Critical care nephrology: the journey has begun.
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Biomedical subjects
Publications and source records attributed to Claudio Ronco.
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Explore the source record for details and available documents.
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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.
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.
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.
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.
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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.
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.
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.
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.