Need For Additional Uterotonic Drugs Research Articles

The Efficacy and Safety of Intrauterine Misoprostol During Cesarean Section in Prevention of Primary Post-Partum Hemorrhage - A Randomized Controlled Trial

Postpartum hemorrhage remains the most common cause of maternal death globally [1]. and has persisted in low-income countries due to the prevalence of home deliveries and limited access to life-saving uterotonic drugs in these countries [2-5]. Many of the global gains in reducing maternal mortality can be attributed to developments in preventing and treating Postpartum Hemorrhage (PPH) [6,7]. PPH is often associated with the failure of the uterus to contract after delivery and is categorized as blood loss of 500 mL or more following a vaginal delivery or 1,000 mL after cesarean delivery [8,9]. PPH is categorized as primary if it occurs within 24 hours of delivery and secondary if excessive blood loss occurs at 24 hours or more after delivery. To compare the efficacy and safety of intrauterine misoprostol with intravenous oxytocin during Cesarean Section (CS) in prevention of primary post-partum hemorrhage. A total of 150 pregnant women at term (37-40 weeks) gestation who were scheduled for either elective or emergency caesarean delivery were enrolled. They were equally randomized into two groups: women who received 400mcg intrauterine misoprostol in addition to intravenous infusion of 10 IU oxytocin as Group I while women who received an intravenous infusion of 10 IU oxytocin after delivery of the neonate as Group II. The Primary outcome measures were Estimated Blood Loss (EBL) during caesarean section and need for additional uterotonic drugs intraoperatively. Secondary outcomes included the occurrence of excessive blood loss (>1000mL) within the first 6 hours postoperatively and the occurrence of any maternal or fetal side effects. The difference in the postoperative haemoglobin and postoperative hematocrit was found to be highly significant between the two groups (10.12 ± 1.55 vs 9.24 ± 1.52; p < 0.01) and (2.48 ± 1.38 vs 3.75 ± 1.77; p < 0.001) respectively. Estimated blood loss in two groups was found to be very highly significant (440.19 ± 257.75 vs 677.38 ± 343.04; p < 0.001). Intraoperative blood loss was significantly lower in the group I compared to group II (408.27 ± 123.34 vs 486.04 ± 135.84; p < 0.001). Blood loss during the first 6 hours after delivery was also lower in the group I (58.87 ± 9.86 mL vs 63.29 ± 12.39 mL; p < 0.05). Fewer women in the intrauterine misoprostol group needed additional uterotonics (7 vs 11; p > 0.05). The difference in the side effects of both the groups was found to be statistically non-significant. Apgar scores at 1 and 5 minutes were comparable in both the groups. The combined use of intrauterine misoprostol (400 mg), when added to oxytocin infusion during caesarean section is effective in decreasing the intraoperative blood loss, post-operative blood loss and prevent postpartum hemorrhage. keywords: Intrauterine misoprostol; Intraoperative estimated blood loss; Cesarean section; Postpartum hemorrhage

Heat stable carbetocin vs. oxytocin for the prevention of post-partum hemorrhage in emergency caesarean delivery: a randomized controlled trial.

To evaluate the uterotonic effect of carbetocin compared with oxytocin in emergency cesarean delivery in Iraq. A double-blinded randomized noninferiority single center trial. Three-hundred patients were systematically randomized to intravenous bolus injection of 10 IU oxytocin or 100mcg carbetocin after delivery in a ratio of 2:1. The primary outcome was additional uterotonic use when inadequate uterine tone occur in the first 24h after delivery. Secondary outcomes include the need for blood transfusion, blood pressure and pulse rate changes within an hour of drugs administration. Noninferiority margins for the relative risks outcomes was 4%. Addition uterotonics use was significantly lower in carbetocin group with a risk ratio of 0.36. Carbetocin was superior to oxytocin in reducing the need for additional uterotonic drugs by 12% and non-inferior to oxytocin for blood transfusion 3.5%. Noninferiority was not shown for the outcome of sever blood loss. Miner changes in blood pressure and pulse rate were observed in carbetocin group compared to oxytocin but clinically were not significant. Heat stable carbetocin is effective in reducing additional uterotonics use compared to oxytocin without clinically significant change in blood pressure or pulse rate, therefore, can be a potential alternative in Iraq.

