Management of pain associated with up-to-9-weeks medical termination of pregnancy (MToP) using mifepristone-misoprostol regimens: expert consensus based on a systematic literature review.

Evidence-based guidelines on the management of pain associated with first-trimester medical abortion are lacking. Most published clinical trials have failed to report on this important aspect of the procedure. The aim of this comprehensive work was to provide clinical advice based on a comprehensive literature review, supplemented by the clinical experience of a group of European experts in case no evidence is available. Pain level ranged from 5 to 8 in 80% of studies where pain was measured on a 0-10 visual analogue scale; severe pain was reported by 20-80% of women. Pain assessment was rarely reported in studies. Pain treatment should be preventive and avoidance of unnecessary uterine contractions should be considered. Analgesic treatment should follow the WHO three-step ladder, starting with the use of NSAIDs and allowing for easily available back-up treatment with weak opioids.

Management of pain associated with the insertion of intrauterine contraceptives.

BACKGROUND: Most intrauterine contraception (IUC) placements do not require pain relief. However, small proportions of nulliparous (∼17%) and parous (∼11%) women experience substantial pain that needs to be proactively managed. This review critically evaluates the evidence for pain management strategies, formulates evidence-based recommendations and identifies data gaps and areas for further research. METHODS: A PubMed literature search was undertaken. Relevant articles on management of pain associated with IUC insertion, published in English between 1980 and November 2012, were identified using the following search terms: 'intrauterine contraception', 'insertion' and 'pain'. RCTs were included; further relevant articles were also identified and included as appropriate. RESULTS: Seventeen studies were identified and included: 12 RCTs and one non-randomized study of pre-insertion oral analgesia, cervical priming and local anaesthesia; one systematic review and one RCT on post-insertion analgesia and two non-randomized studies on non-pharmacological interventions. There was no conclusive evidence that any prophylactic pharmacological intervention reduces pain associated with IUC insertion. However, most of the regimens studied were adopted from hysteroscopy or abortion and effectiveness in specific subsets of women has not been studied adequately. A systematic review found non-steroidal anti-inflammatory agents (NSAID) to be effective in reactively treating post-insertion pain, but no benefit was found with prophylactic use. CONCLUSIONS: No prophylactic pharmacological intervention has been adequately evaluated to support routine use for pain reduction during or after IUC insertion. Women's anxiety about the procedure may contribute to higher levels of perceived pain, which highlights the importance of counselling, and creating a trustworthy, unhurried and professional atmosphere in which the experience of the provider also has a major role; a situation frequently referred to as 'verbal anaesthesia'.

Early luteal phase treatment with mifepristone (RU 486) for fertility regulation.

Mifepristone (RU 486) is an antiprogestin which interacts with progesterone at the receptor level. Administration of mifepristone immediately after ovulation does not upset the menstrual cycle. However, the maturation and function of the endometrium is inhibited and uterine contractility is changed. To test if these effects are sufficient to prevent implantation, 21 women agreed to use one single treatment with 200 mg mifepristone on day luteinizing hormone (LH) + 2 monthly as their only contraceptive method. The women were treated for 1-12 months. The time of the LH peak was determined in the urine by the women themselves using a rapid LH test (Ovu-quick, Organon). The overall number of cycles studied was 169. In 12 cycles the women were unable to detect the LH peak. In these cycles no treatment was given and the women advised to use barrier methods during the time to menstruation. The remaining 157 cycles with a detectable LH peak were all ovulatory based on plasma progesterone measurement. One pregnancy occurred. On the basis of the time of the LH peak, it was retrospectively calculated that in 124 cycles at least one act of intercourse occurred during the period 3 days before to 1 day after ovulation. The probability of pregnancy in this period of the menstrual cycle is thus 0.008. The women did not complain of any treatment-related side-effects apart from slight bleeding for 2-3 days starting a few days after the day of treatment in 35% of the cycles.(ABSTRACT TRUNCATED AT 250 WORDS)

