Robinson, Randal D. MD; Casablanca, Yovanni MD; Pagano, Katherine E. MD; Arthur, Nancy A. RN; Bates, G Wright MD; Propst, Anthony M. MD
The hysterosalpingogram (HSG) is an integral part of the evaluation for anatomic etiologies of female infertility. The majority of women regard a hysterosalpingogram as acutely painful since it involves placement of a cervical tenaculum, traction on the cervix, and instillation of dye through a cervical cannula. Different techniques have been used in attempts to make the procedure less painful, including use of balloon catheters rather than cannulas, but this has not been shown to be uniformly effective.1 Previous studies have shown a reduction in overall pain during HSG after premedication with oral nonsteroidal anti-inflammatory drugs.2,3 Benzocaine gel (20%) applied to the cervix has also been shown to reduce pain.2 Conversely, a study of premedication with paracetamol (acetaminophen) showed no statistical improvement in pain perception.4 Additionally, transcervical intrauterine instillation of lidocaine has been shown in randomized studies to not improve pain scores and may actually increase pain after the procedure is complete.5,6 A MEDLINE literature search of papers written in English from January 1966 to August 2005, using the keywords “hysterosalpingogram,” “analgesia,” “paracervical,” and “intracervical,” did not reveal any prior studies on the use of an intracervical block before hysterosalpingography. A paracervical block has been shown to decrease pain with therapeutic abortions, endometrial biopsy, and office hysteroscopy.7,8 We hypothesized that an intracervical block would also decrease pain during a hysterosalpingogram.
MATERIALS AND METHODS
Between July 2002 and September 2004, we performed a three-armed, randomized controlled trial comparing pain control after a 1% lidocaine intracervical block, saline injection, and no injection in patients undergoing HSG. Blinding of the physician and the subject as to whether they would receive lidocaine versus saline was performed for the injection arms of the study. Our protocol was approved by the Wilford Hall Medical Center Institutional Review Board. Experimental procedures followed the ethical standards for experimentation on humans established by the Declaration of Helsinki of 1975, revised 1983.
Subjects were recruited from the infertility clinic at Wilford Hall Medical Center, Lackland Air Force Base, located in San Antonio, Texas. The subjects were either active duty or reserve members of the armed forces or were dependants of military personnel. All patients without a known cause for their infertility who were undergoing a HSG were eligible for enrollment. Exclusion criteria included a history of any allergies to local anesthetics, radio-opaque dye, or anti-inflammatory medications. All participants were 18–40 years of age and married.
Once the patients were found to meet enrollment criteria, written informed consent was obtained. The women were then randomized by permuted block randomization using a random number table to one of the three groups. Sequentially numbered, opaque sealed envelopes were used to assign patients to receive either the intracervical block with 1% lidocaine, saline injection, or no injection. These envelopes were opened and viewed by the pharmacist preparing the medication, and the specific injection arms of the assignments were not available to the provider performing the HSG or to the patients. Unblinding of the injection arms of the study was not completed until the time of data analysis. Subjects were not given prophylactic antibiotics before the procedure. All subjects were instructed to take 800 mg of ibuprofen 30 minutes before the procedure, and compliance was confirmed with all subjects before beginning the study. The intracervical block with lidocaine or saline was then performed, and 5 minutes were allowed to elapse before proceeding. The cervix was then grasped at the anterior aspect with a single toothed tenaculum, and an acorn cannula was then advanced into the external cervical os. The cannula and tenaculum were secured together, and the speculum was removed. Traction was placed on the tenaculum, and dye was instilled via the cannula while the necessary images were obtained. The cannula and tenaculum were then removed.
The study group received a total of 60 mg (6 mL) of 1% lidocaine injected at six points (12, 2, 4, 6, 8, and 10 o'clock) circumferentially into the cervix (1 mL at each point) before proceeding with the hysterosalpingogram. The six points were standardized and illustrated on a diagram available in the radiology suite. The second group received a total of 6 mL of sterile saline injection at the same points. This group served as the control for the placebo effect, as well as for determining whether the increased hydrostatic pressure from the injection within the stroma of the cervix had an effect on pain scores. The third group served as a control and had the procedure performed without injection. If at any point the patient was unable to continue with the HSG, the procedure was terminated.
