Abstract
Objective:
To evaluate the effect of oral gabapentin in conjunction with usual oral pain management regimens of lorazepam, ibuprofen, oxycodone and acetaminophen for surgical abortion on pain five minutes post-procedure.
Methods:
This was a randomized, double-blind, placebo-controlled trial of patients from 6 weeks 0 days to 14 weeks 6 days gestation scheduled to receive surgical abortion at the Duke Family Planning Clinic. Participants were administered 600mg of oral gabapentin versus placebo with usual oral pain management. Pain score was assessed using a 100-mm visual analog scale (VAS), with the primary outcome being pain score five minutes after the procedure. The effect of gabapentin was assessed using a linear regression model controlling for baseline pain. We also measured pain perception at 24-hours after the procedure. Secondary outcome measures included anxiety, side effects, and usage of opiate pain medication in the 24-hour post-operative period.
Results:
Out of 113 women screened for this study; 96 women were recruited, enrolled and randomized to study treatment arm from August 2016 to June 2018. Pain at five minutes after the procedure was similar between the gabapentin and placebo groups (β = 3.40; 95% CI = [−8.20, 15.0]; p = 0.56). Gabapentin and placebo were well tolerated, with no statistically significant difference in side effects or anxiety levels. While prescription of opioids after the procedure were not standardized among patients, 73% of women received a short-term prescription for oxycodone. A lower percentage of women in the gabapentin group self-reported taking opioids in the 24 hours post-procedure (18% vs. 47%; OR = 0.26; 95% CI = [0.09, 0.75]).
Conclusion:
The addition of gabapentin to usual oral pain management regimens with paracervical block did not reduce post-operative pain for patients undergoing outpatient surgical abortion. While the addition of gabapentin was well-tolerated and reduced oral opiate use 24 hours post-procedure, it did not impact the experience of pain during and immediately after the procedure.
Clinical Trial Registration:
ClinicalTrials.gov, www.clinicaltrials.gov, NCT02725710.
PRECIS
Gabapentin in addition to usual pain regimens prior to surgical abortion, while well tolerated, does not improve peri-procedural pain.
INTRODUCTION
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 post-operative pain following surgical abortion; however, their use is limited due to cost, staffing and potential additional risks.2–3 Unfortunately, other recently examined adjuncts to pain control such as other NSAID derivatives (intramuscular ketorolac), acetaminophen and codeine, and alverine as a muscle relaxant have not proven to be beneficial in this setting.4–5 There is similarly limited data on non-pharmacologic 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 post operative pain for major and minor procedure with minimal side effects and few contraindications, including in common obstetrics and gynecology procedures such as cesarean birth and hysterectomy.8–12 Particlarly 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 post-operative 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 at 24 hours after the procedure, side effects and use of opioids post-operatively.
METHODS
This was a prospective, randomized, double-blind, placebo-controlled trial approved by the Duke Health Institutional Review Board (Pro00063872). Subjects from 6 weeks 0 days to 14 weeks 6 days gestation scheduled to receive uterine aspiration were approached by the clinic nurse of physician for enrollment in the study at the time of presentation for the procedure. Inclusion criteria included age ≥ 18 years, 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 or with pre-existing 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 prior to 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 pre-procedure counseling by our clinical coordinator. A determination was made if 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 prior to the final clinical preoperative review. Participants were compensated US $30 for their participation in this study.
Randomization of participants in variable blocks of eight and ten 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 one to two hours prior to uterine aspiration allocated by the clinic nurse, as is standard practice in our clinic. Usual perioperative medications in our clinical setting include 2mg lorazepam, 800mg ibuprofen, 325mg acetaminophen and 5mg oxycodone. Previous studies of gabapentin in a preoperative setting found effective administration time as one to two hours prior to procedure start.14 In addition to the usual perioperative medications, all participants received the usual paracervical block immediately prior to uterine aspiration, which included 40 ml of 0.5% lidocaine.
