were investigated by using Fisher's test and calculating the relative risk for nominal data, and the Student's t test for continuous data.
RESULTS Three hundred and ®fty-one women attended the Vabra clinic between October 1997 and October 1998; 23 women did not wish to undergo an outpatient procedure, eight women refused to participate in the trial. Three hundred and twenty women agreed to participate and were randomised. The procedure was abandoned in 12 women because of cervical stenosis. Of the remaining 308 women, 157 (51%) were randomly allocated to receive anaesthetic gel immediately before the procedure and 151 (49%) to receive inert gel. The baseline characteristics of these 308 women, including the histological ®ndings, were evenly distributed between the two study groups. They are summarised in Table 1 and 2, respecTable 2. Outcomes of 308 women participating in the trial. Values are given as n.
No. Pain scores after sampling ,6 $6 Missing data Histological ®ndings Normal Insuf®cient sample Simple hyperplasia Complex hyperplasia (architectural atypia) Atypical hyperplasia (cytological atypia) Adenocarcinoma Missing data a
Lignocaine gel
Placebo
157
151
107 38 a 12
93 46 12
121 30 0 3
114 30 2 1
0
1
1 2
0 3
RR 0.79 (CI 0.55±1.14)
q RCOG 2001 Br J Obstet Gynaecol 108, pp. 87±90
REDUCTION OF PAIN WITH TWO PERCENT LIGNOCAINE
tively. None of the women whose sample was insuf®cient had an abnormal ®nding on further assessment. Two hundred and eighty-four women (92%) completed a pain scale before and immediately after the procedure. Only two women (1%) recorded a pain score of $ 6 immediately before the procedure; one (1%) received anaesthetic gel and one (1%) inert gel (Table 1). After the procedure, 84 women (30%) recorded a pain score of $ 6; 38 (45.2%) received anaesthetic and 46 (54.8%) inert gel. The results are summarised in Table 2. The difference in the proportion of women recording a pain score of $ 6 between the two study groups was not significant (for the anaesthetic gel RR 0.79±95% CI 0.55, 1.14). Two hundred and sixty women in the trial completed the short version of the Spielberger's State Trait Anxiety Inventory before and immediately after the procedure. The mean (SD) anxiety score in the 129 of 145 women who received anaesthetic gel (82%) was 47.1 (13.2) before the procedure and 42.1 (13.5) following the procedure. The mean (SD) anxiety score in the 131 of 139 women receiving inert gel (87%) was 45.9 (13.7) before and 42.6 (12.9) after the procedure. The change in mean anxiety scores was ±4.96 (15.2) and ±3.31 (14.95) in the anaesthetic and inert gel groups respectively; the observed difference in the change in mean anxiety scores of ±1.65 between the study groups was not statistically signi®cant (t 20.88, df 258, P 0.379; 95% CI for difference in change in mean anxiety scores 25.34 to 2.05). DISCUSSION An increasing number of gynaecological procedures are being performed in the clinic setting. It has long been recognised that endometrial sampling and instrumentation are painful and that an adequate form of analgesia is required 10,11. Vabra aspiration, without any analgesia, caused median pain scores of 4.5 similar to the discomfort experienced during the insertion of an intrauterine contraceptive device 6, hysteroscopy and endometrial sampling 12 and other studies using Vabra aspiration 11,13. Nerve endings are present within the endometrial mucosa. The cervix uteri and especially the region of the functional internal os have a richer nervous supply than the rest of the body of the uterus. The sensory nerve supply of the cervix and the lower part of the body of the uterus is derived from the parasympathetic plexus (S2± S4) while the upper part of the uterus, including the fundus, derives its sensory innervation from the ovarian nerve plexus 14. Johnson et al and Broadbent et al commented that the existence of different types of nerve endings in the cervix and the endometrium might explain why intracervical in®ltration with lignocaine will be effective in reducing the sensitivity of the cervix, but q RCOG 2001 Br J Obstet Gynaecol 108, pp. 87±90
89
