First-trimester abortions in the United States are routinely performed under local anesthesia because the use of general anesthesia increases morbidity and mortality.1 Paracervical block is the most common anesthetic technique used for women undergoing first-trimester abortions. Local anesthesia (paracervical block), however, does not provide complete pain relief.2–4 In fact, 97% of women undergoing abortions with only local anesthesia reported pain.5 Paracervical blocks do not appear to completely anesthetize the uterus. Many clinicians use adjunctive medications to improve patient pain control, including oral and intravenous narcotics, anti-inflammatory medication, and anxiolytics. It is unclear, however, whether these supplemental medications decrease patient discomfort.6
Recent studies have investigated the use of local anesthetics (ie, lidocaine, mepivacaine) to lessen the pain experienced with minor gynecologic procedures, that is, endometrial biopsy and office hysteroscopy.7–9 Local anesthetic injected into the uterine cavity has been demonstrated as effective in decreasing patient pain associated with these intrauterine procedures. Based on this evidence, we hypothesized that intrauterine lidocaine infusion may reduce patient pain during first-trimester abortions.
For a normal healthy adult, the maximum dose of lidocaine without epinephrine should not exceed 4.5 mg/kg or a total maximum dose not to exceed 300 mg.10 The rate and amount of lidocaine absorption is dependent on the route of administration. The absorptive capacity of a pregnant uterus is unknown. Therefore, a secondary goal of this study was to document lidocaine serum levels after intrauterine infusion to obtain information regarding intrauterine absorption.
MATERIALS AND METHODS
A randomized, double-blind, placebo-controlled trial was conducted at Planned Parenthood of the Columbia Willamette in Portland, Oregon, from July 2002 to February 2003. The Institutional Review Board at Oregon Health & Sciences University and The Planned Parenthood of the Columbia Willamette Research Oversight Committee approved the study protocol.
Women requesting termination of pregnancy at less than 11 weeks from the first day of the last menstrual period were recruited only after their decision to proceed with an abortion was confirmed. All women who met the following criteria were invited to participate: aged more than 18 years, good general health, English speaking, confirmation of gestational age by ultrasonography, and body weight more than 100 lbs. The weight limit was based on manufacturer maximum dosing recommendations of 2 mg/kg.10 Study participants had the potential to receive a total of 200 mg of lidocaine with the administration of 10 mL of 1% lidocaine in both the paracervical block and the intrauterine infusion (the maximum dose for a 100-lb person). Approximately 20–30 minutes before the procedure, patients were premedicated with 800 mg of ibuprofen and, if requested, 5 mg of valium. Exclusion criteria included subject refusal or inability to receive ibuprofen and/or paracervical blocks or request for intravenous narcotics.
Preprocedure counseling and evaluation were consistent with clinic protocols. Participants completed a demographics form before their procedure.
Subjects were randomly assigned to receive either a 10-mL 1% lidocaine infusion or 10-mL sterile saline infusion. An investigator not involved with recruitment generated a block randomization sequence by computer (block size = 20). Only this investigator, the study coordinator, and the study nurse had knowledge of the block size and randomization sequence. The study coordinator and nurse prepared all patient data sheets and study syringes without the knowledge of the investigator enrolling patients. No difference in appearance existed between the 2 study solutions. The syringes and patient data sheets were labeled with, and subjects enrolled by, consecutive numbers. No identifiers of treatment group were placed on patient data sheets or syringes, only the number in order of enrollment (ie, 1, 2, 3, 4).
