Blood Purification最新文献

Introduction Sepsis and sepsis-associated acute kidney injury (AKI) are associated with increased patient morbidity and mortality. The immediate host response aimed at combating infection can become dysregulated, leading to uncontrolled inflammation and multi-organ failure, including AKI. Therapies targeting one protein component of the sepsis pathway have largely failed to improve patient outcomes, and currently only organ support therapies are used clinically to provide time for innate organ recovery to occur. The Selective Cytopheretic Device (SCD) is a continuous cell processing immunomodulatory device that attracts activated neutrophils and monocytes its biomimetic membrane surface. The activated leukocytes are transformed to a less pro-inflammatory phenotype and released back into the circulation when exposed to low ionized calcium concentration established in the SCD by standard regional citrate anticoagulation protocols used in continuous renal replacement therapy. Review In this review, we detail the history of the SCD and our experience with it, from discovery to pre-clinical testing to translational research application at the bedside. We discuss the SCD mechanism of action, its immunomodulatory effect, and the human studies involving critically ill adult pediatric patients with AKI who require continuous renal replacement therapy as part of the standard of care. We conclude discussing ongoing and future application of the SCD in both acute and chronic inflammatory states that would benefit from immunomodulation.

Background: There is growing interest in hemoadsorption (HA) therapies in critically ill patients although their precise indications remain to be established. Several devices are available on the market with heterogeneous properties and capabilities.

Summary: Due to the nonspecific removal associated with most HA techniques, concerns have been raised on their unintended removal of drugs such as anti-infectives in sepsis. On the other hand, drug removal might be beneficial in certain situations for instance antithrombotic medications in patients requiring emergency surgery or in case of accidental or self-induced intoxication. In this review, we summarize available in vitro, in vivo, and clinical studies reporting on the influence of various HA techniques on drugs pharmacokinetics.

Key message: We conclude that further studies should aim at providing drug dosing recommendations during HA and confirm its safety, efficacy, and practicalities when used for intoxications.

Background: Despite significant efforts to improve outcomes for patients with sepsis and septic shock, mortality rates remain alarmingly high.

Summary: Beyond standard management, novel adjuvant treatments seek to improve outcomes through a personalized approach. Among these, immunomodulation strategies aim to reestablish a balance in the dysregulated immune system, managing both pro-inflammatory and anti-inflammatory mediators. In recent years, various techniques utilizing extracorporeal circuits equipped with filters or cartridges, collectively referred to as blood purification therapies, have been developed and introduced to the market. Hemoadsorption, whether used alone or in conjunction with hemofiltration, may clear a broad range of substances from the blood, including inflammatory mediators, drugs, trace elements, bacteria, and viruses.

Key messages: Understanding the fundamental principles of blood purification techniques is essential for enhancing survival probabilities, keeping in mind the principle of primum non nocere as a guiding tenet of our daily practice. This review aimed to give an overview of hemoadsorption techniques by presenting current evidence and highlighting key areas that require further investigation.

Introduction: The air trap chamber used in continuous renal replacement therapy (CRRT) often causes clot formation due to gas interface, blood stasis and turbulent flow. The designs of this chamber vary widely. Few studies have quantitatively evaluated ex vivo quasi-blood stasis for different chamber types.

Methods: Flow retention characteristics at 20, 30, 40, 50, and 60 s in a top-feed chamber (where blood flow enters vertically from the top and passes through a mesh within the air trap chamber with a chamber 12 mL in volume) and a side-feed chamber (where blood flow enters from the side and bottom, without a mesh filter, with a flow deviator and 6 mL chamber volume) were evaluated using a 30% glycerin and iodine povidone-solution. Still images of the chambers at each time point were converted to 8-bit grayscale using Image J software (ver.1.54, Maryland, USA), with a brightness threshold in the range of 1-80 to compare the two chamber designs.

Results: Both chambers showed a decrease in the values of the highlighted areas over time; however, from 20 s, the side-feed chamber showed significantly lower values of the highlighted areas compared with the top-feed chamber. Similar to the findings at 20 s, significant differences in the values of the highlighted areas favored the side-feed chamber and persisted at 30, 40, 50, and 60 s. Furthermore, pseudo blood remained superficially in the top-feed chamber, while the side-feed chamber exhibited vortex flow, less stasis, turbulence, and stagnation.

