Search PubMed⌕ Search

Biomedical subjects

Claudio Ronco

Publications and source records attributed to Claudio Ronco.

At least 145 records · Page 8Linked to original sources

Hemodialyzer: from macro-design to membrane nanostructure; the case of the FX-class of hemodialyzers.

Very few innovations have characterized the different components of the hemodialyzers in the past 20 years. Most improvements have concerned membrane biocompatibility. In this article, we focus our attention on the most recent advances in hemodialyzer components from the macro design of the unit to the nanostructure of the membrane. For this purpose, we took as an example the FX class of hemodialyzers (FMC, Bad Homburg, Germany). The studied devices were chosen as an example representing some of the most recent hemodialyzers and are well suited to describe technical innovations occurring in the field of dialyzer technology. In vitro and in vivo studies were performed to characterize hemodynamic parameters of three models (1.4-1, 8, and 2.2 m2) and to determine membrane permeability, sieving coefficients, and solute clearances. The units were characterized by a relatively high resistance of the blood and dialysate compartments, leading to an increased internal filtration if compared with similar hemodialyzers of other series. Nevertheless, the flow distribution in both compartments was homogeneous and well balanced. This effect was obtained by the improved blood and dialysate ports design, the increased packing density of the fibers and a reduction of the inner diameter of the fibers from 200 to 180 microm. At the same time, the sieving coefficients for middle-large solutes such as beta2 microglobulin and insulin were higher than those observed in standard high flux dialysers. The same effect was noted for the clearance values of these solutes. This was observed in the absence of significant albumin leakage. These results were obtained thanks to a new nano-controlled spinning technology applied to the fiber. The innermost layer of the membrane is in fact characterized by a homogeneous porosity, with increased number of pores of large dimension but a sharp cutoff of the membrane excluding albumin losses. In conclusion, new technologies and new diagnostic tools today allow for improvement in hemodialyzer design from its macro-components to its nano-structure. The application of nanotechnology to hemodialysis will probably contribute to further developments in hemodialyzer manufacturing.

Equipment Design↗

Endotoxin and cytokine removal in sepsis.

Sepsis, the leading cause of mortality in intensive care units, is a complex series of interrelated effects caused by the overproduction of multiple mediators and their unrestrained biological activity. Both proinflammatory and antiinflammatory mediators participate in the high complexity of sepsis and explain the failure of specific therapies to improve survival. Continuous extracorporeal therapies have been proposed as therapeutic options and as tools for blood purification in sepsis. Along these lines and in order to achieve higher clearances and mass removal rates, we studied the effects of plasmafiltration coupled with adsorption and provided in vitro and in vivo evidence that adsoprtion of multiple cytokines, activated complement components, and lipid mediators such as the platelet-activating factor occurs. We also showed that such treatment may lead to improved survival in a rabbit model of sepsis and to improved hemodynamics, reduced norepinephrine dose, and restoration of near-to-normal responsiveness of blood leukocytes to endotoxin in humans. It is anticipated that treatment of plasma, as a modular device to conventional hemofiltration, may pave the way to innovative approaches in the extracorporeal treatment of septic patients.

Adsorption↗

Online monitoring of cerebral hemodynamics during hemodialysis.

BACKGROUND: Several factors, including anemia, diabetes, and hypertension, potentially could disturb the cerebral autoregulation mechanism in hemodialysis (HD) patients. This study examined the effect of hemodynamic and rheological changes on mean cerebral blood flow (CBF) velocity (MV) during HD. METHODS: Continuous online monitoring of MV and pulsatility index in the middle cerebral artery were performed in 18 HD patients by transcranial Doppler ultrasound during the entire HD period (range, 3 to 4 hours). In addition, blood pressure, hematocrit (Hct), and relative decrease in blood volume were continuously monitored. Blood samples were obtained at the beginning and end of HD to measure hemorheological variables. RESULTS: After HD, Hct increased significantly from 33.6% +/- 5.9% to 41.4% +/- 5.7% (P < 0.001). Blood and plasma viscosity increased significantly from 3.33 +/- 0.77 to 4.36 +/- 1.3 mPa.s (P < 0.001) and from 1.35 +/- 0.29 to 1.54 +/- 0.38 mPa.s (P < 0.001), respectively. The change in MV (DeltaMV) was not significantly different from zero and correlated significantly with change in Hct. During HD, mean arterial pressure (MAP) in 15 patients changed within the normal range (group I), whereas 3 patients developed hypotension (group II) and their MAP decreased from 99 +/- 5 to 60 +/- 8 mm Hg (P < 0.05). In both groups, DeltaMV were not significant. CONCLUSION: Results of this study suggest that CBF does not appear to be diminished significantly during HD.

