Systemic administration of escin for posttraumatic or post-operative soft tissue edema: a systematic review of randomized clinical trials

Background. Treatment of post-traumatic and post-operative soft tissue edema is especially relevant due to the high incidence of these conditions. They have a profound effect on patients´ quality of life and recovery process, as edema contributes to microcirculation impairment, pain exacerbation, fibrosis development, and limitation of motion. Escin, a promising treatment for edema, is a naturally derived compound with anti-edematous, angio- and endothelioprotective, anti-inflammatory, analgesic, and other effects.

The aim of the review — to summarize the clinical trial data on the efficacy and safety of systemically administered escin medications in the treatment of post-traumatic or post-operative soft tissue edema.

Methods. The review was conducted following the PRISMA-2020, ROBIS, and AMSTAR-2 guidelines and included clinical trials (CTs) that met the PICO(S) criteria. The search was carried out on January 8, 2025 in the PubMed, eLIBRARY, SciELO, Cochrane Library databases, and in the US, EU, and UK clinical trial registers. Qualitative evidence synthesis was performed in a narrative approach with confidence assessment by the GRADE-CERQual method. Risk of bias in individual CT was assessed using the RoB 2 tool.

Results. The review included three open-label, randomized, parallel-group CTs devoted to the anti-edematous effect of escin for managing post-operative edema in chronic venous disease (1 CT, n = 87), trauma-related skin flap transplantation (1 CT, n = 90), and surgical treatment for blunt limb trauma (1 CT, n = 102). In all trials reviewed, systemic administration of escin was effective in correcting local edema, did not significantly differ from comparison groups in terms of safety and tolerability, and had a positive effect on several pathogenetic laboratory markers of edema. All included CTs raised some concerns regarding the overall risk of bias, mainly due to the absence of blinding and randomization protection. The outcome reporting and publication bias for the evidence synthesis was deemed low.

Conclusions. The review has shown that systemic (oral or parenteral) administration of escin in the acute post-traumatic and post-operative periods effectively reduced the severity of edema (moderate confidence by GRADE-CERQual) and was well-tolerated. The incidence of adverse events did not significantly differ from the negative control, the active comparator (mannitol) (moderate confidence by GRADE-CERQual). The findings of this review may find further application as a basis for novel, more advanced approaches to the drug correction of edema of various etiologies.