Each patient was asked by the radiology technician to rate her pain in writing using the visual analog scale (VAS) and the verbal descriptive score at six time periods during the procedure: before beginning the procedure, with placement of the last intracervical injection or speculum placement (whichever was applicable), after the placement of the cervical tenaculum, after counter traction on the tenaculum, with instillation of the dye, and 1 minute after the HSG was completed and the cannula and tenaculum were removed. We also used a five-category verbal descriptive score with the following options for pain description: none, mild, moderate, severe, or unbearable to qualitatively assess pain severity at the same time points that the VAS was obtained.
The primary end point was differences among the three groups in pain scores using the VAS and verbal descriptive score. In addition, results of the HSG were also collected to include presence of cervical stenosis, intracavitary filling defects, hydrosalpinx, and patency of fallopian tubes. This allowed for a subgroup analysis to evaluate whether particular pathology had an effect on pain scores.
The minimum difference in VAS pain scores required to signify clinical importance is estimated to be 9–18 mm, depending on type and location of pain assessed.9–11 Our sample size calculation revealed that 40 subjects in each arm would be adequate to detect a 10-mm difference between arms at a significance of P<.05 and at a power of 90%. Thus, at least 120 subjects were required for sample size to be adequate. A total of 124 women were enrolled to achieve this because four women disenrolled from the study before having their HSG performed, but after randomization had occurred. Data were analyzed as intention to treat for each woman who underwent the HSG. Demographic characteristics were explored using parametric and nonparametric techniques to show baseline comparability among groups. An analysis of variance (ANOVA) was used to estimate whether there was a difference of pain between the three groups. Post hoc procedures for the ANOVA were accomplished using the Tukey honest significant difference test. Median values in Table 1 were compared using Kruskal-Wallis ANOVA, and categorical values were compared using χ2 tests or Fisher exact test, where appropriate. Analysis of variance was used to compare mean ages. Continuous data were expressed as means±standard deviations. Repeated measures analysis of variance was used to estimate the differences in pain perception as measured by the VAS among the three groups and across time. In addition, single-factor ANOVAs were calculated for the individual time points with a Bonferroni correction. Post hoc analyses were accomplished using the Tukey honest significant difference test. Kruskal-Wallis ANOVA on ranks was used to evaluate the verbal descriptive score data with a Bonferroni correction for multiple comparisons. The significance value after applying the Bonferroni correction was set at 0.05/12 or P<.004. Statistical analyses were performed with SPSS 13 (SPSS Inc, Chicago, IL).
Complete pain scores were collected from 116 participants. Four subjects were missing data points for a few of the times assessed. One patient in the saline group missed the verbal descriptive score for time points 3, 5, and 6 and VAS for time points 5 and 6. One patient in the control group missed one verbal descriptive score at time point 3, one patient missed VAS and verbal descriptive score for time point 6, and one patient missed data collection for time points 5 and 6 for VAS and verbal descriptive score. All subjects who were randomized and underwent the HSG and who recorded any pain scores were included as intention to treat for purposes of statistical analysis of the data points that were available.
Demographic data on age, ethnicity, smoking status, gravidity, parity, history of bilateral tubal ligation, and results of the hysterosalpingogram are presented in Table 1 and were statistically similar in all the groups. The ethnicity within all groups was predominantly white, which is representative of our baseline population. The mean age of study subjects was 31 years. There were no adverse outcomes during the study, and no patient had an allergic reaction to the dye media or injected medications. There were no cases of cervicitis, endometritis, or pelvic inflammatory disease in the study participants.
The qualitative pain assessments (verbal descriptive score) found equivalent results to those seen with the VAS among the three groups. Statistically significant differences in mean pain scores using the VAS were also statistically significant using the median pain scores of the verbal descriptive score for each arm of the study and for each time point that was statistically significant for the VAS (Tables 2 and 3). Baseline pain assessment was equal in all three groups using both the VAS and verbal descriptive score (Tables 2 and 3). The intracervical saline injection resulted in a statistically significant increased mean pain score for women in this group, using the VAS, when compared with subjects in the noninjection, control group and those who underwent lidocaine injection (2.647 cm versus 1.232 cm and 1.476 cm, respectively; P<.001). The difference was also significant when median verbal descriptive score scores were compared (Table 3; 2 versus 1 versus 2, P<.001). Using the VAS, the pain scores with intracervical injection in the lidocaine and noninjection control groups were statistically similar.
