The Effect of an Oxytocin Decision Support Checklist on Oxytocin Use and Maternal and Neonatal Outcomes: A Retrospective Cohort Study.

OBJECTIVE: To assess the association between use of an oxytocin decision support checklist with oxytocin usage and clinical outcomes. STUDY DESIGN: We conducted a retrospective cohort study of patients with singleton gestations at 370/7 weeks or greater who received oxytocin during labor from October 2012 to February 2017 at an integrated community health care system during three exposure periods: (1) prechecklist; (2) after paper checklist implementation; and (3) after checklist integration into the electronic medical record (EMR). The checklist was a clinical decision support tool to standardize the dosing and management of oxytocin. Thus, our primary outcomes included oxytocin infusion rates and cumulative dose. Secondary outcomes included maternal and neonatal outcomes. We controlled for maternal risk factors with multivariable regression analysis and stratified by mode of delivery. RESULTS: A total of 34,269 deliveries were included. Unadjusted analyses showed that compared with prechecklist, deliveries during the paper and EMR-integrated periods had a lower cumulative dose (4,670 ± 6,174 vs. 4,318 ± 5,719 and 4,286 ± 5,579 mU, p < 0.001 for both), lower maximal infusion rate (9.9 ± 6.8 vs. 8.7 ± 5.8 and 8.4 ± 5.6 mU/min, p < 0.001 for both), and longer duration of oxytocin use (576 ± 442 vs. 609 ± 476 and 627 ± 488 minutes, p < 0.001 and p = 0.01, respectively). The unadjusted rates of cesarean, 5-minute Apgar <7, mechanical ventilation, and neonatal hospital length of stay were similar between periods. The adjusted mean difference in time from admission to delivery was longer during the EMR-integrated period compared with prechecklist (3.0 [95% confidence interval: 2.7-3.3] hours, p < 0.001). CONCLUSION: Oxytocin checklist use was associated with decreased oxytocin use patterns at the expense of longer labor times. Findings were more pronounced with EMR integration. KEY POINTS: · An oxytocin decision support checklist is associated with reduced amounts of oxytocin used.. · However, checklists were associated with longer duration of oxytocin use and of labor.. · Results were more pronounced in the EMR-integrated checklist compared with paper checklist..

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.

Comparative study between oxytocin and combination of tranexamic acid and ethamsylate in reducing intra-operative bleeding during emergency and elective cesarean section after 38 weeks of normal pregnancy.

OBJECTIVE: Cesarean Section (CS) is associated with an increased risk of hemorrhage. Many drugs are used to decrease this risk. We aim to compare the combination of ethamsylate and tranexamic acid, oxytocin, and placebo in women undergoing CS. METHODS: We conducted a double-blinded, randomized, placebo-controlled trial between October and December 2020 in four university hospitals in Egypt. The study included all pregnant women in labor without any complications who accepted to participate in the study between October and December 2020. The participants were divided into three groups. The subjects were randomly allocated to receive either oxytocin (30 IU in 500 ml normal saline during cesarean section), combined one gram of tranexamic acid with 250 mg of ethamsylate once before skin incision, or distilled water. Our main outcome was the amount of blood loss during the operation. The secondary outcomes were the need for blood transfusion, hemoglobin and hematocrit changes, hospital stay, operative complications, and the need for a hysterectomy. The one-way ANCOVA test was used to compare the quantitative variables between the three groups while the Chi-square test was used to compare the qualitative variables. Post hoc analysis then was performed to compare the difference between every two groups regarding the quantitative variables. RESULTS: Our study included 300 patients who were divided equally into three groups. Tranexamic acid with ethamsylate showed the least intra-operative blood loss (605.34 ± 158.8 ml) compared to oxytocin (625.26 ± 144.06) and placebo (669.73 ± 170.69), P = 0.015. In post hoc analysis, only tranexamic acid with ethamsylate was effective in decreasing the blood loss compared to placebo (P = 0.013); however, oxytocin did not reduce blood loss compared to saline (P = 0.211) nor to tranexamic acid with ethamsylate (P = 1). Other outcomes and CS complications showed no significant difference between the three groups except for post-operative thrombosis which was significantly higher in the tranexamic and ethamsylate group, P < 0.00001 and the need for a hysterectomy which was significantly increased in the placebo group, P = 0.017. CONCLUSION: The combination of tranexamic acid and ethamsylate was significantly associated with the least amount of blood loss. However, in pairwise comparisons, only tranexamic acid with ethamsylate was significantly better than saline but not with oxytocin. Both oxytocin and tranexamic acid with ethamsylate were equally effective in reducing intra-operative blood loss and the risk of hysterectomy; however, tranexamic acid with ethamsylate increased the risk of thrombotic events. Further research with a larger number of participants is needed. TRIAL REGISTRATION: The study was registered on Pan African Clinical Trials Registry with the following number: PACTR202009736186159 and was approved on 04/09/2020.

