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Biomedical subjects

Claudio Ronco

Publications and source records attributed to Claudio Ronco.

At least 19 recordsLinked to original sources

Solute mass balance during isovolaemic high volume haemofiltration.

OBJECTIVE: To evaluate the effect of changing the amount of pre-dilution replacement fluid on the sieving coefficient (SC) and mass transfer of small solutes during isovolaemic high-volume haemofiltration (HVHF). DESIGN AND SETTING: Prospective interventional study in the intensive care unit of a tertiary university hospital. PATIENTS: Eight patients with septic shock. INTERVENTIONS: Isovolaemic HVHF (6 l/h of replacement fluid) was performed. The proportion of replacement fluid delivered in pre-filter was altered to progressively decrease it from 6 to 0 l/h. Samples were simultaneously taken from the "pre-filter", "post-filter" and ultrafiltrate (UF) sampling ports. MEASUREMENTS AND RESULTS: Sodium, potassium, chloride, total calcium, total magnesium, phosphate, total CO(2), urea, creatinine and glucose concentrations were measured in each sample. The sieving coefficients of chloride, total CO(2), phosphate, urea and glucose were higher than 1 in most pre-dilution states. The sieving coefficients of sodium, potassium, calcium, magnesium, total CO(2) and urea decreased significantly with decreasing pre-dilution fluid rate. The sieving coefficients of chloride and glucose increased with decreasing pre-dilution fluid rate. There was a significant mass gain of sodium and glucose under all pre-dilution conditions. Mass chloride gains decreased with decreasing pre-dilution rates and changed into chloride loss during 6 l/h of post-dilution. Decreasing pre-dilution improved urea and creatinine mass removal. CONCLUSIONS: Small solute SC and mass transfer during isovolaemic HVHF are significantly affected by the proportion of replacement fluid administered pre-filter. Isovolaemic HVHF is neither isonatraemic nor isochloraemic.

Adult↗

Breath ethane in dialysis patients and control subjects.

Oxidant stress may play a role in the accelerated pathology of patients on dialysis, especially in the development of cardiovascular disease, which is a frequent condition in end-stage renal disease (ESRD) patients. Measurement of hydrocarbons can be employed to assess oxidant stress since breath hydrocarbons have been directly traced to in vivo breakdown of lipid hydroperoxides. We undertook to measure ethane, a major breath hydrocarbon, in 15 control subjects, 13 patients on peritoneal dialysis (PD), and 35 patients on hemodialysis (HD). Within the HD group, we separately examined 12 diabetic and 23 nondiabetic patients. Breath samples were collected after patients had breathed purified air for 4 min, and ethane content was measured by GC and expressed as pmoles/kg-body weight-minute (pmol/kg-min). As the data for the hemodialysis patients appeared skewed, nonparametric statistical techniques were employed to analyze these data, which are reported as median and interquartile range (IQR). Ethane levels were similar in 15 control subjects (median, 2.50 pmol [1.38-3.30]/kg-min] and 13 PD patients (median, 2.51 pmol [1.57-3.17]/kg-min). Breath ethane was significantly elevated in a portion (18 of 35 patients, 52%) of the HD patients (median, 6.16 pmol [4.46-8.88]/kg-min) (p <.001 vs. control, Mann-Whitney U test). Two of the diabetic HD patients showed extremely high values of breath ethane. Breath ethane was not altered by a single hemodialysis session, suggesting that long-term metabolic processes contribute to its elevation. Measurement of breath ethane may provide insight into severity of oxidant stress and metabolic disturbances, and provide guidance for optimal therapy and prevention of pathology in patients on long-term hemodialysis.

Adult↗

Coupled plasma filtration adsorption.

BACKGROUND: Severe sepsis and septic shock are perhaps the major cause of morbidity and mortality in Intensive Care. Their pathogenesis is only partly understood. Circulating peptides and lipid-derived substances (so-called mediators), however, appear to participate in the development of organ dysfunction. It might be possible to treat plasma in such a way that the injurious effect of mediators can be attenuated. INVESTIGATIONS: Several ex vivo studies have shown that it is technically possible to adsorb mediators by means of specially developed sorbents. The application of these sorbents to the treatment of plasma in animals with experimental sepsis has shown that several markers of inflammation can be attenuated and that animal survival can be increased. We have recently transferred such technology to the treatment of human septic shock using a technique called Coupled Plasma Filtration Adsorption (CPFA). CPFA was found to attenuate the hypotension of septic shock and to dramatically alter the immuno-paralytic toxicity of septic plasma. Monocytes of patients treated with CPFA underwent a major improvement in their ability to respond to endotoxin. CONCLUSIONS: CPFA represents a promising new approach to blood purification in sepsis. The findings associated with its application to humans highlight the importance of continuing to investigate blood purification as a possible approach to the treatment of septic shock, the potential usefulness of the humoral theory of sepsis, and the dominant state of immunosuppression associated with established septic shock.

