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Intrauterine infusion of lidocaine was not useful for pain control during hysterosalpingography
ARTICLE IN PRESS GYNECOLOGY
Intrauterine infusion of lidocaine was not useful for pain control during hysterosalpingography Frishman GN, Spencer PK, Weitzen S, Plosker S, Shafi F.The use of intrauterine lidocaine to minimize pain during hysterosalpingography: a randomized trial. Obstet Gynecol 2004; 103:1261^1266.
OBJECTIVE To evaluate the use of instilled intrauterine lidocaine for pain control during hysterosalpingography in infertile women.
The women had been instructed to take a nonsteroidal analgesic on the morning of the procedure and about 75% of women did so.
DESIGN Randomized, double-blind, placebocontrolled trial. Allocation was computer-generated in blocks, using sealed envelopes and coded solutions prepared by the pharmacy. The study had su⁄cient power to detect an absolute di¡erence of 22% in the proportion of women experiencing moderate/severe pain.
MAIN OUTCOME MEASURES Proportion of women reporting moderate/severe pain (X5 on a visual analogue scale of 0^10), pain levels during, immediately after, and 10 min after the procedure.
SETTING University hospital in the USA.
SUBJECTS A total of 127 women, mean age 34 years, who were undergoing a hysterosalpingogram for investigation of infertility. Forty-¢ve percent of women were nulliparous, 61% had a history of dysmenorrhea, and 25% had had a hysterosalpingogram previously.
INTERVENTION Randomization allocated 63 women to receive 3 mL of 2% bu¡ered lidocaine solution and 64 women to receive plain saline as placebo, instilled into the uterus before the procedure.
1361-259x/$ - see front matter & 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.ebobgyn.2004.09.011
MAIN RESULTS The mean (7SD) maximum pain level during the hysterosalpingogram (as reported immediately afterwards) was 5.373.2 in both groups. Moderate/severe pain was reported by 58% of women in the lidocaine group, compared to 60% in the placebo group (p ¼ 0:81). The mean pain scores were 2.3 and 2.0, respectively, immediately after the procedure (NS), and 1.8 and 1.2, respectively, 10 min later (p ¼ 0:07).* Assessments by the attending physician and radiology sta¡ of visible signs of patient discomfort were similar between the two groups.
CONCLUSION Intrauterine instillation of 3 mL of 2% bu¡ered lidocaine, compared to 3 mL of plain saline, did not reduce the pain experienced during and after hysterosalpingography. * Estimated from graph in article
Evidence-based Obstetrics and Gynecology (2004) 6,177^180
177
ARTICLE IN PRESS
Intrauterine infusion of lidocaine was not useful for pain control during surgical abortion Edelman A, Nichols MD, Leclair C, Astley S, Shy K, Jensen JT. Intrauterine lidocaine infusion for pain management in first-trimester abortions. Obstet Gynecol 2004; 103:1267^1272.
OBJECTIVE To evaluate the use of instilled intrauterine lidocaine for control of uterine pain during ¢rst-trimester surgical abortion.
random allocation) 1% lidocaine (n ¼ 40) or plain saline as placebo (n ¼ 40). After an interval of 3 min, cervical dilation and suction aspiration were performed.
DESIGN Randomized, double-blind, placebocontrolled trial. Allocation was computer-generated in blocks, using coded solutions prepared by the study nurse. The allocation sequence was unknown to the physician recruiting the subjects. The study had su⁄cient power to detect a 17-mm di¡erence in mean pain score on a 100-mm visual analogue scale.
MAIN OUTCOME MEASURES Pain levels (assessed on a visual analogue scale of 0^100) immediately after cervical dilation and aspiration, and 30 min after the procedure, patient satisfaction.
SETTING Family planning clinic in the USA.
SUBJECTS Atotal of 80 women, aged 418 (mean 25) years, who requested surgical termination of pregnancy at o11 (mean 7) weeks gestation. Thirty-three percent of women were primigravid, 55% had a history of dysmenorrhea, and 63% had had an abortion previously.
