Is polymyxin B-immobilized fiber column ineffective for septic shock? A discussion on the press release for EUPHRATES trial.
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SUBMITTER: Iba T
PROVIDER: S-EPMC5496228 | biostudies-other | 2017
REPOSITORIES: biostudies-other
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Project description:BackgroundPolymyxin B-immobilized fiber column hemoperfusion (PMX) has been reported to be effective for patients with septic shock. It remains unclear, however, how the efficacy of PMX varies according to the characteristics and underlying conditions of the patients treated. The objective of the present study was to clarify the factors that result in clinical efficacy of PMX treatment.MethodsWe retrospectively investigated 78 consecutive patients with severe sepsis or septic shock who underwent PMX treatment. We reviewed the demographic data, routine biochemistry, microbiological data, infection focus, Acute Physiology and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA) score, change in mean arterial pressure (MAP), inotropic score, vasopressor dependency index, plasma levels of endotoxin and lactate, PaO2/FIO2 ratio, and survival time. We also divided the patients into two groups for comparison, namely, those whose inotropic scores improved after PMX treatment (improvement group) and those whose inotropic scores did not improve (non-improvement group).ResultsThe inotropic score and the vasopressor dependency index significantly decreased from 18.1 to 9.9 (p < 0.05) and from 0.27 to 0.14 (p < 0.05), respectively, after PMX treatment in the overall study population, while no significant change in the PaO2/FIO2 ratio was observed (p = 0.96). The inotropic score at pre-PMX treatment was significantly higher in the improvement group than in the non-improvement group (p < 0.01). The improvement of the PaO2/FIO2 ratio after PMX treatment was significant in the improvement group (p < 0.05).ConclusionsThe improvement group's inotropic score was higher, because of peripheral blood vessels dilatation and requirement for more catecholamines. Therefore, our study suggests that PMX treatment is particularly useful for improving hemodynamics in septic shock patients with excessively dilated peripheral blood vessels.
| S-EPMC4392791 | biostudies-literature
Project description:Septic shock-associated mortality in intensive care units (ICUs) remains high, with reported rates ranging 30-50%. In particular, Gram-negative bacilli (GNB), which induce significant inflammation and consequent multiple organ failure, are the etiological bacterial agent in 40% of severe sepsis cases. Hemoperfusion using polymyxin B-immobilized fiber (PMX), which adsorbs endotoxin, is expected to reduce the inflammatory sepsis cascade due to GNB. However, the clinical efficacy of this treatment has not yet been demonstrated. Here, we aimed to verify the efficacy of endotoxin adsorption therapy using PMX through a retrospective analysis of 413 patients who received broad spectrum antimicrobial treatment for GNB-related septic shock between January 2009 and December 2012 in 11 ICUs of Japanese tertiary hospitals. After aligning the patients' treatment time phases, we classified patients in two groups depending on whether PMX hemoperfusion (PMXHP) therapy was administered or not within 24 hours after ICU admission (PMXHP group: n = 134, conventional group: n = 279). The primary study endpoint was the mortality rate at 28 days after ICU admission. The mean age was 72.4 (standard deviation: 12.6) years, and the mean Sequential Organ Failure Assessment score at ICU admission was 9.9 (3.4). The infection sites included intra-abdominal (38.0%), pulmonary (18.9%), and urinary tract (32.2%), and two thirds of all patients had GNB-related bacteremia. Notably, the mortality at 28 days after ICU admission did not differ between the groups (PMXHP: 29.1% vs. conventional: 29.0%, P = 0.98), and PMXHP therapy was not found to improve this outcome in a Cox regression analysis (hazard ratio = 1.16; 95% confidence interval, 0.81-1.64, P = 0.407). We conclude that PMX-based endotoxin adsorption within 24 hours from ICU admission was not associated with mortality among patients with septic shock due to GNB.Trial registrationUniversity Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR ID: UMIN000012748).
| S-EPMC5373513 | biostudies-literature
Project description:ObjectiveTo evaluate the efficacy and safety of direct hemoperfusion using a polymyxin B-immobilized polystyrene column (PMX-DHP) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive pneumonia patients.MethodsThis study was a case series conducted at a designated infectious diseases hospital. Twelve SARS-CoV-2-positive patients with partial pressure of arterial oxygen/percentage of inspired oxygen (P/F) ratio < 300 were treated with PMX-DHP on two consecutive days each during hospitalization. We defined day 1 as the first day when PMX-DHP was performed. PMX-DHP efficacy was assessed on days 7 and 14 after the first treatment based on eight categories. Subsequently, improvement in P/F ratio and urinary biomarkers on days 4 and 8, malfunctions, and ventilator and extracorporeal membrane oxygenation avoidance rates were also evaluated.ResultsOn day 14 after the first treatment, disease severity decreased in 58.3% of the patients. P/F ratio increased while urine β2-microglobulin decreased on days 4 and 8. Cytokine measurement pre- and post-PMX-DHP revealed decreased levels of interleukin-6 and the factors involved in vascular endothelial injury, including vascular endothelial growth factor. Twenty-two PMX-DHPs were performed, of which seven and five PMX-DHPs led to increased inlet pressure and membrane coagulation, respectively. When the membranes coagulated, the circuitry needed to be reconfigured. Circuit problems were usually observed when D-dimer and fibrin degradation product levels were high before PMX-DHP.ConclusionsFuture studies are expected to determine the therapeutic effect of PMX-DHP on COVID-19. Because of the relatively high risk of circuit coagulation, coagulation capacity should be assessed beforehand.
