Chronic peritoneal dialysis catheters: challenges and design solutions.

Although highly successful as transcutaneous access devices, today's peritoneal dialysis catheters still have imperfect hydraulic function, biocompatibility and resistance to infection. Success of Tenckhoff catheters is greatly improved by the proper positioning of deep and subcutaneous cuffs and intraperitoneal segment. Newer peritoneal catheter designs are intended to improve hydraulic function, avoid outflow failure, and diminish exit site infection. These catheter designs serve as excellent alternatives for patients with various types of failure of Tenckhoff catheters. Catheters have been designed for Continuous Flow Peritoneal Dialysis, and have generally been successful in providing high peritoneal dialysis flow rate, but not always successful in optimally distributing flow of peritoneal fluid. Improvements in catheter design may expand the use of peritoneal dialysis as a successful home dialysis therapy.

The Ash Split CathTM as long-term IJ access: Hydraulic performance and longevity.

A prospective observational study was performed to determine the duration of use of the Ash Split Cath placed as primary or bridge access in ESRD patients; 164 ESRD patients received a Split Cath in the IJ location, with transcutaneous placement guided by ultrasound. Mean follow-up time was 19.3 months (maximum up to 48 months). During the follow-up, there were 36 catheter failures resulting in removal, 53% due to infection and the others due to outflow failure or break (leak) of the catheter. By Kaplan-Maier analysis 82% of placed catheters were functional at 12 months and half-life of catheter duration was 26 months. Blood flow rates during dialysis were not distinguishable between IJ catheter patients and those with functioning grafts or fistulas. Function, safety and duration of use of the Split Cath in the IJ location all compare favorably to AV grafts.

The evolution and function of central venous catheters for dialysis.

The use of central venous catheters (CVC) for acute or chronic dialysis has been a relatively recent innovation in Nephrology. The first problem addressed has been how to allow removal and return of blood at high flow rates throughout a dialysis treatment. Four solutions have emerged: place the lumens within the right atrium; place the removal lumen on the inside of the catheter; use a large catheter size; or provide independent limbs with multiple blood-entry ports to draw and return blood in all directions. Many other requirements include resistance to infection, especially the passage of organisms around the catheter. A subcutaneous Dacron cuff within a tunnel has successfully accomplished this goal for most chronic CVC dialysis catheters, but other immobilizing devices such as plugs have also been successful. Materials for CVC dialysis catheters have improved, providing strength to allow the catheters to last for several years, with flexibility to avoid vein damage (in general). However, component and material failures still occur, and some materials are incompatible with medications placed at the exit site. CVC for dialysis will remain a necessary choice for many patients beginning and continuing dialysis therapy.

Treatment of systemic inflammatory response syndrome by push-pull powdered sorbent pheresis: a Phase 1 clinical trial.

An FDA-approved Phase 1 feasibility study was performed in two centers to determine the safety of the BioLogic-DTPF (detoxifier/plasma filter) system for the treatment of patients with systemic inflammatory response syndrome (SIRS). This device combines hemodiabsorption (dialysis of blood against powdered sorbents with the BioLogic-DT system) with push-pull sorbent-based pheresis (the PF add-on module). Eight adult ICU patients with both SIRS and multiple organ failure participated in the study. One 6 h treatment was planned for each patient with powdered charcoal as sorbent for 4 patients and a combination of charcoal/silica in the PF sorbent bag for 4 patients. The treatments appeared to have no negative effects in 7 patients, but 1 patient died during treatment due to progressive cardiac failure. Sepsis was resolved in 5 of the 8 patients. However, there were only 2 long-term survivors of the group. The addition of the PF module should improve the chemical function of the BioLogic-DT by allowing removal of protein-bound toxins such as cytokines. The selected patients tolerated treatment by the DTPF system well, but proof of benefit of the device remains to be proven in a Phase 2 clinical trial with randomized controls.

Powdered sorbent liver dialysis and pheresis in treatment of hepatic failure.

