Impact of combined propranolol and oxytocin on the process and outcomes of labor: a meta-analysis of randomized controlled trials.

PURPOSE: To systematically review the impact of propranolol combined with oxytocin on the process and outcomes of labor. METHODS: A comprehensive literature search was performed across multiple databases, including China National Knowledge Infrastructure (CNKI), VIP, Wanfang, China Biomedical Literature Database, PubMed, Embase, and the Cochrane Library. All publicly published randomized controlled trials (RCTs) of propranolol combined with oxytocin compared to the use of oxytocin alone in labor were collected. After screening the literature and extracting data, the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0 recommended bias risk assessment tool was used to assess the quality of the included studies. A meta-analysis was conducted using RevMan 5.3 software, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to rate the quality of evidence for outcome measures. RESULTS: Meta-analysis results showed that the group receiving propranolol combined with oxytocin was more capable of reducing the cesarean section rate (eight studies, 815 women, RR = 0.67, 95% CI (0.53, 0.86), P = 0.001) and shortening the duration of the latent phase (two studies, 206 women, MD = - 1.20, 95% CI (- 1.97, - 0.43), P = 0.002) and the duration of the active phase on day 1 (two studies, 296 women, MD = - 0.69, 95% CI (- 0.83, - 0.54), P < 0.00001), compared to the oxytocin monotherapy group. No significant difference was found between the two groups in terms of the 5-min Apgar score (five studies, 609 women, MD = - 0.05, 95% CI (- 0.14, 0.04), P = 0.32) and the rate of admissions to the Neonatal Intensive Care Unit (NICU) (three studies, 359 women, RR = 0.82, 95% CI (0.38, 1.79), P = 0.62). CONCLUSION: The combined use of propranolol and oxytocin can significantly reduce the cesarean section rate, shorten the duration of the latent phase and the duration of the active phase on day 1, and is safe. However, due to the limitations, the conclusions of this article still need to be verified by large-sample, multicenter, rigorously designed high-quality clinical RCTs. TRIAL REGISTRATION: Registration number is INPLASY202390107.

Third stage of labor: evidence-based practice for prevention of adverse maternal and neonatal outcomes.

The third stage of labor is defined as the time period between delivery of the fetus through delivery of the placenta. During a normal third stage, uterine contractions lead to separation and expulsion of the placenta from the uterus. Postpartum hemorrhage is a relatively common complication of the third stage of labor. Strategies have been studied to mitigate the risk of postpartum hemorrhage, leading to the widespread implementation of active management of the third stage of labor. Initially, active management of the third stage of labor consisted of a bundle of interventions including administration of a uterotonic agent, early cord clamping, controlled cord traction, and external uterine massage. However, the effectiveness of these interventions as a bundle has been questioned, leading to abandonment of some components in recent years. Despite this, upon review of selected international guidelines, we found that the term "active management of the third stage of labor" was still used, but recommendations for and against individual interventions were variable and not necessarily supported by current evidence. In this review, we: (1) examine the physiology of the third stage of labor, (2) present evidence related to interventions that prevent postpartum hemorrhage and promote maternal and neonatal health, (3) review current global guidelines and recommendations for practice, and (4) propose future areas of investigation. The interventions in this review include pharmacologic agents to prevent postpartum hemorrhage, cord clamping, cord milking, cord traction, cord drainage, early skin-to-skin contact, and nipple stimulation. Treatment of complications of the third stage of labor is outside of the scope of this review. We conclude that current evidence supports the use of effective pharmacologic postpartum hemorrhage prophylaxis, delayed cord clamping, early skin-to-skin contact, and controlled cord traction at delivery when feasible. The most effective uterotonic regimens for preventing postpartum hemorrhage after vaginal delivery include oxytocin plus ergometrine; oxytocin plus misoprostol; or carbetocin. After cesarean delivery, carbetocin or oxytocin as a bolus are the most effective regimens. There is inconsistent evidence regarding the use of tranexamic acid in addition to a uterotonic compared with a uterotonic alone for postpartum hemorrhage prevention after all deliveries. Because of differences in patient comorbidities, costs, and availability of resources and staff, decisions to use specific prevention strategies are dependent on patient- and system-level factors. We recommend that the term "active management of the third stage of labor" as a combined intervention no longer be used. Instead, we recommend that "third stage care" be adopted, which promotes the implementation of evidence-based interventions that incorporate practices that are safe and beneficial for both the woman and neonate.

Single-balloon catheter with concomitant vaginal misoprostol is the most effective strategy for labor induction: a meta-review with network meta-analysis.