PIP: Mifepristone (RU-486) is an antiprogestin which interacts with progesterone at the receptor level. The objective was to determine whether the effects on endometrial development and function and on uterine contractility of immediate post-ovulatory treatment with mifepristone could prevent pregnancy. 21 fertile, sexually active women with regular menstrual cycles were treated with a single dose of 200 mg mifepristone 2 days after the luteinizing hormone (LH) surge (LH + 2) on a monthly basis for 1-12 months. The time of the LH peak was determined in the urine by the women themselves using a rapid LH test (Ovu-quick, Organon), and this was confirmed later by radioimmunoassay. All the women, except one, had previously had at least 1 delivery and 1 pregnancy terminated. Each woman measured the urine concentration of LH twice daily, starting about 4 days prior to the expected time of ovulation (normally day 10 of the cycle) and continuing until 1 day after the maximum LH concentration. The plasma concentration of progesterone was measured 5 days and human chorionic gonadotrophin (HCG) 2 weeks after the treatment in all cycles. The overall number of cycles studied was 169. In 12 cycles the women were unable to detect the LH peak. The remaining 157 cycles with a detectable LH peak were all ovulatory based on plasma progesterone measurement. 1 pregnancy occurred and was terminated by vacuum aspiration. Based on the time of the LH peak, it was retrospectively calculated that in 124 cycles at least 1 act of intercourse occurred between 3 days before and 1 day after ovulation. The probability of pregnancy in this period of the menstrual cycle was thus 0.008. The were no treatment-related side effects apart from slight bleeding for 2-3 days starting a few days after the day of treatment in 35% of the cycles. The effect of mifepristone on the endometrium was sufficient to prevent pregnancy, therefore it can be used for contraception.

Local anaesthesia in elderly patients. An experimental study of oral infiltration anaesthesia.

The proportion of elderly people is increasing. Normal ageing causes a reduced physiological capacity and ability to meet challenges. In future more elderly people will have functioning natural dentitions and undergo routine dental procedures for which local anaesthesia is required. In this experimental investigation the effect of infiltration anaesthesia from 3 commonly used agents was compared in healthy elderly and young subjects. The subjects comprised 40 volunteers and the anaesthetic agents tested were lidocaine (20 mg/ml) with epinephrine (12.5 micrograms/ml), prilocaine (30 mg/ml) with felypressin (0.54 microgram/ml) and mepivacaine (30 mg/ml). The elderly subjects had a highly significantly shorter onset time compared to the young group. There was no statistically significant difference in duration of tooth anaesthesia between lidocaine with epinephrine and prilocaine with felypressin. Because elderly people have lower drug tolerance, prilocaine with felypressin is therefore recommended for routine dentistry.

The effect of polyphloretin phosphate (PPP) on oral infiltration anaesthesia. An experimental investigation.

The possibilities to discontinue the anaesthetic effect using supplementary substances were studied. This investigation showed that administration of polyphloretin phosphate (PPP), 15 minutes after local anaesthetic injection, decreased the duration of infiltration anaesthesia of human teeth. The same result was also found when PPP was replaced by saline solution. However no effect on the duration of soft tissue anaesthesia was noted. There were no signs of adverse reactions.

Periodontal ligament injection. An experimental study in the monkey.

In an experimental double blind, cross-over study in monkeys, the reactions of the periodontal tissue after periodontal ligament injection of local anaesthetic solution were investigated. Lidocaine 20 mg/ml with adrenaline 12.5 micrograms/ml and mepivacaine 30 mg/ml were used, and the injection times were 5 or 20 s. Histopathological analysis showed cell damage in the tissues near the injection areas immediately after the experimental procedure. In the specimens obtained one week after the periodontal ligament injections, the tissues were found to be normal.

Long-acting local anesthetics in oral surgery: an experimental evaluation of bupivacaine and etidocaine for oral infiltration anesthesia.

The effect of bupivacaine 7.5 mg/ml with epinephrine 5µg/ml, etidocaine 15 mg/ml with epinephrine 5 µg/ml, and lidocaine 20 mg/ml with epinephrine 12.5 µg/ml was studied when used for oral infiltration anesthesia. Twenty healthy volunteers took part in the experimental and double-blind study. One ml of the respective anesthetic solution was deposited supraperiosteally in the apical area of the maxillary right lateral incisor. Onset time, frequency of analgesia, gingival spread, and duration of tooth analgesia were studied and duration of soft-tissue numbness registered. The present investigation showed that lidocaine had a shorter onset time compared with bupivacaine. No difference with regard to frequency was found. Bupivacaine and etidocaine had a longer period of soft-tissue numbness, but a significantly shorter duration of tooth analgesia than lidocaine.

Aspiration in oral local anaesthesia. Frequency of blood in cartridges in an undergraduate student material.

In an experimental study, comprising 1662 injections performed by 120 dental students, the number of aspirations, which were positive for blood was recorded. The highest frequency of positive blood findings in the cartridges by aspiration was found with the mandibular block injections (11,3 per cent). The results are similar to those described in earlier investigations, in which experienced clinicians made the injections. Thus, the clinical experience does not seem to be of determining importance in this connection.