Hemoperfusion In Patients 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.

Factors associated with refusing hemoperfusion in patients with acute paraquat poisoning.

Paraquat poisoning remains a critical public health issue with no established effective treatment. Hemoperfusion (HP) has been recognized for its potential to remove toxins and is widely employed in several developing countries for managing acute paraquat poisoning cases. However, the reluctance of some patients to undergo this recommended treatment has been observed but not thoroughly investigated. This study aimed to explore the factors associated with the refusal of HP in patients suffering from paraquat intoxication. In this retrospective study, data of 358 patients with acute paraquat poisoning were analyzed in Xi'an, China. The outcome of our study was mortality, and the influential factors were age, gender, marital status, educational level, symptoms at presentation, and laboratory findings. A logistic regression model was utilized to explore the independent risk factors. In a total of 358 paraquat-poisoned patients, the significant differences were found between patients who underwent HP and those who did not, particularly regarding mean age (48.02 years vs. 42.32 years; P = 0.01), mental disorders (15.6% vs. 6.1%; P = 0.01), poisoning severity score (2.36 vs. 2.57; P = 0.03), organ failure (10.9% vs. 23.5%; P = 0.02), and mechanical ventilation (18.8% vs. 33.3%; P = 0.02). Patients who refused HP exhibited a higher mortality (20.3% vs. 10.9%; P = 0.03) compared to those who received HP. Age (odds ratio (OR), 1.76; 95% confidence interval (CI): 1.01-3.82; P = 0.01) and history of mental disorders (OR, 2.81; 95% CI: 1.19-6.61; P = 0.02) were identified as significant independent predictors for the refusal of HP. The results of this study showed that elderly individuals and those with a history of mental disorders were independently associated with refusing HP in patients with acute paraquat poisoning.

VASOPRESSOR REDUCTION EFFECT OF POLYMYXIN B HEMOPERFUSION IN PATIENTS WITH PERITONITIS-INDUCED SEPTIC SHOCK: A PROPENSITY SCORE-MATCHED ANALYSIS.

Background : This study aimed to evaluate the effect of polymyxin B hemoperfusion (PMX-HP) in patients with peritonitis-induced septic shock who still required high-dose vasopressors after surgical source control. Methods : This retrospective study included adult patients admitted to the surgical intensive care unit (ICU) at Seoul National University Hospital between July 2014 and February 2021 who underwent major abdominal surgery to control the source of sepsis. Patients were divided into two groups based on whether PMX-HP was applied after surgery or not. The primary and secondary endpoints were the vasopressor reduction effect, and in-ICU mortality, respectively. Propensity score matching was performed to compare the vasopressor reduction effect. Results : A total of 338 patients met the inclusion criteria, of which 23 patients underwent PMX-HP postoperatively, whereas 315 patients did not during the study period. Serum norepinephrine concentration decreased over time regardless of whether PMX-HP was applied. However, it decreased more rapidly in the PMX-HP(+) group than in the PMX-HP(-) group. There were no significant differences in demographics including age, sex, body mass index, and most underlying comorbidities between the two groups. Risk factors for in-ICU mortality were identified by comparing patient characteristics and perioperative factors between the two groups using multivariate analysis. Conclusion : For patients with peritonitis-induced septic shock, PMX-HP rapidly reduces the requirement of vasopressors immediately after surgery but does not reduce in-ICU mortality. This effect could potentially accelerate recovery from shock, reduce sequelae from vasopressors, and ultimately improve quality of life after discharge.

Outcome and Complications of Hemoperfusion in Patients with COVID-19 in Intensive Care Unit: A Cross-Sectional Study.

The use of the hemoperfusion method is recommended for treating cytokine storms and reducing complications in patients with COVID-19. The side effects of this treatment are not known; therefore, this study was performed to determine the final outcome and complications of hemoperfusion in patients with COVID-19 hospitalized in ICU. In this retrospective cross-sectional study, all patients with severe COVID-19 without any comorbidities or organ failure underwent hemoperfusion treatment in ICU at Kosar Hospital in Semnan, Iran, from March to November 2021 were included. The clinical data and short-term complications up to 10 days after hemoperfusion and the final outcome were extracted from medical files. The mean age of 40 patients with severe COVID-19 undergoing hemoperfusion was 57.5±15.9 years. Most (24, 60%) patients were male. The time interval from hospitalization to hemoperfusion and the time interval between hemoperfusion and final outcome was 4.85 days and 8.30 days, respectively. Arrhythmia, bleeding, thrombocytopenia, and coagulation disorders were the most common short-term complications of hemoperfusion in patients with COVID-19, respectively. Most complications occurred on the second and third days after hemoperfusion. Mortality occurred in 20 (50 %) patients with severe COVID-19 undergoing hemoperfusion in ICU. It seems that the short-term complications and deaths due to hemoperfusion are relatively high in patients with COVID-19 admitted to the ICU. Further studies are recommended.

