Rectally administered misoprostol versus intravenous oxytocin infusion during cesarean delivery to reduce intraoperative and postoperative blood loss

Objective

To compare the efficacy of rectally administered misoprostol with intravenous oxytocin infusion in preventing uterine atony and blood loss during cesarean delivery.

Methods

In this prospective, randomized, double-blind trial, 200 women undergoing cesarean delivery who did not have risk factors for postpartum hemorrhage were randomly allocated to receive either 800 µg of rectal misoprostol at the time of peritoneal incision or an intravenous infusion of oxytocin after delivery of the neonate. Primary outcome measures were estimated amount of intraoperative and postoperative (8 hours) blood loss and changes in hemoglobin levels 24 hours after delivery.

Results

A total of 96 and 94 women were analyzed in the misoprostol and oxytocin groups, respectively. Intraoperative and postoperative blood loss was significantly lower in the misoprostol group than in the oxytocin group (503 vs 592 mL, P = 0.003 and 74 vs 114 mL, P = 0.045, respectively). The incidence of shivering was higher in the misoprostol group (8.3% vs 1.1%, P = 0.018; RR 7.83; 95% confidence interval, 0.99-61.42).

Conclusion

Rectal misoprostol appears to be an effective alternative to intravenous oxytocin in preventing blood loss for routine use during cesarean delivery. Clinical Trials Registration: CTRI/2009/091/000075.     

Rectal misoprostol versus intravenous oxytocin for prevention of postpartum hemorrhage

Objective

To assess the effectiveness of 800 μg of rectal misoprostol compared with an intravenous infusion of 5 IU of oxytocin as prophylaxis against postpartum hemorrhage (PPH).

Methods

A total of 514 women in labor were randomized into two groups (257 women in each). Within 1 minute of delivery of the anterior shoulder participants in group 1 received 800 μg of rectal misoprostol and 1 ampoule of normal saline in 5 mL lactated Ringer solution intravenously; group 2 received a rectal placebo tablet and 5 IU of oxytocin in 5 mL lactated Ringer solution intravenously.

Results

Both groups were comparable regarding the need for uterotonics, blood transfusion, and hematocrit drop of 10% or greater, 24 hours post partum (P = 0.54, P = 0.25, and P = 0.85, respectively). Fever was significantly higher among misoprostol patients (18.7% vs 0.8%, P < 0.001).

Conclusions

Routine use of 800 μg of rectal misoprostol was effective in reducing blood loss after delivery. We recommend the regimen for low-resource, busy obstetric settings.     

Oral misoprostol versus intracervical prostaglandin E2 gel for active management of premature rupture of membranes at term

Objective

To compare the efficacy and safety of oral misoprostol with intracervical prostaglandin E2 (PGE2) gel for the active management of premature rupture of membranes (PROM) at term.

Methods

Women with pregnancies between 37 and 42 weeks presenting with PROM at term and a Bishop score of 5 or less were randomly assigned to receive either a 4-hourly oral dose of 50 µg of misoprostol up to a maximum of 3 doses or 2 applications of intracervical PGE2 gel at a 6-hour interval. Oxytocin was given if labor had not started after 12 hours.

Results

Twenty women in the misoprostol group (n = 31) delivered within 12 hours compared with 5 in the PGE2 group (n = 30) (P < 0.001). The induction-to-delivery interval in the misoprostol group was shorter than in the PGE2 gel group (615 min vs 1070 min; P < 0.001). The mode of delivery was comparable between the 2 groups (P = 0.821). Abnormalities in uterine contractions and neonatal outcomes were also comparable. The requirement for oxytocin was lower and patient satisfaction was better in the misoprostol group.

Conclusion

Oral misoprostol is a safe and efficacious alternative to intracervical PGE2 gel in the active management of PROM at term.     

Comparison of sublingual misoprostol, intravenous oxytocin, and intravenous methylergometrine in active management of the third stage of labor

Objective

To compare the efficacy and adverse effects of sublingual misoprostol, intravenous oxytocin, and intravenous methylergometrine in active management of the third stage of labor (AMTSL).

Methods

A double-blind randomized trial of 300 women with a healthy singleton pregnancy allocated into 4 groups to receive either: 400 µg or 600 µg of sublingual misoprostol, 5 IU of intravenous oxytocin, or 200 µg of intravenous methylergometrine. The primary outcome measure was blood loss in the third and fourth stage of labor; secondary measures were duration of the third stage of labor, changes in hemoglobin levels, and adverse effects.

