Coupled Plasma Filtration Research Articles

Coupled Plasma Filtration and Adsorption treatment in COVID-19 patients with special health condition

Coupled Plasma Filtration and Adsorption treatment in COVID-19 patients with special health condition

Hemoperfusion in anesthesia and intensive care medicine: benefits, risks, and evidence for different systems

Hemoperfusion is atechnique for the extracorporeal elimination of endogenous and exogenous toxins and harmful mediators by adsorption. It can be used as astand-alone device, as part of aheart-lung machine or extracorporeal membrane oxygenation (ECMO) or, as is currently the case, integrated into akidney replacement procedure. In the meantime, various suppliers offer devices with different technologies. The aim of this work was to evaluate the benefits, risks and evidence of the different systems, how they work and for which indications they are approved in Germany. To achieve this goal, anarrative assessment of the existing literature and guidelines for different indications was performed. The focus was on in vivo studies. In principle, adistinction must be made in adsorption techniques between pure adsorption and the combination as adsorption and kidney replacement therapy. The adsorbers available in Germany include Cytosorb®, HA-330, Seraph®-100 and Toraymyxin. Combined procedures (adsorption and kidney replacement) are offered with coupled plasma filtration and adsorption (CPFA) and oXiris®. Most adsorbers have been developed for cytokine and endotoxin removal in patients with sepsis; however, to date, no randomized controlled trial (RCT) has demonstrated asurvival benefit when using hemoperfusion. Therefore, the S3 guidelines for treatment of sepsis and the surviving sepsis campaign guidelines advise against its routine use. When the corona pandemic began, hemoperfusion was considered as apromising therapeutic approach. Cytosorb®, Seraph®-100, and oXiris® received emergency approval by the FDA to be used in critically ill patients with COVID-19, so questions arose about the appropriateness and importance of its use; however, the data generated did not show positive results, so its use cannot be recommended routinely either. In addition, they are not mentioned as atreatment option in the current guidelines. The use of adsorption procedures in patients with liver failure and rhabdomyolysis has only been rudimentarily studied, so any evidence is currently lacking. The only adsorber that has CE approval in Germany for both applications is Cytosorb®. In the next few years, studies will have to follow that investigate the efficacy and thus either justify or refute the use in clinical routine. Hemoperfusion procedures are used in the heart-lung machine as part of cardiac surgery for either cytokine or anticoagulant adsorption. No congruent data are available to support the use for the elimination of cytokines. If emergency cardiac surgery is required in apatient with pre-existing anticoagulation, hemoperfusion procedures can be used to prevent bleeding complications. Cytosorb® has CE approval for this indication. All available techniques are nonselective adsorption processes, so that adsorption of known and unknown substances can occur. Unintentional adsorption of drugs, such as various anti-infective agents is arelevant risk, especially when used in patients with sepsis. Various adsorption systems can eliminate different known and unknown substances. Currently, there is alack of evidence for all indications and systems to justify their routine use except in clinical trials. Future clinical trials should evaluate the potential benefits but also dangers, so that in the meantime the routine use can be justified or arecommendation against the use can be given.

Alternative Treatment Method for Crimean Congo Hemorrhagic Fever: Coupled Plasma Filtration and Adsorption

Alternative Treatment Method for Crimean Congo Hemorrhagic Fever: Coupled Plasma Filtration and Adsorption

Antimicrobial Exposure in Critically Ill Patients with Sepsis-Associated Multi-Organ Dysfunction Requiring Extracorporeal Organ Support: A Narrative Review.

Sepsis is a leading cause of disability and mortality worldwide. The pathophysiology of sepsis relies on the maladaptive host response to pathogens that fosters unbalanced organ crosstalk and induces multi-organ dysfunction, whose severity was directly associated with mortality. In septic patients, etiologic interventions aiming to reduce the pathogen load via appropriate antimicrobial therapy and the effective control of the source infection were demonstrated to improve clinical outcomes. Nonetheless, extracorporeal organ support represents a complementary intervention that may play a role in mitigating life-threatening complications caused by sepsis-associated multi-organ dysfunction. In this setting, an increasing amount of research raised concerns about the risk of suboptimal antimicrobial exposure in critically ill patients with sepsis, which may be worsened by the concomitant delivery of extracorporeal organ support. Accordingly, several strategies have been implemented to overcome this issue. In this narrative review, we discussed the pharmacokinetic features of antimicrobials and mechanisms that may favor drug removal during renal replacement therapy, coupled plasma filtration and absorption, therapeutic plasma exchange, hemoperfusion, extracorporeal CO2 removal and extracorporeal membrane oxygenation. We also provided an overview of evidence-based strategies that may help the physician to safely prescribe effective antimicrobial doses in critically ill patients with sepsis-associated multi-organ dysfunction who receive extracorporeal organ support.

