Effect of preoperative prophylactic intravenous tranexamic acid on perioperative blood loss control in patients undergoing cesarean delivery: a systematic review and meta-analysis
BMC pregnancy and childbirth. 2023;23(1):420
BACKGROUND Postpartum hemorrhage (PPH) is one of the important risk factors leading to maternal mortality and intervention is essential. Oxytocin therapy is widely used clinically, but the effect is unsatisfactory. The efficacy of tranexamic acid (TXA) in hemostasis is notable, whereas its use in preventing PPH warrants exploration. AIMS To evaluate the effect of prophylactic administration of TXA on perioperative blood loss in women undergoing cesarean section by systematic review and meta-analysis of published studies. METHODS Bibliographic databases were screened from their inception to December 2022 to retrieve relevant studies. Study outcomes including blood loss during cesarean section, 2-h postpartum blood loss, total blood loss (during cesarean section and 2-h postpartum), and 6-h postpartum, as well as hemoglobin changes were extracted and compared. RESULTS A total of 21 studies, nine randomized clinical trials and 12 cohort studies, involving 1896 patients given TXA prophylactically and 1909 patients given placebo or no treatment, were analyzed. Compared with the control group, the preoperative prophylactic intravenous administration of TXA significantly reduced the intraoperative (RCT: P < 0.00001, cohort studies: P < 0.00001), 2-h postpartum (RCT: P = 0.02, cohort studies: P < 0.00001) and total blood loss (RCT: P < 0.00001, cohort studies: P = 0.0002), and reduced the decline in hemoglobin (RCT: P < 0.00001, cohort studies: P = 0.0001), but did not significantly affect blood loss at 6-h postpartum (P = 0.05). CONCLUSION Prophylactic intravenous TXA before cesarean section is helpful in preventing perioperative bleeding in women. TRIAL REGISTRATION http://www.crd.york.ac.uk/PROSPERO , identifier: CRD 42022363450.
Effects of misoprostol in reducing blood loss during abdominal myomectomy in Nigeria
Nigerian journal of clinical practice. 2023;26(4):454-462
BACKGROUND Despite using a tourniquet to reduce bleeding during abdominal myomectomy, the procedure is still complicated by significant intraoperative bleeding. AIM: To determine whether misoprostol and tourniquet compared with tourniquet alone would significantly reduce bleeding during abdominal myomectomy at two tertiary hospitals in Enugu. MATERIALS AND METHODS This study is an open-label randomized controlled trial. A total of 126 consenting participants were recruited from women booked for abdominal myomectomy at the study centers over 7 months. They were randomized into groups A (vaginal misoprostol 400 μg) and B (no misoprostol) one hour before surgery. Intraoperatively, all participants had a tourniquet application. Intraoperative and postoperative blood loss was compared between the two groups. Descriptive and inferential analyses were carried out using IBM SPSS Version 22.0. A P- value of < 0.05 was considered statistically significant. RESULTS An intention-to-treat analysis was carried out. All 63 participants (100%) and 56 (90%) completed the study according to the protocol in groups A and B, respectively. Socio-demographic characteristics were not significantly different in both groups. The mean intraoperative blood loss in the "misoprostol group" (522.6 ± 127.91 ml) was significantly lower than in the "no-misoprostol group" (583.5 ± 186.20 ml), with P = 0.028. The difference in mean hemoglobin (g/dl) was lower in the "misoprostol group" than in the "no-misoprostol group" (1.3 ± 0.79 vs. 1.9 ± 0.89, P < 0.001). The mean 48 hours postoperative blood loss (ml) between the two groups was 323.8 ± 221.44 vs. 549.4 ± 519.72), with P = 0.001. CONCLUSION Among women receiving tourniquet during myomectomy in Enugu, the additional use of vaginal misoprostol 400 μg significantly reduced intraoperative blood loss.