will be ineffective at blocking fundal innervation of the uterus 15,16. Hence anaesthetic techniques used for the treatment of cervical intraepithelial neoplasia will not necessarily alleviate pain during hysteroscopy or endometrial sampling procedures 12,16,17. This was recently con®rmed by Lau et al. 18 who, in a randomised doubleblind placebo controlled study using lignocaine or saline paracervically, concluded that it not only failed to reduce pain during outpatient hysteroscopy and endometrial biopsy, but also carried a risk of inducing bradycardia and hypotension. The demonstration by Siddle et al. 13 that naproxen sodium, a potent prostaglandin synthetase inhibitor, failed to relieve pain at the time of Vabra aspiration implied that this pain is not caused by prostaglandin release. Tramadol, a centrally acting analgesic, was assessed and its analgesic effects were similar to those of naproxen sodium 19. On the other hand, topical application of mepivacaine and lignocaine was found to reduce ef®ciently the discomfort experienced during hysteroscopy, endometrial biopsy 20 and insertion of intrauterine contraceptive devices 6. Despite these positive ®ndings we were unable to show that the use of an intrauterine topical analgesic, in the form of 2% lignocaine gel, signi®cantly reduced the frequency with which women experienced unacceptable levels of pain or anxiety during vabra aspiration compared with placebo. Our choice of threshold for `unacceptable' pain of 6 may be considered arbitrary. When a threshold of 5 was used the difference in the proportion of women recording a pain score of 5 or above between the two study groups only just failed to reach statistical signi®cance (relative risk for the anaesthetic gel 0.75; 95% CI 0.56±1.00). However, we do not consider the difference in pain scores of this magnitude to be clinically signi®cant. Further investigation of alternative methods of pain control should be encouraged. Acknowledgements The authors would like to thank the women who took part in the study, the nursing staff on the Women's Day Care Centre, and the library staff at the Postgraduate Centre, Warrington Hospital. We also like to thank Dr P. Dey, Lecturer in Public Health Medicine, Centre for Cancer Epidemiology, University of Manchester for her help with the randomisation and statistical analysis. We are also very grateful to CliniMed Ltd for supplying the Instillagel, Endosgel and Instillaquill used in this study. There were no con¯icts of interest. References 1. RCOG Guidelines. In-patient treatment: D&C in women aged 40 or less. Royal College of Obstetricians and Gynaecologists, London.
90 E. KOZMAN ET AL. 2. Batool T, Reginald P, Hughes H. Outpatient pipelle endometrial biopsy in the investigation of postmenopausal bleeding. Br J Obstet Gynaecol 1994;101:545±546. 3. Ferry J, Farnsworth A, Webster M, Wren B. The ef®cacy of the pipelle endometrial biopsy in detecting endometrial carcinoma. Aust NZ J Obstet Gynaecol 1993;33:76±78. 4. Rodriguez G, Yaqub N, King M. A comparison of the pipelle device and the Vabra aspirator as measured by endometrial denudation in hysterectomy specimens: the pipelle device samples signi®cantly less of the endometrial surface than the Vabra aspirator. Am J Obstet Gynecol 1993;168:55±59. 5. Kitchener H. The postmenopausal bleeding clinic. The Yearbook of the RCOG. London: RCOG Press, 1995:173±179. 6. Oloto E, Bromham D, Murty J. Pain and discomfort perception at IUD insertionÐeffect of short duration, low-volume, intracervical application of two percent lignocaine gel (Instillagel) - a preliminary study. Br J Fam Plann 1996;22:177±180. 7. Huskisson E. Measurement of pain. Lancet 1974;2:1127±1131. 8. Revill S, Robinson J, Rosen M, Hogg M. The reliability of a linear analogue scale for evaluating pain. Anaesthesia 1976;31:1191± 1198. 9. Marteau T, Bekker H. The development of a six-item short form of the state scale of the Spielberger State-Trait Anxiety Inventory (STAI). Br J Clin Psychol 1992;31:301±306. 10. Sledmere C, Reading A, Young O, Siddle N. Psychological aspects of Vabra curettage in menopause clinics. Maturitas 1981;3:205±213. 11. Dambso N. Diagnostic vacuum aspiration curettage and biopsy without anaesthesia in general practice. Scand J Prim Health Care 1988;6:225± 227.
