Thrombotic microangiopathy due to primary antiphospholipid syndrome: successful treatment with eculizumab.

Antiphospholipid syndrome nephropathy includes a variety of histological lesions, including thrombotic microangiopathy, which is not included among the diagnostic criteria of antiphospholipid syndrome. Whereas in secondary antiphospholipid syndrome, e.g. to systemic lupus erythematosus, there is emerging evidence of a benefit from complement blockade with eculizumab, optimal treatment of primary antiphospholipid syndrome-associated thrombotic microangiopathy is currently unknown. We report the case of a 36-year-old male patient with primary antiphospholipid syndrome-associated thrombotic microangiopathy, presenting with a clinical picture of atypical hemolytic-uremic syndrome with frequent relapses, treated with eculizumab (four 900 mg weekly doses followed by 1200 mg fortnightly infusions) leading to resolution of hemolysis, long-term remission and partial kidney function recovery (peak serum creatinine 3.8 mg/dL, decreased and stabilized around 2.5 mg/dL) over a follow up period of over 2 years.

[Reorganization of haemodialysis during COVID-19 emergency: a report from Dialysis Centers of Parma province].

The epidemic wave that hit Italy from February 21st, 2020, when the Italian National Institute of Health confirmed the first case of SARS­CoV­2 infection, led to a rapid and efficient reorganization of Dialysis Centers' activities, in order to contain large-scale spread of disease in this clinical setting. We herein report the experience of the Hemodialysis Unit of Parma University Hospital (Azienda Ospedaliero-Universitaria, Parma, Italy) and the Dialysis Centers of Parma territory, in the period from March 1st, 2020 to June 15, 2020. Among patients undergoing chronic haemodialysis, 37/283 (13%) had positive swabs for SARS­CoV­2, 9/37 (24%) died because of COVID-19. Twenty-three patients required hospitalization, while the remaining were managed at home. The primary measures applied to contain the infection were: the strengthening of personal protective equipment use by doctors and nurses, early identification of infected subjects by performing oro-pharyngeal swabs in every patient and in the healthcare personnel, the institution of a triage protocol when entering Dialysis Room, and finally the institution of two separate sections, managed by different doctors and dialysis nurses, to physically separate affected from unaffected patients and to manage "grey" patients. Our experience highlights the importance and effectiveness of afore-mentioned measures in order to contain the spread of the virus; moreover, we observed a higher lethality rate of COVID-19 in dialysis patients as compared to the general population.

Integrated strategies to prevent intradialytic hypotension: research protocol of the DialHypot study, a prospective randomised clinical trial in hypotension-prone haemodialysis patients.

INTRODUCTION: In patients on maintenance haemodialysis (HD), intradialytic hypotension (IDH) is a clinical problem that nephrologists and dialysis nurses face daily in their clinical routine. Despite the technological advances in the field of HD, the incidence of hypotensive events occurring during a standard dialytic treatment is still very high. Frequently recurring hypotensive episodes during HD sessions expose patients not only to severe immediate complications but also to a higher mortality risk in the medium term. Various strategies aimed at preventing IDH are currently available, but there is lack of conclusive data on more integrated approaches combining different interventions. METHODS AND ANALYSIS: This is a prospective, randomised, open-label, crossover trial (each subject will be used as his/her own control) that will be performed in two distinct phases, each of which is divided into several subphases. In the first phase, 27 HD sessions for each patient will be used, and will be aimed at the validation of a new ultrafiltration (UF) profile, designed with an ascending/descending shape, and a standard dialysate sodium concentration. In the second phase, 33 HD sessions for each patient will be used and will be aimed at evaluating the combination of different UF and sodium profiling strategies through individualised dialysate sodium concentration. ETHICS AND DISSEMINATION: The trial protocol has been reviewed and approved by the local Institutional Ethics Committee (Comitato Etico AVEN, prot. 43391 22.10.19). The results of the trial will be presented at local and international conferences and submitted for publication to a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT03949088).

[Extracorporeal renal replacement therapies in lithium intoxication].

