Surgical abortions in North America are typically performed using either local anesthetic with oral analgesics or moderate sedation. Surgical abortions may be performed in an office setting using manual or electric vacuum aspiration. This procedure is 99.5% effective at terminating pregnancy and is generally well tolerated.1 Conscious sedation and general anesthesia can be useful in some settings to reduce intraoperative and postoperative pain after surgical abortion; however, their use is limited owing to cost, staffing, and potential additional risks.2,3 Unfortunately, other recently examined adjuncts to pain control such as other nonsteroidal antiinflammatory drug derivatives (intramuscular ketorolac), acetaminophen and codeine, and alverine as a muscle relaxant have not proven to be beneficial in this setting.4,5 There are similarly limited data on nonpharmacologic methods to decrease pain including hypnosis, playing music, and doula support.6,7
There is substantial evidence to support use and safety of gabapentin in reducing perioperative and postoperative pain for major and minor procedures with minimal side effects and few contraindications, including common obstetrics and gynecology procedures such as cesarean delivery and hysterectomy.8–12 Particularly in the context of the opioid-use epidemic in the United States, adjunct medications such as gabapentin may be an important addition to perioperative pain management.
As uterine aspiration is among the most common surgical procedures performed around the world, improvement of pain control by adding a low-cost and well-tolerated medication would have potential implications for not only surgical abortions but also other common outpatient gynecologic procedures. Further, in a survey of facilities providing first trimester abortions, 30% of facilities provided patients opiate tablets or prescriptions in the postoperative period.13 Here, we assessed the effect of oral gabapentin administration in conjunction with oral sedation for surgical abortion by uterine aspiration on reducing perioperative pain scores. Additionally, we evaluated pain perception 24 hours after the procedure, side effects, and use of opioids postoperatively.
This was a prospective, randomized, double-blind, placebo-controlled trial approved by the Duke Health Institutional Review Board (Pro00063872). Patients from 6 0/7–14 6/7 weeks of gestation scheduled to undergo uterine aspiration were approached by the clinic nurse or physician for enrollment in the study at the time of presentation for the procedure. Inclusion criteria included age 18 years or older, presentation for surgical abortion, no contraindications for outpatient abortion, fluency in English, and ability to provide informed consent. Exclusion criteria included allergy, sensitivity, or contraindication to gabapentin, presence of severe renal disease with a previously identified creatinine clearance of less than 30 mL/min, and current use of gabapentin or pregabalin. Although patients on any chronic pain medications, with preexisting pain conditions, or history of alcohol or drug use may exhibit differential metabolism or effect of clinic-administered drugs, these women were not excluded.
This study was performed at the Duke Family Planning Clinic at the Duke Gynecology Outpatient Clinic. The Duke Family Planning Clinic is a hospital-affiliated clinic that provides care to both insured and uninsured patients in Durham, North Carolina. Clinical care is provided by attending and resident physicians affiliated with Duke University Hospital. Women attending the clinic for uterine aspiration were approached during their preoperative evaluation or by telephone before their appointment to determine interest in participating in the study, during which time they were also screened for eligibility. All participants were scheduled and provided standardized preprocedure counseling by our clinical coordinator. A determination was made whether the patient was eligible for an outpatient procedure with oral sedation medications. A standard recruitment script was provided to all personnel performing candidate screening. Those eligible after screening reviewed the informed consent and signed the consent form before the final clinical preoperative review. Participants were compensated $30 for their participation in this study.
Randomization of participants in variable blocks of eight and 10 was accomplished using computer-generated random numbers (http://www.randomization.com). Allocation concealment was maintained by identically labeled, sealed, sequentially numbered opaque pill containers. Our institutional drug service pharmacists prepared the gabapentin and placebo pills to appear identical. To maintain double-blinding for both investigators and participants, individuals not associated with study conduct created the randomization sequence and allocation containers. Randomization assignments were revealed only at the point of data analysis.
