Extracorporeal detoxification methods in the comprehensive therapy of severe cholangiogenic sepsis: a prospective observational study

Background. Severe cholangiogenic sepsis is associated with mortality rates of 18–35 % despite advances in modern medicine. Endogenous intoxication represents one of the key pathogenetic components, and extracorporeal detoxification (ECD) methods provide direct elimination of bacterial endotoxins, pro-inflammatory cytokines, and inflammation mediators. However, evidence supporting differentiated, severity-stratified application of these techniques in cholangiogenic sepsis remains limited. The purpose was to evaluate the clinical efficacy of a differentiated, severity-stratified algorithm of extracorporeal detoxification methods in patients with severe cholangiogenic sepsis. Materials and methods. A prospective observational cohort study was conducted in 93 consecutive patients with cholangiogenic sepsis admitted to the surgical departments of the Samarkand Branch of the Republican Research Center of Emergency Medicine (Uzbekistan) between January 2021 and December 2024. Patients were stratified according to Tokyo Guidelines 2018 (grade I: n = 27 (29.0 %); grade II: n = 39 (41.9 %); grade III: n = 27 (29.0 %)). A three-tier ECD algorithm was applied based on quantitative assessment of endogenous intoxication (middle-mass molecules, MMM) and organ dysfunction (Sequential Organ Failure Assessment, SOFA): basic detoxification for mild intoxication; therapeutic plasmapheresis and low-intensity laser blood irradiation for moderate intoxication; an extended program including continuous veno-venous hemodiafiltration (CVVHDF), selective hemosorption (Toraymyxin ­PMX-20R or oXiris), or molecular adsorbent recirculating system (MARS) for severe intoxication. Primary endpoints included reduction in MMM, procalcitonin, interleukin-6, tumor necrosis factor α, and lipopolysaccharide endotoxin. Statistical analysis was performed using IBM SPSS Statistics v.26.0 with Mann-Whitney U-test, Friedman ANOVA, and log-rank test; significance was set at p < 0.05. Results. ECD methods were applied in 46 patients (49.5 %): therapeutic plasmapheresis in 38 (40.9 %), CVVHDF in 32 (34.4 %), selective hemosorption in 15 (16.1 %), cascade plasmafiltration in 9 (9.7 %), and MARS in 2 (2.2 %). Therapeutic plasmapheresis achieved 54.0 ± 6.0 % reduction in MMM and 48.0 ± 5.0 % reduction in procalcitonin after three sessions. CVVHDF reduced interleukin-6 by 64.0 ± 8.0 % and tumor necrosis factor α by 52.0 ± 6.0 % within 24 hours. Selective hemosorption with Toraymyxin reduced lipopolysaccharide endotoxin levels by 58.0 ± 6.0 % after one session and by 78.0 ± 8.0 % after two sessions, accompanied by a 3.2 ± 0.5-point reduction in SOFA score within 48 hours. Median time to MMM normalization (≤ 0.24 AU) was significantly shorter in the extended detoxification program (3.5 days, 95% CI 3.0–4.0) compared with standard infusion therapy (8.5 days, 95% CI 8.0–9.0; log-rank p < 0.001). No life-threatening complications were observed; minor adverse events occurred in 12 of 282 sessions (4.3 %). Conclusions. A differentiated, severity-stratified application of extracorporeal detoxification methods in severe cholangiogenic sepsis, based on quantitative assessment of endogenous intoxication and organ dysfunction, provides accelerated resolution of endotoxemia and systemic inflammatory response. The algorithm represents a clinically applicable framework for individualized management of this high-mortality condition and warrants validation in larger multicenter randomized trials.

Hali tarjima qilinmagan