Clinical use of plasmafiltration coupled with adsorption

Coupled plasma filtration adsorption is an extracorporeal therapy that combines plasma separation and adsorption of inflammatory mediators and toxins, followed by hemofiltration to control volume overload and removal of small and medium-sized water-soluble mediators. Although it is not new, there are still doubts about its clinical role. Evidence indicates that the coupled plasma filtration adsorption is highly efficient in removing inflammatory molecules in sepsis. So far it has not been shown to reduce mortality, but it is possible to achieve a better hemodynamic benefit over convective therapies. On the other hand, the absorptive component makes it possible to purify larger mediators associated with causes of non-septic acute kidney injury, such as myoglobin, toxins associated with liver failure and others, allowing that coupled plasma filtration adsorption indications to be expanded to various clinical settings with a high inflammatory component, particularly when it is required to manage several organ dysfunctions simultaneously.

Coupled plasma filtration adsorption for the treatment of sepsis or septic shock: a systematic review and meta-analysis

BackgroundThe effect of coupled plasma filtration adsorption (CPFA) for the treatment of sepsis or septic shock is controversial. A systematic review and meta-analysis was performed to evaluate the impact of CPFA on all-cause mortality in patients with sepsis or septic shock.MethodsWe searched the PubMed, Cochrane, and Embase databases for randomized controlled trials (RCTs) and cohort studies from inception to the 1st of May 2022. We included studies involving patients (˃ 14 years) with sepsis or septic shock. All authors reported our primary outcome of all-cause mortality (hospital mortality, 28-day mortality or 30-day mortality). Results were expressed as odds ratio (OR) with accompanying 95% confidence interval (CI).ResultsSix studies including 537 patients were included. The primary outcome of this meta-analysis showed that the all-cause mortality was about 54.2% (119/243 in the CPFA group and 172/294 in the control group). There was no statistically significant difference in the all-cause mortality between two groups (odds ratio [OR] = 0.75; 95% CI 0.53 to 1.06; P = 0.11; Chi2 = 14.04; I2 = 64%).ConclusionsThe treatment of CPFA failed to decrease all-cause mortality of sepsis or septic shock patients. Further large-scale randomized controlled trials (RCTs) evaluating the ability of this therapy to improve clinical outcomes are still required to confirm these results.

Results of Coupled Plasma Filtration Adsorption (CPFA) Treatment Applied to Critical COVID-19 Patients in Intensive Care Unit

Objective: The novel coronavirus, called SARS-CoV-2, causes COVID-19 disease and began a pandemic on a global scale. Uncontrolled cytokine production is observed especially in COVID-19 cases with severe progression and this situation is thought to be one of the causes of more severe disease progression and increased mortality.
 In our study, we aimed to assess the efficacy of Coupled Plasma Filtration Adsorption (CPFA) treatment in situations with severe disease progression like sepsis, septic shock and multiple organ failure, considered to be secondary to cytokine storm, in COVID-19 disease.
 Methods: Our study retrospectively screened data from 20 patients admitted to our intensive care unit and administered CPFA. CPFA was administered as 10 hours each session and 2 sessions with 12 hours interval.
 Results: After our CPFA treatment, there were statistically significant ameliorations in clinical and laboratory findings like SOFA scores, mainly, Horowitz values, fever and IL-6 values.
 Conclusion: The CPFA treatment removes the uncontrolled production of harmful cytokines/chemokines and toxic substances from the blood and shows promise in the treatment of the cytokine storm that develops in COVID-19 disease.

High dose coupled plasma filtration and adsorption in septic shock patients. Results of the COMPACT-2: a multicentre, adaptive, randomised clinical trial.