INTERVENTION A half-hour before the procedure, all women received ibuprofen and, if requested, diazepam. At the start of the procedure, all women received a paracervical block (10 mL of 1% nonbu¡ered lidocaine solution injected at 3 positions on and around the cervix), then an intrauterine infusion of 10 mL of the study solution, either (by
178
Evidence-based Obstetrics and Gynecology (2004) 6,177^180
MAIN RESULTS The mean levels of anticipated pain, and pain at speculum insertion and at intrauterine infusion were similar in the two groups. The mean (7SD) pain score reported after cervical dilation was 33 728 in the lidocaine group and 36 725 in the placebo group (p ¼ 0:69). The mean pain scores reported after aspiration were 47 728 and 51 726, respectively (p ¼ 0:51). At 30 min after the procedure, the mean pain score was 28 721 in the lidocaine group and 21 721 in the placebo group (p ¼ 0:09). The level of pain anticipated correlated with the pain experienced in the placebo group, but not in the lidocaine group. Patient satisfaction with treatment was similar in the two groups (mean 83 and 82 out of 100).
CONCLUSION Intrauterine infusion of 10 mL of1% nonbu¡ered lidocaine, compared to 10 mL of plain saline, did not reduce the pain experienced during and after vacuum abortion.
ARTICLE IN PRESS Commentary Procaine-analog anesthetics work by blocking sodium ion reflux across neuronal cell membranes. Since 1925, they have been a mainstay for pain control for off|ce gynecological procedures, including diagnostic dilation and curettage, hysteroscopy, colposcopy, loop electrosurgical excision procedure, hysterosalpingography, endometrial ablation, pregnancy termination, and, more recently, endoscopic tubal sterilization. For example, a 1997 survey of North American providers of pregnancy termination disclosed that local anesthesia (with or without oral medications) was used by more than 40% of the 202 respondent clinics in 80% or more of their f|rst trimester cases.1 A 2002 re-survey of these providers (unpublished) revealed an increase in the use of local blocks: half of the 263 respondent clinics now used local anesthesia (with or without oral medications) in 80% or more of abortions, and half also incorporated them with intravenous medications X80% of the time. Despite their ubiquity and value, there are relatively few studies of the eff|cacy of local anesthetics for gynecological procedures. However, some constants emerge from the literature. One is that the source of acute pain with gynecological procedures is cervical dilation, rather than external cervical or intrauterine instrumentation. Another is the preference for amides, such as lidocaine, mepivacaine, and bupivacaine, over the more expensive, unstable, and allergenic esters, such as procaine and 2-chloroprocaine. What are the preferred techniques? Wiebe’s landmark study of 163 women established that routinely using 6 (instead of the traditional 3) injection sites into the cervico-vaginal folds and, most importantly, increasing the depth of injection from 0.5 inch (1.2 cm) to1.0 ^1.5 inches (2.5^3.5 cm) improved pain scores significantly (by 25%) in women undergoing vacuum abortion.2 The most dramatic pain reduction was seen with cervical dilation (p ¼ 0:0001), but overall procedural pain also showed signif|cant improvement (p ¼ 0:018). Another interesting subject is mode of action: does local injection work primarily by diffusion, in which case saline alone would be enough, or by interference with intracellular sodium transport, implying an advantage for procaine-analog drugs? In a 1996 abortion study in the US, 52 women were randomized to receive either 20 mL of bacteriostatic saline (containing 0.9% benzyl alcohol) or 20 mL of 1% buffered lidocaine. A standard 3site technique (at 12, 4 and 8 o’clock) no deeper than 1cm (less than 0.5 inch) was used. Saline was nearly as effective as lidocaine, producing a nonsignif|cant 4% increase in pain. A second well-conducted randomized trial among 140 women undergoing fractional curettage in Thailand compared 20 mL of 1% non-buffered lidocaine and plain saline (without alcohol) given at 2 sites (3 and 9 o’clock) no greater than1cm in depth. Only 8 of 140 women required instrumental cervical dilation; still, pain scores were signif|cantly better during curettage, but not otherwise, with lidocaine. The US study may have introduced a confounder, because benzyl alcohol alone has been reported to be an effective anesthetic during skin surgery. Failure to use a 6 -site, deep injection technique in these studies may have blunted any differences in effect. As matters currently stand, well-conducted trials do not show clearly that saline cervical block by injection can replace procaine-analog drugs for pain control, but the optimal 6 site technique of deep injections with plain saline has not been tested. Finally, a recent line of inquiry proposes that the uterine cavity be anesthetized by infusion of active agents. The rationale is that the endometrium is an avid absorber of topical compounds