Results

Patients who received 600 µg of misoprostol had the lowest blood loss (96.05 ± 21.1 mL), followed by 400 µg of misoprostol (126.24 ± 49.3 mL), oxytocin (154.7 ± 45.7 mL), and methylergometrine (223.4 ± 73.7 mL) (P < 0.01). Shortest mean duration of the third stage of labor (5.74 minutes) was with 600 µg of misoprostol, while methylergometrine had the longest (6.83 minutes) (P < 0.05). Pyrexia was observed in the misoprostol groups, and raised blood pressure in the methylergometrine group (P < 0.001). The 24-hour postpartum hemoglobin level was similar among the groups (P > 0.05).

Conclusion

Administration of 600 µg of sublingual misoprostol was more effective than 400 µg of misoprostol, intravenous oxytocin, and intravenous methylergometrine for AMTSL.     

Comparison of induction of labor with vaginal misoprostol plus oxytocin versus oxytocin alone in term primigravidae

Objective.?To compare the efficacy and complications of intravaginal misoprostol application before starting oxytocin infusion with oxytocin infusion alone for labor induction in term primigravidae pregnancies with low-Bishop score.

Methods.?This randomized study included 101 primigravidae women with singleton pregnancies >38 weeks and a Bishop score of <6. Group 1 (50 patients) received a 50-μg dose of intravaginal misoprostol, with an oxytocin infusion started 3?h later. Group 2 (51 patients) received only an oxytocin infusion for labor induction. The time from induction to delivery, the route of delivery and complications were analyzed.

Results.?The mean time from induction to delivery was 10.4?±?2.1?h in Group 1 and 13.7?±?3.4 in Group 2 (p?<?0.001). The rates of vaginal delivery, Apgar scores at 1st and 5th min, placental abruption, and postpartum hemorrhage were similar between the two groups.

Conclusion.?Intravaginal application of 50-μg misoprostol before starting oxytocin infusion is a more effective method of labor induction than oxytocin infusion alone in term primigravidae pregnant women with low-Bishop scores.     

Risk factors for uterine rupture during a vaginal birth after one previous caesarean section: a case-control study

Objective

To study risk factors for uterine rupture (UR) in women with one previous caesarean section (CS) undergoing a vaginal birth after CS (VBAC).

Study design

A nested case-control study was conducted. Baseline characteristics, general obstetric history, details of the previous CS, current delivery and maternal and neonatal outcome were analysed for 41 cases with a UR and 157 controls (no rupture). Data were extracted from 21 Dutch hospitals.

Results

Labour induction was more common in cases than in controls (51% vs. 25% respectively, P = 0.001), and in case of induction therapy especially the use of prostaglandins (PGE2) was more frequent in the case group (86% vs. 46%, P = 0.014 for cases and controls respectively). Patients with UR had a significantly lower Bishop score (median: 2.0 vs. 4.0, P = 0.005) and received more augmentation of labour compared to controls (36% vs. 18%, P = 0.010). In the multivariate analysis induction with PGE2 and oxytocin, induction with PGE2 alone, and augmentation of labour were independent variables affecting the occurrence of UR (respectively OR 13.0, CI 2.3-74.2; OR 4.6, CI 1.9-11.3 and OR 2.7, CI 1.2-6.3). Forty-four percent of the ruptures can be explained by induction of labour with prostaglandins ± oxytocin.

Conclusion

Having studied baseline characteristics, general obstetric history, details of the previous CS and of the current delivery, we show that no factors other than the use of PGE2 (±oxytocin) in response to a low Bishop score, and augmentation of labour with oxytocin are associated with an increased risk for UR in women undergoing VBAC after one previous CS.     

Second- and third-trimester management of medical termination of pregnancy and fetal death in utero after prior caesarean section

Objectives

To evaluate the results and risks of a protocol for second- and third-trimester termination of pregnancy after prior caesarean section.