Participants received both usual perioperative pain management and either oral placebo or gabapentin 600 mg 1 to 2 hours before uterine aspiration allocated by the clinic nurse, as is standard practice in our clinic. Usual perioperative medications in our clinical setting include 2 mg lorazepam, 800 mg ibuprofen, 325 mg acetaminophen and 5 mg oxycodone. Previous studies of gabapentin in a preoperative setting found effective administration time as 1 to 2 hours before procedure start.14 In addition to the usual perioperative medications, all participants received the usual paracervical block immediately before uterine aspiration, which included 40 mL of 0.5% lidocaine.
Patients with gestational age greater than 12 weeks used a 400-microgram dose of vaginal misoprostol 2 hours before their appointment for cervical preparation. Patients underwent manual or electric vacuum aspiration based on gestational age. Patients at less than 11 weeks of gestation underwent manual vacuum aspiration, and those at 11 weeks of gestation or more underwent electric vacuum aspiration. Providers completing these procedures included attending and resident physicians who had all been trained on this method of surgical abortion.
Questionnaires including a visual analog scale (VAS) were administered by study staff preoperatively, intraoperatively, and postoperatively at predetermined time intervals of 5, 10, and 30 minutes after the procedure and on discharge. Intraoperative pain was assessed at speculum insertion, at the time of paracervical block, during dilation, during suction, and at speculum removal. The primary study outcome measure was pain score, assessed using a 100-mm VAS measured 5 minutes after removal of the speculum.
Secondary pain outcomes included pain immediately before the procedure, during the procedure, immediately after the procedure, 10 and 30 minutes after the procedure, and on discharge, also using the VAS scale. We assessed the time in minutes that gabapentin or placebo was administered before the different pain assessments. Nausea, vomiting, and anxiety were also assessed as secondary outcomes using a similar VAS scale at the same time points. Other side effects were assessed using a checklist before discharge. Participants were also contacted by study staff 24 hours after the procedure to assess pain, nausea, vomiting, and side effects after the procedure (on a 5-point Likert scale). The quality of recovery survey was used to assess patient symptoms.15 The type of pain medication prescribed on discharge was abstracted from the clinical record, and the amount of pain medication used up to 24 hours postoperatively was assessed on the phone by patient self-report. Patients typically receive a prescription for 600 mg ibuprofen to be taken every 6 hours as needed after discharge from clinic. At the initiation of the study, all patients received a limited number of oxycodone pills for pain control; however, our practice shifted to limit postoperative opioid prescriptions if deemed necessary for pain control by the physician.
We collected baseline characteristics and other variables of interest including: demographics (age, race–ethnicity, marital status, education level, income level, insurance status), medical history (gravidity, parity, prior abortions [medical and surgical], gestational age, drug or alcohol use, psychiatric or sexual assault history), medications used at home and given preoperatively at the clinic, and indication for procedure (personal or social, fetal or maternal health).
For our primary outcome, we assumed an SD of 26 mm on the 100-mm VAS for pain, as reported from prior abortion pain research studies, and a type I error rate of 0.05, and determined the number of participants needed to achieve 80% power to detect a 15-mm difference in pain at 5 minutes postprocedure.2,12 A difference of 15–20 mm has been deemed to be clinically meaningful in prior studies.16,17 Based on our sample size calculation, we planned to recruit and enroll a total of 96 women with equal allocation to the placebo and gabapentin groups.
