Coupled Plasma Filtration Adsorption Research Articles

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.

International clinical research of critical care medicine in 2021

The progress of critical care medicine in 2021 is still encouraging. The new international guideline for management of sepsis and septic shock came out after 4 years. Besides, a couple of preferable clinical evidences were released including restrictive blood transfusion strategy for patients with acute myocardial infarction, prevention of peripheral venous catheter infection, heparin inhalation and driving pressure setting in patients with acute respiratory distress syndrome (ARDS), lower oxygenation target for acute hypoxemic respiratory failure, low level positive end-expiratory pressure in non-ARDS patients with respiratory failure, light sedation or non-sedation strategy, biological phenotypes, as well machine learning in sepsis and ARDS. However, we also encounter negative results such as balanced solution during fluid resuscitation, hypothermia therapy after out-of-hospital cardiac arrest or traumatic brain injury, adrenomedullin-specific antibody adrecizumab therapy and coupled plasma filtration-adsorption (CPFA) therapy for patients with septic shock, extracorporeal carbon dioxide removal (ECCO2R) implementation in acute hypoxic respiratory failure, continuous infusion of hypertonic saline in patients with traumatic brain injury. Collectively, in the future, individualized diagnosis and management based on the principle of "wise choice" will become the daily practice scene for all intensivists.

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.

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.

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.”

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

Chemical and microbiological stability, anticoagulant efficacy and toxicity of 35 and 90 mM trisodium citrate solutions stored in plastic syringes

BackgroundTrisodium citrate is an interesting alternative to heparin for the prevention of circuit clotting during extracorporeal procedures, but some protocols require non-commercially available citrate concentrations. Little published information is available...

The Use of Coupled Plasma Filtration Adsorption in Traumatic Rhabdomyolysis

Severe musculoskeletal injuries induce the release of sarcoplasmic elements such as muscle enzymes, potassium, and myoglobin in the systemic circulation. The circulating myoglobin damages the glomerulus and renal tubules. Conventional haemodialysis is not able to remove myoglobin, due to its high molecular weight (17,8 kilodaltons [kDa]). We treated four traumatic rhabdomyolysis patients with Coupled Plasma Filtration Adsorption (CPFA) in order to remove myoglobin followed by 14 hours of Continuous Veno-Venous Hemofiltration (CVVH). During the treatment, all patients showed clinical improvement with a decrease in muscular (creatine kinase [CK] and myoglobin) and renal (creatinine and potassium) damage indices. One patient, in spite of full renal recovery, died of cerebral haemorrhage on the 26th day of hospital stay.

Extracorporeal Sorbent Technologies: Basic Concepts and Clinical Application.

Limitations imposed by the characteristics of some solutes and the structure of dialysis membranes have spurred new interest in the use of mechanisms beyond diffusion and convection for extracorporeal solute removal. Sorbents have been utilized for more than 50 years in extracorporeal blood treatments for specific purposes, and better understanding of their basic aspects may further expand the potential for their clinical application. In this chapter, the basic principles applying to sorbents are discussed, including composition and structure, along with the fundamental mechanisms of solute removal. The critical importance of sorbent biocompatibility is also highlighted. With these basic principles in mind, the clinical application of sorbents is discussed, with an emphasis on the use of hemoperfusion and coupled plasma filtration-adsorption for sepsis-related disorders. Finally, new sorbent-based clinical approaches for acute conditions and end-stage renal disease are presented, emphasizing that sorbent technologies may assume a larger role for a variety of clinical disorders in the future.

