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

Abstract

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.

Perioperative oxytocin infusion versus tranexamic acid and ethamsylate in reducing intraoperative blood loss during caesarean section: a systematic review and meta-analysis

“…In this study of intraoperative blood loss, the TXAEth group demonstrated significantly lower intraoperative blood loss than the oxytocin group. This result is consistent in all included studies [19][20][21]. It is affirmed that TXA and Eth are associated with a significant reduction in intraoperative blood loss compared to a placebo [22].…”

“…Although a statistically significant distinction in postoperative hematocrit levels was observed between the two cohorts, there was no analogous difference in hemoglobin levels. Nevertheless, the decline in both Hb (-0.5 ± 0.2 and -1.77 ± 1.16 vs -0.9 ± 0.2 and -1.78 ± 1.12) and Hct (-1.5 ± 1.4 and -5.84 ± 3.91 vs -2.57 ± 1.6 and -5.84 ± 3.91) was less pronounced in the TXAEth group compared to the oxytocin group (Table 2) [19,21]. This implies that TXAEth might exhibit greater efficacy in mitigating blood loss during surgical procedures.…”

“…Regarding safety, the incidence of PPH is lower in the TXAEth group than in the oxytocin group (Table 3) [19,20]. Nonetheless, TXA in combination with Eth demonstrated a heightened occurrence of thrombotic events, although it is essential to note that only one study reported such incidents.…”

“…The WOMAN trial compared 1 gram of TXA or placebo and concluded that TXA decreased death due to bleeding (155 [1.5%] vs. 191 [1.9%]) [25]. However, one study included emergency CS, which has differing risks of PPH, potentially influencing heterogeneity [19,26,27].…”

“…The pooled studies were heterogeneous (Q=110.58 P<0.0001 I 2 =98. 19). The forest plot of the data is shown in Figure 5.…”