OBJECTIVE: Several systematic reviews and meta-analyses have been conducted to summarize the evidence for the efficacy of various labor induction agents. However, the most effective agents or strategies have not been conclusively determined. We aimed to perform a meta-review and network meta-analysis of published systematic reviews to determine the efficacy and safety of currently employed pharmacologic, mechanical, and combined methods of labor induction. DATA SOURCES: With the assistance of an experienced medical librarian, we performed a systematic search of the literature using PubMed, EMBASE, and the Cochrane Central Register of Control Trials. We systematically searched electronic databases from inception to May 31, 2021. STUDY ELIGIBILITY CRITERIA: We considered systematic reviews and meta-analyses of randomized controlled trials comparing different agents or methods for inpatient labor induction. METHODS: We conducted a frequentist random-effects network meta-analysis employing data from randomized controlled trials of published systematic reviews. We performed direct pairwise meta-analyses to compare the efficacy of the various labor induction agents and placebo or no treatment. We performed ranking to determine the best treatment using the surface under the cumulative ranking curve. The main outcomes assessed were cesarean delivery, vaginal delivery within 24 hours, operative vaginal delivery, hyperstimulation, neonatal intensive care unit admissions, and Apgar scores of <7 at 5 minutes of birth. RESULTS: We included 11 systematic reviews and extracted data from 207 randomized controlled trials with a total of 40,854 participants. When assessing the efficacy of all agents and methods, the combination of a single-balloon catheter with misoprostol was the most effective in reducing the odds of cesarean delivery and vaginal birth >24 hours (surface under the cumulative ranking curve of 0.9 for each). Among the pharmacologic agents, low-dose vaginal misoprostol was the most effective in reducing the odds of cesarean delivery, whereas high-dose vaginal misoprostol was the most effective in achieving vaginal delivery within 24 hours (surface under the cumulative ranking curve of 0.9 for each). Single-balloon catheter (surface under the cumulative ranking curve of 0.8) and double-balloon catheter (surface under the cumulative ranking curve of 0.9) were the most effective in reducing the odds of operative vaginal delivery and hyperstimulation. Buccal or sublingual misoprostol (surface under the cumulative ranking curve of 0.9) and the combination of single-balloon catheter and misoprostol (surface under the cumulative ranking curve of 0.9) most effectively reduced the odds of abnormal Apgar scores and neonatal intensive care unit admissions. CONCLUSION: The combination of a single-balloon catheter with misoprostol was the most effective method in reducing the odds for cesarean delivery and prolonged time to vaginal delivery. This method was associated with a reduction in admissions to the neonatal intensive care unit.

Outpatient cervical ripening and labor induction with low-dose vaginal misoprostol reduces the interval to delivery: a systematic review and network meta-analysis.

OBJECTIVE: Several systematic reviews and meta-analyses have summarized the evidence on the efficacy and safety of various outpatient cervical ripening methods. However, the method with the highest efficacy and safety profile has not been determined conclusively. We performed a systematic review and network meta-analysis of published randomized controlled trials to assess the efficacy and safety of cervical ripening methods currently employed in the outpatient setting. DATA SOURCES: With the assistance of an experienced medical librarian, we performed a systematic search of the literature using MEDLINE, Embase, Scopus, Web of Science, Cochrane Library, and ClinicalTrials.gov. We systematically searched electronic databases from inception to January 14, 2020. STUDY ELIGIBILITY CRITERIA: We considered randomized controlled trials comparing a variety of methods for outpatient cervical ripening. METHODS: We conducted a frequentist random effects network meta-analysis employing data from randomized controlled trials. We performed a direct, pairwise meta-analysis to compare the efficacy of various outpatient cervical ripening methods, including placebo. We employed ranking strategies to determine the most efficacious method using the surface under the cumulative ranking curve; a higher surface under the cumulative ranking curve value implied a more efficacious method. We assessed the following outcomes: time from intervention to delivery, cesarean delivery rates, changes in the Bishop score, need for additional ripening methods, incidence of Apgar scores <7 at 5 minutes, and uterine hyperstimulation. RESULTS: We included data from 42 randomized controlled trials including 6093 participants. When assessing the efficacy of all methods, 25 µg vaginal misoprostol was the most efficacious in reducing the time from intervention to delivery (surface under the cumulative ranking curve of 1.0) without increasing the odds of cesarean delivery, the need for additional ripening methods, the incidence of a low Apgar score, or uterine hyperstimulation. Acupressure (surface under the cumulative ranking curve of 0.3) and primrose oil (surface under the cumulative ranking curve of 0.2) were the least effective methods in reducing the time to delivery interval. Among effective methods, 50 mg oral mifepristone was associated with the lowest odds of cesarean delivery (surface under the cumulative ranking curve of 0.9). CONCLUSION: When balancing efficacy and safety, vaginal misoprostol 25 µg represents the best method for outpatient cervical ripening.

Tranexamic acid versus oxytocin for primary postpartum Haemorrhage in the out-of-hospital setting: A systematic review with implications for rural practice.

