In vitro use of standard fluid infusion central venous catheter for slow continuous ultrafiltration feasibility assessment.

BACKGROUND: Slow continuous ultrafiltration (SCUF) by central venous catheter (CVC) for hemodialysis is a simple extracorporeal ultrafiltration that can reduce and control fluid overload in patients with chronic or acute chronic heart failure unresponsive to medical therapy. In order to avoid complications and risks related to the catheterization with a standard CVC for hemodialysis to provide the SCUF, considering that hospitalized patients affected by congestive heart failure commonly undergo CVC placement for medications delivering, we tested an in vitro model to use a standard CVC for infusion to perform SCUF. METHODS: We performed an in vitro SCUF experimental model through two different lumens of a triple (8Fr × 20 cm Tri-lumen catheter Kit-Envans Extra) and a quad-lumen CVC (8.5Fr × 20 cm Quad-lumen catheter kit-Benefis Medical Devices) commonly used in our Intensive Care Unit for fluids and medications infusions. We used Prismaflex with the HF-20 set (Baxter, IL, USA) to perform the SCUF treatment. RESULTS: Our in vitro data confirm the technical feasibility of the use of standard CVC for fluid infusion to perform a SCUF treatment with a theoretical weight loss of up to 200 ml/h by a blood flow ranging from 30 to 45 ml/min. CONCLUSIONS: The use of standard infusion CVC could be utilized in the intensive care unit to perform SCUF not exposing patients to the risks and complications related to the placement and permanence of CVC for hemodialysis.

Photoinactivation of Pseudomonas aeruginosa Biofilm by Dicationic Diaryl-Porphyrin.

In recent years, antimicrobial photodynamic therapy (aPDT) has received increasing attention as a promising tool aimed at both treating microbial infections and sanitizing environments. Since biofilm formation on biological and inert surfaces makes difficult the eradication of bacterial communities, further studies are needed to investigate such tricky issue. In this work, a panel of 13 diaryl-porphyrins (neutral, mono- and di-cationic) was taken in consideration to photoinactivate Pseudomonas aeruginosa. Among cationic photosensitizers (PSs) able to efficiently bind cells, in this study two dicationic showed to be intrinsically toxic and were ruled out by further investigations. In particular, the dicationic porphyrin (P11) that was not toxic, showed a better photoinactivation rate than monocationic in suspended cells. Furthermore, it was very efficient in inhibiting the biofilms produced by the model microorganism Pseudomonas aeruginosa PAO1 and by clinical strains derived from urinary tract infection and cystic fibrosis patients. Since P. aeruginosa represents a target very difficult to inactivate, this study confirms the potential of dicationic diaryl-porphyrins as photo-activated antimicrobials in different applicative fields, from clinical to environmental ones.

Influence of patients' clinical features at intensive care unit admission on performance of cell cycle arrest biomarkers in predicting acute kidney injury.

Objectives: Identification of acute kidney injury (AKI) can be challenging in patients with a variety of clinical features at intensive care unit (ICU) admission, and the capacity of biomarkers in this subpopulation has been poorly studied. In our study we examined the influence that patients' clinical features at ICU admission have over the predicting ability of the combination of urinary tissue inhibitor of metalloproteinase-2 (TIMP2) and insulin-like growth factor binding protein 7 (IGFBP7). Methods: Urinary [TIMP2]•[IGFBP7] were measured for all patients upon admission to ICU. We calculated the receiver operating characteristics (ROC) curves for AKI prediction in the overall cohort and for subgroups of patients according to etiology of ICU admission, which included: sepsis, trauma, neurological conditions, cardiovascular diseases, respiratory diseases, and non-classifiable causes. Results: In the overall cohort of 719 patients, 239 (33.2%) developed AKI in the first seven days. [TIMP2]•[IGFBP7] at ICU admission were significantly higher in AKI patients than in non-AKI patients. This is true not only for the overall cohort but also in the other subgroups. The area under the ROC curve (AUC) for [TIMP2]•[IGFBP7] in predicting AKI in the first seven days was 0.633 (95% CI 0.588-0.678), for the overall cohort, with sensitivity and specificity of 66.1 and 51.9% respectively. When we considered patients with combined sepsis, trauma, and respiratory disease we found a higher AUC than patients without these conditions (0.711 vs. 0.575; p=0.002). Conclusions: The accuracy of [TIMP2]•[IGFBP7] in predicting the risk of AKI in the first seven days after ICU admission has significant variability when the reason for ICU admission is considered.

