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C Ronco

Publications and source records attributed to C Ronco.

At least 55 records · Page 3Linked to original sources

Artificial organ treatment for multiple organ failure, acute renal failure, and sepsis: recent new trends.

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. At variance with targeting single mediators, therapeutic intervention aimed at the nonselective removal of pro- and anti-inflammatory mediators seems a rational concept and a possible key to successful extracorporeal therapies. A further advantage may lie in the continuous nature of such therapy. With such continuous therapy, sequentially appearing peaks of systemic mediator overflow may be attenuated and persistently high plasma levels reduced. This theoretical framework is proposed as the underlying biological rationale for a series of innovative modalities in sepsis. In this editorial, we will review recent animal and human trials that lend support to this concept. We will also review the importance of treatment dose during continuous renal replacement therapy as a major factor affecting survival in critically ill patients with acute renal failure. Additionally, we will review novel information related to other blood purification techniques using large pore membranes or plasma filtration with adsorbent perfusion. Although these approaches are still in the early stages of clinical testing, they are conceptually promising and might represent an important advance.

Acute Kidney Injury↗

Defining death in non-heart beating organ donors.

Protocols for retrieving vital organs in consenting patients in cardiovascular arrest (non-heart beating donors, NHBD) rest on the assumptions that irreversible asystole a) identifies the instant of biological death, and b) is clinically assessable at the time when retrieval of vital organs is possible. Unfortunately both assumptions are flawed. We argue that traditional life/death definitions could be actually inadequate to represent the reality of dying under intensive support, and we suggest redefining NHBD protocols on moral, social, and anthropological criteria, admitting that irreversible (however defined) asystole can only equate a clinically determinable point of no return in the process of dying, where organ retrieval can be morally and socially accepted in previously consenting patients.

Attitude to Death↗

Impact of continuous veno-venous hemofiltration on acid-base balance.

BACKGROUND: Continuous veno-venous hemofiltration (CVVH) appears to have a significant and variable impact on acid-base balance. However, the pathogenesis of these acid-base effects remains poorly understood. The aim of this study was to understand the nature of acid-base changes in critically ill patients with acute renal failure during continuous veno-venous hemofiltration by applying quantitative methods of biophysical analysis (Stewart-Figge methodology). METHODS: We studied forty patients with ARF receiving CVVH in the intensive care unit. We retrieved the biochemical data from computerized records and conducted quantitative biophysical analysis. We measured serum Na+, K+, Mg2+, Cl-, HCO3-, phosphate, ionized Ca2+, albumin, lactate and arterial blood gases and calculated the following Stewart-Figge variables: Strong Ion Difference apparent (SIDa), Strong Ion Difference Effective (SIDe) and Strong Ion Gap (SIG). RESULTS: Before treatment, patients had mild acidemia (pH: 7.31) secondary to metabolic acidosis (bicarbonate: 19.8 mmol/L and base excess: -5.9 mEq/L). This acidosis was due to increased unmeasured anions (SIG: 12.3 mEq/L), hyperphosphatemia (1.86 mmol/L) and hyperlactatemia (2.08 mmol/L). It was attenuated by the alkalinizing effect of hypoalbuminemia (22.5 g/L). After commencing CVVH, the acidemia was corrected within 24 hours (pH 7.31 vs 7.41, p<0.0001). This correction was associated with a decreased strong ion gap (SIG) (12.3 vs. 8.8 mEq/L, p<0.0001), phosphate concentration (1.86 vs. 1.49 mmol/L, p<0.0001) and serum chloride concentration (102 vs. 98.5 mmol/L, p<0.0001). After 3 days of CVVH, however, patients developed alkalemia (pH: 7.46) secondary to metabolic alkalosis (bicarbonate: 29.8 mmol/L, base excess: 6.7 mEq/L). This alkalemia appeared secondary to a further decrease in SIG to 6.7 mEq/L (p<0.0001) and a further decrease in serum phosphate to 0.77 mmol/L (p<0.0001) in the setting of persistent hypoalbuminemia (21.0 g/L; p=0.56). CONCLUSIONS: CVVH corrects metabolic acidosis in acute renal failure patients through its effect on unmeasured anions, phosphate and chloride. Such correction coupled with the effect of hypoalbuminemia, results in the development of a metabolic alkalosis after 72 hours of treatment.

Acid-Base Equilibrium↗

Effects of novel manufacturing technology on blood and dialysate flow distribution in a new low flux "alpha Polysulfone" hemodialyzer.