Two experienced investigators performed all abortions in this study with an electric vacuum pump device using rigid curved cannulas. After speculum placement, all subjects underwent paracervical block through injection of 1 mL of 1% nonbuffered lidocaine on the anterior or posterior lip of the cervix and then 4.5 mL of 1% lidocaine at the 4- and 8-o'clock positions (a total 10 mL of lidocaine). After this, a 3-mm Novak curette was passed through the cervix into the miduterine cavity, and an intrauterine infusion of study solution (either 10 mL of 1% lidocaine or sterile saline) was administered and the curette was held in place for 3 minutes. After this, cervical dilation and suction aspiration took place. The amount of cervical dilation and canula diameter size in millimeters was equal to or 1 mm less than the estimated gestational age in weeks. Subjects rated their pain using a 100-mm visual analogue scale (anchors: 0 = none, 100 mm = worst imaginable) at several time points: 1) before the procedure started (anticipatory pain or “How much pain do you expect with today's procedure?”); 2) after the insertion of the speculum; 3) after the intrauterine infusion: 4) after cervical dilation; 5) after suction aspiration; and 6) 30 minutes later in the recovery room. Before discharge from the clinic subjects also reported their overall satisfaction level regarding their abortion experience using the visual analogue scale. To provide independent answers, subjects were unable to access their prior responses.
To obtain information on intrauterine absorption, serum lidocaine levels were drawn in a subset of subjects. All participants in the main study were asked to volunteer for a series of blood samples, and recruitment in the substudy continued until a total of 20 subjects (10 saline, 10 lidocaine) was enrolled. An indwelling intravenous line was placed before the procedure, and serum levels were drawn at 10, 20, 30, 45, and 60 minutes. Samples were frozen until serum from all 20 participants had been collected. Results were kept from the study investigators until the completion of the study. The protocol also stipulated that lidocaine levels would be drawn in any subject who displayed clinical evidence of lidocaine toxicity (overt confusion, loss of consciousness, cardiac arrest, or seizures). The abortion provider was responsible for recording acute complications from the procedure. Any delayed complications were noted by nurse practitioners at the patient's 2-week follow-up visit (by phone or clinic appointment).
The sociodemographic profiles of the 2 study groups were compared by using descriptive statistics (χ2 for nominal data and t tests for continuous data). A t test was used to compare the mean magnitude of pain at each of the 4 time points between the 2 study groups. Each time point was compared with its corresponding anticipatory pain score by using a Pearson correlation coefficient. The lidocaine levels at 10, 20, 30, 45, and 60 minutes were plotted to determine normality. All statistical tests were conducted by using 2-tailed P values of .05. All analysis was done based on intent to treat.
Sample size was determined under the assumption that a 15-mm difference in visual analogue scores would have clinical relevance. The standard deviation of 23 mm was derived from prior work at our institution.11 For the primary outcome of patient pain ratings (100-mm visual analogue scale) after aspiration with and without intrauterine lidocaine infusion, the study had an 80% power at an α of .05 to identify a 15-mm difference. This translated to a sample size of 40 in each study group. Statistical analyses were performed by using the Statistical Program for Social Sciences (SPSS for Windows; SPSS Inc, Chicago, IL).
Eighty women were recruited (40 saline, 40 lidocaine), and 20 women volunteered for serial serum lidocaine levels (10 saline, 10 lidocaine). One protocol violation occurred in the lidocaine group with the inadvertent enrollment of a patient who was not premedicated with ibuprofen. In addition, 1 patient from the lidocaine group received intravenous narcotics for an immediate reaspiration under ultrasound guidance for an early gestation. Her pain scales were completed during the initial procedure, but her 30-minute visual analogue scale was conducted after her reaspiration. Both subjects completed the study, and their information was analyzed in accordance with intent to treat (Figure 1). The numbers reported in the flow diagram for “total number of patients presenting for abortions” and “ineligible patients” are close approximates obtained from Planned Parenthood of Columbia Willamette's internal computerized tracking system. Not all potentially eligible subjects received counseling regarding study participation for a variety of reasons (ie, staffing issues); therefore, the exact number of eligible patients who were offered the study but declined cannot be determined.
Demographic characteristics showed no differences between groups (Table 1). The average subject was a white female in her mid-twenties with a 7-week gestation. Approximately 70% of both groups returned for a follow-visit or made phone contact.