Adsorption↗

The impact of lactate-buffered high-volume hemofiltration on acid-base balance.

OBJECTIVE: To evaluate the effect of high-volume hemofiltration (HVHF) with lactate-buffered replacement fluids on acid-base balance. DESIGN: Randomized crossover study. SETTING: Intensive Care Unit of Tertiary Medical Center PARTICIPANTS: Ten patients with septic shock and acute renal failure. INTERVENTIONS: Random allocation to 8 h of isovolemic high-volume hemofiltration (ultrafiltration rate: 6 l/h) or 8 h of isovolemic continuous venovenous hemofiltration (ultrafiltration rate: 1 l/h) with lactate-buffered replacement fluid with subsequent crossover. MEASUREMENTS AND RESULTS: We measured blood gases, electrolytes, albumin, and lactate concentrations and completed quantitative biophysical analysis of acid-base balance changes. Before high-volume hemofiltration, patients had a slight metabolic alkalosis [pH: 7.42; base excess (BE) 2.4 mEq/l] despite hyperlactatemia (lactate: 2.51 mmol/l). After 2 h of high-volume hemofiltration, the mean lactate concentration increased to 7.30 mmol/l ( p=0.0001). However, a decrease in chloride, strong ion difference effective, and strong ion gap (SIG) compensated for the effect of iatrogenic hyperlactatemia so that the pH only decreased to 7.39 ( p=0.05) and the BE to -0.15 ( p=0.001). After 6 h, despite persistent hyperlactatemia (7 mmol/l), the pH had returned to 7.42 and the BE to 2.45 mEq/l. These changes remained essentially stable at 8 h. Similar but less intense changes occurred during continuous venovenous hemofiltration. CONCLUSIONS: HVHF with lactate-buffered replacement fluids induces iatrogenic hyperlactatemia. However, such hyperlactatemia only has a mild and transient acidifying effect. A decrease in chloride and strong ion difference effective and the removal of unmeasured anions all rapidly compensate for this effect.

Acid-Base Equilibrium↗

Measurement of intraperitoneal volume by segmental bioimpedance analysis during peritoneal dialysis.

BACKGROUND: Currently, ultrafiltration during peritoneal dialysis is determined from direct measurement of weight differences between the initial filling and final draining volumes. A new technique based on segmental bioimpedance analysis (SBIA) has been developed to accurately measure intraperitoneal volume continuously during peritoneal dialysis. METHODS: Twenty-two peritoneal dialysis patients were studied in a supine position during peritoneal dialysis consisting of 4 tidal exchanges (TPD). For bioimpedance measurements, 4 electrodes were placed, 1 on each hand and foot, to inject an alternating current. Sensing electrodes were placed on the lower ribs and the buttocks on both sides of the body. Calibration of the SBIA method was performed by first filling a known volume of dialysate to establish the relationship between change in resistance and a known fluid volume in the peritoneal cavity. The increase of fluid volume in the peritoneal cavity during dwell time was considered to be equal to net ultrafiltration volume occurring during this period. These measurements were compared with those obtained by the difference in weight between the total filling and draining volumes. RESULTS: The change in intraperitoneal volumes measured by differences in weight (0.39 +/- 0.29 L) did not differ significantly from those established from SBIA (0.41 +/- 0.31 L). Bland-Altman analysis yielded limits of agreement of 0.12 L. CONCLUSION: The SBIA technique provides a continuous noninvasive approach to the measurement of changes in intraperitoneal fluid volume.

Adult↗

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↗

Interpreting the mechanisms of continuous renal replacement therapy in sepsis: the peak concentration hypothesis.