The use of a short course of Ulipristal Acetate for acute abnormal uterine bleeding in women without uterine fibroids
Facts, views & vision in ObGyn. 2023;15(2):99-105
BACKGROUND Ulipristal Acetate (UPA) is a synthetic selective progesterone receptor modulator. It is used as emergency contraception and to reduce pain and blood loss in women of reproductive age with uterine fibroids. The first mechanism of action is myometrial apoptosis, the second is on the hypo-thalamic-pituitary-ovarian axis and the third action, is an anti-proliferative effect on the endometrium. Mainly based on the latter two, UPA is increasingly used off-label in women with abnormal uterine bleeding (AUB) without fibroids. OBJECTIVES The aim of this paper is to find evidence for a short course of UPA to treat acute AUB without fibroids, performing a systematic review as well as scrutinising literature data on the pharmacokinetics and on short term bleeding control in women with fibroids. MATERIALS AND METHODS A systematic electronic literature review was performed in February 2022. Inclusion criteria were UPA administered to women without myomas in a setting of acute uterine bleeding. Further criteria included papers describing early bleeding control using UPA, deemed independent of the presence of fibroids, with specific attention to the median time to amenorrhoea. MAIN OUTCOME MEASURES The main outcome measured was the bleeding control within 10 days. RESULTS One case report was identified. The data on symptomatic women with fibroids using 5 mg or 10 mg daily revealed bleeding control was reported within 10 days in 81% and 89% respectively, with amenorrhoea in 57% and in 78% respectively. CONCLUSION A short-term administration may prove effective in abnormal uterine bleeding irrespective of the presence of uterine fibroids. However, more randomised controlled trials are needed and should be performed before implementation in general clinical practice. WHAT IS NEW? A short course of Ulipristal acetate as promising treatment for acute uterine bleeding without fibroids.
Tranexamic Acid to Prevent Obstetrical Hemorrhage after Cesarean Delivery
The New England journal of medicine. 2023;388(15):1365-1375
BACKGROUND Prophylactic use of tranexamic acid at the time of cesarean delivery has been shown to decrease the calculated blood loss, but the effect on the need for blood transfusions is unclear. METHODS We randomly assigned patients undergoing cesarean delivery at 31 U.S. hospitals to receive either tranexamic acid or placebo after umbilical-cord clamping. The primary outcome was a composite of maternal death or blood transfusion by hospital discharge or 7 days post partum, whichever came first. Key secondary outcomes were estimated intraoperative blood loss of more than 1 liter (prespecified as a major secondary outcome), interventions for bleeding and related complications, the preoperative-to-postoperative change in the hemoglobin level, and postpartum infectious complications. Adverse events were assessed. RESULTS A total of 11,000 participants underwent randomization (5529 to the tranexamic acid group and 5471 to the placebo group); scheduled cesarean delivery accounted for 50.1% and 49.2% of the deliveries in the respective groups. A primary-outcome event occurred in 201 of 5525 participants (3.6%) in the tranexamic acid group and in 233 of 5470 (4.3%) in the placebo group (adjusted relative risk, 0.89; 95.26% confidence interval [CI], 0.74 to 1.07; Pâ€‰=â€‰0.19). Estimated intraoperative blood loss of more than 1 liter occurred in 7.3% of the participants in the tranexamic acid group and in 8.0% of those in the placebo group (relative risk, 0.91; 95% CI, 0.79 to 1.05). Interventions for bleeding complications occurred in 16.1% of the participants in the tranexamic acid group and in 18.0% of those in the placebo group (relative risk, 0.90; 95% CI, 0.82 to 0.97); the change in the hemoglobin level was -1.8 g per deciliter and -1.9 g per deciliter, respectively (mean difference, -0.1 g per deciliter; 95% CI, -0.2 to -0.1); and postpartum infectious complications occurred in 3.2% and 2.5% of the participants, respectively (relative risk, 1.28; 95% CI, 1.02 to 1.61). The frequencies of thromboembolic events and other adverse events were similar in the two groups. CONCLUSIONS Prophylactic use of tranexamic acid during cesarean delivery did not lead to a significantly lower risk of a composite outcome of maternal death or blood transfusion than placebo. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT03364491.).
Patients undergoing caesarean delivery at 31 U.S. hospitals (n= 11,000).
Tranexamic acid (n= 5,529).
Placebo (n= 5,471).