There were no statistically significant differences between groups in pain scores at any time point (Table 2). Mean pain scores for all time points stayed at or below 50 mm with the highest scores reported for anticipatory, cervical dilation, and aspiration pain. Patients’ anticipatory pain scores in both groups were an overestimation of pain at all time points except for aspiration.
A positive correlation was found between anticipatory and aspiration pain scores for the placebo group, Pearson correlation coefficient 0.53, P = .001. Only the placebo group had significant correlations at speculum insertion, cervical dilation, and aspiration (Table 3). Overall satisfaction rates were high in both groups (100 mm = very satisfied; saline 83 mm ± 20 and lidocaine 82 mm ± 23; P = .76).
No patient developed overt symptoms of lidocaine toxicity. Peak serum levels occurred at approximately 10 minutes after intrauterine lidocaine infusion. The maximum level demonstrated in a single patient (lidocaine group) was 2.5 μg/mL. The serum lidocaine levels were not normally distributed; therefore the natural log (ln) is illustrated in Figure 2. Of note, the laboratory does not report levels less than 1 μg/mL; any values equal to or less than 1.0 μg/mL were set to 0.99.
Adverse events were rare. Three patients were prescribed antibiotics at their follow-up visit. All 3 patients were in the lidocaine treatment arm. Two of these patients were found to have minor uterine tenderness on examination with no fevers or other signs of clinical endometritis. The third patient had a known exposure to Chlamydia after her procedure. Two patients required reaspiration for retained products; both were early gestations at 4 weeks. The immediate-reaspiration patient was in the lidocaine arm (discussed earlier in the Results section). The delayed reaspiration patient was in the placebo arm and had prolonged bleeding that did not respond to medical management (misoprostol).
Procedural pain from minor intrauterine procedures appears to arise from 2 separate anatomical structures, the cervix and the uterus. The paracervical block aids in decreasing pain from cervical origin, but the extent of its effect on pain arising from uterine activity is controversial, especially in women with significant dysmenorrhea.2–4 During first-trimester abortions, it is clinically apparent that patients seem to have the most intense pain during and immediately after aspiration. Unfortunately, the innervation of the endometrium and myometrium is poorly understood. Decreasing patient pain response may be related to decreasing uterine activity or by dampening pain fiber response. Nonsteroidal anti-inflammatory medications have been shown to decrease uterine activity by reducing circulating prostaglandins, thereby decreasing dysmenorrhea.12 Intrauterine transcutaneous electrical nerve stimulation has been shown to decrease pain of dysmenorrhea by directly altering the body's ability to perceive pain from the uterus.13 A local or topical anesthetic injected into the uterine cavity may have similar results on inhibiting nerve responses. Our results, however, do not demonstrate a reduction in the perception of patient pain associated with the use of a 1% intrauterine lidocaine infusion.
Trolice et al8 randomly assigned 57 perimenopausal and postmenopausal women to receive either intrauterine lidocaine or normal saline before having an office endometrial biopsy. Five millimeters of 2% lidocaine was infused with a 3-minute time delay before obtaining the biopsy. They found a statistically significant reduction in pain in women receiving the lidocaine infusion. In a second study, Cicinelli et al7 randomly assigned 80 women to receive 2 mL of 2% mepivacaine or normal saline with a 5-minute delay before an office hysteroscopy and/or endometrial biopsy. Results also showed a statistically significant reduction in pain by women receiving the mepivacaine infusion. Zupi et al9 repeated this study in a group of 45 women but found the reduction in pain not statistically significant. A single study of a 2-mL infusion of 2% lidocaine, in addition to oral naproxen sodium, before hysterosalpingography demonstrated no reduction of pain and the possibility of increased postprocedural pain.14
