Paola Inguaggiato

A pilot study of coupled plasma filtration with adsorption in septic shock

ObjectiveTo test the hypothesis that nonselective plasma adsorption by a hydrophobic resin (coupled plasmafiltration and adsorption) could improve hemodynamics and restore leukocyte responsiveness in patients with septic shock. DesignProspective, pilot, crossover clinical trial. SettingGeneral intensive care unit in a teaching hospital. SubjectsTen patients with hyperdynamic septic shock. InterventionsPatients were randomly allocated to 10 hrs of either coupled plasma filtration adsorption plus hemodialysis (treatment A) or continuous venovenous hemodiafiltration (treatment B) in random order. We measured the change in mean arterial pressure, norepinephrine requirements, and leukocyte tumor necrosis factor-&agr; (TNF-&agr;) production (both spontaneous and lipopolysaccharide-stimulated) after 10 hrs of each treatment. We also tested TNF-&agr; production from normal human adherent monocytes incubated with patients’ plasma obtained before and after the resin, both with or without incubation with an anti-interleukin-10 monoclonal antibody. ResultsMean arterial pressure increased after 10 hr by 11.8 mm Hg with treatment A and by 5.5 mm Hg with treatment B (p = .001). There was an average decrease of norepinephrine requirement of 0.08 &mgr;g/kg/min with treatment A and 0.0049 &mgr;g/kg/min with treatment B (p = .003). All patients but one survived. Spontaneous and lipopolysaccharide-induced TNF-&agr; production from patients’ whole blood increased over time with treatment A. This increase was more marked in blood drawn after the device (plasmafiltrate-sorbent plus hemodialyzer) (p = .009). Preresin plasma suppressed lipopolysaccharide-stimulated production of TNF-&agr; by 1 × 106 cultured adherent monocytes from healthy donors. This suppressive effect was significantly reduced after passage of plasma through the resin (p = .019) and after incubation with anti-interleukin-10 monoclonal antibodies (p = .028). ConclusionsIn patients with septic shock, coupled plasmafiltration-adsorption combined with hemodialysis was associated with improved hemodynamics compared with continuous venovenous hemodiafiltration. This result might be related to its ability to restore leukocyte responsiveness to lipopolysaccharide. These findings suggest a potential role for blood purification in the treatment of septic shock.

An Overview of Haemodialysis and Oxidant Stress

Today’s patient population is increasingly older. Patients with chronic renal failure therefore start extracorporeal substitutive treatment having congestive heart failure, chronic liver disease, diabetes and so forth. In these patients, however, long-term haemodialytic treatment may add further aggravation on their pre-existing pathological conditions. Oxidative stress and alterations in lipid metabolism are caused by haemodialysis mainly due to (1) bioincompatibility type of reactions such as production of reactive oxygen species by inflammatory cells due to complement-mediated or -independent pathways, and (2) the imbalance between oxidants and antioxidants due to the diffusive loss of hydrophilic vitamins such as ascorbic acid. The events related to the oxidant stress may sustain a state of chronic inflammation. Recent advances suggest that atherosclerosis and proliferation of the smooth muscle are initiated and sustained by inflammatory mechanisms. Therefore, attempts to counterbalance the prooxidant effect of haemodialysis and to reduce the chronic inflammatory state will be presented.

Biofilms Invade Nephrology: Effects in Hemodialysis

Bacteria attach to surfaces and aggregate in a biopolymer matrix to form biofilm. Studies on biofilm have shown its presence in many prosthetic devices used in nephrology as well as in fluid pathways of hemodialysis plants and monitors. Once present, this community of bacteria increases resistance to biocide due to slime production and, as a result, chemical products for dialysis monitor disinfection and descaling procedures do not result in an effective treatment. Ultrapure dialysate is a goal in modern hemodialysis, and ultrafiltration is used to obtain sterile and apyrogen fluids. Microbial colonisation of ultrafilters may occur if, due to inadequate disinfection protocols, membrane is exposed to persistent bacterial contamination, and biofilm is allowed to form and to grow. As more and more data link final dialysate microbial contamination to clinical effects of bioincompatibility from chronic inflammation in dialysis patients, attention has to be focused on possibilities of biofilm avoidance.