This study aimed at evaluating the efficacy and safety of high-dose (> 0.2 L/kg of treated plasma per day) coupled plasma filtration-adsorption (CPFA) in treating patients with septic shock. Multicentre, randomised, adaptive trial, performed in 12 Italian intensive care units (ICUs). Patients aged 14 or more, admitted to the ICU with septic shock, or had developed it during the stay were eligible. The final outcome was mortality at discharge from the last hospital at which the patient received care. Between May 2015, and October 2017, 115 patients were randomised. The first interim analysis revealed a number of early deaths, prompting an unplanned analysis. Last hospital mortality was non-significantly higher in the CPFA (55.6%) than in the control group (46.2%, p = 0.35). The 90-day survival curves diverged in favour of the controls early after randomisation and remained separated afterwards (p = 0.100). An unplanned analysis showed higher mortality in CPFA compared to controls among patients without severe renal failure (p = 0.025); a dose-response relationship was observed between treated plasma volume and mortality (p = 0.010). The COMPACT-2 trial was stopped due to the possible harmful effect of CPFA in patients with septic shock. The harmful effect, if present, was particularly marked in the early phase of septic shock. Patients not requiring renal replacement therapy seemed most exposed to the possible harm, with evidence of a dose-response effect. Until the mechanisms behind these results are fully understood, the use of CPFA for the treatment of patients with septic shock is not recommended.

Effect of Extracorporeal Blood Purification on Mortality in Sepsis: A Meta-Analysis and Trial Sequential Analysis

Objective: The objective of this study was to conduct a meta-analysis and trial sequential analysis (TSA) of published randomized controlled trials (RCTs) to determine whether mortality benefit exists for extracorporeal blood purification techniques in sepsis. Data Sources: A systematic search on MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for RCTs was performed. Study Selection: RCTs investigating the effect of extracorporeal blood purification device use on mortality among critically ill septic patients were selected. Data Extraction: Mortality was assessed using Mantel-Haenszel models, and I2 was used for heterogeneity. Data are presented as odds ratios (OR); 95% confidence intervals (CIs); p values; I2. Using the control event mortality proportion, we performed a TSA and calculated the required information size using an anticipated intervention effect of a 14% relative reduction in mortality. Data Synthesis: Thirty-nine RCTs were identified, with 2,729 patients. Fourteen studies used hemofiltration (n = 789), 17 used endotoxin adsorption devices (n = 1,363), 3 used nonspecific adsorption (n = 110), 2 were cytokine removal devices (n = 117), 2 used coupled plasma filtration adsorption (CPFA) (n = 207), 2 combined hemofiltration and perfusion (n = 40), and 1 used plasma exchange (n = 106). On conventional meta-analysis, hemofiltration (OR 0.56 [0.40–0.79]; p < 0.001; I2 = 0%), endotoxin removal devices (OR 0.40 [0.23–0.67], p < 0.001; I2 = 71%), and nonspecific adsorption devices (OR 0.32 [0.13–0.82]; p = 0.02; I2 = 23%) were associated with mortality benefit, but not cytokine removal (OR 0.99 [0.07–13.42], p = 0.99; I2 = 64%), CPFA (OR 0.50 [0.10–2.47]; p = 0.40; I2 = 64%), or combined hemofiltration and adsorption (OR 0.71 [0.13–3.79]; p = 0.69; I2 = 0%). TSA however revealed that based on the number of existing patients recruited for RCTs, neither hemofiltration (TSA-adjusted CI 0.29–1.10), endotoxin removal devices (CI 0.05–3.40), nor nonspecific adsorption devices (CI 0.01–14.31) were associated with mortality benefit. Conclusion: There are inadequate data at present to conclude that the use of extracorporeal blood purification techniques in sepsis is beneficial. Further adequately powered RCTs are required to confirm any potential mortality benefit, which may be most evident in patients at greatest risk of death.

TO013ADSORPTION THERAPY AND SEPTIC SHOCK: A RETROSPECTIVE STUDY COMPARING COUPLED PLASMA FILTRATION-ADSORPTION AND CYTOSORB

