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ORIGINAL RESEARCH |
From the Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, Oregon.
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ABSTRACT |
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 ABSTRACT MATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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METHODS: A randomized, double-blind, placebo-controlled trial of 80 women receiving either a 5-mL 4% lidocaine (n = 40) or saline (n = 40) intrauterine infusion and a standard paracervical block before first-trimester abortion. Women completed a series of 100-mm visual analog scales (anchors: 0 = none, 100 mm = worst imaginable) to measure their perceived pain (anticipated pain, after speculum insertion, after intrauterine infusion, after cervical dilation, after suction aspiration, and 30 minutes postprocedure). Eight women volunteered for serum lidocaine levels after the lidocaine infusion.
RESULTS: Groups were similar in respect to age, parity, prior abortion, ethnicity, gestational age, and level of dysmenorrhea. Pain scores demonstrated a significant difference between groups during cervical dilation (saline 55 mm ± 26, lidocaine 35 mm ± 30, P < .01) and during aspiration (saline 71 mm ± 20, lidocaine 43 mm ± 30, P < .01). The lidocaine group reported significantly more symptoms (ie, oral numbness and tingling) than the saline group (saline 0/39, lidocaine 16/38, 42%, P < .01). The highest serum lidocaine level recorded was 4.0 µg/mL (lidocaine group). There was no difference in overall satisfaction between the 2 groups.
CONCLUSION: Compared with paracervical block alone, the addition of a 4% intrauterine lidocaine infusion resulted in a significant reduction in patient perception of pain during first-trimester abortion. Although subjective symptoms of systemic lidocaine effect were common, no subjects demonstrated serum levels consistent with lidocaine toxicity. However, further studies to determine safety are needed.
LEVEL OF EVIDENCE: I
Based on this evidence, we hypothesized that an intrauterine lidocaine infusion may reduce patient pain during first-trimester abortions. Because of the safety concerns and the lack of knowledge surrounding lidocaine absorption by a pregnant uterus, we used a lower concentration of lidocaine (1%) than these prior studies for our initial investigation.4 A 1% intrauterine lidocaine infusion demonstrated no improvement in patient pain. However, toxicity was not observed, and a small sampling of serum lidocaine levels showed values well below the toxicity range.
Given that the results observed with a 1% lidocaine infusion in a pregnant uterus were inconsistent with the effect observed in studies using higher concentrations of lidocaine in a nonpregnant uterus, further investigations were initiated. Lack of an effect on pain relief may have been due to insufficient absorption, a larger drug distribution area secondary to a larger pregnant uterus, and/or simply a need for a higher lidocaine concentration. The absence of significant adverse effects and safe serum levels observed in our previous study indicated the feasibility of increasing the lidocaine concentration. Because a 2% lidocaine infusion had had inconsistent results in prior studies, the decision was made to increase the concentration to 4% rather than 2%, but to reduce the volume to 5 mL to keep the total amount of lidocaine similar to 10 mL of 2% lidocaine.3,5 Therefore, the present study was designed to test the hypothesis that intrauterine administration of a more concentrated 4% lidocaine solution may reduce patient pain during first-trimester abortions.
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MATERIALS AND METHODS |
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ABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Women requesting termination of pregnancy at less than 11 weeks from the first day of the last menstrual period and confirmed by vaginal probe ultrasound examination were recruited only after a decision to proceed with an abortion had been made. All women who met the following criteria were invited to participate: age more than 18 years, good general health, English speaking, confirmation of gestational age by ultrasound examination, and body weight more than 100 lbs (approximately 45 kg). The lidocaine dose was based on the manufacturer maximum dosing recommendation that a total maximal lidocaine dose in an adult should not exceed 300 mg.6 Study participants received a total of 300 mg of lidocaine with the administration of 5 mL of 4% lidocaine in the intrauterine infusion and 10 mL of 1% lidocaine in the paracervical block. Approximately 20–30 minutes before the procedure, subjects were premedicated with 800 mg of ibuprofen and, if requested, 5 mg of diazepam. 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 the procedure.
