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Biomedical subjects

Alessandra Brendolan

Publications and source records attributed to Alessandra Brendolan.

At least 19 recordsLinked to original sources
PubMed2007

Effectiveness of sodium hypochlorite in the prevention of catheter related infections.

Vascular access in hemodialysis is a major point of concern in the management of chronic patients. Although arteriovenous fistula remains as the access of first choice, tunneled central venous catheters are still commonly used. Infection remains the principal cause of catheter dysfunction or loss. Many protocols have been used in order to prevent exit site infections and bacteremia. We describe our experience with the use of sodium hypochlorite, an electrolytic chloroxidizer used as a topical disinfectant. It has been shown to be active against a broad spectrum of potential pathogens and has other specific advantages compared to other cleansing agents, including its non-toxic, non-irritating nature and its low cost. We conclude that sodium hypochlorite solution in different concentrations (10 and 50%) is effective in preventing exit site infections and bacteremia associated with tunneled central venous catheters in chronic hemodialysis patients.

Bacteremia↗
PubMed2006

Flow distribution analysis by helical scanning in polysulfone hemodialyzers: effects of fiber structure and design on flow patterns and solute clearances.

The efficiency of a hemodialyzer is largely dependent on its ability to facilitate diffusion, as this is the main mechanism by which small solutes are removed. The diffusion process can be impaired if there is a mismatch between blood and dialysate flow distribution in the dialyzer. The objective of the paper was to study the impact of different fiber bundle configurations on blood and dialysate flow distribution and urea clearances. The Optiflux 200 NR hemodialyzer was studied and the standard F 80 A hemodialyzer was used as a control for the study. Six dialyzers of each type were studied in vitro in the radiology department utilizing a new generation of helical computed tomography (CT) scan following contrast medium injection into the blood and dialysate compartment. Dynamic sequential imaging of longitudinal sections of the dialyzer was undertaken to detect flow distribution, average and peak velocities, and calculate wall shear rates. Six patients were dialyzed with 2 different dialyzers in random consecutive sequence. In these patients, 2 consecutive dialyses were carried out with identical operational parameters (Qb = 300 mL/min, Qd = 500 mL/min). In each session, blood and dialysate side urea clearances were measured at 30 and 150 min of treatment. Macroscopic and densitometrical analysis revealed that flow distribution was most homogeneous in the dialyzer with a new bundle configuration. Significantly increased urea clearances (p < 0.001) were seen with the Optiflux dialyzer compared with the standard dialyzer. In conclusion, more homogeneous dialysate blood and dialysate flow distribution and improved small solute clearances can be achieved by modifying the configuration of the filter bundle. These effects are achieved probably as a result of reduced blood to dialysate mismatch with reduction of flow channeling. The used radiological technique allows detailed flow distribution analysis and has the potential for testing future modifications to dialyzer design.

Blood Flow Velocity↗
PubMed2005

Early isovolaemic haemofiltration in oliguric patients with septic shock.

OBJECTIVE: To evaluate the effects of early short-term, isovolaemic haemofiltration at 45 ml/kg/h on physiological and clinical outcomes in patients with septic shock. DESIGN: Retrospective study before and after a change of unit protocol (study period 8 years). SETTING: Intensive care unit of metropolitan hospital. PATIENTS: Eighty patients with septic shock. INTERVENTIONS: Introduction of a new septic shock protocol based on early isovolaemic haemofiltration (EIHF). In the pre-EIHF period (before), 40 patients received conventional supportive therapy. In the post-EIHF period (after), 40 patients received EIHF at 45 ml/kg/h of plasma-water exchange over 6 h followed by conventional continuous venovenous haemofiltration (CVVH). Anticoagulation policy remained unchanged. MEASUREMENTS AND MAIN RESULTS: The two groups were comparable for age, gender and baseline APACHE II score. Delivered haemofiltration dose was above 85% of prescription in all patients. PaO2/FiO2 ratio increased from 117+/-59 to 240+/-50 in EIHF, while it changed from 125+/-55 to 160+/-50 in the control group (p<0.05). In EIHF patients, mean arterial pressure increased (95+/-10 vs 60+/-12 mmHg; p<0.05), and norepinephrine dose decreased (0.20+/-2 vs 0.02+/-0.2 microg/kg/min; p<0.05). Among EIHF patients, 28 (70%) were successfully weaned from the ventilator compared with 15 (37%) in the control group (p<0.01). Similarly, 28-day survival was 55% compared with 27.5% (p<0.05). Length of stay in the ICU was 9+/-5 days compared with 16+/-4 days (p<0.002). CONCLUSIONS: In patients with septic shock, EIHF was associated with improved gas exchange, haemodynamics, greater likelihood of successful weaning and greater 28-day survival compared with conventional therapy.