With the knowledge of these positive results, we were hopeful that this technique could reduce pain during first-trimester abortions. Although these prior studies used 2–5 mL of 2% lidocaine or mepivacaine, we chose a larger volume to fill the potential space of a pregnant uterus. Because of the safety concerns and the lack of knowledge surrounding lidocaine absorption by a pregnant uterus, a lower lidocaine concentration was used. One percent lidocaine is also readily available in outpatient settings, making the possible incorporation of this technique simple. The null results of our study, however, may be the result of using a concentration too low. The low levels of absorption demonstrated by the serum lidocaine levels in the lidocaine infusion subjects allows for the opportunity to test a higher lidocaine concentration. The volume of lidocaine appeared sufficient because no visible leakage from the cervix occurred during the instillation process. However, it is possible that tubal extravasation occurred or that the intrauterine volume was higher than expected, such that 10 mL was insufficient to cover all surfaces. To demonstrate a clinically detectible effect on procedural pain, the 3-minute infusion period may be too short. Peak levels of lidocaine were observed at 10 minutes, but to lengthen the infusion time would make this type of anesthesia less practical for most busy abortion clinics and less acceptable to patients. Another possible explanation is that intrauterine lidocaine in conjunction with paracervical block provides sufficient uterine anesthesia only for minor intrauterine exploration (like endometrial biopsy), but not suction curettage. In prior studies of intrauterine infusion for pain, there was one with negative results.14 This study, like ours, is the only study that reports premedication with a nonsteroidal anti-inflammatory agent. It may be possible that intrauterine lidocaine infusion does have a small effect but not enough to surpass that of nonsteroidal anti-inflammatories. Finally, our study investigated the effects of intrauterine lidocaine in the pregnant uterus. The physiologic changes associated with pregnancy, that is, increased uterine blood flow, may also affect the local actions of lidocaine or patient pain perception.
Our results demonstrate that measurement of anticipatory pain may be of value in future abortion studies. A significant and positive correlation for anticipated and experienced pain was found with speculum insertion, cervical dilation, and aspiration for the placebo group but not the lidocaine group (Table 3). The placebo group both anticipated and experienced higher pain levels at these time points. Although the lidocaine group had a similar level of anticipatory pain as the placebo group, the difference between each group's anticipatory pain and all subsequent time points was lower in the lidocaine group (Table 2). Although the overall visual analogue scale pain measurements (t tests) were no different between the 2 groups, these correlations may imply a subtle treatment effect. In other words, as both groups reported similar levels of anticipatory pain, we would have expected a similar positive correlation with actual pain. The lack of any positive correlation in the treatment group suggests a possible treatment effect.
But why would the placebo group have a positive correlation between anticipatory pain and speculum insertion before the initiation of the treatment? It is likely that the speculum insertion measurement is a surrogate for a patient's overall tolerance of pain and/or anxiety. Pain with speculum insertion occurs in many conditions such as dyspareunia, vulvar vestibular syndrome, and vaginismus. Women with vaginal insertional pain (vaginismus) have been shown to be psychologically different from other women.15,16 Inspection of each individual pain score for speculum insertion reveals that a value above 59 mm was an outlier. To control for possible confounding as the result of a nonequal distribution of women with insertional pain, we reanalyzed the data and excluded those subjects with speculum insertion pain greater than 59 mm (placebo = 3, lidocaine = 1). After excluding these subjects, the positive correlation with speculum insertion was eliminated in the placebo group. More importantly, the significant correlations with respect to cervical dilation and aspiration persisted, further reinforces the impression of a treatment effect.
It is not likely that ascertainment bias explains the failure to demonstrate a reduction in pain with the visual analogue scale. Ten-centimeter visual analogue scales have been used successfully in prior abortion pain studies.11,17 Visual analogue scale, the verbal 11-point box scale, and the 21-point box scale have all been shown to be effective at measuring pain for medical procedures, but the later 2 seem to be more difficult for a patient undergoing a procedure to use.18 Anxiety may be a potential confounder. An anxiety assessment tool may prove useful to control at estimation of procedural pain.19
Overall, our results demonstrate that an intrauterine infusion of 1% lidocaine before first-trimester abortion does not result in a reduction of pain during or after suction aspiration. The intrauterine infusion with paracervical block did not produce levels of lidocaine toxicity, although rare cases of toxicity would not necessarily be detected in a study with 80 women.
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