Carbetocin versus Oxytocin in Active Management of 3rd stage of Labour following Vaginal Delivery

Background: Every day more than 220 women around the world die from severe bleeding after childbirth. Globally post-partum hemorrhage is the number one direct cause of maternal mortality. Most postpartum hemorrhages are caused by uterine atony and occur in the immediate postpartum period. Most of these tragic deaths can be prevented by active management of third stage of labour. Active management of the third stage of labor should be practiced routinely to decrease the risk of postpartum hemorrhage. Oxytocin is used for enhancing uterine contraction after delivery. But oxytocin has some limitations like shorter half- life, less contraction time and more side effects, whereas carbetocin has prolonged duration of action which ensures more contraction time and less adverse effects. This study was done to see the efficacy and safety of carbetocin over oxytocin for prevention of PPH after vaginal delivery.
 Methodology: A randomized controlled clinical trial was conducted in the Department of Obstetrics and Gynecology, Shaheed Suhrawardy Medical College and Hospital, Dhaka, Bangladesh over a period of 9 months from January 2015 to September 2015. Ninety four patients undergoing vaginal delivery at term were randomized into two groups receiving either 10IU oxytocin or 100 μg carbetocin. Outcome measures such as primary PPH, massive blood loss, need for additional uterotonic drug, additional blood transfusion as well as adverse effects were documented.
 Results: In this study, massive blood loss did not occur none of patients in carbetocin group. But massive blood loss occured 6.4% women of oxytocin group. Further fundal massage , immediate blood transfusion and additional uterotonics didn’t need any patient in carbetocin group. In oxytocin group, fundal massage required in 8.5% of women, blood transfusion needed in 10.6% patients and additional uterotonics needed in 10.6% women. Average amount of blood loss was 88 ml less in carbetocin group and adverse effects of drugs were almost similar in both group. Primary PPH developed in oxytocin group 8.5% but none of patients had developed PPH in carbetocin group.
 Conclusion: Carbetocin is an effective new drug than oxytocin for prevention of postpartum hemorrhage in vaginal delivery.
 Bioresearch Commu. 7(1): 927-931, 2021 (January)

Oxytocin at elective caesarean delivery: a dose-finding study in women with obesity.

Prophylactic oxytocin administration at the third stage of labour reduces blood loss and the need for additional uterotonic drugs. Obesity is known to be associated with an increased risk of uterine atony and postpartum haemorrhage. It is unknown whether women with obesity require higher doses of oxytocin in order to achieve adequate uterine tone after delivery. The purpose of this study was to establish the bolus dose of oxytocin required to initiate effective uterine contraction in 90% of women with obesity (the ED90 ) at elective caesarean delivery. We conducted a double-blind dose-finding study using the biased coin up-down design method. Term pregnant women with a BMI≥40kg.m-2 undergoing elective caesarean delivery under regional anaesthesia were included. Those with conditions predisposing to postpartum haemorrhage were not included. Oxytocin was administered as an intravenous bolus over 1minute upon delivery of the fetus. With the first woman receiving 0.5IU, oxytocin doses were administered according to a sequential allocation scheme. The primary outcome measure was satisfactory uterine tone, as assessed by the operating obstetrician 2minutes after administration of the oxytocin bolus. Secondary outcomes included the need for rescue uterotonic drugs, adverse effects and estimated blood loss. We studied 30 women with a mean (SD) BMI of 52.3 (7.6) kg.m-2 . The ED90 for oxytocin was 0.75IU (95%CI 0.5-0.93IU) by isotonic regression and 0.78IU (95%CI 0.68-0.88IU) by the Dixon and Mood method. Our results suggest that women with a BMI≥40kg.m-2 require approximately twice as much oxytocin as those with a BMI<40kg.m-2 , in whom an ED90 of 0.35IU (95%CI 0.15-0.52IU) has previously been demonstrated.