Patients with a gestational age greater than 12 weeks used a 400 microgram dose of vaginal misoprostol 2 hours prior to their appointment for cervical preparation. Patients underwent manual or electric vacuum aspiration based on gestational age. Patients under 11 weeks gestational age underwent a manual vacuum aspiration, while those at 11 weeks gestation or above underwent an 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 pre-operatively, intra-operatively, and post-operatively at pre-determined time intervals of five, 10 and 30 minutes after the procedure and upon discharge. Intra-operative 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 five 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 upon discharge, also using the VAS scale. We assessed the time in minutes that gabapentin or placebo was administered prior to 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 prior to discharge. Participants were also contacted by study staff 24 hours after the procedure to assess pain, nausea, vomiting and side effects following 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 post-operatively was assessed on the phone by patient self-report. Patients typically receive a prescription for 600mg 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 for pain control, however our practice shifted to limit post-operative opioid prescriptions if deemed necessary for pain control by the physician.
We collected baseline characteristics and other variables of interest including: demographics (age, race and 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 a standard deviation 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 five minutes post-procedure.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 ninety-six 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, Nashville, TN). All data collected was 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 (CHMP) regarding the analysis of clinical trials, we controlled for baseline pain.18
A binary indicator of high post-operative 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 post-procedure 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 five 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 post-operative medication usage. The analysis was performed in SAS 9.4 (SAS Institute, Cary, NC) at a significance level of 0.05, two-tailed. No adjustments for multiple testing were made for the secondary outcomes.
RESULTS
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 (Figure 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 received their allocated intervention. As this participant dropped out prior to 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 following the procedure, and another participant in the placebo group was not available to complete the 24-hour post-procedure phone call. The trial was stopped after all 96 anticipated participants were recruited and enrolled.
Figure 1.
CONSORT Flow Diagram of Participant Recruitment, Enrollment, Randomization, Follow-Up and Analysis.
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 prior to the procedure (14.6% in the placebo group and 10.6% in the gabapentin group).
Table 1.
Patient Characteristics at Baseline by Treatment Group
| Patient Characteristics | Gabapentin (N=47) | Placebo (N=48) | Total (N=95) |
|---|---|---|---|
| Age in years, mean ± SD | 31.7 ± 6.1 | 31.8 ± 6.3 | 31.7 ± 6.1 |
| Race, N (%) | |||
| Asian | 5 (11) | 5 (10) | 10 (11) |
| Black or African American | 16 (34) | 15 (31) | 31 (33) |
| White or Caucasian | 26 (55) | 27 (56) | 53 (56) |
| Unknown or not reported | 0 (0) | 1 (2) | 1 (1) |
| Hispanic or Latino, N (%) | 3 (6) | 5 (10) | 8 (8) |
| Marital status, N (%) | |||
| Single/divorced/widowed | 19 (40) | 19 (40) | 38 (40) |
| Married | 28 (60) | 28 (58) | 56 (59) |
| Cohabitating | 0 (0) | 1 (2) | 1 (1) |
| Highest level of education completed, N (%) | |||
| Less than high-school | 1 (2) | 1 (2) | 2 (2) |
| High-school diploma or GED | 5 (11) | 7 (15) | 12 (13) |
| Some college | 5 (11) | 6 (13) | 11 (12) |
| Associates degree or Technical Certification | 7 (15) | 5 (10) | 12 (13) |
| Bachelor’s degree | 15 (32) | 13 (27) | 28 (29) |
| Master’s degree/Doctoral degree | 14 (30) | 16 (33) | 30 (32) |
| Annual household income in USD, N (%) | |||
| < 10,000 | 3 (6) | 2 (4) | 5 (5) |
| 10–25,000 | 3 (6) | 3 (6) | 6 (6) |
| 25–50,000 | 7 (15) | 10 (21) | 17 (18) |
| 50–75,000 | 2 (4) | 6 (13) | 8 (8) |
| 75–100,000 | 4 (9) | 5 (10) | 9 (10) |
| > 100,000 | 20 (43) | 12 (25) | 32 (34) |
| Don’t know/refused | 8 (17) | 10 (21) | 18 (19) |
| History of sexual/physical assault, N (%) | 10 (21) | 3 (6) | 13 (14) |
| Baseline pain, median (Q1, Q3) | 3.0 (0.0, 9.0) | 3.3 (0.5, 22.3) | 3.0 (0.0, 14.0) |
| Parity, median (Q1, Q3) | 0 (0, 1) | 1 (0, 1) | 1 (0, 1) |
| History of vaginal birth, N (%) | 18 (38) | 18 (38) | 36 (38) |
| History of C-section, N (%) | 6 (13) | 12 (25) | 18 (19) |
| History of abortion, N (%) | 9 (29) | 8 (26) | 17 (27) |
| History of anxiety, N (%) | 21 (45) | 21 (44) | 42 (44) |
| History of taking opiate pain medication in the past 6 months, N (%) | 5 (11) | 7 (15) | 12 (13) |
Post-operative Pain
Primary outcome:
For the primary outcome, there was no difference in the pain score, controlling for baseline pain, (mean ± SD) five minutes after removal of the speculum in the gabapentin group (37.1 ± 30.4 gabapentin compared to 35.7 ± 27.5 placebo group, β = 3.40; 95% CI = [−8.20, 15.0]; p = 0.56).
