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Anesthetic Efficacy of Intrauterine Lidocaine for Endometrial Biopsy: A Randomized Double-Masked Trial

From the Department of Obstetrics and Gynecology, Carolinas Medical Center, Charlotte, North Carolina.

Address reprint requests to: Mark P. Trolice, MD Reproductive Health Institute Arnold Palmer Hospital for Children and Women 22 Underwood Street Orlando, FL 32806 E-mail: mtrolice{at}orhs.org

	Abstract

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Objective: To determine the efficacy of intrauterine lidocaine for decreasing pain associated with endometrial biopsy using the Pipelle instrument (Unimar; Wilton, CT).

Methods: Forty-one premenopausal and postmenopausal women had 5 mL of either 2% lidocaine or saline instilled in their uteri before endometrial biopsies. Subsequently, each woman completed a 20-cm visual analogue scale for subjective pain experience. We compared histologic findings in endometrial specimens.

Results: Before the study, analysis of specimens (n = 6) found no histologic effect on ability to interpret endometrial biopsies by pathologists who were masked to lidocaine or saline. There was no statistically significant difference in age, parity, race, history of chronic pelvic pain, menopausal status, use of tenaculum, or prior endometrial biopsy. The procedure was easy, with no clinically significant side effects. On the visual pain scale, the median (range) score for the lidocaine group (4.7, 0–19.7) compared with the placebo group (9.9, 1.6–20) showed significant reduction in pain corresponding with a decrease from moderate to mild (P < .01).

Conclusion: Intrauterine lidocaine is simple and effective for decreasing pain associated with the Pipelle endometrial biopsy.

Endometrial biopsy is a common outpatient office procedure, with studies supporting its use in many disorders, including abnormal uterine bleeding, postmenopausal bleeding, abnormal cytology, hormone therapy monitoring, and infertility.^1,2 Although most women have some degree of discomfort with the procedure, few studies have evaluated possible methods of adequate pain relief. We conducted a MEDLINE search from 1966 to July 1999 (search terms endometrial biopsy, intrauterine, analgesia, anesthesia) and were unable to find a study that examined intrauterine analgesia with endometrial biopsy alone. Prior studies addressed intrauterine analgesia in women who had concurrent office hysteroscopies and endometrial biopsies, with only one that found a significant difference compared with placebo.^3–6 Hysteroscopy with endometrial biopsy adds a variable that limits generalizing those results to endometrial biopsy. Those studies did not show any side effects or morbidity from intrauterine or direct peritoneal cavity instillation of mepivacaine or lidocaine.⁷ That observation provides precedence for safety of intrauterine topical anesthesia.

Intrauterine instillation³ of topical anesthetic is easy, relatively painless, and promising for adequate analgesia during endometrial biopsy. This technique could be ideal anesthesia for office endometrial biopsies. The goal of this study was to determine pain during endometrial biopsy by comparing intrauterine lidocaine and placebo in a randomized, double-masked trial in premenopausal and postmenopausal women.

	Materials and Methods

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This was a randomized, placebo-controlled, double-masked trial with women recruited from our residency gynecology clinics. Pathologists at our institution did a preliminary analysis; they were masked to lidocaine or saline and reviewed six endometrial biopsy samples. Our institutional review board gave full approval of the study and procedures.