Drug poisoning is a significant source of morbidity, mortality and health care expenditure worldwide. Lithium, methanol, ethylene glycol and salicylates are the most important ones, included in the list of poisons, that may require extracorporeal depuration. Lithium is the cornerstone of treatment for bipolar disorders, but it has a narrow therapeutic window. The therapeutic range is 0.6-1.2 mEq/L and toxicity manifestations begin to appear as soon as serum levels exceed 1.5 mEq/L. Severe toxicity can be observed when plasma levels are more than 3.5 mEq/L. Lithium poisoning can be life threatening and extracorporeal renal replacement therapies can reverse toxic symptoms. Currently, conventional intermittent hemodialysis (IHD) is the preferred extracorporeal treatment modality. Preliminary data with prolonged intermittent renal replacement (PIRRT) therapies - hybrid forms of renal replacement therapy (RRT) such as sustained low efficiency dialysis (SLED) - seem to justify their role as potential alternative to conventional IHD. Indeed, SLED allows rapid and effective lithium removal with resolution of symptoms, also minimizing rebound phenomenon.

Electrocardiographic T wave alterations and prediction of hyperkalemia in patients with acute kidney injury.

Electrocardiographic (ECG) alterations are common in hyperkalemic patients. While the presence of peaked T waves is the most frequent ECG alteration, reported findings on ECG sensitivity in detecting hyperkalemia are conflicting. Moreover, no studies have been conducted specifically in patients with acute kidney injury (AKI). We used the best subset selection and cross-validation methods [via linear and logistic regression and leave-one-out cross-validation (LOOCV)] to assess the ability of T waves to predict serum potassium levels or hyperkalemia (defined as serum potassium ≥ 5.5 mEq/L). We included the following clinical variables as a candidate for the predictive models: peaked T waves, T wave maximum amplitude, T wave/R wave maximum amplitude ratio, age, and indicator variates for oliguria, use of ACE-inhibitors, sartans, mineralocorticoid receptor antagonists, and loop diuretics. Peaked T waves poorly predicted the serum potassium levels in both full and test sample (R2 = 0.03 and R2 = 0.01, respectively), and also poorly predicted hyperkalemia. The selection algorithm based on Bayesian information criterion identified T wave amplitude and use of loop diuretics as the best subset of variables predicting serum potassium. Nonetheless, the model accuracy was poor in both full and test sample [root mean square error (RMSE) = 0.96 mEq/L and adjR2 = 0.08 and RMSE = 0.97 mEq/L, adjR2 = 0.06, respectively]. T wave amplitude and the use of loop diuretics had also poor accuracy in predicting hyperkalemia in both full and test sample [area-under-curve (AUC) at receiver-operator curve (ROC) analysis 0.74 and AUC 0.72, respectively]. Our findings show that, in patients with AKI, electrocardiographic changes in T waves are poor predictors of serum potassium levels and of the presence of hyperkalemia.

Sustained low-efficiency dialysis for metformin-associated lactic acidosis in patients with acute kidney injury.

BACKGROUND: The choice of the specific modality and treatment duration of renal replacement therapy (RRT) to adopt in metformin-associated lactic acidosis (MALA) is still debated. We aimed to verify if sustained low-efficiency dialysis (SLED) is a rational choice in patients with MALA and acute kidney injury (AKI). METHODS: We collected serial serum metformin measurements, clinical parameters, and outcome data in ten consecutive patients (mean age 77 years [range 58-88], 5 males) admitted to our renal intensive care unit for suspected MALA associated with AKI and hemodynamic instability. Patients underwent a 16-h SLED session performed with either conventional dialysis machines or machines for continuous RRT (CRRT). A 2-compartment open-infusion pharmacokinetic model with first-order elimination was fitted to each subject's serum concentration-time data to model post-SLED rebound and predict the need for further treatments. RESULTS: Two patients died within 24 h after SLED start. Three patients needed one further dialysis session. Surviving patients (n = 8) were dialysis-free at discharge. Metformin levels were in the toxic range at baseline (median [range] 32.5 mg/l [13.6-75.6]) and decreased rapidly by the end of SLED (8.1 mg/l [4.5-15.8], p < 0.001 vs. baseline), without differences according to the dialysis machine used (p = 0.84). We observed a slight 4-h post-SLED rebound (9.7 mg/l [3.5-22.0]), which could be predicted by our pharmacokinetic model. Accordingly, we predicted that the majority of patients would need one additional dialysis session performed the following day to restore safe metformin levels. CONCLUSIONS: A 16-h SLED session, performed with either conventional dialysis machines or CRRT machines, allows effective metformin removal in patients with MALA and AKI. However, due to possible post-SLED rebound in serum metformin levels, one additional dialysis treatment is required the following day in the majority of patients.

