Intravenous Tranexamic acid versus placebo during Caesarian section: A comparative study
Pakistan journal of medical sciences. 2022;38(5):1183-1187
OBJECTIVES To evaluate the effectiveness of Tranexamic Acid in preventing postpartum hemorrhage against placebo in high-risk women undergoing cesarean section. METHODS A double-blinded placebo-controlled comparative trial was conducted at the Obstetrics and Gynecology Department of Nishtar Hospital for one year, from 15(th) June 2020 to 15(th) June 2021. A total of 60 women who were at high risk of postpartum hemorrhage and had to undergo elective cesarean sections were included in the study. Among them, initial 30 patients were administered Tranexamic Acid before skin incision whereas later 30 were treated as the placebo group. These women were then observed for blood loss during surgery and within 24 hrs. after surgery and any postoperative complications such as thromboembolic events, the need for additional uterotonic agents, and blood transfusions. RESULTS Out of 60 women, 30 were placed in each group. The groups had no significant difference in terms of baseline data and post-partum hemorrhage-associated risk factors (p>0.05). However, the occurrence rate of primary post-partum hemorrhage (blood loss greater than 1000 ml) was significantly less in a tranexamic acid group than the placebo group (16.6% vs 60%, respectively, p<0.01). Similarly, the requirement of additional uterotonic agents (13.3% vs 43.3%, respectively) and the need for blood transfusion (6.0% vs 23.3%, respectively) was lower in a tranexamic group than in the placebo group. CONCLUSION The study highlighted the significance of tranexamic acid in controlling post-partum hemorrhages, the requirement of additional uterotonic agents, improving post-partum hemoglobin, and the need for blood transfusion.
Rotational Thromboelastometry for the Transfusion Management of Postpartum Hemorrhage after Cesarean or Vaginal Delivery: A Single-Center Randomized Controlled Trial
Journal of gynecology obstetrics and human reproduction. 2022;:102470
Tranexamic Acid for the Prevention of Blood Loss after Cesarean Among Women With Twins. A Secondary Analysis of the TRAAP2 Randomized Clinical Trial
American journal of obstetrics and gynecology. 2022
BACKGROUND Although prophylactic tranexamic acid administration at cesarean delivery resulted in a lower incidence of calculated estimated blood loss > 1000 mL or red-cell transfusion by day 2, its failure to reduce the incidence of hemorrhage-related secondary clinical outcomes (TRAAP2 trial) makes its use questionable. The magnitude of its effect may differ in women at higher risk of blood loss, including those with multiple pregnancies. OBJECTIVE To compare the effect of tranexamic acid vs placebo to prevent blood loss at cesarean delivery among women with multiple pregnancies. STUDY DESIGN Secondary analysis of the TRAAP2 trial data including 319 women with multiple pregnancies in this double-blind, randomized controlled trial from March 2018 through January 2020 in 27 French maternity hospitals. Women with a cesarean before or during labor at 34 or more gestational weeks were randomized to receive intravenously 1 g of tranexamic acid (n=160) or placebo (n=159), both with prophylactic uterotonics. The primary outcome was a calculated estimated blood loss > 1000 mL or a red blood cell transfusion by 2 days after delivery. Secondary outcomes included clinical and laboratory blood loss measurements. RESULTS Of the 4551 women randomized in this trial, 319 had a multiple pregnancy and cesarean delivery, 298 (93.4%) with primary outcome data available. This outcome occurred in 62 of 147 women (42.2%) in the tranexamic acid group and 67 of 152 (44.1%) receiving placebo (adjusted risk ratio, 0.97; 95% CI 0.68-1.38; P=.86). No significant between-group differences occurred for any hemorrhage-related clinical outcomes: gravimetrically estimated blood loss, provider-assessed clinically significant hemorrhage, additional uterotonics, postpartum blood transfusion, arterial embolization, and emergency surgery (P>.05 for all comparisons). CONCLUSION Among women with a multiple pregnancy and cesarean delivery, prophylactic tranexamic acid did not reduce the incidence of any blood loss-related outcomes.