and this mode of administration would avoid the pain of injection and the risk of intravenous entry, making it potentially useful for procedures in which the pain usually experienced is of moderate or low intensity. A randomized trial evaluating the eff|cacy of 5 mL of 2% lidocaine during endometrial biopsy (n ¼ 57)3, and another trial of 2 mL of 2% mepivacaine used for hysteroscopy or endometrial biopsy (n ¼ 80)4 showed signif|cant superiority over plain saline in postmenopausal women. However, a more recent 4 -armed randomized trial during endometrial biopsy (n ¼ 120) in both premenopausal and postmenopausal women showed equivalent pain control with oral naproxen sodium 550 mg or an intrauterine infusion of 5 mL of 2% lidocaine; a combination of the two treatments showed superiority over either alone.5 Unfortunately, infusion techniques for hysterosalpingography (HSG) have not been encouraging: a previously published randomized trial (n ¼ 110) showed no advantage for 2 mL of 2% nonbuffered lidocaine over plain saline before HSG.6 Coincidentally, the present study by Frishman et al was undertaken during the same period. Its study design and sample size (n ¼ 127) were virtually identical to those of Costello et al, except for the addition of the buffer to the lidocaine (to reduce possible pain from its acidic pH). Results were similarly unpromising: maximum pain scores in the lidocaine and saline arms were the same (5.3 cm 7 0.4 SE on a10-cmvisual analog scale) and, of concern, 58% (lidocaine) and 60% (saline) of women reported moderate to severe pain despite having received a nonsteroidal analgesic that morning. In the second study, Edelman et al. attempted a similar strategy for vacuum abortion.These authors randomized 80 subjects to intrauterine infusions of10 mL1% lidocaine or plain saline after f|rst giving each woman a ‘‘standard’’ 3-site (12, 4 and 8 o’clock) paracervical block, presumably to a maximum depth of 1cm.Their intent was to dampen the pain of dilation with the cervical block and lessen the cramping from the aspiration procedure with the infusion. Pain scores were similar for both arms; approximately 15 mm higher for aspiration than dilation on a 100 -mm visual analog pain scale. Thus, the infusion method seemed to have little, if any, analgesic effect. The authors wondered if increasing duration, concentration, or volume of the lidocaine might have improved results, but, based on the eff|cacy of similar infusion regimens for endometrial biopsy and hysteroscopy, it may be simply that the level of pain with hysterosalpingography and vacuum abortion is more than any infusion technique can suppress satisfactorily. A rise in pain scores after 10 min in both HSG trials may indicate the brevity of the effect of infusion techniques on uterine pain. Taken together, the well-conducted randomized trials presented here, as well as the study of Costello et al,6 provide level I evidence that infusion of concentrated procaine amide anesthetics into the uterus has minimal analgesic benef|t in vacuum abortion and hysterosalpingography. E. Steve Lichtenberg, MD, MPH NORTHWESTERN UNIVERSITY, CHICAGO, IL, USA
Literature cited 1. Lichtenberg ES, Paul M, Jones H.First trimester surgical abortion practices: a survey of National Abortion Federation members. Contraception 2001; 64: 345^352. 2. Wiebe ER. Comparison of the eff|cacy of different local anesthetics and techniques of local anesthesia in therapeutic abortions. Am J Obstet Gynecol 1992; 167: 131^134.
Evidence-based Obstetrics and Gynecology (2004) 6,177^180
179
ARTICLE IN PRESS 3. Trolice MP, Fishburne Jr C, McGrady S. Anesthetic eff|cacy of intrauterine lidocaine for endometrial biopsy: randomized double-masked trial. Obstet Gynecol 2000; 95: 345^347. 4. Cicinelli E, DidonnaT, Ambrosi G, et al.Topical anesthesia for diagnostic hysteroscopy and endometrial biopsy in postmenopausal women: a randomised placebo-controlled double-blind study. Br J Obstet Gynaecol 1997; 104: 316 ^319.
180
Evidence-based Obstetrics and Gynecology (2004) 6,177^180
5. Dogan E, Celiloglu, Sarihan E, Demir A. Anesthetic effect of intrauterine lidocaine plus naproxen sodium in endometrial biopsy. Obstet Gynecol 2004; 103: 347^351. 6. Costello MF, Horrowitz S, Steigrad S, et al. Transcervical intrauterine topical local anesthetic at hysterosalpingography; a prospective, randomized double-blind, placebo-controlled trial. Fertil Steril 2002; 78: 1116^1122.