Aged↗

Continuous renal replacement therapy: opinions and evidence.

Continuous arteriovenous haemofiltration (CAVH) is the first example of continuous renal replacement therapy (CRRT). CAVH was first applied for the treatment of diuretic unresponsive fluid overload. Subsequently, CRRT has undergone a remarkable growth, and it is now performed with pump technology (CVVH) and via double-lumen central venous catheters. In many intensive care units, especially in Australia and in Europe, CRRT has become the dominant, if not exclusive, form of artificial renal support. Continuous haemofiltration is now used beyond the original indications of blood purification, for the treatment of certain drug intoxications, for severe cardiac failure, for volume control during, after cardiopulmonary bypass, and to decrease the toxicity of chemotherapy. Furthermore, there is strong ongoing research into its role or that of derived techniques as possible adjuvant therapies during severe sepsis. Despite its large use, the current state of CRRT is surrounded by some controversies, and an effort should be made to give a dispassionate distillation of the literature for a final common definition of what is based on opinions and what carries sufficient evidence.

Equipment Design↗

The Acute Dialysis Quality Initiative: the New York conference.

Over 300,000 Americans develop acute renal failure each year, and half die. In recent years, there have been considerable advances in our understanding and technical capabilities, but consensus over the optimal way to deliver care does not exist. Consequently, a conference held in New York in the year 2000 has given birth to the Acute Dialysis Quality Initiative (ADQI). The conference aimed at establishing an evidence-based appraisal and set of consensus recommendations to standardize care and direct further research on the application of continuous renal replacement therapy (CRRT). CRRT is being used at ever-increasing rates in the United States. Today, approximately one quarter of all patients with acute renal failure are treated with CRRT. Despite the increasing use, there are presently no published standards for the application of this therapy, and practice patterns vary widely between individual centers. Results from recent clinical trials on selection of dialysis membranes and dialysis dose provide strong, yet often conflicting, evidence to guide therapy. Other areas of uncertainty have not been sufficiently addressed by clinical studies and directives for future research are needed. Finally, the success of multicentered clinical trials in supportive care in the intensive care unit (transfusion thresholds and ventilator management) have intensified and renewed interest in the study of supportive care methods as a major target for future research. These developments have set the stage for the first ADQI conference; the final objectives are the development of evidence-based practice guidelines and directions for future research.

Congresses as Topic↗

The Acute Dialysis Quality Initiative II: the Vicenza conference.

A large number of patients develop acute renal failure in the intensive care unit and nephrology wards, and mortality remains high. In recent years, there have been considerable advances in our understanding and technical capabilities, but consensus over the optimal way to diagnose and treat acute renal failure does not exist. Consequently, a consensus conference under the auspices of the Acute Dialysis Quality Initiative (ADQI) has been held in Vicenza in the year 2002 after the previous conference held in New York in the year 2000. The ADQI aims at establishing an evidence-based appraisal and set of consensus recommendations to standardize care and direct further research. The first of these conferences held in June 2000 in New York focused on continuous renal replacement therapy (CRRT). The reports from this first consensus conference are now available online at www.ADQI.net and are also published in part in this issue. However, there remains a need for consensus in several other areas of acute renal failure. Acute renal failure has no accepted definition or rather there are over 30 definitions used in the literature and no consensus as to which one should be used. Studies designed to prevent or treat acute renal failure often use clinical and physiologic endpoints that are not comparable to other studies making it difficult to compare the results of one study to another. Finally, the success of multicentered clinical trials in supportive care in the intensive care unit (transfusion thresholds and ventilator management) have intensified and renewed interest in the study of supportive care methods as a major target for future research. These developments have set the stage for the first conference and have now driven the spirit of the second. Once again, the final objectives are the development of evidence-based guidelines and directions for future research.

