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Misoprostol 1 to 3 h preprocedure vs. overnight osmotic dilators prior to early second-trimester surgical abortion
Contraception xx (2015) xxx – xxx
Original research article
Misoprostol 1 to 3 h preprocedure vs. overnight osmotic dilators prior to early second-trimester surgical abortion☆ Shanthi Ramesh a , Alicia Roston b , Lindsay Zimmerman b , Ashlesha Patel a, b , E. Steve Lichtenberg a, c , Julie Chor b,⁎ a
Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA b Department of Obstetrics and Gynecology, The John H. Stroger, Jr. Hospital of Cook County, Chicago, IL, USA c Family Planning Associates Medical Group, Limited, Chicago, IL, USA Received 30 July 2014; revised 9 April 2015; accepted 9 April 2015
Abstract Objectives: We sought to compare the effectiveness of at least 1 h of 400 mcg of buccal misoprostol to overnight osmotic dilators for early second-trimester surgical abortion cervical preparation. Design: We conducted a retrospective cohort study, reviewing 145 consecutive charts to compare procedure duration for women who received 400 mcg of buccal misoprostol at least 1 h preprocedure vs. overnight osmotic dilators before dilation and evacuation between 14 weeks, 0 days and 15 weeks, 6 days' gestation. Primary outcome was procedure duration and secondary outcomes included maximum mechanical dilator size, estimated blood loss and side effects. Results: Sixty-four women (44.1%) received buccal misoprostol (mean 1.6 h), and 81 women (55.9%) received overnight osmotic dilators. Groups did not differ regarding mean gestational age or gynecologic history. All procedures in both groups were completed. Procedure duration was not significantly different between the misoprostol and osmotic dilator groups (median 11.0 min vs. 10.0 min, p=.22), even after multivariable linear regression (p=.17). The mean total cervical preparation duration was 1.6 h for women in the misoprostol group compared to 20.3 h in the osmotic dilator group (pb.001). Secondary outcomes did not differ between groups. Conclusions: We found that at least 1 h of preprocedure misoprostol decreased the duration of cervical preparation for early second-trimester procedures performed by an experienced surgeon. Implications: In this small, retrospective review, at least 1 h of preprocedure buccal misoprostol decreased the duration from cervical preparation initiation to procedure completion in early second-trimester procedures performed by an experienced surgeon. These results should be considered as a pilot evaluation, and further prospective study is needed to further clarify whether this short interval could be applied in general practice. © 2015 Elsevier Inc. All rights reserved. Keywords: Surgical abortion; Cervical preparation; Misoprostol; Osmotic dilators
1. Introduction Cervical preparation prior to dilation and evacuation (D&E) is an important measure to decrease complications [1–5]. Protocols for cervical preparation include using osmotic dilators, prostaglandins and/or antiprogestins to reduce the
☆
Presented at the American Congress of Obstetricians and Gynecologists Annual Clinical Meeting, April 26–30, 2014, Chicago, IL, USA. ⁎ Corresponding author at: 5841 South Maryland Avenue, MC 2050, Chicago, IL 60637, USA. E-mail address: [email protected] (J. Chor). http://dx.doi.org/10.1016/j.contraception.2015.04.005 0010-7824/© 2015 Elsevier Inc. All rights reserved.
need for additional mechanical dilation that may result in increased risk of cervical trauma and uterine perforation [2–8]. Misoprostol alone for cervical preparation is of clinical interest, as it facilitates same-day procedures compared to 2-day procedures often required with osmotic dilators. Additional advantages include patient acceptability of oral or buccal medications and decreased cost [9]. Several studies demonstrate increased dilation, greater ease of dilation and shorter procedure time when using 400 mcg of misoprostol administered buccally or vaginally 1–2 h prior to first-trimester surgical abortion [10,11]. However, data regarding the use of misoprostol alone prior to second-trimester surgical abortion are less clear. Existing studies vary regarding gestational age
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range, route of administration and duration of use with inconsistent results on overall procedure time and ease of dilation [12–16]. Despite conflicting data, in a 2001 survey of National Abortion Federation clinics, 40% of respondents reported routinely using misoprostol alone for cervical preparation at 16 weeks or less [17]. Protocols requiring a shorter duration of cervical preparation allow for the convenience of a same-day procedure, likely increasing accessibility and acceptability of early second-trimester abortion. Nucatola et al. [18] reported data from 6620 early second-trimester surgical abortions performed at Planned Parenthood of Los Angeles, which had been using 90 min of misoprostol alone for early second-trimester cervical preparation since 2001. This new approach to cervical preparation was not associated with an increase in serious adverse events, including uterine perforation [18]. Pharmacokinetic data demonstrate that over 75% of individuals who receive 400 mcg of buccal misoprostol reach peak serum levels between 30 and 90 min [19]. Building on this existing literature, we present initial data comparing procedure duration using at least 1 h preprocedure 400 mcg of buccal misoprostol vs. overnight osmotic dilators before early second-trimester D&E.