Coupled Plasma Filtration Adsorption

Sepsis is one of the main causes of death in critically ill patients worldwide, and in many cases it is associated with renal and/or other organ failure. However, we do not have a unique efficient therapy to reduce this extremely high mortality rate. In the last years interest around the use of extracorporeal blood purification techniques has increased. One of the emerging treatments in patients with severe sepsis and septic shock is coupled plasma filtration adsorption (CPFA), a novel extracorporeal blood purification therapy aimed at a nonselective reduction of the circulating levels and activities of both pro- and anti-inflammatory mediators. Early experimental studies and the following clinical trials have demonstrated impressive results regarding hemodynamics and respiratory parameters, even in patients without concomitant acute renal injury, paralleled by a quick tapering of vasoactive drugs. Considering the still high morbidity and mortality rates in septic shock patients, this new blood purification technique seems to have benefits when applied early in the course of sepsis, also without renal indications, suggesting that it might be performed to prevent rather than to treat acute kidney injury.

Rasburicase therapy in acute hyperuricemia and renal dysfunction.

Neoplastic disorders may be complicated by acute renal failure (ARF). Different tumors may cause ARF: solid tumors involving the kidney, solid tumors not of hematological origin and not primarily involving the kidney or, more frequently, rapidly developing hematological tumors. The pathogenesis of ARF is different depending on the type of cancer, but the most frequent clinical feature is the acute tumor lysis syndrome, characterized by hyperuricemia, hyperphosphatemia, hyperkalemia, hypocalcemia and acute, frequently oliguric, ARF. The presence of a neoplastic disorder and associated acute illness may sometimes lead to the presence of immunodysfunction, septic complications and multiple organ dysfunction. In these settings patients develop systemic inflammation and diffuse endothelial damage, related to different mediators. Among these substances, in cancer patients, high circulating levels of uric acid are a common finding. Hyperuricemia is caused by the increase of purine metabolism, which is result of the increased cellular turnover or the aggressive cancer chemotherapy regimens that worsen cell lysis and release of purine metabolites. Even if hyperuricemia is not the first insult to the kidney, its development might represent a concomitant factor aggravating other previous or simultaneous insults. The most efficient therapy for lowering uric acid is rasburicase, a recombinant form of urate oxidase, a nonhuman proteolytic enzyme that oxidizes uric acid to allantoin. It is efficacious in reducing serum uric acid levels with associated diuresis more effectively and much faster than allopurinol, and to correct renal dysfunction more rapidly than allopurinol.

Choosing new adsorbents for endogenous ultrapure infusion fluid: performances, safety and flow distribution.

Adsorption may notably contribute to the removal of uremic toxins and to the efficiency of hemodialysis. We examined different uncoated stationary matrixes, charcoals and synthetic resins to establish their adsorptive capacities in relation to low (urea, creatinine) and high molecular weight (β2-microglobulin, myoglobin) compounds in in vitro conditions (steady state and flow-through) using isotonic solutions or uremic ultrafiltrate. Trace metal, particle release analyses and scanning electron microscopy of different adsorbents were performed. Dynamic flow-distribution studies were made using 99Technetium and analysing the different regions of interest by single head γ-camera. We show that adsorbents may differ greatly as to their adsorptive capacity depending on flow rate, nature, and total mass of the compounds to be removed from the ultrafiltrate. These studies suggest a methodological approach for screening stationary matrixes for possible application in hemodialysis.