Intravenous tranexamic acid vs. sublingual misoprostol in high-risk women for postpartum haemorrhage following cesarean delivery; a randomised clinical trial.

OBJECTIVE: This study compares the effectiveness of administering sublingual misoprostol combined with oxytocin to that of IV tranexamic acid combined with oxytocin to reduce intra and post-operative blood loss in high-risk women for postpartum haemorrhage (PPH) following cesarean section (CS). METHODS: About 315 high-risk pregnant women undergoing CS participated in this trial. They were randomly assigned into three groups; tranexamic group, misoprostol group, and control group, according to the medication given in the operative theatre. All patients received oxytocin intraoperatively. They were assessed regarding intraoperative blood loss, the incidence of PPH, and the reduction in haemoglobin and hematocrit values. RESULTS: Both tranexamic and misoprostol groups had similar results in reducing intra and post-operative blood loss. However, the reduction in haemoglobin and hematocrit were significantly lower in tranexamic and misoprostol groups compared to the control group (-0.78 ± 0.57 vs. -0.83 ± 0.52 vs. -1.32 ± 0.57 gm/dl, P < 0.001 and - 3.05 ± 1.28 vs. -3.06 ± 1.13 vs. -4.94 ± 1.82%, P < 0.001 respectively). In addition, the estimated blood loss was significantly lower in the tranexamic and misoprostol groups compared to the control group (641.6 ± 271.9 vs. 617.9 ± 207.4 vs. 1002.4 ± 340.7 ml, P < 0.001). CONCLUSION: Both tranexamic acid and misoprostol are equally capable of reducing blood loss, but the results were significantly better compared to using oxytocin alone in high-risk patients. CLINICAL TRIAL REGISTRATION: Registered at www. CLINICALTRIALS: govon07/10/2019 with registration number NCT04117243.

Weight-based oxytocin infusion for preventing uterine atony during caesarean delivery in non-labouring patients: A dose-response study.

Postpartum haemorrhage remains a significant cause of maternal morbidity and mortality with the commonest reason being uterine atony. For prevention of uterine atony during caesarean delivery, oxytocin is advocated as a first line drug. There is however no published data regarding utility of a weight-based oxytocin infusion. The present study evaluated dose-response relationship for oxytocin infusion when used as weight-based regimen. A total of 55 non-labouring patients without risk factors for uterine atony and scheduled for caesarean delivery under spinal anaesthesia were enrolled. Randomization was done to receive oxytocin infusion in a dose of 0.1, 0.15, 0.2, 0.25 or 0.3 IU kg-1  h-1 (n = 11 each), initiated at the time of cord clamping and continued until the end of surgery. Successful outcome was defined as attaining an adequate uterine response at 4 min of initiation of infusion and maintained till end of surgery. Oxytocin associated hypotension, tachycardia, ST-T changes, nausea/vomiting, flushing and chest pain were also observed. A significant linear trend for adequate intraoperative uterine tone was seen with increasing dose of weight-based oxytocin infusion (P < 0.001). The effective dose in 90% population (ED90) was 0.29 IU kg-1  h-1 (95% CI = 0.25-0.42). Amongst the oxytocin associated side effects, a significant linear trend was seen between increasing dose of oxytocin infusion and hypotension as well as nausea/vomiting (p = 0.016 and 0.023 respectively). Thus, oxytocin infusion during caesarean delivery may be used as per the patient's body weight.