Continuous kidney replacement therapy in critically ill neonates and infants: a retrospective analysis of clinical results with a dedicated device.

BACKGROUND: Providing extracorporeal renal support to neonates and infants involves a number of technical and clinical issues, possibly discouraging early utilization. This report aims to describe a multicenter experience of continuous kidney replacement therapy (CKRT) delivery to small infants using a device specifically designed for this age group. METHODS: A retrospective cohort analysis of all patients treated with the Carpediem™ machine (Bellco-Medtronic, Mirandola, Italy) in 6 centers between June 2013 and December 2016. RESULTS: Twenty-six neonates and small infants received 165 CKRT sessions in convective modality. Median age at neonatal intensive care unit admission 1 day (IQR 1-11), median body weight 2.9 kg (IQR 2.2-3.6). Median circuit duration 14 h (IQR 10-22), with delivered/prescribed time ratio of 84%. CKRT was conducted using 4 Fr (27%), 5 Fr (35%), 6.5 Fr (11%), and 7 Fr (3%) vascular access, and with umbilical and peripheral accesses (11% each) allowing overall median blood flow of 4.5 ml/kg/min (IQR 3.4-6) and median effluent flow rate 35 ml/kg/h (IQR 28-42). Circuits were primed with normal saline in 58% of treatments, colloids in 31%, and packed red blood cells in 11%. No serious adverse events directly related to machine application were reported by any center. Twenty-five (96%) patients survived their CKRT course and 13 patients (50%) survived to ICU discharge. CONCLUSIONS: CKRT in neonates was easy to initiate and conduct when performed with small central vascular accesses coupled with this device. A dedicated technology for infant CKRT delivery enables patients to be safely treated avoiding technical complications. Graphical abstract.

The Dialyzer Identification Code (DIC): A filter characteristics codification for dialyzer choice in renal replacement therapy.

The dialyzer is the core element of extracorporeal blood purification therapies where several processes take place depending on specific membrane characteristics. To date, the filter choice requires preliminary knowledge of all its characteristics as they cannot be easily deduced from the commercial trade name, hence the difficulty in identifying easily equivalent dialyzers and clearly comparing single-filter characteristics. The choice of improper dialyzers for a specific treatment can determine a less-effective blood purification and potentially harmful treatments. We aimed to propose a univocal and standardized alphanumeric string to summarize essential filter properties in the Dialyzer Identification Code (DIC). DIC clearly describes device characteristics and allows to compare different dialyzer performances without resorting to the technical data sheets. Therefore, the presence of the DIC on every device facilitates information retrieval on the dialyzer, its intended use, and can facilitate matching the dialysis modality to correct dialyzers achieving a personalized renal replacement therapy. The standard filter characteristics codification by the DIC may further optimize correct extracorporeal blood purification prescriptions and the use of equivalent filters from different providers avoiding treatment inefficiency, clinical complications, and improving patient safety.

Tissue inhibitor metalloproteinase-2 (TIMP-2) • IGF-binding protein-7 (IGFBP7) levels are associated with adverse outcomes in patients in the intensive care unit with acute kidney injury.