[Metabolic acidosis]. / Acidosi metabolica.

Metabolic acidosis is frequently observed in clinical practice, especially among critically ill patients and/or in the course of renal failure. Complex mechanisms are involved, in most cases identifiable by medical history, pathophysiology-based diagnostic reasoning and measure of some key acid-base parameters that are easily available or calculable. On this basis the bedside differential diagnosis of metabolic acidosis should be started from the identification of the two main subtypes of metabolic acidosis: the high anion gap metabolic acidosis and the normal anion gap (or hyperchloremic) metabolic acidosis. Metabolic acidosis, especially in its acute forms with elevated anion gap such as is the case of lactic acidosis, diabetic and acute intoxications, may significantly affect metabolic body homeostasis and patients hemodynamic status, setting the stage for true medical emergencies. The therapeutic approach should be first aimed at early correction of concurrent clinical problems (e.g. fluids and hemodynamic optimization in case of shock, mechanical ventilation in case of concomitant respiratory failure, hemodialysis for acute intoxications etc.), in parallel to the formulation of a diagnosis. In case of severe acidosis, the administration of alkalizing agents should be carefully evaluated, taking into account the risk of side effects, as well as the potential need of renal replacement therapy.

[Metformin-associated lactic acidosis and acute kidney injury]. / Acidosi lattica associata a metformina e insufficienza renale acuta.

Metformin is recommended as the treatment of choice in patients with type 2 diabetes mellitus because of its efficacy, general tolerability and low cost. Recent guidelines have extended the use of metformin to patients with Chronic Kidney Disease (CKD) up to stage III. However, in the recent literature, cases of MALA (metformin-associated lactic acidosis) are increasingly reported. MALA is the most dangerous side effect of the drug, with an incidence rate of 2-9 cases per 100000 person-years of exposure. We report on two patients with accidental metformin overdose, severe lactic acidosis and acute kidney injury. In both cases, the usual dose of metformin was inappropriate with respect to the level of kidney dysfunction (CKD stage III). As both patients met the criteria for renal replacement therapy in metformin poisoning, they were treated effectively with sustained low-efficiency dialysis until normalization of serum lactate and bicarbonate values. Clinical status and kidney function improved and both patients could be discharged from the hospital.

Prealbumin improves death risk prediction of BNP-added Seattle Heart Failure Model: results from a pilot study in elderly chronic heart failure patients.

BACKGROUND: An accurate prognosis prediction represents a key element in chronic heart failure (CHF) management. Seattle Heart Failure Model (SHFM) prognostic power, a validated risk score for predicting mortality in CHF, is improved by adding B-type natriuretic peptide (BNP). We evaluated in a prospective study the incremental value of several biomarkers, linked to different biological domains, on death risk prediction of BNP-added SHFM. METHODS: Troponin I (cTnI), norepinephrine, plasma renin activity, aldosterone, high sensitivity-C reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), interleukin 2 soluble receptor, leptin, prealbumin, free malondialdehyde, and 15-F2t-isoprostane were measured in plasma from 142 consecutive ambulatory, non-diabetic stable CHF (mean NYHA-class 2.6) patients (mean age 75±8years). Calibration, discrimination, and risk reclassification of BNP-added SHFM were evaluated after individual biomarker addition. RESULTS: Individual addition of biomarkers to BNP-added SHFM did not improve death prediction, except for prealbumin (HR 0.49 CI: (0.31-0.76) p=0.002) and cTnI (HR 2.03 CI: (1.20-3.45) p=0.009). In fact, with respect to BNP-added SHFM (Harrell's C-statistic 0.702), prealbumin emerged as a stronger predictor of death showing the highest improvement in model discrimination (+0.021, p=0.033) and only a trend was observed for cTn I (+0.023, p=0.063). These biomarkers showed also the best reclassification statistic (Integrated Discrimination Improvement-IDI) at 1-year (IDI: cTnI, p=0.002; prealbumin, p=0.020), 2-years (IDI: cTnI, p=0.018; prealbumin: p=0.006) and 3-years of follow-up (IDI: cTnI p=0.024; prealbumin: p=0.012). CONCLUSIONS: Individual addition of prealbumin allows a more accurate prediction of mortality of BNP enriched SHFM in ambulatory elderly CHF suggesting its potential use in identifying those at high-risk that need nutritional surveillance.