Oxytocin versus a combination of tranexamic acid and ethamsylate in reducing intraoperative bleeding during abdominal myomectomy: a randomized clinical trial.

OBJECTIVE: Myomectomy is the preferred surgical approach to manage uterine fibroids. However, uterine fibroids are highly vascular tumors and, consequently, extremely susceptible to problems from myomectomy-related hemorrhage. Hence, we aim to compare oxytocin efficacy and safety profile versus tranexamic acid (TA) with ethamsylate for reducing bleeding during myomectomy. METHODS: This randomized, double-blinded multicenter study was performed between 20th August 2020 and 20th October 2020 at El-Galaa Teaching Hospital, El Hussein University Hospital, Al-Azhar University Hospitals of Assiut, and Al-Azhar University Hospitals of Damietta. One hundred and eighty patients were enrolled and divided into three groups: group (1) received an injection of 30 IU of oxytocin in 500 ml of normal saline; group (2) received injections of 1 g of TA, 250 mg of Ethamsylate, and 110 ml of normal saline IV; and group (3) received an injection of 110 ml of normal saline IV just before surgical incision. RESULTS: In 180 premenopausal women, oxytocin and TA with ethamsylate had no significant value in lowering intraoperative blood loss compared with the placebo for abdominal myomectomy (666.25 ± 183.03, 630.72 ± 145.83, and 646.67 ± 168.92, respectively (P = 0.506)). Non-significant trends were observed for a reduction in operation time (P = 0.760), intra/postoperative blood transfusion (P = 0.624), hospital stay (P = 0.986), postoperative fever (P = 0.659), and wound infection (P = 1). CONCLUSION: Oxytocin and TA with ethamsylate had no significant value in lowering intraoperative blood loss compared with the placebo for abdominal myomectomy which opens a new question about the role of the use of the hemostatic drug during myomectomy especially in centers with limited resources and had higher rates. TRIAL REGISTRATION: The study was registered on Pan African Clinical Trials Registry with the following number: PACTR202008739887429 and was approved on 24/08/2020.

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.

Tranexamic Acid in the Prevention and Treatment of Postpartum Hemorrhage: A Review.

Postpartum hemorrhage (PPH) continues to be one of the leading causes of maternal morbidity and mortality worldwide. The four main causes of PPH are uterine atony, lacerations, retained placenta, and bleeding diathesis. In the patient with PPH, immediate evaluation is needed to diagnose and treat the underlying cause of hemorrhage. Uterotonic agents such as oxytocin remain first line for prevention and treatment of uterine atony. Studies have evaluated the antifibrinolytic tranexamic acid (TXA) as an adjunctive therapy in the prevention and treatment of PPH. TXA has been shown to reduce blood loss, bleeding-associated mortality, and transfusion rates in a variety of clinical settings and thus may serve a role in treating PPH. Current studies have demonstrated that TXA is an effective treatment option with limited risk of adverse events in appropriately selected patients; however, additional studies are needed to further clarify the role of TXA in the prevention of PPH.

Uterine atony.

PURPOSE OF REVIEW: Postpartum hemorrhage (PPH) is the leading preventable cause of maternal morbidity and mortality worldwide. Uterine atony is identified as the underlying etiology in up to 80% of PPH. This serves as a contemporary review of the epidemiology, risk factors, pathophysiology, and treatment of uterine atony. RECENT FINDINGS: Rates of postpartum hemorrhage continue to rise worldwide with the largest fraction attributed to uterine atony. A simple 0-10 numerical rating score for uterine tone was recently validated for use during cesarean delivery and may allow for more standardized assessment in clinical and research settings. The optimal prophylactic dose of oxytocin differs depending on the patient population, but less than 5 units and as low as a fraction of one unit is needed for PPH prevention, with an increased requirements within that range for cesarean birth, those on magnesium, and advanced maternal age. Carbetocin is an appropriate alternative to oxytocin. Misoprostol shows limited to no efficacy for uterine atony in recent studies. Several uncontrolled case studies demonstrate novel mechanical and surgical interventions for treating uterine atony. SUMMARY: There is a critical, unmet need for contemporary, controlled studies to address the increasing threat of atonic PPH.