Acute Kidney Injury↗
PubMed2005

Study protocol: the DOse REsponse Multicentre International collaborative initiative (DO-RE-MI).

INTRODUCTION: Current practices for renal replacement therapy in intensive care units (ICUs) remain poorly defined. The DOse REsponse Multicentre International collaborative initiative (DO-RE-MI) will address the issue of how the different modes of renal replacement therapy are currently chosen and performed. Here, we describe the study protocol, which was approved by the Scientific and Steering Committees. METHODS: DO-RE-MI is an observational, multicentre study conducted in ICUs. The primary end-point will be the delivered dose of dialysis, which will be compared with ICU mortality, 28-day mortality, hospital mortality, ICU length of stay and number of days of mechanical ventilation. The secondary end-point will be the haemodynamic response to renal replacement therapy, expressed as percentage reduction in noradrenaline (norepinephrine) requirement. Based on the the sample analysis calculation, at least 162 patients must be recruited. Anonymized patient data will be entered online in electronic case report forms and uploaded to an internet website. Each participating centre will have 2 months to become acquainted with the electronic case report forms. After this period official recruitment will begin. Patient data belong to the respective centre, which may use the database for its own needs. However, all centres have agreed to participate in a joint effort to achieve the sample size needed for statistical analysis. CONCLUSION: The study will hopefully help to collect useful information on the current practice of renal replacement therapy in ICUs. It will also provide a centre-based collection of data that will be useful for monitoring all aspects of extracorporeal support, such as incidence, frequency, and duration.

Blood Pressure↗
PubMed2005

Pulse high-volume haemofiltration for treatment of severe sepsis: effects on hemodynamics and survival.

INTRODUCTION: Severe sepsis is the leading cause of mortality in critically ill patients. Abnormal concentrations of inflammatory mediators appear to be involved in the pathogenesis of sepsis. Based on the humoral theory of sepsis, a potential therapeutic approach involves high-volume haemofiltration (HVHF), which has exhibited beneficial effects in severe sepsis, improving haemodynamics and unselectively removing proinflammatory and anti-inflammatory mediators. However, concerns have been expressed about the feasibility and costs of continuous HVHF. Here we evaluate a new modality, namely pulse HVHF (PHVHF; 24-hour schedule: HVHF 85 ml/kg per hour for 6-8 hours followed by continuous venovenous haemofiltration 35 ml/kg per hour for 16-18 hours). METHOD: Fifteen critically ill patients (seven male; mean Acute Physiology and Chronic Health Evaluation [APACHE] II score 31.2, mean Simplified Acute Physiology Score [SAPS] II 62, and mean Sequential Organ Failure Assessment 14.2) with severe sepsis underwent daily PHVHF. We measured changes in haemodynamic variables and evaluated the dose of noradrenaline required to maintain mean arterial pressure above 70 mmHg during and after pulse therapy at 6 and 12 hours. PHVHF was performed with 250 ml/min blood flow rate. The bicarbonate-based replacement fluid was used at a 1:1 ratio in simultaneous pre-dilution and post-dilution. RESULTS: No treatment was prematurely discontinued. Haemodynamics were improved by PHVHF, allowing a significant reduction in noradrenaline dose during and at the end of the PHVHF session; this reduction was maintained at 6 and 12 hours after pulse treatment (P = 0.001). There was also an improvement in systolic blood pressure (P = 0.04). There were no changes in temperature, cardiac index, oxygenation, arterial pH or urine output during the period of observation. The mean daily Kt/V was 1.92. Predicted mortality rates were 72% (based on APACHE II score) and 68% (based on SAPS II score), and the observed 28-day mortality was 47%. CONCLUSION: PHVHF is a feasible modality and improves haemodynamics both during and after therapy. It may be a beneficial adjuvant treatment for severe sepsis/septic shock in terms of patient survival, and it represents a compromise between continuous renal replacement therapy and HVHF.