The Liver Dialysis Unit (the Unit) is a liver-assist device that employs hemodiabsorption (dialysis of blood against powdered sorbents) to selectively remove numerous small molecular weight toxins of hepatic failure. The Unit has been cleared by the Food and Drug Administration and is indicated and marketed for treatment of acute hepatic encephalopathy (AHE) due to decompensation of chronic liver disease (A-on-C) or fulminant hepatic failure (FHF). Controlled, prospective, and randomized studies of liver dialysis were conducted at several centers, enrolling 56 patients with AHE, grades II-IV with or without renal and respiratory insufficiency or failure. Liver dialysis treatments were for 6 h daily, 1-5 days with similar observation periods for control patients. Physiologic status, neurologic status, and outcome (recovery of hepatic function, improvement for transplant, or death) were measured, and results were compared for treated patients versus controls for patients with A-on-C and patients with FHF. Liver dialysis resulted in physiologic and neurologic improvement of patients with AHE, regardless of etiology. Liver dialysis significantly improved the incidence of positive outcomes (recovery of hepatic function or improvement for transplant) of A-on-C patients versus controls (71.5% treated, 35.7% control, p = 0.036), but had an insignificant improvement in the outcome of patients with FHF as compared with the control group. Among the overall 31 treated patients, 51.6% survived. Outcome was not negatively affected by the presence of kidney failure or respiratory failure. The plasmafilter unit (PF-Unit) combines hemodiabsorption with push-pull sorbent-based pheresis (the PF add-on module, with powdered sorbent surrounding plasmafilters). At blood flow rates of 200 ml/min, the system clears creatinine and aromatic amino acids at 120-160 ml/min, unconjugated bilirubin at 20-40 ml/min, and cytokines at 15-25 ml/min. The PF-Unit has been tested in a few patients with hepatic failure with Grades III and IV encephalopathy, and respiratory, and kidney insufficiency. Treatment appeared to be safe, and there were no significant hematologic changes. Physiologic changes included improved blood pressure, and encephalopathy, and stable urine output. Chemical changes included a decrease in the plasma levels of bilirubin, aromatic amino acids, ammonium, creatinine, and IL-1beta. The PF add-on module adds the capability to the Unit to remove bilirubin and other strongly protein-bound toxins from treated patients and may be of clinical benefit in the management of patients with the most severe hepatic failure and encephalopathy, including patients with FHF or concomitant sepsis.

Effect of hemodiabsorption and sorbent-based pheresis on amino acid levels in hepatic failure.

Changes in plasma amino acid concentrations were measured in patients with hepatic failure during extracorporeal hemodiabsorption (using the Liver Dialysis Unit, "the Unit") or hemodiabsorption plus sorbent-based pheresis treatment (using the Liver Dialysis Plasmafilter Unit, "the PF-Unit") Systems. Eight patients with hepatic failure, grade 3 or 4 encephalopathy, elevated bilirubin and/or creatinine levels and respiratory or renal failure were treated for 1-3 days with the Unit alone. Three of these were also treated with the Unit containing 10 g of BCAA in the sorbent suspension. Four patients with hepatic failure treated with the PF Unit also had 10 g of branched chain amino acid (BCAA) added to the sorbents of the Unit portion of this device. Pre- and post-plasma samples were drawn and high performance liquid chromatography (HPLC) was used to separate and detect amino acids in the plasma. Both the Unit and the PF-Unit have the capability to selectively remove various amino acids, especially aromatic amino acids (AAA). The pre-treatment amino acid profiles of plasma were typical for hepatic failure, with abnormally high levels of phenylalanine, tyrosine, tryptophan, and methionine and decreased levels of valine, leucine and isbolucine. The average pre-treatment Fischer ratio (BCAA/AAA) for both Unit and PF-Unit patients was 1.43 (+/- 0.58). Treatments by both systems resulted in an increase of BCAA levels in blood and concomitant decrease of AAA levels, with an average Fischer ratio improvement of 30-38% for the Unit and PF-Unit without BCAA. The Fischer ratio improved by 90% (average) for the Unit with BCAA. Levels of many other amino acids (such as alanine, glycine, proline or lysine) increased during both Unit and PF-Unit treatments. The removal of strongly protein-bound toxin and amino acids such as tryptophan and sulphydryl amino acids was more effective by the PF-Unit. Both the Unit and the PF-Unit have the unique capability to remove toxic aromatic amino acids while increasing BCAA levels in patient. The increase in many amino acid levels may be related to the removal of toxins that interfere with normal amino acid metabolism. The addition of the PF module improves the removal of bilirubin and similarly protein-bound chemicals. Changes in amino acid profiles by the Unit and the PF-Unit contrast markedly with other extracorporeal devices.