The primary outcome was a composite of maternal death or blood transfusion by hospital discharge or 7 days postpartum, whichever came first. A primary-outcome event occurred in 201 of 5,525 participants (3.6%) in the tranexamic acid group and in 233 of 5,470 (4.3%) in the placebo group (adjusted relative risk, 0.89; 95.26% CI [0.74, 1.07]). Estimated intraoperative blood loss of more than 1 litre occurred in 7.3% of the participants in the tranexamic acid group and in 8.0% of those in the placebo group (relative risk, 0.91; 95% CI [0.79, 1.05]). Interventions for bleeding complications occurred in 16.1% of the participants in the tranexamic acid group and in 18.0% of those in the placebo group (relative risk, 0.90; 95% CI [0.82, 0.97]); the change in the haemoglobin level was -1.8 g per decilitre and -1.9 g per decilitre, respectively (mean difference, -0.1 g per decilitre; 95% CI [-0.2, -0.1]); and postpartum infectious complications occurred in 3.2% and 2.5% of the participants, respectively (relative risk, 1.28; 95% CI [1.02, 1.61]). The frequencies of thromboembolic events and other adverse events were similar in the two groups.
Prophylactic Tranexamic Acid Prevents Postpartum Hemorrhage and Transfusions in Cesarean Deliveries: A Systematic Review and Meta-analysis
American journal of perinatology. 2023
INTRODUCTION Postpartum hemorrhage (PPH) is the leading cause of maternal mortality worldwide and PPH resulting in transfusion is the most common maternal morbidity in the United States. Literature demonstrates that tranexamic acid (TXA) can reduce blood loss in cesarean deliveries; however, there is little consensus on the impact on major morbidities like PPH and transfusions. OBJECTIVE We conducted a systematic review/meta-analysis of randomized controlled trials (RCTs) to evaluate if administration of prophylactic IV TXA prevents PPH and/or transfusions following low-risk cesarean delivery. METHODS PRISMA guidelines were followed. Five databases were searched: Cochrane, EBSCO, Ovid, PubMed, and ClinicalKey. RCTs published in English between January 2000 and December 2021 were included. Studies compared PPH and transfusions in cesarean deliveries between prophylactic IV TXA and control (placebo or no placebo). The primary outcome was PPH, and the secondary outcome was transfusions. Random effects models were used to calculate effect size (ES) of exposure in Mantel-Haenszel Risk Ratios (RR). All analysis was done at a confidence level (CI) of alpha=0.5. RESULTS Modeling showed that TXA led to significantly less risk of PPH than control (RR: 0.43, 95% CI: 0.28-0.67). The effect on transfusion was comparable (RR: 0.39, 95% CI: 0.21-0.73). Heterogeneity was minimal (I2 = 0%). CONCLUSION Due to the large sample sizes needed, many RCTs are not powered to interpret TXA's effect on PPH and transfusions. Pooling these studies in a meta-analysis allows for more power and analysis but is limited by the heterogeneity of studies. Our results minimize heterogeneity while demonstrating that prophylactic TXA reduces the risk for PPH and transfusion. This has the potential to address blood shortages, transfusion-associated risks, and healthcare costs. We suggest considering prophylactic IV TXA as the standard of care in low-risk cesarean deliveries.
The efficacy of three regimes of uterotonic agents for prevention of postpartum blood loss at undergoing cesarean section: a prospective randomized clinical trial
Ginekologia polska. 2023
OBJECTIVES To compare the efficacy of three regimes of uterotonic agents on PPH in women undergoing cesarean section in our RCT. MATERIAL AND METHODS This study was a randomized controlled study (NCT05083910) performed at the Bezmialem Vakif University between July 2021 and January 2022. All women were randomly allocated into three groups: Group I (n = 52) - oxytocin only; Group II (n = 52) - the combination of oxytocin plus intrauterine misoprostol; Group III (n = 52) - carbetocin only. The primary outcome measures were: PPH to evaluate with the change between the concentrations of preoperative and postoperative hemoglobin, hematocrit and intraoperative blood loss. RESULTS The blood loss characteristics, including the change in hemoglobin and the change in hematocrit concentration, intraoperative blood loss, intraoperative additional hemostatic uterine sutures and the need for additional uterotonics, were lowest in group III, although all groups were comparable in terms of blood loss parameters. Group III had the highest blood loss ratio, exceeding 1000 mL. For the combination of oxytocin and intrauterine misoprostol, the ARR was 3.8% (95% CI 20.02-12.33), with a RR of 1.18 (95% CI 0.58-2.39) and a NNT of 26 (95% CI 8.1-4.9); for carbetocin, the ARR was 5.8% (95% CI 22.15-10.61), with a RR of 1.27 (95% CI 0.63-2.53) and a NNT of 17 (95% CI 9.41-4.51). CONCLUSIONS Our results demonstrate that carbetocin shows no superiority in the prevention of PPH in women undergoing cesarean section. Oxytocin still seems to be a highly effective alternative to prevent PPH.