Secondary outcomes:
Similarly, for the binary outcome of high post-operative pain, the odds of experiencing high pain was not statistically significant (25.5% gabapentin versus 18.8% placebo; OR 1.77; 95% CI = [0.63, 4.95]; p = 0.28).
In addition to pain measured five minutes after speculum removal, the entire experience of pain during and after the procedure was similar between gabapentin and placebo groups (Figure 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.
Figure 2.
Mean Reported Pain Scores Throughout the Study, by Treatment Group.
Finally, pain was assessed 24 hours post-operatively 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 = 0.63 and p = 0.95, respectively, Table 2).
Table 2.
Quality of Recovery Survey 24 Hours Post-Operatively by Treatment Group
| Pain Score | Gabapentin (N=47) | Placebo (N=47)* | Total (N=94) | P-value |
|---|---|---|---|---|
| Moderate pain, median (Q1, Q3) | 8 (5, 9) | 7 (5, 9) | 7 (5, 9) | 0.63 |
| Severe pain, median (Q1, Q3) | 10 (9, 10) | 10 (8, 10) | 10 (9, 10) | 0.95 |
One patient in the placebo group did not have quality of recovery survey information
Post-operative Anxiety
Anxiety levels five minutes after speculum removal at the conclusion of the procedure were also similar between groups, remaining similar at 10 and 30 minutes post-operatively and at discharge (Table 3). Median anxiety levels decreased over time after the procedure, with a median anxiety level of 24/100 at five minutes after the procedure and 10/100 upon discharge.
Table 3.
Anxiety at Post-Operative Assessments by Treatment Group
| Anxiety Score | Gabapentin (N=47) | Placebo (N=48) | Total (N=95) | P-value |
|---|---|---|---|---|
| Anxiety 5 minutes post-op, median (Q1, Q3) | 23.5 (6.0, 49.5) | 24.5 (10.0, 50.5) | 24.0 (8.0, 50.0) | 0.95 |
| Anxiety 10 minutes post-op, median (Q1, Q3) | 11.0 (4.0, 36.0) | 14.5 (3.8, 43.5) | 11.5 (4.0, 37.0) | 0.74 |
| Anxiety 30 minutes post-op, median (Q1, Q3) | 7.0 (2.5, 27.5) | 13.3 (2.8, 25.0) | 9.5 (2.5, 26.5) | 0.74 |
| Anxiety at discharge, median (Q1, Q3)* | 8.0 (3.0, 23.0) | 10.5 (2.0, 27.0) | 9.8 (2.5, 25.0) | 0.99 |
One patient in the placebo group did not have anxiety at discharge measured
Influence of Time on Post-procedure Pain
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 five-minute post-procedure assessment (95% CI = [−18.7, −1.28]; p = 0.03). Caution should be used applying this trend after two hours, as only 10% of patients started their procedures more than 105 minutes after receiving their allocated pain medications.
Side Effects
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.
Table 4.