Carbetocin Versus Oxytocin for Prophylaxis of PPH Used During Caesarean Section: An Open Label Randomized Control Trial

Background: Postpartum hemorrhage is the leading cause of maternal mortality; uterineatony is the most important cause. Uterotonics are used to prevent uterine atony. Carbetocin,a synthetic anallague of oxytocin seems to be an effective and safe new drug for preventionof PPH after caesarean&#x0D; The Aim of Study:To find out the efficacy and safety of carbetocin over oxytocin for theprevention of PPH during caesarean section.Patients and Methods: A randomized-controlled trial was conducted in the Dept. of Obs &amp;Gyane, Rangpur Medical College and Hospital, Rangpur, Bangladesh over a period of twelvemonths from June 2016 to June 2017. One hundred admitted patients undergoing cesareansection at term were randomized into two groups receiving either 10 IU oxytocin or 100 μgcarbetocin after caesarean section. Outcome measures such as primary PPH, massiveblood loss, need for additional uterotonic drug, additional blood transfusion as well as adverseeffects were all documented.&#x0D; Results: Massive blood loss occurred in 6% patients, blood transfusion needed in 20% patientsand additional uterotonic needed for 36% patients in Oxytocin group but in Carbetocin groupno massive blood lossoccurred, only 2%patients needed immediate blood transfusion and4% patients were required additional uterotonics. There were no major adverse effectsobserved in both the groups. No patients had developed PPH in carbetocin group. But 8%(4)patients had developed PPH in oxytocin group.&#x0D; Conclusion: Carbetocin appears to be an effective new drug than Oxytocin for the preventionof postpartum hemorrhage following caesarean section.&#x0D; Bangladesh J Obstet Gynaecol, 2018; Vol. 33(2) : 113-118

Efficacy and Safety of Carbetocin for the Prevention of Primary PPH During Caesarean Section: An Open Label Single Arm Study

Background: The risk of postpartum haemorrhage is much higher for women undergoingcaesarean section, particularly in developing countries where the majority of operations arecarried out as an emergency procedure. Postpartum haemorrhage is the leading cause ofmaternal mortality worldwide. Around 67–80% of cases are caused by uterine atony.Preventive measures include prophylactic drugs use to aid uterine contraction after delivery,thus avoiding severe blood loss and reducing maternal morbidity and mortality. Carbetocin asynthetic analogue of oxytocin is currently indicated for prevention of uterine atony afterdelivery by caesarean section in spinal or epidural anaesthesia.&#x0D; The Aim of Study: To see the efficacy and safety of Carbetocin for the prophylaxis of PPHduring caesarean section.Patients and Methods: An open label single arm clinical trial was conducted in the BagerhatSadar Hospital, Bangladesh over a period of six months from May 2017 to October 2017.Ninety patients who had got admitted in Bagerhat Sadar Hospital, undergoing cesareansection at term were selected. Each patient obtained a single dose of 100 microgramcarbetocin intravenously during cesarean section, immediately after the delivery of the babyand prior to the delivery of the placenta. Outcome measures such as primary PPH, bloodloss was observed and measured by weighing sanitary napkin observed for six hours. Needfor additional uterotonic drug, additional blood transfusion as well as adverse effects were alldocumented.&#x0D; Results: Massive blood loss occurred only in 3.3% patients. Among the study population96.7% patients did not need any additional uterotonics. No patient had developed fever,arrhythmia, pulmonary edema, tremor, abdominal pain and pruritus. Only 2.2% had nausea,only 3.3% had hypotention, only 3.3% had vomiting and only 2.2% had headache which wasnot statistically significant. Only 4.4% patients developed PPH.&#x0D; Conclusion: Carbetocin appears to be an effective new drug for the prophylaxis of postpartumhemorrhage in cesarean section.&#x0D; Bangladesh J Obstet Gynaecol, 2018; Vol. 33(2) : 119-124

Carbetocin at elective caesarean section: a sequential allocation trial to determine the minimum effective dose in obese women.

Postpartum haemorrhage is a leading cause of maternal death during childbirth. There is an increasing incidence of atonic postpartum haemorrhage in developed countries, and maternal obesity has been proposed as a contributing factor. The dose-response relationship of carbetocin in obese women has not yet been determined. We conducted a double-blind, dose-finding study of carbetocin using a biased coin up-and-down design in women with a body mass index ≥40kg.m-2 undergoing elective caesarean section. The determinant for a successful response was satisfactory uterine tone, with no intra-operative need for additional uterotonic drugs. Secondary outcomes included the use of additional uterotonic drugs postoperatively, estimated blood loss and adverse effects of carbetocin administration. Thirty women were recruited to the study. The median (IQR [range]) body mass index was 44.93 (41.5-55.2 [40-66.5]) kg.m-2 . The ED90 of carbetocin was estimated as 62.9 (95%CI 57.0-68.7) μg using the truncated Dixon and Mood method, and 68 (95%CI 52-77) μg using the isotonic regression method. The estimated blood loss was 880 (621-1178 [75-2442]) ml. The overall rates of hypotension and hypertension after delivery were 40% and 6.7%, respectively, while nausea occurred in 26.7% of women. The ED90 for carbetocin in obese women at elective caesarean section is lower than the dose of 100μg currently recommended by the Society of Obstetricians and Gynaecologists of Canada, but is approximately four times higher than the previously demonstrated ED90 of 14.8μg in women with body mass index <40kg.m-2 .