INTRODUCTION: Primary postpartum haemorrhage causes approximately 25% of global maternal deaths and accounts for significant maternal morbidity. While high certainty evidence demonstrates that tranexamic acid reduces comparative blood loss in postpartum haemorrhage in hospital settings, limited data exist on the specific pharmacological management of this condition in out-of-hospital settings, and the implications for rural communities. OBJECTIVE: To determine the efficacy of oxytocin compared to tranexamic acid in women suffering postpartum haemorrhage in the out-of-hospital environment. DESIGN: A systematic review comparing evidence containing patients with postpartum haemorrhage in the out-of-hospital and/or rural setting, in which oxytocin/tranexamic acid were used. Outcome measures were comparative blood loss/haemorrhagic shock, the need for further interventions and maternal/neonatal morbidity/mortality. FINDINGS: No randomised control trials have been conducted in an out-of-hospital environment in relation to oxytocin/tranexamic acid. In this setting, there is no difference in outcome measures when using oxytocin compared to no intervention, or oxytocin compared to standard care. Data are lacking on the effect of tranexamic acid on the same outcome measures. DISCUSSION: Rural and out-of-hospital management of postpartum haemorrhage is limited by resource availability and practitioner availability, capacity and experience. In-hospital evidence may lack transferability, therefore direct evidence on the efficacy of pharmacological management in these contexts is scant and requires redress. CONCLUSION: There is no difference in blood loss, neonatal or maternal mortality or morbidity, or need for further interventions, when using oxytocin or TXA compared to no intervention, or compared to standard care, for PPH. Further studies are needed on the efficacy of these drugs, and alternate or co-drug therapies, for PPH in the out-of-hospital environment and rural clinical practice.

A Comparison of the Efficacy and Safety of Mifepristone and Misoprostol Versus Misoprostol alone for Induction of Labour in Nigerian Women with Intrauterine Fetal Death: A Triple Blind Randomized Controlled Trial.

BACKGROUND: Intrauterine foetal death (IUFD) is an unpleasant pregnancy outcome and prompt delivery of the dead foetus is usually desired by mothers. Unfortunately, spontaneous labour and delivery may not occur early and prolonged retention of the dead foetus in utero is life-threatening. Many of the agents currently used for the induction of labour may result in a prolonged delivery process. OBJECTIVES: To compare the efficacy and safety of mifepristone and misoprostol versus misoprostol alone for induction of labour in women with intrauterine foetal death. MATERIALS AND METHODS: This was a triple-blind randomized controlled trial. Eighty women were randomized into two groups. The intervention group received a single oral dose of 200 mg mifepristone, followed by 6-hourly 50 µg misoprostol vaginal insertion, after 24-hour intervals. The control group received a placebo, followed by 6-hourly 50 µg misoprostol vaginal insertion, after 24-hour intervals. The primary outcome measure was the induction to delivery interval. RESULTS: Maternal age, gestational age, parity and pre-induction bishop's score were comparable between the two groups. The mean induction to the delivery interval in the intervention group was significantly less in the intervention group than the control group (18.78 ± 6.51 hours versus 37.10 ± 10.10; P < 0.001). The total dose of misoprostol required for induction of labour; the need for oxytocin augmentation of labour; and the observed side effects of misoprostol were all significantly less in intervention group than control group (P < 0.001; P < 0.01; and P = 0.03, respectively). CONCLUSION: The combination of mifepristone and misoprostol has greater efficacy and better safety profile than the use of misoprostol alone for induction of labour. This combination should be considered when induction of labour is indicated for IUFD.

Evidence Based Management of Labor.

Importance: Induction of labor (IOL) is a common obstetric intervention. Augmentation of labor and active management of the second stage is frequently required in obstetric practice. However, techniques around labor and induction management vary widely. Evidence-based practice regarding induction and labor management can reduce birth complications such as infection and hemorrhage and decrease rates of cesarean delivery. Objective: To review existing evidence on IOL and labor management strategies with respect to preparing for induction, cervical ripening, induction and augmentation, and second stage of labor techniques. Evidence acquisition: Review of recent original research, review articles, and guidelines on IOL using PubMed (2000-2022). Results: Preinduction, pelvic floor training and perineal massage reduce postpartum urinary incontinence and perineal trauma, respectively. Timely membrane sweeping (38 weeks) can promote spontaneous labor and prevent postterm inductions. Outpatient Foley bulb placement in low-risk nulliparous patients with planned IOL reduces time to delivery. Inpatient Foley bulb use beyond 6 to 12 hours shows no benefit. When synthetic prostaglandins are indicated, vaginal misoprostol should be preferred. For nulliparous patients and those with obesity, oxytocin should be titrated using a high-dose protocol. Once cervical dilation is complete, pushing should begin immediately. Warm compresses and perineal massage decrease risk of perineal trauma. Conclusion and relevance: Several strategies exist to assist in successful IOL and promote vaginal delivery. Evidence-based strategies should be used to improve outcomes and decrease risk of complications and cesarean delivery. Recommendations should be shared across interdisciplinary team members, creating a model that promotes safe patient care.

Feasibility Study to Compare Oxytocin Function Between Body Mass Index Groups at Term Labor Induction.

OBJECTIVE: To determine the feasibility of a protocol to examine the association between oxytocin system function and birth outcomes in women with and without obesity before induction of labor. DESIGN: Prospective descriptive. SETTING: Academic medical center in the U.S. Midwest. PARTICIPANTS: Pregnant women scheduled for induction of labor at 40 weeks of gestation or greater (n = 15 normal weight; n = 15 obese). METHODS: We collected blood samples and abstracted data by chart review. We used percentages to examine adherence to protocol. We used t tests and chi-square tests to describe differences in sample characteristics, oxytocin system function variables, and birth outcomes between the body mass index groups. RESULTS: The recruitment rate was 85.7%, protocol adherence was 97.1%, and questionnaire completion was 80.0%. Mean plasma oxytocin concentration was higher in the obese group (M = 2774.4 pg/ml, SD = 797.4) than in the normal weight group (M = 2193.5 pg/ml, SD = 469.8). Oxytocin receptor DNA percentage methylation (CpG -934) was higher in the obese group than in the normal weight group. CONCLUSION: Our protocol was feasible and can serve as a foundation for estimating sample sizes in forthcoming studies investigating the diversity in oxytocin system measurements and childbirth outcomes among pregnant women in different body mass index categories.