Abstract Background and Aims Septic shock is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Excessive release of cytokines and other inflammatory mediators is a key mechanism and cytokines adsorption therapies are applied in this context to restore a balanced immune homeostasis. Different adsorption techniques are available but there are no studies comparing these different adsorption approaches. The aim of this retrospective observational study was to compare Coupled Plasma Filtration Adsorption (CPFA) and CytoSorbTM in terms of hemodynamic and clinical response, mortality and renal function recovery. Method A retrospective observational study was designed enrolling all patients admitted to ICU with a diagnosis of septic shock treated with blood adsorption, either CPFA or CytoSorbTM, from January 2015 to December 2017. Primary endpoints of the study were the assessment of changes in NE dosage, MAP values, SOFA score and PCT levels before and after blood adsorption. Secondary endpoints ICU length of stay (LOS), mortality at 30, 60 and 90 days from adsorption initiation; renal outcome at 30 and 90 days from adsorption initiation. Results The study included 28 patients (14 CPFA, 14 CytosorbTM). Adsorption treatment was associated with a significant (p=0.03) improvement in hemodynamics with a Norepinephrine/Mean Arterial Pressure ratio (NE/MAP) of 0.64 (0.14-2.6) pre-treatment vs 0.11 (0.0-0.32) post-treatment regardless of the applied technique. Furthermore, a significant (p&amp;lt;0.001) procalcitonin (PCT) post treatment reduction was demonstrated with a comparable effect in the two groups (p=0.32) (Fig.1). No difference has been found in SOFA score changes (p=0.06) and again without any difference between groups (p=0.17). Overall Survival (OS) rate at 30 days was comparable between groups being 64.3% in CPFA and 78.6% in CytoSorbTM group (p=0.34). Finally, a complete recovery of kidney function at 30 and 90 days has been obtained in respectively 90% and 100% of survived patients without any difference between groups (p=1.00) (Fig.2). Conclusion These data confirmed the effectiveness of adsorption in terms of short-term clinical improvement independently from the applied technique, supporting the role of both these adjunctive therapies in septic shock treatment. CPFA and CytosorbTM have comparable effects in terms of hemodynamic improvement, clinical outcome, mortality and recovery of kidney function from septic shock AKI.

Coupled-plasma filtration and adsorption for severe burn patients with septic shock and acute kidney injury treated with renal replacement therapy

BackgroundCoupled-plasma filtration adsorption (CPFA) is a sorbent-based technology aimed at removing soluble mediators of septic shock. We present our experience on the use of CPFA in septic shock severe burn patients with acute kidney injury (AKI) needing renal replacement therapy (RRT) with the main goal to evaluate efficacy and safety of CPFA in this specific subset of septic shock patients. MethodsIn this observational study, we retrospectively reviewed the medical notes of all burn patients admitted to our adult Burn Center who received CPFA, as part of the septic shock treatment requiring RRT, between January 2001 and December 2017 (CPFA group).We compared CPFA group with all the burn patients admitted to our Center in the same period of time, with the same range of relevant clinical characteristics, who developed AKI and were treated with RRT, but not CPFA (control group). We collected demographic characteristics, burn size, Sequential Organ Assessment Failure (SOFA) score, microbiological data, and patient outcome, in terms of in-hospital mortality rate and the probability of survival calculated using the revised Baux score. We also collected data regarding CPFA safety (hemorrhagic episodes, catheter associated-complications, hypersensitivity reactions) and efficiency (number and duration of CPFA sessions, plasma treated amount, plasma processed dose). Results39 severe burn patients were treated with CPFA (CPFA group) (mean age 46.0 years, range 40.0–56.0 years; mean burn size 48.0% TBSA, range 35.0–60.0% TBSA), and 87 patients treated with RRT, but not CPFA, who had similar clinical characteristics (control group). Observed mortality rate was 51.3% in the CPFA group and 77.1% in the control group (p 0.004). Regarding factors affecting survival in the CPFA group, SOFA score on the 1st day of CPFA resulted significant (OR 2.016, 95% CI, 1.221–3.326; p < 0.004) in the multivariate analysis logistic model. ConclusionsCPFA treatment for burn patients with AKI-RRT and septic shock, sustained by bacterial strains non or poorly responsive to therapy, was associated with a lower mortality rate, compared to RRT alone. However, further research, such as large prospective studies, is required to clarify the role of CPFA in the treatment of burns with septic shock and AKI-RRT.

LPS-Binding Protein Modulates Acute Renal Fibrosis by Inducing Pericyte-to-Myofibroblast Trans-Differentiation through TLR-4 Signaling.