2. Materials and methods We conducted a retrospective cohort study comparing outcomes of women who received at least 1 h of buccal misoprostol or overnight osmotic dilators (combination of laminaria and/or Dilapan-S) for cervical preparation prior to early second-trimester D&E. We reviewed all charts of women presenting for surgical abortion between 14 weeks, 0 days and 15 weeks, 6 days of gestation from January 1, 2011 through June 30, 2011 at a high-volume pregnancy termination clinic, Family Planning Associates (FPA), in Chicago, Illinois. The primary outcome for this study was procedure duration. Secondary outcomes included mechanical dilator size, estimated blood loss and side effects, including postoperative bleeding, postoperative nausea/vomiting and postoperative pain. The institutional review board at the John H. Stroger, Jr. Hospital of Cook County approved the study. A study team member not directly involved in statistical analysis extracted all study data from patient charts. Inclusion criteria included all women who underwent surgical termination between 14 weeks, 0 days and 15 weeks, 6 days' gestation during the study period. Women who did not receive cervical preparation, who received less than 1 h of misoprostol at the discretion of the attending surgeon, or for whom the method of cervical preparation was not recorded in the chart were excluded from the study. Data collected were de-identified and included sociodemographic, reproductive health and procedure details. The primary outcome, procedure duration, was measured to the nearest minute by a highly experienced certified registered nurse anesthetist (CRNA) from the time of speculum insertion to speculum removal. Data for postoper-
ative vaginal bleeding (none/scant/small/moderate/heavy), pain (none/minimal/moderate/severe) and nausea and vomiting (none/emesis) were extracted from the nursing record using a standardized form. During the study period, all women presenting to FPA for surgical abortion 14 weeks, 0 days and 15 weeks, 6 days' gestational age underwent ultrasound confirmation of gestational age, preoperative evaluation, preoperative counseling and consent. At this gestational age, all women visited the clinic on 2 consecutive days for a preoperative visit and surgery. During the preoperative visit, advanced practice nurses (APNs) provided preprocedure counseling, including counseling regarding cervical preparation. The first option, overnight osmotic dilators, would require a shorter waiting time on the day of surgery, as the patient could arrive at the clinic on the day of surgery ready for her procedure. The second option, 400 mcg of buccal misoprostol, would require a longer waiting time on the day of surgery, as it would be administered that day, at least 1 h in advance of the procedure. Accordingly, APNs offered misoprostol as an option if the clinic's volume on the day of surgery could accommodate the longer waiting time that misoprostol requires. Prior to surgical days when the clinic anticipated shorter clinical hours due to a low volume of procedures, women received overnight dilators at their preoperative visit. Prior to a surgical day when the clinic anticipated longer hours due to a high volume of procedures, women were offered the option of either overnight osmotic dilators or day-of-procedure misoprostol. Experienced advanced practice clinicians performed all osmotic dilator placements (laminaria and Dilapan-S) with consultation as indicated by supervising physicians. Dilator placements were often performed after pre-dilation of the cervix using serial mechanical dilation with Hegar dilators up to 12 mm, as allowable without application of undue force. During osmotic dilator insertion, the advanced practice clinicians injected 2–3 ml of a 1% procaine analog to the anterior lip of the cervix (to minimize tenaculum pain) with or without additional paracervical block as needed. Intravenous or intramuscular injections of an analgesic agent (e.g., butorphanol or ketorolac) were also immediately available per standard clinic protocol as clinically indicated. One experienced, board-certified obstetrician-gynecologist performed all D&E procedures under general anesthesia using a 12-mm rigid suction curette and Sopher forceps. Mechanical dilators were used for additional dilation, and the maximum serial Hegar dilator used was recorded in millimeters for all cases prior to evacuation of the uterus. Pain control in every case was provided by a CRNA who used a combination of bolus intravenous propofol and ketorolac, the latter primarily for postoperative pain. Ketamine was used adjunctively for women with a body mass index (BMI) N 35 kg/m 2. Patients were not intubated. Trainee physicians did not participate in any of the procedures. Study team members not involved in data collection conducted descriptive statistics, comparing by cervical preparation type, to determine whether the groups differed
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by sociodemographic factors, medical and obstetric history, and procedure variables. We performed bivariate linear regression to evaluate the association of each potential confounder on procedure duration, including gravidity, prior vaginal delivery, prior cesarean section, prior abortion, BMI, gestational age and age. We then assessed effect modification by conducting t tests of procedure duration by cervical preparation type within each strata of each confounder assessed in bivariate linear regression. We subsequently performed multivariable linear regression adjusting for possible confounders to compare procedure duration between the groups. All variables included in bivariate linear regression were considered clinically relevant to procedure duration and were, therefore, also included in the multivariable linear regression model. We used SAS version 9.3 (SAS Institute Inc., Cary, NC, USA) to conduct analyses and considered pb.05 to be statistically significant.
3. Results In review of clinic logs during the study period, we identified 148 consecutive charts of women who received cervical dilators or misoprostol for at least 1 h and met the gestational age criteria. Three charts were excluded due to missing procedure durations, resulting in 145 charts for evaluation, including 64 women who received misoprostol and 81 who received overnight osmotic dilator preparation. Women in the misoprostol group were more likely to be employed and be uninsured compared to the laminaria group. The two groups did not otherwise differ with regard to sociodemographic, medical and obstetric history factors (Table 1). The groups were also similar with regard to gestational age (Table 2). The total duration from initiation of cervical preparation to completion of surgery was significantly longer in the osmotic dilator group (pb.001) (Table 2). Women who received misoprostol for cervical preparation had on average 95.6 min of preprocedure preparation with range of 61–182 min. Median duration of misoprostol exposure did not differ between the 24 nulliparous women (83.0 min, range 61.0–170.0 min) and the 40 parous women (88.5 min, range 62.0–182.0 min, p=.44). Women received between 3–8 laminaria and 0–2 Dilapan-S osmotic dilators. Duration of procedure, however, did not differ between women who received misoprostol with regard to cervical preparation type (median 11.0 min, range 3.0–24.0 min) and overnight dilators (median 10.0 min, range 3.0–20.0 min, p=.22) (Fig. 1). We conducted a post hoc power calculation using the mean duration and standard deviation from the laminaria group with an alpha of .05. Based on these values, our sample size had 85% power to detect a clinically relevant 1.5-min difference in procedure duration between the two groups. The surgeon's estimated blood loss measurements were 100 cc for all procedures, with the exception of one procedure in the misoprostol group that had an estimated
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Table 1 Sociodemographic, medical and obstetric history factors by cervical preparation type. Misoprostol Osmotic dilator p Value group (n=64) group (n=81) Race/Ethnicity a African American 45 (71.4) Hispanic/Latina 10 (15.9) White 7 (11.1) Other 1 (1.6) Age Mean (SD) 23.7 (5.7) b 20 y 15 (23.4) 20–29 y 41 (64.1) ≥ 30 y 8 (12.5) BMI Mean (SD) 28.3 (7.4) Underweight/Normal weight 22 (34.4) Overweight (BMI 25–29.99 kg/m2) 20 (31.2) 22 (34.4) Obese (BMI ≥ 30.0 kg/m 2) Educationa ≤ 8th grade 2 (3.2) Some high school 14 (22.2) High school graduate 19 (30.2) Some college 23 (36.5) College/postgraduate degree 5 (7.9) Marital status a Single 53 (84.1) Previously married 0 (0.0) Living with partner 6 (9.5) Married 4 (6.4) Employment a Unemployed 38 (60.3) Employed 25 (39.7) Health insurance status a No insurance 20 (32.2) Public insurance 29 (46.8) Private insurance 13 (21.0) Gravidity 1 16 (25.0) 2 10 (15.6) ≥3 38 (59.4) Prior vaginal delivery 0 24 (37.5) ≥1 40 (62.5) Prior cesarean section 0 55 (85.9) ≥1 9 (14.1) Prior abortion 0 27 (42.2) ≥1 37 (57.8)
.64 b 55 13 12 0
(68.8) (16.3) (15.0) (0.0) .58
23.9 (5.9) 24 (29.6) 45 (55.6) 12 (14.8) .73 27.7 (6.4) 33 (40.7) 22 (27.2) 26 (32.1) .83 b 1 20 22 28 10
(1.2) (24.7) (27.2) (34.6) (12.4) .49 b
66 3 7 3
(83.5) (3.8) (8.9) (3.8) .040
61 (76.3) 19 (23.8) .023 11 (13.6) 52 (64.2) 18 (22.2) .39 13 (16.1) 16 (19.7) 52 (64.2) .10 20 (24.7) 61 (75.3) .21 63 (77.8) 18 (22.2) .39 40 (49.4) 41 (50.6)
Data are n (%) unless otherwise specified. p Values were derived from t tests and chi-square tests unless otherwise noted. a Two patients had missing values for race/ethnicity, employment status and health insurance status; 1 patient had missing values for education; and 3 patients had missing values for marital status. b p Value was derived from a Fisher's Exact Test.
