Randomized controlled trial comparing carbetocin, misoprostol, and oxytocin for the prevention of postpartum hemorrhage following an elective cesarean delivery.

OBJECTIVE: To compare the effectiveness and safety of carbetocin, misoprostol, and oxytocin for the prevention of postpartum hemorrhage following cesarean deliveries. METHODS: A double-blind randomized controlled trial enrolled patients with a singleton pregnancy scheduled for an elective cesarean delivery at a maternity hospital in Cairo, Egypt, between October 1, 2012 and June 30, 2013. Participants were randomized using a computer-generated sequence to receive treatment with carbetocin, misoprostol, or oxytocin. The primary outcome was the occurrence of uterine atony necessitating additional uterotonics. Per-protocol analyses were performed. Patients, investigators, and data analysts were masked to treatment assignments. RESULTS: The present study enrolled 263 patients; data were analyzed from 88 patients treated with carbetocin, 89 treated with misoprostol, and 86 women treated with oxytocin. Further uterotonics were needed for the treatment of 5 (6%) patients who were treated with carbetocin, 20 (22%) patients treated with misoprostol, and 11 (13%) patients treated with oxytocin. In the prevention of uterine atony, carbetocin was comparable with oxytocin (RR 0.41, 95%CI 0.14-1.25) and superior to misoprostol (RR 0.21, 95%CI 0.07-0.58). CONCLUSION: Additional uterotonics were needed less frequently by patients treated with carbetocin. Carbetocin was comparable to oxytocin and superior to misoprostol in the prevention of uterine atony following an elective cesarean delivery. ClinicalTrials.gov: NCT02053922.

A preliminary pilot randomized crossover study of uzara (Xysmalobium undulatum) versus ibuprofen in the treatment of primary dysmenorrhea.

OBJECTIVE: Preliminary evaluation of efficacy and safety of uzara use in treatment of moderate and severe primary dysmenorrhea in comparison to ibuprofen. MATERIALS AND METHODS: This randomized, comparative two way cross-over study comprised 60 single female students at Faculty of Medicine, Ain Shams University, Egypt, aged 19-28 years with moderate (n = 46) or severe (n = 14) primary dysmenorrhea. Participants were randomized to take either uzara (80 mg/8 hours for two doses, then 40 mg/8 hours) then ibuprofen (400 mg/6 hours) in two subsequent cycles or vice versa. The pain intensity, using VAS, was recorded immediately before taking the medication (0 hour) and after 4, 12, 24, 48-60, 96-120 hours. Main outcome measures included effectiveness of pain relief defined as drop of VAS to 3 or less, patient's global evaluation of the drug, absence from school, the use of a rescue medication, and, in those who continued the treatment, the pain intensity difference (PID) at different points after start of medication and its sum (SPID). RESULTS: Uzara was comparably effective to ibuprofen (78.3% vs. 86.7% of cycles; respectively), with comparable rates of effectiveness on global evaluation (being around 50% for either drug), and rates of school absences (11.7% vs. 13.3%; respectively). The need for rescue medication was different (18.3% and 10%; respectively), albeit with no statistical significance. The means of PID at different time points and SPID were comparable, with significantly lower average mean of VAS scores compared to that felt with no medication (1.6 vs. 6.8, p<0.001). Side effects were less with uzara than ibuprofen (0% vs. 8.3%, p<0.05). CONCLUSIONS: Uzara might be as effective as ibuprofen in management of primary dysmenorrhea but with less side effects. These findings need to be confirmed by a properly designed trial with a larger sample size. TRIAL REGISTRATION: Current Controlled Trials ISRCTN25618258.

Intravenous infusion of paracetamol for intrapartum analgesia.

AIM: To evaluate the efficacy and adverse effects of an i.v. infusion of paracetamol during the active phase of labor as compared with sterile water (placebo) as a method for intrapartum analgesia. METHODS: In a triple-blind, randomized, placebo-controlled trial, 120 low-risk primiparous women presenting in active labor at Ain Shams University Maternity Hospital, Cairo, Egypt, between August 2011 and October 2012, were allocated to receive either 1000 mg i.v. of paracetamol (n = 60) or sterile water (n = 60). The primary outcomes were the efficacy of the drug to supply adequate analgesia as measured by a change in the visual analog scale (VAS) pain intensity score at various time points after drug administration and the need for additional rescue analgesia. The secondary outcomes included the presence of adverse maternal or fetal events. RESULTS: Compared to controls, i.v. infusion of paracetamol was associated with significantly lower VAS score 15 and 30 min after the start of medication; also, there was a significantly lower incidence of need for rescue medication (8/57 [14%] vs 49/59 [83.1%], P < 0.001) at 60 min after the start of medication. There were no recorded maternal adverse effects in either group. There were no differences in occurrence of intrapartum fetal distress or neonatal Apgar scores between both groups. CONCLUSION: Paracetamol appears to be a safe and effective medicine that can be used during the intrapartum period.

Vaginal acidity enhancement with a 3% acetic acid gel prior to misoprostol treatment for pregnancy termination in the midtrimester.