12. Vercellini P, Oldani S, Colombo A, et al. Paracervical anaesthesia for outpatient hysteroscopy. Fertil Steril 1994;62(5):1083±1085. 13. Siddle N, Young O, Sledmere C, Reading A, Whithead M. A controlled trial of naproxen sodium for relief of pain associated with Vabra suction curettage. Br J Obstet Gynaecol 1983;90:864±869. 14. Williams P, Warwick R, Dyson H, Bannister LH. Gray's Anatomy. Edinburgh: Churchill Livingstone 1989:1167±1168. 15. Johnson N, Crompton A, Ramsden S. The ef®cacy of paracervical injections of lignocaine before laser ablation of the cervical transformation zone: a randomised placebo-controlled double-blind trial. Br J Obstet Gynaecol 1989;96:1410±1412. 16. Broadbent J, Hill N, Molnar B, et al. Randomised placebo controlled trial to assess the role of intracervical lignocaine in outpatient hysteroscopy. Br J Obstet Gynaecol 1992;99:777±780. 17. Finnikiotis G, Tsocanos S. Outpatient hysteroscopy: a comparison of 2 methods of local analgesia. Aust NZ J Obstet Gynaecol 1992;32(4): 373±374. 18. Lau W, Lo W, Tam W, Yuen P. Paracervical anaesthesia in outpatient hysteroscopy: a randomised double-blind placebo-controlled trial. Br J Obstet Gynaecol 1999;106:356±359. 19. Peters A, Witte E, Damen A, et al. Pain relief during and following outpatient curettage and hysterosalpingography: a double blind study to compare the ef®cacy and safety of tramadol versus naproxen. Eur J Obstet Gynecol Reprod Biol 1996;51:51±56. 20. Cicinelli E, Didonna T, Ambrosi G, et al. Topical anaesthesia for diagnostic hysteroscopy and endometrial biopsy in postmenopausal women: a randomised placebo-controlled double-blind study. Br J Obstet Gynaecol 1997;104:316±319. Accepted 21 August 2000
q RCOG 2001 Br J Obstet Gynaecol 108, pp. 87±90
The effect of an intrauterine application of two percent lignocaine gel on pain perception during Vabra endometrial sampling: a randomised double-blind, placebo-controlled trial Ezzat Kozman a,*, Peter Collins a, Ann Howard a, Tolu Akanmu a, Alan Gibbs b, Malcolm Frazer a Objective To determine whether two percent lignocaine gel can reduce the perception of pain during Vabra endometrial aspiration. Design Randomised, double-blind placebo-controlled trial. Setting Women's Health Directorate, Warrington Hospital NHS Trust. Population Women were referred to the endometrial sampling clinic for the investigation of pre and postmenopausal vaginal bleeding. Methods Randomisation to either pre-sampling intrauterine two percent lignocaine gel or an inert gel. Patients, recruiters and assessors were blinded to the gel used. Main outcome measures The difference between the study groups in the proportion of women who, after Vabra sampling, recorded a pain score of $6 out of 10 on a visual analogue scale. Results Three hundred and eight women were randomised, 284 (92%) completed a pain scale before and immediately after the procedure. After the procedure, 84 women (30%) recorded a pain score of $6, 38 (26%) received anaesthetic and 46 (33%) an inert gel. The difference in the proportion of women recording a pain score of 6 or above between the two study groups was not signi®cant (relative risk (RR) for the anaesthetic gel 0.79 95% CI, 0.55, 1.14). Conclusions Intrauterine application of 2% lignocaine gel did not signi®cantly reduce the frequency with which women experienced unacceptable levels of pain or anxiety during endometrial aspiration compared with placebo.
