Abstract
Abstract
Introduction
Materials and Methods
Seventy-two women with abnormal Papanicolaou smears, who were referred to the colposcopy clinic at Khon Kaen Hospital. Muang, Khon Kaen, Thailand, between June and August 2009, and who needed LEEP for tissue diagnosis, were recruited after ethics committee approval and individual written informed consents were obtained. Women who had the following conditions were excluded from the study: pregnancy; previous hysterectomy; clinical cervical infection or inflammation; allergy to anesthetics; having taken any analgesics in the previous 24 hours; currently taking psychotropic drugs or anticoagulants; and having a history of bleeding disorders. The women were randomly assigned into two groups using a computer-generated randomization method. Sequentially opaque, sealed envelopes containing the treatment allocation were prepared and opened by the operator. Group 1 was assigned to receive Xylocaine spray (5 puffs applied onto the cervix), and group 2 received 2 mL of 1% Xylocaine injected at the 3, 6, 9, and 12 o'clock positions on the cervix, at a 2-cm depth from the superficial layer of the cervix, using a dental syringe with a 27-gauge needle. LEEP was performed 2 minutes after the anesthetic drug was given. Procedure time was recorded from the beginning of LEEP until procedure finished.
Outcome measures
The primary outcome was pain score measured by patients using a 10-cm long, unmarked continuous horizontal line as a visual analogue scale (VAS) for three different timepoints (speculum placement, during LEEP, and 15 minutes after LEEP). Patients were informed that the far left point represented “no pain” and the far right point represented “unbearable pain.” Then, they were asked to mark the vertical line across the VAS three times to determine their pain levels. The secondary outcomes were adverse effects and additional drug requirement, as assessed by a nurse who was not involved in the previous procedures and was thus blinded to which patient received which intervention. Adverse effects were evaluated after anesthetic application until 30 minutes after LEEP. Patients were asked if they had any symptoms—such as dizziness or nausea and/or vomiting and stinging, or a cold sensation—after drug administration. The answers were classified into “yes” and “no,” and, if the answer was “yes,” daily life activity disturbance was asked about. Blood pressure (BP) and pulse rate were recorded before, during, and after the procedure. A vagovagal reaction was defined as bradycardia (heart rate [HR]<60 beats per minute [bpm]) or hypotension (a reduction in BP>20%, compared with baseline) associated with one or more of the following symptoms: dizziness; faintness; sweating; nausea; or vomiting. Patients' requirements for postoperative analgesia were recorded as “yes” or “no.” If “yes” was chosen, type of analgesics and doses were specified.
Statistical analysis
The sample size calculation revealed that 35 participants in each group would be adequate to detect the difference between the study arms with a significance of p<0.05, at the power of 80%. A χ2 test was used for categorical data and a Student's t-test was used for continuous data and these were presented as means and standard deviations (SDs). In cases of skewed data and large SDs, a nonparametric test was used and this was expressed by median and interquartile ranges (IQRs). It was reasoned that a difference of 2 points on the 10-point pain scale (VAS) would be clinically meaningful. Statistical analysis was performed with SPSS version 16.0 (SPSS Inc, Chicago, IL).
Results
Seventy-five eligible women were enrolled to the study. Three were excluded because 1 was pregnant and 2 were taking anticoagulants. The remaining 72 women were randomly assigned into two groups, cervical spray and intracervical injection. The patients' baseline characteristics, regarding age, menopausal status, and loop size, were not different between the groups, except for parity. There were only 4 nulliparous women in the cervical-spray group and procedure time was shorter than for the intracervical-injection group, with statistical significance (Table 1). The mean age was 42.2±11.5 years. Sixty-eight of 72 (94.4%) women were multiparous. Eighty-one percent (50/72) were premenopausal. The average procedure time was 7.9±3.4 minutes. There were no adverse outcomes during the study, and no one had allergic reactions to the anesthetic drugs. The primary outcome was pain score, which was assessed at three timepoints(speculum placement, during LEEP, and 15 minutes after LEEP). Pain assessment was performed using a VAS at the three time points. There was no significant difference in median pain score at speculum placement; median pain scores were 1.2 (0.5–3.6) and 0.7 (0.2–1.5) in the cervical-spray and intracervical-injection groups, respectively (p>0.05). Median pain scores during LEEP were 5.1 (2.2–8.2) in the cervical-spray group and 1.8 (0.4–5.7) in the intracervical-injection group (p<0.05). At 15 minutes after LEEP, median pain scores were 0.9 (0.3–2.3) and 0.3 (0.1–1.0) in the cervical-spray and intracervical-injection groups, with a significant difference (p<0.05; Table 2). There was no significant different in pain perception between pre- and postmenopausal women at the three timepoints (Table 3). BP and pulse rate recorded before, during, and after the procedure showed that BP at the three different periods was indistinguishable in the two groups, except that pulse rate during LEEP was significantly increased in the intracervical-injection group (p<0.05) (Table 4). There were no serious adverse effects observed; only 4 women in the intracervical-injection group had nausea, vomiting, and dizziness. No additional analgesic drugs were requested.
SD, standard deviation.