Study design

This is a retrospective study, conducted in a level 3 (university hospital) maternity unit between January 2001 and September 2008. 67 women with a history of caesarean section underwent second- and third-trimester termination of pregnancy. The protocol was administration of 600 mg mifepristone the first day and application of laminaria tents the second day. One the third day, 48 h after mifepristone, two 200 μg tablets of misoprostol were given orally every 3 h until delivery. Epidural analgesia was performed routinely. Complications analysed were uterine rupture, labour lasting over 12 h, and bleeding requiring blood transfusion.

Results

Delivery was vaginal in 64 cases (95.5%), a median 4 h 20 min (P25: 3 h 5 min, P75: 7 h 7 min) after administration of misoprostol (median number of tablets 2; P25: 2, P75: 4). The median number of tablets of misoprostol was significantly higher for termination of pregnancy than for fetal death in utero (4 vs. 2; p = 0.002). The rate of uterine rupture was 4.8% [95% CI: 1.2-14.2]. Bleeding during delivery requiring a transfusion occurred in 2 cases (3.0%; 95% CI: 0.5-11.3).

Conclusion

A high rate of vaginal delivery was achieved at low doses of misoprostol, with a short median induction-to-delivery interval, and a rate of uterine rupture higher than that observed during attempted vaginal delivery at term in a caesarean scar pregnancy. The rate of severe bleeding during delivery was low.     

Community-based distribution of misoprostol for treatment or prevention of postpartum hemorrhage: Cost-effectiveness, mortality, and morbidity reduction analysis

Objective

To compare the cost-effectiveness of community-based distribution of misoprostol for prevention with misoprostol for treatment of postpartum hemorrhage (PPH).

Methods

A Monte Carlo simulation depicted mortality and anemia-related morbidity attributable to PPH among 3 scenarios of 10 000 women delivering at home in rural India: (1) standard management; (2) standard management plus 800 µg of sublingual misoprostol for PPH treatment; and (3) standard management plus 600 µg of prophylactic oral misoprostol. The model included costs of drugs, birth attendant training, and transport for women who did not respond to misoprostol.

Results

Misoprostol lowered mortality by 70% and 81% in scenarios 2 and 3, respectively. Scenarios 2 and 3 raise costs by 6% and 35%, respectively. Incremental cost per disability-adjusted life year (DALY) saved is estimated at $6 and $170, respectively.

Conclusion

Both interventions were more effective at decreasing mortality and anemia than standard management. The most efficient scale-up plan would focus initially on increasing coverage with the treatment strategy ($6 per DALY).     

A double-blind, randomized, placebo-controlled trial of misoprostol and routine uterotonics for the prevention of postpartum hemorrhage

Objective

To assess the effects of 400-μg sublingual misoprostol plus routine uterotonics on postpartum hemorrhage.

Methods

A double-blind, placebo-controlled, randomized study was performed. After delivery of the child, eligible women received routine uterotonics and were randomly allocated to receive 400-μg misoprostol or placebo sublingually. The primary outcome measure was blood loss of at least 500 mL within 1 hour of taking the trial tablets.

Results

In total, 672 women received misoprostol and 673 received placebo. The baseline data were similar for both groups. Misoprostol plus routine uterotonics reduced postpartum blood loss, but the effect was not significant for blood loss of at least 500 mL (relative risk [RR] 0.96; 95% confidence interval [CI], 0.63-1.45) or blood loss of at least 1000 mL (RR 0.50; 95% CI, 0.15-1.66). Misoprostol also reduced the need for non-routine oxytocin, manual removal of the placenta, and hysterectomy, but these differences were not significant either. Misoprostol was associated with pyrexia and moderate/severe shivering. There was no death in either group.

Conclusion

Misoprostol plus routine uterotonics resulted in modest reductions of blood loss in the third stage of labor, but the effects did not reach statistical significance. Larger studies are recommended.     

Association between gestational age and induction-to-abortion interval in mid-trimester pregnancy termination using misoprostol

Objective

The study was aimed to evaluate the effectiveness, outcome, and pain intensity of the vaginal administration of misoprostol for the induction of abortion between 13 and 24 gestational weeks.

Study design

A retrospective study was conducted at our tertiary medical center from January 2006 to December 2009 on 122 consecutive women who underwent termination of pregnancy (TOP) in the mid-trimester. They were given 400 mcg of vaginal misoprostol every 6 h, up to four doses. The induction-to-abortion interval and the level of pain experienced during the process were assessed. Success was defined by the fetus being expelled within 48 h.