The main target for low flux hemodialyzers is an efficient low molecular weight solutes clearance. Such efficiency is largely dependent on the optimization of diffusion between blood and dialysis solution. The diffusion process can be impaired if there is a mismatch between blood and dialysate flow distribution in the dialyzer. Thus optimized flow distribution both in the blood and dialysate compartment becomes quintessential for the maximal efficiency of the diffusion process within the hemodialyzer. The present paper describes the distribution of the blood and dialysate flows in a new low flux polysulfone hollow fiber hemodialyzer characterized by a specific undulation of the fibers and a new cutting technology of the fibers for an improved micro-flow condition in the blood compartment headers. Twelve Diacap alpha Polysulfone LO PS 15 (1.5 sqm) (B. Braun Medizintechnologie, Melsungen Germany) were employed for the study. Six were analyzed in vitro and six were studied in vivo. Blood flow distribution was studied in vitro by dye injection in the blood compartment during experimental extracorporeal circulation utilizing human blood with hematocrit adjusted at 33%. Sequential images were obtained with a helical scanner in a fixed longitudinal section of the dialyzer 1 cm thick. Average and regional blood flow velocities were measured utilizing the reconstructed imaging sequence. The method allowed the calculation of single fiber blood flow (SF Qb) and the mass transfer zone (MTR) definition in digitally subtracted images. The patterns 20-10 and 40-30 were utilized. The same technology was used to evaluate flow distribution in the dialysate compartment after dye injection in the Hansen's connector. Regional dialysate flow was calculated in central and peripheral sample areas of 1 cm2. Six in vivo hemodialysis treatments on patients with end stage renal disease were performed at three different blood flow rates (250-350 and 450 ml/min) in order to measure urea, creatinine and phosphate clearance. Macroscopic and densitometrical analysis revealed that flow distribution was homogeneous in the blood compartment while in the dialysate compartment a slight difference between the peripheral and central regions in terms of flow velocity was observed. This however was not generating channeling phenomena. Urea creatinine and phosphate clearances were remarkably high and so were the Kt/V observed in all sessions, especially in relation to the studied blood flows. In conclusion, a significant blood to dialysate flow match with optimized countercurrent flow condition was observed in the studied hollow fiber hemodialyzers. Such optimization might be due both to the improved dialyzer design at the level of the blood header and to the specific fiber undulation that prevents dialysate channeling.

Biocompatible Materials↗

Continuous renal replacement therapy: does technique influence electrolyte and bicarbonate control?

BACKGROUND AND OBJECTIVES: Different techniques of continuous renal replacement therapy (CRRT) might have different effects on electrolyte and acid-base control. The aim of this study was to determine whether continuous veno-venous hemodiafiltration (CVVHDF) or continuous veno-venous hemofiltration (CVVH) achieve better control of serum sodium, potassium and bicarbonate concentrations. 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 sodium and potassium values and arterial bicarbonate levels from computerized biochemical records before and after the initiation of CRRT for up to 2 weeks of treatment. Statistical comparison of findings. MEASUREMENTS AND RESULTS: Before treatment, abnormal (high or low) values were frequently observed for sodium (65.1% for CVVHDF vs. 80.0% for CVVH; NS), potassium (45.9% vs. 34.0%; NS), and bicarbonate (73.3% vs. 68.0%; NS). After treatment, however, CVVHDF was more likely to achieve serum sodium concentrations within the normal range (74.1% vs. 62.9%; p=0.0026). Both treatments decreased the mean serum potassium concentration over the first 48 h (p=0.0059 and p<0.0001, respectively), but there was no difference in terms of the normalization of serum potassium concentration during the entire treatment period (88.3% vs. 90.5%; NS). Both treatments increased the mean arterial bicarbonate concentration over the first 48 hours (p=0.011 and p<0.0001, respectively). However, CVVH was associated with a lower incidence of metabolic acidosis (13.8% for CVVH vs. 34.5% for CVVHDF; p<0.0001) and a higher incidence of metabolic alkalosis (38.9% vs. 1.1%; p<0.0001) during the entire treatment period. CONCLUSIONS: CRRT strategies based on different techniques have a significantly different impact on sodium and bicarbonate control.

Acute Kidney Injury↗

Caspase-3 and -8 activation and cytokine removal with a novel cellulose triacetate super-permeable membrane in an in vitro sepsis model.

