PubMed Health⌕ Search

Biomedical subjects

Ciro Tetta

Publications and source records attributed to Ciro Tetta.

At least 37 records · Page 2Linked to original sources

Hemodynamic response to coupled plasmafiltration-adsorption in human septic shock.

OBJECTIVE: The objective was to examine the effect of repeated applications of coupled plasmafiltration-adsorption on the hemodynamic response in septic shock patients hospitalized in intensive care units (ICUs). DESIGN: Prospective, intention-to-treat. SETTING: General ICU of a tertiary care, non-teaching, 400-bed, city hospital. PATIENTS AND PARTICIPANTS: Twelve consecutive mechanically ventilated septic shock patients, with or without concomitant acute renal failure (ARF). INTERVENTION: A median of 10 consecutive sessions (prescribed treatment time: 10 h/session; delivered duration: 8.43+/-1.37 h/min) of coupled plasmafiltration-adsorption for each patient. MEASUREMENTS AND RESULTS: Mean arterial pressure (77.2+/-12.5 [CI 95%; 74.5-79.8] vs. 83.3+/-14.1 [CI 95%; 80.3-86.3] mm Hg; [ p<0.001]), cardiac index (4.03+/-0.89 [CI 95%; 3.83-4.22] vs. 3.46+/-0.82 [CI 95%; 3.28-3.64] L/m(2)/min; [ p<0.001]), systemic vascular resistance index (1,388+/-496 [CI 95%; 1,278-1,497] vs. 1,753+/-516 [CI 95%; 1,639-1,867] dynes x s/cm(5); [ p<0.001]), PO2/FIO2 ratio (204+/-87 [CI 95%; 185-223] vs. 238+/-82 [CI 95%; 220-256]; [ p<0.001]), significantly improved during 100 global treatments (pre- vs. post-treatment values). Intra-thoracic blood volume and extra-vascular lung water did not change across treatments. Vasopressor requirement was reduced: norepinephrine decrease from an infusion rate of 0.13+/-0.07 (CI 95%; 0.06-0.16) to 0 gamma/kg/min after a mean of 5.3+/-2.7 sessions. C reactive protein (CRP) significantly decreased (from 29.3+/-7.3 vs. 7.9+/-4.8; p<0.0001) during treatment. Survival was 90% at day 28 and 70% at day 90. CONCLUSION: Coupled plasmafiltration-adsorption was a feasible and safe extracorporeal treatment and exerted a remarkable improvement in the hemodynamics, the pulmonary function, and the outcome in septic shock patients with or without concomitant ARF.

APACHE↗

Review on uremic toxins: classification, concentration, and interindividual variability.

BACKGROUND: The choice of the correct concentration of potential uremic toxins for in vitro, ex vivo, and in vivo experiments remains a major area of concern; errors at this level might result in incorrect decisions regarding therpeutic correction of uremia and related clinical complications. METHODS: An encyclopedic list of uremic retention solutes was composed, containing their mean normal concentration (CN), their highest mean/median uremic concentration (CU), their highest concentration ever reported in uremia (CMAX), and their molecular weight. A literature search of 857 publications on uremic toxicity resulted in the selection of data reported in 55 publications on 90 compounds, published between 1968 and 2002. RESULTS: For all compounds, CU and/or CMAX exceeded CN. Molecular weight was lower than 500 D for 68 compounds; of the remaining 22 middle molecules, 12 exceeded 12,000 D. CU ranged from 32.0 ng/L (methionine-enkephalin) up to 2.3 g/L (urea). CU in the ng/L range was found especially for the middle molecules (10/22; 45.5%), compared with 2/68 (2.9%) for a molecular weight <500 D (P < 0.002). Twenty-five solutes (27.8%) were protein bound. Most of them had a molecular weight <500 D except for leptin and retinol-binding protein. The ratio CU/CN, an index of the concentration range over which toxicity is exerted, exceeded 15 in the case of 20 compounds. The highest values were registered for several guanidines, protein-bound compounds, and middle molecules, to a large extent compounds with known toxicity. A ratio of CMAX/CU <4, pointing to a Gaussian distribution, was found for the majority of the compounds (74/90; 82%). For some compounds, however, this ratio largely exceeded 4 [e.g., for leptin (6.81) or indole-3-acetic acid (10.37)], pointing to other influencing factors than renal function, such as gender, genetic predisposition, proteolytic breakdown, posttranslation modification, general condition, or nutritional status. CONCLUSION: Concentrations of retention solutes in uremia vary over a broad range, from nanograms per liter to grams per liter. Low concentrations are found especially for the middle molecules. A substantial number of molecules are protein bound and/or middle molecules, and many of these exert toxicity and are characterized by a high range of toxic over normal concentration (CU/CN ratio). Hence, uremic retention is a complex problem that concerns many more solutes than the current markers of urea and creatinine alone. This list provides a basis for systematic analytic approaches to map the relative importance of the enlisted families of toxins.

