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Background: Patients affected by hilar cholangiocarcinoma are eligible for surgery only in the 20-30% of the cases and postoperative mortality is 40-50%. Many specialists are involved in the treatment of this disease, like surgeons, gastroenterologists, oncologists and radiotherapists. Recent studies have shown that preoperative bilirubinaemia is a predictor of morbidity and mortality after surgery. Coupled Plasma Filtration and Adsorption (CPFA) is a blood purification extracorporeal therapy recommended for sepsis and able to reduce bilirubinaemia., Methods: We treated 10 patients referred to our centre affected by hilar cholangiocarcinoma complicated by obstructive jaundice with 34 CPFA sessions to test its ability to reduce preoperative bilirubin levels and we checked for mortality at 90 days., Results: CPFA reduced preoperative bilirubin of 30% for session; it also improved others inflammation and coagulation tests. Mortality at 90 days was 40%., Conclusions: CPFA is an effective therapy for hyperbilirubinaemia. Lowering preoperative bilirubinaemia and improvement of coagulation tests subsidized the management of the patients but in our study did not affect postoperative mortality. Further studies to evaluate the indications for treatments that remove bilirubin in this setting are needed.

During sepsis, lipopolysaccharide released by gram-negative bacteria induces activation of inflammatory pathways resulting in organ dysfunction and failure. Extracorporeal therapies that remove this molecule and support organ function are useful in critically ill patients in ICUs. Today, blood purification therapies such as high-volume hemofiltration, polymyxin B hemoperfusion, and coupled plasma filtration adsorption are easy to perform. According to the reconciliation of the three sepsis theories and thanks to the removal of lipopolysaccharide (the first inflammatory stimulus) from the blood, we can provide an effective and useful extracoporeal therapy for this clinical condition.

Coupled plasma filtration absorption (CPFA) can increase blood pressure in septic shock and reduce fever during and after treatment. It is not able to stop the activation of intravascular coagulation and does not reduce the need for dialysis or the overall mortality.

The utilization of renal replacement therapies in cardiac patients has received increasing attention in recent years. In fact, isolated ultrafiltration has been proposed in patients with heart failure as a means for rapidly relieving fluid overload while preserving renal function; moreover, periprocedural hemofiltration (HF) has been suggested for radiocontrast-induced nephropathy (RCIN) prophylaxis. As a matter of fact fluid overload, with the ensuing systemic and pulmonary congestion, remains a major problem in patients with heart failure, and diuretic resistance is not an uncommon feature in the more advanced stages of the syndrome. In the same way, RCIN is increasingly indicated as a major complication of the use of iodinated contrast media, accounting for a significant number of hospital-acquired acute kidney injury episodes; moreover, it is thought to be associated with short- and long-term adverse effects on patient prognosis and increased economic burden. This article is aimed at reviewing the background of renal replacement therapies in the clinical context of cardiology wards, with special regard to isolated ultrafiltration and HF, as well as the current evidence regarding the safety and efficacy of these procedures, and their economic impact. From a theoretical point of view, isolated ultrafiltration could have a number of potential heart- and kidney-related advantages if compared to standard therapy (mainly diuretics). However, currently available clinical evidence does not support these concepts for its widespread utilization. Thus, isolated ultrafiltration should be reserved for selected patients with advanced heart failure and diuretic resistance, as part of a more complex strategy devoted to the control of fluid retention. There is currently no sound evidence for routinely recommending periprocedural HF in coronary angiography procedures, even in patients at high risk for RCIN.

High-volume hemofiltration (HVHF) and coupled plasma filtration adsorption (CPFA) have shown potential to improve the treatment of sepsis in animals, but there have been no studies comparing these two treatments in humans. Our aim was to compare the hemodynamic effects of HVHF and CPFA in septic shock patients with acute kidney injury (AKI) undergoing continuous renal replacement therapy (CRRT). We performed a cross-over study enrolling patients with septic shock and AKI who were receiving CRRT. Patients were treated with pulse HVHF and continuous veno-venous hemofiltration (CVV H) on day 1 and CPFA and CVV H on day 2 or vice versa. HVHF was performed for 8-10 hours with a replacement fluid rate of 85 mL/kg/h. CPFA was performed for 8-10 hours with a plasma flow rate of 15%. CVV H was performed for the rest of the day with a replacement fluid rate of 35 mL/kg/h. The primary endpoints were changes in mean arterial pressure, vasopressor requirement (expressed as vasopressor score, VS), and noradrenaline dose after pulse HVHF and CPFA. The two treatments were compared using nonparametric tests. We enrolled 8 patients (median age 70.5 years, SOFA 12.5, SAPS II 69.5). There was a trend towards a reduction in VS with HVHF and CPFA (HVHF p=0.13, CPFA p<0.05). There was no significant difference between the two treatments in terms of percentage change in VS score (p=0.22). The data from this pilot study provide no evidence for a difference in hemodynamic effects between pulse HVHF and CPFA in patients with septic shock already receiving CRRT. A larger sample size is needed to adequately explore this issue.