Conclusion: The two chambers tested emptied of pseudo blood at different rates, with varying retention characteristics, with the side-feed chamber showing less pseudo-blood retention at all-time points assessed.

Introduction: Sepsis is a life-threatening condition characterized by dysregulated inflammatory responses, often leading to multiple organ dysfunction and high mortality rates. Continuous renal replacement therapy (CRRT) and extracorporeal blood purification therapies have emerged as vital adjuncts to manage fluid overload and modulate immune responses in septic shock. This study evaluates the impact of daily fluid balance variation on 90-day mortality and hospital length of stay in ICU patients undergoing CRRT for septic shock with endotoxin activity.

Methods: A post hoc analysis of the EUPHAS 2 project was conducted on 61 ICU patients with nonresponsive endotoxin shock at San Bortolo Hospital (2016-2021). Bayesian joint models assessed the relationship between fluid balance and mortality. Mediation analysis explored the impact of CRRT on mechanical ventilation duration and hospital stay.

Results: Fluid overload and excessive ultrafiltration were associated with prolonged mechanical ventilation and extended hospital stays. Targeted fluid balance management reduced 90-day mortality risk by 50%. CRRT reduced hospital length of stay directly by 5.31 days but indirectly extended it by 11.78 days due to mechanical ventilation. Optimal fluid balance was critical for minimizing mortality and complications.

Conclusions: Careful and tailored fluid management in CRRT is essential for improving survival rates and clinical outcomes in septic shock patients. Continuous monitoring of fluid dynamics is necessary to optimize hemodynamic stability and avoid complications. Future multicenter studies are needed to validate these findings and refine fluid management protocols.

Background: Polymethyl methacrylate (PMMA) membranes are increasingly recognized for their effectiveness in treating acute kidney injury (AKI) due to their strong adsorption capabilities, particularly for inflammatory mediators like β2-microglobulin and IL-6. These membranes ensure mechanical stability and chemical inertness, minimizing adverse reactions during blood filtration.

Summary: In acute conditions such as sepsis and acute respiratory distress syndrome (ARDS), PMMA membranes show promising findings. In sepsis, they may help reduce multiorgan failure by modulating immune responses, although further research is needed to confirm their routine use. For ARDS, PMMA membranes could mitigate "cytokine storms" by adsorbing key cytokines, improving oxygenation and hemodynamic stability, which may reduce ICU stays and reliance on mechanical ventilation. Monitoring biomarkers like IL-6, TNF-α is critical for tracking efficacy and tailoring therapy to individual needs. In chronic conditions, such as hemodialysis for chronic kidney disease, PMMA membranes help lower oxidative stress and β2-microglobulin levels, reducing complications such as amyloidosis. By decreasing oxidative damage, they provide long-term protective benefits for dialysis patients.

Key message: While these advantages are notable, large-scale studies are needed to establish PMMA's efficacy, refine treatment protocols, and confirm its broader role in acute and chronic disease management. The potential of PMMA membranes highlights their value, but standardized clinical evidence is necessary for widespread adoption.

Background: Historically, extracorporeal blood purification (EBP) treatment for sepsis was mainly used as an adjunctive therapy for the management of multiple organ failure rather than targeting the removal of toxins from the body that are contributing to the disease state. Approximately 10-15% of sepsis cases, or approximately one-third to half of patients with septic shock, exhibit high levels of endotoxin activity in their blood. Humans are exquisitely sensitive to endotoxin making endotoxic septic shock (ESS) particularly deadly. Today, we have an emerging class of EBP that is specific to endotoxin - targeted rapid endotoxin adsorption (TREA) - that can be used for the treatment of ESS.

Summary: In septic patients, evidence for the use of hemofiltration and therapeutic plasma exchange, the two most prevalent forms of EBP, has been difficult to obtain. Additionally, broad-spectrum EBP therapies that target multiple solutes for removal have struggled to identify the right patients. There is significant clinical heterogeneity of the innate immune response across patients with sepsis. In contrast, targeted EBP therapies, which involve measuring a single solute, then choosing appropriate therapy to target its removal, allow for the specific selection of a suitable patient. Unfortunately, measuring the target can prove challenging. Endotoxin can be measured in whole blood using the endotoxin activity assay. However, owing to the size of intact endotoxin molecule, it cannot be filtered using hemofiltration membranes. Adsorption, which only requires the contact of blood or plasma with a sorbent, is therefore a suitable model to target its removal. TREA technologies include devices that specifically target endotoxin (Alteco LPS Adsorber, MATISSE adsorber, Toraymyxin 20R, Toxipak sorption column) and those for which endotoxin removal is included in a more broad-spectrum device (Efferon LPS, oXiris).