Humans↗

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↗

Effects of biofilm formation on haemodialysis monitor disinfection.

BACKGROUND: Biofilms are composed of communities of micro-organisms adhering to essentially any surface. We evaluated whether biofilm formation in the hydraulic circuit of a purposely contaminated haemodialysis monitor would modify the efficacy of different disinfection modalities against bacteria and endotoxin concentrations. METHODS: A water-borne Pseudomonas aeruginosa (109) suspension was recirculated for 1 h and was left standing for 72 h (stationary phase) in the hydraulic circuit of the monitor. The monitor was then washed and disinfected by different physical (heat, 85 degrees C) or chemical (hypochlorite or peracetic acid) disinfection modalities (protocol A). In protocol B, the bacterial suspension was also recirculated for 1 h, but the monitor was then immediately washed and disinfected by different chemical disinfection modalities (hypochlorite or peracetic acid). RESULTS: Biofilm formation was revealed by scanning and confocal laser electron microscopy after the stationary phase (protocol A), but was absent when the monitor was immediately washed and disinfected (protocol B). In the presence of biofilm (protocol A), heat in association with citric acid was the most effective modality for reducing both colony forming units and endotoxin concentrations, whereas heat by itself was the least effective method of disinfection. Dwelling (60 h) with diluted peracetic acid completely prevented the formation of biofilm. In the absence of biofilm (protocol B), chemical disinfection proved to be effective against both colony forming units and endotoxin concentrations. CONCLUSIONS: We found that biofilm formation may markedly reduce the efficacy of presently available disinfection modalities. Therefore, different disinfection modalities and the combined action of descaling (by citric acid) and disinfection (physical/chemical agents) should be used periodically in haemodialysis monitors. In addition, dwelling with diluted peracetic acid should be adopted whenever monitors are not in use.

Bacterial Infections↗

Oxidative stress during ex vivo hemodialysis of blood is decreased by a novel hemolipodialysis procedure utilizing antioxidants.

The high cardiovascular mortality in patients receiving hemodialysis (HD) has been attributed, in part, to oxidative stress. Here we examined the effectiveness of antioxidants introduced by means of a novel hemolipodialysis (HLD) procedure in terms of reducing oxidative stress during ex vivo blood circulation. Oxidative stress was studied in a model HD system resembling the extracorporeal circulation of blood during clinical HD. Blood circulation produced an increase of up to 280% in free hemoglobin levels and an increase of 320% in electronegative LDL (LDL(-)) subfraction. A significant correlation between LDL(-) and free hemoglobin levels confirmed previous findings that LDL(-) formation during ex vivo circulation of blood can be mediated by the oxidative activity of free hemoglobin. These effects were significantly attenuated during HLD using a dialysis circuit containing vitamin E with or without vitamin C. By contrast, HLD with vitamin C alone had a marked pro-oxidant effect. TBARS, lipid hydroperoxides, vitamin E and beta-carotene content in LDL were not significantly altered by the HD procedure. These findings demonstrate the occurrence of oxidative stress in human plasma where lipoproteins are a target and indicate antioxidant-HLD treatment as a specific new approach to decreasing the adverse oxidative stress frequently associated with cardiovascular complications in high-risk populations of uremic patients.