Subjects were randomized to receive either a 5-mL 4% lidocaine infusion or a 5-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 subject data sheets and study syringes without the knowledge of the investigator enrolling subjects. No difference in appearance existed between the 2 study solutions. The syringes and subject data sheets were labeled with, and subjects enrolled by, consecutive numbers. No identifiers of treatment group were placed on subject data sheets or syringes, only the number in order of enrollment.
Five experienced surgeons 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 4 and 8 o’clock, with a depth of injection of approximately 1.5 inches (a total 10 mL of lidocaine). After this, a 3-mm Novak curette was passed through the cervix into the mid-uterine cavity, and an intrauterine infusion of study solution (either 5 mL of 4% lidocaine or sterile saline) was rapidly administered and the curette held in place for 3 minutes. Next, 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 analog scale (VAS; 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) following speculum insertion; 3) after the intrauterine infusion: 4) following cervical dilation; 5) after suction aspiration; and 6) 30 minutes later in the recovery room. Before discharge from the clinic, each subject also reported her overall satisfaction level regarding her abortion experience using the VAS. Subjects performed all VAS scales concurrently with each step and not from memory.
To obtain safety data, 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 8 subjects (4 saline, 4 lidocaine) were enrolled. An indwelling intravenous line was placed before the procedure, and serum levels were drawn at 10, 20, and 30 minutes (time-point zero was defined as the start of the intrauterine infusion). The first sample was drawn at 10 minutes so as not to interfere with the procedure, and Blanco et al7 demonstrated that lidocaine levels after a 20-mL paracervical block peak at 10 minutes. Samples were frozen at –70°F until serum from all 8 participants had been collected (4 months). Lidocaine levels remain stable when frozen.8 The protocol also stipulated that lidocaine levels would be drawn and immediately analyzed 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 and reporting to the study’s safety monitoring committee. Any delayed complications were noted by nurse practitioners at the subject’s 2-week follow-up visit (by phone or clinic appointment).
The sociodemographic profiles of the 2 study groups were compared using descriptive statistics (
2 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, and 30 minutes were plotted to determine peak levels. All statistical tests were conducted 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 VAS scores would have clinical relevance. The standard deviation (SD) of 23 mm was derived from prior work at our institution.9 For the primary outcome of patient pain ratings (100 mm VAS) after aspiration with and without intrauterine lidocaine infusion, the study had an 80% power at an alpha of 0.05 to identify a 15-mm difference. This translated to a sample size of 40 in each study group. Statistical analyses were performed with SPSS 10.0 for Windows (SPSS Inc, Chicago, IL).
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RESULTS |
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The numbers reported in the flow diagram for total number of subjects presenting for abortions and ineligible subjects are close approximates obtained from Planned Parenthood of the Columbia Willamette’s internal computerized tracking system (Fig. 1). 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.
An interim analysis was performed after enrolling 37 women (18 saline, 19 lidocaine) because of concerns of potential lidocaine toxicity after symptoms of lidocaine effects were reported in several subjects. Although investigators orally reported that other women experienced minor symptoms typical of those seen with a paracervical block, these subjects were noted to have more severe responses (ie, numbness, tingling, ear ringing, confusion, anxiety) but no evidence of seizures or loss of consciousness. The study’s safety monitoring committee broke the randomization code without revealing the code to the investigators involved in enrollment and found that these women had received intrauterine lidocaine infusions. Investigators were able to complete the abortion procedure in all cases, and all women had uneventful recoveries. No subjects required any additional drug treatments, and none were hospitalized. As per protocol, serum samples were obtained from 3 women with more overt symptoms (all 3 from the lidocaine infusion group) and from 8 women prospectively agreeing to such analyses. None of the samples from either group revealed lidocaine levels in the range of toxicity (Fig. 2). The safety monitoring committee recommended several minor protocol changes to reduce the likelihood of an adverse event, including diazepam for all subjects to raise the seizure threshold, slowing intrauterine instillation over the entire 3 minutes rather than rapid instillation, and asking subjects to report symptoms (Did you experience ear ringing, mouth or tongue numbness, tingling, or other unusual sensations during the infusion?). Enrollment was temporarily suspended (March 2004 to June 2004) until the institutional review board reviewed and approved continuation of the study with the above proposed protocol changes. Additionally in July 2004, Planned Parenthood of the Columbia Willamette clinics converted to a problem-based postabortion follow-up visit instead of a routine postabortion visit.