Intra-umbilical vein injection of carbetocin versus oxytocin in the management of retained placenta

IntroductionRetained placenta can be defined as lack of expulsion of the placenta within 30 min of delivery of the infant. It is a significant cause of maternal mortality and morbidity throughout the developing world. Aim of the workThe aim of this study was to compare the efficacy of intra-umbilical vein injection of carbetocin versus oxytocin in the management of retained placenta. Patients and methodsA total of 200 women were included in this study. They were divided into two groups; each 100 women. The first group received intra-umbilical vein injection of 1 mL carbetocin (containing 100 μg carbetocin) diluted in 20 mL normal saline 0.9% and the second group received intra-umbilical vein injection of 20 IU oxytocin diluted in 20 mL normal saline 0.9%. ResultsTotal blood loss (ml) and duration of the third stage of labor (minutes) were significantly lower in carbetocin group when compared to oxytocin group. Postoperative Hb concentration (g/dl) was significantly higher in carbetocin group. Also there was a highly significant difference between both groups as regard change in Hb concentration (g/dl) with less change in the carbetocin group. The need for additional uterotonic drugs following placental delivery and the occurrence of postpartum hemorrhage and the need for blood transfusion were significantly lower in the carbetocin group. ConclusionIntra-umbilical carbetocin is more effective than intra-umbilical oytocin as a method for management of retained placenta. Intra-umbilical carbetocin seems to have more acceptable hemodynamic safety profile when compared to intra-umbilical oxytocin in the management of retained placenta.

Efficacy and Safety of Carbetocin in Comparison to Oxytocin for the Prevention of Primary PPH during Caesarean Section: An Open Label Randomized Control Trial

&#x0D; Background: Postpartum hemorrhage (PPH) is a potentially life-threatening complication of both vaginal and caesarean delivery. The most frequent cause of postpartum hemorrhage is uterine atony, when the uterus fails to contract fully after delivery of the placenta. For the prevention of this uterine atony we need an effective uterotonic drug. Till now oxytocin is used for enhancing uterine contraction after delivery. But oxytocin has some limitations like shorter halflife, less contraction time and more side effects, whereas carbetocin has prolonged duration of action which ensures more contraction time and less adverse effects. So, carbetocin considered as a good alternative over oxytocin for the prevention of primary PPH in caesarean section.&#x0D; The Aim of Study: To see the efficacy and safety of carbetocin over oxytocin for the prevention of primary PPH during caesarean section.&#x0D; Patients and Methods: A randomized-controlled trial was conducted in the Institute of Child and Mother Health (ICMH), Dhaka, Bangladesh over a period of nine months from January to September 2016. Ninety-four patients who had got admitted in ICMH undergoing caesarean section at term were randomized into two groups receiving either 10IU oxytocin or 100μg carbetocin, after the operation. Outcome measures such as primary PPH, massive blood loss, need for additional uterotonic drug, additional blood transfusion as well as adverse effects were all documented.&#x0D; Results: This study had shown that carbetocin is superior in comparison to oxytocin for the prevention of primary PPH following caesarean section. Each patient obtained either a single dose of 100 microgram carbetocin intravenously or 10 IU of oxytocin during caesarean section. Massive blood loss occurred in 6.4%patients, blood transfusion needed in 17% patients and additional uterotonic needed for 25.5% patients in oxytocin group but in carbetocin group no massive blood loss occurred, only 2.1% patient needed immediate blood transfusion and no patient was required additional uterotonics. There were no major adverse effects observed in both the groups. No patients had developed PPH in carbetocin group. But 12.8% patients had developed primary PPH in oxytocin group.&#x0D; Conclusion: Carbetocin appears to be an effective new drug than oxytocin for the prevention of primary postpartum hemorrhage in caesarean section.&#x0D; J Bangladesh Coll Phys Surg 2019; 37(1): 19-24&#x0D; &#x0D;

Randomized controlled trial of tranexamic acid among parturients at increased risk for postpartum hemorrhage undergoing cesarean delivery.