Severe sepsis and septic shock are the primary causes of multiple organ dysfunction syndrome (MODS), which is the most frequent cause of death in intensive care unit patients. Many water-soluble mediators with pro- and anti-inflammatory action such as TNF, IL-6, IL-8, and IL-10 play a strategic role in septic syndrome. In intensive care medicine, blocking any one mediator has not led to a measurable outcome improvement in patients with sepsis. CRRT is a continuously acting therapy, which removes in a nonselective way pro- and anti-inflammatory mediators; "the peak concentration hypothesis" is the concept of cutting peaks of soluble mediators through continuous hemofiltration. Furthermore, there is evidence of increased efficacy of high-volume hemofiltration compared to conventional CVVH, and other blood purification techniques that utilize large-pore membranes or sorbent plasmafiltration are conceptually interesting.

Acute Kidney Injury↗

Mononuclear leukocyte apoptosis in haemodialysis patients: the role of cell thiols and vitamin E.

BACKGROUND: An increased apoptotic rate of peripheral blood mononuclear leukocytes (PBMLs) in haemodialysis (HD) patients has been reported in several studies, but its underlying mechanisms remain poorly understood. Oxidant stress is a well known cause of cell damage, and several lines of evidence suggest that it might influence the induction and signalling steps of mononuclear cell apoptosis through different mechanisms so as to provoke disturbances of the intracellular pool of thiols (SHi). In this study, we investigated the in vitro apoptotic rate and SHi of PBMLs in end-stage renal disease (ESRD) patients on HD or peritoneal dialysis (PD). METHODS: Apoptosis and SHi were evaluated in vitro in PBMLs obtained from 40 ESRD patients (HD, n = 30 and PD, n = 10) and 10 healthy controls. A subgroup of HD patients was also studied before and after 1 month of treatment with a vitamin E-coated dialyser (CL-E). Cell thiols and viability were also assessed in the monocyte-like cell line U937 and PBMLs after incubation in the presence of uraemic plasma with or without supplementation of the antioxidants vitamin E (70 micro M) or N-acetyl-cysteine (NAC) (0.5 mM). RESULTS: After 24 h in culture, the PBMLs of HD patients, but not those of CAPD patients, showed an apoptotic rate twice that of healthy controls and a 40% decrease of SHi levels (P < 0.01 in both). A negative correlation between the apoptotic rate and SHi was observed in both patients and controls (r = 0.648, P < 0.001). Plasma and ultrafiltrate samples from HD patients contained solutes (mainly in the low-middle molecular weight range) able to trigger apoptosis and oxidative stress in U937 cells. The treatment of HD patients with CL-E, as well as the in vitro supplementation of U937 cells with vitamin E or NAC during the exposure to uraemic plasma, decreased the rate of apoptosis and partially restored SHi. CONCLUSIONS: This study showed an association between an increased apoptotic rate and decreased SHi in PBML of HD patients, but not of CAPD patients. These changes are partially due to different pro-apoptogens that accumulate in the plasma and are at least partially prevented by exogenous antioxidants able to restore SHi, such as vitamin E or thiol suppliers.

Aged↗

Prevention of acute renal failure in the critically ill.

Acute renal failure (ARF) is a common and important complication of critical illness and many interventions have been proposed to prevent it. The pathogenesis of acute renal failure during critical illness is poorly understood. Animal models are based on the induction of renal ischemia and do not reflect the dominance of sepsis as a cause of ARF in the clinical arena. Although biological rationale exists for several interventions, none have been shown to be effective in large randomized double-blind multicentre trials. The only interventions with close to level I evidence are confined to the attenuation of radiocontrast nephropathy. The effect on such interventions is, however, of limited clinical relevance to critically ill patients. The maintenance of adequate intravascular filling, cardiac output and renal perfusion pressure and the avoidance of hypoxemia, marked anemia and nephrotoxins remain the only justifiable interventions at this time.

Acute Kidney Injury↗

Methods and reproducibility of measurement of resistivity in the calf using regional bioimpedance analysis.