Study on Application Effect of Seamless Nursing in CRRT Combined with Hemoperfusion in Patients with Acute Pancreatitis Complicated with Hyperlipidemia

Study on Application Effect of Seamless Nursing in CRRT Combined with Hemoperfusion in Patients with Acute Pancreatitis Complicated with Hyperlipidemia

Development and validation of a prediction model of deep venous thrombosis for patients with acute poisoning following hemoperfusion: a retrospective analysis.

ObjectiveTo develop and confirm an individualized predictive model to ascertain the probability of deep venous thrombosis in patients with acute poisoning after undergoing hemoperfusion.MethodsThree hundred eleven patients with acute poisoning who were admitted to a hospital in China between October 2017 and February 2019 were included in the development group. Eighty patients with acute poisoning who were admitted between February and May 2019 were included in the validation group. The independent risk factors for deep venous thrombosis were examined. An individualized predictive model was developed using regression coefficients.ResultsThe number of catheter indwelling days, having a catheter while being transported, elevated serum homocysteine concentrations, and dyslipidemia were independent risk factors for deep venous thrombosis following hemoperfusion in patients with acute poisoning. The areas under the receiver operating characteristic curve of the development and validation groups were 0.713 and 0.702, respectively, which suggested that the prediction model had good discrimination capacity. The calibration belts of the two groups were ideal.ConclusionsOur prediction model has a moderate predictive effect for the occurrence of deep venous thrombosis in patients with acute poisoning. In clinical practice, this model could be combined with a common thrombosis risk assessment model.

POS-875 THE CLINICAL PROFILE AND OUTCOME OF PATIENTS WITH COVID 19 WHO UNDERWENT HEMOPERFUSION IN BATAAN GENERAL HOSPITAL AND MEDICAL CENTER

The outbreak of COVID-19 was declared a pandemic without definitive therapies. Extracorporeal blood purification has been proposed as one of the therapeutic approaches in patients with Covid-19 because of its beneficial impact on elimination of inflammatory cytokines. Considering the association of increased cytokine release with severity of COVID disease and the effect of hemoperfusion on removal of these cytokines, this study was conducted to determine the outcome of hemoperfusion in patients with severe and critical COVID admitted at Bataan General Hospital and Medical Center (BGHMC).

P16‐48: The prognostic marker of polymyxin B‐immobilized fiber column‐direct hemoperfusion in patients who developed acute exacerbation of chronic fibrosing idiopathic interstitial pneumonia

P16‐48: The prognostic marker of polymyxin B‐immobilized fiber column‐direct hemoperfusion in patients who developed acute exacerbation of chronic fibrosing idiopathic interstitial pneumonia

Effects of polymyxin B hemoperfusion in patients with sepsis requiring continuous hemodiafiltration: Analysis of a nationwide administrative database in Japan.

This study investigated sepsis patients' current status with continuous hemodiafiltration (CHDF) with or without polymyxin B hemoperfusion (PMX). We identified 17 367 adult sepsis patients treated with CHDF and PMX using the Japanese diagnosis procedure combination (DPC) database from April 2016 to March 2019. More than half of the patients in this category resulted in death in the hospital, which means that patients in this group were critically ill. Among the patients who received CHDF, the 28-day survival rate of PMX-treated patients was significantly higher than that of non-treated patients, after adjusting the patient background by propensity score matching (69.5% vs. 65.4%, p< 0.0001). Furthermore, the length of hospital stay and intensive care unit stay was significantly shorter in PMX-treated patients than that of non-treated patients. These results suggest that PMX may provide benefits to patients with severe sepsis requiring CHDF.

Uncertain Clinical Effect of Polymyxin B Hemoperfusion in Patients with Septic Acute Kidney Injury Requiring Continuous Renal Replacement Therapy.