blood loss of 50 cc. The maximum cervical dilation was recorded as 14 mm for all but one procedure (one procedure in the misoprostol group had a maximum cervical dilation of 16 mm). Postoperative vaginal bleeding, pain, and nausea and vomiting were not significantly different between groups, with a majority experiencing moderate blood loss,
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Table 2 Procedure variables by cervical preparation type. Misoprostol group (n=64)
Osmotic dilator group (n=81)
Gestational age (days) Mean (SD) 102.9 (4.5) 103.7 (4.8) 14 weeks 34 (53.1) 37 (45.7) 15 weeks 30 (46.9) 44 (54.3) Osmotic dilator received Laminaria only NA 44 (54.3) Dilapan only 0 (0.0) Both laminaria and dilapan 37 (45.7) Duration of preparation (h) Mean (SD) 1.6 (0.5) 20.3 (2.3) Duration of surgery (min) Median (range) 11.0 (3.0–24.0) 10.0 (3.0–20.0) Preparation initiation to completion of surgery (h) Mean (SD) 1.8 (0.5) 20.5 (2.3) Maximum cervical dilation (mm)b,c 14 62 (98.4) 81 (100.0) 16 1 (1.6) 0 (0.0)
Table 3 Postoperative factors/side effects by cervical preparation type. p Value .37
NA
NA b.001 .22 a b.001 .44 d
Data are n (%) unless otherwise specified. p Values were derived from t tests and chi-square tests unless otherwise noted. a p Value was derived from a Wilcoxon rank sum test. b One patient a had missing value for dilator size. c Estimated by the surgeon, using Hegar dilators. d p Value was derived from a Fisher's Exact Test.
minimal pain and no nausea/vomiting (Table 3). No surgical complications were noted in either group, and all procedures in both groups were completed. No perioperative medications including paracervical block anesthesia or uterotonic agents were administered to either group. On bivariate analyses, gestational age was the only variable significantly related to procedure duration, such
Median procedure duration (minutes)
30
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Misoprostol Osmotic dilator p Value group (n=64) group (n= 81) Postoperative vaginal bleedinga None Scant Small Moderate Heavy Postoperative pain a None Minimal Moderate/severe Postoperative nausea/vomiting a None Emesis
.70 b 1 12 9 34 2
(1.7) (20.7) (15.5) (58.6) (3.5)
0 12 16 46 2
(0.0) (15.8) (21.1) (60.5) (2.6) .99 b
20 (37.7) 30 (56.6) 3 (5.7)
21 (36.8) 33 (57.9) 3 (5.3)
62 (100.0) 0 (0.0)
76 (100.0) 0 (0.0)
NA
Data are n (%). a Eleven patients had missing values for postoperative vaginal bleeding, 35 patients had missing values for pain, and 7 patients had missing values for nausea/vomiting. b p Value was derived from a Fisher's Exact Test.
that the procedure lasted 1.15 min longer for women of 15 weeks' gestation compared to women of 14 weeks' gestation (p=.039) (Table 4). When comparing by preparation type, the mean procedure duration did not differ within any strata of the confounders, and therefore, effect modification was not observed. After adjusting for potential confounders of interest (gravidity, prior vaginal delivery, prior cesarean section, prior abortion, BMI, gestational age and patient age), procedure duration was not different between the cervical preparation groups (p=.17) (Table 4). Women with a history of a prior abortion had longer procedure duration compared to women with no history of a prior abortion (p=.036). Gestational age and a history of prior cesarean section approached statistical significance (p=.06 for both variables). Procedure duration did not differ according to prior vaginal deliveries.
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4. Discussion 15
10
5
0 Misoprostol Group n=64
Osmotic Dilator Group n=81
p-Value=.22a
Fig. 1. Median procedure duration by cervical preparation group.
Our results indicate no statistically or clinically significant difference in procedure duration between using at least 1 h of preprocedure buccal misoprostol vs. overnight osmotic dilators prior to early second-trimester surgical abortion in this practice setting. No differences were noted between maximum mechanical dilation, estimated blood loss and postoperative side effects, and all procedures in both groups were able to be completed. With an experienced surgeon, the use of this preprocedure misoprostol protocol significantly shortened the overall time associated with cervical preparation prior to early second-trimester surgical abortion by 19 h and avoided the potential discomfort of osmotic dilator insertion [20]. Therefore, use of at least 1 h of preprocedure buccal misoprostol for this gestational age may
S. Ramesh et al. / Contraception xx (2015) xxx–xxx
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Table 4 Bivariate and multivariable linear regression of relationship between individual factors and procedure duration. Bivariate
Cervical preparation type Osmotic dilator Misoprostol Gravidity 1 2 ≥3 Prior vaginal delivery 0 ≥1 Prior cesarean section 0 ≥1 Prior abortion 0 ≥1 BMI Underweight/Normal weight Overweight Obese Gestational age 14 weeks and 0–6 days 15 weeks and 0–6 days Age b 20 20–29 ≥ 30
Multivariable
Estimate
95% Confidence limits
Estimate a
95% Confidence limits
Reference 0.79
– − 0.31 to 1.89
Reference 0.77
– − 0.33 to 1.88
Reference − 0.07 − 1.26
– − 1.83 to 1.70 − 2.66 to 0.14
Reference − 1.42 − 3.60
– − 3.81 to 0.97 − 6.69 to − 0.50
Reference − 0.57
– − 1.77 to 0.62
Reference 1.12
– − 0.88 to 3.13
Reference 0.82
– − 0.59 to 2.22
Reference 1.46
– − 0.04 to 2.95
Reference 0.02
– − 1.09 to 1.12
Reference 1.71
– 0.12 to 3.29
Reference − 0.01 0.39
– − 1.36 to 1.36 − 0.92 to 1.71
Reference 0.41 0.69
– − 0.96 to 1.78 − 0.52 to 2.19
Reference 1.15
– 0.06 to 2.23
Reference 0.55
– − 0.02 to 2.13
0.88 Reference − 0.96
− 0.38 to 2.15 – − 2.59 to 0.67
0.73 Reference − 0.46
− 0.89 to 2.31 – − 2.13 to 1.21
a
Differences in procedure duration (minutes) on average after controlling for gravidity, prior vaginal delivery, prior cesarean section, prior abortion, BMI, gestational age and patient age.