Intrauterine infusion of lidocaine was not useful for pain control during hysterosalpingography Frishman GN, Spencer PK, Weitzen S, Plosker S, Shafi F.The use of intrauterine lidocaine to minimize pain during hysterosalpingography: a randomized trial. Obstet Gynecol 2004; 103:1261^1266.
OBJECTIVE To evaluate the use of instilled intrauterine lidocaine for pain control during hysterosalpingography in infertile women.
The women had been instructed to take a nonsteroidal analgesic on the morning of the procedure and about 75% of women did so.
DESIGN Randomized, double-blind, placebocontrolled trial. Allocation was computer-generated in blocks, using sealed envelopes and coded solutions prepared by the pharmacy. The study had su⁄cient power to detect an absolute di¡erence of 22% in the proportion of women experiencing moderate/severe pain.
MAIN OUTCOME MEASURES Proportion of women reporting moderate/severe pain (X5 on a visual analogue scale of 0^10), pain levels during, immediately after, and 10 min after the procedure.
SETTING University hospital in the USA.
SUBJECTS A total of 127 women, mean age 34 years, who were undergoing a hysterosalpingogram for investigation of infertility. Forty-¢ve percent of women were nulliparous, 61% had a history of dysmenorrhea, and 25% had had a hysterosalpingogram previously.
INTERVENTION Randomization allocated 63 women to receive 3 mL of 2% bu¡ered lidocaine solution and 64 women to receive plain saline as placebo, instilled into the uterus before the procedure.
1361-259x/$ - see front matter & 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.ebobgyn.2004.09.011
MAIN RESULTS The mean (7SD) maximum pain level during the hysterosalpingogram (as reported immediately afterwards) was 5.373.2 in both groups. Moderate/severe pain was reported by 58% of women in the lidocaine group, compared to 60% in the placebo group (p ¼ 0:81). The mean pain scores were 2.3 and 2.0, respectively, immediately after the procedure (NS), and 1.8 and 1.2, respectively, 10 min later (p ¼ 0:07).* Assessments by the attending physician and radiology sta¡ of visible signs of patient discomfort were similar between the two groups.
CONCLUSION Intrauterine instillation of 3 mL of 2% bu¡ered lidocaine, compared to 3 mL of plain saline, did not reduce the pain experienced during and after hysterosalpingography. * Estimated from graph in article
Evidence-based Obstetrics and Gynecology (2004) 6,177^180
177
ARTICLE IN PRESS
Intrauterine infusion of lidocaine was not useful for pain control during surgical abortion Edelman A, Nichols MD, Leclair C, Astley S, Shy K, Jensen JT. Intrauterine lidocaine infusion for pain management in first-trimester abortions. Obstet Gynecol 2004; 103:1267^1272.
OBJECTIVE To evaluate the use of instilled intrauterine lidocaine for control of uterine pain during ¢rst-trimester surgical abortion.
random allocation) 1% lidocaine (n ¼ 40) or plain saline as placebo (n ¼ 40). After an interval of 3 min, cervical dilation and suction aspiration were performed.
DESIGN Randomized, double-blind, placebocontrolled trial. Allocation was computer-generated in blocks, using coded solutions prepared by the study nurse. The allocation sequence was unknown to the physician recruiting the subjects. The study had su⁄cient power to detect a 17-mm di¡erence in mean pain score on a 100-mm visual analogue scale.
MAIN OUTCOME MEASURES Pain levels (assessed on a visual analogue scale of 0^100) immediately after cervical dilation and aspiration, and 30 min after the procedure, patient satisfaction.
SETTING Family planning clinic in the USA.
SUBJECTS Atotal of 80 women, aged 418 (mean 25) years, who requested surgical termination of pregnancy at o11 (mean 7) weeks gestation. Thirty-three percent of women were primigravid, 55% had a history of dysmenorrhea, and 63% had had an abortion previously.