Polymyxin B hemoperfusion (PMX-HP) may improve the clinical outcomes of patients with sepsis and gram-negative bacteremia by reducing endotoxin levels. However, the recent studies with the variable degree of renal support have shown that the improvement of survival rate by PMX-HP remains unclear in such patients. Therefore, we investigated whether the addition of PMX-HP to continuous renal replacement therapy (CRRT) could improve the survival rate than CRRT alone. This study included 231 patients with sepsis undergoing CRRT alone or PMX-HP with CRRT. Primary outcomes were 28-day and 90-day all-cause mortality. Urine output, ventilator support, and Sequential Organ Failure Assessment (SOFA) score were not significantly different between the two groups. Crude 28-day and 90-day mortality rates were higher in the PMX-HP with CRRT group than in the CRRT-alone group. To correct for disease severity, propensity score (PS) matching was performed with acute respiratory distress syndrome, mechanical ventilation support, extracorporeal membrane oxygenation, infection source (abdomen), age, inotropic score, SOFA score, C-reactive protein, and procalcitonin levels. Sixty-six PS-matched pairs revealed significantly higher 28-day and 90-day mortality rates in the PMX-HP with CRRT group than in the CRRT-alone group. Considering the mortality rates after PS matching, the additional use of PMX-HP does not improve the clinical outcomes of patients with sepsis and acute kidney injury requiring CRRT.

Hemoperfusion in patients with severe COVID-19 respiratory failure, lifesaving or not?

Background:The new coronavirus outbreak quickly filled hospital beds and stunned the world. Intensive care is required for 5% of patients, and the mortality rate for critically ill patients is 49%. The “cytokine storm” is considered as the main cause of pathogenesis for coronavirus disease-19 (COVID-19)-related respiratory failure, hemoperfusion may be a modality for treatment of disease.Materials and Methods:Thirty-seven an patients with positive real-time polymerase chain reaction for SARStions2 in an upper respiratory tract sample or typical chest computed tomography lesion were eligible for this case–control study. Patients meeting the criteria for hemoperfusion including clinical and laboratory indices, were evaluated for outcomes such as hospitalization length and mortality. Patients were divided into three groups, i.e., patients who received hemoperfusion without a need for mechanical ventilation (MV), patients who received hemoperfusion before MV, and patients who received hemoperfusion after MV.Results:Among 37 patients with COVID-19 respiratory failure, 32% were female with a mean age of 55.54 (standard deviation 14.1) years. There was no statistically significant difference between the three groups in terms of length of hospital stay and intensive care unit (ICU) stay (P-tayns: 0.593 and 0.243, respectively, confidence interval [CI]: 95%). Heart rate, respiratory rate, PaO2/FIO2, high-sensitivity C-reactive protein, and ferritin significantly improved after the application of hemoperfusion in all groups (P < 0.05, CI: 95%).Conclusion:It seems that applying hemoperfusion in the inflammatory phase of the disease, especially before the intubation, reduce the need for MV. However, hemoperfusion does not have any impacts on the duration of hospital and ICU stay.

Application of a risk stratification-based model for prediction of acute kidney injury combined with hemoperfusion in patients with sepsis: a prospective, observational, pilot study

