Effectiveness of polymyxin B hemoperfusion for sepsis depends on the baseline SOFA score: a nationwide observational study.
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ABSTRACT: Background
Polymyxin B hemoperfusion (PMX) aims to treat septic shock by removing endotoxin from the patient's blood. However, the relationship between the severity of the patient's organ damage and the survival benefit of PMX treatment is not clear.Methods
We analyzed the efficacy of PMX on adult sepsis patients using the propensity score matching method and the Japanese Diagnosis Procedure Combination (DPC) national inpatient database from April 2018 to March 2020. We stratified the patients into five categories based on their baseline Sequential Organ Failure Assessment (SOFA) score and compared the mortality between PMX-treated and non-treated groups in each category. We also compared continuous hemodiafiltration (CHDF)-, ventilator- and noradrenaline-free days between the groups.Results
Of 44,177 patients included in the study, 2191 received PMX. After 1:1 propensity score matching, we created matched cohorts of 2033 pairs. PMX significantly improved the survival of the patients in the SOFA score categories of 7-9 and 10-12. On the other hand, there was no significant difference in the survival rate in SOFA score categories of 0-6, 13-15, and 16-24. In analyzing organ support-free days, PMX was also beneficial in the 7-9 and 10-12 SOFA categories compared to other categories.Conclusion
Analysis of a large-scale Japanese inpatient database found a significant association between PMX efficacy and baseline SOFA score. This result indicates higher efficacy in patients with medium SOFA scores in the range of 7-12. The result provides a promising hypothesis for selecting appropriate patients for PMX and should be validated in future RCTs.
SUBMITTER: Fujimori K
PROVIDER: S-EPMC8473472 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectivesTo evaluate the use of direct hemoperfusion with polymyxin B-immobilized fiber (PMX-DHP) as adjunctive therapy during pediatric patients with septic shock.DesignProspective observational study.SettingNine-bed PICUs at university referral hospital.PatientsChildren (30 d to 15 yr) with septic shock and Pediatric Logistic Organ Dysfunction (PELOD)-2 score greater than or equal to 10 or Pediatric Risk of Mortality (PRISM) 3 score greater than or equal to 15, who were also receiving at least one inotrope.InterventionPatients received 2-4 hour treatment with PMX-DHP 20R column on 2 consecutive days.Measurements and main resultsWe enrolled six children aged 21-167 months old (median, 99-mo old), with a body weight of 10-50 kg (median, 28 kg). All six patients had both PELOD-2 greater than or equal to 10 and PRISM-3 greater than or equal to 15, required invasive mechanical ventilation, and received standard treatment for septic shock before enrollment. We observed significant improvement in PELOD-2 score from baseline to 72 hours after the start of PMX-DHP (mean [95% CI] from 14.3 [12.2-16.5] to 6.0 [0.3-11.7]; p = 0.006). The vasoactive inotropic score (VIS) and lactate concentration also significantly decreased from baseline to 72 hours (VIS, 60 mmol/L [25-95 mmol/L] to 4.0 mmol/L [44.1-12 mmol/L]; p = 0.003; lactate, 2.4 mmol/L [1.0-3.8 mmol/L] to 1.0 mmol/L [0.5-1.5 mmol/L]; p = 0.01). Five of six patients survived. There was no device-related adverse event in these patients.ConclusionsIn this case series of treatment with PMX-DHP as adjunctive therapy in children with refractory septic shock and high baseline severity, we have shown that patient recruitment is feasible. We have also found that clinical hemodynamic and severity of illness scores at 72 hours may be potential end points for testing in future randomized controlled trials.