Results

Vaginal misoprostol was effective in 84% (98/122) of patients. The median duration of the induction-to-abortion interval was 16 (5-48) h. The induction-to-abortion interval was correlated with gestational age, while inversely correlated with parity. A correlation was also found between gestational age and pain intensity at 12 h from induction.

Conclusion

Misoprostol is safe and effective in mid-trimester abortion induction. The induction-to-abortion interval is shorter and abortion less painful with lower gestational age. Higher parity is also associated with shorter induction to abortion interval.     

Comparison of four perioperative misoprostol regimens for surgical termination of first-trimester pregnancy

Objective

To compare the outcomes of 4 different perioperative misoprostol regimens for surgical termination of first-trimester pregnancy.

Methods

Retrospective analysis of the records of 4000 women (4 cohorts of 1000 each) who underwent surgical termination of pregnancy. The 4 cohorts received: no misoprostol; 200 μg of oral misoprostol 30 minutes preoperatively; 200 μg of sublingual misoprostol 30 minutes preoperatively; or 200 μg of oral misoprostol 3 hours preoperatively plus 200 μg of vaginal misoprostol postoperatively. Adverse effects of the last regimen were surveyed in 1000 women.

Results

In the cohorts that received misoprostol, the difficulty of cervical dilatation was reduced (P < 0.001) compared with the cohort of women that did not receive misoprostol. The frequency with which women made postoperative contacts with the clinic was also reduced in the cohorts that received misoprostol (P < 0.05). Adverse effects were minimal.

Conclusions

This retrospective study showed an association between perioperative administration of misoprostol, reduced difficulty for operators, and reduced demand for postoperative care. The regimen associated with the greatest reduction in difficult cervical dilatations and postoperative consultations was 200 μg of oral misoprostol 3 hours preoperatively plus 200 μg of misoprostol vaginally at the end of the surgical procedure.     

Carbetocina vs. oxitocina para la prevención de hemorragia posparto en pacientes grandes multíparas: estudio aleatorizado controlado

Objective

Carbetocin is a long-acting oxytocin analogue that can be used as a uterotonic agent in the management of postpartum hemorrhage. The purpose of this study was to compare the effectiveness of carbetocin (100 μg IV) with that of oxytocin (20 U IV) in the prevention of postpartum bleeding in grand multiparous patients (five or more pregnancies).

Design

Prospective, randomized controlled trial.

Population

Patients with vaginal deliveries of singleton pregnancies (≥28 weeks).

Methods

A total of 135 patients were selected to receive 100 μg of carbetocin in a single IV dose or 400 mU oxytocin/min (LR 1000 cc+20 U oxytocin, 100 cc/h) at the end of the third stage of labor.Main outcome measures: Postpartum hemorrhage despite the medication used, requiring the use of alternative measures.

Results

There were no statistically significant differences in the frequency of therapeutic failures or the need to transfuse blood products. The use of carbetocin was associated with a lesser need to manually explore the uterus (RR: 0.12; 95% CL 0.03-0.48). The incidence of adverse effects was similar in both groups. There were no differences in the effects of drugs on breastfeeding.

Conclusions

The use of a single IV dose of carbetocin is as effective as 20 IV units of oxytocin in the prevention of postpartum hemorrhage in grand multiparous women after vaginal delivery. The incidence of adverse effects and complications was similar in the two groups. Carbetocin should be considered a useful alternative to conventional uterotonics in the prevention of postpartum bleeding in grand multiparous patients.     

Management of complex pelvic masses using a multivariate index assay: a decision analysis

Objective

To develop a cost-minimization analysis of a multivariate index assay (MIA) used for women with complex pelvic masses.

Methods

A decision analysis model was used to evaluate 81,000 hypothetical patients with a complex pelvic mass requiring surgery. Three strategies were evaluated: (1) referral to a gynecologic oncologist (GO) based on clinical assessment including physical exam, ultrasonography, and CA125 (CLINICAL); (2) utilization of a multivariate index assay (MIA); or (3) referral of all patients to a GO (REFER ALL). Various reoperation rates were evaluated with sensitivity analyses. Actual payer costs were compared between each strategy.