Cost Implications of Using Carbetocin Injection to Prevent Postpartum Hemorrhage in a Canadian Urban Hospital.

OBJECTIVE: Recent World Health Organization (WHO) recommendations regarding uterotonics for the prevention of postpartum hemorrhage (PPH) state that carbetocin should be considered a first-line prophylactic agent for all births where its cost is comparable to other effective uterotonics. This study evaluated whether a room temperature stable formulation of carbetocin met this recommendation in a Canadian urban hospital setting. METHODS: A decision tree model was developed to assess the financial implications of replacing oxytocin with carbetocin as a first-line prophylactic agent for PPH prevention in a Greater Toronto Area (GTA) hospital. The analysis accounted for the mode of delivery, efficacies of carbetocin and oxytocin in PPH prevention, occurrence of PPH-related health outcomes, and health care resource costs for PPH interventions. RESULTS: This study found that a GTA hospital, with 3242 deliveries per year, could save over CAD $349 000 annually by switching to room temperature stable carbetocin for PPH prevention. Carbetocin was able to lower institution costs by reducing the use of health care resources for PPH management in low-risk and high-risk PPH patients. The cost-saving potential of carbetocin relative to oxytocin was largely attributed to its greater efficacy in preventing the consequences of PPH. CONCLUSION: The use of room temperature stable carbetocin as a first-line prophylactic agent for PPH prevention meets WHO recommendations regarding uterotonics for PPH in a GTA hospital. The model from this study can be used to determine the financial impact of switching from oxytocin to carbetocin in other jurisdictions while diversifying a hospital's pool of PPH prophylactic agents.

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

OBJECTIVES: To evaluate the uterotonic effect of carbetocin compared with oxytocin in emergency cesarean delivery in Iraq. METHODS: A double-blinded randomized noninferiority single center trial. Three-hundred patients were systematically randomized to intravenous bolus injection of 10 IU oxytocin or 100 mcg carbetocin after delivery in a ratio of 2:1. The primary outcome was additional uterotonic use when inadequate uterine tone occur in the first 24 h 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%. RESULTS: 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. CONCLUSIONS: 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.

Effectiveness and safety of carboxytocin versus oxytocin in preventing postpartum hemorrhage: A systematic review and meta-analysis.

OBJECTIVE: This study compared the effectiveness and safety of carbetocin and oxytocin in preventing postpartum hemorrhage (PPH). METHODS: A systematic literature search was performed on PubMed, Embase, and the Cochrane Library for relevant studies published up to February 2019. Next, two independent reviewers screened the studies according to the selection criteria as well as the strategies recommended by the Cochrane Collaboration. Data were then extracted and evaluated. All statistical analyses were performed using RevMan 5.1. RESULTS: A total of 24 studies involving 37 383 patients were included for analysis. For cesarean section patients, carbetocin was superior to oxytocin in reduction of the need for additional uterine contraction (odds ratio [OR] = 0.48, 95% confidence interval [CI] [0.35, 0.65], p < 0.00001), PPH (OR = 0.70, 95% CI [0.51, 0.95], p = 0.02), blood loss (mean [MD] = -64.36, 95% CI [-107.78, -20.93], p = 0.004), and transfusion (OR = 0.59, 95% CI [0.42, 0.82], p = 0.002), and there was no significant difference in severe PPH (OR = 0.84, 95% CI [0.66, 1.090], p = 0.19). For vaginal delivery patients, carbetocin was superior to oxytocin in reduction of the need for additional uterine contractions (OR = 0.48, 95% CI [0.25, 0.93], p = 0.03), PPH (OR = 0.28, 95% CI [0.09, 0.91], p = 0.03), and blood loss (MD = -63.52, 95% CI [-113.43, -13.60], p = 0.01), and there were no significant differences in severe PPH (OR = 0.82, 95% CI [0.40, 1.69], p = 0.59) and transfusion (OR = 0.60, 95% CI [0.22, 1.61], p = 0.31). With regard to safety, for cesarean section patients, carbetocin was superior to oxytocin in reduction of the incidence of headache (OR = 0.72, [0.55, 0.95], p = 0.02), and there were no significant differences in nausea, vomiting, abdominal pain, flushing, tremors, itching, dizziness, and fever. For vaginal delivery patients, there were no significant differences in nausea, vomiting, headache, abdominal pain, flushing, tremors, itching, dizziness, and fever between the two drugs. CONCLUSION: For patients undergoing cesarean section and vaginal delivery, carbetocin was superior to oxytocin in effectiveness and similar in safety. Therefore, carbetocin is expected to be an alternative uterine contraction agent for preventing PPH.