| S-EPMC9345520 | biostudies-literature
Project description:Direct hemoperfusion therapy with polymyxin B immobilized fiber cartridge (PMX-DHP) is an established strategy in the treatment of septic shock in Japan and parts of Western Europe. PMX-DHP is currently the subject of a pivotal North American randomized controlled trial (EUPHRATES) in patients with septic shock and confirmed endotoxemia, as measured by the endotoxin activity assay. The major mechanism of action of this therapy is the removal of circulating endotoxin. High affinity binding of circulating endotoxin by the PMX-DHP column may decrease circulating endotoxin levels by up to 90% after two standard treatments. Basic research has shown reductions in circulating cytokine levels and in renal tubular apoptosis. Clinical research has shown that PMX-DHP therapy results in hemodynamic improvements, improvements in oxygenation, renal function, and reductions in mortality. Further research is needed to further define additional patient populations with endotoxemia that may benefit from PMX-DHP therapy as well as to further elucidate dosing, timing, and additional information on mechanisms of action. This review will present the mechanistic rationale for this targeted strategy of endotoxin removal using PMX-DHP in endotoxemic septic patients, highlighting both the specific effects of the therapy and the evidence accumulated so far of clinical improvement following this therapy in terms of recovery of organ function.
| S-EPMC4077196 | biostudies-literature
Project description:Background:Sepsis is a global threat but insufficiently studied in Southeast Asia. The objective was to evaluate management, outcomes, adherence to sepsis bundles, and mortality prediction of maximum Sequential Organ Failure Assessment (SOFA) scores in patients with community-acquired sepsis in Southeast Asia. Methods:We prospectively recruited hospitalized adults within 24 h of admission with community-acquired infection at nine public hospitals in Indonesia (n?=?3), Thailand (n?=?3), and Vietnam (n?=?3). In patients with organ dysfunction (total SOFA score ??2), we analyzed sepsis management and outcomes and evaluated mortality prediction of the SOFA scores. Organ failure was defined as the maximum SOFA score ??3 for an individual organ system. Results:From December 2013 to December 2015, 454 adult patients presenting with community-acquired sepsis due to diverse etiologies were enrolled. Compliance with sepsis bundles within 24 h of admission was low: broad-spectrum antibiotics in 76% (344/454), ??1500 mL fluid in 50% of patients with hypotension or lactate ??4 mmol/L (115/231), and adrenergic agents in 71% of patients with hypotension (135/191). Three hundred and fifty-five patients (78%) were managed outside of ICUs. Ninety-nine patients (22%) died. Total SOFA score on admission of those who subsequently died was significantly higher than that of those who survived (6.7 vs. 4.6, p?<?0.001). The number of organ failures showed a significant correlation with 28-day mortality, which ranged from 7% in patients without any organ failure to 47% in those with failure of at least four organs (p?<?0.001). The area under the receiver operating characteristic curve of the total SOFA score for discrimination of mortality was 0.68 (95% CI 0.62-0.74). Conclusions:Community-acquired sepsis in Southeast Asia due to a variety of pathogens is usually managed outside the ICU and with poor compliance to sepsis bundles. In this population, calculation of SOFA scores is feasible and SOFA scores are associated with mortality. Trial registration:ClinicalTrials.gov, NCT02157259. Registered 5 June 2014, retrospectively registered.
| S-EPMC5813360 | biostudies-literature
Project description:ObjectiveTo test the hypothesis that extracorporeal therapy with polymyxin B (PMX-B) may prevent Gram-negative sepsis-induced acute renal failure (ARF) by reducing the activity of proapoptotic circulating factors.SettingMedical-Surgical Intensive Care Units.Patients and interventionsSixteen patients with Gram-negative sepsis were randomized to receive standard care (Surviving Sepsis Campaign guidelines) or standard care plus extracorporeal therapy with PMX-B.Measurements and resultsCell viability, apoptosis, polarity, morphogenesis, and epithelial integrity were evaluated in cultured tubular cells and glomerular podocytes incubated with plasma from patients of both groups. Renal function was evaluated as SOFA and RIFLE scores, proteinuria, and tubular enzymes. A significant decrease of plasma-induced proapoptotic activity was observed after PMX-B treatment on cultured renal cells. SOFA and RIFLE scores, proteinuria, and urine tubular enzymes were all significantly reduced after PMX-B treatment. Loss of plasma-induced polarity and permeability of cell cultures was abrogated with the plasma of patients treated with PMX-B. These results were associated to a preserved expression of molecules crucial for tubular and glomerular functional integrity.ConclusionsExtracorporeal therapy with PMX-B reduces the proapoptotic activity of the plasma of septic patients on cultured renal cells. These data confirm the role of apoptosis in the development of sepsis-related ARF.