Pro-apoptotic molecules are generated during sepsis which may be responsible for alteration of organ function in sepsis. Removal of systemic apoptotic activity may affect recovery from sepsis. Current high flux membranes might not be sufficiently permeable to eliminate pro-apoptotic factors. We evaluated the elimination of pro-apoptotic factors induced by LPS in human whole blood by a super-permeable cellulose triacetate membrane (SUREFLUX FH 150, Nipro, Osaka, Japan) in comparison to a standard high flux cellulose triacetate membrane (UT 700, Nipro, Osaka, Japan) and a polyethersulfone plasmafilter (Bellco, Mirandola Italy) in an in vitro blood circulation. We spiked human whole blood with lipopolysaccharide from Escherichia coli (Serotype 026-86, 10 mg/ml), incubated it for 3 hours to allow cytokine generation and recirculated it at 300 ml/min for 3 hours. The UF line was first returned to the blood module at 10 min. After this, the UF was drained from 10 to 60 min at a rate of 1000 ml/h. Zero balance was obtained by re-infusion of bicarbonate buffered hemofiltration fluid. Apoptosis was assessed on U937 monocytes (incubated with plasma or ultrafiltrate) by fluorescence microscopy dyes (Hoechst 33342, propidium iodide) and annexin V flow cytometry. Caspase-3 and Caspase-8 activity was assessed on the recirculated blood monocytes by spectrophotometric methods. IL-2, IL-10 and TNFalpha were determined by commercially available ELISAs. Sieving coefficients and clearances were determined for the different cytokines. Caspase-3 and Caspase-8 were activated by LPS and remained either stable or increased during in vitro circulation. Apoptosis activity of U937 cells, when incubated with the ultrafiltrate, increased in parallel with arterial plasma values (for Uf: UT700 = 23.1%; Sureflux FH150 = 42.5%). However, by 60 min the apoptotic activity recorded with the ultrafiltrate was reduced to the levels of arterial plasma (for Uf: UT700 = 19.8%; Sureflux FH150 = 11.2%). Sieving coefficients in the super-permeable membrane were significantly higher for all measured cytokines in comparison to the standard high flux membrane (e.g. TNFalpha 0.72 vs 0.03 p < 0.001) and close to the values observed for the plasmafiltration membrane. Nevertheless protein losses measured by albumin leakage were much lower with the Sureflux filter in comparison to the plasmafilter. In conclusion, pro-apoptotic factors can be eliminated by dialytic membranes with the removal rate maximized by using super high flux dialysers which may represent a compromise between hemofiltration and plasmafiltration membranes.

Apoptosis↗

Continuous flow peritoneal dialysis: a new double lumen catheter.

Continuous flow peritoneal dialysis (CFPD) is a therapy originally utilized in the sixties. It was then abandoned because of technical reasons, but, today, a new interest in this technique is emerging, because of new technical solutions and new hardware capabilities. CFPD is a peritoneal dialysis technique in which a certain amount of fluid is maintained in the peritoneal cavity, while a continuous inflow and outflow is provided via twin catheters or through a double lumen catheter. In this paper a new double lumen catheter is presented. The catheter is characterized by the presence of a diffuser in the inflow lumen, while a standard coiled shape characterizes the outflow lumen. The diffuser allows the use of high dialysate flows without peritoneal damage and with an excellent distribution of the fluid. The other feature of the catheter is the removable hub which allows for an easy subcutaneous tunneling of the catheter with a subsequent connection to the y segment. The special shape also guarantees a minimum recirculation during treatment. Data obtained in the first implanted catheter showed a progressive increase in small solute clearances in relation to an increase of the flow and the tidal volume in the peritoneal cavity. In particular, urea clearances up to 48 ml/min and creatinine clearances up to 39 ml/min were obtained. No major complications were observed after one year of use of the catheter.

Catheters, Indwelling↗

When the ICU patient refuses vital supports.

The aim of this paper is to discuss the problem of caring for ICU patients who request forgoing of intensive supports; in particular, evaluating their competence and building effective relationships among the patients themselves, their relatives and the health care team. The histories of 2 adult competent ICU patients 2 asked that vital intervention be forgone are presented, together with the discussion of problems posed by such a request and of possible solutions which respect patients' autonomy and bystanders needs. These patients were hospitalized in an Italian general 14 bed ICU. The patients' request were weighted against their prognosis and their view of life, in order to evaluate their reliability. Also the refusal of either treatment or outcome was evaluated, in order to effectively safeguard the patients' interests. The request of one patient was satisfied and he was allowed to die, after all the involved people had understood and accepted the final decision. The second patient, who was somehow forced to undergo intensive treatment, is alive and satisfied with having been cured. In Italy too, autonomy is an increasingly applied principle in end-of-life decisions in ICUs. It is usually tempered by a consideration about the patients' best interest as perceived by involved bystanders.