INTRODUCTION Some form of endometrial sampling is mandatory in the investigation of irregular premenopausal and postmenopausal vaginal bleeding. The use of high resolution ultrasound scan, although of value in the investigation of women presenting with postmenopausal bleeding, is of no particular bene®t in women with pre- or perimenopausal bleeding, or those with irregular bleeding on hormone replacement therapy 1. Hysteroscopy is another alternative diagnostic tool provided there is not excessive bleeding, but an endometrial sampling may still be required. Over the years many sampling techniques have been described. Common practice in the United
a
Department of Obstetrics and Gynaecology, Warrington Hospital NHS Trust, Warrington, UK b Centre for Cancer Epidemiology, University of Manchester, UK * Correspondence: Mr E.L. Kozman, Department of Obstetrics and Gynaecology, Warrington Hospital NHS Trust, Lovely Lane, Warrington WA5 1QG, UK.
q RCOG 2001 British Journal of Obstetrics and Gynaecology PII: S 0306-545 6(00)00005-X
Kingdom is to perform endometrial sampling without any form of analgesia or anaesthesia. Some samplers, like the Pipelle device (Prodemed, Nevilly-en-Thelle, France), gained popularity mainly because the procedure was well-tolerated and the tissue obtained correlated well with subsequent curettage 2. But the accuracy of the Pipelle device has been questioned by Ferry et al. 3, due to the fact that the Pipelle only samples 4.2% of the endometrial surface area when compared with the Vabra sampler (Berkeley Medevices, Berkeley, California, USA) which samples 41.6% 4. However, the use of more effective endometrial samplers, like Vabra, is not without pain and discomfort. In an effort to reduce discomfort during sampling, we decided to investigate the effect of an intrauterine application of a two percent lignocaine gel on the pain perception during Vabra sampling as suggested by Kitchener 5. A 2% lignocaine gel has also been assessed by Oloto et al. 6 prior to the insertion of intrauterine contraceptive devices in a family planning clinic. We undertook a randomised controlled trial to assess the effectiveness of topical lignocaine gel in reducing pain experienced during endometrial sampling.
www.bjog-elsevier.com
88 E. KOZMAN ET AL.
METHODS Women undergoing endometrial aspiration for investigation of abnormal vaginal bleeding in the Vabra Clinic at Warrington Hospital were randomly allocated to application of an intrauterine topical application of 2% lignocaine gel (Instillagel; CliniMed Ltd), prior to the procedure or to an inert equivalent (Endosgel; CliniMed Ltd,) made of sodium lactate, chlorhexidine digluconate, methyl P-hydroxybenzoate and propyl P-hydroxybenzoate. The study was approved by the local research ethics committee and informed consent obtained. The Instillagel and Endosgel were supplied in pre-loaded, sterile 11 ml syringes that could be connected to an appropriate quill (Instillaquill; CliniMed Ltd). The gels were supplied in identical packaging only identi®ed by a number designated by a predetermined randomisation organised in blocks of four, held by the pharmacy department. Patients, recruiters, operators and outcome assessors remained blind to the nature of the gel. Endometrial aspiration was performed using a standard technique. With the patient in the dorsal lithotomy position, a bimanual vaginal examination was performed to determine the position and the size of the uterus. A bivalve speculum was then inserted and the cervix cleansed using normal saline solution. The 3 mm quill attached to the pre-loaded syringe of gel was inserted into the vagina. One ml of gel was applied to the anterior cervical lip as in some women an application of a Volsellum and occasionally a passage of a uterine sound was considered necessary. The quill was then introduced into the cervical canal beyond the external os, but not through the internal os, and the rest of the gel was then applied. After a delay of 3 minutes, the Vabra aspirator, a 3 mm disposable stainless steel cannula, was inserted into the Table 1. Baseline characteristics of 308 women participating in the trial. Values are given as n (%) or mean {SD} [range]. Lignocain gel No. Age (years) Parity Parous Nulliparous Missing data Currently on HRT Missing data Postmenopausal bleeding Missing data Use of volsellum during procedure Missing data Anxiety at baseline Pain scores before sampling ,6 $6 Missing data