be a safe option for early second-trimester surgical abortions, under the appropriate circumstances. Previously published literature is heterogeneous with regard to route, dosage and preprocedure duration of misoprostol for cervical preparation between 14 and 20 weeks. Existing literature describes using routes including vaginal and buccal doses ranging from 200 to 800 mcg, and durations of use between as little as 90 min to 3–4 h [9,12–16]. Nucatola and colleagues' [18] case series of 6620 surgical abortions between 12 and 16 weeks performed after 90 min of cervical preparation with misoprostol (400 mcg via either vaginal or buccal administration) noted a 0.45/1000 uterine perforation rate, similar to baseline risk reported in the literature of 0.8–7/1000 uterine perforations/surgical second-trimester abortions. Our study is a comparative study to evaluate procedure duration after using as little as 1 h of misoprostol cervical preparation vs. overnight osmotic dilators. While the mean misoprostol exposure time in this cohort of women was 95.6 min, some women received as few as 61 min. It is possible that this duration was not long enough for some women to benefit from the misoprostol. However, pharmacokinetic data from Meckstroth and colleagues [19] demonstrate that most women in this cohort likely reached peak levels. Together with prior studies demonstrating the safety of using 90 min of misoprostol cervical preparation and the time frame
to reach peak misoprostol levels, this study further supports considering the use of a shorter duration of misoprostol prior to early second-trimester surgical abortion [18,19]. However, further study is needed to determine if local action of misoprostol at the cervix is maximized at the time of peak serum levels or at a later time point. In addition, due to the small size of this study and the high level of experience of the surgeon who performed all procedures, our results may indicate that as little as 1 h, misoprostol had minimal effect on the cervix and that our procedure durations instead reflect the experience of the provider. This study's results are limited by the retrospective design of this study. Because women were not randomly assigned to a method of cervical preparation and offering of the different methods by APNs was subjective, selection bias is highly possible. Certain patient characteristics may have influenced how APNs counseled women about cervical preparation and whether APNs offered women the option of misoprostol. Although evaluation of obstetric and gynecologic characteristics demonstrated no differences between women receiving different types of cervical preparation, statistical manipulation cannot completely mitigate potential biases. While we found no difference in reported postoperative side effects, we did not have data available on preoperative side effects. Patients receiving overnight laminaria and same-day misoprostol likely
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experience differences in preprocedure side effects, such as cramping, nausea and vomiting [6,21–23]. Additionally, the surgeon's high level of experience and the routine use of general anesthesia may limit the generalizability of our study findings, especially in settings with trainees or where intravenous conscious sedation is the primary pain control regimen. However, the fact that the same highly experienced surgeon completed all procedures did ensure standardization of procedure technique. Our sample size also introduces additional limitations to this study. We were adequately powered to detect a clinically significant 1.5-min difference in procedure durations between the two groups. However, we were inadequately powered to compare differences between nulliparous and parous women who received misoprostol. The median procedure durations of 11.0 min for the misoprostol group and 10.0 min for the osmotic dilator group are longer than procedure durations previously reported for similar procedures. This difference is likely due in part to the use of speculum placement to define the surgical start time as opposed to introduction of mechanical dilators or a suction cannula as reported in some prospective studies. In addition, since all patients received general anesthesia, the surgeon had no need to feel rushed to complete the procedure on account of potential patient discomfort. This longer procedure duration may have diluted a potential impact of cervical preparation on the duration of the evacuation. That women with one or more prior abortion had longer procedure durations compared to women without a prior abortion may suggest that prior cervical procedures may result in more challenging surgeries. However, prior research has found no association between prior abortion and duration of procedure and this finding may, therefore, be attributed to chance [8]. Finally, although we had no adverse events in our study, our study was not powered for these rare outcomes. Large prospective studies are needed to evaluate for differences in rare complications such as cervical laceration and uterine perforation. In a clinical setting with a highly experienced surgeon and the use of general anesthesia, at least 1 h of preprocedure misoprostol significantly decreased the duration of cervical preparation for women presenting for early second-trimester surgical abortion. Based on our results, at least 1 h of preprocedure misoprostol prior to early second-trimester surgical abortion may be an appropriate method of cervical preparation in specific practice settings. Further studies are needed to determine optimal dosing and duration of misoprostol for cervical preparation, acceptability of misoprostol associated preoperative side effects, risk/rates of complications with misoprostol alone for cervical preparation as well as the role of adjunctive mifepristone. In this practice setting, where all women visited the clinic on 2 consecutive days regardless of method of cervical preparation, the use of same-day misoprostol did not decrease women's total abortion duration (from initiation of counseling to completion of procedure). Should additional studies further demonstrate the effectiveness of this approach
to cervical preparation, same-day surgical procedures with very short durations of cervical preparation can be achieved. Acknowledgments The authors would like to thank Dr. Darwin Jackson, the surgeon who performed the procedures analyzed in this study. References [1] Grimes D, Schulz K. Morbidity and mortality from second trimester abortions. J Reprod Med 1985;30:505–14. [2] Schulz K, Grimes D, Cates W. Measures to prevent cervical injury during suction curettage abortion. Lancet 1983;8335:1182–5. [3] Grossman D, Blanchard K, Blumenthal P. Complications after second trimester surgical and medical abortion. Reprod Health Matters 2008;16:173–82. [4] Hammond C, Chasen S. Dilation and evacuation. In: Paul M, Lichtenberg E, Borgatta L, Grimes D, Stubblefield P, & Creinin M, editors. Management of unintended and abnormal pregnancy. Chichester, West Sussex, UK: Wiley-Blackwell; 2009, pp. 157–77. [5] Jacot FR, Poulin C, Bilodeau AP, Morin M, Moreau S, Gendron F, et al. A five-year experience with second-trimester induced abortions: no increase in complication rate as compared to the first trimester. Am J Obstet Gynecol 1993;168:633–7. [6] Fox M, Krajewski C. Cervical preparation for second trimester surgical abortion prior to 20 weeks of gestation: SPF guideline #2013-4. Contraception 2014;89:75–84. [7] Searle L, Tait J, Langdana F, Maharaj D. Efficacy of