Polymyxin B-immobilized Hemoperfusion Research Articles

The role of polymyxin B-immobilized hemoperfusion in reducing mortality and enhancing hemodynamics in patients with sepsis and septic shock: A systematic review and meta-analysis

PurposePolymyxin B-immobilized hemoperfusion (PMX-HP) is a therapeutic strategy for removing circulating endotoxins from patients with sepsis or septic shock. However, the survival advantage of PMX-HP treatment remains controversial for patients with sepsis/septic shock. Therefore, this study collected all the clinical trials to assess the effect and the safety of PMX-HP treatment. MethodsPubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for eligible trials fromtheir inception through June 30, 2023. All clinical trials that investigated the effect of polymyxin B hemoperfusion in patients who died with sepsis or septic shock within 28-day mortality were eligible. The Cochrane Risk of Bias Assessment instrument and the ROBINS-I tool were used to assess the risk of bias. ResultsA total of 30 trials, including 25680 adult patients, were included. PMX-HP decreased 28-day mortality (OR 0.75, 95 % CI 0.65–0.88; p＜0.00001). Subgroup analysis revealed that 28-day mortality was significantly reduced after PMX-HP treatment in the mixed infection site group and in the age under 70 years old group. PMX-HP might also lower endotoxin levels (MD -1.22, 95 % CI -1.62 – 0.81, p < 0.00001) and improve SOFA scores (MD -2.11, 95 % CI -3.80- 0.43, p = 0.01). PMX-HP was not linked to the development of significant adverse events (p = 0. 05). ConclusionOur findings suggest that PMX-HP therapy can reduce 28-day mortality in individuals with sepsis or septic shock. The therapeutic effect may be due to the ability of PMX-HP to lower endotoxin levels and enhance hemodynamics. However, further assessment of the clinical effects of PMX-HP on sepsis or septic shock is required.

Effectiveness of polymyxin B-immobilized hemoperfusion against sepsis and septic shock: A systematic review and meta-analysis.

To evaluate the efficacy and safety of Polymyxin B-immobilized hemoperfusion (PMX-HP) against sepsis or septic shock. We searched databases (PubMed, EMBASE and Cochrane Library) to identify eligible randomized controlled trials (RCTs). The primary outcomes we included in this review were mortality at the longest follow-up available and serious adverse events associated with treatments. We used the Cochrane risk of bias assessment tool to evaluate risk of bias. Trial Sequential Analysis (TSA) was performed to assess the conclusion reached in our research. Thirteen studies including 1163 patients were identified. Use of PMX-HP could reduce overall mortality [relative risk (RR) 0.68, 95% confidence interval (CI) 0.51-0.91, P=0.01]. An interesting finding was that the mortality of patients in Acute Physiology and Chronic Health Evaluation (APACHE II) scores <25 group (RR 0.64, 95% CI 0.52-0.78, P<0.0001) and sepsis group (RR 0.48, 95% CI 0.32-0.72, P=0.0003) significantly decreased after PMX-HP treatment. The result also showed that PMX-HP could reduce endotoxin levels [Standardized mean difference (SMD) -1.53, 95% CI -2.92- -0.13, P=0.03] and improve mean arterial pressure (SMD 1.07, 95% CI 0.14-2.01, P=0.02). Serious adverse events between the PMX-HP group and standard therapy group were not significantly different (RR 2.16, 95% CI 0.97-4.80, I2=0%, P=0.06). However, TSA did not provide conclusive evidence and more high quality RCTs were required. Using PMX-HP to treat patients with less severe sepsis can reduce overall mortality and is safe. Treatment efficacy may benefit from the reduction of endotoxin level and the improvement of hemodynamics. More high quality RCTs are required to further evaluate the clinical role of PMX-HP against severe sepsis or septic shock.

Correction to: Polymyxin B-immobilized hemoperfusion and mortality in critically ill adult patients with sepsis/septic shock: a systematic review with meta-analysis and trial sequential analysis.

Owing to an oversight by the authors, Figure2 in this article was not the version intended for publication. The correct Figure2, reproduced here, features footnote symbols and Figure2b includes three studies as described in the main text.

Polymyxin B-immobilized hemoperfusion and mortality in critically ill adult patients with sepsis/septic shock: a systematic review with meta-analysis and trial sequential analysis.