The efficacy of misoprostol in reducing intraoperative blood loss in women undergoing elective cesarean section. A systematic review and meta-analysis.

OBJECTIVES: To evaluate the efficacy of misoprostol to minimized blood loss during and after cesarean delivery (CD). SEARCH STRATEGY: Screening of MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials from inception to February 2021 using the keywords related to misoprostol, CD, postpartum hemorrhage, and intraoperative blood loss and their MeSH terms. SELECTION CRITERIA: Only RCTs were included. Participants included women undergoing CD whether elective or selective. Thirty studies including 6593 women, 26 in English, 2 in Thai, 1 in French, and 1 in Chinese. DATA COLLECTION AND ANALYSIS: Data from all selected studies were extracted independently by two authors. Data extracted included location of the trial, sample size, inclusion and exclusion criteria, participants characteristics, intervention details including timing, dose, and route of drug administration. Outcomes assessed included estimated intraoperative and postoperative blood loss, occurrence of postpartum hemorrhage, the need for additional uterotonics, and hemoglobin difference. MAIN RESULTS: Four studies (968 women) compared preoperative to postoperative misoprostol and found a mean difference in intraoperative blood loss of -205.00 (-339.22, -70.77), p = 0.003 and in postoperative blood loss -216.27 (-347.08, -85.46), p < 0.001 and a significantly lower need for additional uterotonics with a risk ratio of 0.54 (0.46, 0.64), p < 0.00001. Twenty-two studies (4701 participants) compared misoprostol to oxytocin. There was a mean difference in intraoperative blood loss of -108.43 (-156.04, -60.82), p < 0.0001. Nine of these trials with 1978 participants evaluated postoperative blood loss. These found a mean difference of -64.12 (-116.19, -12.04) with a p = 0.02. Fourteen trials with 3166 participants measured the difference between preoperative and postoperative hemoglobin. These found a mean difference of -0.25 (-0.35, -0.15) with a p < 0.001. Twenty trials with 4416 participants measured the need for administration of additional uterotonics. These found a risk ratio of 0.62 (0.49, 0.78) with a p value of <0.001. CONCLUSION: The combined use of misoprostol and oxytocin during CD is effective in reducing blood loss during and after CD.

Comparison of Oxytocin vs. Carbetocin Uterotonic Activity after Caesarean Delivery Assessed by Electrohysterography: A Randomised Trial.