The G1 cell cycle inhibitors tissue inhibitor metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) have been identified as novel biomarkers for the prediction of moderate to severe acute kidney injury (AKI) risk. However, the prognostic value of [TIMP-2]•[IGFBP7] in predicting adverse outcomes in intensive care unit (ICU) patients with AKI was not previously described. To evaluate this, we conducted a cohort study, measuring [TIMP2]•[IGFBP7] levels in critically ill patients admitted to the ICU and classified the patients as NephroCheck (NC) (+) or NC (-) according to [TIMP-2]•[IGFBP7] values and AKI (+) or AKI (-) according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We then evaluated the incidence of continuous renal replacement therapy initiation, all-cause mortality and a composite endpoint of both in the four groups. Baseline [TIMP-2]•[IGFBP7] values were available for 719 patients, of whom 239 developed AKI and 151 met the composite endpoint. Compared to NC (-)/AKI (+) patients, NC (+)/AKI (+) patients had a significant risk of ICU mortality and the composite endpoint. Kaplan-Meier curves showed that the survival estimate for the composite endpoint of NC (+)/AKI (+) patients was 34.4%; significantly worse than NC (-)/AKI (+) patients (67.4%). Multivariate analyses showed strong association between NC positivity and the composite endpoint. The inflammatory marker, procalcitonin, was an additional prognostic biomarker to compare and confirm the incremental value of NephroCheck. No association between procalcitonin and the composite endpoint was found, especially in patients with AKI, suggesting that NephroCheck may be more kidney specific. Thus, the [TIMP-2]•[IGFBP7] values can serve to identify patients with AKI at increased risk for adverse outcomes in the ICU.

Choice of Catheter Size for Infants in Continuous Renal Replacement Therapy: Bigger Is Not Always Better.

OBJECTIVES: Renal replacement therapy in infants and small children is the treatment of choice for severe oligoanuric renal dysfunction, with an increasing consensus that early initiation might contribute to preventing acute kidney injury complications. Safer renal replacement therapy devices specifically designed for neonates may contribute to ameliorating outcomes and increasing chances of survival. One of the crucial factors to achieve an effective renal replacement therapy in small infants is adequate vascular access. The interaction of small size central vascular catheters with renal replacement therapy devices has never been investigated. The aim of this study was to characterize both the operating conditions and performance of three different central vascular catheters sizes (4F, 5F, and 7F) connected to two different extracorporeal blood circulation models (adult and pediatric). The rheologic performance of each vascular access size in combination with the adult and pediatric renal replacement therapy models was described. DESIGN: Series of experimental extracorporeal circulation circuit tests were conducted with different setups. A two-roller pump was used to simulate a standard adult dialysis machine, whereas a small three-roller pump served as pediatric renal replacement therapy device. SETTING: A pressure-flow setup aimed to collect pressure and flow values under different test conditions. A second experiment focused on hemolysis estimation induced by the extracorporeal system. Hemolysis exclusively induced by the 4F catheter was also evaluated. Finally, our data were applied to estimate the optimal catheter size theoretically capable of delivering adequate doses basing on anthropometric data (patient weight and cannulation site) in absence of direct ultrasound vessel measurement. SUBJECTS: In vitro tests conducted on simulated extracorporeal circuit models of continuous pediatric and neonatal renal replacement therapy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: When 4F and 5F catheters are used, maximal blood flows within safe circuit pressures can be set at the values of 13 and 29 mL/min, respectively, when a small pump is used. Differently, when using adult roller pumps, only maximal flows of 10 and 20 mL/min are reached. However, hemolysis is higher when using a three-roller pump compared with the two-roller. The clinical impact of this increased hemolytic burden is likely not relevant. CONCLUSIONS: Small size central vascular catheters display optimal rheologic performances in terms of pressures and flows particularly when the renal replacement therapy device is equipped with pumps proportional to central vascular catheters sizes, and even when relatively high blood flows are set. This is achieved at the risk of a higher hemolysis rate.

Continuous Veno-Venous Hemodialysis Using the Cardio-Renal Pediatric Dialysis Emergency MachineTM: First Clinical Experiences.

We report the first worldwide experience with continuous veno-venous hemodialysis (CVVHD) in children using the last generation Cardio-Renal Pediatric Dialysis Emergency Machine (CARPEDIEM)TM device. Thirteen children received 1,008 h of CVVHD during 95 sessions, using a 0.15 (n = 7) or a 0.25 m2 (n = 6) hemofilter. The median weight was 3 kg (interquartile range [IQR] 2.5-6.2). In 10 patients, CVVHD was conducted using a 5 Fr double-lumen central vascular access, whereas in 3 children, bigger sizes were used (6.5 and 8 Ch). The median prescribed Qb was 17 mL/min (IQR 10-29.5), with a median Qd of 10 mL/min. Circuits were primed with 5% albumin in 12 out of 13 patients, using anticoagulation with heparin in all 13 cases. The median delivered/prescribed time ratio yielded a 100% result (95-100%). The most common cause for "downtime" was clotting that however occurred in only 3% of all treatments. Survivals at continuous renal replacement therapy discontinuation and ICU discharge were 100 and 69% respectively. The CARPEDIEMTM machine allowed successful delivery of diffusive blood purification modality to very small patients, using small catheters, no blood primes, and excellent concordance between delivered and prescribed treatment duration.

