Paracervical block as pain treatment during second-trimester medical termination of pregnancy: an RCT with bupivacaine versus sodium chloride.

STUDY QUESTION

Can paracervical block (PCB) administered before the onset of pain decrease women's pain experience during second-trimester medical termination of pregnancy (MToP)?

SUMMARY ANSWER

There were no clinically significant differences between groups receiving PCB with bupivacaine or saline with regard to the highest and lowest pain intensity, morphine consumption or induction-to abortion interval.

WHAT IS KNOWN ALREADY

The most common side effect of misoprostol is pain; nevertheless, there are sparse studies in pain and pain treatment during MToP, especially in second-trimester abortion. Pain reported in second-trimester medical abortion is often intense, and peaks when the fetal expulsion occurs.

STUDY DESIGN, SIZE, DURATION: A double-blinded RCT was carried out from May 2012 until April 2015. A power calculation was based on a previous pilot study showing that the proportion of women with severe pain [visual analogue scale (VAS) ≥7] was 63%. A clinically significant reduction was considered to yield 35% with severe pain, and with a power of 80% and significance level of 5% (two-sided) 112 women were needed. Accounting for a 20% drop-out rate, a total of 140 women were needed. The primary outcome, pain intensity measured as any VAS ≥7, was analysed using a generalized estimating equations model. The level of significance was set to P < 0.05 two-sided. A computer generated randomization list with block size of 10 was used. The treatment allocation was placed in a sealed, opaque, envelope and picked consecutively.

PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 589 women attending a gynaecological clinic had a second-trimester abortion during the study period and 276 were invited to participate. A total of 113 women undergoing abortion from 13 weeks of gestation and above were recruited, of which 55 were randomly allocated to receive a PCB with bupivacaine and 58 a PCB with sodium chloride 1 h after the first dose of misoprostol. The full analysis set (FAS) population was defined as all randomized women that had at least one value for any of the outcomes (n = 102). The per-protocol (PP) population was defined as a subset of the FAS excluding patients with major protocol deviations or without a value for the primary outcome (n = 99). Pain was measured by VAS at misoprostol initiation (baseline) and repeated every 30 min until fetal expulsion. The primary outcome was the highest VAS pain intensity at any time point.

MAIN RESULTS AND THE ROLE OF CHANCE

The highest pain intensity, did not show any differences at a cut-off of VAS ≥7 [risk ratio (RR): 1.1; 95% confidence interval (CI): 0.9-1.5; P = 0.0.292]. In the PP analyses, there were 75% women in the bupivacaine group and 64% in the sodium chloride group with VAS ≥7 (RR: 1.2; 95% CI: 0.9-1.5; P = 0.235). Most women did not experience pain at the misoprostol start, 19 women scored a VAS of >0, ranging from 1 to 4 with a mean of 1.8 and median of 2 (P = 1.000). Immediately prior to PCB, 61 women scored a VAS of >0, from 1 to 10 with a mean of 2.0 and median of 1 (P = 0.771). There was a 48% loss of VAS scores at the time of expulsion and the remaining scores did not differ between groups (RR: 1.5; 95% CI: 0.9-2.5). A subgroup analysis of primipara did not show any difference in highest pain intensity VAS ≥7 (RR: 1.2; 95% CI: 0.9-1.6; P = 0.283). No statistically significant differences were observed between groups with regard to the highest and lowest (P = 553 and 0.182) pain intensity and morphine consumption (P = 0.772). Side effects were reported by 28 women (14 women in each group), with no differences between groups. Most common was nausea and vomiting in connection to morphine injection.

LIMITATIONS, REASONS FOR CAUTION: Nearly 60% of the invited women did not want to participate in the study (fear of needles and fear of receiving the placebo) therefore women who tolerate pain may have been overrepresented in the study population. Data collection was stopped, in error, when 113 participants had been recruited. The loss to follow-up was, however, only 11 women (10%), which was lower than expected but intrinsically the study did not fully reach the intended number of women, which may have influenced the results. In addition, the obstetrical and gynaecological background of participating women differs. The participants were informed that they had a 50% chance of receiving a PCB with active substance, which could theoretically have affected their expectations and pain experience (placebo effect). The frequent attention at VAS scoring and the overall care provided may also have affected the participants in a positive way, and helped women to feel supported and more relaxed during the abortion.

WIDER IMPLICATIONS OF THE FINDINGS

The highest pain intensity was severe (VAS: 7-10) among 65-75% of the participants, as reported for first-trimester medical abortion; however, the maximal pain scores remain high despite the PCB. There is, therefore, a clear need for more optimal pain treatment but only limited data exist on pain treatment during MToP over all gestational lengths. As PCB was well tolerated, did not cause any serious side effects and had no negative impact on the abortion process and efficacy, another approach may be worth exploring, namely PCB given on demand at the onset of painful contractions.

STUDY FUNDING/COMPETING INTERESTS: The study was supported by grants from the Swedish Research Council (grant no: 2012-2844), ALF (Karolinska Institutet - Stockholm County Council, Agreement on Medical Research and Training) funding, the Karolinska Institutet, Stockholm South General Hospital, and Swedish Nurses in the Area of Pain - SSOS together with GlaxoSmithKline. None of the authors have any conflicts of interest.

TRIAL REGISTRATION NUMBER

The trial was registered with ClinicalTrials.gov (identifier: NCT01617564) and The EudraCT (number: 2010-020780-21) and was approved by The Regional Ethical Review Board at Karolinska Institutet (dnr: 2007/1277-31/2 and 2010/410-31/1).

TRIAL REGISTRATION DATE

Clinical trial registration was done in May 2012 before initiation of patient recruitment.

DATE OF FIRST PATIENT'S ENROLMENT: 29 May 2012.