To evaluate the efficacy and safety of a risk stratification-based model for prediction of acute kidney injury (AKI) combined with hemoperfusion (HP) in the treatment of patients with sepsis. A prospective, observational, pilot trial was conducted. The patients who met the Sepsis-3 diagnostic criteria admitted to intensive care unit of Lanzhou University Second Hospital from May to December in 2019 were enrolled as the research objects. Through the AKI early warning model established by the research group in the early stage, AKI risk > 30% was defined as AKI high risk. Patients with AKI high risk were enrolled in the observation group, and the remaining patients were enrolled in the control group. All patients were given conventional treatment, including the search and treatment of original infection sites, the use of antibiotics and main organ function support. Patients in the observation group were combined with HP treatment on the basis of conventional treatment, 2.5 hours per day for 3 days. The baseline data of gender, age, infection site, acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score, mean arterial pressure (MAP) and serum creatinine (SCr) were recorded. The inflammatory indexes such as interleukin-6 (IL-6), lipopolysaccharide (LPS) and procalcitonin (PCT) were detected at ICU admission, 24 hours and 72 hours after ICU admission, and the length of ICU stay, ICU mortality and bleeding were recorded. Among the 49 patients with sepsis enrolled in this study, the main diagnosis was pneumonia, and Gram-negative (G-) bacilli were the main pathogenic bacteria [61.2% (30/49)]. Among them, 30 patients with AKI risk > 30% were in the observation group, and the remaining 19 patients were in the control group. There was no significant difference in gender, age, infection site, APACHE II score, SOFA score, MAP or other baseline data between the two groups, but the baseline value of SCr in the observation group was significantly higher than that in the control group (μmol/L: 112.2±34.4 vs. 93.4±13.0, P < 0.05). At ICU admission, there was no significant difference in IL-6, LPS or PCT between the two groups. However, with the extension of ICU time, the inflammatory indexes of the two groups showed a downward trend. At 24 hours after ICU admission, there was no significant difference in IL-6, LPS or PCT between the two groups. At 72 hours after ICU admission, IL-6 in the experimental group decreased significantly as compared with the control group (ng/L: 90.9±38.1 vs. 119.1±41.9, P < 0.05), but there was no significant difference in LPS or PCT between the two groups. The length of ICU stay in the experimental group was significantly shorter than that in the control group (days: 9.77±2.76 vs. 12.47±3.85, P < 0.01), but there was no significant difference in the ICU mortality between the experimental group and control group (20.0% vs. 21.1%, P > 0.05). None of the 49 patients had severe bleeding events. The application of a risk stratification-based model for prediction of AKI combined with HP in septic patients is feasible both in theory and in clinical practice, and shortens the length of ICU stay, but fails to effectively remove inflammatory mediators or reduce sepsis mortality. A large sample, multicenter, randomized controlled study is still needed for further verification.

Impact of hemoperfusion with polymyxin B added to hemofiltration in patients with endotoxic shock: a case\u2013control study

BackgroundSeptic shock is a leading cause of death in critical patients. In patients with gram-negative septic shock, hemoperfusion with polymyxin B aims to remove endotoxins from plasma. We analyzed the clinical and biological response to hemoperfusion in patients with septic shock and acute kidney injury.MethodsThis prospective case–control study in the medical–surgical intensive care unit of a university hospital included consecutive adults patients with septic shock and suspected gram-negative bacteria infection with elevated plasma endotoxin activity (EAA > 0.6 EU/ml) and acute kidney injury requiring continuous renal replacement therapy (CRRT). At onset of septic shock, half underwent CRRT plus hemoperfusion with polymyxin B for two hours a day during two consecutive days (hemoperfusion group) and half received only CRRT (control group). We measured clinical, physiological, and biological parameters (EAA, C-reactive protein, procalcitonin, and cytokines) daily during the first 5 days.ResultsWe included 18 patients (male, 33%; mean age, 67.5; mean SOFA score, 11.3). Abdominal infections predominated (50% had peritonitis). At the beginning of CRRT, RIFLE classification was “failure” for 72% and “injury” for 28%. Baseline characteristics did not differ between groups. Patients in the hemoperfusion group required longer mechanical ventilation (12.4 vs. 9.4 days, p = 0.03) and CRRT (8.5 vs. 6 days, p = 0.01) than in the control group. Noradrenaline doses, lactate, procalcitonin, and C-reactive protein decreased in both groups. At day 5, EAA was significantly lower in the hemoperfusion group (0.58 EU/ml vs. 0.73 EU/ml in controls, p = 0.03). There were no significant differences between groups in other biomarkers or ICU mortality (33.3% in the treatment group vs. 44.4% in the control group, p = 0.5). No adverse effects of hemoperfusion were observed.ConclusionsHemoperfusion with polymyxin B added to CRRT resulted in faster decrease in endotoxin levels, but we observed no improvements in clinical, physiological, or biological parameters.