Push-pull sorbent-based pheresis and hemodiabsorption in the treatment of hepatic failure: preliminary results of a clinical trial with the BioLogic-DTPF System.

The BioLogic-DTPF System combines hemodiabsorption (the BioLogic-DT System with dialysis against powdered sorbent) with push-pull sorbent-based pheresis (the BioLogic-PF System with powdered sorbent surrounding plasma filters). At blood flow rates of 200 ml/min, the system clears creatinine and aromatic amino acids at 120-160 ml/min, unconjugated bilirubin at 20-40 ml/min, and cytokines at 15-25 ml/min. This article outlines a study of the DTPF System in treatment of patients with hepatic failure with Grade 3 or 4 encephalopathy and respiratory and kidney insufficiency. Treatment appeared to be safe, and there are no significant hematologic changes. Physiologic changes include improved blood pressure and encephalopathy and stable urine output. Chemical changes include decrease in plasma levels of bilirubin, aromatic amino acids, ammonium, creatinine, and interleukin-3 (IL-1beta). The BioLogic-DT System is now marketed for treatment of acute hepatic failure with encephalopathy. The BioLogic-DTPF System adds the capability of removing bilirubin and other strongly protein-bound toxins from treated patients and may be of clinical benefit in management of patients with the most severe hepatic failure and encephalopathy.

Innovative peritoneal dialysis: flow-thru and dialysate regeneration.

As the peritoneal dialysis (PD) patient's residual renal function declines, the dialysis dose must be increased. However, the options for increasing the dose are limited to increasing the number of exchanges and/or the volume of each exchange. A review of the literature indicates that the dialysis dose can be significantly increased by flow-through PD, wherein the dialysate flows continuously into the peritoneal cavity through one catheter and out another and/or by regenerating the spent dialysate, thereby, significantly increasing the dialysate flow rate. Flow-thru PD has been used with and without dialysate regeneration. Regeneration has been used with standard inflow/outflow PD. In nearly all cases, substantially increased clearances over standard PD were obtained with reported urea and creatinine clearances as high as 58 and 48 ml/min, respectively. Applying flow-thru to the PD patient would require two catheters or a dual lumen catheter, and to obtain optimum clearances, the dialysate should be pumped through the peritoneal cavity at a high flow rate. Regenerating the dialysate allows high dialysate flow rates while reducing the total amount of dialysate required. For the continuous ambulatory peritoneal dialysis (CAPD) patient, the unit would have to be wearable; whereas for the patient on automated PD, flow-thru and/or regeneration PD could be incorporated into the equipment. With sorbent regeneration, the protein in the spent PD could be purified and returned to the patient thereby minimizing protein loss, increasing ultrafiltration, and enhancing the removal of protein-bound metabolic toxins.

Push-pull sorbent-based pheresis treatment in an experimental canine endotoxemia model: preliminary report.