Serum adipokine zinc α2-glycoprotein and lipolysis in cachectic and noncachectic heart failure patients: relationship with neurohormonal and inflammatory biomarkers.

Chronic heart failure is often complicated by the development of cachexia with the loss of fat mass. Zinc α2-glycoprotein (ZAG) is a serum adipokine with lipolytic effects in cancer cachexia. We evaluated in patients with advanced heart failure with (CxHF) or without cachexia (nCxHF) the relationship of ZAG with circulating free fatty acid (FFA), as an index of lipolysis, and with other neurohormonal and inflammatory biomarkers. Two groups, nCxHF (n = 46) and CxHF (n = 18), the latter having a documented, involuntary, edema-free loss of body weight of at least 7.5% in the previous 6 months, underwent plasma determination of FFA, ZAG, norepinephrine (NE), tumor necrosis factor-α, and natriuretic peptide levels (atrial natriuretic, B-type natriuretic peptide). The patients were compared with age-matched healthy controls (CTR) (n = 21). Zinc α2-glycoprotein, atrial natriuretic peptide, B-type natriuretic peptide, and tumor necrosis factor-α circulating levels were similarly greater in CxHF and nCxHF than in CTR. Free fatty acid and NE were higher in CxHF than in nCxHF. A positive correlation between FFA and NE was found in both CxHF (r = 0.73, P < .01) and nCxHF (r = 0.48, P < .01) but only in CxHF between ZAG and FFA (r = 0.54, P = .02) and between ZAG and NE (r = 0.70, P < .01). No correlations between natriuretic peptides and ZAG were found. Serum ZAG levels are increased in advanced heart failure patients compared with CTR, without differences between CxHF and nCxHF. Only in CxHF, ZAG levels are directly correlated to circulating levels of FFA and NE, suggesting a close interaction of ZAG with sympathetic-mediated lipolysis.

Ultrafiltration in heart failure.

Fluid overload is a key pathophysiologic mechanism underlying both the acute decompensation episodes of heart failure and the progression of the syndrome. Moreover, it represents the most important factor responsible for the high readmission rates observed in these patients and is often associated with renal function worsening, which by itself increases mortality risk. In this clinical context, ultrafiltration (UF) has been proposed as an alternative to diuretics to obtain a quicker relief of pulmonary/systemic congestion. This review illustrates technical issues, mechanisms, efficacy, safety, costs, and indications of UF in heart failure. The available evidence does not support the widespread use of UF as a substitute for diuretic therapy. Owing to its operative characteristics, UF cannot be expected to directly influence serum electrolyte levels, azotemia, and acid-base balance, or to remove high-molecular-weight substances (eg, cytokines) in clinically relevant amounts. Ultrafiltration should be used neither as a quicker way to achieve a sort of mechanical diuresis nor as a remedy for an inadequately prescribed and administered diuretic therapy. Instead, it should be reserved to selected patients with advanced heart failure and true diuretic resistance, as part of a more complex strategy aiming at an adequate control of fluid retention.

[Ultrafiltration and hemofiltration in the cardiology unit]. / Ultrafiltrazione ed emofiltrazione nel paziente cardiologico.

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.

The relation between the incidence of hypernatremia and mortality in patients with severe traumatic brain injury.