Acid-Base Equilibrium↗
PubMed2005

Phosphate kinetics during different dialysis modalities.

BACKGROUND: An abnormal serum phosphate concentration is common in acute renal failure patients, with a reported incidence of 65-80%. Phosphate removal and kinetics during intermittent hemodialysis (IHD) have been investigated, but there is no information on its kinetics during slow low-efficiency dialysis (SLED) and continuous renal replacement therapy (CRRT). METHODS: Eight IHD, 8 SLED, and 10 continuous venovenous hemofiltration (CVVH) patients with a residual renal clearance of <4.0 ml/min were studied during a single treatment to evaluate phosphate removal and kinetics. CVVH was studied the first 24 h after initiation. Dialysis/replacement fluid contained no phosphate. Kt/V, clearance of urea (Ku), inorganic phosphate (Kp) and solute removal was determined by direct dialysate quantification (DDQ). RESULTS: Kp recorded with the three techniques were: IHD, 126.9 +/- 18.4 ml/min; SLED, 58.0 +/- 15.8 ml/min, and CVVH, 31.5 +/- 6.0 ml/min. However, in shorter dialysis treatment the total removal of phosphate was significantly lower than in longer dialysis (IHD, 29.9 +/- 7.7 mmol; SLED, 37.6 +/- 9.6 mmol; CVVH, 66.7 +/- 18.9 mmol, p = 0.001). The duration of treatment is the only factor determining phosphate removal (r = 0.7, p < 0.0001 by linear correlation model). Like IHD, phosphate kinetics during SLED could not be explained by the two-pool kinetic model, and the rebound of phosphate extended beyond 1 h after dialysis. Rebound, however, is less marked than in short dialysis. CONCLUSION: These results are reliable evidence about amount of phosphate removal and behavior of intradialytic phosphate kinetics in renal failure patients undergoing different dialysis modalities. These data will help clinicians plan phosphate supplementation and treatment intensity.

Aged↗
PubMed2004

Monocyte apoptosis in uremia is normalized with continuous blood purification modalities.

Uremia is associated with a state of immune dysfunction. Dysregulation of homeostasis may be directly related to abnormal apoptosis regulation in uremia, which is crucial for the maintenance of the biological system. We demonstrated that plasma from three groups of uremic subjects, i.e. hemodialysis (HD) patients, peritoneal dialysis (PD) patients and patients with predialysis chronic renal failure (CRF), has different apoptotic potential on U937 monocytes. The plasma of HD and CRF subjects when incubated with U937 cells induced higher levels of apoptosis compared with that of PD and control subjects (HD 26.08 +/- 11.39, CRF 24.87 +/- 9.07, PD 12.13 +/- 4.51, controls 11.69 +/- 4.02). Furthermore, the phagocytic ability of U937 cells incubated with the various plasma demonstrated an impaired response in the HD and CRF subjects (HD 27.56 +/- 6.67, CRF 30.24 +/- 9.08, PD 36.55 +/- 9.80, controls 40.04 +/- 6.98). These results suggest that continuous blood purification, such as in PD, may have advantages over intermittent therapies in removing uremic apoptotic molecules and potentially maintaining biological function and homeostasis.

Apoptosis↗
PubMed2004

Ultrafiltration in patients with hypervolemia and congestive heart failure.