The Biologic-DTPF System (DTPF), an extracorporeal blood treatment device with potential to treat sepsis, was tested in a preliminary study using a canine endotoxemia model. Six dogs were used and they formed four treatment groups, as control group (n=1) and three groups based on the type of sorbent present in the plasma filter (PF) system: sham treatment with no sorbent (n=1), charcoal as sorbent (n=2), and charcoal/silica as sorbent ("silica" group, n=2). Cardiodynamic data were recorded before treatment and every 30 minutes, and blood samples were collected to determine blood chemistry and to detect the levels of endotoxin and selected plasma cytokines: interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF). The dogs were given Escherichia coli endotoxin (2 mg/kg) as an intravenous drip (extended over a period of 30 minutes). Thirty minutes after the end of infusion all animals except the control were treated with the DTPF system for four hours. To determine the effect of treatment, data collected at one hour from the initiation of treatment until the end of treatment were compared between control and treated dogs. The endotoxin levels in the control dog were higher (P < 0.05) than other groups. The control dog had lower levels of TNF than other groups. The control dog had similar levels of IL-1 (P > 0.05) and higher levels (P < 0.05) at 4 hours into treatment compared to other groups. The control dog had similar levels of IL-6 as other groups (P > 0.05). In the control dog, the mean arterial pressure (MAP) fell and then remained low but stable at 1-4 hours. The charcoal group had lower MAP than the control dog at 1-4 hours (P < 0.05). The silica group had higher MAP levels similar to the control dog. After treatment, the control dog had higher (P < 0.05) values of hematocrit, hemoglobin, calcium, potassium, and albumin compared to the treated groups. As expected for a system removing plasma during sepsis, the DTPF System had some adverse effects on the physiologic status of the dogs, especially when loaded with charcoal sorbent only. The findings of the present study suggest that the filters are capable of eliminating endotoxin and there is some evidence of cytokine removal. Although the charcoal dogs did poorly, addition of silica to the sorbent offset any negative effects. Further work is underway to improve the efficiency of the system, primarily to enhance the capacity of the sorbents for cytokines. A more realistic canine sepsis model with mortality after several days (the Escherichia coli- infected intraperitoneal clot) will also be considered in future studies.

Cytokines and endotoxin removal by sorbents and its application in push-pull sorbent-based pheresis: the BioLogic-DTPF System.

The BioLogic-DTPF System (DTPF) combines the Biologic-DT hemodiabsorption system (DT) in series with the Biologic PF push-pull pheresis system (PF) in which PF membranes separate plasma for direct contact between plasma proteins and the sorbents. Preliminary studies conducted in bovine serum albumin (BSA) solution and in bovine plasma allowed charcoal and silica to be evaluated as adsorbents for the PF module. Equilibrium binding experiments in BSA showed a high capacity of cytokine (IL-1 beta, TNF alpha) binding by powdered charcoal, 70-90 ng/g. Kinetic binding studies in bovine plasma revealed relatively quick adsorption of IL-1 beta and IL-6 by charcoal with the capacity range of 1.2-2.0 ng/g for tested cytokines (IL-1 beta and TNF alpha). Further laboratory studies with plasma have shown that powdered silica has an even greater binding capacity, up to 13 ng/g for TNF alpha depending upon particle size, and more rapid binding for all tested cytokines than powdered charcoal. Cholestyramine is a more efficient sorbent for removal of endotoxin than either charcoal or silica. In vitro tests using whole blood have demonstrated that the DTPF, with powdered charcoal as the sorbent, clears cytokines (TNF alpha, IL-1 beta, and IL-6) at 12.6-23.4 ml/min, bilirubin at 17.8-34.7 ml/min, and creatinine at 53.6-82.6 ml/min. The removal of some cytokines during the first clinical trial is also discussed.

Comparison of blood flow rates and hydraulic resistance between the Mahurkar catheter, the Tesio twin catheter, and the Ash Split Cath.

The Ash Split Cath (Medcomp, Harleysville, PA) is a recently introduced dual lumen permanent catheter designed to be placed through the internal jugular vein into the superior vena cava by single venipuncture technique. The transcutaneous portion is a 14 French cylindrically shaped catheter with D-shaped lumens and a Dacron (DuPont, Wilmington, DE) cuff. At the entrance to the jugular vein, the catheter splits into two separate D-shaped limbs that then merge into multiholed cylindrical tips in the vena cava. Split Caths (n = 10) have been placed in patients with end-stage renal disease and used for outpatient dialysis for approximately 2 months. Flow rates and hydraulic resistance have been compared with Mahurkar (Bard, Salt Lake City, UT) (n = 22) and Tesio (Medcomp) (n = 17) catheters in the same unit. Average blood flow rates (Qb) were 295 +/- 42 (SD) for Ash Split Caths vs 279 +/- 38 and 300 +/- 39 ml3/min for Mahurkar and Tesio catheters, respectively, and hydraulic resistances were 0.44 +/- 0.17, 0.52 +/- 0.15, and 0.56 +/- 0.11 mmHg/ml/min, respectively (not significant). No Split Caths have been removed for bleeding or flow complications. The Split Cath provides the simplicity of placement and removal of a single-bodied catheter with flow advantages of independent, cylindrical, multiholed tips.