Nano-LC–MS/MS for the identification of proteins trapped in sorbent cartridges used for coupled plasma filtration-adsorption treatments of healthy pigs

A dedicated proteomic approach based on nano-Liquid Chromatography coupled with tandem mass spectrometry in ion trap is proposed for the analysis of proteins trapped in sorbent resin cartridges used to remove inflammatory mediators from blood by coupled plasma filtration adsorption (CPFA). The final purpose of the proposed proteomic approach was to obtain a reference map of plasma proteins trapped in CPFA sorbents used for the extracorporeal blood purification of healthy pigs, with the potential impact to design new bio-filters able to control the inflammatory imbalance under pathological conditions, such as severe sepsis. The five main steps of the proteomics analysis, (i) protein extraction from resin cartridges, (ii) two-dimensional gel electrophoresis (2D-PAGE) for protein separation and profiling, (iii) in-gel proteolytic digestion, (iv) tandem mass analysis of peptides resulting from enzymatic cleavage and (v) bioinformatics, for protein identification and post-processing validation of MS/MS data sets, have been carefully evaluated. Prior to electrophoresis, the efficiency of different extraction solutions and procedures to recovery plasma proteins trapped into the sorbents were tested. Then, a rapid one-step procedure for protein extraction was optimized. Protein bands corresponding to the main plasma proteins, namely porcine serum albumin, serotransferrin and immunoglobulins, were identified. In addition, the presence of haptoglobin, hemopexin, α-1 acid glycoprotein and fetuin-A, that are known as acute-phase reaction proteins, was observed, suggesting that CPFA resins led to a non-specifically protein depletion from plasma, rather than targeting specific molecules.

Mortality Reduction in Septic Shock by Plasma Adsorption (ROMPA): a protocol for a randomised clinical trial.

IntroductionThere is a lack of evidence in the efficacy of the coupled plasma filtration adsorption (CPFA) to reduce the mortality rate in septic shock. To fill this gap, we have designed the ROMPA study (Mortality Reduction in Septic Shock by Plasma Adsorption) to confirm whether treatment with an adequate dose of treated plasma by CPFA could confer a clinical benefit.Methods and analysisOur study is a multicentric randomised clinical trial with a 28-day and 90-day follow-up and allocation ratio 1:1. Its aim is to clarify whether the application of high doses of CPFA (treated plasma ≥0.20 L/kg/day) in the first 3 days after randomisation, in addition to the current clinical practice, is able to reduce hospital mortality in patients with septic shock in intensive care units (ICUs) at 28 and 90 days after initiation of the therapy. The study will be performed in 10 ICUs in the Southeast of Spain which follow the same protocol in this disease (based on the Surviving Sepsis Campaign). Our trial is designed to be able to demonstrate an absolute mortality reduction of 20% (α=0.05; 1−β=0.8; n=190(95×2)). The severity of the process, ensuring the recruitment of patients with a high probability of death (50% in the control group), will be achieved through an adequate stratification by using both severity scores and classical definitions of severe sepsis/septic shock and dynamic parameters. Our centres are fully aware of the many pitfalls associated with previous medical device trials. Trying to reduce these problems, we have developed a training programme to improve the CPFA use (especially clotting problems).Ethics and disseminationThe protocol was approved by the Ethics Committees of all the participant centres. The findings of the trial will be disseminated through peer-reviewed journals, as well as national and international conference presentations.Trial registration numberNCT02357433; Pre-results.

Coupled plasma filtration adsorption improves hemodynamics in septic shock

PurposeSeptic shock involves a dysregulation of the immune response to an infection. This may lead to hemodynamic dysfunction and multiple-organ failure. The main aim of this study was to evaluate the effect of coupled plasma filtration adsorption (CPFA) on the hemodynamic profile in patients with septic shock. Materials and methodsWe retrospectively analyzed data from 21 adult patients admitted to the intensive care unit with a diagnosis of septic shock, comparing data between pre-CPFA and post-CPFA treatment. They received a maximum of 5 cycles of treatment. ResultsCoupled plasma filtration adsorption treatment was associated with a significant increase of mean arterial pressure (P < .001), reduction of the vasoactive/inotropic requirement (P = .007), and renal improvement. In patients with leukocytosis or leucopenia, the leukocyte count was restored to a reference range of values. ConclusionTreatment with CPFA improves hemodynamic parameters in septic shock patients, ameliorating organ failure.

Citrate pharmacokinetics at high levels of circuit citratemia during coupled plasma filtration adsorption.