Cardiopulmonary Resuscitation↗

Extracorporeal treatments in sepsis: are there new perspectives?

Sepsis continues to provide a major challenge to clinicians. Despite vast advancements achieved in the understanding of its pathways and mechanisms, the incidence of sepsis is increasing and the mortality and morbidity rates remain high, generating a considerable burden to health budgets worldwide. Unfortunately, no definitive therapy yet exists that can successfully treat sepsis and its complications. At variance with targeting single mediators, therapeutic intervention aimed at the non-selective removal of pro- and anti-inflammatory mediators seems a rational concept and a possible key to successful extra-corporeal therapies. A further advantage may lie in the continuous nature of such therapy. With such continuous therapy, sequentially appearing peaks of systemic mediator overflow may be attenuated and persistently high plasma levels reduced. This theoretical framework is proposed as the underlying biological rationale for a series of innovative modalities in sepsis. In this editorial, we will review recent animal and human trials which lend support to this concept. We will also review the importance of treatment dose during continuous renal replacement therapy as a major factor affecting survival in critically ill patients with acute renal failure. We will also review novel information related to other blood purification techniques using largo pore membranes or plasma filtration with adsorbent perfusion. Although these approaches are still in the early stages of clinical testing, they are conceptually promising and might represent an important advance.

Acute Kidney Injury↗

Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial.

BACKGROUND: Continuous veno-venous haemofiltration is increasingly used to treat acute renal failure in critically ill patients, but a clear definition of an adequate treatment dose has not been established. We undertook a prospective randomised study of the impact of different ultrafiltration doses in continuous renal replacement therapy on survival. METHODS: We enrolled 425 patients, with a mean age of 61 years, in intensive care who had acute renal failure. Patients were randomly assigned ultrafiltration at 20 ml/h-1/kg(-1) (group 1, n = 146), 35 ml/h(-1)/kg(-1) (group 2, n = 139), or 45 ml/h(-1)/ kg(-1) (group 3, n = 140). The primary endpoint was survival at 15 days after stopping haemofiltration. We also assessed recovery of renal function and frequency of complications during treatment. Analysis was by intention to treat. RESULTS: Survival in group 1 was significantly lower than in groups 2 (p = 0.0007) and 3 (p = 0.0013). Survival in groups 2 and 3 did not differ significantly (p = 0.87). Adjustment for possible confounding factors did not change the pattern of differences among the groups. Survivors in all groups had lower concentrations of blood urea nitrogen before continuous haemofiltration was started than non-survivors. 95%, 92% and 90% of survivors in groups 1, 2 and 3, respectively, had full recovery of renal function. The frequency of complications was similarly low in all groups. INTERPRETATION: Mortality among these critically ill patients was high, but increase in the rate of ultrafiltration improved survival significantly We recommend that ultrafiltration should be prescribed according to patient's bodyweight and should reach at least 35 ml/h(-1)/kg(-1).

APACHE↗

Importance of increased ultrafiltration volume and impact on mortality: sepsis and cytokine story and the role for CVVH.

There is growing interest in extracorporeal blood purification therapies (EBPT) as adjuvants in the complex therapy of sepsis and multiple organ dysfunction syndrome (MODS). Nowadays the only routinely used purification technique is 'renal replacement therapy' (RRT) during acute renal failure (ARF), one of the almost inevitable and deadly components of MODS. RRT has been the first and still is the most utilised and effective type of EBPT. Evidence is growing about its ability to maintain homeostatic balance in critically ill patients, and specifically in septic patients with MODS. Clinical trials have been recently designed to modify or improve these therapies. In detail, the following issues have been currently addressed: effects on blood purification provided by different therapies, adequacy of prescription and delivery of therapy, toxins and solutes to be removed with these techniques. Based on these speculations we will briefly review the current understanding of these issues and the rationale for application of RRT in the intensive care unit (ICU). In particular, we will focus on the importance of increased ultrafiltration volume and its impact on mortality in the general ICU population and in septic patients.

Acute Kidney Injury↗

Coupled plasma filtration adsorption.