Placebo
157 51 {8.4} [22±76]
151 51 {9.3} [35±82]
151 (96) 6 0 46 (30) 0 54 (35) 0 53 (34)
148 (98) 2 1 52 (34) 2 42 (28) 2 40 (27)
2 47 {13.5} [20±80]
2 45.8 {13.4} [20±80]
153 1 3
141 1 9
uterine cavity. A suction machine producing a negative pressure of 500 to 600 mg of mercury was then activated and the whole endometrial cavity curretted clockwise. The curettage was repeated twice. Women completed a 0±10 visual analogue scale 7,8 and a short version of the Spielberger's State Trait Anxiety Inventory range 20±80, least anxious to morbid anxiety, (females having a mean score of 39.4) 9 immediately before the procedure (in the waiting area) and ®ve minutes following the sampling. A pilot study undertaken in 75 women showed that 32% of women undergoing Vabra aspiration recorded a pain score of $ 6. We estimated that to detect a difference of 15% between the two study groups, we would require 282 women for a study power of 80% at the 5% two sided signi®cance level. Differences between the two groups in the outcomes of interest were investigated by using Fisher's test and calculating the relative risk for nominal data, and the Student's t test for continuous data.
RESULTS Three hundred and ®fty-one women attended the Vabra clinic between October 1997 and October 1998; 23 women did not wish to undergo an outpatient procedure, eight women refused to participate in the trial. Three hundred and twenty women agreed to participate and were randomised. The procedure was abandoned in 12 women because of cervical stenosis. Of the remaining 308 women, 157 (51%) were randomly allocated to receive anaesthetic gel immediately before the procedure and 151 (49%) to receive inert gel. The baseline characteristics of these 308 women, including the histological ®ndings, were evenly distributed between the two study groups. They are summarised in Table 1 and 2, respecTable 2. Outcomes of 308 women participating in the trial. Values are given as n.
No. Pain scores after sampling ,6 $6 Missing data Histological ®ndings Normal Insuf®cient sample Simple hyperplasia Complex hyperplasia (architectural atypia) Atypical hyperplasia (cytological atypia) Adenocarcinoma Missing data a
Lignocaine gel
Placebo
157
151
107 38 a 12
93 46 12
121 30 0 3
114 30 2 1
0
1
1 2
0 3
RR 0.79 (CI 0.55±1.14)
q RCOG 2001 Br J Obstet Gynaecol 108, pp. 87±90
REDUCTION OF PAIN WITH TWO PERCENT LIGNOCAINE
tively. None of the women whose sample was insuf®cient had an abnormal ®nding on further assessment. Two hundred and eighty-four women (92%) completed a pain scale before and immediately after the procedure. Only two women (1%) recorded a pain score of $ 6 immediately before the procedure; one (1%) received anaesthetic gel and one (1%) inert gel (Table 1). After the procedure, 84 women (30%) recorded a pain score of $ 6; 38 (45.2%) received anaesthetic and 46 (54.8%) inert gel. The results are summarised in Table 2. The difference in the proportion of women recording a pain score of $ 6 between the two study groups was not significant (for the anaesthetic gel RR 0.79±95% CI 0.55, 1.14). Two hundred and sixty women in the trial completed the short version of the Spielberger's State Trait Anxiety Inventory before and immediately after the procedure. The mean (SD) anxiety score in the 129 of 145 women who received anaesthetic gel (82%) was 47.1 (13.2) before the procedure and 42.1 (13.5) following the procedure. The mean (SD) anxiety score in the 131 of 139 women receiving inert gel (87%) was 45.9 (13.7) before and 42.6 (12.9) after the procedure. The change in mean anxiety scores was ±4.96 (15.2) and ±3.31 (14.95) in the anaesthetic and inert gel groups respectively; the observed difference in the change in mean anxiety scores