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Analysis of demographic characteristics revealed no difference between groups (Table 1). The average subject was a white female in her mid-twenties with an 8-week gestation. The percentage of subjects returning for a follow-up visit was the same before and after the Planned Parenthood of the Columbia Willamette protocol change.
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Pain scores by VAS demonstrated a significant difference between groups during cervical dilation (saline 55 mm ± 26, lidocaine 35 mm ± 30, P < .01) and during aspiration (saline 71 mm ± 20, lidocaine 43 mm ± 30, P < .01) (Table 2).
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Overall satisfaction rates were high in both groups (100 mm = very satisfied; saline 80 mm ± 23 and lidocaine 85 mm ± 19, P = .31). Overall satisfaction did not differ and remained high in women who reported lidocaine-related symptoms compared with those who did not (lidocaine symptoms 79 ± 24 and no symptoms 83 ± 20).
No subject developed overt symptoms of severe lidocaine toxicity (ie, seizures, cardiac arrest, loss of consciousness) but lidocaine subjects did report more symptoms, including ear ringing, perioral numbness, and tingling (Table 3). Eight volunteers (4 saline, 4 lidocaine) received lidocaine levels, and an additional 3 subjects received levels secondary to clinical concern regarding reported symptoms. The 3 lidocaine subjects who reported more severe symptoms on average had slightly higher, but not statistically significantly higher, lidocaine levels at all time points than did lidocaine subjects voluntarily having lidocaine levels drawn (10 minutes: 2.7 [SD 1.6] versus 1.2 [SD 0.4]; 20 minutes: 2.0 [SD 1.1] versus 1.1 [SD 0.3]; 30 minutes: 2.0 [SD 0.8] versus 1.0 [0.4]). Overall, peak serum levels were observed at the 10-minute sample after intrauterine lidocaine infusion (Fig. 2). The maximum level demonstrated in a single subject (lidocaine group) was 4.0 µg/mL. In 3 subjects, one blood draw each was missed because of technical difficulties at 10 (saline), 20 (saline), and 30 (lidocaine) minutes.
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Other adverse events were rare. Two saline subjects were prescribed antibiotics at their follow-up visit. Both subjects were found to have minor uterine tenderness on examination, with no fevers or other signs of clinical endometritis. Two subjects between 8 and 9 weeks of gestation (one in each study arm) required immediate reaspiration for retained products.
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DISCUSSION |
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ABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Intrauterine lidocaine infusions have been proven in several studies to decrease pain in other minor gynecological procedures, including endometrial biopsy and office hysteroscopy.1–3,13,14 However, other reports,5,15 including a prior study of ours,4 find no difference in pain with an intrauterine lidocaine infusion for hysterosalpingography and first-trimester suction aspiration. The differences in results may be due to the type of procedure and/or the amount and concentration of local anesthesia. The null results of our prior study appear to be secondary to a lidocaine concentration that was too low because the infusion technique and type of procedure were similar between the 2 studies.
The intrauterine infusion with paracervical block did not produce symptoms of severe lidocaine toxicity (ie, seizures, coma, death) in our small sample, although rare cases of toxicity would not necessarily be detected in a study with 80 women. A blinded interim analysis was performed with subsequent changes to the protocol and reapproval by the institutional review board because subjects reported perioral numbness, tingling, and ear ringing. Any patient reporting severe symptoms was required to have a serum lidocaine sample drawn (n = 3). Although none of our serum lidocaine levels exceeded the toxic range of 5.0 µg/mL, the peak values were observed in the first samples collected at 10 minutes. Because no samples were obtained before this time, it is possible that transient toxic levels could occur in some women before 10 minutes, particularly those with very low body mass. Although the study was limited to women weighing over 100 lbs, weight was otherwise not objectively collected as a data point to be able to prove this theory.