During sepsis, the increased synthesis of circulating lipopolysaccharide (LPS)-binding protein (LBP) activates LPS/TLR4 signaling in renal resident cells, leading to acute kidney injury (AKI). Pericytes are the major source of myofibroblasts during chronic kidney disease (CKD), but their involvement in AKI is poorly understood. Here, we investigate the occurrence of pericyte-to-myofibroblast trans-differentiation (PMT) in sepsis-induced AKI. In a swine model of sepsis-induced AKI, PMT was detected within 9 h from LPS injection, as evaluated by the reduction of physiologic PDGFRβ expression and the dysfunctional α-SMA increase in peritubular pericytes. The therapeutic intervention by citrate-based coupled plasma filtration adsorption (CPFA) significantly reduced LBP, TGF-β, and endothelin-1 (ET-1) serum levels, and furthermore preserved PDGFRβ and decreased α-SMA expression in renal biopsies. In vitro, both LPS and septic sera led to PMT with a significant increase in Collagen I synthesis and α-SMA reorganization in contractile fibers by both SMAD2/3-dependent and -independent TGF-β signaling. Interestingly, the removal of LBP from septic plasma inhibited PMT. Finally, LPS-stimulated pericytes secreted LBP and TGF-β and underwent PMT also upon TGF-β receptor-blocking, indicating the crucial pro-fibrotic role of TLR4 signaling. Our data demonstrate that the selective removal of LBP may represent a therapeutic option to prevent PMT and the development of acute renal fibrosis in sepsis-induced AKI.

Efficacy of Coupled Plasma Filtration Adsorption in Treating Patients with Severe Intra-Abdominal Infection: A Retrospective Study.

Background: Coupled plasma filtration adsorption (CPFA) is an extracorporeal treatment based on plasma filtration associated with an adsorbent cartridge and hemofiltration. CPFA is able to remove inflammatory mediators and it has been used to treat severe sepsis and multiple organ dysfunction. Limited experience exists on the use of CPFA in treating intra-abdominal infection (IAI). Methods: In this study, the efficacy of CPFA in treating patients with severe IAI and liver failure was evaluated in a retrospective analysis of 76 cases. Results: The survival rate of patients treated with CPFA was 82.6%, with effective removal of endotoxin and inflammatory mediators. Conclusion: Our data suggest that CPFA can be safely and effectively used to lower morbidity and mortality rates of patients with severe IAI and liver failure.

LPS removal reduces CD80-mediated albuminuria in critically ill patients with Gram-negative sepsis.

LPS-induced sepsis is a leading cause of acute kidney injury (AKI) in critically ill patients. LPS may induce CD80 expression in podocytes with subsequent onset of proteinuria, a risk factor for progressive chronic kidney disease (CKD) frequently observed after AKI. This study aimed to investigate the therapeutic efficacy of LPS removal in decreasing albuminuria through the reduction of podocyte CD80 expression. Between January 2015 and December 2017, 70 consecutive patients with Gram-negative sepsis-induced AKI were randomized to either have coupled plasma filtration and adsorption (CPFA) added to the standard care ( n = 35) or not ( n = 35). To elucidate the possible relationship between LPS-induced renal damage, proteinuria, and CD80 expression in Gram sepsis, a swine model of LPS-induced AKI was set up. Three hours after LPS infusion, animals were treated or not with CPFA for 6 h. Treatment with CPFA significantly reduced serum cytokines, C-reactive protein, procalcitonin, and endotoxin levels in patients with Gram-negative sepsis-induced AKI. CPFA significantly lowered also proteinuria and CD80 urinary excretion. In the swine model of LPS-induced AKI, CD80 glomerular expression, which was undetectable in control pigs, was markedly increased at the podocyte level in LPS-exposed animals. CPFA significantly reduced LPS-induced proteinuria and podocyte CD80 expression in septic pigs. Our data indicate that LPS induces albuminuria via podocyte expression of CD80 and suggest a possible role of timely LPS removal in preventing the maladaptive repair of the podocytes and the consequent increased risk of CKD in sepsis-induced AKI.