INTRODUCTION: The study was aimed at verifying whether the occurrence of hypernatremia during the intensive care unit (ICU) stay increases the risk of death in patients with severe traumatic brain injury (TBI). We performed a retrospective study on a prospectively collected database including all patients consecutively admitted over a 3-year period with a diagnosis of TBI (post-resuscitation Glasgow Coma Score < or = 8) to a general/neurotrauma ICU of a university hospital, providing critical care services in a catchment area of about 1,200,000 inhabitants. METHODS: Demographic, clinical, and ICU laboratory data were prospectively collected; serum sodium was assessed an average of three times per day. Hypernatremia was defined as two daily values of serum sodium above 145 mmol/l. The major outcome was death in the ICU after 14 days. Cox proportional-hazards regression models were used, with time-dependent variates designed to reflect exposure over time during the ICU stay: hypernatremia, desmopressin acetate (DDAVP) administration as a surrogate marker for the presence of central diabetes insipidus, and urinary output. The same models were adjusted for potential confounding factors. RESULTS: We included in the study 130 TBI patients (mean age 52 years (standard deviation 23); males 74%; median Glasgow Coma Score 3 (range 3 to 8); mean Simplified Acute Physiology Score II 50 (standard deviation 15)); all were mechanically ventilated; 35 (26.9%) died within 14 days after ICU admission. Hypernatremia was detected in 51.5% of the patients and in 15.9% of the 1,103 patient-day ICU follow-up. In most instances hypernatremia was mild (mean 150 mmol/l, interquartile range 148 to 152). The occurrence of hypernatremia was highest (P = 0.003) in patients with suspected central diabetes insipidus (25/130, 19.2%), a condition that was associated with increased severity of brain injury and ICU mortality. After adjustment for the baseline risk, the incidence of hypernatremia over the course of the ICU stay was significantly related with increased mortality (hazard ratio 3.00 (95% confidence interval: 1.34 to 6.51; P = 0.003)). However, DDAVP use modified this relation (P = 0.06), hypernatremia providing no additional prognostic information in the instances of suspected central diabetes insipidus. CONCLUSIONS: Mild hypernatremia is associated with an increased risk of death in patients with severe TBI. In a proportion of the patients the association between hypernatremia and death is accounted for by the presence of central diabetes insipidus.

Nutritional support in acute kidney injury.

Acute kidney injury (AKI), at least in critically ill patients, seldom occurs as isolated organ failure. Much more often it emerges as a component of the multiple organ failure syndrome, within the framework of the severe and prolonged catabolic phase determined by critical illness, and intensified by specific derangements in substrate utilization due to the acute loss of kidney function. On these bases, patients with AKI often have protein-energy wasting (preexisting and/or hospital acquired), which represents a major negative prognostic factor. Thus, nutritional support is frequently required, under the form of parenteral and/or enteral nutrition, even though no formal demonstration exists for its favorable effect on major outcomes. The primary goals of nutritional support in AKI are basically the same as those suggested for critically ill patients with normal renal function: i.e., to ensure the delivery of adequate amounts of nutrients, to prevent protein-energy wasting with the attendant metabolic complications, to promote wound healing and tissue reparation, to support immune system function and to reduce mortality. Patients with AKI on renal replacement therapy (RRT) should receive at least 1.5 g/kg per day of proteins, and no more than 30 kcal nonprotein calories or 1.3 x BEE (basal energy expenditure) calculated by the Harris-Benedict equation, with lipid supply representing about 30%-35% of energy. The enteral route should be the preferred route for nutrient delivery; however, parenteral nutrition is often required to target nutritional requirements. Due to the loss of the kidney's homeostatic function, and the frequent need of RRT, patients with AKI are especially prone to complications of nutritional support, such as hyperglycemia, hypertriglyceridemia, fluid retention, electrolyte and acid-base derangements. Since AKI comprises a highly heterogeneous group of subjects with nutrient needs widely varying even along the clinical course in the same patient, nutritional requirements should be frequently reassessed, individualized and carefully integrated with RRT.

Sustained low-efficiency dialysis (SLED) for acute lithium intoxication.

Acute lithium intoxication may cause serious neurologic and cardiac manifestations, up to the patient's death. Owing to its low molecular weight, relatively small volume of distribution close to that of total body water, and its negligible protein binding, lithium can be efficiently removed by any extracorporeal modality of renal replacement therapy (RRT). However, the shift from the intracellular to the extracellular compartment, with the inherent rebound phenomenon after the end of RRT, might limit the efficacy of the conventional, short-lasting haemodialysis. There have been no published studies up to now concerning the use of sustained low-efficiency dialysis (SLED) in lithium intoxication. This report describes a woman with a voluntary acute lithium ingestion of 40 tablets of lithium carbonate (8.12 mEq lithium each). The lithium concentration increased up to 4.18 mEq/l about 24 h after admission, notwithstanding treatment with intravenous crystalloids and gastric lavage. She developed mental status changes, oliguria, hypotension and bradycardia. We started SLED (8 h) with a blood flow of 200 ml/min and countercurrent dialysate flow of 300 ml/min. Lithium serum levels decreased by 86% during treatment, and the patient fully awoke recovering a normal mental status within the first 4 h of treatment. SLED was completed safely within the prescribed time. After the end of treatment, the rebound of lithium concentration was unremarkable. Renal function fully recovered, and the patient was transferred into a psychiatric facility 3 days after admission.