A database was developed using a web-based, password-protected relational database (REDCap, Vanderbilt University). All data collected were recorded on clinical research forms and entered into the database. Source documents were filed and stored for future reference. Summary statistics for baseline characteristics of interest were calculated stratifying by treatment arm. Continuous variables were summarized as either mean±SD or median (Q1, Q3), and categorical variables as n (%). We compared the primary outcome between the two treatment arms using linear regression. Following the recommendations of the Committee for Medicinal Products for Human Use regarding the analysis of clinical trials, we controlled for baseline pain.18
A binary indicator of high postoperative pain, defined as a pain score greater than or equal to 65/100 mm (approximately the 80th percentile across all participants) at the five-minute assessment, was created. A logistic regression model was then fit to test the effect of gabapentin on high pain, again controlling for baseline pain. Wilcoxon rank sum tests were used to compare moderate pain, severe pain, and nausea or vomiting on the quality of recovery survey, anxiety at various postprocedure time points, and nausea at 10 minutes between treatment arms. Linear regression controlling for baseline pain was used to assess the effect of medication administration time on pain 5 minutes after the procedure. Chi-square or Fisher's exact test was used to evaluate the effect of treatment group on each side effect of interest and postoperative medication usage. The analysis was performed in SAS 9.4 at a significance level of 0.05, two-tailed. No adjustments for multiple testing were made for the secondary outcomes.
Ninety-six women were recruited, enrolled, and randomized in the study; 48 in each of the placebo and gabapentin groups from August 2016 to June 2018 (Fig. 1).19 An additional 17 women were approached regarding the study but chose not to participate (85.0% participation rate), for a total of 113 women approached for enrollment. One patient in the gabapentin group did not complete the procedure, for a total of 95 patients who underwent their allocated intervention. As this participant dropped out before any intervention, they were not included in an intention-to-treat analysis. One participant in the placebo group did not complete the survey on discharge after the procedure, and another participant in the placebo group was not available to complete the 24-hour postprocedure phone call. The trial was stopped after all 96 anticipated participants were recruited and enrolled.
As expected, the placebo and gabapentin groups were similar across multiple measures, including parity, history of vaginal birth, history of anxiety, and baseline pain (Table 1). Approximately 13% of the women reported use of an opiate pain medication in the 6 months before the procedure (14.6% in the placebo group and 10.6% in the gabapentin group).
For the primary outcome, there was no difference in the pain score, controlling for baseline pain (mean±SD) 5 minutes after removal of the speculum in the gabapentin group (37.1±30.4 gabapentin vs 35.7±27.5 placebo group, β=3.40; 95% CI −8.20 to 15.0; P=.56).
Similarly, for the binary outcome of high postoperative pain, the odds of experiencing high pain was not statistically significant (25.5% gabapentin vs 18.8% placebo; odds ratio [OR] 1.77; 95% CI 0.63–4.95; P=.28).
In addition to pain measured 5 minutes after speculum removal, the entire experience of pain during and after the procedure was similar between gabapentin and placebo groups (Fig. 2). Pain steadily increased from before the start of the procedure to during suction. Pain was reduced on removal of the speculum and end of the procedure, continuing to decrease through discharge.
Finally, pain was assessed 24 hours postoperatively based on patient subjective self-report of moderate or severe pain in the quality of recovery survey. Moderate and severe pain was rated on a scale from 0 to 10, where a 0 response indicated “all of the time” and 10 response indicated “none of the time.” There was not a significant difference between the gabapentin and placebo groups with regards to the moderate pain and severe pain scales (P=.63 and P=.95, respectively, Table 2).
Anxiety levels 5 minutes after speculum removal at the conclusion of the procedure were also similar between groups, remaining similar at 10 and 30 minutes postoperatively and at discharge (Table 3). Median anxiety levels decreased over time after the procedure, with a median anxiety level of 24 out of 100 at 5 minutes after the procedure and 10 out of 100 on discharge.
The average time between medication administration of both usual perioperative pain management and either oral placebo or gabapentin and procedure was 78 and 83 minutes for the gabapentin and placebo groups, respectively. Every half hour waited to start the procedure was associated with a 10 mm decrease in pain score at the 5-minute postprocedure assessment (95% CI −18.7 to −1.28; P=.03). Caution should be used applying this trend after 2 hours, as only 10% of patients started their procedures more than 105 minutes after receiving their allocated pain medications.
No significant differences were observed in any of the side effects (Table 4). Both somnolence and asthenia were noted in more than half of the patients in the study (82.1% and 61.1%, respectively); however, these side effects were not different based on gabapentin use.