Clinical Effects of Polymyxin B Hemoperfusion in Patients With Septic Shock Caused by Urinary Tract Infection

Direct hemoperfusion with polymyxin B-immobilized fiber (PMX-DHP) has been widely used for severe sepsis and septic shock. However, data are limited regarding the clinical experience and efficacy of PMX-DHP for septic shock resulting from urinary tract infection (UTI). At our institution, 15 patients with septic shock resulting from a UTI received PMX-DHP from January 2013 to July 2017. The cause of the urosepsis was mainly obstructive pyelonephritis secondary to ureterolithiasis or neurogenic bladder. Average Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores were 25.9 ± 4.3 and 10.5 ± 2.2, respectively. If patients were still hypotensive after initial resuscitation, we began PMX-DHP. Mean arterial pressure increased significantly from 58.3 ± 9.6 mm Hg to 93.6 ± 14.8 mm Hg just after PMX-DHP and to 94.7 ± 16.9 mm Hg (P < 0.0001) 24 h after the treatment. Catecholamine index decreased significantly from 20.7 ± 11.3 to 9.3 ± 13.5 (P = 0.0001) 24 h after the treatment. Of 15 patients, 14 (93.3%) had survived 28 days after admission. Our results suggest a possible role for PMX-DHP in the rapid stabilization of hemodynamics in patients with septic shock with an underlying UTI. These patients may be good candidates for PMX-DHP.

腹部感染症に対する PMX-DHP長時間施行の安全性の検討

腹部感染症に対する PMX-DHP長時間施行の安全性の検討

Impact of polymyxin B hemoperfusion in the treatment of patients with sepsis and septic shock: a meta-analysis of randomized controlled trials.

Polymyxin B hemoperfusion is a strategy to remove circulating endotoxin in patients with sepsis. Previous systematic reviews derived from randomized and non-randomized studies suggested that use of polymyxin B hemoperfusion reduced mortality, based on the pooled data from various time points in the clinical course of sepsis. We conducted a meta-analysis of randomized controlled trials to assess the impact of polymyxin B hemoperfusion specifically on 28-day mortality in patients with sepsis and septic shock. PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for eligible trials from inception through July 30, 2017. All randomized controlled trials were eligible if they examined the impact of polymyxin B hemoperfusion on 28-day mortality in patients with sepsis and septic shock. Risk of bias was evaluated with the Cochrane risk of bias assessment tool. Data were pooled using the DerSimonian and Laird random-effects model. Seven trials involving 586 participants were identified for the analysis. Use of polymyxin B hemoperfusion was not associated with a reduced risk of 28-day mortality [risk ratio (RR), 0.76; 95% CI, 0.54-1.07] compared with usual care. One unpublished trial also showed no significant 28-day survival benefit. There is no evidence to support the use of polymyxin B hemoperfusion for patients with sepsis and septic shock with respect to 28-day mortality.

Potential survival benefit of polymyxin B hemoperfusion in patients with septic shock: a propensity-matched cohort study

BackgroundThe purpose of this study was to investigate whether polymyxin B hemoperfusion (PMX-HP) improves the survival of patients with septic shock.MethodsThis was a retrospective, multicenter study conducted on patients treated during a 3-year period. We performed propensity-score analyses of the Japan Septic Disseminated Intravascular Coagulation (JSEPTIC DIC) study database. The study included data on 1723 patients with septic shock aged 16 years or older. Furthermore, we divided patients into to PMX-HP- and non-PMX-HP-treated groups. The primary endpoint was all-cause hospital mortality; secondary endpoints included intensive care unit (ICU) mortality and number of ICU-free days (ICUFDs) in the first 28 days.ResultsOf 1,723 eligible patients, 522 had received PMX-HP. Propensity score matching created 262 matched pairs (i.e., 262 patients in each of the non-PMX-HP and PMX-HP groups). The proportion of all-cause hospital mortality was significantly lower in the PMX-HP group than in the non-PMX-HP group (32.8% vs. 41.2%; odds ratio (OR): 0.681; 95% confidence interval (CI): 0.470–0.987; P = 0.042). The number of ICUFD in the first 28 days was significantly higher in the PMX-HP group than in the non-PMX-HP group (18 (0-22) vs. 14 (0-22) days, respectively; P = 0.045). On the other hand, there was no significant difference in ICU mortality between the two groups (21.8% vs. 24.4%; OR: 0.844; CI: 0.548–1.300; P = 0.443).ConclusionsOur results strongly suggest that PMX-HP reduces all-cause hospital mortality and length of ICU stay in patients with septic shock.

Early use of polymyxin B hemoperfusion in patients with septic shock due to peritonitis: a multicenter randomized control trial.