The Molecular Adsorbent Recirculating System (MARS) clears the blood from catabolites that either occur free in the plasma water (through dialysis), such as uremic toxins and ammonia, or are bound by albumin, such as hepatic toxins. The latter are transferred from the albumin in the blood to the albumin circulating in a closed loop where toxins are removed by adsorption on resins (charcoal and ion-exchange resin). The efficacy of this extracorporeal blood purification method in the treatment of acute or acute-on-chronic liver failure (also associated with renal failure) has been demonstrated in numerous studies. Fifty-one patients, 5 affected by acute liver failure and 46 by acute-onchronic liver failure (8 of them with additional renal failure) were treated with MARS. The results demonstrated that the method, which effectively removes ammonia, bilirubin, bile acids and uremic toxins, reduces the blood concentration of these molecules. It thereby improves the patient's clinical condition and biochemical parameters including cholinesterase, alkaline phosphatase and prothrombin activity, eliminating, in addition, the drug-refractory pruritus that is a very frequent symptom in cholestatic liver disease. These results agree with those reported in the literature concerning the efficacy of MARS in the replacement of the detoxifying function of kidneys and liver.

Among various methods and models to evaluate the dialysis dose, the on-line measure of ionic dialysance gives good results. Compared to measured KT/V, ionic dialysance does not require blood sampling and, consequently, it reduces the risks and the costs. Functional evaluations during acetate free biofiltration (AFB treatments) confirm the usefulness of the on-line continuous measure by biosensors, especially when they are integrated in the dialysis machinery.

Aim: To study safety, clinical and operative feasibility of continuous veno-venous hemofiltration (CVVH) with anticoagulation only of the filter in patients at risk for bleeding., Methods: This prospective, comparative, non randomised study was completed at an intensive care unit of a teaching NHS hospital. Sixteen liver transplant (LT) recipients with acute renal failure needing CVVH were treated with a regional anticoagulation protocol (heparin and protamine were administered respectively pre- and post-filter) and compared to 11 critically ill subjects who received a standard low-heparin treatment. Activated coagulation time (ACT) monitoring was used to adjust anticoagulation and heparin neutralization., Results: Mean circuit life was 35.8+/-13.6 hours (95% CI 28.5-43.1) in patients receiving regional anticoagulation and 34.4+/-14 hours in controls (95% CI 25.5-43.3; p=0.7). Fourty-eight circuits (47.5% of the total) in the heparin-protamine group had a life-span longer than 30 hours and other 22 (21.7%) were changed intentionally after 24 hours of use in absence of clots. None of the patients in both the studied groups had bleeding or hemodynamic complications and their azotemic control was always satisfactory., Conclusion: In LT recipients, regional anticoagulation can achieve a circuits life-span comparable to that from systemic anticoagulation with satisfactory safety and simplicity of use.

Background: The congestive heart failure (IV cl. NYHA) refractory to medical therapy, can be treated with ultrafiltrative method such as extracorporeal ultrafiltration (UF), intermittent veno-venosus hemofiltration, intermittent peritoneal dialysis (IPD) or chronic ambulatory peritoneal dialysis (CAPD)., Methods: Sixty-one patients suffering from SCC have been managed by combining medical therapy with ultrafiltrative treatment., Results: 28% (17 patients) died within a week from ultrafiltrative therapy beginning. 39% (24 patients) took up to respond to medical therapy (responders). 33% (20 patients) didn't give a proper response to pharmacological therapy (non responders), therefore a ultrafiltration program with chronic ambulatory peritoneal dialysis (CAPD) has been undertaken. Among ultrafiltrative methods applied to patients, IVVH is the most effective. Clinical parameters analysis, relevant to dehydration acute phase, points out: an evident loss of corporeal weight between dehydration pre-post phases in all 3 groups, with statistically significant results; a SAP values reduction between the beginning and the end of treatment in all 3 groups; a PAD values reduction in the group of deceased and non responders. This value remains stable in responders group. Non responders patients, inserted in a ultrafiltration program with CAPD present the following survival rate: 55%: 6 months; 35%: 1 years; 15%: 4 years. These patients maintain a good self-management in 50%, sufficient in 35% and totally partner-dependent in 15%., Conclusions: Ultrafiltration method together with pharmacological therapy allows a resetting of neuro-endocrine and electrolytic system in refractory congestive heart failure patients and a recovery of a pharmacological response. Without such a response a cardio-circulatory balance can be maintained through a CAPD method.