Perfluorocarbon solutions limit tubular epithelial cell injury and promote CD133+ kidney progenitor differentiation: potential use in renal assist devices for sepsis-associated acute kidney injury and multiple organ failure.

Background: The renal assist device (RAD) is a blood purification system containing viable renal tubular epithelial cells (TECs) that has been proposed for the treatment of acute kidney injury (AKI) and multiple organ failure. Perfluorocarbons (PFCs) are oxygen carriers used for organ preservation in transplantation. The aim of this study was to investigate the effect of PFCs on hypoxia- and sepsis-induced TEC injury and on renal CD133+ progenitor differentiation in a microenvironment similar to the RAD. Methods: TECs were seeded in a polysulphone hollow fibre under hypoxia or cultured with plasma from 10 patients with sepsis-associated AKI in the presence or absence of PFCs and were tested for cytotoxicity (XTT assay), apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling assay, caspases, enzyme-linked immunosorbent assay, Fas/Fas Ligand pathway activation), mitochondrial activity, cell polarity [transepithelial electrical resistance (TEER)] and adenosine triphosphate production. The effect of PFCs on proliferation and differentiation of human CD133+ progenitors was also studied. Results: In the presence of PFCs, TECs seeded into the polysulphone hollow fibre showed increased viability and expression of insulin-like growth factor 1, hepatocyte growth factor and macrophage-stimulating protein. Plasma from septic patients induced TEC apoptosis, disruption of oxidative metabolism, alteration of cell polarity and albumin uptake, down-regulation of the tight junction protein ZO-1 and the endocytic receptor megalin on the TEC surface. These detrimental effects were significantly reduced by PFCs. Moreover, PFCs induced CD133+ renal progenitor cell proliferation and differentiation towards an epithelial/tubular-like phenotype. Conclusions: PFCs improved the viability and metabolic function of TECs seeded within a polysulphone hollow fibre and subjected to plasma from septic AKI patients. Additionally, PFCs promoted differentiation towards a tubular/epithelial phenotype of CD133+ renal progenitor cells.

Fistula Cannulation with a Novel Fistula Cannula: A Review of Cannulation Devices and Procedures.

Arteriovenous fistula cannulation for dialysis treatments in Europe has traditionally been done by metal needles. In -Japan, plastic cannulas have been available for many years and are used in the majority of the dialysis patients. The mechanical structure and the cannulation procedure of the plastic cannulas differ from those of the metal needles. These differences are particularly beneficial for patients with delicate fistulas, tortuous vessels, metal allergies, oligophrenic patients, and also for the safety of the medical staff. In this paper, we present the main features of a novel fistula plastic cannula and the innovations introduced by it compared to the traditional metal needles.

Standardized Protocol for Hemodialysis Vascular Access Assessment: The Role of Ultrasound and ColorDoppler.

INTRODUCTION: Ultrasound and colorDoppler technique, which is relatively inexpensive, rapid, non-invasive and repeatable is a powerful tool used for early diagnosis of vascular access (VA) complications in hemodialysis patients. To date a standard and widely comprehensible echocolorDoppler (ECD) protocol is not available. MATERIALS AND METHODS: A simple step-by-step protocol based on anatomical and hemodynamic parameters of VA has been developed during a 3-years VA ECD follow-up. It consists of an ECD study scheme. The algorithm created involves the calculation of brachial artery flow, description of artero-venous and/or graft-vascular anastomosis and efferent vessel and/or graft. RESULTS: The algorithm allows to formulate a medical report that takes into account both anatomic and hemodynamic parameters of the VA. Reduction of complications and the prevention of chronic complications as well as the early detection of acute problems were achieved. DISCUSSION AND CONCLUSION: The creation of a step-by-step protocol may simplify the multidisciplinary management of VA, its monitoring and the early diagnosis of its complications.