After placement of the tenaculum, the control group and the saline group had similarly heightened mean pain scores using VAS (3.354 cm and 3.384 cm, respectively). Both were significantly higher than those in the lidocaine arm (1.303 cm, 61% less compared with both the saline injection group and the noninjection control group, P<.001). Using the verbal descriptive score, the lidocaine group also showed a statistically lower pain score than both the saline and control groups (1 versus 3 and 2, P<.001). Of note, the pain scores in the lidocaine group did not worsen with tenaculum placement (VAS: 1.476 prior, 1.303 after; verbal descriptive score: 2 prior, 1 after).
Upon traction of the cervix with the tenaculum, pain scores increased in all three groups, but the lidocaine group remained at a statistically lower level (approximately 40% less for the VAS) than both the saline and control groups on both scales (VAS: 2.804 cm versus 4.705 cm and 4.961 cm, P<.001; verbal descriptive score: 2 versus 3 and 3, P<.001). Pain scores were statistically similar in the saline and control groups.
With instillation of the dye, pain increased again in all subjects. There was no statistically significant improvement in pain perception during instillation of the contrast in the lidocaine group compared with the saline group or control group (VAS 4.158 versus 5.437 saline and 5.229 control, P=.073; verbal descriptive score: 3 versus 3 saline and 3 control, P=.221). After the procedure was complete, all groups had similar pain scores (VAS: 2.849 lidocaine, 2.658 saline, 3.312 control; verbal descriptive score: 2 lidocaine, 2 saline, 2 control, P=.433). In all groups, pain scores were increased when compared with those before the procedure. In a subgroup analysis of those with filling defects, hydrosalpinx, and nonpatent tubes, there was not a significant difference in pain scores at any points (data not shown).
This study illustrates that pain with tenaculum placement and cervical traction is significantly reduced with a lidocaine intracervical block in women undergoing a hysterosalpingogram. The acute discomfort from the injection is short-lived, because pain scores after the lidocaine injection are similar to those of patients who received no injection. The intracervical injection without local anesthetic resulted in statistically greater pain scores than with either no injection or injection with local anesthetic. The inclusion of this third arm of saline injection helped to control for the placebo affect of the injection itself and proved the value of an intracervical block with lidocaine. Also, it does not appear that lidocaine intracervical injection increases pain after completing the HSG as previously seen in studies of intrauterine instillation of lidocaine.5 The data were not powered to make significant conclusions on pain and anatomic pathology seen on HSG, but in our data there was no correlation.
The VAS has been shown in multiple studies to be a reliable method of assessing pain.12,13 It is easy to use, and allows data to be analyzed in a continuous fashion: from 0–10 cm on a linear scale. The significance of differences assessed with the VAS is also maintained regardless of the severity of the pain.14 It has also been shown to correlate well with categorical scales, such as the verbal descriptive score, which allows for estimation of severity of pain as mild, moderate, or severe and may better illustrate clinical significance of results.15
Our study did not find an increased risk of infection with the intracervical injection, although the small number of patients undergoing injection in this study is not enough to confirm the safety of the injection. However, our lack of complications suggests that this is the case.
Drawbacks to performing intracervical blocks are that the administration of a lidocaine block does require knowledge of cervical anatomy and proper injection technique. Radiologists who perform a large number of hysterosalpingograms in the United States might need additional training to become proficient with performing intracervical blocks, but this is a commonly performed procedure for gynecologists. In addition, the risk of allergic reaction to the local anesthesia is assumed when lidocaine block is offered despite the fact that none of the patients in our study experienced this complication. The injection does require an additional 5–10 minutes to perform and to allow the block to be effective, and this would increase the time required to perform the procedure. Finally, the addition of intracervical block would slightly increase the cost of the HSG because of the use of an additional syringe, spinal needle, and local anesthetic, as well as the time required to perform the procedure.
Hysterosalpingography is an established procedure for infertility evaluations and is commonly performed before receiving fertility treatment. It is openly regarded as a painful procedure and thus causes anxiety and fear for many patients undergoing these studies. These results show promise that lidocaine intracervical block can be used to make the overall experience of a hysterosalpingogram less painful. However, an intracervical block did not decrease pain perception during the most painful component of the HSG, which is the instillation of contrast into the uterus. A method that will significantly decrease pain for this portion of the procedure is still needed. This study suggests that an intracervical block should be offered, in conjunction with premedication with nonsteroidal anti-inflammatory drugs, to all patients undergoing HSG.
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