Pharmacokinetics of Curative Tranexamic Acid in Parturients Undergoing Cesarean Delivery
The aim of this study was to evaluate the population pharmacokinetics of tranexamic acid (TXA) administered intravenously at a single dose of 0.5 or 1 g in parturients undergoing active hemorrhagic cesarean delivery and to evaluate the influence of patient variables on TXA pharmacokinetics. Subjects from three recruiting centers were included in this PK sub-study if randomized in the experimental group (i.v TXA 0.5 g or 1 g over one minute) of the TRACES study. Blood samples and two urinary samples were collected within 6 h after TXA injection. Parametric non-linear mixed-effect modeling (Monolix v2020R1) was computed. The final covariate model building used 315 blood and 117 urinary concentrations from seventy-nine patients. A two-compartment model with a double first-order elimination from the central compartment best described the data. The population estimates of clearance (CL), central volume of distribution (V1), and half-life for a typical 70 kg patient with an estimated renal clearance of 150 mL/min (Cockroft-Gault) were 0.14 L/h, 9.25 L, and 1.8 h. A correlation between estimated creatinine clearance and CL, body weight before pregnancy, and V1 was found and partly explained the PK variability. The final model was internally validated using a 500-run bootstrap. The first population pharmacokinetic model of TXA in active hemorrhagic caesarean section was successfully developed and internally validated.
Effect of intravenous ascorbic acid administration on hemorrhage and wound complications in total abdominal hysterectomy: A prospective randomized clinical trial
Clinical nutrition ESPEN. 2022;49:74-78
OBJECTIVE Previous studies mentioned the beneficial effects of vitamin C on the hemorrhage and wound healing. We evaluated the effects of vitamin C on the hemorrhage, hemoglobin concentration, and wound complications in total abdominal hysterectomy. MATERIALS AND METHODS In this randomized, double-blind, placebo-controlled trial, 80 patients with total abdominal hysterectomy were randomly divided into the study and control groups to receive either intravenous 2 g of vitamin C in normal saline or solely normal saline therapy. The first 1-g dose of ascorbic acid was administrated the night before surgery, and the second 1 g was administrated during surgery. RESULTS The mean age of the participants was 37.8 ± 4.8 years with a mean preoperative plasma vitamin C concentration of 5.07 ± 2.1 mg/dL, close to the subclinical deficiency. The basal characteristics of both groups were the same. The hemorrhage volume was slightly higher in the control group (345.2 ± 31.8 ml vs. 388.1 ± 28.3 ml, P < 0.001). CONCLUSION Intravenous vitamin C administration had a positive effect on reducing hemorrhage during total abdominal hysterectomy. TRIAL REGISTRATION Clinicaltrials.gov.identifier: NCT03965637.
Prophylactic tranexamic acid during myomectomy: A systematic review and meta-analysis of randomized controlled trials
European journal of obstetrics, gynecology, and reproductive biology. 2022;276:82-91
OBJECTIVE To conduct a systematic review and meta-analysis of randomized controlled trials on the clinical efficacy and safety of prophylactic tranexamic acid (TXA) versus control (normal saline/no treatment) during myomectomy. METHODS Six databases were screened from inception until 21-February-2022. The eligible studies were assessed for risk of bias. The outcomes were summarized as mean difference (MD) and risk ratio (RR) with 95% confidence intervals (CI) in a random-effects model. RESULTS Seven studies, comprising eight arms and 571 patients (TXA = 304 patients, control = 267 patients) were analyzed. The included studies had an overall low risk of bias. The mean intraoperative blood loss (MD = -224.34 ml, 95% CI [-303.06, -145.61], p < 0.001), mean postoperative blood loss, and mean total blood loss were significantly reduced in favor of the prophylactic TXA group. Additionally, the mean postoperative hemoglobin (MD = 0.4 mg/dl, 95% CI [0.11, 0.68], p = 0.006) and mean postoperative hematocrit levels were significantly higher in favor of the prophylactic TXA group. While the mean hospital stay was significantly reduced in favor of the prophylactic TXA group (MD = -0.39 d, 95% [-0.74, -0.04], p = 0.03), there was no significant difference between both groups regarding the mean operation time and rate of blood transfusion. None of the participants in both groups developed any incidence of thromboembolic events. The rate of nausea was significantly higher in disfavor of the prophylactic TXA group (RR = 2.68, 95% CI [1.11, 6.43], p = 0.03). CONCLUSION Among patients undergoing myomectomy, prophylactic TXA was largely safe and linked to substantial reductions in perioperative blood loss and related morbidities.