IQR, interquartile range; LEEP, loop electrosurgical excision procedure.
LEEP, loop electrosurgical excision procedure.
BP, blood pressure; bpm; beats per minute; LEEP, loop electrocergical excision procedure.
Discussion
At present, there is no standard method of anesthesia for pain relief during LEEP. Most colposcopists prefer intracervical or paracervical lidocaine injection, but its effectiveness is still unclear. After an extensive review of the literature, no prior study was found that compared the effectiveness of pain relief via intracervical lidocaine injection or cervical spray. Sopracordevole et al. 8 conducted RCTs comparing the effectiveness of pain reduction via lidocaine injection and no anesthesia. Oyama et al. 9 compared the effectiveness of Xylocaine spray and placebo, and found that both forms of Xylocaine reduced pain during cervical biopsy or LEEP better than placebo or no anesthesia. The current study found that intracervical injection was statistically significantly more effective for pain reduction during LEEP than cervical spray (5.1 [2.2–8.2] and 1.8 [0.4–5.7], p<0.05). Effectiveness of pain reduction at 15 minutes after LEEP was also significantly greater with intracervical injection than with cervical spray. Intracervical injection can provide more adequate pain reduction, which might be the result of its having more effective absorption than spray. The effectiveness of a cervical spray might be limited to the superficial layer and not be enough to reduce pain in cases of deep cutting. However, the limitation of intracervical injection is bleeding from the puncture sites, which could obscure lesions and prolong procedure time. The results of the current study showed that procedure time in the cervical-spray group was statistically significantly shorter than for the intracervical-injection group. Ferber et al. 10 observed that the level of pain and anxiety expected to be present during the procedure was higher than the actual level of pain and anxiety experienced. Cardiovascular effects of anesthetic agents were recorded before, during, and 15 minutes after LEEP, and it was found that pulse rate during LEEP in the intracervical-injection group was significantly increased. This finding might have occured because of pain and anxiety during injection. No additional drugs were requested during or after the procedure. LEEP itself was mostly performed in not longer than 10 seconds, during electrical loop cutting through the cervical tissue. Therefore, the patients were unlikely to request more analgesia. However, it was also found that even 15 minutes after LEEP, no additional drugs were requested. Adverse effects of Xylocaine injection were blurred vision, dizziness, tinnitus, hypotension, bradycardia, nausea, and/or vomiting. Although several of the adverse effects described could be found after administration of Xylocaine injection, no serious adverse effect was observed in this study. It is possible that the minimal effective volume of Xylocaine was not exceeded. Adverse effects of Xylocaine spray include stinging and a cold sensation. This agent also had less systemic absorption, therefore adverse effects were not observed in the group who received the cervical spray. Known prognostic factors were taken into account, such as age, parity, menstrual status, procedure time, and loop size. Church et al. 6 found that older age correlated with less pain on biopsy but not on speculum placement and also revealed that, for every 10-year increase of age, pain perception decreased 0.75 on a 10-point VAS. There were only 4 women who were nulliparous, and all of them were in the cervical-spray group. Based on the data from the current study, most of the women who had a abnormal Papanicolaou smear swere multiparous women; the ratio between nulliparous and multiparous women was 1:5. As a result, it was difficult to define the correlation between parity and pain level because stratification by parity had not been planned before collecting the data. Wire loops are of different sizes, varying from 8 mm to 25 mm. Each size reaches different cervical tissue depths and widths. However, pain is a complex sensation that is difficult to measure and compare among individuals. Degree of pain is not directly related to the extent of tissue damage. Theoretically, menstrual status plays the important role in pain perception, because vaginal elasticity in menopausal women usually decreases and dry mucosa could affect pain perception, especially during speculum placement. However, the current study showed no significant difference in pain perception between pre- and postmenopausal women at any of three timepoints. Procedure time was significantly longer in the intracervical-injection group than in the cervical-spray group. This longer time might have been caused by bleeding at the injection sites, which could have obscured lesions and might have caused multiple cutting and prolonged the hemostatic procedure. Nonetheless, when the pain perception between shorter and longer procedure time was compared, no significant difference was found. Despite several reasons that have an impact on pain perception, the current study found no significant difference in correlation between those factors and pain perception. Other factors—such as anxiety, history of menstrual cramping, presence of a supportive person, and physician's performance—which could play important roles in pain perception, were not evaluated, but these are difficult to evaluate and interpret. It is possible that the sample size was not big enough to explore the correlation between these factors and pain levels, or there were other factors that affected pain levels with significant differences.
Conclusions
Intracervical injection significantly reduced pain during and 15 minutes after LEEP more than cervical spray did, without serious adverse effects. This study suggests that intracervical injection should be administered to all patients who need LEEP, particularly in cases of deep cutting, and that cervical spray should be provided for biopsy or shallow cutting.
Footnotes
Acknowledgments
The authors thank all of nurses and nurses aides at the gynecologic outpatient department for their assistance, and the head of department of obstetrics and gynecology at Khon Kaen Hospital, for giving her permission to conduct this study.
Author Disclosure Statement
No competing financial interests exist.