Remote Monitoring of Automated Peritoneal Dialysis Improves Personalization of Dialytic Prescription and Patient's Independence.

BACKGROUND: Remote monitoring (RM) supports a healthcare model that enhances patients' self-management. We evaluated the utility of RM in patients undergoing automated peritoneal dialysis (APD). METHODS: We observed 37 -RM-APD patients, 16 incidents, and 21 prevalents switched from traditional APD (T-APD). We observed the number of changes for APD prescription, the frequency of visits, and PD adequacy parameters during 1 year of RM utilization in APD. RESULTS: The APD prescriptions were modified more frequently in RM-APD vs. T-APD in incident (p = 0.002) and prevalent patients (p = 0.045). Visits were significant less in -RM-APD than in T-APD for incident patient (p = 0.008). No significant difference was found between prevalent populations. PD adequacy was similar in both groups. CONCLUSIONS: Our results demonstrate that RM allows an efficient use of healthcare resources, helping to improve personalization of APD prescription and to intervene early with "trouble shooting", thereby reducing the frequency of in-person visits for emergency problems.

Predicting Acute Kidney Injury in Intensive Care Unit Patients: The Role of Tissue Inhibitor of Metalloproteinases-2 and Insulin-Like Growth Factor-Binding Protein-7 Biomarkers.

BACKGROUND: Acute kidney injury (AKI) diagnosis is based on a rise in serum creatinine and/or fall in urine output. It has been shown that there are patients that fulfill AKI definition but do not have AKI, and there are also patients with evidence of renal injury who do not meet any criteria for AKI. Recently the innovative and emerging proteomic technology has enabled the identification of novel biomarkers that allow improved risk stratification. METHODS: Tissue inhibitor of metalloproteinases-2 (TIMP-2), insulin-like growth factor-binding protein 7 (IGFBP7) were measured to a cohort of 719 consecutive patients admitted to Intensive Care Unit (ICU). The primary endpoint was the evaluation of clinical performances of the biomarkers focusing on the probability do develop AKI in the first 7 days. RESULTS: The Kaplan-Meier analysis considering the first 7 days of ICU stay suggested a lower risk of developing AKI (p < 0.0001) for patients with a negative (<0.3; TIMP-2*IGFBP7) test. CONCLUSION: (TIMP-2*IGFBP7) at ICU admission has a good performance in predicting AKI, especially in the first 4 days in ICU.

The future of critical care: renal support in 2027.

Since its inception four decades ago, both the clinical and technologic aspects of continuous renal replacement therapy (CRRT) have evolved substantially. Devices now specifically designed for critically ill patients with acute kidney injury are widely available and the clinical challenges associated with treating this complex patient population continue to be addressed. However, several important questions remain unanswered, leaving doubts in the minds of many clinicians about therapy prescription/delivery and patient management. Specifically, questions surrounding therapy dosing, timing of initiation and termination, fluid management, anticoagulation, drug dosing, and data analytics may lead to inconsistent delivery of CRRT and even reluctance to prescribe it. In this review, we discuss current limitations of CRRT and potential solutions over the next decade from both a patient management and a technology perspective. We also address the issue of sustainability for CRRT and related therapies beyond 2027 and raise several points for consideration.

Therapeutic Plasma Exchange in Neonates and Infants: Successful Use of a Miniaturized Machine.

Therapeutic plasma exchange (TPE) in neonates and small infants is a treatment method at the forefront that may become a potentially life-saving procedure in a wide array of severe conditions. Indications for TPE in the pediatric population have been mainly derived from adult literature, with neonatal hyperbilirubinemia being the most notable exception. The only alternative to TPE in small pediatric patients is manual blood exchange transfusion, which, however, bears an unacceptably high risk of severe complications. Still, technical issues due to extracorporeal circulation in neonates have burdened TPE so far, since machines developed for adults require a relatively large blood volume to operate. We in this study, describe our preliminary experience of TPE for treating 2 potentially life-threatening conditions in neonatal age. To overcome the aforementioned limitations, plasmapheresis was performed in both cases using a machine specifically designed for patients weighing less than 10 kg.