To assess the effects of tranexamic acid among patients undergoing cesarean delivery who were at high risk of postpartum hemorrhage. Between August 1, 2012, and April 30, 2013, a randomized controlled trial was performed at a tertiary care center in India. Women undergoing an elective or emergency cesarean delivery who were at high risk for postpartum hemorrhage were enrolled. They were randomly assigned using sealed, opaque envelopes to receive 10mg/kg tranexamic acid or normal saline 10min before skin incision. Anesthesiologists were not masked to group assignment, but patients and obstetricians were. The primary outcome was need for additional uterotonic drugs within 24h after delivery. Analyses were by intention to treat. Thirty patients were assigned to each group. Additional uterotonic drugs were required in 7 (23%) patients assigned to tranexamic acid and 25 (83%) patients in the control group (P<0.001). Intravenous tranexamic acid, administered before skin incision, significantly reduced the requirement for additional uterotonics among women at increased risk for postpartum hemorrhage. Clinical Trials Registry India: CTRI/2015/05/005752.

Randomized double-blind placebo-controlled trial of buccal misoprostol to reduce the need for additional uterotonic drugs during cesarean delivery.

To determine whether buccal misoprostol during cesarean delivery in conjunction with active management of the third stage of labor reduces the need for additional uterotonic drugs. A double-blind, randomized, placebo-controlled trial was performed in Monterrey, Mexico, between February 2008 and December 2013. Eligible women had risk factors for uterine atony and were to undergo cesarean delivery under epidural block. Using a computer-generated sequence and blocks of six, patients were randomly assigned to receive 400μg misoprostol or 800μg placebo buccally after cord clamping. Both groups received an intravenous oxytocin infusion. The primary outcome was the need for additional uterotonic drugs. Analyses were performed per protocol. Patients, investigators, and data analysts were masked to group assignment. A total of 120 women were included in analyses (60 in each group). At least one additional uterotonic drug was required in 24 (40%) women in the placebo group versus 6 (10%) women in the misoprostol group (relative risk 0.16; 95% confidence interval 0.06-0.44). No adverse effects due to misoprostol were recorded. Buccal misoprostol during cesarean delivery reduced the need for additional uterotonic drugs to treat uterine atony. ClinicalTrials.gov:NCT01733329.

Carbetocin at Cesarean delivery for labour arrest: a sequential allocation trial to determine the effective dose.

The aim of this study was to estimate the effective dose 90% (ED90) of carbetocin to provide adequate uterine tone at Cesarean delivery (CD) for labour arrest. We conducted a double-blind dose-finding study of carbetocin using a biased-coin up-and-down design in women undergoing CD for labour arrest under epidural anesthesia. Forty healthy term pregnant women who had received at least three hours of oxytocin infusion during labour were recruited for the study. Carbetocin was administered intravenously upon delivery of the anterior shoulder of the fetus. The first patient received 20µg, and the dose for the subsequent patient was determined according to the response of the previous patient as per the biased-coin allocation scheme using increments or decrements of 20µg (maximum 140µg). Uterine tone was assessed by the obstetrician and rated as satisfactory or unsatisfactory throughout the intraoperative period. The primary outcome was satisfactory uterine tone with no need for additional uterotonic drugs intraoperatively. Secondary outcomes included use of additional uterotonic drugs postoperatively in the first 24hr, estimated blood loss, and adverse effects. The ED90 of carbetocin to produce adequate uterine tone was estimated at 121µg (95% confidence interval [CI]: 111 to 130; 99% CI: 108 to 133) using the truncated Dixon and Mood (DM) method. The isotonic estimator of ED90 was 140µg; however, the observed response rate across all doses was<90%. Also, the 95% CI of the DM estimator is likely to have lower than expected coverage, while the 99% CI may have about 90% coverage. Therefore, these results should be interpreted with caution. The overall median (range) estimated blood loss was 1,014 (104-2,436)mL. The overall incidence of hypotension and tachycardia were 45% and 57.5%, respectively. At a dose of 140µg, the incidence of tachycardia and intraoperative arrhythmias was 76% and 14%, respectively. The ED90 of carbetocin at CD for labour arrest, as determined in our study, should be interpreted with caution since it may be underestimated. This dose is higher than the currently recommended dose of 100µg at elective CD and should not be used routinely given the uncertainty regarding its efficacy and the high incidence of arrhythmias at higher doses. This trial was registered at ClinicalTrials.gov, number: NCT01725243.