The heparin requirement for coupled plasma filtration adsorption (CPFA) is usually high. Heparin administration often cannot be adherent to prescription, leading to a premature clotting of circuit and an insufficient volume of treated plasma. Regional citrate anticoagulation (RCA) could be an attractive alternative; however, no data are available on citrate pharmacokinetics at high levels of circuit citratemia. Fifteen septic shock patients with acute kidney injury undergoing CPFA with RCA at target circuit citratemia of 6 mmol/L were treated with CPFA-haemofiltration in pure predilution (CPFA-HF predilution group, n = 5 patients), or predilution haemodiafiltration (CPFA-HDF predilution group, n = 5 patients) or pre- and postdilution haemofiltration (CPFA-HF pre/postdilution group, n = 5 patients). Citrate pharmacokinetics was carried out through its determination in systemic and circuit blood, and effluent at time 0, 0.2, 1, 3, 6 and 9 h. The systemic concentrations of citrate in the CPFA-HF predilution group significantly increased over the sessions (from basal level of 0.21 to 0.76 mmol/L at 3 h), whereas they did not change in CPFA-HDF predilution and CPFA-HF pre/postdilution groups. Circuit plasma citrate concentrations (from 3 to 8 mmol/L) correlated strongly with circuit iCa++ levels (Spearman R = -0.7022, P < 0.01). Sieving coefficients of citrate were near the unit in all three groups and unrelated to blood and infusion flow rates in predilution. However, the amount of citrate removed by effluent was ∼40% for the CPFA-HF predilution group and reached 60% for both the CPFA-HDF predilution and CPFA-HF pre/postdilution groups (P < 0.05). As for the efficiency of plasmafiltration, the plasmafiltrate volume (from 17 to 20 mL/kg/day) was not significantly different among the groups. These results demonstrated that in refractory septic shock patients on CPFA at circuit citratemia of 6 mmol/L both HDF predilution and HF pre/postdilution were the best dialysis modalities to maintain a normal systemic citratemia through a high rate of citrate loss in the effluent.

Extracorporeal blood therapy in sepsis and acute respiratory distress syndrome: the “purifying dream”

Objective To discuss the rationale, hypothesis, modality of extracorporeal blood purification (EBP) techniques for the critically ill animal models or patients, and to summarize the experimental and clinical studies with inconsistent data which explored the EBP's efficacy in the areas of critical care medicine. Data sources Articles referred in this review were collected from the database of PubMed published in English up to June 2014. Study selection We had done a literature search by using the term “(sepsis OR acute lung injury OR acute respiratory distress syndrome) AND (extracorporeal blood purification OR hemofiltration OR hemoperfusion OR plasma exchange OR plasmapheresis OR adsorpiton)”. Related original or review articles were included and carefully analyzed. Results Acute cellular and humoral immune disturbances occur in both sepsis and acute respiratory distress syndrome (ARDS). Treatments aimed at targeting one single pro-/anti-inflammatory mediator have largely failed with no proven clinical benefits. Such failure shifts the therapeutic rationale to the nonspecific, broad-spectrum methods for modulating the over-activated inflammatory and anti-inflammatory response. Therefore, EBP techniques have become the potential weapons with high promise for removing the circulating pro-/anti-inflammatory mediators and promoting immune reconstitution. Over the years, multiple extracorporeal techniques for the critically ill animal models or patients have been developed, including hemofiltration (HF), high-volume hemofiltration (HVHF), high-cutoff hemofiltration (HCO-HF), hemo-perfusion or -adsorption (HP/HA), coupled plasma filtration adsorption (CPFA), and plasma exchange (PE). These previous studies showed that EBP therapy was feasible and safe for the critically ill animal models or patients. However, data on their efficacy (especially on the clinical benefits, such as mortality) were inconsistent. Conclusions It is not now to conclude that EBP intervention can purify septic or ARDS patients with high clinical efficacy from current experimental and clinical practice. Prospective, randomized controlled, and well-designed clinical or experimental studies and most suitable EBP modalities should be further developed.