Nomenclature for renal replacement therapy and blood purification techniques in critically ill patients: practical applications.

This article reports the conclusions of the second part of a consensus expert conference on the nomenclature of renal replacement therapy (RRT) techniques currently utilized to manage acute kidney injury and other organ dysfunction syndromes in critically ill patients. A multidisciplinary approach was taken to achieve harmonization of definitions, components, techniques, and operations of the extracorporeal therapies. The article describes the RRT techniques in detail with the relevant technology, procedures, and phases of treatment and key aspects of volume management/fluid balance in critically ill patients. In addition, the article describes recent developments in other extracorporeal therapies, including therapeutic plasma exchange, multiple organ support therapy, liver support, lung support, and blood purification in sepsis. This is a consensus report on nomenclature harmonization in extracorporeal blood purification therapies, such as hemofiltration, plasma exchange, multiple organ support therapies, and blood purification in sepsis.

Nomenclature for renal replacement therapy in acute kidney injury: basic principles.

This article reports the conclusions of a consensus expert conference on the basic principles and nomenclature of renal replacement therapy (RRT) currently utilized to manage acute kidney injury (AKI). This multidisciplinary consensus conference discusses common definitions, components, techniques, and operations of the machines and platforms used to deliver extracorporeal therapies, utilizing a "machine-centric" rather than a "patient-centric" approach. We provide a detailed description of the performance characteristics of membranes, filters, transmembrane transport of solutes and fluid, flows, and methods of measurement of delivered treatment, focusing on continuous renal replacement therapies (CRRT) which are utilized in the management of critically ill patients with AKI. This is a consensus report on nomenclature harmonization for principles of extracorporeal renal replacement therapies. Devices and operations are classified and defined in detail to serve as guidelines for future use of terminology in papers and research.

CVVHD treatment with CARPEDIEM: small solute clearance at different blood and dialysate flows with three different surface area filter configurations.

BACKGROUND: The CARdiorenal PEDIatric EMergency (CARPEDIEM) machine was originally designed to perform only continuous venovenous hemofiltration (CVVH) in neonatal and pediatric patients. In some cases, adequate convective clearance may not be reached because of a limited blood flow. In such conditions, the application of diffusive clearance [continuous venovenous hemodialysis (CVVHD)] would help optimize blood purification. In this study, the CARPEDIEM™ machine was modified to enable the circulation of dialysis through the filter allowing testing of the performance of CARPEDIEM™ machine in CVVHD. METHODS: Three different polyethersulfone hemodialyzers (surface area = 0.1 m(2), 0.2 m(2), and 0.35 m(2), respectively) were tested in vitro with a scheduled combination of plasma flow rates (Qp = 10-20-30 ml/min) and dialysis fluid flow rate (Qd = 5-10-15 ml/min). Three sessions were performed in co-current and one in counter-current configuration (as control) for each filter size. Clearance was measured from the blood and dialysate sides and results with mass balance error greater than 5 % were discarded. RESULTS: Urea and creatinine clearances for each plasma/dialysate combination are reported: clearance increase progressively for every filter proportionally to plasma flow rates. Similarly, clearances increase progressively with dialysate flow rates at a given plasma flow. The clearance curve tends to present a steep increase for small increases in plasma flow in the range below 10 ml/min, while the curve tends to plateau for values averaging 30 ml/min. As expected, the plateau is reached earlier with the smaller filter showing the effect of membrane surface-area limitation. At every plasma flow, the effect of dialysate flow increase is evident and well defined, showing that saturation of effluent was not achieved completely in any of the experimental conditions explored. No differences (p > 0.05 for all values) were obtained in experiments using whole blood instead of plasma or using co-current versus counter-current dialysate flow configuration. CONCLUSIONS: Although plasma flow and filter surface give an important contribution to the level of clearance urea and creatinine, it appears evident that dialysate flow plays an essential role in the blood purification process, justifying the use of CVVHD versus CVVH in case of high dialysis dose requirement and/or limited blood flow rate.

Con-Current versus Counter-Current Dialysate Flow during CVVHD. A Comparative Study for Creatinine and Urea Removal.