| S-EPMC8246724 | biostudies-literature
Project description:BACKGROUND:Direct hemoperfusion with polymyxin B-immobilized fiber (PMX-DHP) has been widely used for patients with septic shock around the world, but the prognostic factors have not been fully understood. We conducted a retrospective analysis to determine the prognostic factors in patients with septic shock who underwent PMX-DHP. METHODS:Twenty-nine patients with septic shock who underwent PMX-DHP were included in the study. The patients were divided into groups based on survival (n?=?23) and non-survival (n?=?6) 28 days after PMX-DHP, and the clinical data for the two groups before and after PMX-DHP were compared. RESULTS:In non-survivors, the vasopressor dependency index before PMX-DHP was significantly higher (p?=?0.046), and the leukocyte count before PMX-DHP was significantly lower (p?=?0.024) than in survivors. Furthermore, base excess after PMX-DHP was significantly lower in non-survivors (p?=?0.007) than in survivors. The optimal cutoff points of the vasopressor dependency index, leukocyte count, and base excess identified by receiver operating characteristic curves were 0.499/mmHg, 1360/?L, and -6.4 mmol/L, respectively. And the score using these three cutoffs, termed the prognostic score, was related to the prognosis of septic shock patients who underwent PMX-DHP (area under the curve?=?0.946). CONCLUSIONS:The prognostic score, using three parameters which are immediately and readily available in early phase after starting PMX-DHP, might be useful to predict the prognosis of these patients.
| S-EPMC4908858 | biostudies-literature
Project description:BACKGROUND:Hemoperfusion through a column containing polymyxin B-immobilized fiber (PMX-HP) is beneficial in abdominal sepsis. We assessed the effects of PMX-HP in a model of severe Pseudomonas aeruginosa pneumonia. METHODS:Eighteen pigs with severe P. aeruginosa pneumonia were mechanically ventilated for 76 h. Pigs were randomized to receive standard treatment with fluids and vasoactive drugs, or standard treatment with two 3-h PMX-HP sessions. Antibiotics against P. aeruginosa were never administered. We assessed endotoxemia through the endotoxin activity assay (EA). We measured the static lung elastance, ratio of arterial partial pressure per inspiratory fraction of oxygen (PaO2/FIO2), mean arterial pressure, cardiac output, systemic vascular resistance and inotropic score. Finally, every 24 h, we assessed complete blood count. RESULTS:In comparison with the control group, PMX-HP decreased percentage of circulating neutrophils from 47.4 ± 13.8 to 40.8 ± 11.5 % (p = 0.009). In a subgroup of animals with the worst hemodynamic impairment, EA in the control and PMX-HP groups was 0.50 ± 0.29 and 0.29 ± 0.14, respectively (p = 0.018). Additionally, in the control and PMX-HP groups, static lung elastance was 26.9 ± 8.7 and 25.3 ± 7.5 cm H2O/L (p = 0.558), PaO2/FIO2 was 347.3 ± 61.9 and 356.4 ± 84.0 mmHg (p = 0.118), mean arterial pressure was 81.2 ± 10.3 and 81.6 ± 13.1 mmHg (p = 0.960), cardiac output was 3.30 ± 1.11 and 3.28 ± 1.19 L/min (p = 0.535), systemic vascular resistance was 1982.6 ± 608.4 and 2011.8 ± 750.0 dyne/s/cm(-5) (p = 0.939), and inotropic score was 0.25 ± 0.10 and 0.26 ± 0.18 (p = 0.864). CONCLUSIONS:In mechanically ventilated pigs with severe P. aeruginosa pneumonia, PMX-HP does not have any valuable clinical benefit, and studies are warranted to fully evaluate a potential role of PMX-HP in septic shock associated with severe pulmonary infections.