Acute Kidney Injury↗

Ionized serum calcium levels during acute renal failure: intermittent hemodialysis vs. Continuous hemodiafiltration.

BACKGROUND: Achieving "adequacy of dialysis" includes the maintenance of normal serum ionized calcium concentrations and is an important therapeutic goal in the treatment of acute renal failure (ARF). It is unknown whether this goal is best achieved with intermittent or continuous renal replacement therapy. METHODS: We compared the effects of continuous veno-venous hemodiafiltration (CVVHDF) and intermittent hemodialysis (IHD) on serum ionized calcium concentrations using daily morning blood tests in 88 consecutive intensive care patients of which half were treated with IHD and half with CRRT. RESULTS: Mean patient age was 54 +/- 14 years for IHD and 60 +/- 14 years for CVVHDF (NS). However, patients who received CVVHDF were significantly more critically ill (mean APACHE II scores: 24.4 +/- 5.1 for IHD vs. 29.2 +/- 5.7 for CVVHDF, p < 0.003). Before treatment, the mean ionized calcium concentration was 1.177 +/- 0.03 mmol/l for IHD and 1.172 +/- 0.04 mmol/l for CVVHDF (NS), with abnormal values in 51.6% of IHD patients and in 68% of CVVHDF patients (NS). During treatment, hypocalcemia was significantly more common among CVVHDF patients (24.5% vs. 14.9%; p < 0.011) while hypercalcemia was more frequent during IHD (36.1% vs. 25.6%; p < 0.019). CONCLUSIONS: Abnormal serum ionized calcium concentrations are frequent in ARF patients before and during renal replacement. Once dialytic therapy is applied, CVVHDF is more likely to lower serum calcium concentrations, while IHD is more likely to induce hypercalcemia. Appreciation of these different biochemical effects may assist clinicians in adjusting dialytic therapy in selected patients.

Acute Kidney Injury↗

Continuous renal replacement therapy: does technique influence azotemic control?

BACKGROUND AND OBJECTIVES: Different techniques of continuous renal replacement therapy (CRRT) might have different effects on azotemic control. Accordingly, we tested whether continuous veno-venous hemodiafiltration (CVVHDF) or continuous veno-venous hemofiltration (CVVH) would achieve better control of serum creatinine and plasma urea levels. DESIGN: Retrospective controlled study. SETTING: Two tertiary Intensive Care Units. PATIENTS: Critically ill patients with acute renal failure (ARF) treated with CVVHDF (n = 49) or CVVH (n = 50). INTERVENTIONS: Retrieval of daily morning urea and creatinine values before and after the initiation of CRRT for up to 2 weeks of treatment. MEASUREMENTS AND RESULTS: Before treatment, serum urea and creatinine concentrations were significantly lower in the CVVH group than in CVVHDF group (urea: 31.0 +/- 15.0 mmol/L for CVVHDF and 24.7 +/- 16.1 mmol/L for CVVH, p = 0.01, creatinine: 547 +/- 308 micromol/L vs. 326 +/- 250 micromol/L, p < 0.0001). These differences were still significant after 48 h of treatment (urea: 20.1 +/- 8.3 mmol/L vs. 14.1 +/- 6.1 mmol/L; p = 0.0003, creatinine: 360 +/- 189pmol/L vs. 215 +/- 118 micromol/L; p < 0.0001). Throughout the duration of therapy, mean urea levels (22.3 +/- 9.0 mmol/L for CVVHDF vs. 16.7 +/- 7.8 mmol/L for CVVH, p < 0.0001) and mean creatinine levels (302 +/- 167 vs. 211 +/- 103 micromol/L, p < 0.0001) were better controlled in the CVVH group. CONCLUSIONS: CRRT strategies based on different techniques might have a significantly different impact on azotemic control.