Polymyxin B-immobilized hemoperfusion (PMX-HP) is an adjuvant therapy for sepsis or septic shock that clears circulating endotoxin. Prior trials have shown that PMX-HP improves surrogate endpoints. We aimed to conduct an evidence synthesis to evaluate the efficacy and safety of PMX-HP in critically ill adult patients with sepsis or septic shock. We searched for randomized controlled trials (RCTs) in MEDLINE, EMBASE, the Cochrane Library, the Health Technology Assessment Database, CINAHL, "Igaku Chuo Zasshi", the National Institute of Health Clinical Trials Register, the World Health Organization International Clinical Trials Registry Platform, the University Hospital Medical Information Network Clinical Trials Registry, the reference lists of retrieved articles, and publications by manufacturers of PMX-HP. The primary outcomes were 28-day all-cause mortality, the number of patients with at least one serious adverse event, and organ dysfunction scores. The GRADE methodology for the certainty of evidence was used. Six trials (857 participants; weighted mean age 62.5years) proved eligible. Patient-oriented primary outcomes were assessed. The pooled risk ratio (RR) for 28-day mortality associated with PMX-HP was 1.03 [95% confidence interval (CI) 0.78-1.36; I 2=25%; n=797]. The pooled RR for adverse events was 2.17 (95% CI 0.68-6.94; I 2=0%; n=717). Organ dysfunction scores over 24-72h after PMX-HP treatment did not change significantly (standardized mean difference - 0.26; 95% CI - 0.64 to 0.12; I 2=78%; n=797). The certainty of the body of evidence was judged as low for both benefit and harm using the GRADE methodology. There is currently insufficient evidence to support the routine use of PMX-HP to treat patients with sepsis or septic shock. PROSPERO International Prospective Register of Systematic Reviews (CRD42016038356).

Polymyxin B Alleviates Angiotensin II-Induced Stress Fiber Formation and Cellular Hypertrophy

Polymyxin B is widely used antibiotic in the clinic for resistant Gram-negative infections. In addition, polymyxin B-immobilized hemoperfusion cartridge has been used for endotoxin removal therapy in patients with septic shock. The aim of this study was to investigate the anti-fibrotic and anti-cellular hypertrophic effects of polymyxin B, and further to explore its possible mechanism. Polymyxin B (3, 10 μM) significantly inhibited stress fiber formation induced by angiotensin II (Ang II) in rat heart-derived H9c2 cells. Furthermore, polymyxin B (1 - 10 μM) showed a potent inhibitory effect on Ang II-induced cellular hypertrophy in H9c2 cells. Under the mechanism study, the inhibitory activities of polymyxin B against kinases involved in cellular hypertrophy such as AKT1, CAMK, GRK5, GSK3β, MLCK, PKC, PKD2, AMPK, ROCK2, p70S6K, SGK1were evaluated. Polymyxin B possesses a potent G protein related kinase 5 (GKR5) inhibitory activity with IC50 value of 1.1 μM, and has an ATP non-competitive inhibitory mode. Taken together, these results indicate that polymyxin B alleviates Ang II-induced stress fiber formation and cellular hypertrophy, and propose that one mechanism underlying these effects involves inhibition of the GRK5 pathway.

Endotoxin Removal with a Polymyxin B-Immobilized Hemoperfusion Cartridge Improves Cardiopulmonary Function After Cardiopulmonary Bypass

Cardiac surgery using cardiopulmonary bypass (CPB) is performed widely, given the progress in cardioprotective methods. However, endotoxemia caused by CPB leads to systemic inflammatory response syndrome and deterioration of organ function. We evaluated the effectiveness of endotoxin removal with a polymyxin B-immobilized hemoperfusion cartridge (PMX) in CPB. Pigs weighing about 25 kg were divided into control (n = 5) and PMX (n = 5) groups. Normothermic CPB was performed in the control group, while endotoxin was removed with PMX under normothermic CPB in the PMX group. Endotoxin removal was performed from the start to end of CPB. The end-systolic pressure-volume ratio (E(max)), left ventricular pressure (LVP), maximum and minimum rates of increase in LVP (+/-LVdp/dt), and cardiac output (CO) were measured 2 h after CPB, and the recovery rates of the parameters were compared between the two groups. A histopathological study was also conducted. The recovery rates of E(max), CO, and LVP were significantly better (P < 0.05) in the PMX group than in the control group. The PaO(2) 2 h after CPB was significantly higher (P < 0.05) in the PMX group than in the control group. The interleukin (IL)-8 level 2 h after CPB was significantly lower (P < 0.05) in the PMX group. Histopathologically, the heart and pulmonary tissues were better preserved in the PMX group. The PMX treatment reduced the inflammatory reaction caused by CPB, and cardiac and pulmonary functions after normothermic CPB were well preserved.

Blood purification therapy for sepsis

Accumulating evidences of underlining pathogenesis of sepsis have contributed to the therapeutic strategy for sepsis. Not only endotoxin and cytokine, but also signal transduction through Toll-like receptors could be a strategic target for the management of sepsis. Blood purification therapy including polymyxin B-immobilized hemoperfusion cartridge and continuous hemodiafiltration has shown the beneficial effect on patients with sepsis in Japan. Although they were initially designed to remove endotoxin and cytokines respectively, they might eliminate unexpected mediators responsible for sepsis. Further elucidation of mechanism and randomized controlled studies are needed to establish the role of blood purification therapy in sepsis.