mifepristone for cervical priming for second-trimester surgical termination of pregnancy. Int J Obstet Gynecol 2014;124:38–41. [8] Borgatta L, Roncari D, Sonalkar S, Mark A, Hou M, Finneseth M, et al. Mifepristone vs. osmotic dilator insertion for cervical preparation prior to surgical abortion at 14–16 weeks: a randomized trial. Contraception 2012;86:567–71. [9] Patel A, Talmont E, Morfesis J, Pelta M, Gatter M, Momtaz M, et al. Adequacy and safety of buccal misoprostol for cervical preparation prior to termination of second-trimester pregnancy. Contraception 2006;73:420–30. [10] Panchal H, Godfrey E, Patel A. Buccal misoprostol for cervical ripening prior to first trimester abortion. Contraception 2010;81:161–4. [11] Allen RH, Goldberg AB. Cervical dilation before first-trimester surgical abortion (b14 weeks gestation). SFP Guideline 20071. Contraception 2007;76:139–56. [12] Peterson WF, Berry FN, Grace MR, Gulbranson CL. Second-trimester abortion by dilation and evacuation: an analysis of 11,747 cases. Obstet Gynecol 1983;62:185–90. [13] MacIsaac L, Grossman D, Balistreri E, Darney P. A randomized controlled trial of laminaria, oral misoprostol, and vaginal misoprostol before abortion. Obstet Gynecol 1999;93:766–70. [14] Todd C, Soler M, Castleman L, Rogers M, Blumenthal P. Buccal misoprostol as cervical preparation for second trimester pregnancy termination. Contraception 2002;65:415–8. [15] Bartz D, Maurer R, Allen R, Fortin J, Kuang B, Goldberg A. Buccal misoprostol compared with synthetic osmotic cervical dilator before surgical abortion. Obstet Gynecol 2013;122:57–63. [16] Goldberg A, Drey E, Whitaker A, Kang A, Meckstroth K, Darney P. Misoprostol compared with laminaria before early second trimester surgical abortion: a randomized trial. Obstet Gynecol 2005;106:234–41. [17] O'Connell K, Jones HE, Lichtenberg ES, Paul M. Second-trimester surgical abortion practices: a survey of National Abortion Federation members. Contraception 2008;78:492–9. [18] Nucatola D, Roth N, Saulsberry V, Gatter M. Serious adverse events associated with the use of misoprostol alone for cervical preparation
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Original research article
Misoprostol 1 to 3 h preprocedure vs. overnight osmotic dilators prior to early second-trimester surgical abortion☆ Shanthi Ramesh a , Alicia Roston b , Lindsay Zimmerman b , Ashlesha Patel a, b , E. Steve Lichtenberg a, c , Julie Chor b,⁎ a
Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA b Department of Obstetrics and Gynecology, The John H. Stroger, Jr. Hospital of Cook County, Chicago, IL, USA c Family Planning Associates Medical Group, Limited, Chicago, IL, USA Received 30 July 2014; revised 9 April 2015; accepted 9 April 2015
Abstract Objectives: We sought to compare the effectiveness of at least 1 h of 400 mcg of buccal misoprostol to overnight osmotic dilators for early second-trimester surgical abortion cervical preparation. Design: We conducted a retrospective cohort study, reviewing 145 consecutive charts to compare procedure duration for women who received 400 mcg of buccal misoprostol at least 1 h preprocedure vs. overnight osmotic dilators before dilation and evacuation between 14 weeks, 0 days and 15 weeks, 6 days' gestation. Primary outcome was procedure duration and secondary outcomes included maximum mechanical dilator size, estimated blood loss and side effects. Results: Sixty-four women (44.1%) received buccal misoprostol (mean 1.6 h), and 81 women (55.9%) received overnight osmotic dilators. Groups did not differ regarding mean gestational age or gynecologic history. All procedures in both groups were completed. Procedure duration was not significantly different between the misoprostol and osmotic dilator groups (median 11.0 min vs. 10.0 min, p=.22), even after multivariable linear regression (p=.17). The mean total cervical preparation duration was 1.6 h for women in the misoprostol group compared to 20.3 h in the osmotic dilator group (pb.001). Secondary outcomes did not differ between groups. Conclusions: We found that at least 1 h of preprocedure misoprostol decreased the duration of cervical preparation for early second-trimester procedures performed by an experienced surgeon. Implications: In this small, retrospective review, at least 1 h of preprocedure buccal misoprostol decreased the duration from cervical preparation initiation to procedure completion in early second-trimester procedures performed by an experienced surgeon. These results should be considered as a pilot evaluation, and further prospective study is needed to further clarify whether this short interval could be applied in general practice. © 2015 Elsevier Inc. All rights reserved. Keywords: Surgical abortion; Cervical preparation; Misoprostol; Osmotic dilators
1. Introduction Cervical preparation prior to dilation and evacuation (D&E) is an important measure to decrease complications [1–5]. Protocols for cervical preparation include using osmotic dilators, prostaglandins and/or antiprogestins to reduce the
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Presented at the American Congress of Obstetricians and Gynecologists Annual Clinical Meeting, April 26–30, 2014, Chicago, IL, USA. ⁎ Corresponding author at: 5841 South Maryland Avenue, MC 2050, Chicago, IL 60637, USA. E-mail address: [email protected] (J. Chor). http://dx.doi.org/10.1016/j.contraception.2015.04.005 0010-7824/© 2015 Elsevier Inc. All rights reserved.
need for additional mechanical dilation that may result in increased risk of cervical trauma and uterine perforation [2–8]. Misoprostol alone for cervical preparation is of clinical interest, as it facilitates same-day procedures compared to 2-day procedures often required with osmotic dilators. Additional advantages include patient acceptability of oral or buccal medications and decreased cost [9]. Several studies demonstrate increased dilation, greater ease of dilation and shorter procedure time when using 400 mcg of misoprostol administered buccally or vaginally 1–2 h prior to first-trimester surgical abortion [10,11]. However, data regarding the use of misoprostol alone prior to second-trimester surgical abortion are less clear. Existing studies vary regarding gestational age
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range, route of administration and duration of use with inconsistent results on overall procedure time and ease of dilation [12–16]. Despite conflicting data, in a 2001 survey of National Abortion Federation clinics, 40% of respondents reported routinely using misoprostol alone for cervical preparation at 16 weeks or less [17]. Protocols requiring a shorter duration of cervical preparation allow for the convenience of a same-day procedure, likely increasing accessibility and acceptability of early second-trimester abortion. Nucatola et al. [18] reported data from 6620 early second-trimester surgical abortions performed at Planned Parenthood of Los Angeles, which had been using 90 min of misoprostol alone for early second-trimester cervical preparation since 2001. This new approach to cervical preparation was not associated with an increase in serious adverse events, including uterine perforation [18]. Pharmacokinetic data demonstrate that over 75% of individuals who receive 400 mcg of buccal misoprostol reach peak serum levels between 30 and 90 min [19]. Building on this existing literature, we present initial data comparing procedure duration using at least 1 h preprocedure 400 mcg of buccal misoprostol vs. overnight osmotic dilators before early second-trimester D&E.