| S-EPMC2517091 | biostudies-literature
Project description:The most common scoring system for critically ill patients is the Sequential Organ Failure Assessment (SOFA) score. Little is known about specific molecular signaling networks underlying the SOFA criteria. We characterized these networks and identified specific key regulatory molecules. We prospectively studied seven patients with sepsis and six controls with high-throughput RNA sequencing (RNAseq). Quantitative reverse transcription PCR (RT-qPCR) confirmation was performed in a second independent cohort. Differentially and significantly expressed miRNAs and their target mRNA transcripts were filtered for admission SOFA criteria and marker RNAs for the respective criteria identified. We bioinformatically constructed molecular signaling networks specifically reflecting these criteria followed by RT-qPCR confirmation of RNAs with important regulatory functions in the networks in the second cohort. RNAseq identified 82 miRNAs (45% upregulated) and 3254 mRNAs (50% upregulated) differentially expressed between sepsis patients and controls. Bioinformatic analysis characterized 6 miRNAs and 76 mRNA target transcripts specific for the SOFA criteria. RT-qPCR validated miRNA and mRNAs included IGFBP2 (respiratory system); MMP9 and PDE4B (nervous system); PPARG (cardiovascular system); AKR1B1, ANXA1, and LNC2/NGAL (acute kidney injury); GFER/ALR (liver); and miR-30c-3p (coagulopathy). There are specific canonical networks underlying the SOFA score. Key regulatory miRNA and mRNA transcripts support its biologic validity.
| S-EPMC8468706 | biostudies-literature
Project description:BackgroundRecent randomized trials have not found that polymyxin B hemoperfusion (PMX-HP) improves outcomes for patients with sepsis. However, it remains unclear whether the therapy could provide benefit for highly selected patients. Monocyte human leukocyte antigen (mHLA-DR) expression, a critical step in the immune response, is decreased during sepsis and leads to worsening sepsis outcomes. One recent study found that PMX-HP increased mHLA-DR expression while another found that the treatment removed HLA-DR-positive cells.MethodsWe conducted a randomized controlled trial in patients with blood endotoxin activity assay (EAA) level ≥ 0.6. Patients in the PMX-HP group received a 2-h PMX-HP treatment plus standard treatment for 2 consecutive days. Patients in the non-PMX-HP group received only standard treatment. The primary outcome compared the groups on median change in mHLA-DR expression between day 3 and baseline. Secondary outcomes compared the groups on the mean or median change in CD11b expression, neutrophil chemotaxis, presepsin, cardiovascular Sequential Organ Failure Assessment (CVS SOFA) score, vasopressor dose, and EAA level between day 3 and baseline. We further compared the groups on mortality, ICU-free days, ventilator-free days, dialysis dependence status, renal recovery, serum creatinine, vasopressor-free days, and major adverse kidney events (MAKE 28), measured on day 28.ResultsFifty-nine patients were randomized to PMX-HP (n = 29) and non-PMX-HP (n = 30) groups. At baseline, mHLA-DR expression, CD11b, neutrophil chemotaxis, and clinical parameters were comparable between groups. The median change in mHLA-DR expression between day 3 and baseline was higher in PMX-HP patients than in patients receiving standard therapy alone (P = 0.027). The mean change in CD11b between day 3 and baseline was significantly lower in the PMX-HP group than in the non-PMX-HP group (P = 0.002). There were no significant changes from baseline in neutrophil chemotaxis, presepsin, CVS SOFA scores, vasopressor doses, or EAA level between groups. On day 28 after enrollment, mortality, ICU-free days, ventilator-free days, dialysis dependence status, renal recovery, serum creatinine, vasopressor-free days, and MAKE 28 were comparable between groups.ConclusionPMX-HP improved mHLA-DR expression in severe sepsis patients. Future studies should examine the potential benefit of PMX-HP in patients with low mHLA-DR expression.Trial registrationClinicalTrials.gov, NCT02413541 . Registered on 3 March 2015.