Tranexamic acid for the prevention of blood loss after cesarean section: an updated systematic review and meta-analysis of randomized controlled trials
American journal of obstetrics & gynecology MFM. 2023;:101049
OBJECTIVE Tranexamic acid (TXA) is a cost-effective intervention for the prevention of postpartum hemorrhage (PPH) in women undergoing cesarean section but the evidence to support its use is conflicting. We conducted this meta-analysis to evaluate the efficacy and safety of TXA in low- and high-risk cesarean deliveries. DATA SOURCES We searched MEDLINE (via PubMed), Embase, the Cochrane Library, ClinicalTrials.gov, and WHO International Clinical Trials Registry Platform (ICTRP) portal from inception to April 2022 (updated October 2022 and February 2023) with no language restrictions. Additionally, grey literature sources were also explored. STUDY ELIGIBILITY CRITERIA All randomized controlled trials (RCTs) investigating the prophylactic use of intravenous TXA in addition to standard uterotonic agents in women undergoing cesarean deliveries as compared to placebo, standard treatment, or prostaglandins were included in this meta-analysis. METHODS We used the revised Cochrane "Risk of Bias" tool (RoB 2.0) to assess the quality of included RCTs. RevMan 5.4 was used to conduct all statistical analyses under a random-effects model. RESULTS We included 50 RCTs (6 in only high-risk patients and 2 with prostaglandins as the comparator) evaluating TXA in our meta-analysis. TXA reduced the risk of blood loss >1000 mL, mean total blood loss, and the need for blood transfusion in both low- and high-risk patients. TXA was associated with a beneficial effect in our secondary outcomes including decline in hemoglobin levels and the need for additional uterotonic agents. TXA increased the risk of non-thromboembolic adverse events but, based on limited data, did not increase the incidence of thromboembolic events. The administration of TXA before skin incision, but not after cord clamping, was associated with a large benefit. The quality of evidence was rated as low to very low for outcomes in the low-risk population and moderate for most outcomes in the high-risk subgroup. CONCLUSIONS TXA may reduce the risk of blood loss in cesarean deliveries with a higher benefit observed in high-risk patients but the lack of high-quality evidence precludes any strong conclusions. Additional studies, especially in the high-risk population and evaluating the timing of TXA administration, are needed to confirm or refute these findings.
Effectiveness of prophylactic pharmacological hemostatic agents for reduction of blood loss at vaginal surgery: a systematic review and meta-analysis
International urogynecology journal. 2023
INTRODUCTION AND HYPOTHESIS The objective was to evaluate the effectiveness of pharmacological hemostatic agents in the reduction of blood loss at vaginal surgery. METHODS A systematic review of randomized control trials (RCTs) was completed. We searched PubMed (1946-2022), Embase, and CINAHL, using search terms related to vaginal hysterectomies and reconstructive surgeries combined with peri-operative use of hemostatic agents. RCTs comparing hemostatic interventions with placebo or with standard care were analyzed with the primary outcome of estimated blood loss. Secondary outcomes included peri-operative complications, length of stay, blood transfusion, and readmission. Risk of bias was assessed using the Risk of Bias 2 tool. RESULTS Nine RCTs were included with a total of 903 participants. All trials were considered to have an overall low risk of bias. Meta-analysis of six RCTs (491 participants) favored the use of vasoconstrictive agent (vasopressin/ornipressin) at the surgical site for an overall effect estimate of decreased blood loss by 70 ml (95% CI -125, -14 ml). There was significant heterogeneity of studies with both dose and technique of vasoconstrictive agents used. Only one RCT evaluated tranexamic acid and found a benefit in the prophylactic use of intravenous tranexamic acid. CONCLUSIONS Peri-operative use of vasoconstrictive agents slightly reduces bleeding in women undergoing elective vaginal surgery. Additional studies evaluating alternative pharmacological agents such as tranexamic acid may be of benefit.