UNLABELLED: The usefulness of regional bioimpedance analysis (RBIA) in determining the dry weight in dialysis patients is currently being investigated. The aim of this study was to evaluate the reproducibility of measurement of resistivity in the calf. METHODS: Twenty-five normal subjects and 10 patients undergoing regular hemodialysis were studied. Four electrodes inserted into a blood pressure cuff were placed on the calf. Bioimpedance was continuously measured over 3- to 5-min periods (Xitron Hydra). After a resting period of 1 min, cuff pressure was increased to above the systolic blood pressure (SBP) for a few seconds to expel excess ECF fluid and then deflated. The effect on recordings of moving the electrodes 2 cm higher and then 2 cm lower than the normal position was studied in 8 normal subjects. In a second study of reproducibility, post-dialysis measurements were made twice in 10 patients who maintained the same post-dialysis target weight throughout the study period. RESULTS: The mean resting resistivity rho(0) in normal subjects was 532.6 +/- 95 omega.cm rising to 583.9 +/- 99.7 omega.cm when cuff pressure was applied rho(p). The average values of rho(0) and rho(p) in patients post-dialysis were 489 +/- 74 and 537 +/- 77 respectively showing that there were no significant differences in rho(0) and rho(p) between normal subjects and patients post-dialysis. The mean values of change in resistivity when the electrodes were shifted between the lowest and highest positions on the calf were -3.66 +/- 4.45 and -1.44 +/- 3.82%, respectively. Repeat measurement of resistivity in patients post-dialysis varied by 2.04 +/- 2.29% while post-dialysis body weight varied by 0.17 +/- 0.47%. CONCLUSION: In this study, resistivity measurement by RBIA at the calf showed similar levels of fluid loading in patients post-dialysis as in normal subjects. This study also showed that change in electrode position resulted in a mean change in resistivity of <5% and repeated measurements showed a change in resistivity <3% while body weight changes were <0.2%. This technique appears to have an acceptable level of reproducibility for its application to the assessment of patient hydration.

Adult↗

Sorbents in acute renal failure and the systemic inflammatory response syndrome.

Renal replacement therapy in acute renal failure is currently focused on the use of modifications of dialysis (continuous arteriovenous hemofiltration and hemodiafiltration) to remove middle molecular weight toxins, consisting of small proteins, and cytokines involved in the systemic inflammatory response syndrome (SIRS). Conventional high-flux dialyzers are not efficient at removing these molecules, prompting the investigation of sorbents to augment or replace dialysis. Sorbents have been developed to modulate SIRS by targeting cytokines such as IL-1, IL-6, IL-10, IL-18 and TNF, among others. Extensive pre-clinical studies are underway to demonstrate the clinical utility and safety of either adding sorbent hemoadsorption devices to hemodialysis, or the use of such devices alone in SIRS, sepsis, acute renal failure, cardiopulmonary bypass and end-stage renal disease.

Acute Kidney Injury↗

Slow continuous intracorporeal plasmapheresis for acute fluid overload.

Intermittent dialysis is still the predominant treatment for acute or chronic renal insufficiency in the USA despite increasing evidence that slower and longer fluid management therapies are more beneficial to the patient. We have investigated the use of slow continuous intracorporeal plasmapheresis (SCIP) as a more efficient and hemodynamically stable alternative means of treating acute fluid overload. In this paper we discuss preliminary observations on the safety of SCIP catheter insertion, fluid removal, extraction and pathology in Yorkshire pigs. SCIP catheters removed plasma for extracorporeal plasma water removal without significant gross or histopathological changes. Blood chemistry and cell counts remained stable during therapy. Toxicological studies indicated no pyrogenicity, hemolysis, cytotoxicity, acute systemic toxicity, delayed-type hypersensitivity, or blood recalcification coagulation inhibition. Intracutaneous extracts caused only mild irritation. SCIP therapy appears to be safe for use in the removal of plasma and plasma water from experimental animals.

Acute Disease↗

Blood purification in non-renal critical illness.

Extracorporeal therapies designed to remove substances from the circulation now include hemodialysis, hemofiltration, hemoadsorption, plasma filtration, cell-based therapies and combinations of any of the above. In recent years, there have been considerable advances in our understanding and technical capabilities, but consensus over the optimal way, and under what conditions to use these therapies does not exist. Consequently, we have initiated a series of conferences under the auspices of the Acute Dialysis Quality Initiative (ADQI). ADQI aims at establishing an evidence-based appraisal and set of consensus recommendations to standardize care and direct further research. The results of previous consensus conferences are available on-line at www.ADQI.net. ADQI conferences have focused on research and management of renal disease. However, extracorporeal therapies are being used or investigated in the management of many other disease processes including systemic inflammation, liver disease, cardiac disease and thrombotic diseases.

Animals↗