| S-EPMC6204024 | biostudies-literature
Project description:BackgroundThe Sepsis-3 criteria introduced the system that uses the Sequential Organ-Failure Assessment (SOFA) score to define sepsis. The cardiovascular SOFA (CV SOFA) scoring system needs modification due to the change in guideline-recommended vasopressors. In this study, we aimed to develop and to validate the modified CV SOFA score.MethodsWe developed, internally validated, and externally validated the modified CV SOFA score using the suspected infection cohort, sepsis cohort, and septic shock cohort. The primary outcome was 28-day mortality. The modified CV SOFA score system was constructed with consideration of the recently recommended use of the vasopressor norepinephrine with or without lactate level. The predictive validity of the modified SOFA score was evaluated by the discrimination for the primary outcome. Discrimination was assessed using the area under the receiver operating characteristics curve (AUC). Calibration was assessed using the calibration curve. We compared the prognostic performance of the original CV/total SOFA score and the modified CV/total SOFA score to detect mortality in patients with suspected infection, sepsis, or septic shock.ResultsWe identified 7,393 patients in the suspected cohort, 4038 patients in the sepsis cohort, and 3,107 patients in the septic shock cohort in seven Korean emergency departments (EDs). The 28-day mortality rates were 7.9%, 21.4%, and 20.5%, respectively, in the suspected infection, sepsis, and septic shock cohorts. The model performance is higher when vasopressor and lactate were used in combination than the vasopressor only used model. The modified CV/total SOFA score was well-developed and internally and externally validated in terms of discrimination and calibration. Predictive validity of the modified CV SOFA was significantly higher than that of the original CV SOFA in the development set (0.682 vs 0.624, p < 0.001), test set (0.716 vs 0.638), and all other cohorts (0.648 vs 0.557, 0.674 vs 0.589). Calibration was modest. In the suspected infection cohort, the modified model classified more patients to sepsis (66.0 vs 62.5%) and identified more patients at risk of septic mortality than the SOFA score (92.6 vs 89.5%).ConclusionsAmong ED patients with suspected infection, sepsis, and septic shock, the newly-developed modified CV/total SOFA score had higher predictive validity and identified more patients at risk of septic mortality.
| S-EPMC9394016 | biostudies-literature
Project description:PurposeThe Quick Sequential Organ Failure Assessment (qSOFA) score proposed by Sepsis-3 as a sepsis screening tool has shown suboptimal accuracy. Heparin-binding protein (HBP) has been shown to identify early sepsis with high accuracy. Herein, we aim to investigate whether or not HBP improves the model performance of qSOFA.MethodsWe conducted a multicenter prospective observational study of 794 adult patients who presented to the emergency department (ED) with presumed sepsis between 2018 and 2019. For each participant, serum HBP levels were measured and the hospital course was followed. The qSOFA score was used as the comparator. The data was split into a training dataset (n = 556) and a validation dataset (n = 238). The primary endpoint was 30-day all-cause mortality.ResultsCompared with survivors, non-survivors had significantly higher serum HBP levels (median: 71.5 ng/mL vs 209.5 ng/mL, p < 0.001). Serum level of HBP weakly correlated with qSOFA class (r 2 = 0.240, p < 0.001). Compared with the qSOFA model alone, the addition of admission HBP level to the qSOFA model significantly improved 30-day mortality discrimination (AUC, 0.70 vs. 0.80; P < 0.001), net reclassification improvement [26% (CI, 17-35%); P < 0.001], and integrated discrimination improvement [12% (CI, 9-14%); P < 0.001]. Addition of C-reactive protein (CRP) level or neutrophil-to-lymphocyte ratio (NLR) to qSOFA did not improve its performance. A web-based mortality risk prediction calculator was created to facilitate clinical implementation.ConclusionThis study confirms the value of combining qSOFA and HBP in predicting sepsis mortality. The web calculator provides a user-friendly tool for clinical implementation. Further validation in different patient populations is needed before widespread application of this prediction model.