2. Materials and methods We conducted a retrospective cohort study comparing outcomes of women who received at least 1 h of buccal misoprostol or overnight osmotic dilators (combination of laminaria and/or Dilapan-S) for cervical preparation prior to early second-trimester D&E. We reviewed all charts of women presenting for surgical abortion between 14 weeks, 0 days and 15 weeks, 6 days of gestation from January 1, 2011 through June 30, 2011 at a high-volume pregnancy termination clinic, Family Planning Associates (FPA), in Chicago, Illinois. The primary outcome for this study was procedure duration. Secondary outcomes included mechanical dilator size, estimated blood loss and side effects, including postoperative bleeding, postoperative nausea/vomiting and postoperative pain. The institutional review board at the John H. Stroger, Jr. Hospital of Cook County approved the study. A study team member not directly involved in statistical analysis extracted all study data from patient charts. Inclusion criteria included all women who underwent surgical termination between 14 weeks, 0 days and 15 weeks, 6 days' gestation during the study period. Women who did not receive cervical preparation, who received less than 1 h of misoprostol at the discretion of the attending surgeon, or for whom the method of cervical preparation was not recorded in the chart were excluded from the study. Data collected were de-identified and included sociodemographic, reproductive health and procedure details. The primary outcome, procedure duration, was measured to the nearest minute by a highly experienced certified registered nurse anesthetist (CRNA) from the time of speculum insertion to speculum removal. Data for postoper-
ative vaginal bleeding (none/scant/small/moderate/heavy), pain (none/minimal/moderate/severe) and nausea and vomiting (none/emesis) were extracted from the nursing record using a standardized form. During the study period, all women presenting to FPA for surgical abortion 14 weeks, 0 days and 15 weeks, 6 days' gestational age underwent ultrasound confirmation of gestational age, preoperative evaluation, preoperative counseling and consent. At this gestational age, all women visited the clinic on 2 consecutive days for a preoperative visit and surgery. During the preoperative visit, advanced practice nurses (APNs) provided preprocedure counseling, including counseling regarding cervical preparation. The first option, overnight osmotic dilators, would require a shorter waiting time on the day of surgery, as the patient could arrive at the clinic on the day of surgery ready for her procedure. The second option, 400 mcg of buccal misoprostol, would require a longer waiting time on the day of surgery, as it would be administered that day, at least 1 h in advance of the procedure. Accordingly, APNs offered misoprostol as an option if the clinic's volume on the day of surgery could accommodate the longer waiting time that misoprostol requires. Prior to surgical days when the clinic anticipated shorter clinical hours due to a low volume of procedures, women received overnight dilators at their preoperative visit. Prior to a surgical day when the clinic anticipated longer hours due to a high volume of procedures, women were offered the option of either overnight osmotic dilators or day-of-procedure misoprostol. Experienced advanced practice clinicians performed all osmotic dilator placements (laminaria and Dilapan-S) with consultation as indicated by supervising physicians. Dilator placements were often performed after pre-dilation of the cervix using serial mechanical dilation with Hegar dilators up to 12 mm, as allowable without application of undue force. During osmotic dilator insertion, the advanced practice clinicians injected 2–3 ml of a 1% procaine analog to the anterior lip of the cervix (to minimize tenaculum pain) with or without additional paracervical block as needed. Intravenous or intramuscular injections of an analgesic agent (e.g., butorphanol or ketorolac) were also immediately available per standard clinic protocol as clinically indicated. One experienced, board-certified obstetrician-gynecologist performed all D&E procedures under general anesthesia using a 12-mm rigid suction curette and Sopher forceps. Mechanical dilators were used for additional dilation, and the maximum serial Hegar dilator used was recorded in millimeters for all cases prior to evacuation of the uterus. Pain control in every case was provided by a CRNA who used a combination of bolus intravenous propofol and ketorolac, the latter primarily for postoperative pain. Ketamine was used adjunctively for women with a body mass index (BMI) N 35 kg/m 2. Patients were not intubated. Trainee physicians did not participate in any of the procedures. Study team members not involved in data collection conducted descriptive statistics, comparing by cervical preparation type, to determine whether the groups differed
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by sociodemographic factors, medical and obstetric history, and procedure variables. We performed bivariate linear regression to evaluate the association of each potential confounder on procedure duration, including gravidity, prior vaginal delivery, prior cesarean section, prior abortion, BMI, gestational age and age. We then assessed effect modification by conducting t tests of procedure duration by cervical preparation type within each strata of each confounder assessed in bivariate linear regression. We subsequently performed multivariable linear regression adjusting for possible confounders to compare procedure duration between the groups. All variables included in bivariate linear regression were considered clinically relevant to procedure duration and were, therefore, also included in the multivariable linear regression model. We used SAS version 9.3 (SAS Institute Inc., Cary, NC, USA) to conduct analyses and considered pb.05 to be statistically significant.