PurposeTo test whether the polymyxin B hemoperfusion (PMX HP) fiber column reduces mortality and organ failure in peritonitis-induced septic shock (SS) from abdominal infections.MethodProspective, multicenter, randomized controlled trial in 18 French intensive care units from October 2010 to March 2013, enrolling 243 patients with SS within 12 h after emergency surgery for peritonitis related to organ perforation. The PMX HP group received conventional therapy plus two sessions of PMX HP. Primary outcome was mortality on day 28; secondary outcomes were mortality on day 90 and a reduction in the severity of organ failures based on Sequential Organ Failure Assessment (SOFA) scores.ResultsPrimary outcome: day 28 mortality in the PMX HP group (n = 119) was 27.7 versus 19.5 % in the conventional group (n = 113), p = 0.14 (OR 1.5872, 95 % CI 0.8583–2.935). Secondary endpoints: mortality rate at day 90 was 33.6 % in PMX-HP versus 24 % in conventional groups, p = 0.10 (OR 1.6128, 95 % CI 0.9067–2.8685); reduction in SOFA score from day 0 to day 7 was −5 (−11 to 6) in PMX-HP versus −5 (−11 to 9), p = 0.78. Comparable results were observed in the predefined subgroups (presence of comorbidity; adequacy of surgery, <2 sessions of hemoperfusion) and for SOFA reduction from day 0 to day 3.ConclusionThis multicenter randomized controlled study demonstrated a non-significant increase in mortality and no improvement in organ failure with PMX HP treatment compared to conventional treatment of peritonitis-induced SS.Electronic supplementary materialThe online version of this article (doi:10.1007/s00134-015-3751-z) contains supplementary material, which is available to authorized users.

Effectiveness of polymyxin b immobilized fiber hemoperfusion in patients with septic shock due to Gram-negative bacillus infection: the PMXHP study

Mortality from septic shock in the ICU remains high, ranging from 30 to 50%. In particular, Gram-negative bacilli (GNB) account for 40% of the causative bacteria of severe sepsis, which progresses to multiorgan failure due to significant inflammation. Hemoperfusion with polymyxin B-immobilized fiber (PMX) adsorbs endotoxin and can reduce the inflammatory cascade of sepsis due to GNB. However, the clinical efficacy of this treatment has not been demonstrated. We aimed to verify the efficacy of endotoxin adsorption therapy by using PMX.

The EUPHRATES trial (Evaluating the Use of Polymyxin B Hemoperfusion in a Randomized controlled trial of Adults Treated for Endotoxemia and Septic shock): study protocol for a randomized controlled trial.

BackgroundSeptic shock is common and has unacceptably high morbidity, mortality, and associated cost with numerous failed attempts at developing effective therapies. Endotoxin, one of the most potent mediators of sepsis, is found in high levels in approximately 50% of patients with septic shock. Polymyxin B (PMX) hemoperfusion has been shown in numerous studies to successfully remove endotoxin and potentially improve outcomes. EUPHRATES (Evaluating the Use of Polymyxin B Hemoperfusion in a Randomized controlled trial of Adults Treated for Endotoxemia and Septic shock) is a theragnostic trial (matching blood measurement to treatment capability) of PMX hemoperfusion in patients with septic shock and confirmed endotoxemia as measured by the endotoxin activity assay (EAA).MethodsEUPHRATES is a pivotal regulatory trial that is multi-centered, placebo-controlled and blinded. The trial is being conducted in fifty ICUs in the United States and Canada and is powered to enroll 360 patients. Patients with persistent septic shock despite adequate fluid resuscitation on vasopressors for more than 2 and less than 30 hours are eligible for measurement of the EAA. Those with EAA ≥0.60 are eligible to be randomized to treatment with two sessions of PMX hemoperfusion 24 hours apart. The primary endpoint for the trial is 28-day all-cause mortality.DiscussionUnique features of the trial include absence of systemic inflammatory response (SIRS) criteria as a requirement for inclusion, use of the EAA to confirm endotoxemia as a requisite for treatment, and use of a detailed “façade” hemoperfusion event as a blinding mechanism. The outcomes of the second interim analysis included a resizing of the trial to 650 patients and the addition of an exclusion criterion of subjects with multiple organ dysfunction score (MODS) ≤ 9. Results are anticipated in 2016.Trial registrationClinicaltrials.gov identifier: NCT01046669. Registered: January 8, 2010.