INTERVENTION A half-hour before the procedure, all women received ibuprofen and, if requested, diazepam. At the start of the procedure, all women received a paracervical block (10 mL of 1% nonbu¡ered lidocaine solution injected at 3 positions on and around the cervix), then an intrauterine infusion of 10 mL of the study solution, either (by
178
Evidence-based Obstetrics and Gynecology (2004) 6,177^180
MAIN RESULTS The mean levels of anticipated pain, and pain at speculum insertion and at intrauterine infusion were similar in the two groups. The mean (7SD) pain score reported after cervical dilation was 33 728 in the lidocaine group and 36 725 in the placebo group (p ¼ 0:69). The mean pain scores reported after aspiration were 47 728 and 51 726, respectively (p ¼ 0:51). At 30 min after the procedure, the mean pain score was 28 721 in the lidocaine group and 21 721 in the placebo group (p ¼ 0:09). The level of pain anticipated correlated with the pain experienced in the placebo group, but not in the lidocaine group. Patient satisfaction with treatment was similar in the two groups (mean 83 and 82 out of 100).
CONCLUSION Intrauterine infusion of 10 mL of1% nonbu¡ered lidocaine, compared to 10 mL of plain saline, did not reduce the pain experienced during and after vacuum abortion.
ARTICLE IN PRESS Commentary Procaine-analog anesthetics work by blocking sodium ion reflux across neuronal cell membranes. Since 1925, they have been a mainstay for pain control for off|ce gynecological procedures, including diagnostic dilation and curettage, hysteroscopy, colposcopy, loop electrosurgical excision procedure, hysterosalpingography, endometrial ablation, pregnancy termination, and, more recently, endoscopic tubal sterilization. For example, a 1997 survey of North American providers of pregnancy termination disclosed that local anesthesia (with or without oral medications) was used by more than 40% of the 202 respondent clinics in 80% or more of their f|rst trimester cases.1 A 2002 re-survey of these providers (unpublished) revealed an increase in the use of local blocks: half of the 263 respondent clinics now used local anesthesia (with or without oral medications) in 80% or more of abortions, and half also incorporated them with intravenous medications X80% of the time. Despite their ubiquity and value, there are relatively few studies of the eff|cacy of local anesthetics for gynecological procedures. However, some constants emerge from the literature. One is that the source of acute pain with gynecological procedures is cervical dilation, rather than external cervical or intrauterine instrumentation. Another is the preference for amides, such as lidocaine, mepivacaine, and bupivacaine, over the more expensive, unstable, and allergenic esters, such as procaine and 2-chloroprocaine. What are the preferred techniques? Wiebe’s landmark study of 163 women established that routinely using 6 (instead of the traditional 3) injection sites into the cervico-vaginal folds and, most importantly, increasing the depth of injection from 0.5 inch (1.2 cm) to1.0 ^1.5 inches (2.5^3.5 cm) improved pain scores significantly (by 25%) in women undergoing vacuum abortion.2 The most dramatic pain reduction was seen with cervical dilation (p ¼ 0:0001), but overall procedural pain also showed signif|cant improvement (p ¼ 0:018). Another interesting subject is mode of action: does local injection work primarily by diffusion, in which case saline alone would be enough, or by interference with intracellular sodium transport, implying an advantage for procaine-analog drugs? In a 1996 abortion study in the US, 52 women were randomized to receive either 20 mL of bacteriostatic saline (containing 0.9% benzyl alcohol) or 20 mL of 1% buffered lidocaine. A standard 3site technique (at 12, 4 and 8 o’clock) no deeper than 1cm (less than 0.5 inch) was used. Saline was nearly as effective as lidocaine, producing a nonsignif|cant 4% increase in pain. A second well-conducted randomized trial among 140 women undergoing fractional curettage in Thailand compared 20 mL of 1% non-buffered lidocaine and plain saline (without alcohol) given at 2 sites (3 and 9 o’clock) no greater than1cm in depth. Only 8 of 140 women required instrumental cervical dilation; still, pain scores were signif|cantly better during curettage, but not otherwise, with lidocaine. The US study may have introduced a confounder, because benzyl alcohol alone has been reported to be an effective anesthetic during skin surgery. Failure to use a 6 -site, deep injection technique in these studies may have blunted any differences in effect. As matters currently stand, well-conducted trials do not show clearly that saline cervical block by injection can replace procaine-analog drugs for pain control, but the optimal 6 site technique of deep injections with plain saline has not been tested. Finally, a recent line of inquiry proposes that the uterine cavity be anesthetized by infusion of active agents. The rationale is that the endometrium is an avid absorber of topical compounds