| S-EPMC9402998 | biostudies-literature
Project description:BackgroundIn 2010, the EUPHAS 2 collaborative group created a registry with the purpose of recording data from critically ill patients suffering from severe sepsis and septic shock treated with polymyxin-B hemoperfusion (PMX-HP) for endotoxin removal. The aim of the registry was to verify the application of PMX-HP in the daily clinical practice.MethodsThe EUPHAS 2 registry involved 57 centers between January 2010 and December 2014, collecting retrospective data of 357 patients (297 in Europe and 60 in Asia) suffering from severe sepsis and septic shock caused by proved or suspected infection related to Gram negative bacteria. All patients received atleast one cycle of extracorporeal endotoxin removal by PMX-HP.ResultsSeptic shock was diagnosed in 305 (85.4 %) patients. The most common source of infection was abdominal (44.0 %) followed by pulmonary (17.6 %). Gram negative bacteria represented 60.6 % of the pathogens responsible of infection. After 72 h from the first cycle of PMX-HP, some of the SOFA score components significantly improved with respect to baseline: cardiovascular (2.16 ± 1.77 from 3.32 ± 1.29, p < 0.0001), respiratory (1.95 ± 0.95 from 2.40 ± 1.06, p < 0.001) and renal (1.84 ± 1.77 from 2.23 ± 1.62, p = 0.013). Overall 28-day survival rate was 54.5 % (60.4 % in abdominal and 47.5 % in pulmonary infection). Patients with abdominal infection treated with PMX-HP within 24 h from the diagnosis of septic shock had a 28-day survival rate of 64.5 %. Patients showing a significantly cardiovascular improvement after PMX-HP had a 28-survival rate of 75 % in comparison to the 39 % of patients who did not (p < 0.001). Cox regression analysis found the variation of cardiovascular, respiratory and coagulation SOFA to be independent covariates for 28-day survival. In European patients were observed a higher 28-day (58.8 vs. 34.5 %, p = 0.003), ICU (59 vs. 36.7 %, p = 0.006) and hospital survival rate (53.2 vs. 35 %, p = 0.02) than in Asian patients. However, the two populations were highly heterogeneous in terms of source of infection and severity scores at admission.ConclusionThe EUPHAS 2 is the largest registry conducted outside Japan on the clinical use of PMX-HP in septic patients. Data analysis confirmed the feasibility of PMX-HP to treat septic patients in daily clinical practice, showing clinical benefits associated with endotoxin removal without significant adverse events related to the extracorporeal technique.
| S-EPMC4977232 | biostudies-literature
Project description:BackgroundSepsis is a common critical condition caused by the body's overwhelming response to certain infective agents. Many biomarkers, including the serum lactate level, have been used for sepsis diagnosis and guiding treatment. Recently, the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) recommended the Sequential Organ Failure Assessment (SOFA) and the quick SOFA (qSOFA) rather than lactate for screening sepsis and assess prognosis. Here, we aim to explore and compare the prognostic accuracy of the lactate level, the SOFA score and the qSOFA score for mortality in septic patients using the public Medical Information Mart for Intensive Care III database (MIMIC III).MethodsThe baseline characteristics, laboratory test results and outcomes for sepsis patients were retrieved from MIMIC III. Survival was analysed by the Kaplan-Meier method. Univariate and multivariate analysis was performed to identify predictors of prognosis. Receiver operating characteristic curve (ROC) analysis was conducted to compare lactate with SOFA and qSOFA scores.ResultsA total of 3713 cases were initially identified. The analysis cohort included 1865 patients. The 24-h average lactate levels and the worst scores during the first 24 h of ICU admission were collected. Patients in the higher lactate group had higher mortality than those in the lower lactate group. Lactate was an independent predictor of sepsis prognosis. The AUROC of lactate (AUROC, 0.664 [95% CI, 0.639-0.689]) was significantly higher than that of qSOFA (AUROC, 0.547 [95% CI, 0.521-0.574]), and it was similar to the AUROC of SOFA (AUROC, 0.686 [95% CI, 0.661-0.710]). But the timing of lactate relative to SOFA and qSOFA scores was inconsistent.ConclusionLactate is an independent prognostic predictor of mortality for patients with sepsis. It has superior discriminative power to qSOFA, and shows discriminative ability similar to that of SOFA.
| S-EPMC6492372 | biostudies-literature