The minimum effective dose (ED90) of prophylactic oxytocin infusion during cesarean delivery in patients with and without obesity: an up-down sequential allocation dose-response study.

BACKGROUND: Obesity is associated with greater oxytocin requirement during labor induction or augmentation. There are scant data exploring the intra-operative requirement during cesarean delivery in patients with obesity, and none comparing it with those without obesity. We evaluated the minimum effective dose (ED90) of an oxytocin infusion to achieve adequate uterine tone during cesarean delivery in patients with and without obesity. METHODS: Patients (body mass index ≥30 kg/m2 represented patients with obesity) undergoing cesarean delivery using subarachnoid block were included. This prospective dual-arm dose-finding study used a 9:1 biased sequential allocation design. Oxytocin infusion was initiated at 13 IU/h at cord clamping in the first patient of each group. Uterine tone was graded as satisfactory or unsatisfactory by the obstetrician four minutes after initiation of the infusion. The dose of oxytocin infusion for subsequent patients was determined according to the response of the previous patient in the group. Oxytocin-associated side effects were evaluated. Dose-response data for the groups was evaluated using log-logistic function and ED90 estimates derived from fitted equations using the delta method. RESULTS: The ED90 of oxytocin was significantly higher for patients with obesity (n = 40) compared with those without obesity (n = 40) [25.7 IU/h, 95% CI 18.6 to 32.9) vs. 16.6 IU/h, 95% CI 14.9 to 18.3)]; relative ratio 1.55 [95% CI 1.09 to 2.01] (P = 0.019). CONCLUSIONS: Patients with obesity require a higher intra-operative oxytocin infusion dose rate to achieve a satisfactorily contracted uterus after fetal delivery when compared with patients without obesity.

Preoperative versus postoperative misoprostol use for prevention of blood loss during caesarean section in pregnant women at term: a multi-centre randomised controlled trial.

OBJECTIVE: Caesarean section is associated with higher blood loss than vaginal delivery. This study was performed to compare the safety and efficacy of preoperative versus postoperative rectal and sublingual misoprostol use for prevention of blood loss in women undergoing elective caesarean delivery. METHODS: Eligible patients in Southeast Nigeria were randomly classified into those that received 600 µg of preoperative rectal, postoperative rectal, preoperative sublingual, and postoperative sublingual misoprostol. All patients received 10 units of intravenous oxytocin immediately after delivery. Data were analysed with SPSS Version 23. RESULTS: Preoperative sublingual misoprostol use caused the highest postoperative packed cell volume, least change in the packed cell volume, and lowest intraoperative blood loss. Preoperative sublingual and rectal misoprostol use was associated with better haematological indices and maternal outcomes than postoperative use by these routes. However, preoperative sublingual and rectal use caused more maternal side effects than postoperative use by these routes. CONCLUSION: Preoperative sublingual misoprostol was associated with the most favourable haematological indices. Although preoperative sublingual and rectal misoprostol use caused more maternal side effects, these routes were associated with better haematological indices and maternal outcomes than postoperative sublingual and rectal misoprostol use.

Carbetocin versus Oxytocin with or without Tranexamic Acid for Prophylactic Prevention of Postpartum Hemorrhage after a Vaginal Delivery: A Randomized Clinical Trial.

OBJECTIVE: Our study's primary objective was to examine the effects of four different prophylactic protocols on the prevention of postpartum hemorrhage following vaginal birth, including carbetocin only, oxytocin only, and a combination of carbetocin or oxytocin with tranexamic acid. DESIGN: A multicentric randomized controlled trial. PARTICIPANTS/MATERIALS, SETTING, AND METHODS: This multicentric center prospective randomized controlled trial was conducted at the Department of Obstetrics and Gynecology of Bezmialem University and Van Health Teaching and Research Hospital from August 2022 to January 2023. The collected data included age, gravidity, parity, gestational age at birth, duration of delivery stages, prepartum hemoglobin and hematocrit concentrations, changes in hemoglobin and hematocrit concentrations, intrapartum blood loss, estimated blood loss after 2 h of vaginal delivery, Apgar scores at 1 and 5 min, birth weight, and neonatal intensive care unit (NICU) admission. Intrapartum blood loss was objectively measured in milliliters using a postpartum drape with a calibrated bag. The amount of bleeding was measured by subtracting the empty weight of the pads placed under the patient in the patient's bed within 2 h after delivery. Group I: carbetocin 100 µg/mL (n = 75), group II: oxytocin 5 IU/mL (n = 75), group III: carbetocin and tranexamic acid 50 mg/mL (n = 75), group IV: oxytocin and tranexamic acid (n = 75). RESULTS: The hemoglobin concentration decrease significantly differed between groups (1.03 ± 1.04, 1.3 ± 0.85, 1.4 ± 0.85, 1.41 ± 0.87, respectively; p < 0.001). Group 4 has the highest decrease in hemoglobin and hematocrit concentrations. When we investigated the subgroup differences, the decrease in hemoglobin concentration was significantly higher in group 2 than group 1 (1.30 ± 0.85 vs. 1.03 ± 1.04; p = 0.023), in group 2 than group 3 (1.3 ± 0.85 vs. 1.04 ± 0.9; p = 0.013), and in group 4 than group 3 (1.41 ± 0.87 vs. 1.04 ± 0.9; p < 0.001). The decrease in hematocrit level was significantly different between groups (3.07 ± 3.23, 3.55 ± 2.44, 2.13 ± 3.09, 4.25 ± 2.52; p < 0.001, respectively). No significant differences were observed in terms of mean blood loss between the four groups (277.19 ± 208.10, 294.13 ± 198.64, 274.33 ± 199.57, and 283.97 ± 178.11; p = 0.445, respectively). Furthermore, there was no significant difference between the groups in the rate of need for blood transfusion (1.3%, 5.4%, 4%, and 4%, respectively; p = 0.6). LIMITATIONS: The most important limitation of the study is a relatively small number of participants. CONCLUSION: In conclusion, our findings suggest that carbetocin may be more successful than oxytocin and oxytocin plus tranexamic acid regimens in terms of postpartum hemoglobin reduction, and there is no difference in terms of the need for blood transfusion when it is used for postpartum hemorrhage prophylaxis after vaginal delivery.