OC36 IMPROVEMENT OF HAEMODYNAMIC AND RESPIRATORY PARAMETERS DURING COUPLED PLASMA FILTRATION AND ADSORPTION (CPFA) AND CORRELATION WITH CLEARANCE OF THE INFLAMMATORY MEDIATORS IN SEPTIC PATIENTS: A PROPENSITY MATCHED STUDY

Abstract Background and aim: Sepsis is a severe complication in cardiac surgery, but data on new therapies are inconclusive and new tretments are warranted. Coupled plasma filtration adsorption (CPFA) is a new extracorporeal technology which combines plasma filtration and ultrafiltration. The aim of this study is to evaluate in septic patients submitted to CPFA: Methods: Overall coohort study and a propensity–matched analysys included 96 patients admitted to three ICU with a diagnosis of septic shock. 73 patients were submitted to CPFA and 23 patients to RRT. In the CPFA group Heparine ev was used as anticoagulant in 22 patients and citrate in 11. In the RRT group Heparine was used in all the patients. IL-6, Procalcitonin, cardiorespiratory indices and SOFA score were compared before (T0) and at the end of the treatments (T1). Results: Of 73 patients submitted to CPFA 32 could be matched to the 22 septic patients who received RRT. 10 patients in the CPFA group experienced clotting of the adsorbing filter. Results are shown in table. Conclusions: Data from this study confirm that CPFA improves haemodynamics during septic shock. This improvement may be related to the reduction of IL-6 and of Procalcitonin. As shown in previous studies, clotting of the filter is an important problem. Anticoagulation with citrate may improve the patency of the circuit.

TREATMENT OF SEVERE HYPERBILIRUBINEMIA THROUGH COUPLED PLASMA FILTRATION ADSORPTION

The development of severe hyperbilirubinemia after cardiac surgery performed with cardiopulmonary bypass is a possible life-threatening challenging complication because its mechanism is still not completely clarified, and there are only a few specific therapies available for acute hepatobiliary injury. Here, we report the case of an 80-year-old male scheduled for elective aortic valve replacement, during the 1st post-operative day (POD 1), developed acute systo-diastolic cardiac failure, with a severe aortic paravalvular leak. The surgeon decided reoperation to correct prosthesis dehiscence. There was a continuous total serum bilirubin increase, with a peak value of 24.50 mg/dl on POD 16. It was diagnosed as a “cholestatic post-cardiac surgery syndrome,” and we performed seven cycles of coupled plasma filtration adsorption (CPFA), with definitive stable bilirubinemia reduction to 3.0 mg/dl at the discharge. CPFA was found to be a good hemodepurative technique to manage successfully severe hyperbilirubinemia of “cholestatic post-cardiac surgery syndrome.”

Influence of Timing of Initiation and Volume of Processed Plasma on the Outcome of Septic Shock Patients Treated with Coupled Plasma Filtration and Adsorption

Background: The extracorporeal removal of mediators is a rescue strategy for septic shock patients, which is still under investigation. Several techniques are available: coupled plasma filtration and adsorption (CPFA) combines plasma processing with renal replacement therapy. Methods: The study aimed to elucidate the role of both timing of initiation and intensity of treatment on the outcome, for which we retrospectively studied 52 patients. We collected the overall pre-CPFA time interval, starting from the first episode of hypotension in the wards and the volume of processed plasma (Vp), which we used as a proxy for intensity of treatment. Results: Timing of initiation did not significantly differ between survivors and non-survivors (25 vs. 27 h), while the Vp did (0.25 vs. 0.17 L/kg/session, p < 0.05). The significance of Vp was confirmed by a multiple logistic regression model. Conclusion: Our study confirms that intensity of CPFA, but not its timing of initiation, correlates with survival of septic shock patients.

Immune disorders in sepsis and their treatment as a significant problem of modern intensive care.

Despite the great advances in the treatment of sepsis over the past 20 years, sepsis remains the main cause of death in intensive care units. In the context of new possibilities of treating sepsis, a comprehensive response of the immune system to the infection, immunosuppression, in particular, has in recent years gained considerable interest. There is vast evidence pointing to the correlation between comorbid immunosuppression and an increased risk of recurrent infections and death. Immune disorders may impact the clinical course of sepsis. This applies in particular to patients with deteriorated clinical response to infections. They usually suffer from comorbidities and conditions accompanied by immunosuppression. Sepsis disrupts innate and adaptive immunity. The key to diagnose the immune disorders in sepsis and undertake targeted immunomodulatory therapy is to define the right biomarkers and laboratory methods, which permit prompt "bedside" diagnosis. Flow cytometry is a laboratory tool that meets these criteria. Two therapeutic methods are currently being suggested to restore the immune homeostasis of sepsis patients. Excessive inflammatory response may be controlled through extracorporeal blood purification techniques, in large part derived from renal replacement therapy. These are such techniques as high-volume haemofiltration, cascade haemofiltration, plasma exchange, coupled plasma filtration and adsorption, high-absorption membranes, high cut-off membranes. The main task of theses techniques is the selective elimination of middle molecular weight molecules, such as cytokines. Pharmacotherapy with the use of such immunostimulants as interleukin 7, granulocyte-macrophage colony-stimulating factor, interferon gamma, PD-1, PD-L1 and CTLA-4 antagonists, intravenous immunoglobulins may help fight immunosuppressive immune disorders.

