| Summary: | Abstract Background This study aimed to assess the efficacy of tranexamic acid (TXA) mixed in a periarticular multimodal cocktail (PAMC) as a topical administration and to determine whether combined use of intravenous and topical administration is more effective than a single administration of TXA. Methods A total of 240 patients who underwent primary total knee arthroplasty (TKA) was enrolled for this prospective randomized controlled study. Patients were divided into three groups of 80 patients each. Baseline data were comparable for all groups. Average follow-up was 18.7 months. Group 1 consisted of patients who received intravenous (IV) TXA, Group 2 patients were those who received TXA in a PAMC injection for topical administration, and Group 3 consisted of patients who received a combination of both intravenous and topical administration of TXA. Primary outcomes were postoperative hemoglobin drop and amount of suction drainage. Secondary outcomes were estimated blood loss (EBL), postoperative transfusion rate, and complications. Results The mean postoperative hemoglobin drop was significantly lower in Group 3 (2.13 ± 0.77 g/dL, p=0.004), and there was no difference between Group 1 and Group 2 (2.56 ± 1.07 g/dL vs 2.55 ± 0.86 g/dL, p=0.999). The mean drainage amount was significantly lower in Group 3 (326.58 ± 57.55 ml, p<0.001), and there was no difference between Group 1 and Group 2 (367.93 ± 87.26 ml vs 397.66 ± 104.10 ml, p=0.072). Similarly, the mean EBL was significantly lower in Group 3 (p=0.003), and there was no significant difference between Group 1 and Group 2 (p=0.992). There were no significant differences in requirement for postoperative transfusion rate or incidence of complications among the three groups. Conclusion TXA mixed in a PAMC injection showed a similar effect to IV administration of TXA following TKA. Furthermore, combined use of both IV and PAMC injection provided better perioperative bleeding control with similar safety in patients without relevant comorbidities. Trial registration WHO ICTRP identifier KCT0005703 . Retrospectively registered: 12/24/2020
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