A significant number of subjects in the lidocaine infusion group reported symptoms attributed to lidocaine exposure, including numbness, tingling, and ear ringing. The symptoms were not severe enough to affect the completion of the procedure but may have been noticeable enough to unblind the clinicians performing the procedures. Abortion providers were not involved in recording patient pain scales and/or symptoms, and they treated patients with and those without symptoms in a similar fashion (same verbal cues regarding the procedure). Therefore, the impact on the study results should be minimal. In addition, all subjects were informed that they might experience symptoms, so subject blinding to study arms should have been unaffected by any symptoms experienced.
Women in both groups reported high satisfaction ratings in regard to their experience. This level of satisfaction persisted for women who experienced lidocaine-associated adverse effects, which gives credence to the idea that the lidocaine infusion was well tolerated. To detect a difference between satisfaction levels may not be possible because women undergoing abortion consistently report high levels of satisfaction unless they experience a complication (ie, need for reaspiration).16 One might suggest that further attempts to reduce discomfort with abortion are not warranted, since satisfaction is high. However, as clinicians, we recognize that many women suffer considerable discomfort with abortion and that steps to reduce this suffering improve the overall abortion experience for patients and health care providers.
One strategy to reduce potential toxicity would be to reduce the total amount of local anesthetic given. Paracervical block alone can cause similar symptoms of low-level lidocaine toxicity.7,17 No studies have demonstrated that paracervical block reduces pain associated with suction curettage, and the benefit for cervical dilation is at best minimal. Abandoning paracervical block in favor of intrauterine lidocaine may increase patient comfort while reducing the chance of symptoms and toxicity. Conceivably, cervical preparation with misoprostol or laminaria may offer superior reduction in cervical dilation pain compared with paracervical block.
Overall, our results demonstrate that an intrauterine infusion of 4% lidocaine before first-trimester abortion provides significant reduction of pain during cervical dilation and suction aspiration. Given that the majority of the more than 1 million suction curettage procedures performed each year are performed under local anesthesia in outpatient settings, the use of intrauterine lidocaine might represent an important breakthrough in abortion practice. However, more extensive safety studies should be performed before the technique can be recommended for routine practice.
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Footnotes |
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Corresponding author: Alison Edelman, MD, Assistant Professor, Ob/Gyn Department, Mail code UHN 50, Oregon Health & Science University, Portland, OR 97239; e-mail: edelmana{at}ohsu.edu.
doi:10.1097/01.AOG.0000194204.71925.4a
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REFERENCES |
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2. Trolice MP, Fishburne C Jr, McGrady S. Anesthetic efficacy of intrauterine lidocaine for endometrial biopsy: a randomized double-masked trial. Obstet Gynecol 2000;95:345–7.
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7. Blanco LJ, Reid PR, King TM. Plasma lidocaine levels following paracervical infiltration for aspiration abortion. Obstet Gynecol 1982;60:506–8.
8. Adams HA, Pawlik D, Bauer H, Mautgreve W. Stability of local anesthetics in heparinized blood, plasma and sulfuric acid. Acta Anaesthesiol Scand 1998;42:783–5.[Medline]
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17. Miller L, Jensen MP, Stenchever MA. A double-blind randomized comparison of lidocaine and saline for cervical anesthesia. Obstet Gynecol 1996;87:600–4.[Abstract]
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19. Kan AS, Ng EH, Ho PC. The role and comparison of two techniques of paracervical block for pain relief during suction evacuation for first-trimester pregnancy termination. Contraception 2004;70:159–63.[Medline]
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