| S-EPMC4932027 | biostudies-literature
Project description:ObjectivesRapidly progressive interstitial pneumonia is a fatal disease with no established therapeutic options. The aim of this systematic review is to clarify the efficacy of interstitial pneumonia treatment utilizing direct hemoperfusion with a polymyxin B-immobilized fibre column.MethodsAll patients with adult-onset rapidly progressive interstitial pneumonia including acute exacerbation of underlying chronic interstitial pneumonia were eligible. Primary studies of any design, which compared outcomes of direct hemoperfusion with a polymyxin B-immobilized fibre column treatment such as oxygenation and all-cause mortality with those of conventional therapy, were included. Electronic databases such as Medline and EMBASE were searched through October 7, 2018, and ICHUSHI, the largest database for medical articles in Japan, was also searched. Two reviewers independently extracted the relevant data and assessed the risk of bias in individual studies. The results were reported qualitatively due to substantial heterogeneity between studies.ResultsOut of 775 records retrieved, 10 reports were eligible and 8 of them were included for further analysis. They were all retrospective studies including a total of 327 patients and contained some risk of bias. There was variation in the administration method of direct hemoperfusion with a polymyxin B-immobilized fibre column treatment such as the timing, frequency, duration and interval. Multivariate analyses of only two studies with historical controls demonstrated beneficial effects of direct hemoperfusion with a polymyxin B-immobilized fibre column treatment over conventional therapy with all-cause mortality hazard ratios of 0.345 (95% confidence interval: 0.127-0.936) and 0.505 (95% confidence interval: 0.270-0.904), respectively. A significant difference of an improvement in the ratio of partial arterial oxygen pressure to the fraction of inspired oxygen in-between two treatment groups was also reported in two studies utilizing historical controls with mean differences of 56.8 and 57.5 mmHg, respectively.ConclusionsThere is currently insufficient data to support the use of direct hemoperfusion with a polymyxin B-immobilized fibre column treatment for rapidly progressive interstitial pneumonia. It should be instituted for research purposes only until new evidence is available.
| S-EPMC6614938 | biostudies-literature
Project description: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.
| S-EPMC5463489 | biostudies-literature
Project description:Polymyxin B is an antibiotic that shows strong bactericidal activity against Gram-negative bacteria, by binding to and inactivating endotoxin. Systemic administration of polymyxin B in humans is restricted because of its nephrotoxicity and neurotoxicity, and this compound was therefore considered a strong candidate ligand for the extracorporeal selective adsorption of circulating endotoxin in the blood. Toraymyxin® is a direct hemoperfusion column that uses polymyxin B attached to an insoluble carrier to bind endotoxin in the blood. In 1994, the Japanese National Health Insurance system approved the use of Toraymyxin for the treatment of endotoxemia and septic shock.In this chapter, we will review the development, clinical use, and efficacy of Toraymyxin, examine the structure of the Toraymyxin column, and comment on the current position of Toraymyxin in the treatment of severe sepsis and septic shock. We will also highlight some potential new applications of Toraymyxin for pulmonary diseases.
| S-EPMC7123644 | biostudies-literature
Project description:In an ongoing translational research program involving microarray-based expression profiles in pediatric septic shock, we have now conducted longitudinal studies focused on the temporal expression profiles of canonical signaling pathways and gene networks. Genome-level expression profiles were generated from whole blood-derived RNA samples of children with septic shock (n = 30 individual patients) corresponding to days 1 and 3 of admission to the pediatric intensive care unit. Based on sequential statistical and expression filters, day 1 and day 3 of septic shock were characterized by differential regulation of 2,142 and 2,504 gene probes, respectively, relative to normal control patients. Venn analysis demonstrated 239 unique genes in the day 1 data set, 598 unique genes in the day 3 data set, and 1,906 genes common to both data sets. Analyses targeted toward derivation of biological function from these data sets demonstrated time-dependent, differential regulation of genes involved in multiple canonical signaling pathways and gene networks primarily related to immunity and inflammation. Notably, multiple and distinct gene networks involving T cell- and MHC antigen-related biological processes were persistently downregulated from day 1 to day 3. Further analyses demonstrated large scale and persistent downregulation of genes corresponding to functional annotations related to zinc homeostasis. These data represent the largest reported cohort of patients with septic shock, which has undergone longitudinal genome-level expression profiling. The data further advance our genome-level understanding of pediatric septic shock and support novel hypotheses that can be readily tested at both the experimental and translational levels. Keywords: Inflammation; sepsis; innate immunity; T cells; MHC antigen Keywords: to be updated
2007-06-14 | GSE8121 | GEO
Project description:To test whether the polymyxin B hemoperfusion (PMX HP) fiber column reduces mortality and organ failure in peritonitis-induced septic shock (SS) from abdominal infections.Prospective, 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.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.This 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.
| S-EPMC4477725 | biostudies-literature