Background: In the course of Continuous Veno-Venous Hemofiltration (CVVH), bicarbonate buffer instead of lactate is suitable for the treatment of combined renal and hepatic failure and for patients suffering from lactic acidosis, type A or B, joined with acute renal failure (ARF)., Methods: We applied the CVVH buffered with bicarbonate for the treatment of two patients affected by ARF and severe lactic acidosis type B (due to biguanide intoxication) and we evaluated its ability to correct the acid-base balance., Results: Clinical and laboratory data show that this technique, performed in standard conditions (plasma flow: 70 ml/min, ultrafiltration: 25 ml/min, bicarbonate concentration in the infusion fluid: 30 mEq/L), was inadequate to compensate for the high requirement of bicarbonate (approximately 280 mEq/hr during the first 6 hours of observation) and the severe metabolic acidosis, thus additional bicarbonate infusion was needed., Conclusions: In particular, from ascertained data and theoretical considerations, in the course of lactic acidosis caused by biguanide, in order to correct acidosis a positive balance of bicarbonate could be obtained only by means of a bicarbonate-based replacement fluid and of a continuous high flow hemofiltration, such as to assure an ultrafiltrate volume exceeding 150 ml/min.

The efficacy of the dialysis in the heart failure non responsive to the traditional methods is well known. In our study we have evaluated the effects of three different dialytic methods (UFI: ultrafiltration isolate; HF: hemofiltration; CAVH: continuous arteriovenous hemofiltration). These methods are used to cause a good depletion in the patients with intractable heart failure following from ischaemic valvular or primitive cardiomiopathy. We have treated 18 patients (6 for each method) and the patients with organic or functional renal disease were treated with the methods (HF and CAVH) that have depletive and depurative effects. Each of these methods is capable, without important differences, of achieving the following aim: the hydro-sodium depletion, the correction of the haemodynamic alteration and the re-establishment of the response to the traditional medical treatment. Using the hemofiltration and continuous arteriovenous hemofiltration, both soft methods, we have obtained values of dehydratation, absolute and for each session, higher than isolated ultrafiltration. The follow-up has not pointed out differences, of both prognosis and survival among patients treated with the three methods studied, whose effects are always only temporary; only the heart transplantation or the valvular correction, by operating in a very important way on the basal cardiopathy, is the resolutive event.

Objective: To describe the use of an automatic fluid control system, Equaline, during high flux continuous hemofiltration., Design: Prospective descriptive study., Setting: General intensive care unit in a general hospital., Patients: 15 consecutive patients suffering from septic shock, hypercatabolic with acute renal failure., Intervention: Pump driven continuous veno-venous hemofiltration (PDCVVH) with high flux was performed. All pts were intubated, under mechanical ventilation and treated with vasoactive agents for hemodynamic instability. Fluid balance was achieved with an automatic fluid control system, Equaline, on daily basis according to clinical needs., Measures: Length of treatment, daily amount of ultrafiltrate and urea removal, urea and creatinine blood level before and after the treatment were registered., Results: Age was 59.1 years, SAPS 17.2. Patients were treated for an average period of 9 days obtaining a daily ultrafiltrate production of 21.4 L. In all pts, though the high catabolism (daily nitrogen production > 30 g), there was a significant decrease of urea and creatinine concentration., Conclusion: Equaline system was able to maintain intravascular volume in the face of high ultrafiltration rate avoiding clinically important discrepancies between ultrafiltrate formation and fluid replacement. We conclude that PDCVVH management is greatly improved with use of such servo-controlled feedback system.