Electrohysterography has been used for monitoring uterine contractility in pregnancy and labour. Effective uterine contractility is crucial for preventing postpartum haemorrhage. The objective of our study was to compare postpartum electrohysterograms in women receiving oxytocin vs. carbetocin for postpartum haemorrhage prevention after caesarean delivery. The trial is registered at ClinicalTrials.gov with the identifier NCT04201665. We included 64 healthy women with uncomplicated singleton pregnancies at term scheduled for caesarean section after one previous caesarean section. After surgery, a 15 min electrohysterogram was obtained after which women were randomised to receive either five IU of oxytocin intravenously or 100 µg of carbetocin intramuscularly. A 30 min electrohysterogram was performed two hours after drug application. Changes in power density spectrum peak frequency of electrohysterogram pseudo-bursts were analysed. A significant reduction in power density spectrum peak frequency in the first two hours was observed after carbetocin but not after oxytocin (median = 0.07 (interquartile range (IQR): 0.87 Hz) compared to median = -0.63 (IQR: 0.20) Hz; p = 0.004). Electrohysterography can be used for objective comparison of uterotonic effects. We found significantly higher power density spectrum peak frequency two hours after oxytocin compared to carbetocin.

Oxytocin infusion rates for maintaining uterine tone during non-elective cesarean section in laboring patients: a randomized, controlled trial.

PURPOSE: Oxytocin infusions for uterine tone maintenance are recommended following initial low oxytocin doses during cesarean section. Very limited literature is available on the optimal infusion rates in laboring patients who have been earlier exposed to oxytocin. METHODS: 105 patients, having received oxytocin for induction/augmentation of labor, received oxytocin infusions at rates of 2.5 IU/h (Group 2.5), 5 IU/h (Group 5) or 10 IU/h (Group 10) following 3 IU slow bolus. The primary outcome measure was estimated intraoperative blood loss; secondary outcome measures included uterine tone adequacy, requirements for additional uterotonics, and any side effects. Minor postpartum hemorrhage (PPH) was defined as blood loss > 500 ml and major/severe hemorrhage as blood loss > 1000 ml. RESULTS: Group 10 had minimum blood loss (311.1 ± 44.9 ml) and uterotonic requirements compared to other groups (p < 0.001). Group 2.5 had maximum blood loss (549.4 ± 74.3 ml) and uterotonic requirements; Group 5 had intermediate values (402.0 ± 49.5 ml). Twenty-six patients in group 2.5 had minor PPH against only one in group 5 and none in group 10 (p < 0.001). No patient in either group had major PPH. The incidence of hypotension was higher in group 10 than in group 2.5 (p = 0.004). Nausea and vomiting were also more frequent in group 10 than in the other two groups. CONCLUSION: Oxytocin infusions at 5 IU/h and 10 IU/h are more effective in reducing blood loss and preventing PPH than 2.5 IU/h. The dose of 10 IU/h, although the most efficacious, is associated with a high incidence of side effects. Hence, further studies are needed to find out the optimal maintenance infusion rate of oxytocin during cesarean section in laboring patients who have received oxytocin earlier.

Effects of skin-to-skin contact on afterpain and postpartum hemorrhage: A randomized controlled trial.

This study determined the effects of skin-to-skin contact between the mother and the infant during the third stage of labor on postpartum hemorrhage and pain. This assessor-blinded randomized controlled trial was conducted with primiparous women. Skin-to-skin contact interventions between the infants and their mothers occurred for 30 min after birth (n = 34), whereas the infants in the control group were provided routine care (n = 34). Data were gathered using a Personal Information Form, the Visual Analog Scale-Pain, postpartum bleeding follow-up bags, and records of blood oxytocin and beta endorphin levels. There was no significant difference in beta-endorphin levels in both groups (p = 0.771), whereas it was determined that the 30th min oxytocin level was significantly higher in the intervention group (The Visual Analog Scale-Pain score at the postpartum sixth hour was significantly lower in the intervention group. It was found that skin-to-skin contact made at the third stage of labor reduced the amount of postpartum hemorrhage. The results of this study suggested that skin-to-skin contact intervention may have beneficial effects on postpartum pain and postpartum hemorrhage in the early postpartum period.

[A multicenter, double-blind, randomized controlled clinical trial comparing ergometrine with oxytocin and oxytocin alone for prevention of postpartum hemorrhage at cesarean section].