A comparison of misoprostol with and without methylergometrine and oxytocin in outpatient medical abortion: a phase III randomized controlled trial.

OBJECTIVE: The complications associated with miscarriages have surfaced as a major concern in maintaining women's physical and mental health. The present study evaluated the efficacy of three medication regimes for the complete expulsion of retained intrauterine tissues in patients who underwent a miscarriage. METHODS: In this randomized clinical trial, 90 patients participated with their gestational age below 12 weeks, each having undergone a recent miscarriage. After being screened for underlying diseases and coagulative blood disorders, they were randomly allocated into three groups. For the first group, labeled as the control group, misoprostol was administered alone. In contrast, the combination of misoprostol plus methylergometrine and misoprostol plus oxytocin was prescribed for the second and third groups, respectively. Further, the data obtained were analyzed by descriptive and inferential statistics using Stata software version 14. RESULTS: The mean age of participants and gestational age were 29.76 ± 5.53 years and 8.23 ± 2.29 weeks, respectively. There was no significant difference between the three treatment groups regarding the amount of bleeding after the abortion(P = 0.627). Regarding pain severity, the group that received Misoprostol plus Methylergometrine had less pain intensity than the other two groups(p = 0.004). The mean rate of RPOC expulsion was in the Misoprostol plus Oxytocin (9.68 ± 10.36) group, Misoprostol plus Methylergometrine (11.73 ± 12.86), and Misoprostol groups (19.07 ± 14.31)(p = 0.013). The success rate in outpatient medical abortion in the misoprostol plus oxytocin and misoprostol plus methylergonovine group was 93.33%, but in patients treated by misoprostol alone was 83.33%. CONCLUSION: The effectiveness of the drugs in the two drug groups combined with oxytocin and methylergometrine is higher than the misoprostol group alone. An outpatient approach was deemed more satisfactory against surgical maneuvers and hospitalizations by patients since family support influenced their pain coping mechanism. TRIAL REGISTRATION: The trial was registered in the Iranian registry of clinical trials on 04/10/2019. ( https://fa.irct.ir/trial/34519 ; registration number: IRCT20150407021653N19).

Effect of Carbetocin on Uterine Tone during Cesarean Section: A Comparison between Subarachnoid Block and General Anesthesia.

Background: Postpartum hemorrhage remains a challenge in obstetric practice in developing climes and contributes immensely to the horrendous figures of maternal mortality worldwide. Aim: The aim was to compare the effect of intravenous (IV) carbetocin on uterine tone under different anesthetic techniques for elective cesarean section. Methods: Four hundred and seventy-eight consecutive women scheduled for elective cesarean section were recruited into two groups by convenience. While 445 parturients received subarachnoid block (SAB), 33 had general anesthesia (GA). At delivery, IV carbetocin was administered. The uterine tone was assessed manually and blood loss from intraoperative period to the 24th h was determined. Other variables such as hemodynamic profiles and Apgar scores were determined and recorded. Results: The bio-characteristics between the two groups were essentially the same in terms of age, weight, height, body mass index, preoperative hemoglobin, and gestational age. While the response to the administered carbetocin was slower in the GA group, there was no need for additional dose. The mean estimated intraoperative blood loss under SAB was 250.44 ± 50.59 ml and that under GA was 470.89 ± 35.70 ml, P = 0.000000. The ephedrine consumption was 6.25 ± 2.05 mg in the SAB group while it was 11.25 ± 2.49 mg, P = 0.000000. There was no further maternal blood loss observed after the intraoperative period until the end of 24-h period. The hemodynamic profiles were significantly different in terms of mean systolic blood pressure, mean diastolic blood pressure, and mean arterial blood pressure, P = 0.006, P = 0.002, and P = 0.003, respectively. However, the difference in the mean heart rate was not statistically significant, P = 0.304. While the Apgar scores between groups were not statistically significant, the mean umbilical pH was 7.34 ± 0.09 in the SAB group, it was 7.35 ± 0.02 in the GA group, P = 0.071. Conclusion: Intraoperative maternal blood loss was more among the parturients who received GA than subarachnoid blood. This could probably be due to the effect of the halogenated vapor used for the GA on the uterine tone. There was no further blood loss after the intraoperative period. The hemodynamic profile was better under SAB as evidenced by the total ephedrine consumption.