Fluid overload may occur in patients with myocardial dysfunction and different clinical problems. Myocoardial dysfunction may be a consequence of heart dilatation with reduced contractility, ventricular stiffness with diastolic dysfunction or the consequence of myocardial injury or circulating myocardial depressant factors as seen in sepsis. In all cases, cardiac support can be achieved by the optimization of fluid balance, the reduction in organ edema and the restoration of desirable levels of pre- and afterload. Several reports have shown that myocardial elastance can improve after hemofiltration with restoration of adequate fluid balance. In such conditions, continuous extracorporeal therapy may result in remarkable cardiovascular stability with maintenance of hemodynamic parameters, including mean arterial pressure, heart rate and systemic vascular resistance. Such stability, which is achieved through the slow continuous ultrafiltration and continuous refilling of the intravascular volume from the interstitium, enables the stability of the circulating blood volume and the preservation of organ perfusion. This is also crucial for renal recovery during acute renal failure.

Blood Volume↗
PubMed2003

Do circulating cytokines really matter in sepsis?

Sepsis remains the major cause of mortality worldwide, claiming millions of lives each year. The past decade has seen major advances in the understanding of the biological mechanisms involved in this complex process. Unfortunately, no definitive therapy yet exists that can successfully treat sepsis and its complications. In this review, we will address the significance of circulating cytokines in the pathophysiology of sepsis and its relevance to new approaches in extracorporeal therapies.

Cytokines↗
PubMed2003

Erythropoeitin dose variation in different facilities in different countries and its relationship to drug resistance.

BACKGROUND: The correction of anemia using erythropoeitin (EPO) is accorded high priority in the management of patients undergoing hemodialysis (HD). Target hemoglobin (Hb) levels have been established in many countries. Following an observation that the mean facility EPO dose in a chain of facilities in the United States varied by more than two-fold, an examination of the practice of anemia correction in other settings was carried out. METHODS: We reviewed demographic and laboratory parameters in prevalent HD patients in 50 United States facilities and in a single HD facility in Vicenza, Italy. The mean EPO dose profile of the United States facilities was compared with the profiles in 10 facilities in the eastern United Kingdom (UKER) and in 20 facilities reporting to the United Kingdom Renal Registry (UKRR). Analysis of the factors that correlate with EPO resistance was carried out using the United States and Italian data. RESULTS: The average EPO doses, by facility, in the 51 United States, the 10 UKER, and the 19 UKRR facilities were 19,569, 8,416, and 7,992 international units per week (IU/wk), respectively. While examination of the UKRR revealed a similar degree of inter-facility variation (2.6-fold), much larger doses of EPO were being administered in the United States patients, particularly in the low Hb group. Multivariate analysis of the United States data suggested that factors related to inflammation, including low albumin, the use of tunneled catheters for vascular access, and low protein catabolic rate (enPCR) correlated with low Hb and relative EPO resistance. CONCLUSION: Despite similar guidelines for anemia management, significant differences in practice are observed. While there seems to be a reluctance to administer large EPO doses to individual patients in Europe, this does not seem to apply in the United States, where more EPO is given. EPO resistance seems relative rather than absolute in many patients, allowing some to respond to the higher doses.

Aged↗
PubMed2003

Coupled plasma filtration adsorption: rationale, technical development and early clinical experience.

The adjuvant treatment of sepsis remains a major therapeutic challenge. Blood purification is theoretically appealing if the humoral theory of sepsis is accepted as the basis for intervention. In this setting, blood purification would provide a broad-based restoration of humoral homeostasis thereby avoiding both excessive inflammation and counterinflammation. Several techniques of blood purification have been tried or are under active investigation. One of these is the so-called coupled plasma filtration adsorption (CPFA). CPFA is a novel extracorporeal blood purification therapy aimed at nonselectively reducing the circulating levels and activities of both pro- and anti-inflammatory mediators during sepsis and multiorgan failure. In vitro studies have shown CPFA to be effective in binding a broad range of such mediators proving its technical efficacy. Subsequent animal models have shown a beneficial effect on survival in endotoxemia. These studies have provided the necessary technical developments and biologic rationale for initial human studies. Two phase I/IIa clinical studies have now been performed. Both studies have shown that CPFA improves blood pressure and restores immune function in patients with severe sepsis and multiorgan dysfunction. In this article, we will discuss some of the basic principles involved in sorbent technology, and how these may contribute to treatment efficacy, review animal experiments with CPFA and finally discuss the results of recent human studies and their implications.

Adsorption↗
PubMed2002

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↗
PubMed2002

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↗