A Comparative Study of the Efficacy of Intraoperative Intravenous Oxytocin and Intramuscular Oxytocin Versus Conventional Intramuscular Oxytocin for Third-Stage Labour in Elective Cesarean Section
Objective To study the efficacy of intraoperative IV oxytocin and intramuscular (IM) oxytocin versus conventional intramuscular oxytocin alone for active management of the third stage of labor in lower segment cesarean section (CS). The study was performed to determine the effect of 5 IU (International Unit) oxytocin infusion at the time of skin incision and that of 10 IU IM oxytocin infusion after delivery in reducing blood loss during and after CS, in comparison with the effect of administrating conventional 10 IU IM oxytocin in the same time period. In addition, it assessed the ability of the IV+IM oxytocin group to reduce the need for additional uterotonic as well as its safety determination and postoperative blood transfusion in CS. Materials and methods It is a randomized control study. The effect of 5 IU of oxytocin infusion at the time of skin incision and 10 IU of IM oxytocin (IV+IM) in reducing blood loss during and after the CS was compared to conventional 10 IU IM oxytocin. Results The study showed that the IV+IM group had a mean blood loss of 316.5 ± 74.36 ml, while the IM group had a mean loss of 403.90 ± 107.2 ml (p-value < 0.001) from placental delivery to the end of CS. A total of 90% of the patients in the IV+IM group had blood loss <50 ml compared to 95% of patients in the IM group who had a blood loss between 50 and 100 ml range from the end of cesarean to two hours postpartum. When total blood loss was compared in both groups, 84% of patients had a blood loss between 300 and 400 ml, compared to 81% of the patients in the IM group who had blood loss of 400-500 ml. Total blood loss in the IM group was 483.20 ± 115.86 ml, which was significantly higher compared to the IV group, 362.60 ± 78.07 ml (p-value=<0.001). Conclusion 5IU oxytocin infusion at the time of skin incision and 10 IU IM oxytocin after delivery of the baby significantly reduced the amount of blood loss, need for blood transfusion, and additional uterotonics during and after lower segment CS.
Investigation of The Effects of Oxytocin Administration Timing on Postpartum Hemorrhage during Cesarean Section
Medicina (Kaunas, Lithuania). 2023;59(2)
Background and Objectives: To determine and compare the effects of the timing of oxytocin administration (routinely used for intraoperative uterotonic purposes in cesarean section (CS) deliveries in our clinic) on the severity of postpartum hemorrhage following CS. Materials and Methods: All study participants (n = 216) had previous cesarean deliveries, were 38-40 weeks pregnant, and had CS planned under elective conditions. The cases were randomly divided into two groups: one group (n = 108) receiving oxytocin administration before the removal of the placenta (AOBRP) and another group (n = 108) receiving oxytocin administration after the removal of the placenta (AOARP). In all cases, the placenta was removed using the manual traction method. The standard dose of oxytocin is administered as an intravenous (IV) push of 3 international units (IU); simultaneously, 10 IU of oxytocin is added to 1000 cc isotonic fluid and given as an IV infusion at a rate of 250 cc/h. All methods and procedures applied to both groups were identical, except for the timing of administration of the standard oxytocin dose. Age, body mass index (BMI), parity, gestational week, preoperative hemoglobin (HB) and hematocrit (HTC), postoperative 6th and 24th hour HB-HTC, intraoperative hemorrhage, additional uterotonic need during cesarean section, postoperative hemorrhage (number of pads), need for blood transfusion during or after cesarean section, cesarean section time, and postpartum newborn baby weight were evaluated. Results: Age (year), BMI (kg/m(2)), parity, gestational week, surgical time, and newborn weight (g) did not differ between the groups (p > 0.05). The AOBRP group had significantly higher postoperative 6th hour HB and HTC and postoperative 24th hour HB and HTC values (p < 0.05). The intraoperative hemorrhage level was higher in the AOARP group (p = 0.000). Conclusions: The administration of oxytocin before placenta removal did not change the volume of bleeding in the postoperative period but significantly reduced the volume of bleeding in the intraoperative period. Therefore, in the postoperative period, the HB and HTC values of the AOBRP group were higher than those of the AOARP group.