Acute Kidney Injury↗

The effect of coupled haemofiltration and adsorption on inflammatory cytokines in an ex vivo model.

BACKGROUND: The objective of this study was to evaluate the ex vivo removal of cytokines with an extracorporeal circuit using coupled large-pore haemofiltration and sorbent adsorption. METHODS: The setting for this study was a laboratory attached to the Intensive Care Unit of a tertiary hospital. Six healthy volunteers donated blood, which was incubated with endotoxin. Control blood was left at room temperature. Treatment blood was recirculated for 6 h through a closed circuit with a large-pore polysulfone haemofilter (average pore size 150 kDa) and an activated charcoal cartridge. Blood and ultrafiltrate were sampled hourly from three sites (pre-haemofilter for the circulating concentration, at cartridge inlet and cartridge outlet) to measure the concentrations of interleukins (IL)-1beta, -6, -8 and -10, and tumour necrosis factor (TNF). RESULTS: Control cytokine concentrations remained the same or increased slightly. Most of the preformed circuit cytokines were removed, with the exception of IL-10. The average sieving coefficients were 0.61 for IL-1beta, 1.34 for IL-6, 0.30 for IL-8, and 0.56 for TNF. Average single-pass clearances were 49, 107, 24 and 45 ml/min, respectively. The cartridge adsorbed 90% of IL-1beta, 72% of IL-6, 100% of IL-8, and 7% of TNF during each pass. CONCLUSION: The combination of a large-pore haemofilter and charcoal cartridge removed several cytokines efficiently under ex vivo conditions. This technique can now be tested for cytokine removal in vivo.

Adsorption↗

A phase II randomized, controlled trial of continuous hemofiltration in sepsis.

OBJECTIVE: To study the effect of early and continuous venovenous hemofiltration (CVVH) on the plasma concentrations of several humoral mediators of inflammation and subsequent organ dysfunction in septic patients. DESIGN: Randomized, controlled trial. SETTING: Intensive care unit of a tertiary hospital. PATIENTS: Twenty-four patients with early septic shock or septic organ dysfunction. INTERVENTIONS: Random allocation to receive 48 hrs of isovolemic CVVH at 2 L/hr of fluid exchange or no hemofiltration. MEASUREMENTS AND MAIN RESULTS: We measured the plasma concentrations of complement fractions C3a and C5a, interleukins 6, 8, and 10, and tumor necrosis factor alpha at baseline and 2, 24, 26, 48, and 72 hrs. A multiple organ dysfunction score (MODS) was calculated daily for each patient until death or discharge from the intensive care unit. The concentrations of most mediators decreased between baseline and 72 hrs. Some significant falls in concentration could be identified between specific time points, but CVVH was not associated with an overall reduction in any plasma cytokine concentrations. There was also no difference between the mean cumulative MODS for control survivors (43.3 +/- 19.7) and CVVH survivors (33.2 +/- 19.0; p = .30), and no difference between the average MODS calculated for all controls (4.1 +/- 1.9) and all CVVH subjects (3.3 +/- 1.7; p = .26). CVVH did not improve oxygenation, lower the platelet count, or reduce the duration of vasopressor support and mechanical ventilation. CONCLUSIONS: Early use of CVVH at 2 L/hr did not reduce the circulating concentrations of several cytokines and anaphylatoxins associated with septic shock, or the organ dysfunction that followed severe sepsis. CVVH using current technology cannot be recommended as an adjunct to the treatment of septic shock unless severe acute renal failure is present.

Aged↗

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

OBJECTIVE: To 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. DESIGN: Prospective, pilot, crossover clinical trial. SETTING: General intensive care unit in a teaching hospital. SUBJECTS: Ten patients with hyperdynamic septic shock. INTERVENTIONS: Patients 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-alpha (TNF-alpha) production (both spontaneous and lipopolysaccharide-stimulated) after 10 hrs of each treatment. We also tested TNF-alpha 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. RESULTS: Mean 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 microg/kg/min with treatment A and 0.0049 microg/kg/min with treatment B (p =.003). All patients but one survived. Spontaneous and lipopolysaccharide-induced TNF-alpha 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-alpha by 1 x 10(6)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). CONCLUSIONS: In 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.