Electrolyte and acid-base balance was evaluated in 14 high UF (124 +/- 7 ml/min) hemodiafiltration sessions. The dialysate contained (in mEq/l): Na 138-140, K 2-3, Ca 3.5, Mg 0.5-0.7, Cl 106-110, acetate 38 or acetate 3 and bicarbonate 35-38. The fluid, infused in postdilutional mode, was 23.5 +/- 21 per session (session length 203 +/- 22 minuti), 80% containing Na 138, K 2, Ca 3.5, Mg 1, Cl 109.5, acetate 35 and 20% Na 145, HCO3 100, Cl 45. The balance was: negative for Na (-255 +/- 220 mEq), for K (-74 +/- 22 mEq) and for Mg (-166 +/- 141 mg), positive for Ca (215 +/- 147 mg) and for acetate (590 +/- 15 and 966 +/- 412 mmol); the electrolytes and bicarbonate plasma values were within of close to normal limits during the session. An unphysiological feature was the positive balance of acetate which, though, was metabolized during the interdialytic period as to return to normal predialytic values. Therefore, in high UF HDF, the above combination of dialysate and reinfusate allows a reasonable electrolyte and acid-base balance; however, bicarbonate should be the only buffer in order to avoid unphysiological levels of other buffers in the biological fluids.

A group of well nourished young patients was examined during 2 longterm consecutive high efficiency dialytic schedules to detect possible clinical and biochemical differences. The patients were first studied during hemodialysis with a 1.2 m2 cuprophan membrane and blood flow of 400 ml/min and, then, during hemodiafiltration with an ultrafiltration rate greater than 100 ml/min by using high permeability membranes with a surface greater than or equal to 1.4 m2. As expected by the higher clearances obtained on hemodiafiltration, this technique resulted in a significant reduction of dialysis time and of BUN and serum creatinine, associated with a significant increase of hemoglobin, possibly related to a better deintoxication. Furthermore, the dry body weight decreased significantly during hemodialysis, whereas it increased significantly during hemodiafiltration, despite unchanged dietary habits, indicating possible differences in the nutrients utilization during the 2 dialytic schedules. Therefore, in chronically dialyzed patients, highly permeable synthetic membranes should be preferred to cuprophan because of a supposed better biocompatibility and should be used with the highest ultrafiltration rate in order to obtain a better dialytic efficiency and to avoid the risk of backfiltration.

The risks of back-filtration that occur with the use of high hydraulic permeability membranes with haemodialytic techniques in the course of which the difference between forced and necessary ultrafiltration is compensated for by correcting transmembrane pressure in favour of the dialyser compartment. In this way a form of concealed haemodiafiltration is attained in which the replacement fluid is the dialysing solution, annulling, owing to the possible consequences of the transit of bacterial endotoxins into the circulation, all the advantages linked to the use of these membranes. It is concluded by suggesting the implementation of well controlled haemodiafiltration through the careful quali-quantitative evaluation of the replacement fluid.

A new hemodiafiltration technique, acetate free biofiltration (AFB), has been recently introduced in the treatment of chronic uremia. It is performed with a buffer free dialysate and a simultaneous infusion in post-dilution mode of a sodium bicarbonate solution (concentration 145-166 mEq/l; infusion rate 1.2-2 l/h). A polyacrylonitrile hollow fiber AN69 HF 1.2 sqm dialyzer is employed. In acute studies pCO2 remains stable throughout the treatment, as well as pCO2. We have found a significant inverse correlation between delta[HCO3-] pre and post treatment and basal [HCO3-] (r = -0.88; p less than 0.001), with an excellent correction of uremic acidosis, avoiding post dialytic alkalosis. Our long term experience on 6 patients followed up to 31 months, allows us to consider AFB as a feasible and safe treatment, offering a good correction of uremic acidosis and an excellent hemodynamic tolerance. We propose AFB as a competitive technique with respect to bicarbonate hemodialysis, hemodiafiltration and standard biofiltration.

We evaluated the use of activated charcoal plasmaperfusion in four patients already treated with synthetic antithyroid agents affected by severe hyperthyroid. Our patients showed no significant side-effect and a rapid improvement of their symptoms. Thyroid hormone levels were 30% lower after the procedure, but returned to previous levels after 7-10 days. Activated charcoal plasmaperfusion may represent a useful therapeutic adjunct to antithyroid drugs in patients affected by severe hyperthyroidism or thyrotoxic storm.

Mortality rate among patients with septic, oliguric, multiple organ failure is high. Conventional hemodialysis has often detrimental effects on critically ill patients. Continuous arteriovenous hemofiltration (CAVH), continuous arteriovenous hemodialysis (CAVH/D) and continuous arteriovenous hemodialysis associated with sequential plasmapheresis (CAVHP/D) could reduce mortality in septic (hypercatabolic, oliguric) ARDS induced MOF patients. These techniques are simple and can be managed without superspecialized personnel.