Prophylactic vasopressin to reduce intraoperative blood loss and associated morbidities during myomectomy: a systematic review and meta-analysis of 11 controlled trials
Journal of gynecology obstetrics and human reproduction. 2022;:102485
OBJECTIVE To collate evidence from randomized controlled trials (RCTs) and nonrandomized controlled trials (NCTs) on the efficacy and safety of vasopressin versus passive control (placebo/no treatment) during myomectomy. METHODS Six information sources were screened until 25-June-2022. The Cochrane Collaboration tool and Newcastle-Ottawa Scale were used to evaluate the risk of bias. Data were summarized as mean difference or risk ratio with 95% confidence interval in a random-effects model. RESULTS Eleven studies, comprising 1067 patients (vasopressin=567 and control=500) were analyzed. For RCTs (n=8), the overall quality included 'high risk' (n=4), 'low risk' (n=2), and 'some concerns' (n=2). For NCTs (n=3), the overall quality included 'good' (n=2) and 'fair' (n=1). The mean intraoperative blood loss, mean difference in hemoglobin level, mean difference in hematocrit level, rate of perioperative blood transfusion, and mean operative time were significantly reduced in favor of the vasopressin group compared with the control group. However, there was no significant difference between both groups regarding the mean hospital stay. Pertaining to safety endpoints, after omission of an outlier study, the rate of drug-related cardiovascular adverse events did not significantly differ between both groups. There was no quantitative evidence of publication bias for the endpoint of intraoperative blood loss. CONCLUSION Among patients undergoing myomectomy, prophylactic administration of vasopressin was largely safe and correlated with significant reductions in intraoperative blood loss and associated morbidities compared with a passive control intervention. Nonetheless, the conclusions should be cautiously interpreted owing to the low-evidence quality and the used doses varied greatly between studies.
Impact of "natural" cesarean delivery on peripartum blood loss: A randomized controlled trial
American journal of obstetrics & gynecology MFM. 2022;:100642
BACKGROUND Early skin to skin contact after vaginal delivery increases milk production and may increase oxytocin release, leading to reduction in postpartum hemorrhage (PPH) rate. OBJECTIVE To examine the impact of "natural" cesarean deliveries (NCD) on perioperative maternal blood loss. STUDY DESIGN This is a randomized controlled trial conducted at a single university affiliated medical center, between August 2016 and February 2018. Term singleton gestations scheduled for a planned CD under spinal anesthesia were included. Women were randomized at a ratio of 1:1 to NCD (study group) or traditional CD (control group) during the routine preoperative assessment. Women in the study group watched fetal extraction, had early skin to skin contact, and breastfed until the end of surgery. Neonates in the control group were presented to the mother for few minutes. Blood samples were drawn from all women, during fascia closure, to determine oxytocin levels using an ELISA kit. The Laboratory component was performed after recruitment completion and was accomplished in February 2019. The primary outcome was postpartum hemoglobin (Hb) levels. To detect a difference of 0.5 g/dL between the groups with α = .05 and β = 80%, 214 women were needed. RESULTS Of 214 women that were randomized, 23 were excluded. There were no significant differences in demographic and obstetric variables between the groups. Postpartum Hb levels were 10.1±1.1 and 10.3±1.3 g/dL in the study and control groups, respectively (P = .19). There were no significant differences in rates of PPH and blood transfusion. Maternal pain scores, satisfaction, and exclusive breastfeeding, were comparable. Maternal oxytocin blood levels were 389.5±183.7 and 408.5±233.6 pg/mL in the study and control groups, respectively (P = .96). Incidence of neonatal hypothermia was comparable between the groups (P=.13). CONCLUSIONS NCD does not affect perioperative Hb level or maternal oxytocin blood concentration. CLINICAL TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT02768142.