Characterization of myocardial hypertrophy in prehypertensive spontaneously hypertensive rats: interaction between adrenergic and nitrosative pathways.

OBJECTIVE AND METHODS: Left ventricular hypertrophy in human and experimental hypertension is not always associated with pressure overload but seems to precede an increase in blood pressure. In this study, performed in male 5-week-old prehypertensive spontaneously hypertensive rats (SHR; n = 65) and age-matched Wistar-Kyoto rats (n = 56), the relationship between myocardial structure and activation of the adrenergic and nitric oxide systems was evaluated. RESULTS: Body weight, blood pressure and heart rate were similar in both groups. A higher left ventricle/body weight ratio was found in SHR, as a result of greater mononuclear (+47%) and binuclear (+43%) myocyte volumes, without changes in interstitial collagen. Both adrenergic and nitric oxide pathways were activated in SHR, as expressed by higher myocardial norepinephrine content, tyrosine hydroxylase activity, myocardial nitric oxide synthase 3 expression and protein nitration, indicating greater peroxynitrite (ONOO) generation from nitric oxide and superoxide. No difference was measured in nitric oxide synthase 1 expression, whereas nitric oxide synthase 2 was undetectable. A positive correlation between myocardial tyrosine hydroxylase activity and protein nitration was observed in SHR (r = 0.328; P < 0.01). Early treatment with a superoxide dismutase mimetic, 4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl, from the third to the fifth week of age, reduced ONOO generation, protein nitration and sympathetic activation in SHR without changes in myocardial structure. CONCLUSION: In prehypertensive SHR, left ventricular hypertrophy is associated with adrenergic and nitrosative imbalance. Early superoxide dismutase mimetic treatment in SHR effectively reduces higher myocardial ONOO generation, sympathetic activation, and heart rate without affecting the development of myocardial hypertrophy.

Sustained low-efficiency dialysis (SLED) with prostacyclin in critically ill patients with acute renal failure.

BACKGROUND: Prostacyclin is an easy-to-use and safe antihaemostatic drug for continuous renal replacement therapies (RRTs). No study has been performed so far about its use in critically ill patients with acute renal failure (ARF) treated with sustained low-efficiency dialysis (SLED), a hybrid modality between conventional intermittent and continuous RRTs. METHODS: We studied 35 consecutive ICU patients with ARF, in whom data on safety and efficacy were prospectively collected in a single-centre experience over 15 months since August 2001. There were 25 males and 10 females; mean age, 72.1 (SD 11.4); mean APACHE II score at ICU admission, 24 (range 14-43); at RRT start, 27.4 (20-43); 28 patients (80%) were on mechanical ventilation and 17 (48.6%) had sepsis. SLED was performed using a conventional dialysis machine, with blood flow at 200 ml/min, bicarbonate-based ultrapure dialysate running at 100 ml/min, dialysate temperature 35 degrees C and low-flux polysulfone filters. Prostacyclin, under the form of its synthetic analogue epoprostenol, was infused at 6 ng/kg/min before the filter. RESULTS: Out of 185 daily sessions performed (8-10 h, median 4 per patient, range 1-19), 19 (in 11 patients) were prematurely interrupted (10.3%; 95% CI: 5.4-18.6), after an average 58.5% of the prescribed treatment time (nine sessions in six patients for circuit clotting). This finding compared favourably with the experience we had at our unit using SLED with saline flushes. With the use of prostacyclin, two episodes of upper gastrointestinal bleeding were observed in 2/35 patients during SLED (5.7%; 95% CI: 0.7-19.2), corresponding to 1.1 episodes per 100 person-day on SLED. Therapeutic intervention for hypotension (fluids and/or vasopressor increase) was required in 45/185 (in 20 patients) of the sessions monitored (24.3%; 95% CI: 17.4-32.9); two sessions had to be interrupted because of refractory hypotension. Urea reduction ratio was 0.50 (SD 0.12); mean prescribed and obtained net ultrafiltration were 1.96 l (range 0.5-5.0) and 1.99 l (0.5-5.0), respectively. In-hospital mortality was 46%; mortality predicted by the APACHE II model at ICU admission was 42%; at SLED start, 51%. CONCLUSIONS: Prostacyclin is a safe and effective antihaemostatic agent for SLED.