of ±1.65 between the study groups was not statistically signi®cant (t 20.88, df 258, P 0.379; 95% CI for difference in change in mean anxiety scores 25.34 to 2.05). DISCUSSION An increasing number of gynaecological procedures are being performed in the clinic setting. It has long been recognised that endometrial sampling and instrumentation are painful and that an adequate form of analgesia is required 10,11. Vabra aspiration, without any analgesia, caused median pain scores of 4.5 similar to the discomfort experienced during the insertion of an intrauterine contraceptive device 6, hysteroscopy and endometrial sampling 12 and other studies using Vabra aspiration 11,13. Nerve endings are present within the endometrial mucosa. The cervix uteri and especially the region of the functional internal os have a richer nervous supply than the rest of the body of the uterus. The sensory nerve supply of the cervix and the lower part of the body of the uterus is derived from the parasympathetic plexus (S2± S4) while the upper part of the uterus, including the fundus, derives its sensory innervation from the ovarian nerve plexus 14. Johnson et al and Broadbent et al commented that the existence of different types of nerve endings in the cervix and the endometrium might explain why intracervical in®ltration with lignocaine will be effective in reducing the sensitivity of the cervix, but q RCOG 2001 Br J Obstet Gynaecol 108, pp. 87±90
89
will be ineffective at blocking fundal innervation of the uterus 15,16. Hence anaesthetic techniques used for the treatment of cervical intraepithelial neoplasia will not necessarily alleviate pain during hysteroscopy or endometrial sampling procedures 12,16,17. This was recently con®rmed by Lau et al. 18 who, in a randomised doubleblind placebo controlled study using lignocaine or saline paracervically, concluded that it not only failed to reduce pain during outpatient hysteroscopy and endometrial biopsy, but also carried a risk of inducing bradycardia and hypotension. The demonstration by Siddle et al. 13 that naproxen sodium, a potent prostaglandin synthetase inhibitor, failed to relieve pain at the time of Vabra aspiration implied that this pain is not caused by prostaglandin release. Tramadol, a centrally acting analgesic, was assessed and its analgesic effects were similar to those of naproxen sodium 19. On the other hand, topical application of mepivacaine and lignocaine was found to reduce ef®ciently the discomfort experienced during hysteroscopy, endometrial biopsy 20 and insertion of intrauterine contraceptive devices 6. Despite these positive ®ndings we were unable to show that the use of an intrauterine topical analgesic, in the form of 2% lignocaine gel, signi®cantly reduced the frequency with which women experienced unacceptable levels of pain or anxiety during vabra aspiration compared with placebo. Our choice of threshold for `unacceptable' pain of 6 may be considered arbitrary. When a threshold of 5 was used the difference in the proportion of women recording a pain score of 5 or above between the two study groups only just failed to reach statistical signi®cance (relative risk for the anaesthetic gel 0.75; 95% CI 0.56±1.00). However, we do not consider the difference in pain scores of this magnitude to be clinically signi®cant. Further investigation of alternative methods of pain control should be encouraged. Acknowledgements The authors would like to thank the women who took part in the study, the nursing staff on the Women's Day Care Centre, and the library staff at the Postgraduate Centre, Warrington Hospital. We also like to thank Dr P. Dey, Lecturer in Public Health Medicine, Centre for Cancer Epidemiology, University of Manchester for her help with the randomisation and statistical analysis. We are also very grateful to CliniMed Ltd for supplying the Instillagel, Endosgel and Instillaquill used in this study. There were no con¯icts of interest. References 1. RCOG Guidelines. In-patient treatment: D&C in women aged 40 or less. Royal College of Obstetricians and Gynaecologists, London.