Both pro-inflammatory and anti-inflammatory mediators participate in the pathogenesis of sepsis and explain the failure of specific therapies to improve survival. Continuous extracorporeal therapies have been proposed as a therapeutic option in sepsis. We have studied the effects of plasma filtration associated with adsorption in patients with septic shock. We have shown 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 device modular to conventional hemofiltration, may pave the way to innovative approaches to the extracorporeal treatment of septic patients.

Adsorption↗

Cytokine removal with a large pore cellulose triacetate filter: an ex vivo study.

OBJECTIVE: To test the hypothesis that hemofiltration using a new large pore cellulose triacetate hemofilter can achieve effective ultrafiltration of cytokines. DESIGN: Ex-vivo study. SETTING: Laboratory of Intensive Care Unit in tertiary hospital. SUBJECTS: Six healthy volunteers. INTERVENTIONS: Blood from 6 volunteers was incubated for 4 hours with 1 mg of endotoxin and then circulated through a closed hemofiltration circuit with a large pore cellulose triacetate hemofilter (nominal cut-off point: 60 kilodaltons). Hemofiltration was conducted at 1 L/h or 6 L/h of ultrafiltrate (UF) flow at the start of extra-corporeal circulation, and after 2 and 4 hours. Samples were taken from the arterial, venous and UF sampling ports. MEASUREMENTS AND MAIN RESULTS: IL-Ibeta, IL-6, IL-8, IL-10, TNFalpha, and albumin were measured. Sieving coefficients (SC) above 0.6 were achieved for IL-Ibeta and IL-6 and SCs above 0.3 were achieved for IL-8 and TNF-alpha at 1 L/h. Sieving coefficients of all cytokines (except IL-10, p=0.22) were reduced when the ultrafiltration rate was increased from IL/h to 6 L/h (p<0.01), but the increase in ultrafiltration rate resulted in an overall increase in the clearance of all cytokines (p<0.001). The highest SC for albumin was 0.07 at 4 hours at 1 L/h, and fell to 0.01 at 6 L/h. The SCs for IL-8 fell at 4 hours (p<0.01), but the SCs for other cytokines did not change. No adsorption of cytokines and albumin was observed. CONCLUSION: High volume hemofiltration (HVHF) using a new large pore cellulose triacetate filter achieved cytokine clearances greater than those reported with currently available hemo filters.

Albumins↗

Continuous veno-venous hemodiafiltration or hemofiltration: impact on calcium, phosphate and magnesium concentrations.

BACKGROUND AND OBJECTIVES: Different techniques of continuous renal replacement therapy (CRRT) might have different effects on calcium, phosphate and magnesium concentrations. Accordingly, we tested whether continuous veno-venous hemodia filtration (CVVHDF) or continuous venovenous hemofiltration (CVVH) would achieve better control of these electrolytes. 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 ionized calcium, phosphate and magnesium before and after the initiation of CRRT for up to 2 weeks of treatment. MEASUREMENTS AND RESULTS: Before treatment, both groups had a high incidence of abnormal ionized calcium concentrations (57.2% for CVVHDF vs 46.0% for CVVH; NS). After treatment, both groups showed a significant increase in serum calcium concentration over the first 48 h (p=0.041 vs p=0.0048) but hypercalcemia was more common during CVVHDF (15.3% vs 0.4%; p<0.0001). However, in both groups, hypocalcemia remained common (30.9% vs 36.7%; NS). Before treatment, abnormal serum phosphate concentrations were also common (65.1% for CVVHDF vs 78.1% for CVVH; NS). After treatment, both groups achieved a significant reduction of serum phosphate within 48 hours (p<0.0001 in both groups). There was no difference in the prevalence of abnormal phosphate levels during treatment (45.5% vs 42.4%; NS). Before treatment, both groups had a high incidence of abnormal magnesium concentrations (50.0% for CVVHDF vs 51.2% for CVVH; NS). During treatment, there was no significant change in serum magnesium concentrations during the first 48 hours or in the prevalence of abnormal magnesium concentrations (56.3% vs 63.4%; p=0.13). However CVVHDF was associated with a higher prevalence of hypomagnesemia (8.1% vs 0.4%; p<0.0001) and a lower incidence of hypermagnesemia (48.2% vs. 63.0%; p=0.0014). CONCLUSIONS: In critically ill patients with ARF, calcium, phosphate and magnesium were commonly abnormal and they were only partly corrected by CRRT. CVVH and CVVHDF had a different effect on serum magnesium concentrations.

Acute Kidney Injury↗