Key messages: While only a small number of devices are currently available in the TREA class of EBP, there is an opportunity here to bring precision medicine to sepsis.

Introduction: The purpose of this meta-analysis was to assess the association between hypoalbuminemia and the risk of peritoneal dialysis-associated peritonitis (PDAP) in patients receiving peritoneal dialysis (PD).

Methods: By the specified deadline of November 13, 2023, a systematic search across various databases was conducted to identify relevant literature. The databases searched included PubMed, Embase, the Cochrane Library, Web of Science, the China National Knowledge Infrastructure (CNKI), WanFang, and VIP. The effect sizes were quantified using odds ratios (OR) or hazard ratios (HR) and were presented with 95% confidence intervals (CI). The analysis was stratified by the type of PD [continuous ambulatory peritoneal dialysis (CAPD), mixed] and the timing of albumin (ALB) level measurements (at baseline, after initiation of PD, or average over time).

Results: A total of 14 studies encompassing 6,448 PD patients were incorporated in this meta-analysis. The findings revealed a significantly elevated risk of peritonitis in patients with hypoalbuminemia compared to those with an ALB level above 3.5g/dL (OR: 2.70, 95% CI: 1.78 to 4.09, P <0.001). Stratification by PD modality showed consistent results within the CAPD group (OR: 5.79, 95% CI: 3.57 to 9.41, P <0.001). For the timing of ALB measurements, the baseline measurement group maintained these findings (OR: 2.53, 95% CI: 1.40 to 4.58, P =0.002), while the group with post-PD measurements did not show statistical significance (OR: 0.76, 95% CI: 0.49 to 1.17, P =0.212). The HR analysis similarly indicated an increased risk of peritonitis in hypoalbuminemia patients compared to those with higher serum ALB levels (HR: 1.62, 95% CI: 1.44 to 1.82, P <0.001).

Conclusion: Our meta-analysis reveals that hypoalbuminemia raises the risk of peritonitis in PD patients, particularly at baseline. This finding underscores the need for close monitoring to detect peritonitis early. Further research is needed to understand the impact of ALB levels post-PD initiation on peritonitis risk.

Introduction: Anticoagulation for continuous renal replacement therapy (CRRT) can be performed using systemic anticoagulation or regional citrate anticoagulation (RCA). The 2012 Kidney Disease Improving Global Outcomes guidelines support the use of RCA as the first-line strategy in patients requiring CRRT, with and without bleeding risk. Implementing RCA in the intensive care unit (ICU) implies involving all medical and nursing staff. The primary objective of this study was to report and describe the various anticoagulation strategies for CRRT in French ICUs. The secondary objectives were to determine the rate of RCA use and to identify the factors limiting its implementation.

Methods: An online questionnaire containing 40 questions was sent to attending physicians and fellows practicing in French ICUs between May and September 2021. The questionnaire was sent via several networks: mailing list from the French Society of Anesthesia and Intensive Care Medicine and mailing lists of RRT manufacturers.

Results: A total of 597 responses were analyzed. RCA was used by most of the participants for patients with (81%) and without (80%) increased bleeding risk. The preferred CRRT modality of the participants while using RCA was continuous veno-venous hemodialysis (48%). The clinical situations frequently reported as an absolute contraindication to RCA were uncontrolled shock associated with liver failure and drug poisoning impairing citrate metabolism (62% and 52%, respectively). In case of a higher risk of citrate accumulation, most participants claimed to perform closer biological monitoring (57%) or to modify the CRRT protocol (61%). Among the participants who did not prescribe RCA as a first-line strategy, the main factors limiting its implementation were the lack of nurse (50%) or physician (34%) training.

Conclusion: RCA is the main anticoagulation strategy prescribed for CRRT in France. Providing medical and nursing staff easy access to training may facilitate the understanding and use of RCA as the first-line anticoagulation strategy for CRRT.