3. Results In review of clinic logs during the study period, we identified 148 consecutive charts of women who received cervical dilators or misoprostol for at least 1 h and met the gestational age criteria. Three charts were excluded due to missing procedure durations, resulting in 145 charts for evaluation, including 64 women who received misoprostol and 81 who received overnight osmotic dilator preparation. Women in the misoprostol group were more likely to be employed and be uninsured compared to the laminaria group. The two groups did not otherwise differ with regard to sociodemographic, medical and obstetric history factors (Table 1). The groups were also similar with regard to gestational age (Table 2). The total duration from initiation of cervical preparation to completion of surgery was significantly longer in the osmotic dilator group (pb.001) (Table 2). Women who received misoprostol for cervical preparation had on average 95.6 min of preprocedure preparation with range of 61–182 min. Median duration of misoprostol exposure did not differ between the 24 nulliparous women (83.0 min, range 61.0–170.0 min) and the 40 parous women (88.5 min, range 62.0–182.0 min, p=.44). Women received between 3–8 laminaria and 0–2 Dilapan-S osmotic dilators. Duration of procedure, however, did not differ between women who received misoprostol with regard to cervical preparation type (median 11.0 min, range 3.0–24.0 min) and overnight dilators (median 10.0 min, range 3.0–20.0 min, p=.22) (Fig. 1). We conducted a post hoc power calculation using the mean duration and standard deviation from the laminaria group with an alpha of .05. Based on these values, our sample size had 85% power to detect a clinically relevant 1.5-min difference in procedure duration between the two groups. The surgeon's estimated blood loss measurements were 100 cc for all procedures, with the exception of one procedure in the misoprostol group that had an estimated
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Table 1 Sociodemographic, medical and obstetric history factors by cervical preparation type. Misoprostol Osmotic dilator p Value group (n=64) group (n=81) Race/Ethnicity a African American 45 (71.4) Hispanic/Latina 10 (15.9) White 7 (11.1) Other 1 (1.6) Age Mean (SD) 23.7 (5.7) b 20 y 15 (23.4) 20–29 y 41 (64.1) ≥ 30 y 8 (12.5) BMI Mean (SD) 28.3 (7.4) Underweight/Normal weight 22 (34.4) Overweight (BMI 25–29.99 kg/m2) 20 (31.2) 22 (34.4) Obese (BMI ≥ 30.0 kg/m 2) Educationa ≤ 8th grade 2 (3.2) Some high school 14 (22.2) High school graduate 19 (30.2) Some college 23 (36.5) College/postgraduate degree 5 (7.9) Marital status a Single 53 (84.1) Previously married 0 (0.0) Living with partner 6 (9.5) Married 4 (6.4) Employment a Unemployed 38 (60.3) Employed 25 (39.7) Health insurance status a No insurance 20 (32.2) Public insurance 29 (46.8) Private insurance 13 (21.0) Gravidity 1 16 (25.0) 2 10 (15.6) ≥3 38 (59.4) Prior vaginal delivery 0 24 (37.5) ≥1 40 (62.5) Prior cesarean section 0 55 (85.9) ≥1 9 (14.1) Prior abortion 0 27 (42.2) ≥1 37 (57.8)
.64 b 55 13 12 0
(68.8) (16.3) (15.0) (0.0) .58
23.9 (5.9) 24 (29.6) 45 (55.6) 12 (14.8) .73 27.7 (6.4) 33 (40.7) 22 (27.2) 26 (32.1) .83 b 1 20 22 28 10
(1.2) (24.7) (27.2) (34.6) (12.4) .49 b
66 3 7 3
(83.5) (3.8) (8.9) (3.8) .040
61 (76.3) 19 (23.8) .023 11 (13.6) 52 (64.2) 18 (22.2) .39 13 (16.1) 16 (19.7) 52 (64.2) .10 20 (24.7) 61 (75.3) .21 63 (77.8) 18 (22.2) .39 40 (49.4) 41 (50.6)
Data are n (%) unless otherwise specified. p Values were derived from t tests and chi-square tests unless otherwise noted. a Two patients had missing values for race/ethnicity, employment status and health insurance status; 1 patient had missing values for education; and 3 patients had missing values for marital status. b p Value was derived from a Fisher's Exact Test.
blood loss of 50 cc. The maximum cervical dilation was recorded as 14 mm for all but one procedure (one procedure in the misoprostol group had a maximum cervical dilation of 16 mm). Postoperative vaginal bleeding, pain, and nausea and vomiting were not significantly different between groups, with a majority experiencing moderate blood loss,
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Table 2 Procedure variables by cervical preparation type. Misoprostol group (n=64)
Osmotic dilator group (n=81)
Gestational age (days) Mean (SD) 102.9 (4.5) 103.7 (4.8) 14 weeks 34 (53.1) 37 (45.7) 15 weeks 30 (46.9) 44 (54.3) Osmotic dilator received Laminaria only NA 44 (54.3) Dilapan only 0 (0.0) Both laminaria and dilapan 37 (45.7) Duration of preparation (h) Mean (SD) 1.6 (0.5) 20.3 (2.3) Duration of surgery (min) Median (range) 11.0 (3.0–24.0) 10.0 (3.0–20.0) Preparation initiation to completion of surgery (h) Mean (SD) 1.8 (0.5) 20.5 (2.3) Maximum cervical dilation (mm)b,c 14 62 (98.4) 81 (100.0) 16 1 (1.6) 0 (0.0)
Table 3 Postoperative factors/side effects by cervical preparation type. p Value .37
NA
NA b.001 .22 a b.001 .44 d
Data are n (%) unless otherwise specified. p Values were derived from t tests and chi-square tests unless otherwise noted. a p Value was derived from a Wilcoxon rank sum test. b One patient a had missing value for dilator size. c Estimated by the surgeon, using Hegar dilators. d p Value was derived from a Fisher's Exact Test.
minimal pain and no nausea/vomiting (Table 3). No surgical complications were noted in either group, and all procedures in both groups were completed. No perioperative medications including paracervical block anesthesia or uterotonic agents were administered to either group. On bivariate analyses, gestational age was the only variable significantly related to procedure duration, such
Median procedure duration (minutes)
30
25
Misoprostol Osmotic dilator p Value group (n=64) group (n= 81) Postoperative vaginal bleedinga None Scant Small Moderate Heavy Postoperative pain a None Minimal Moderate/severe Postoperative nausea/vomiting a None Emesis
.70 b 1 12 9 34 2
(1.7) (20.7) (15.5) (58.6) (3.5)
0 12 16 46 2
(0.0) (15.8) (21.1) (60.5) (2.6) .99 b
20 (37.7) 30 (56.6) 3 (5.7)
21 (36.8) 33 (57.9) 3 (5.3)
62 (100.0) 0 (0.0)
76 (100.0) 0 (0.0)
NA
Data are n (%). a Eleven patients had missing values for postoperative vaginal bleeding, 35 patients had missing values for pain, and 7 patients had missing values for nausea/vomiting. b p Value was derived from a Fisher's Exact Test.
that the procedure lasted 1.15 min longer for women of 15 weeks' gestation compared to women of 14 weeks' gestation (p=.039) (Table 4). When comparing by preparation type, the mean procedure duration did not differ within any strata of the confounders, and therefore, effect modification was not observed. After adjusting for potential confounders of interest (gravidity, prior vaginal delivery, prior cesarean section, prior abortion, BMI, gestational age and patient age), procedure duration was not different between the cervical preparation groups (p=.17) (Table 4). Women with a history of a prior abortion had longer procedure duration compared to women with no history of a prior abortion (p=.036). Gestational age and a history of prior cesarean section approached statistical significance (p=.06 for both variables). Procedure duration did not differ according to prior vaginal deliveries.
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4. Discussion 15
10
5
0 Misoprostol Group n=64
Osmotic Dilator Group n=81
p-Value=.22a
Fig. 1. Median procedure duration by cervical preparation group.
