Department of Obstetrics and Gynaecology, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China
1 To whom correspondence should be addressed at: 6/F, Professorial Block, Department of Obstetrics and Gynaecology, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong SAR. China. e-mail: ostang{at}graduate.hku.hk
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Abstract |
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Key words: cervical priming/misoprostol/sublingual/vaginal
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Introduction |
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We have studied a new route of sublingual administration of misoprostol in medical abortion recently (Tang et al., 2002b,c). Misoprostol is absorbed through the vaginal mucosa in vaginal administration. The buccal muscosa, being very vascular, should be able to serve the same purpose. The misoprostol tablet is very soluble in water and dissolves within 1015 min when administered under the tongue. Sublingual administration of misoprostol avoids the first-pass effect via the liver as in oral administration. A pharmacokinetic study showed that sublingual misoprostol was absorbed as rapidly as oral misoprostol and more rapidly than vaginal misoprostol (Tang et al., 2002a
). The peak serum concentration after sublingual misoprostol and the area under the curve was also significantly higher than those after oral or vaginal misoprostol. We have shown that sublingual misoprostol is effective in medical abortion and the management of miscarriage (Tang et al., 2002b,c, 2003
). Sublingual misoprostol is convenient to use, avoids vaginal administration and avoids the ingestion of water before anaesthesia. It is the aim of this randomized study to compare the efficacy of sublingual with vaginal misoprostol for pre-operative cervical priming before surgical termination of pregnancy in the first trimester.
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Methods |
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The 80 women were allocated to the sublingual group and vaginal group by computer-generated random numbers produced and kept by the nurse. They were given misoprostol 400 µg either sublingually or vaginally 3 h before the scheduled operation. The randomization was unknown to the surgeon.
They were admitted to the hospital on the morning of the surgical evacuation. Vacuum aspiration was performed by a single operator (K.H.M.). The blood pressure, pulse rate, temperature and the side-effects were recorded before the operation. The operation was performed under conscious sedation. All subjects were given i.v. fentanyl 25 µg and midazolam 2 mg before the operation. A cervical tonometer (West of Scotland Health Board, Department of Clinical Physics and Bio-engineeing, UK) was used to measure the peak force required to enter the cervical os with successive dilators from 3 to 8 mm. It consisted of a series of tapered dilators attached to a force-sensing handle as described by Hazem et al. (1994). The force required to dilate the cervix was then recorded by the tonometer via a force transducer. The resistance of the cervix to dilatation was objectively assessed when the cervix was dilated using the series of tapered dilators from 3 to 8 mm. Baseline dilatation was defined as the first dilator requiring a peak force of 3 Newton (N) to enter the internal os. Force <3 N was considered to be negligible and this would define the dilatation achieved by misoprostol alone. The cumulative force required to dilate the cervix was calculated by adding the peak force needed for each dilator up to 8 mm. Vacuum aspiration was performed by a Karman curette after the cervix was adequately dilated. The intra-operative blood loss was measured as the volume of the uterine aspirate after sieving away the products of conception. The women were observed for 3 h before discharge from the hospital.
The primary outcome measure was the pre-operative cervical dilatation and was used to calculate the sample size required. The cumulative force required to dilate the cervix from 3 to 8 mm, the intra-operative blood loss and side-effects were also compared. A previous study using similar doses of vaginal misoprostol showed that the baseline dilatation was 7.2 mm and the SD was 1.4 mm (Ngai et al., 1999). A difference of 1 mm in baseline dilatation is considered as clinically significant. Therefore, a sample size of 36 in each arm will have a power of 0.8 at the 5% significance level to detect such a difference in baseline dilatation. Assuming that 10% of the subjects data cannot be used for analysis, the total number of subjects required is 40.
SPSS 10.0 for Windows Statistical Package was used for statistical analysis. Differences in continuous variables were analysed with Students t-test for normally distributed data and the MannWhitney U-test for skewed data. Differences in discontinuous variables were analysed by 2-test and the Fisher exact test as appropriate. P (two-tailed) < 0.05 was considered statistically significant.
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Results |
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Discussion |
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Pharmacological agents have the advantage over osmotic dilators as cervical priming agents since the former does not require a trained medical personnel to administer. Mifepristone and prostaglandin E1 analogues are effective cervical priming agents (El-Refaey et al., 1994; Ngai et al., 1996
). However, mifepristone is expensive, not available in many countries and has the disadvantage of requiring 3648 h for adequate cervical priming effect. Therefore, prostaglandin E1 analogue is usually the drug of choice. It takes a few hours for its action and is convenient for surgical abortion performed as a day case. Misoprostol is the drug of choice although it is not licensed for this purpose since it is cheap and stable at room temperature. A randomized controlled trial has shown that both misoprostol and gemeprost are effective cervical priming agents in the first trimester. However, misoprostol was associated with fewer gastrointestinal side-effects (Henry et al., 1999
).
Various routes of administration of misoprostol have been used for cervical priming in the first trimester. Both oral and vaginal routes were shown to be equally effective when given 3 h before the vacuum aspiration (Ngai et al., 1999). However, both the oral and vaginal routes have drawbacks. Some women found vaginal administration of drug inconvenient and unacceptable (Ho et al., 1997
) and it is more convenient to give a drug by mouth in a day surgery setting. At the same time, it is better to avoid oral intake of fluid before operation, especially if this is done under general anaesthesia. Sublingual misoprostol can avoid the uncomfortable vaginal application and oral intake of fluid before operation. Its clinical effectiveness in cervical priming was proven to be the same as vaginal misoprostol in this study.
Vaginal bleeding and abdominal pain were the commonest side-effects after misoprostol. These side-effects are undesirable because it may affect the acceptability of the method. Severe abdominal pain and heavy bleeding may warrant an emergency vacuum aspiration before the scheduled time. Sometimes the woman may pass the products of conception before the operation. Additional manpower may be required to handle these situations and this may affect the smooth running of the day surgery schedule. In this study, very few women complained of heavy bleeding or severe abdominal pain and none of the women passed the product of conception, which illustrated that both regimens are good for the purpose of cervical priming before first trimester surgical termination of pregnancy in a day surgery setting.
In conclusion, both sublingual and vaginal misoprostol are effective routes of administration for cervical priming prior to surgical termination of pregnancy in the first trimester. Sublingual misoprostol has the advantage of being more convenient to administer and may be more suitable for day surgery.
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Acknowledgements |
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References |
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Submitted on September 29, 2003; resubmitted on November 25, 2003; accepted on December 2, 2003.