Approximately 74% of women undergoing surgical abortions in this study received opiate prescriptions for 5 mg oxycodone and 325 mg acetaminophen after the procedure, which was not significantly different between groups (80.9% among gabapentin arm, 66.7% among placebo arm; OR 2.11; 95% CI 0.82–5.42; P=.12). Use of no pain medications and use of ibuprofen were not statistically different between groups. Fewer women in the gabapentin group used opioids during the postoperative period (18% vs 47%; OR 0.26; 95% CI 0.09–0.75; P=.01; Table 5).
The addition of oral gabapentin to usual oral pain management regimens does not influence postoperative pain or anxiety associated with uterine aspiration in an outpatient setting. This study plotted women's experience of pain throughout the process of surgical abortion in the outpatient setting. It is notable that women experience the most pain during suction, confirming previous studies.20,21 Gabapentin did not appear to improve pain at this critical time point, contrary to our hypothesis. Furthermore, our study indicated that pain scores between participants in the gabapentin and placebo groups were similar across multiple time points, including at 5 minutes after the procedure. In contrast, a systematic review of 16 randomized controlled trials of various major surgeries indicated that gabapentin reduced overall pain scores at 6 and 24 hours postoperatively.22 It is possible that the effects of gabapentin were not realized at the time points assessed in this study. However, our study results are consistent with a recent study of patients randomized to receive gabapentin preoperatively and for 72 hours postoperatively undergoing a variety of different surgical operations that found no effect on perioperative pain.23 Further research should examine alternative pain management techniques focusing on intraoperative pain to improve the patient experience.
In abortion literature, recent data suggest that coadministration of pregabalin with misoprostol during medical abortion decreases need for both ibuprofen and opiate pain medications and results in improved patient satisfaction scores with analgesia.24 Although our study investigated the use of gabapentin, both gabapentinoids have similar mechanisms of action and are both are supported in decreasing perioperative pain in other contexts. Gabapentin was chosen during our study owing to availability and cost as compared with pregabalin. We are unable to make generalizations about a class-effect for this medication, and thus evaluating the utility of pregabalin for perioperative pain for uterine aspiration is indicated.
Our study confirmed that gabapentin is well tolerated in the perioperative period, similar to other clinical contexts.8,10 Although side effects such as somnolence and asthenia were common among our participants, these are likely side effects from the usual oral pain medication regimens. Further, these side effects were similar regardless of gabapentin administration, indicating that adverse effects did not seem to be exacerbated by the addition of gabapentin.
Although gabapentin does not affect perioperative pain for patients undergoing uterine aspiration at less than 15 weeks of gestation, we found that gabapentin did reduce opiate pain prescriptions postoperatively. Notably, this was not our primary outcome. Reduced opiate use with gabapentin has been illustrated in prior studies in gynecology as well as other fields.10–12,25,26 Among other surgical procedures, a systematic review illustrated that a single preoperative dose of gabapentin significantly reduced 24-hour opioid consumption.10 This finding has been duplicated in the outpatient setting as well for minor orthopedic procedures and hemorrhoidectomy.27,28 Importantly, there are large variations in clinical practice regarding the routine prescribing of opioids postuterine aspiration, thus finding alternative options that are acceptable are important. There may be an implication for gabapentin use in patients who have existing chronic pain or higher likelihood to require opiates postoperatively.
This study had many strengths, including a comprehensive approach to understanding women's pain experiences during surgical abortion. This was a randomized, controlled, double-blind trial, allowing us to assess the effects of gabapentin in a controlled setting while decreasing selection bias and confounding. In our randomization, we included patients who had a history of chronic pain, opiate use, and sexual trauma; extending the validity of our study to these populations. Further, blinding and use of a placebo treatment decreased the risk of patient or observer bias. Only one participant did not undergo her allocated intervention, and one patient did not follow up through the 24-hour postoperative period, further improving the study's validity. The data exhibited impressive internal consistency, validating the VAS to assess pain in this population. By using VAS measurements of pain, this study is comparable with other studies investigating this topic. However, this study only served to evaluate the effect of gabapentin within the timeframe of 1 to 2 hours preoperatively and as an adjunct to oral lorazepam, ibuprofen, oxycodone, and acetaminophen. Additionally, this study was performed in only one clinic with a single protocol for oral perioperative pain management to which gabapentin or placebo was added. Although the Duke Family Planning Clinic receives patients from a wide catchment area, the study population had higher levels of education and household income than may be seen in other areas. Future research may be useful in evaluating the utility of gabapentin if given at other timepoints, such as 1 day before the procedure at the time of laminaria placement for second trimester procedures, its use among select populations, or as an adjunct to other pain management strategies such as IV sedation or paracervical block alone.