Résumé Contexte: L'hémorragie post-partum reste un défi dans la pratique obstétricale dans les pays en développement et contribue énormément à l'horrible chiffres de la mortalité maternelle dans le monde. Objectif: L'objectif était de comparer l'effet de la carbétocine intraveineuse (IV) sur le tonus utérin sous différentes techniques d'anesthésie pour la césarienne élective. Méthodes: Quatre cent soixante-dix-huit femmes consécutives devant subir une césarienne élective section ont été recrutés en deux groupes par commodité. Alors que 445 parturientes ont reçu un bloc sous-arachnoïdien (SAB), 33 ont eu une anesthésie générale (AG). À l'accouchement, de la carbétocine IV a été administrée. Le tonus utérin a été évalué manuellement et la perte de sang de la période peropératoire à la 24e heure a été déterminé. D'autres variables telles que les profils hémodynamiques et les scores d'Apgar ont été déterminées et enregistrées. Résultats: Les bio-caractéristiques entre les deux groupes étaient essentiellement les mêmes en termes d'âge, de poids, de taille, d'indice de masse corporelle, d'hémoglobine préopératoire et d'âge gestationnel. Tandis que le la réponse à la carbétocine administrée était plus lente dans le groupe GA, aucune dose supplémentaire n'était nécessaire. Le sang peropératoire moyen estimé la perte sous SAB était de 250,44 ± 50,59 ml et celle sous GA était de 470,89 ± 35,70 ml, P = 0,000000. La consommation d'éphédrine était de 6,25 ± 2,05 mg dans le groupe SAB alors qu'il était de 11,25 ± 2,49 mg, P = 0,000000. Il n'y a pas eu d'autre perte de sang maternel observée après la période peropératoire jusqu'à la fin de la période de 24 h. Les profils hémodynamiques étaient significativement différents en termes de tension artérielle systolique moyenne, de tension artérielle diastolique moyenne et la pression artérielle moyenne, P = 0,006, P = 0,002 et P = 0,003, respectivement. Cependant, la différence de fréquence cardiaque moyenne était pas statistiquement significatif, P = 0,304. Alors que les scores d'Apgar entre les groupes n'étaient pas statistiquement significatifs, le pH ombilical moyen était de 7,34 ± 0,09 dans le groupe SAB, elle était de 7,35 ± 0,02 dans le groupe AG, p = 0,071. Conclusion: La perte de sang maternel peropératoire était plus importante chez les parturientes ayant reçu GA que le sang sous-arachnoïdien. Cela pourrait probablement être dû à l'effet de la vapeur halogénée utilisée pour l'AG sur le tonus utérin. Il n'y avait pas perte de sang supplémentaire après la période peropératoire. Le profil hémodynamique était meilleur sous SAB comme en témoigne la consommation totale d'éphédrine. Mots-clés: Perte de sang, anesthésie générale, carbétocine intraveineuse, bloc sous-arachnoïdien, tonus utérin.

Randomized Trial of Early Detection and Treatment of Postpartum Hemorrhage.

BACKGROUND: Delays in the detection or treatment of postpartum hemorrhage can result in complications or death. A blood-collection drape can help provide objective, accurate, and early diagnosis of postpartum hemorrhage, and delayed or inconsistent use of effective interventions may be able to be addressed by a treatment bundle. METHODS: We conducted an international, cluster-randomized trial to assess a multicomponent clinical intervention for postpartum hemorrhage in patients having vaginal delivery. The intervention included a calibrated blood-collection drape for early detection of postpartum hemorrhage and a bundle of first-response treatments (uterine massage, oxytocic drugs, tranexamic acid, intravenous fluids, examination, and escalation), supported by an implementation strategy (intervention group). Hospitals in the control group provided usual care. The primary outcome was a composite of severe postpartum hemorrhage (blood loss, ≥1000 ml), laparotomy for bleeding, or maternal death from bleeding. Key secondary implementation outcomes were the detection of postpartum hemorrhage and adherence to the treatment bundle. RESULTS: A total of 80 secondary-level hospitals across Kenya, Nigeria, South Africa, and Tanzania, in which 210,132 patients underwent vaginal delivery, were randomly assigned to the intervention group or the usual-care group. Among hospitals and patients with data, a primary-outcome event occurred in 1.6% of the patients in the intervention group, as compared with 4.3% of those in the usual-care group (risk ratio, 0.40; 95% confidence interval [CI], 0.32 to 0.50; P<0.001). Postpartum hemorrhage was detected in 93.1% of the patients in the intervention group and in 51.1% of those in the usual-care group (rate ratio, 1.58; 95% CI, 1.41 to 1.76), and the treatment bundle was used in 91.2% and 19.4%, respectively (rate ratio, 4.94; 95% CI, 3.88 to 6.28). CONCLUSIONS: Early detection of postpartum hemorrhage and use of bundled treatment led to a lower risk of the primary outcome, a composite of severe postpartum hemorrhage, laparotomy for bleeding, or death from bleeding, than usual care among patients having vaginal delivery. (Funded by the Bill and Melinda Gates Foundation; E-MOTIVE ClinicalTrials.gov number, NCT04341662.).