Results

The CLINICAL strategy cost $933.9 million (M) and resulted in 72% of patients receiving appropriate initial surgical staging. The REFER ALL strategy cost $939.7 M and all patients were appropriately staged. The MIA strategy cost $976.7 M and resulted in 91% of patients having appropriate initial staging. Using conservative reoperation rates (10-20%), 461 patients required reoperation using CLINICAL strategy compared to 142 patients in MIA strategy. Using aggressive reoperation rates (40-50%), 1715 patients required reoperation using CLINICAL strategy resulting in an incremental cost of $15.2 M compared to 529 patients at $4.7 M in MIA strategy. The increased costs associated with an aggressive reoperation rate resulted in the REFER ALL strategy being the least expensive alternative, with the highest rates of appropriate initial surgery.

Conclusions

Utilizing an MIA resulted in more ovarian cancer patients receiving appropriate initial surgery, but at increased costs. Referring all patients with complex masses avoids the most reoperations at reduced cost compared to using an MIA.     

Cardiotocographic abnormalities associated with misoprostol and dinoprostone cervical ripening and labor induction

Objective

To characterize the incidence and timing of cardiotocographic (CTG) abnormalities associated with misoprostol and dinoprostone vaginal inserts during labor induction.

Study design

This was a secondary analysis of data collected during the misoprostol vaginal insert (MVI) trial, a multi-site, double-masked, randomized trial of women requiring cervical ripening before induction of labor. The timing, incidence and clinical outcomes associated with CTG abnormalities were analyzed among three study groups.

Results

1308 subjects were randomized to receive dinoprostone pessary, misoprostol 50 mcg (MVI 50) or 100 mcg (MVI 100) vaginal insert. 6.8% of MVI 50-treated women had a uterine contractile abnormality (hyperstimulation, hypertonus and/or tachysystole) while the study drug was in situ, compared to 17.4% with dinoprostone insert (p < 0.001) and 17.3% with MVI 100 (p < 0.001). There was no significant difference in incidence of fetal heart rate (FHR) abnormalities that occurred with the study drug—11.2% with dinoprostone, compared to 9.9% with MVI 50 and 10.7% with MVI 100. Cardiotocographic (CTG) abnormalities while the study drug was in situ occurred later in women treated with MVI 50 (7.5 h [6.2-9.8]) compared to dinoprostone (5.5 h [4.2-6.6], p = 0.003) and MVI 100 (7.0 h [5.7-7.9], p = 0.13). Eight participants in MVI 50 group underwent cesarean section secondary to a CTG event that was initially noted with the study drug in situ, compared to eight dinoprostone-treated participants and 16 in the MVI 100 group, but these differences were not statistically significant.

Conclusion

Cardiotocographic abnormalities were less frequent and occurred after longer exposure with MVI 50 than MVI 100 or dinoprostone. Clinical outcomes were similar among the groups.     

Uterine massage to reduce postpartum hemorrhage after vaginal delivery

Objective

To determine the effectiveness of sustained uterine massage started before delivery of the placenta in reducing postpartum hemorrhage.

Methods

A randomized controlled trial conducted in Egypt and South Africa between September 2006 and February 2009. A total of 1964 pregnant women were randomly allocated to 1 of 3 treatment groups: intramuscular oxytocin, sustained uterine massage, or both treatments. Blood loss within 30 minutes of delivery was recorded.

Results

The incidence of blood loss of 300 mL or more within 30 minutes of delivery was significantly higher in the massage group than in the massage plus oxytocin (RR 1.88; 95% CI, 1.29-2.74 in Assiut, and RR 1.3; 95% CI, 1.00-1.68 in SA) and the oxytocin only group (RR 1.7; 95% CI, 1.11-2.61 in Assiut, and RR 2.24; 95% CI, 1.54-3.27 in SA). In both centers, use of additional uterotonics was significantly higher in the uterine massage group compared with the other 2 groups.

Conclusion

Uterine massage was less effective than oxytocin for reducing blood loss after delivery. When oxytocin was used, there was no additional benefit from uterine massage. The effectiveness of uterine massage in the absence of oxytocin was not studied. ACTRN: 12609000372280.     

Cost-effectiveness of misoprostol and prenatal iron supplementation as maternal mortality interventions in home births in rural India

Objective

To determine the cost-effectiveness of prenatal iron supplementation and misoprostol use as interventions to prevent maternal mortality in home births in rural India.