IN VITRO AND IN VIVO EVALUATION OF A NEW POLYSULFONE MEMBRANE FOR HEMODIALYSIS. REFERENCE METHODOLOGY AND CLINICAL RESULTS (PART 1 : IN VITRO STUDY)

Different high flux membranes have been recently developed. The present study is aimed at describing the technical features and the clinical performances of a new high flux polysulfone membrane (T-sulfone, Toray Japan). The study has been carried out on two different dialyzers (surface area = 1.3 and 1.8 m2). The filters have been tested in vitro under definite experimental conditions. The hydraulic flow resistance, the pressure drop in the blood compartment and the hydraulic permeability have been determined in a wide range of in vitro experimental conditions. The in vitro sieving coefficients for various solutes have also been determined utilizing human blood. Hydraulic permeability was found in the range of 28.4 ml/h/mmHg/m2 and sieving coefficients were between 0.96 and 1.0 for all low molecular weight solutes. The sieving coefficient for inulin was 0.95. The pressure drop in the filter at 300 ml/min of blood flow was 95 mmHg for the 1.3 m2 and 57 mmHg for the 1.8 m2. The filters are then designed to operate in the presence of high blood flows without excessive resistance in the blood compartment. The blood compartment analyzed by means of a special radiological sequence obtained with a helical scanner after dye injection confirmed the homogeneous distribution of the blood flow in several cross sections of the bundle. Adequate distribution of dialysate was confirmed with a similar method applied to the dialysate compartment. The new imaging techniques utilized were greatly helpful to determine adequacy of filter design and flows distribution.

Regional citrate anticoagulation for renal replacement therapies in patients with acute kidney injury: a position statement of the Work Group “Renal Replacement Therapies in Critically Ill Patients” of the Italian Society of Nephrology

Patients with acute kidney injury (AKI) on renal replacement therapy (RRT) are at increased risk for bleeding but usually require anticoagulation of the extracorporeal circuit, a key prerequisite for delivery of an adequate RRT dose. To this end, many anti-hemostatic strategies have been proposed, unfractionated heparin—with all of its significant drawbacks and complications—being the most common method used so far. In this clinical context, regional citrate anticoagulation (RCA) could represent the most promising strategy, and it has been endorsed by recent guidelines on AKI. The aim of this position statement is to critically review the current evidence on RCA for the extracorporeal circuit of RRT in patients with AKI, in order to provide suggestions for its application in clinical practice. To this purpose, the most relevant clinical studies and recent guidelines on AKI with special regard to anti-hemostatic strategies for RRT circuit maintenance have been reviewed and commented. Experts from the Working Group “Renal Replacement Therapies in Critically Ill Patients” of the Italian Society of Nephrology have prepared this position paper, which discusses the basic principles, advantages and drawbacks of RCA based on the available safety and efficacy data. Advice is given on how to use and monitor RCA in the different RRT modalities, in order to avoid complications while maximizing the delivery of the prescribed RRT dose.

Clinical effects of online dialysate and infusion fluids

Online hemodiafiltration appears to be the most effective technique of renal replacement therapy in many respects. Removal of small and high‐molecular weight substances is enhanced. Modern technology ensures a safe, online production of reinfusion fluids. Nonetheless, stringent maintenance rules are required for the production of sterile and nonpyrogenic‐dialysate solutions. In this review, we will critically review the state of the art of the clinical effects derived from the use of ultrapure dialysate and the online production of dialysate fluids in high‐flux hemodiafiltration.

RETENTION OF LIMULUS AMOEBOCYTE LYSATE REACTIVE BACTERIAL PRODUCTS BY POLYSULFONE DIALYZERS IS AFFECTED BY THE TYPE OF DISINFECTANT

To reduce the level of contamination by bacterial products, ultrafiltration systems have been introduced and validated for their capacity to block the passage of bacterial components reactive to the limulus amoebocyte lysate (LAL) test. In this study, the absorptive capacity of polysulfone membranes undergoing disinfection cycles with free chlorine and peracetic acid were evaluated at various concentrations and contact times. The results of this study implicate a relevant physicochemical derangement of the polysulfone membranes treated with sodium hypochlorite but not with peracetic acid, diluted peracetic acid (Dialox) or Amuchina. The implications for the practical use of ultrafilters are discussed.