Postpartum haemorrhage in high-resource settings: Variations in clinical management and future research directions based on a comparative study of national guidelines.

OBJECTIVE: To compare guidelines from eight high-income countries on prevention and management of postpartum haemorrhage (PPH), with a particular focus on severe PPH. DESIGN: Comparative study. SETTING: High-resource countries. POPULATION: Women with PPH. METHODS: Systematic comparison of guidance on PPH from eight high-income countries. MAIN OUTCOME MEASURES: Definition of PPH, prophylactic management, measurement of blood loss, initial PPH-management, second-line uterotonics, non-pharmacological management, resuscitation/transfusion management, organisation of care, quality/methodological rigour. CONCLUSIONS: Our study highlights areas where strong evidence is lacking. There is need for a universal definition of (severe) PPH. Consensus is required on how and when to quantify blood loss to identify PPH promptly. Future research may focus on timing and sequence of second-line uterotonics and non-pharmacological interventions and how these impact maternal outcome. Until more data are available, different transfusion strategies will be applied. The use of clear transfusion-protocols are nonetheless recommended to reduce delays in initiation. There is a need for a collaborative effort to develop standardised, evidence-based PPH guidelines. RESULTS: Definitions of (severe) PPH varied as to the applied cut-off of blood loss and incorporation of clinical parameters. Dose and mode of administration of prophylactic uterotonics and methods of blood loss measurement were heterogeneous. Recommendations on second-line uterotonics differed as to type and dose. Obstetric management diverged particularly regarding procedures for uterine atony. Recommendations on transfusion approaches varied with different thresholds for blood transfusion and supplementation of haemostatic agents. Quality of guidelines varied considerably.

Cost-effectiveness and budget impact of heat-stable carbetocin compared to oxytocin and misoprostol for the prevention of postpartum hemorrhage (PPH) in women giving birth in India.

INTRODUCTION: Low- and middle-income countries (LMICs) are committed to achieving the Sustainable Development Goal 3.1 to reduce maternal mortality. The Ministry of Health and Family Welfare of India recommends prophylactic uterotonic administration to every woman following delivery to reduce the risk of postpartum hemorrhage (PPH), as PPH is the leading cause of maternal mortality in LMICs, including India. In 2018, the World Health Organization first recognized heat-stable carbetocin for PPH prevention. Governments are now considering its introduction into their public health systems. METHODS: A decision-tree model was developed from the public healthcare system perspective to compare the value of heat-stable carbetocin versus oxytocin and misoprostol among women giving birth in public sector healthcare facilities in India. The model accounted for differences in PPH risk and costs based on mode of delivery and healthcare setting, as well as provider behavior to mitigate quality concerns of oxytocin. Model outcomes for each prophylactic uterotonic included the number of PPH events, DALYs due to PPH, deaths due to PPH, and direct medical care costs. The budget impact was estimated based on projected uterotonic uptake between 2022-2026. RESULTS: Compared to oxytocin, heat-stable carbetocin avoided 5,468 additional PPH events, 5 deaths, and 244 DALYs per 100,000 births. Projected direct medical costs to the public healthcare system were lowered by US $171,700 (₹12.8 million; exchange rate of ₹74.65 = US$1 from 2 Feb 2022) per 100,000 births. Benefits were even greater when compared to misoprostol (7,032 fewer PPH events, 10 fewer deaths, 470 fewer DALYs, and $230,248 saved per 100,000 births). In the budget impact analysis, India's public health system is projected to save US$11.4 million (₹849 million) over the next five years if the market share for heat-stable carbetocin grows to 19% of prophylactic uterotonics administered. CONCLUSIONS: Heat-stable carbetocin is expected to reduce the number of PPH events and deaths, avoid more DALYs, and reduce costs to the public healthcare system of India. Greater adoption of heat-stable carbetocin for the prevention of PPH could advance India's efforts to achieve its maternal health goals and increase efficiency of its public health spending.

Implementation of glucose 5% supplementation protocol to reduce the duration of labor among women with cervical ripening by prostaglandins: The GLUCOSHORT before-and-after study.