Antioxidants↗

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↗

Changes of serum albumin and C-reactive protein are related to changes of interleukin-6 release by peripheral blood mononuclear cells in hemodialysis patients treated with different membranes.

Protein malnutrition, a condition associated with an albumin concentration less than 3.5 g/dL, has been shown to be a major risk factor for increased mortality in hemodialysis patients. The aim of this cross-over study was to evaluate the relationship between the type of membrane adopted and serum albumin changes by measuring peripheral blood mononuclear cells (PBMC) interleukin-6 (IL-6) release, serum albumin, and plasma concentrations of C-reactive protein (CRP) in 18 patients dialyzed with different membranes. During the study, all patients were dialyzed with cuprophan (CU), synthetically modified cellulosic (SMC) membrane (a new cellulosic membrane with lesser complement activation), and cellulose diacetate (CD) membrane, and have served as their own controls. IL-6 spontaneous release by PBMC resulted after 3 months of SMC (436.2 +/- 47.4 pg/mL) significantly (P < 0.05) reduced as compared with CU (569.3 +/- 24.5 pg/mL). This effect was more evident after 6 months of dialysis with SMC (220 +/- 35.3 pg/mL, P < 0.01 versus CU and versus 3 months of SMC). The passage to CD membrane was followed by a progressive new increase in the IL-6 PBMC release (332.3 +/- 30.7 after 3 months, and 351.2 +/- 35.8 pg/mL after 6 months, respectively) that, however, remained significantly (P < 0.05) lower than CU. The behavior of CRP plasma levels resembled that of IL-6 PBMC release (23.3 +/- 4.7 in CU, 11.0 +/- 2.1 after 3 months in SMC, and 7.9 +/- 1.5 after 6 months in SMC, respectively). IL-6 release values were positively correlated with circulating levels of CRP (r = 0.3264, P < 0.002). Serum albumin increased after 6 months of dialysis with SMC membranes (3.25 +/- 0.09 g/dL in CU and 3.64 +/- 0.07 g/dL in SMC, P < 0.05). When the patients were switched to CD, serum albumin showed a slight, though not statistically significant, decrease. Serum albumin concentrations negatively correlated with both IL-6 release values (r = -0.247, P < 0.05) and CRP plasma levels (r = -0.433, P < 0.001). In conclusion, our data clearly show that a significant relationship exists between biocompatibility of the membranes and serum albumin changes; serum albumin levels, in fact, are negatively correlated with the PBMC spontaneous IL-6 release values and CRP circulating levels.

Biocompatible Materials↗

The Acute Dialysis Quality Initiative--part V: operational characteristics of CRRT.

This report represents the consensus statement of the ADQI workgroup addressing the operational characteristics of continuous renal replacement therapy (CRRT). Issues addressed included the specific operational characteristics of continuous hemofiltration (HF), continuous hemodialysis (HD), and continuous hemodiafiltration (HDF) and the impact of these different modalities on solute removal. The relative roles of arteriovenous (AV) and venovenous (VV) modalities of therapy were also evaluated. The workgroup also addressed the optimal components of a CRRT system from an operational standpoint.

Hemodiafiltration↗

Evolution of oxidative stress and inflammation during hemodialysis and their contribution to cardiovascular disease.

End-stage renal disease patients have increased cardiovascular morbidity and mortality. These patients have many unique risk factors, such as an accumulation of uremic toxins, electrolyte imbalances, metabolic disturbances, anemia, chronic inflammation, and thrombogenic disturbances. Oxidative stress has been implicated in many of these disturbances. This review will focus on some of the factors that may accelerate cardiovascular disease in uremic patients, with an emphasis on mechanisms and interactions of various components of oxidative stress and inflammation. Understanding the mechanisms of these pathways may be useful in developing effective prevention and treatment strategies.

Cardiovascular Diseases↗

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↗