In summary, gabapentin was not associated with decreased pain at 5 minutes postprocedure in comparison with placebo when combined with usual oral pain management regimens. There is a need for more trials to adequately define patients that will benefit from these interventions as well as mechanistic studies to understand the timeframe that gabapentin may be helpful in the postoperative period. Improving pain management during uterine suction continues to be a priority for further investigation, as well as better understanding relationships between periprocedural pain, opioid use, and adjunctive pain medications.
1. Westfall JM, Sophocles A, Burggraf H, Ellis S. Manual vacuum aspiration for first trimester abortion. Arch Fam Med 1998;7:556–62.
2. Renner RM, Jensen JT, Nichols MD, Edelman A. Pain control in first trimester surgical abortion. The Cochrane Database of Systematic Reviews 2009, Issue 2. Art No.: CD006712. DOI: 10.1002/14651858.CD006712.pub2.
3. Allen RH, Fitzmaurice G, Lifford KL, Lasic M, Goldberg AB. Oral compared with intravenous sedation for first-trimester surgical abortion: a randomized controlled trial. Obstet Gynecol 2009;113:276–83.
4. Jackson E, Kapp N. Pain control in first-trimester and second-trimester medical termination of pregnancy: a systematic review. Contraception 2011;83:116–26.
5. Braaten KP, Hurwitz S, Fortin J, Goldberg AB. Intramuscular ketorolac versus oral ibuprofen for pain relief in first-trimester surgical abortion: a randomized clinical trial. Contraception 2014;89:116–21.
6. Chor J, Hill B, Martins S, Mistretta S, Patel A, Gilliam M. Doula support during first trimester surgical abortion: a randomized controlled trial. Am J Obstet Gynecol 2015;212:45.e1–6.
7. Moayedi G, Tshann M. Pain management for first-trimester uterine aspiration. Obstet Gynecol Surv 2018;73:174–81.
8. Schmidt PC, Ruchelli G, Mackey SC, Carroll IR. Perioperative gabapentinoids: choice of agent, dose, timing, and effects on chronic postsurgical pain. Anesthesiology 2013;119:1215–21.
9. Clarke H, Bonin RP, Orser BA, Englesakis M, Wijeysundera DN, Katz J. The prevention of chronic postsurgical pain using gabapentin and pregabalin: a combined systematic review and meta-analysis. Anesth Analg 2012;115:428–42.
10. Tiippana EM, Hamunen K, Kontinen VK, Kalso E. Do surgical patients benefit from perioperative gabapentin/pregabalin? A systematic review of efficacy and safety. Anesth Analg 2007;104:1545–56.
11. Alayed N, Alghanaim N, Tan X, Tulandi T. Preemptive use of gabapentin in abdominal hysterectomy: a systematic review and meta-analysis. Obstet Gynecol 2014;123:1221–9.
12. Moore A, Costello J, Wieczorek P, Shah V, Taddio A, Carvalho JC. Gabapentin improves postcesarean delivery pain management: a randomized, placebo-controlled trial. Anesth Analg 2011;112:167–73.
13. O'Connell K, Jones HE, Simon M, Saporta V, Paul M, Lichtenberg ES. First-trimester surgical abortion practices: a survey of National Abortion Federation members. Contraception 2009;79:385–92.