Objective: To compare oxytocin combined with ergometrine with oxytocin alone in terms of primary prophylaxis for postpartum hemorrhage (PPH) at the time of cesarean section (CS). Methods: This was a multicenter double-blind randomized controlled interventional study comparing ergometrine combined with oxytocin and oxytocin alone administered at CS. From December 2018 to November 2019, a total of 298 parturients were enrolled in 16 hospitals nationwide. They were randomly divided into experimental group (ergometrine intra-myometrial injection following oxytocin intravenously; 148 cases) and control group (oxytocin intra-myometrial injection following oxytocin intravenously; 150 cases) according to 1∶1 random allocation. The following indexes were compared between the two groups: (1) main index: blood loss 2 hours (h) after delivery; (2) secondary indicators: postpartum blood loss at 6 h and 24 h, placental retention time, incidence of PPH, the proportion of additional use of uterine contraction drugs, hemostatic drugs or other hemostatic measures at 2 h and 24 h after delivery, the proportion requiring blood transfusion, and the proportion of prolonged hospital stay due to poor uterine involution; (3) safety indicators: nausea, vomiting, dizziness and other adverse reactions, and blood pressure at each time point of administration. Results: (1) The blood loss at 2 h after delivery in the experimental group [(402±18) ml] was less than that in the control group [(505±18) ml], and the difference was statistically significant (P<0.05). (2) The blood loss at 6 h and 24 h after delivery in the experimental group were less than those in the control group, and the differences were statistically significant (all P<0.05). There were no significant differences between the two groups in the incidence of PPH, the proportion of additional use of uterine contraction drugs, hemostatic drugs or other hemostatic measures at 2 h and 24 h after delivery, the proportion requiring blood transfusion, and the proportion of prolonged hospital stay due to poor uterine involution (all P>0.05). (3) Adverse reactions occurred in 2 cases (1.4%, 2/148) in the experimental group and 1 case (0.7%, 1/150) in the control group. There was no significant difference between the two groups (P>0.05). The systolic blood pressure within 2.0 h and diastolic blood pressure within 1.5 h of drug administration in the experimental group were higher than those in the control group, and the differences were statistically significant (P<0.05), but the blood pressure of the two groups were in the normal range. Conclusion: The use of ergometrine injection in CS could reduce the amount of PPH, which is safe and feasible.

[Multicenter, Randomized, Double-Blind, and Positive Drug-Controlled Clinical Trial on Prevention of Postpartum Hemorrhage after Vaginal Delivery with Ergometrine Maleate].

Objective: To evaluate the safety and efficacy of using ergometrine maleate injection combined with oxytocin injection, with oxytocin injection as the control, to prevent postpartum hemorrhage after vaginal delivery. Methods: A total of 305 cases who underwent vaginal delivery between December 2018 and November 2019 in 16 hospitals across China were enrolled and included in the full analysis set (FAS) and the safety analysis set (SS). Among the 299 subjects who completed the trial, 277 were included in the per protocol set (PPS). The subjects were randomly assigned by 1∶1 ratio to two groups, 152 cases in Group A, the experimental group receiving oxytocin injection plus ergometrine injection, and 153 cases in Group B, the control group, receiving oxytocin injection. The difference in total bleeding volume at 2 h, 6 h and 24 h postpartum in the two groups was documented and compared. Other measures were also compared between the two groups, including the proportion of additional use of uterotonics and hemostatic drugs or other hemostatic measures 2 h and 24 h postpartum, the proportion of subjects needing blood transfusion, the time of placenta retention, proportion of subjects with prolonged hospital stay due to uterine asthenia, the vital signs, lab test indicators and the incidence of adverse reactions in the two groups. Results: The total bleeding volume at 2 h, 6 h and 24 h after delivery was significantly lower in the experimental group (P<0.05). There was no significant difference between the two groups in the proportion of additional use of uterotonics and hemostatic drugs or other hemostatic measures 2 h and 24 h postpartum, the proportion of subjects needing blood transfusion and the time of placenta retention, heart rate, respiration, lab test indicators, or the incidence of adverse reaction (P>0.05). Conclusion: Ergometrine maleate injection showed evident therapeutic efficacy in preventing hemorrhage after vaginal delivery, causing fewer adverse reactions and ensuring greater safety, and therefore, presenting promising prospects for clinical application.