Study of coupled plasma filtration adsorption therapy for patients with severe infection and multiple organ dysfunction syndromes

Objective To investigate the effect of coupled plasma filtration adsorption (CPFA) on plasma cytokines: TNF-α, IL-1β, IL-6, cellular immunity, blood lactate acid concentration, heart rate, respiration rate, oxygenation index, hemodynamics, blood cells counts, and prognosis in patients with multiple organ dysfunction syndromes (MODS). Methods This was a prospective, randomized clinical trial in 45 patients diagnosed as MODS. Patients were randomly assigned to hemoperfution with resin adsorption (HP)+ continuous venous-venous hemofiltration (CVVH) group, CPFA group and CVVH group. The general clinical data, APACHE Ⅱ score, number of failure organ and previous mentioned biomarkers were documented. Blood samples were collected before and after blood filtration with any one of these procedures. The plasma samples were isolated and stored with frozen at -60 ℃. Data were statistically analyzed with SPSS 13.0 version software. Results In CPFA group, plasma cytokines, TNF-α、IL-1β、IL-6, decreased markedly after plasma adsorption for two hours (P<0.01); and plasma concentrations of IL-6 were further descended after subsequent CVVH for 10 hours (P<0.05). In HP+ CVVH group, plasma cytokines, TNF-α、IL-1β、IL-6, decreased markedly after HP (P<0.01), and plasma concentrations of IL-6 were further descended after subsequent CVVH for 10 hours (P<0.05). In CVVH group, plasma cytokines, TNF-α、IL-1β、IL-6, decreased after CVVH for 12 hours (P<0.05). Blood lactate acid concentration, heart rate, respiration rate, oxygenation index, T-lymphocytes subgroups (CD3+ , CD4+ , CD8+ , CD4+ /CD8+ ratio), clinical symptoms were improved and dose of vasoactive agent was reduced in the patients of three groups without differences among them. The counts of red blood cells, white blood cells and platelets after CPFA and CVVH showed no significant changes. There was no significant difference in blood cell counts between CPFA and CVVH groups. After HP+ CVVH, there was a trend of decrease in platelet count (P<0.05). Platelet counts were significantly higher in patients treated with CPFA and CVVH group than those in patients treated with HP+ CVVH group (P<0.05). There were 6 patients died in HP + CVVH group, 6 patients died in CPFA group and 5 patients died in CVVH group within 28days. Conclusions The comparison of efficacy of blood filtration among 3 modalities of HP+ CVVH, CPFA and CVVH showed CPFA had higher capacity of Inflammatory medium scavenging than CVVH, and had less damage effect on blood visible component , especially on platelet compared with HP+ CVVH. CPFA was an effective and safety modality in the treatment of the patients with multiple organ dysfunction syndrome. Key words: Hemoperfusion with resin adsorption; Coupled plasma filtration adsorption; Continuous venous-venous hemofiltration; Multiple organ dysfunction syndromes; Cytokines

The Hematocrit Affects the Volume of Plasma Treated With Coupled Plasma Filtration and Adsorption With Predilution.

Coupled plasma filtration and adsorption (CPFA) is an extracorporeal blood purification technique proposed for the treatment of septic-shock. By removing pro- and anti-inflammatory mediators from plasma, CPFA is supposed to have a therapeutic effect on the abnormal inflammatory response seen in this condition. Recently, blood predilution with citrate solution has been adopted to prevent clotting in the CPFA circuit-one of the main problems of the technique. Taking into account the patient's hematocrit, we worked out a formula for the volume of plasma effectively treated by CPFA after predilution. Neglecting this effect, as is commonly done, introduces significant distortions in the estimation of the volume, possibly causing under-treatment. The distortion is stronger when the hematocrit and the predilution fraction are large and weaker when both values shrink. By correctly indicating the daily dose of plasma adsorption received by patients, this formula is essential for assessing the therapeutic efficacy of CPFA and, subsequently, establishing its optimal doses.