BACKGROUND: Dialysate fluid connection to the membrane in continuous dialysis may affect solute clearance. Although circuit connections are routinely made counter-current to blood flow in intermittent dialysis, no study has assessed the effect of this dialysate fluid flow direction on removal of small solutes creatinine and urea during treatment using continuous veno-venous haemodialysis (CVVHD). AIMS: To assess if dialysate flow direction during CVVHD affects small solute removal. METHODS: This ethics-approved study recruited a convenience sample of 26 adult ICU patients requiring continuous dialysis to assess urea and creatinine removal for con-current vs. counter-current dialysate flow direction. The circuit was adjusted from continuous veno-venous haemodiafiltration to CVVHD 20 min prior to sampling with no fluid removal. Blood (b) and spent dialysate fluid (f) were taken in both concurrent and counter-current fluid flow at 1 (T1) and 4 (T4) hours with a new treatment. Blood flow was 200 ml/min. Dialysate flow 33 ml/min. Removal of urea and creatinine was expressed as the diafiltrate/plasma concentration ratio: Uf/b and Cf/b respectively. Data lacking normal distribution are presented as median with 25th and 75th interquartile ranges (IQR), otherwise as mean with SD and assessed with the independent t test for paired data. p < 0.5 was considered significant. RESULTS: Fifteen male patients were included with a median (IQR) age of 67 years (52-75), and APACHE x0399;x0399; score 17 (14-19) with all patients meeting RIFLE criteria 'F'. At both times, the counter-current dialysate flow was associated with higher mean (SD) diafiltrate/plasma concentration ratios: T1 0.87 (0.16) vs. 0.77 (0.10), p = 0.006; T2 0.96 (0.16) vs. 0.76 (0.09), p < 0.001 for creatinine and T1 0.98 (0.09) vs. 0.81 (0.09), p < 0.001; T2 0.99 (0.07) vs. 0.82 (0.08), p < 0.001 for urea. CONCLUSION: Counter-current dialysate flow during CVVHD for ICU patients is associated with an approximately 20% increase in removal of small solutes creatinine and urea. Video Journal Club 'Cappuccino with Claudio Ronco' at http://www.karger.com/?doi=441270.

Continuous renal replacement therapy in neonates and small infants: development and first-in-human use of a miniaturised machine (CARPEDIEM).

BACKGROUND: Peritoneal dialysis is the renal replacement therapy of choice for acute kidney injury in neonates, but in some cases is not feasible or effective. Continuous renal replacement therapy (CRRT) machines are used off label in infants smaller than 15 kg and are not designed specifically for small infants. We aimed to design and create a CRRT machine specifically for neonates and small infants. METHODS: We prospectively planned a 5-year project to conceive, design, and create a miniaturised Cardio-Renal Pediatric Dialysis Emergency Machine (CARPEDIEM), specifically for neonates and small infants. We created the new device and assessed it with in-vitro laboratory tests, completed its development to meet regulatory requirements, and obtained a licence for human use. Once approved, we used the machine to treat a critically ill neonate FINDINGS: The main characteristics of CARPEDIEM are the low priming volume of the circuit (less than 30 mL), miniaturised roller pumps, and accurate ultrafiltration control via calibrated scales with a precision of 1 g. In-vitro tests confirmed that both hardware and software met the specifications. We treated a 2·9 kg neonate with haemorrhagic shock, multiple organ dysfunction, and severe fluid overload for more than 400 h with the CARPEDIEM, using continuous venovenous haemofiltration, single-pass albumin dialysis, blood exchange, and plasma exchange. The patient's 65% fluid overload, raised creatinine and bilirubin concentrations, and severe acidosis were all managed safely and effectively. Despite the severity of the illness, organ function was restored and the neonate survived and was discharged from hospital with only mild renal insufficiency that did not require renal replacement therapy. INTERPRETATION: The CARPEDIEM CRRT machine can be used to provide various treatment modalities and support for multiple organ dysfunction in neonates and small infants. The CARPEDIEM could reduce the range of indications for peritoneal dialysis, widen the range of indications for CRRT, make the use of CRRT less traumatic, and expand its use as supportive therapy even when complete renal replacement therapy is not indicated. FUNDING: Associazione Amici del Rene di Vicenza.