Effect of combination drug therapy during cesarean section in preventing postpartum hemorrhage for women with hypertensive disorder complicating pregnancy.

The study was carried out to observe the effect of combination drug therapy during cesarean section in preventing postpartum hemorrhage for women with hypertensive disorder complicating pregnancy (HDCP). The 180 women who had been treated in our hospital for HDCP were enrolled and randomly divided into observation group (sublingual administration of carboprost combined with oxytocin treatment (20IU oxytocin and small pot drip of 10IU oxytocin after delivery) and control group (1mg of carboprost when the fetal head came out and then applied with intramuscular injection of 20IU oxytocin), each containing 90. The comparison of postpartum hemorrhage situation between two groups was carried out. Compared with control group, the observation group had significantly lower intraoperative blood loss and postoperative 1h blood loss, p<0.0, but similar postoperative 2-24h blood loss, p>0.05; in observation, there were 6 cases of postpartum hemorrhage, while the number in control group was 20 cases. The two groups had no difference in blood pressure after treatment, p>0.05.The combination drug therapy during cesarean section is effective and reliable in preventing postpartum hemorrhage for women with HDCP.

Intravenous oxytocin dosing regimens for postpartum hemorrhage prevention following cesarean delivery: a systematic review and meta-analysis.

OBJECTIVE: To compare the available evidence on intravenous oxytocin dosing regimens for the prevention of postpartum hemorrhage following cesarean delivery. DATA SOURCES: We searched Ovid MEDLINE, Embase, Global Index Medicus, Cumulative Index of Nursing and Allied Health Literature, Cochrane Controlled Register of Trials, ClinicalTrials.gov, and the International Clinical Trials Registry Platform for eligible studies published until February 2020. STUDY ELIGIBILITY CRITERIA: We included any randomized or nonrandomized study published in peer-reviewed journals that compared at least 2 different dosing regimens of intravenous oxytocin for postpartum hemorrhage prevention in women undergoing cesarean delivery. METHODS: Two authors independently assessed the eligibility of studies, extracted the data, and assessed the risk of bias. The primary outcome was incidence of postpartum hemorrhage ≥1000 mL. Other review outcomes included use of additional uterotonics, blood loss, and adverse maternal events. Data were analyzed according to the type of intravenous administration (bolus only, infusion only, or bolus plus infusion) and total oxytocin dose. A meta-analysis was performed on randomized trials and the results were reported as risk ratios or mean differences with 95% confidence intervals. The Grading of Recommendations, Assessment, Development, and Evaluations scale was used to rate the certainty of evidence. Findings from dose-finding trials and nonrandomized studies were reported narratively. RESULTS: A total of 35 studies (7333 women) met our inclusion criteria and included 30 randomized trials and 5 nonrandomized studies. There were limited data available from the trials for most outcomes, and the results were not conclusive. Compared with bolus plus infusion regimens, bolus only regimens probably result in slightly higher mean blood loss (mean difference, 52 mL; 95% confidence interval, 0.4-104 mL; moderate certainty). Among the bolus plus infusion regimens, initial bolus doses <5 IU may reduce nausea (risk ratio, 0.26; 95% confidence interval, 0.11-0.63; low certainty) when compared with doses of 5-9 IU. Total oxytocin doses of 5-9 IU vs total doses of 10-19 IU may increase the use of additional uterotonics (risk ratio, 13.00; 95% confidence interval, 1.75-96.37; low certainty). Effects on other outcomes were generally inconclusive. CONCLUSION: There are limited data available for comparisons of IV oxytocin regimens for postpartum hemorrhage prevention following cesarean delivery. Bolus plus infusion regimens may lead to minor reductions in mean blood loss and initial bolus doses of <5 IU may minimize nausea. Bolus only regimens of 10 IU vs bolus only regimens of 5 IU may decrease the need for additional uterotonics, however, further comparative trials are required to understand the effects on other key outcomes, particularly hypotension.