14. Chou R, Gordon DB, de Leon-Casasola OA, Rosenberg JM, Bickler S, Brennan T, et al. Management of postoperative pain: a clinical practice guideline from the American pain society, the American society of regional anesthesia and pain medicine, and the American society of anesthesiologists' committee on regional anesthesia, executive committee, and administrative council. J Pain 2016;17:131–57.
15. Stark PA, Myles PS, Burke JA. Development and psychometric evaluation of a postoperative quality of recovery score: the QoR-15. Anesthesiology 2013;118:1332–40.
16. Todd KH, Funk KG, Funk JP, Bonacci R. Clinical significance of reported changes in pain severity. Ann Emerg Med 1996;27:485–9.
17. Gallagher EJ, Liebman M, Bijur PE. Prospective validation of clinically important changes in pain severity measured on a visual analog scale. Ann Emerg Med 2001;38:633–8.
18. Committee for Proprietary Medicinal Products (CPMP). Points to consider on adjustment for baseline covariates. Stat Med 2004;23:701–9.
19. Schulz KF, Altman DG, Moher D; for the CONSORT Group. CONSORT 2010 statement: updated guidelines for reporting parallel group randomized trials. Obstet Gynecol 2010;115:1063–70.
20. Wong CYG, Ng EHY, Ngai SW, Ho PC. A randomized, double blind, placebo-controlled study to investigate the use of conscious sedation in conjunction with paracervical block for reducing pain in termination of first trimester pregnancy by suction evacuation. Hum Reprod 2002;17:1222–5.
21. Glantz JC, Shomento S. Comparison of paracervical block techniques during first trimester pregnancy termination. Int J Gyn Obstet 2001;72:171–8.
22. Ho KY, Gan TJ, Habib AS. Gabapentin and postoperative pain—a systematic review of randomized controlled trials. Pain 2006;126:91–101.
23. Hah J, Mackey SC, McCue R, Humphreys K, Trafton J, Efron B, et al. Effect of perioperative gabapentin on postoperative pain resolution and opioid cessation in a mixed surgical cohort. JAMA Surgery 2018;132:612–8
24. Friedlander EB, Soon R, Salcedo J, Davis J, Tschann M, Kaneshiro B. Prophylactic pregabalin to decrease pain during medical abortion: a randomized controlled trial. Obstet Gynecol 2018;132:612–8.
25. Hurley RW, Cohen SP, Williams KA, Rowlingson AJ, Wu CL. The analgesic effects of perioperative gabapentin on postoperative pain: a meta-analysis. Reg Anesth Pain Med 2006;31:237–47.
26. Mathiesen O, Møiniche S, Dahl JB. Gabapentin and postoperative pain: a qualitative and quantitative systematic review, with focus on procedure. BMC Anesthesiol 2007;7:6.
27. Mardani-Kivi M, Mobarakeh MK, Keyhani S, Motlagh KH, Ekhtiari KS. Is gabapentin effective on pain management after arthroscopic anterior cruciate ligament reconstruction? A triple blinded randomized controlled trial. Arch Bone Jt Surg 2013;1:18–22.
28. Poylin V, Quinn J, Messer K, Nagle D. Gabapentin significantly decreases posthemorrhoidectomy pain: a prospective study. Int J Colorectal Dis 2014;29:1565–9.
Authors' Data Sharing Statement
- Will individual participant data be available (including data dictionaries)? Yes.
- What data in particular will be shared? All of the individual participant data collected during the trial, after de-identification.
- What other documents will be available? Study protocol.
- When will data be available (start and end dates)? Immediately following publication and ending 5 years following article publication. Researchers should plan on submissionof their publication or presentation of the data within 1 year of receiving the data.
- By what access criteria will data be shared (including with whom, for what types of analyses, and by what mechanism)? Researchers who provide a methodologically sound proposal on their rationale for using this data set, their proposed analyses, and their proposed use for their results. Researchers must complete a Material Transfer Agreement for data transfer between Duke University and the researcher's institution. All results for publication and presentation using this data set must be approved by the author team prior to submission.