Our results indicate no statistically or clinically significant difference in procedure duration between using at least 1 h of preprocedure buccal misoprostol vs. overnight osmotic dilators prior to early second-trimester surgical abortion in this practice setting. No differences were noted between maximum mechanical dilation, estimated blood loss and postoperative side effects, and all procedures in both groups were able to be completed. With an experienced surgeon, the use of this preprocedure misoprostol protocol significantly shortened the overall time associated with cervical preparation prior to early second-trimester surgical abortion by 19 h and avoided the potential discomfort of osmotic dilator insertion [20]. Therefore, use of at least 1 h of preprocedure buccal misoprostol for this gestational age may
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Table 4 Bivariate and multivariable linear regression of relationship between individual factors and procedure duration. Bivariate
Cervical preparation type Osmotic dilator Misoprostol Gravidity 1 2 ≥3 Prior vaginal delivery 0 ≥1 Prior cesarean section 0 ≥1 Prior abortion 0 ≥1 BMI Underweight/Normal weight Overweight Obese Gestational age 14 weeks and 0–6 days 15 weeks and 0–6 days Age b 20 20–29 ≥ 30
Multivariable
Estimate
95% Confidence limits
Estimate a
95% Confidence limits
Reference 0.79
– − 0.31 to 1.89
Reference 0.77
– − 0.33 to 1.88
Reference − 0.07 − 1.26
– − 1.83 to 1.70 − 2.66 to 0.14
Reference − 1.42 − 3.60
– − 3.81 to 0.97 − 6.69 to − 0.50
Reference − 0.57
– − 1.77 to 0.62
Reference 1.12
– − 0.88 to 3.13
Reference 0.82
– − 0.59 to 2.22
Reference 1.46
– − 0.04 to 2.95
Reference 0.02
– − 1.09 to 1.12
Reference 1.71
– 0.12 to 3.29
Reference − 0.01 0.39
– − 1.36 to 1.36 − 0.92 to 1.71
Reference 0.41 0.69
– − 0.96 to 1.78 − 0.52 to 2.19
Reference 1.15
– 0.06 to 2.23
Reference 0.55
– − 0.02 to 2.13
0.88 Reference − 0.96
− 0.38 to 2.15 – − 2.59 to 0.67
0.73 Reference − 0.46
− 0.89 to 2.31 – − 2.13 to 1.21
a
Differences in procedure duration (minutes) on average after controlling for gravidity, prior vaginal delivery, prior cesarean section, prior abortion, BMI, gestational age and patient age.
be a safe option for early second-trimester surgical abortions, under the appropriate circumstances. Previously published literature is heterogeneous with regard to route, dosage and preprocedure duration of misoprostol for cervical preparation between 14 and 20 weeks. Existing literature describes using routes including vaginal and buccal doses ranging from 200 to 800 mcg, and durations of use between as little as 90 min to 3–4 h [9,12–16]. Nucatola and colleagues' [18] case series of 6620 surgical abortions between 12 and 16 weeks performed after 90 min of cervical preparation with misoprostol (400 mcg via either vaginal or buccal administration) noted a 0.45/1000 uterine perforation rate, similar to baseline risk reported in the literature of 0.8–7/1000 uterine perforations/surgical second-trimester abortions. Our study is a comparative study to evaluate procedure duration after using as little as 1 h of misoprostol cervical preparation vs. overnight osmotic dilators. While the mean misoprostol exposure time in this cohort of women was 95.6 min, some women received as few as 61 min. It is possible that this duration was not long enough for some women to benefit from the misoprostol. However, pharmacokinetic data from Meckstroth and colleagues [19] demonstrate that most women in this cohort likely reached peak levels. Together with prior studies demonstrating the safety of using 90 min of misoprostol cervical preparation and the time frame
to reach peak misoprostol levels, this study further supports considering the use of a shorter duration of misoprostol prior to early second-trimester surgical abortion [18,19]. However, further study is needed to determine if local action of misoprostol at the cervix is maximized at the time of peak serum levels or at a later time point. In addition, due to the small size of this study and the high level of experience of the surgeon who performed all procedures, our results may indicate that as little as 1 h, misoprostol had minimal effect on the cervix and that our procedure durations instead reflect the experience of the provider. This study's results are limited by the retrospective design of this study. Because women were not randomly assigned to a method of cervical preparation and offering of the different methods by APNs was subjective, selection bias is highly possible. Certain patient characteristics may have influenced how APNs counseled women about cervical preparation and whether APNs offered women the option of misoprostol. Although evaluation of obstetric and gynecologic characteristics demonstrated no differences between women receiving different types of cervical preparation, statistical manipulation cannot completely mitigate potential biases. While we found no difference in reported postoperative side effects, we did not have data available on preoperative side effects. Patients receiving overnight laminaria and same-day misoprostol likely
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experience differences in preprocedure side effects, such as cramping, nausea and vomiting [6,21–23]. Additionally, the surgeon's high level of experience and the routine use of general anesthesia may limit the generalizability of our study findings, especially in settings with trainees or where intravenous conscious sedation is the primary pain control regimen. However, the fact that the same highly experienced surgeon completed all procedures did ensure standardization of procedure technique. Our sample size also introduces additional limitations to this study. We were adequately powered to detect a clinically significant 1.5-min difference in procedure durations between the two groups. However, we were inadequately powered to compare differences between nulliparous and parous women who received misoprostol. The median procedure durations of 11.0 min for the misoprostol group and 10.0 min for the osmotic dilator group are longer than procedure durations previously reported for similar procedures. This difference is likely due in part to the use of speculum placement to define the surgical start time as opposed to introduction of mechanical dilators or a suction cannula as reported in some prospective studies. In addition, since all patients received general anesthesia, the surgeon had no need to feel rushed to complete the procedure on account of potential patient discomfort. This longer procedure duration may have diluted a potential impact of cervical preparation on the duration of the evacuation. That women with one or more prior abortion had longer procedure durations compared to women without a prior abortion may suggest that prior cervical procedures may result in more challenging surgeries. However, prior research has found no association between prior abortion and duration of procedure and this finding may, therefore, be attributed to chance [8]. Finally, although we had no adverse events in our study, our study was not powered for these rare outcomes. Large prospective studies are needed to evaluate for differences in rare complications such as cervical laceration and uterine perforation. In a clinical setting with a highly experienced surgeon and the use of general anesthesia, at least 1 h of preprocedure misoprostol significantly decreased the duration of cervical preparation for women presenting for early second-trimester surgical abortion. Based on our results, at least 1 h of preprocedure misoprostol prior to early second-trimester surgical abortion may be an appropriate method of cervical preparation in specific practice settings. Further studies are needed to determine optimal dosing and duration of misoprostol for cervical preparation, acceptability of misoprostol associated preoperative side effects, risk/rates of complications with misoprostol alone for cervical preparation as well as the role of adjunctive mifepristone. In this practice setting, where all women visited the clinic on 2 consecutive days regardless of method of cervical preparation, the use of same-day misoprostol did not decrease women's total abortion duration (from initiation of counseling to completion of procedure). Should additional studies further demonstrate the effectiveness of this approach
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