Tranexamic Acid for Prevention of Hemorrhage in Elective Repeat Cesarean Delivery - A Randomized Study
American journal of obstetrics & gynecology MFM. 2022;:100573
BACKGROUND The American College of Obstetricians and Gynecologists states that data is insufficient to recommend Tranexamic acid (TXA) prophylaxis for postpartum hemorrhage. OBJECTIVE This study's objective was to evaluate if prophylactic TXA reduces calculated blood loss versus placebo in women undergoing elective repeat cesarean delivery. STUDY DESIGN A double-blind, randomized, placebo-controlled trial, examining calculated blood loss with prophylactic doses of 1-gram of TXA given before skin incision and after placental delivery and standard uterotonics in women with singleton pregnancies at least 37 weeks' gestation, presenting for their second or third cesarean delivery under neuraxial anesthesia. The primary outcome was calculated blood loss at 24 hours. The calculation was based on the participant's height, weight, and the difference in hematocrit before the start of surgery and 24 hours after delivery. Prespecified secondary outcomes were quantification of maternal coagulation activity during the perioperative course. A sample size of 50 women per group was planned (N=100), based on a meta-analysis of mean reduction in blood loss after TXA. RESULTS 723 women were screened, and 110 women were randomized as follows: 55 to TXA and 55 to placebo. The primary outcome of mean calculated blood for TXA (2274 ± 469 mL) and the placebo group (2407 ± 388 mL), p > 0.05. In the secondary outcomes, D-dimer levels were lower in the TXA group than the placebo group 24 hours after delivery (2.1 ± 1.2 µg/mL versus 4.3 ± 2.4 µg/mL), p < 0.001. CONCLUSIONS Prophylactic tranexamic acid did not decrease mean calculated blood loss. Significantly less participants had calculated blood loss greater than 2000 mL in the tranexamic acid group compared to the placebo group with lower levels of D-dimer at 24 hours.
Women undergoing elective repeat caesarean delivery (n= 110).
Prophylactic doses of tranexamic acid (TXA) before skin incision and after placental delivery (n= 55).
Standard uterotonics (n= 55).
The mean calculated blood loss for TXA was 2,274 ± 469 mL, and for standard uterotonics was 2407 ± 388 mL. D-dimer levels were lower in the TXA group than the placebo group 24 hours after delivery (2.1 ± 1.2 µg/mL vs. 4.3 ± 2.4 µg/mL).
Efficacy of oxytocics on reducing intraoperative blood loss during abdominal myomectomy: a systematic review and meta-analysis of randomized placebo-controlled trials
Journal of gynecology obstetrics and human reproduction. 2022;:102358
OBJECTIVE To conduct a systematic review and meta-analysis on the efficacy of oxytocics administration (oxytocin and carbetocin) on reducing intraoperative bleeding during abdominal myomectomy. METHODS PubMed, Scopus, Web of Science, Cochrane Library, and Google Scholar databases were searched from inception until March 2021. Only randomized placebo-controlled trials (RCTs) were considered. The included RCTs were evaluated for risk of bias. The main outcome measures were mean intraoperative blood loss (ml), mean duration of hospital stay (day), mean operation time (min), mean difference of postoperative hemoglobin (g/dl), mean difference of postoperative hematocrit (%), and rate of blood transfusion (%). Pooled outcomes were summarized as risk ratio (RR) or mean difference (MD) with their 95% confidence interval (CI) in a random-effects model. RESULTS Seven RCTs met the inclusion criteria (n=758 patients; 329 patients per group). Compared with control group, oxytocin and carbetocin resulted in a significantly lower intraoperative blood loss (MD=-281.08 ml, 95% CI [-400.63, -161.53], p<0.001), hospital stay (MD=-0.21 days, 95% CI [-0.31, -0.10], p<0.001), and need for blood transfusion (RR=0.32, 95% CI [0.22, 0.46], p<0.001). Subgroup analysis revealed that oxytocin, but not carbetocin, correlated with a reduced mean difference of postoperative hemoglobin (MD=0.60 g/dl, 95% CI [0.24 to 0.96], p=0.001), postoperative hematocrit (MD=2.29%, 95% CI [1.06, 3.52], p<0.001), and operation time (MD=-14.66 min, 95% CI [-21.04, -8.25], p<0.001) compared with control group. CONCLUSION Among women undergoing abdominal myomectomy, administration of oxytocin and carbetocin correlated with several beneficial clinical outcomes, such as reduced intraoperative blood loss, hospital stay, and blood transfusion requirement.