Assessment of sublingual misoprostol as first‐line treatment for primary post‐partum hemorrhage: Results of a multicenter trial

The study investigated the effectiveness of sublingual misoprostol when used as primary treatment of primary post-partum hemorrhage (PPH) in a low-income country. Maternity care providers in three Nigerian hospitals administrated 800 μm sublingual misoprostol to women experiencing PPH. The outcome variables were estimated blood loss and the need for additional uterotonic drugs after initial treatment with misoprostol. Entry criteria included women in term spontaneous labor, while exclusion criteria were women with operative delivery and those experiencing PPH not due to atonic uterus. One hundred and thirty-one women with PPH were treated over 6 months. Estimated blood loss ranged 500-2500 mL. Twenty women (15.3%) required additional uterotonic drugs to control continuing blood loss. There were no maternal deaths, while seven perinatal deaths were recorded. We conclude that although sublingual misoprostol is effective in reducing blood loss due to PPH, it does not effectively treat all forms of PPH. Additional uterotonics and other ancillary treatments would be required.

Is the Time of administration of misoprostol of value? The uterotonic effect of misoprostol given pre- and post-operative after elective cesarean section

Objective The aim of the current study was to compare blood loss in pre- and post-operatively rectally administered 600 μg of misoprostol in elective cesarean delivery, in order to determine the optimal time for drug administration (CS). Study design A 30-month prospective, single-blind, randomized, clinical trial was done in the Qena University Hospital, Egypt, from January 2010 to October, 2012. Methods Intervention consisted of pre and post-operative rectally administered misoprostol. At baseline, there were no significant differences in the demographic and obstetric variable between groups. Primary outcome measures were differences in intra-operative and postoperative blood loss between groups. Secondary outcomes measures were hemoglobin levels pre and operative (24 h after CS) and the need for additional uterotonic drugs. Results A total of 300 subjects were enrolled (pre-operative administrated rectally misoprostol n = 150, post-operative administrated rectally misoprostol n = 150). Subjects receiving pre-operative misoprostol achieved significantly lower blood loss compared to those receiving post-operative misoprostol (620 ± 291 ml vs. 898 ± 321 ml, p < 0.05), respectively. The need for additional uterotonic was significantly higher in subjects receiving post-operative misoprostol compared to those receiving pre-operative misoprostol (53.3% vs. 30%, p, 0.05), respectively. Conclusion Pre-operative rectally administrated misoprostol appears to be more effective than post-operative rectally administrated misoprostol in reducing blood loss, and in decreasing the need for other uterotonic drugs in cesarean section delivery.

Can Intravenous Injection of Tranexamic Acid Be Used in Routine Practice With Active Management of the Third Stage of Labor in Vaginal Delivery? A Randomized Controlled Study