INTRODUCTION: Previous publications have shown that glucose supplementation could reduce labor duration in women with induction of labor with a favorable cervix but none have shown it for women with an unfavorable cervix.  The purpose of our study was to assess the impact on labor duration of a protocol of glucose supplementation used for induction of labor in women with an unfavorable cervix. MATERIAL AND METHODS: The protocol implemented in November 2017 added glucose supplementation by 5% dextrose at 125 mL/h to Ringer lactate for women with an unfavorable cervix with labor induced with dinoprostone gel. The study included women who underwent this protocol with a singleton, term, cephalic fetus from June 2017 through April 2018. The primary outcome was the labor duration. The secondary outcomes were mode of delivery, postpartum hemorrhage rate, neonatal outcomes, and durations other stage of labor. These outcomes were compared between the pre-intervention (from June 1 to October 31, 2017) and post-intervention (from December 1, 2017 to April 30, 2018) periods. RESULTS: The pre-intervention period included 116 women, and the post-intervention period 123. The characteristics of women and the induction of labor were similar in the two periods. The median duration from induction to delivery was not significantly different between the two periods (13.2 h, IQR 9.1-18.6 versus 13.6 h IQR 9.3-18.3, P=.67). The secondary outcomes did not differ significantly between the two groups. DISCUSSION: Glucose supplementation administered to women with an unfavorable cervix undergoing induction does not appear to reduce the induction-delivery duration.

Prevention of postpartum hemorrhage in vaginal deliveries.

Identification of patients at risk for postpartum hemorrhage (PPH) may allow for prompt diagnosis and intervention. Individual risk factors, risk assessment tools and prediction models have been used for determining a patient's risk of PPH. Measures for the prevention of PPH include identification and management of iron deficiency anemia, unit readiness and preparedness through performing regular simulations and having a PPH cart or medication kit readily available, prophylactic uterotonic - carbetocin alone or dual agents such as oxytocin and misoprostol or oxytocin and methylergometrine or antifibrinolytic (oxytocin and tranexamic acid) use in the third stage of labor immediately after fetal head delivery, and controlled cord traction.

Intracervical Foley catheter plus intravaginal misoprostol compared to intravaginal misoprostol-only for cervical ripening: A systematic review and meta-analysis.

To compare the combination of intracervical Foley catheter and intravaginal misoprostol administration versus intravaginal misoprostol administration-only for cervical ripening. The Medline, EMBASE, ClinicalTrials.gov, PROSPERO, Scopus, and Cochrane Collaboration databases were searched systematically. Randomized controlled trials that included patients with a singleton viable fetus who underwent induction of labor that required cervical ripening with an unfavorable cervix (Bishop ≤ 6) were eligible for inclusion. Primary outcomes was time to delivery and rate of cesarean delivery. Thirteen trials with 2978 subjects met the inclusion criteria. There was no difference in the incidence of cesarean delivery between the two groups (RR, 0.90; 95 % CI, 0.72-1.14; I2 = 69 %). The combination group resulted in comparable time to delivery (MD -2.50 h; 95 % CI 0.38, -5.38; I2 = 97 %), shorter time to vaginal delivery (MD -3.49 h; 95 % CI -4.89, -2.09; I2 = 81 %), lower risk of neonatal intensive care unit (NICU) admission (RR 0.72, 95 % CI 0.58-0.90, I2 = 0 %), meconium-stained fluid (RR 0.48, 95 % CI 0.31-0.73, I2 = 28 %), and tachysystole with fetal heart trace changes (RR 0.49, 95 % CI 0.27-0.86, I2 = 43 %), compared with intravaginal misoprostol-only group. There was no statistical difference in rates of terbutaline use, endometritis or chorioamnionitis between the two groups. The combination of intravaginal misoprostol with intracervical Foley catheter for cervical ripening is not associated with shorter time to delivery. However, the combination group shows significant difference in shorter time to vaginal delivery, NICU admission, meconium-stained fluid, and tachysystole with fetal heart trace changes.

Medical management of secondary postpartum haemorrhage: A prospective cohort study.

BACKGROUND: Secondary postpartum haemorrhage (PPH) complicates ~1% of pregnancies and can cause serious maternal morbidity. However, evidence guiding optimal management is scarce and often based on case series and expert opinion. AIMS: To measure the success of primary medical therapy in managing secondary PPH and to identify factors associated with need for surgical management. MATERIALS AND METHODS: Postpartum patients presenting to a tertiary women's hospital emergency department between July 2020 and October 2021 with secondary PPH were recruited. Data from the acute presentation were prospectively collected. Antenatal and intrapartum data were collected from medical record review. The primary outcome was the success of medical management for secondary PPH, defined by the implementation of medical or expectant measures without subsequent need for surgical intervention. RESULTS: One-hundred and twenty patients underwent primary medical management for secondary PPH. Ninety-eight (82%) were managed successfully with medical management and 22 (18%) required surgery. Medical management involved misoprostol (n = 33; 27.5%), antibiotics (n = 108; 90%), and less commonly other uterotonics (n = 6; 5%). Factors associated with lower rates of successful medical management included: antecedent manual removal of placenta (MROP) (odds ratio (OR) 0.2, P = 0.047), primary PPH ≥500 mL (OR 0.39, P = 0.048) or ≥1 L (OR 0.24, P = 0.009), >200 mL blood loss at presentation (OR 0.17, P = 0.015), increasing time post-delivery (OR 0.84, P = 0.044), retained products of conception (RPOC) on ultrasound (OR 0.024, P = 0.001) and vaginal birth (OR 0.27, P = 0.027). CONCLUSION: Medical management was highly successful. Vaginal birth, MROP, primary PPH, RPOC on ultrasound and increasing time post-delivery were associated with increased need for surgical management.