Side Effects at Post-Operative Assessment by Treatment Group
| Side Effect | Gabapentin (N=47) | Placebo (N=48) | Total (N=95) | P-value |
|---|---|---|---|---|
| Dizziness, N (%) | 20 (43) | 14 (29) | 34 (36) | 0.17 |
| Ataxia, N (%) | 6 (13) | 8 (17) | 14 (15) | 0.59 |
| Somnolence, N (%) | 41 (87) | 37 (77) | 78 (82) | 0.20 |
| Asthenia, N (%) | 27 (58) | 31 (65) | 58 (61) | 0.48 |
| Headache, N (%) | 5 (11) | 5 (10) | 10 (11) | 1.0 |
| Amblyopia, N (%) | 3 (6) | 3 (6) | 6 (6) | 1.0 |
| Nausea 10 minutes post-op, median (Q1, Q3) | 1.0 (0.0, 15.0) | 2.5 (0.0, 14.0) | 2.0 (0.0, 15.0) | 0.88 |
| Vomited within 10 minutes post-op, N (%) | 2 (4) | 1 (2) | 3 (3) | 0.62 |
Influence of Gabapentin on Post-operative Pain Medication Use
Approximately 74% of women undergoing surgical abortions in this study received opiate prescriptions for 5mg oxycodone and 325mg acetaminophen (Percocet) following 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 = 0.12). No pain medication use and use of ibuprofen use were not statistically different between groups. Fewer women in the gabapentin group used opioids during the post-operative period (18% vs. 47%; OR = 0.26; 95% CI = [0.09, 0.75]; p = 0.01; Table 5).
Table 5.
Post-Operative Medication Use by Treatment Group
| Medication type | Gabapentin (N=47) | Placebo (N=48) | Total (N=95) | P-value |
|---|---|---|---|---|
| All patients | 47 | 48 | 95 | |
| No pain medication, N (%) | 17 (36) | 10 (21) | 27 (28) | 0.10 |
| Ibuprofen only, N (%) | 23 (49) | 23 (48) | 46 (48) | 0.92 |
| Received a prescription for opiates | 38 (81) | 32 (67) | 70 (74) | 0.12 |
| Ibuprofen and oxycodone, N (%) | 6 (16) | 9 (28) | 15 (21) | 0.21 |
| Oxycodone only, N (%) | 1 (3) | 6 (19) | 7 (10) | 0.04 |
| Any oxycodone use, N (%) | 7 (18) | 15 (47) | 22 (31) | 0.01 |
DISCUSSION
The addition of oral gabapentin to usual oral pain management regimens does not influence post-operative 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 five minutes after the procedure. In contrast, a systematic review of sixteen randomized controlled trials of various major surgeries indicated that gabapentin reduced overall pain scores at six and 24 hours post-operatively.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 gabapentin for 72 hours undergoing a variety of different surgical operations that found no effect on peri-operative pain. Further research should examine alternative pain management techniques focusing on intraoperative pain to improve the patient experience.
In abortion literature, recent data suggest that co-administration 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.23 While our study investigated the use of gabapentin, both gabapentinoids have similar mechanisms of action and are both are supported in decreasing peri-operative pain in other contexts. Gabapentin was chosen during our study due to availability and cost as compared to 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 peri-operative period, similar to other clinical contexts.8,10 While side effects such as somnolence and asthenia were common among our partiicpants, 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.
While gabapentin does not impact peri-operative pain for patients undergoing uterine aspiration under 15 weeks gestational age, we found gabapentin did reduce opiate pain prescriptions post operatively. Notably, this was not our primary outcome. Reduced opiate use with gabapentin has been illustrated in prior studies in the gynecology as well as other fields.10–12,24–25 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.26–27 Importantly, there are large variations in clinical practice regarding the routine prescribing of opioids post-uterine 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 post-operatively.
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 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 receive their allocated intervention and one patient did not follow up through the 24-hour post-operative period, further improving the study’s validity. The data exhibited impressive internal consistency, validating the VAS to assess pain in this population. By utilizing VAS measurements of pain, this study is comparable to other studies investigating this topic. However, this study only served to evaluate the impact of gabapentin within the timeframe of one to two hours pre-operatively 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 peri-operative pain management to which gabapentin or placebo was added. While 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 one day prior to 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 five minutes post-procedure in comparison to 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 post-operative period. Improving pain management during uterine suction continues to be a priority for further investigation, as well as better understanding relationships between peri-procedural pain, opioid use, and adjunctive pain medications.
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 deidentification.
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 submission of 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 dataset, 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 dataset must be approved by the author team prior to submission.