Obstetric hemorrhage accounts for ∼25% of maternal morbidity. Many methodologies are used to promote active management of the third stage of labor. Tranexamic acid successfully reduces blood loss and transfusion requirements in nonobstetric conditions. This double-blind, randomized, controlled trial was undertaken to estimate the effects of adding tranexamic acid to an active management protocol. The parturients were at 34 to 42 weeks’ gestation, with a live fetus in cephalic presentation, and expecting vaginal birth. The experimental group (n = 228) received 1 g/10 mL tranexamic acid diluted with 20 mL 5% glucose; the placebo group (n = 226) received 30mL5%glucose. Tranexamic acid or placebo was administered intravenously over 5 minutes at delivery of the fetus’ anterior shoulder. Standard management of the third and fourth stages of labor was applied. The primary outcome was the volume of blood loss during the third and fourth stages of labor. Other outcomes were the incidence of postpartum hemorrhage (PPH; >500 mL), severe PPH (>1000 mL), need for blood transfusion, need for additional uterotonic drugs, and adverse effects of tranexamic acid. Participants were contacted 3 weeks after delivery to assess the incidence of thromboembolic events. Data were analyzed on an intent-to-treat basis. The final analysis included 220 and 219 in the tranexamic acid and control groups, respectively. The groups were similar in patient characteristics and risk factors for PPH. At the third and fourth stages of labor, mean estimated blood losses were 261.5 ± 146.8 and 349.98 ± 188.85 mL in the tranexamic acid and control groups, respectively (P < 0.001). Four patients (1.8%) in the tranexamic acid group and 15 (6.8%) in the control group had PPH of greater than 500 mL (RR, 3.76; 95% CI, 1.27–11.15; P = 0.01). Six (2.7%) and 19 (8.7%) women in the tranexamic acid and control groups, respectively, required additional uterotonic agents (RR 3.18; 95% CI, 1.29–7.81; P = 0.007). The groups did not differ in need for blood transfusion. Predelivery hemoglobin and hematocrit levels were the same in the 2 groups, but at 1 day postpartum, hemoglobin levels were 9.9 T 1.4 and 9.3 T 0.9 g/dL (P G 0.001), and hematocrit levels were 30.2% ± 1.2% and 29.0% ± 1.3% (P < 0.001) in the tranexamic acid and placebo groups, respectively. No major complications and no significant changes in prothrombin time, active prothrombin time, or liver or renal function tests were noted in either group. Rates for nausea, vomiting, and diarrhea were 15.0%, 13.6%, and 7.3% in the tranexamic acid group and 5.5%, 6.4%, and 1.8% in the control group. At the clinical checkup 3 weeks postpartum, no episode of thrombosis was reported in patients given tranexamic acid. Tranexamic acid can reduce the average amount of blood loss during the third and fourth stages of labor. Determining the clinical settings in which this medication may be beneficial is critical for future research.

Carbetocin vs. Syntometrine in Prevention of Postpartum Hemorrhage: a Double Blind Randomized Control Trial

BackgroundPostpartum hemorrhage is a significant cause of maternal mortality and morbidity, worldwide.ObjectivesThe aim of this study was to compare the efficacy between carbetocin and syntometrine in prevention of postpartum hemorrhage.Materials and MethodsThis study was a double blind randomized clinical trial that carried out on 200 pregnant women referred to Shabiehkhani maternity center of Kashan, during 2011. The first group received intramuscular syntometrine and the second group received intramuscular carbetocin after placental delivery. All of the participants were followed for 24 hours and blood pressure, pulse rate, uterine tone, hemoglobin concentration at first and 24 hours after delivery, and the need for additional uterotonic drugs and drug side effects were evaluated. Finally all data were analyzed using t-test, chi square tests and logistic regression.ResultsThe mean fall in hemoglobin level in the carbetocin group was significantly lower than the syntometrine group (P < 0.001). Also there were significant differences between the two groups, regarding additional uterotonic drug requirements (P = 0.002). Moreover systolic blood pressure and uterine tone immediately and 30 minutes after drug administration were significantly different (P < 0.001). Incidence rate of tachycardia in the carbetocin group was 13%, in contrast to 5% in the syntometrine group (P = 0.04).ConclusionsThis study revealed that carbetocin is more effective than syntometrine in prevention of postpartum hemorrhages. Thus it can be used as a good alternative of syntometrine for low-risk women.

Sublingual misoprostol versus intramuscular oxytocin for prevention of postpartum hemorrhage in low-risk women

Objective To compare sublingual misoprostol with intramuscular oxytocin for prevention of postpartum hemorrhage (PPH) in low-risk vaginal birth. Methods In a prospective, randomized, double-blind trial, 530 women without risk of PPH were randomly allocated to receive either 400 μg of misoprostol sublingually or 10 units of oxytocin intramuscularly within 1 minute of delivery. The outcome measures were incidence of PPH, postpartum blood loss, drop in hemoglobin level in 24 hours, need for additional uterotonic drug, incidence of adverse effects, and need for blood transfusion. Student t, χ 2, Mann–Whitney U, and Fisher exact tests were used for comparison. Results Incidence of postpartum hemorrhage (≥ 500 mL) and postpartum blood loss in the misoprostol group were similar to those in the oxytocin group (6% versus 5.7%, P = 0.85; 153 mL versus 146 mL, P = 0.36). Shivering and pyrexia were encountered more often in the misoprostol than in the oxytocin group (shivering: 19% versus 0.8%, P < 0.001, relative risk [RR] 0.86, 95% confidence interval [CI] 0.82–0.90; pyrexia: 2.3% versus 0%, P = 0.03, RR 0.97, 95% CI 0.95–0.99). Conclusion The efficacy of 400 μg of misoprostol administered sublingually was equivalent to that of 10 units of oxytocin given intramuscularly for prevention of PPH in low-risk vaginal delivery.