Women who needed endometrial biopsies were invited to participate if they did not have stenotic cervical os, allergy to lidocaine, age less than 18 years, acute cervicitis, need for coincident endocervical curettage, or positive ßhCG test. Before the procedure, each woman completed a demographics form and was randomized with a predetermined computer-generated randomization code to 2% lidocaine or saline placebo before endometrial biopsy. Test solutions were packaged by our pharmacy in identical, clear, 20-mL bottles, and all resident physicians and nurses caring for study subjects were masked to type of solution. Biopsies were done with the Pipelle (Unimar, Wilton, CT), a flexible plastic 3.1-mm-diameter catheter. To maintain consistency and limit confounding variables, resident physicians used the same technique to sample the endometrium. The cervix and vagina were cleansed with betadine, and 5 mL of unlabeled test solution was instilled through the endocervix into the uterine cavity using an 18-gauge angiocatheter advanced to the hub. The angiocatheter was left in place for 3 minutes before it was withdrawn to limit backflow and allow the anesthetic to reach effect. The Pipelle then was pushed into the uterine cavity for three passes to ensure complete sampling. When a tenaculum was used, 2 mL of known 2% lidocaine was infiltrated into the cervix before application, in the saline and lidocaine groups, and those women were reanalyzed separately. After the procedure, each woman completed a 20-cm visual analogue pain scale marked as 0 cm = no pain, 5 cm = mild pain, 10 cm = moderate pain, 15 cm = severe pain, and 20 cm = excruciating pain. Scores were measured from the left and recorded. Subjects were asked to report any symptoms to the physician during or after the procedure. The pathologists at our institution, masked to test solution, analyzed all tissue specimens.

We used standard statistical methods and the SAS System 6.12 (SAS Institute, Cary, NC) to complete analyses. The Wilcoxon rank-sum test was used to compare distribution of visual analogue pain scale scores between groups. Demographic variables were compared between groups with the Wilcoxon rank-sum test, Kruskal-Wallis test when the variables were measured on the interval scale, or Fisher exact test when the variables were measured on the categoric scale. P < .05 was considered statistically significant.

	Results

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Before the study, analysis of specimens (n = 6) by pathologists masked to lidocaine or saline showed no histologic effect on the ability to interpret endometrial biopsies. Fifty-seven women between 21 and 72 years old were enrolled (Figure 1). Sixteen were excluded for stenotic cervical os (n = 8) or protocol violation (n = 8). Forty-one completed the study and provided analyzable data; 19 (46.3%) received lidocaine, 22 (53.7%) placebo. There were no statistically significant differences between groups in age, parity, race, history of chronic pelvic pain, menopausal status, use of a tenaculum, or prior endometrial biopsy (Table 1).

View larger version (15K): [in this window] [in a new window]   Figure 1. Trial profile. Patient numbers in parenthesis.

	Discussion

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According to our MEDLINE search, this is the first study to evaluate efficacy of intrauterine topical anesthesia specifically for endometrial biopsy. Endometrial biopsy has become an established gynecologic office procedure to collect tissue for histologic evaluation of the endometrium. Patient acceptability and compliance with the procedure might be difficult because of associated pain, which is supported by our finding that without analgesia, the biopsy induced moderate discomfort.

Studies of intrauterine topical anesthesia evaluated its use with combined hysteroscopy and endometrial biopsy, a more involved and potentially uncomfortable procedure than endometrial biopsy alone. Hysteroscopy also involves uterine distention, which might be less responsive to topical anesthetic.⁶ Cicinelli et al,³ Zupi et al,⁴ and Davies et al⁵ evaluated intrauterine topical anesthesia for outpatient office hysteroscopy. Several of those women also had concurrent endometrial biopsies. None of the studies found a statistically significant difference between case and placebo groups in patient-reported pain experience.^3–5 Cicinelli et al⁶ showed a mild but statistically significant reduction in pain during office hysteroscopy and endometrial biopsy with intrauterine mepivacaine in postmenopausal women; however, the reduction was limited to parous women.

Several other studies explored either paracervical or intracervical injectable nerve block for outpatient office hysteroscopy.^8,9 Results of those studies did not show clinical efficacy, and instead found that the technique is painful and risks bleeding and intravasation of anesthetic. Therefore, this technique is of limited use for endometrial biopsy, which is a much less involved and uncomfortable procedure than hysteroscopy.