OBJECTIVE: To investigate whether enhancing vaginal acidity improves the success of medical abortions in the midtrimester. METHODS: A double-blind, randomized, placebo-controlled trial was conducted with 48 women with missed midtrimester abortions. Twice daily, the study participants (n=24) were treated with a 3% acetic acid gel and the controls (n=24) with a placebo gel, starting 2 days prior to initiating the misoprostol treatment. The primary outcome measures were the rates of successful abortion within 24 and 48 hours. Secondary measures included gel tolerability and adverse effects of the misoprostol treatment. RESULTS: The success rates were higher in the study group, within both 24 hours (11/23 vs 3/24; P=0.011) and 48 hours (18/23 vs 6/24; P<0.001). Among the women with a vaginal pH of 5 or higher at baseline, acidic gel was also associated with higher success rates within 24 hours (8/13 vs 2/15; P<0.01) and 48 hours (13/13 vs 3/15; P<0,001). The vaginal gels were well tolerated and the misoprostol treatment produced no serious adverse effects. CONCLUSION: A 3% acetic acid gel appears to be an effective and safe preparatory adjuvant to vaginal misoprostol treatment for midtrimester medical abortions, especially in women with a vaginal pH of 5 or higher. www.controlledtrials.com: ISRCTN75746444.

Intravenous infusion of paracetamol versus intravenous pethidine as an intrapartum analgesic in the first stage of labor.

OBJECTIVE: To evaluate the efficacy and adverse effects of an intravenous infusion of 1000 mg of paracetamol as compared with an intravenous injection of 50mg of pethidine hydrochloride for intrapartum analgesia. METHODS: In a randomized prospective study at Ain Shams University, Cairo, Egypt, between April and August 2010, 102 low-risk primiparous women in active labor were allocated to received either paracetamol (n=52) or pethidine hydrochloride (n=50). The primary outcome was the efficacy of the drug to supply adequate analgesia as measured by a change in the visual analog scale (VAS) pain intensity score at various times after drug administration. The secondary outcomes included the need for additional rescue analgesia and the presence of adverse maternal or fetal events. RESULTS: As recorded by the VAS score, there was significant pain reduction at 15 minutes, and at 1 and 2 hours in both groups (P<0.001). The reduction in pain was significantly greater in the pethidine group only at 15 minutes (P=0.004). None of the women in the paracetamol group had adverse effects, as compared with 64% of the women receiving pethidine. CONCLUSION: The effectiveness of intravenous paracetamol was comparable to that of intravenous pethidine, but paracetamol had fewer maternal adverse effects.

Human amnion as a temporary biologic barrier after hysteroscopic lysis of severe intrauterine adhesions: pilot study.

STUDY OBJECTIVE: To estimate the efficacy of fresh and dried amnion graft after hysteroscopic lysis of severe intrauterine adhesions in decreasing its recurrence and encouraging endometrial regeneration. DESIGN: Pilot prospective randomized comparative study (Canadian Task Force classification I). SETTING: Ain Shams Medical School, Cairo, Egypt. PATIENTS: Forty-five patients with severe intrauterine adhesions. Primary symptom was infertility with or without menstrual disorders such as amenorrhea or hypomenorrhea. INTERVENTIONS: Patients were randomized preoperatively using a computer-generated randomization sheet into 3 groups of 15 patients each. Allocation to any group was concealed in an opaque envelope, which was opened at the time of operation. Hysteroscopic lysis of intrauterine adhesions was followed by insertion of an intrauterine balloon only (group 1) or either fresh amnion graft (group 2) or dried amnion graft (group 3) for 2 weeks. Diagnostic hysteroscopy was performed at 2 to 4 months postoperatively. MEASUREMENTS AND MAIN RESULTS: Adhesion grade, menstruation, uterine length, complications, and reproductive outcome were determined. There was significant improvement in adhesion grade with amnion graft vs intrauterine balloon alone (p = .003). Improvement was greater with fresh amnion than with dried amnion (p = .01). Normal menstruation occurred in 4 patients (28.6%) in group 1, 5 (35.7%) in group 2, and 7 (46.7%) in group 3. Of 43 patients, 41 (95.3%) were treated in 2 endoscopic sessions (95.3%), and 2 patients (4.7%) were treated in 3 endoscopic sessions. Uterine perforations occurred in 2 patients (4.7%), and cervical tears in 3 (7.0%). Ten patients (23.3%) achieved pregnancy, 8 (80%) after amnion graft and 2 (20%) without amnion. Six of the 10 patients (60%) miscarried, and 4 (40%) were either still pregnant or delivered at term without complications. CONCLUSION: Hysteroscopic lysis of severe intrauterine adhesions with grafting of either fresh or dried amnion is a promising adjunctive procedure for decreasing recurrence of adhesions and encouraging endometrial regeneration.

Effect of vaginal pH on the efficacy of vaginal misoprostol for induction of midtrimester abortion.

AIM: To evaluate the effect of vaginal pH on the efficacy of misoprostol for induction of midtrimester abortion. METHODS: The study comprised 110 women, with a gestational age of 14-26 weeks, with a missed abortion as an indication for the induction of abortion. On admission, the vaginal pH was measured and two groups were generated: (A) those with pH<5 (n=63); and (B) those with pH >or= 5 (n=47). All of the women received intravaginal misoprostol tablets moistened with 3 mL of 5% acetic acid, 200 microg every 4 h for a maximum of 5 doses within 24 h. If the patient did not have adequate uterine contractions, the same regimen was repeated over the following 24 h and if no response was achieved, this was considered a failure of therapy. RESULTS: All patients aborted within 48 h. A significant positive correlation between vaginal pH and the misoprostol application-abortion interval was found. The mean induction-abortion interval was significantly shorter in group A compared to group B (12.1 vs 23.6 h, P<0.001), with abortion rates at 24 h being 100% and 63.8%, respectively. Moreover, a significantly lower dose of misoprostol was used in group A with a lower incidence of fever and abdominal pain. CONCLUSION: Vaginal pH influences the efficacy of misoprostol administered vaginally for the induction of midtrimester abortion. The presence of this relationship, despite premoistening misoprostol with an acidifying agent, suggests that the effect of vaginal pH might extend beyond affecting the pharmacokinetics of the drug.