Five Unit Bolus Oxytocin at Cesarean Delivery in Women at Risk of Atony

I.v. bolus oxytocin is used routinely during cesarean delivery to prevent postpartum hemorrhage. Its adverse hemodynamic effects are well known, resulting in a recent change in dose from 10 IU to 5. Whether a 5 IU bolus has any advantages over infusion alone is unclear. We tested the hypothesis that a 5 IU i.v. bolus of oxytocin before the initiation of a continuous infusion decreases the need for additional uterotonic drugs in the first 24 hours after delivery in women with risk factors for uterine atony undergoing cesarean delivery, compared with infusion alone. A prospective, randomized, double-blind, controlled trial was conducted in 143 subjects undergoing cesarean delivery with at least 1 risk factor for uterine atony. Subjects received 5 IU bolus of oxytocin or normal saline i.v. over 30 seconds after umbilical cord clamping. All subjects received an infusion of 40 IU oxytocin in 500 mL normal saline over 30 minutes, followed by 20 IU in 1 L over 8 hours. The primary outcome was the need for additional uterotonics in the first 24 hours after delivery. Secondary outcomes included uterine tone as assessed by the surgeon (5-point Likert scale: 0 = "floppy," 4 = "rock hard"), estimated blood loss, side effects of bolus administration, and the oxytocin bolus-placental delivery interval. There was no difference in the need for additional uterotonic drugs in the first 24 hours between groups. There was a significant difference in uterine tone immediately after placental delivery (P < 0.01) (2.8 in the oxytocin group [95% confidence interval 2.6-3.0] vs 2.2 in the saline group [95% confidence interval 1.8-2.5]), which disappeared after 5 minutes. There were no differences in observed or reported side effects between groups. We found that a 5 IU i.v. bolus of oxytocin added to an infusion did not alter the need for additional uterotonic drugs to prevent or treat postpartum hemorrhage in the first 24 hours in women undergoing cesarean delivery with risk factors for uterine atony, despite causing an initial stronger uterine contraction. Our study was not powered to find a difference in side effects between groups. These results suggest that an oxytocin infusion may be adequate without the need for a bolus, even in high-risk patients.

Intravenous oxytocin bolus of 2 units is superior to 5 units during elective Caesarean section

BackgroundThe optimal dose of oxytocin at Caesarean section is unclear. Oxytocin may cause adverse cardiovascular effects, including tachycardia and hypotension, whereas an inadequate dose can result in increased uterine bleeding. We compared the effects of two doses of oxytocin in a randomized double-blind trial. MethodsEighty patients undergoing elective Caesarean section received an i.v. bolus of either 2 or 5 units (u) of oxytocin after delivery, followed by an oxytocin infusion of 10 u h−1. All received combined spinal–epidural anaesthesia with arterial pressure maintained by a phenylephrine infusion. We compared changes in heart rate (HR), mean arterial pressure (MAP), blood loss, uterine tone, the need for additional uterotonic drugs, and emetic symptoms. ResultsThere was a greater increase in mean (sd) HR in patients who received 5 u of oxytocin [32 (17) beats min−1] than in those who received 2 u [24 (13) beats min−1] (P=0.015). There was a larger decrease in MAP in patients who received 5 u [13 (15) mm Hg] than in those who received 2 u [6 (10) mm Hg] (P=0.030). The frequency of nausea and antiemetic use was higher after 5 u (32.5%) than 2 u (5%) (P=0.003). There were no differences in blood loss, uterine tone, or requests for additional uterotonic drugs (17.5% in both groups). ConclusionsIn elective Caesarean section, a 2 u bolus of oxytocin results in less haemodynamic change than 5 u, with less nausea and no difference in the need for additional uterotonics.