APACHE↗

Acute Dialysis Quality Initiative: methodology.

The area of acute renal failure has lagged behind other areas of critical care medicine such as acute respiratory distress syndrome or sepsis in terms of clinical focus, assimilation and interpretation of currently available evidence, and availability of clinical trials. Furthermore, there has been a lack of attention concerning present therapeutic needs and future clinical research direction. These shortcomings stem, in part, from the fragmentation of acute renal failure care and expertise into the fields of nephrology and critical care medicine. To advance the quality of care, make the evidence base for clinical practice more readily available and suitably interpreted, reduce fragmentation, and refocus the goals of future research in this field, a new quality initiative, the Acute Dialysis Quality Initiative, was launched. This initiative brings together experts from different fields and continents, applying an expert-enhanced evidence analysis to achieve its goals. This brief report details the process of the Acute Dialysis Quality Initiative and its goals and methodology.

Acute Kidney Injury↗

Acute Dialysis Quality Initiative: the New York conference.

The need to create a coordinated plan to analyze, summarize, and present current evidence in the treatment of acute renal failure finally found its practical expression in the first international meeting of the Acute Dialysis Quality Initiative in New York. Experts from different fields and continents got together and took the first step in a planned and comprehensive approach to the problem of acute renal failure in all of its facets. In this report, the details of the New York conference, its rationale, and its methodology are presented, and the goals and scope of the Acute Dialysis Quality Initiative are introduced to the critical care community

Acute Kidney Injury↗

Acute Dialysis Quality Initiative II: the Vicenza conference.

The process of tackling all of the issues related to acute renal failure began with the initial focus on its dialytic management (Acute Dialysis Quality Initiative I: the New York conference), because this required urgent attention. However, it was clear from the start that the entire issue of acute renal failure, including its definition, epidemiology inside and outside of the intensive care unit, the animal models used to develop new interventions, the issue of fluid therapy, the application of information technology to its care, the choice of appropriate physiologic goals for phase I and phase II studies, and the need to define appropriate clinical goals for large, randomized, clinical trials, required systematic attention. Accordingly, the second Acute Dialysis Quality Initiative conference in Vicenza, Italy, was organized, and its goals and rationale are presented in this report.

Acute Kidney Injury↗

Intravenous catheter for intracorporeal plasma filtration.

Future advances in dialysis of end-stage renal disease patients may include improvements in therapeutic continuity and patient mobility. Continuous renal replacement therapies could lead to self-contained, mobile and potentially wearable dialysis units. We investigated an experimental, intravenous slow-continuous plasma separation system (IPSS) as a precursor to direct intravenous hemofiltration. An intracorporeal catheter employs asymmetric hollow fibers to separate blood cells from plasma in vivo. The fibers possess a sieving coefficient of 0.7 microm and remove 99.99% of all platelets. In vivo, catheters sustain an average plasma separation flow rate of 3 ml/min over 22 h, sufficient to remove 2 net liters of water from pigs through an extracorporeal hemofilter. Used catheter fibers are relatively free of protein deposition or clots in situ. In vitro studies suggest that human catheters may perform at 3-4 times the rate of porcine catheters. IPSS is proposed for acute fluid removal in CHF patients refractory to diuretics.

Animals↗

The next step from high-flux dialysis: application of sorbent technology.

The current foci of renal replacement therapy with dialysis are middle molecular weight toxins, consisting of small proteins, polypeptides and products of glycosylation and lipoxygenation. Conventional high-flux dialysis is not efficient at removing these molecules, explaining the increased interest in using sorbents to supplement dialysis techniques. Prototype biocompatible sorbents have been developed and investigated for middle molecule removal; these have been shown, in man, to remove beta(2)-microglobulin, angiogenin, leptin, cytokines and other molecules, without reducing platelets and leukocytes. Extensive clinical studies are underway to demonstrate the clinical utility and safety of adding routinely a sorbent hemoperfusion device to hemodialysis.

Adsorption↗