Methods

A cost-effectiveness analysis depicted three hypothetical cohorts of 10 000 pregnant women delivering at home in rural India: one with no intervention, one receiving standard prenatal iron supplements, and 1 receiving 600 µg of misoprostol in the third stage of labor.

Results

Misoprostol used to prevent postpartum hemorrhage resulted in a 38% (95% CI, 5%-73%) decrease in maternal deaths, while prenatal iron supplementation resulted in a 5% (95% CI, 0%-47%) decrease. Misoprostol cost a median US $1401 (IQR US $1008-$1848) prenatal iron supplementation cost a median US $2241 (IQR No Lives Saved-$3882) per life saved compared with the standard care outcome.

Conclusion

Misoprostol is a cost-effective maternal mortality intervention for home births. Iron supplementation may be worthwhile to improve women's health, but it is uncertain whether it can prevent mortality after hemorrhage.     

Effects of visceral peritoneal closure on scar formation at cesarean delivery

Objective

To determine the effect of closure or non-closure of the visceral peritoneum at cesarean delivery on uterine scar formation assessed at repeat cesarean delivery.

Methods

Women undergoing initial cesarean delivery were allocated into 2 groups: group 1 underwent visceral peritoneal closure, while in group 2 the visceral peritoneum was not closed. At repeat cesarean delivery 4 specimens from the initial uterine scar were collected and assessed by light microscopy and scanning electron microscopy.

Results

In group 1, 57% of women had adhesions compared with 20.6% in group 2 (P < 0.05). Light microscopy revealed reactive mesothelial hyperplasia (51.8% vs 13.7%), submesothelial fibrosis (48.1% vs 6.8%), and neoangiogenesis of mesothelial stroma (44.4% vs 12%) in group 1 and group 2 patients, respectively (P < 0.05). Scanning electron microscopy showed more patients with pericytes on the surface of microvessels in group 1 compared with group 2 (26.3 ± 1.4 vs 11.5 ± 1.1 patients; P < 0.05).

Conclusion

Closure of the visceral peritoneum at cesarean delivery may produce an inflammatory reaction and adhesions, evidenced by reactive and regenerative mesothelial hyperplasia and submesothelial fibrosis.     

Induction of labor in toxemia with misoprostol

BACKGROUND: To compare the efficacy and complications of intravaginal misoprostol application with oxytocin infusion for induction of labor in toxemia of pregnancy with a modified Bishop score of < or =4. METHODS: A hundred preeclamptic women with a modified Bishop score of < or =4 were randomized into two groups of 50 patients one group receiving 50 microg intravaginal misoprostol 4 times at 4 hour intervals, the second group receiving oxytocin infusion for induction of labor starting from 1 mIU/per minute, increasing it every 30 minutes with 2 mIU/per minute increments up to maximum of 30 mIU/per minute. Modified Bishop scores 12 hours after induction, the time from induction to delivery, the route of delivery, fetal outcome and maternal complications were recorded. Statistical analyses were performed using Mann Whitney-U, Chi-Square and hypothesis tests about differences for two proportions (t test) to determine differences between the two groups. p< or =0.05 was considered significant. RESULTS: Misoprostol was significantly superior for induction of labor in toxemia of pregnancy with modified Bishop score of < or =4. After 12 hours median modified Bishop scores of misoprostol administered group and oxytocin administered group were 7 and 4 respectively. Misoprostol administered group 1 was significantly better than oxytocin administered group 2 (p=0.027). The rate of patients who were in labor after 12 hours were 94% and 80% in group 1 and 2 respectively and the difference showed significant difference (p<0.05). The median time from induction to delivery was 14 hours and 16 hours in the misoprostol and oxytocin administered group respectively with significant difference between the groups (p=0.003). The rate of vaginal delivery was significantly higher in the misoprostol administered group 1 (82%) when compared with the oxytocin administered group 2 (66%) (p<0.05). The 1 and 5 minutes median Apgar scores were 5-7 and 6-7.5 in group 1 and 2, respectively with no significant differences between the groups (p=0.96, p=0.64). The rate of admission to neonatal intensive care unit was similar in both groups. The complication rates were similar in all groups and no significant detrimental effects were noted. CONCLUSIONS: Intravaginal misoprostol is an efficacious, cheap and safe method of induction of labor in toxemia of pregnancy with modified Bishop score of < or =4.