90 E. KOZMAN ET AL. 2. Batool T, Reginald P, Hughes H. Outpatient pipelle endometrial biopsy in the investigation of postmenopausal bleeding. Br J Obstet Gynaecol 1994;101:545±546. 3. Ferry J, Farnsworth A, Webster M, Wren B. The ef®cacy of the pipelle endometrial biopsy in detecting endometrial carcinoma. Aust NZ J Obstet Gynaecol 1993;33:76±78. 4. Rodriguez G, Yaqub N, King M. A comparison of the pipelle device and the Vabra aspirator as measured by endometrial denudation in hysterectomy specimens: the pipelle device samples signi®cantly less of the endometrial surface than the Vabra aspirator. Am J Obstet Gynecol 1993;168:55±59. 5. Kitchener H. The postmenopausal bleeding clinic. The Yearbook of the RCOG. London: RCOG Press, 1995:173±179. 6. Oloto E, Bromham D, Murty J. Pain and discomfort perception at IUD insertionÐeffect of short duration, low-volume, intracervical application of two percent lignocaine gel (Instillagel) - a preliminary study. Br J Fam Plann 1996;22:177±180. 7. Huskisson E. Measurement of pain. Lancet 1974;2:1127±1131. 8. Revill S, Robinson J, Rosen M, Hogg M. The reliability of a linear analogue scale for evaluating pain. Anaesthesia 1976;31:1191± 1198. 9. Marteau T, Bekker H. The development of a six-item short form of the state scale of the Spielberger State-Trait Anxiety Inventory (STAI). Br J Clin Psychol 1992;31:301±306. 10. Sledmere C, Reading A, Young O, Siddle N. Psychological aspects of Vabra curettage in menopause clinics. Maturitas 1981;3:205±213. 11. Dambso N. Diagnostic vacuum aspiration curettage and biopsy without anaesthesia in general practice. Scand J Prim Health Care 1988;6:225± 227.
12. Vercellini P, Oldani S, Colombo A, et al. Paracervical anaesthesia for outpatient hysteroscopy. Fertil Steril 1994;62(5):1083±1085. 13. Siddle N, Young O, Sledmere C, Reading A, Whithead M. A controlled trial of naproxen sodium for relief of pain associated with Vabra suction curettage. Br J Obstet Gynaecol 1983;90:864±869. 14. Williams P, Warwick R, Dyson H, Bannister LH. Gray's Anatomy. Edinburgh: Churchill Livingstone 1989:1167±1168. 15. Johnson N, Crompton A, Ramsden S. The ef®cacy of paracervical injections of lignocaine before laser ablation of the cervical transformation zone: a randomised placebo-controlled double-blind trial. Br J Obstet Gynaecol 1989;96:1410±1412. 16. Broadbent J, Hill N, Molnar B, et al. Randomised placebo controlled trial to assess the role of intracervical lignocaine in outpatient hysteroscopy. Br J Obstet Gynaecol 1992;99:777±780. 17. Finnikiotis G, Tsocanos S. Outpatient hysteroscopy: a comparison of 2 methods of local analgesia. Aust NZ J Obstet Gynaecol 1992;32(4): 373±374. 18. Lau W, Lo W, Tam W, Yuen P. Paracervical anaesthesia in outpatient hysteroscopy: a randomised double-blind placebo-controlled trial. Br J Obstet Gynaecol 1999;106:356±359. 19. Peters A, Witte E, Damen A, et al. Pain relief during and following outpatient curettage and hysterosalpingography: a double blind study to compare the ef®cacy and safety of tramadol versus naproxen. Eur J Obstet Gynecol Reprod Biol 1996;51:51±56. 20. Cicinelli E, Didonna T, Ambrosi G, et al. Topical anaesthesia for diagnostic hysteroscopy and endometrial biopsy in postmenopausal women: a randomised placebo-controlled double-blind study. Br J Obstet Gynaecol 1997;104:316±319. Accepted 21 August 2000
q RCOG 2001 Br J Obstet Gynaecol 108, pp. 87±90