and this mode of administration would avoid the pain of injection and the risk of intravenous entry, making it potentially useful for procedures in which the pain usually experienced is of moderate or low intensity. A randomized trial evaluating the eff|cacy of 5 mL of 2% lidocaine during endometrial biopsy (n ¼ 57)3, and another trial of 2 mL of 2% mepivacaine used for hysteroscopy or endometrial biopsy (n ¼ 80)4 showed signif|cant superiority over plain saline in postmenopausal women. However, a more recent 4 -armed randomized trial during endometrial biopsy (n ¼ 120) in both premenopausal and postmenopausal women showed equivalent pain control with oral naproxen sodium 550 mg or an intrauterine infusion of 5 mL of 2% lidocaine; a combination of the two treatments showed superiority over either alone.5 Unfortunately, infusion techniques for hysterosalpingography (HSG) have not been encouraging: a previously published randomized trial (n ¼ 110) showed no advantage for 2 mL of 2% nonbuffered lidocaine over plain saline before HSG.6 Coincidentally, the present study by Frishman et al was undertaken during the same period. Its study design and sample size (n ¼ 127) were virtually identical to those of Costello et al, except for the addition of the buffer to the lidocaine (to reduce possible pain from its acidic pH). Results were similarly unpromising: maximum pain scores in the lidocaine and saline arms were the same (5.3 cm 7 0.4 SE on a10-cmvisual analog scale) and, of concern, 58% (lidocaine) and 60% (saline) of women reported moderate to severe pain despite having received a nonsteroidal analgesic that morning. In the second study, Edelman et al. attempted a similar strategy for vacuum abortion.These authors randomized 80 subjects to intrauterine infusions of10 mL1% lidocaine or plain saline after f|rst giving each woman a ‘‘standard’’ 3-site (12, 4 and 8 o’clock) paracervical block, presumably to a maximum depth of 1cm.Their intent was to dampen the pain of dilation with the cervical block and lessen the cramping from the aspiration procedure with the infusion. Pain scores were similar for both arms; approximately 15 mm higher for aspiration than dilation on a 100 -mm visual analog pain scale. Thus, the infusion method seemed to have little, if any, analgesic effect. The authors wondered if increasing duration, concentration, or volume of the lidocaine might have improved results, but, based on the eff|cacy of similar infusion regimens for endometrial biopsy and hysteroscopy, it may be simply that the level of pain with hysterosalpingography and vacuum abortion is more than any infusion technique can suppress satisfactorily. A rise in pain scores after 10 min in both HSG trials may indicate the brevity of the effect of infusion techniques on uterine pain. Taken together, the well-conducted randomized trials presented here, as well as the study of Costello et al,6 provide level I evidence that infusion of concentrated procaine amide anesthetics into the uterus has minimal analgesic benef|t in vacuum abortion and hysterosalpingography. E. Steve Lichtenberg, MD, MPH NORTHWESTERN UNIVERSITY, CHICAGO, IL, USA
Literature cited 1. Lichtenberg ES, Paul M, Jones H.First trimester surgical abortion practices: a survey of National Abortion Federation members. Contraception 2001; 64: 345^352. 2. Wiebe ER. Comparison of the eff|cacy of different local anesthetics and techniques of local anesthesia in therapeutic abortions. Am J Obstet Gynecol 1992; 167: 131^134.
Evidence-based Obstetrics and Gynecology (2004) 6,177^180
179
ARTICLE IN PRESS 3. Trolice MP, Fishburne Jr C, McGrady S. Anesthetic eff|cacy of intrauterine lidocaine for endometrial biopsy: randomized double-masked trial. Obstet Gynecol 2000; 95: 345^347. 4. Cicinelli E, DidonnaT, Ambrosi G, et al.Topical anesthesia for diagnostic hysteroscopy and endometrial biopsy in postmenopausal women: a randomised placebo-controlled double-blind study. Br J Obstet Gynaecol 1997; 104: 316 ^319.
180
Evidence-based Obstetrics and Gynecology (2004) 6,177^180
5. Dogan E, Celiloglu, Sarihan E, Demir A. Anesthetic effect of intrauterine lidocaine plus naproxen sodium in endometrial biopsy. Obstet Gynecol 2004; 103: 347^351. 6. Costello MF, Horrowitz S, Steigrad S, et al. Transcervical intrauterine topical local anesthetic at hysterosalpingography; a prospective, randomized double-blind, placebo-controlled trial. Fertil Steril 2002; 78: 1116^1122.