The presumed mechanism of action of the anesthetic in our study was an effect on the nerve endings within the endometrial mucosa.^3,6 Frankenhauer’s plexus, parasympathetic S2-4, provides the sensory innervation of the cervix and lower portion of the uterus.¹⁰ However, it has been proposed that the fundal region derives its sensory innervation from the ovarian nerve plexus.⁸ We chose 2% lidocaine for intrauterine anesthetic because it has a quicker onset and shorter duration of action than mepivacaine, which was used in previous studies, and 2% lidocaine might have a theoretic greater efficacy than 1%.^3,4,6

We accept that the limitation of our study is the small sample, but statistical analysis did show a significant difference between groups. The sample might not allow for sufficient analysis of the subgroups, increasing the risk of a type II error, but all of the subgroups in Table 1, including history of endometrial biopsy, were not confounding variables.

Analysis of our data showed a statistically significant reduction in pain from moderate to mild on the visual analogue scale, during endometrial biopsy with intrauterine lidocaine in premenopausal and postmenopausal women, regardless of parity. Although instillation might lengthen the procedure, we believe the reduction in patient discomfort outweighs the time factor. Initial patient experience might increase compliance if another biopsy is needed. It is possible that this technique might be applicable to other intrauterine procedures such as early dilation and evacuation.

	Footnotes

 
Supported by a grant of the Carolina HealthCare System Health Services Foundation.

PII S0029-7844(99)00557-8

Received April 9, 1999. Received in revised form August 18, 1999. Accepted September 2, 1999.

	References

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1. Chambers JT, Chambers SK. Endometrial sampling: When? where? why? with what? Clin Obstet Gynecol 1992;35:28–39.[Medline]

2. Fothergill DJ, Brown VA, Hill AS. Histological sampling of the endometrium—a comparison between formal curettage and the Pipelle sampler. Br J Obstet Gynaecol 1992;99:779–80.[Medline]

3. Cicinelli E, Didonna T, Fiore G, Parisi C, Matteo M, Castrovilli G. Topical anesthesia for hysteroscopy in postmenopausal women. J Am Assoc Gynecol Laparosc 1996;4:9–12.[Medline]

4. Zupi E, Luciano AA, Valli E, Marconi D, Maneschi F, Romanini C. The use of topical anesthesia in diagnostic hysteroscopy and endometrial biopsy. Fertil Steril 1995;63:414–6.[Medline]

5. Davies A, Richardson RE, O’Connor H, Baskett TF, Nagele F, Magos AL. Lignocaine aerosol spray in outpatient hysteroscopy: A randomized double-blind placebo-controlled trial. Fertil Steril 1997;67:1019–23.[Medline]

6. Cicinelli E, Didonna T, Ambrosi G, Schonauer LM, Giore G, Matteo MG. Topical anesthesia for diagnostic hysteroscopy and endometrial biopsy in postmenopausal women: A randomised placebo-controlled double-blind study. Br J Obstet Gynaecol 1997;104:316–9.[Medline]

7. Narchi P, Benhamou D, Bouaziz H, Fernandez H, Mazoit JX. Serum concentrations of local anaesthetics following intraperitoneal administration during laparoscopy. Eur J Clin Pharmacol 1992;42:223–5.[Medline]

8. Broadbent JAM, Hill NCW, Molnar BG, Rolfe KJ, Magos AL. Randomized placebo controlled trial to assess the role of intracervical lignocaine in outpatient hysteroscopy. Br J Obstet Gynaecol 1992;99:777–80.[Medline]

9. Vercellini P, Colombo A, Mauro F, Oldani S, Bramante T, Crosignani PG. Paracervical anesthesia for outpatient hysteroscopy. Fertil Steril 1994;62:1083–5.[Medline]

10. Geiffenstuhl G. Practical pelvic anatomy for the gynecologic surgeon. In: Nichols DH, ed. Gynecologic and obstetric surgery. St.Louis, Missouri: Mosby Yearbook, Inc., 1993:26–71.

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