Acknowledgments
Financial support for this research was provided by the Charles B. Hammond Research Fund. The Duke BERD Methods Core’s support of this project was made possible in part by Grant Number UL1TR002553 from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH), and the NIH Roadmap for Medical Research. Its contents are soley the responsibility of the authors and do not necessarily represent the official views of NCATS or NIH.
Footnotes
Each author has confirmed compliance with the journal’s requirements for authorship.
Financial Disclosure: Dr. Gray is an investigator for a phase 3 trial supported by Sebela for the Veracept IUD. This support is not related to the current study and did not overlap with the current study. She also reports money was paid to her institution for Duke AHEAD – a faculty development grant to support REDcap database and technical writing. The other authors did not report any potential conflicts of interest.
Presented at the ACOG 2019 Annual Clinical and Scientific Meeting, Nashville, TN, May 3–6, 2019.
REFERENCES
- 1.Westfall JM, Sophocles A, Burggraf H, Ellis S. Manual vacuum aspiration for first trimester abortion. Arch Fam Med 1998;7(6):556–62. [DOI] [PubMed] [Google Scholar]
- 2.Renner RM, Jensen JT, Nichols MD, Edelman A. Pain control in first trimester surgical abortion. Cochrane Database Syst Rev 2009; (2): CD006712. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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(2 Pt 1):276–83. [DOI] [PubMed] [Google Scholar]
- 4.Jackson E, Kapp N. Pain control in first-trimester and second-trimester medical termination of pregnancy: a systematic review. Contraception 2011;83(2):116–26. [DOI] [PubMed] [Google Scholar]
- 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(2):116–21. [DOI] [PubMed] [Google Scholar]
- 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(1):45.e1–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Moayedi G, Tshann M. Pain Management for First-Trimester Uterine Aspiration. Obstet Gynecol Survey 2018;73(3):174–81. [DOI] [PubMed] [Google Scholar]
- 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(5):1215–21. [DOI] [PubMed] [Google Scholar]
- 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(2):428–42. [DOI] [PubMed] [Google Scholar]
- 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(6):1545–56. [DOI] [PubMed] [Google Scholar]
- 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(6):1221–9. [DOI] [PubMed] [Google Scholar]
- 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(1):167–73. [DOI] [PubMed] [Google Scholar]
- 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. [DOI] [PubMed] [Google Scholar]
- 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(2):131–57. [DOI] [PubMed] [Google Scholar]
- 15.Stark PA, Myles PS, Burke JA. Development and psychometric evaluation of a postoperative quality of recovery score: the QoR-15. Anesthesiology 2013;118(6):1332–40. [DOI] [PubMed] [Google Scholar]
- 16.Todd KH, Funk FG, Funk JP, Bonacci R. Clinical significance of reported changes in pain severity. Ann Emerg Med 1996;27(4):485–9. [DOI] [PubMed] [Google Scholar]
- 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(6):633–8. [DOI] [PubMed] [Google Scholar]
- 18.Committee for Proprietary Medicinal Products (CPMP). Points to Consider on Adjustment for Baseline Covariates. Stat Med 2004;23(5):701–9. [DOI] [PubMed] [Google Scholar]
- 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(5):1063–70. [DOI] [PubMed] [Google Scholar]
- 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(5):1222–5. [DOI] [PubMed] [Google Scholar]
- 21.Glantz JC, Shomento S. Comparison of paracervical block techniques during first trimester pregnancy termination. Int J Gyn Obstet 2001;72(2):171–8. [DOI] [PubMed] [Google Scholar]
- 22.Ho KY, Gan TJ, Habib AS. Gabapentin and postoperative pain - a systematic review of randomized controlled trials. Pain 2006;126:91–101. [DOI] [PubMed] [Google Scholar]
- 23.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(3):612–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.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(3):237–47. [DOI] [PubMed] [Google Scholar]
- 25.Mathiesen O, Moiniche S, Dahl JB. Gabapentin and postoperative pain: a qualitative and quantitative systematic review, with focus on procedure. BMC Anesthesiol 2007;7:6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.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(1):18–22. [PMC free article] [PubMed] [Google Scholar]
- 27.Poylin V, Quinn J, Messer K, Nagle D. Gabapentin significantly decreases posthemorrhoidectomy pain: a prospective study. Int J Colorectal Dis 2014;29(12):1565–9. [DOI] [PubMed] [Google Scholar]