Systemic inflammatory response syndrome treatment by powdered sorbent pheresis: the BioLogic-Detoxification Plasma Filtration System.

Systemic inflammatory response syndrome (SIRS) is one of the most common causes of death in intensive care unit patients. The detoxification plasma filtration (DTPF) system (HemoCleanse, Inc., West Lafayette, IN) combines the DT hemodiabsorption system in series with a push-pull pheresis PF system (a suspension of powdered sorbents surrounding 0.5 microm plasma filter membranes). Bidirectional plasma flow (at 80-100 ml/min) across the PF membranes provides direct contact between plasma proteins and powdered sorbents, as well as clearance of cytokines (tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6) at a rate of 15-25 ml/min, without evidence of saturation for 90 minutes. In a U.S. Food and Drug Administration approved study we treated eight patients with SIRS and organ failure with a single DTPF treatment, using powdered charcoal as sorbent in four patients and powdered charcoal and silica in four patients. Treatments proceeded for 6 hours with proper heparin anticoagulation (activated clotting time 250-300 sec) and appeared safe. All patients improved during the treatments and each had increased blood pressure and decreased need for pressor agents. Plasma cytokine levels stabilized or decreased during treatment and were significantly lower the morning after treatment. Multiple organ dysfunction (MOD) and Acute Physiology Chronic Health Evaluation II scores and organ function gradually improved in most patients, and two patients survived for more than 28 days and two for more than 14 days. The DTPF System may prove beneficial in treatment of patients with sepsis.

Hemodiabsorption in treatment of hepatic failure.

Conducted at the University of California, Los Angeles, this randomized, prospectively controlled study was designed to measure the effects of a hemodiabsorption device in the treatment of 11 patients with hepatic failure and stage III to IV encephalopathy. The results of 5 days of treatment with the hemodiabsorption device were compared with those of standard intensive care procedures. The BioLogic-DT System, a simple sorbent-based system, demonstrated a slight improvement in the neurologic status of patients, a significant improvement in the physiologic status of patients, and an improved outcome for treated patients as opposed to nontreated patients.

Push-pull sorbent based pheresis for treatment of acute hepatic failure: the BioLogic-detoxifier/plasma filter System.

The BioLogic-DT (detoxifier) System is an extracorporeal blood treatment device that uses the membranes of a cellulosic plate dialyzer to propel blood in and out through a single lumen access (on a 12 sec cycle) and circulates a suspension of powdered charcoal and cation exchanger through the dialysate spaces to absorb many soluble toxins in the treatment of hepatic failure. The BioLogic-DTPF (detoxifier/plasma filter) System adds two Gambro plasma filters downstream from the plate dialyzer, which allows most of the blood plasma to pass out of the blood, contact powdered charcoal in a suspension, and then return to the blood during each 12 sec cycle (creating push-pull sorbent based pheresis). A roller pump exchanges charcoal suspension between the plasma filter case and a 700 ml bag of powdered charcoal suspension. At a blood flow rate of 150-200 ml/min, 100 ml/min of plasma moves bidirectionally through the plasma filter membranes. Direct contact of plasma with charcoal outside the plasma filter membranes removes creatinine with a clearance rate equal to plasma flow (100 ml/min); clearance of strongly protein bound toxins, such as unconjugated bilirubin, is lower (10-40 ml/min). In this article, the authors explain the mechanisms of operation of this system and present in vitro tests that define its chemical efficiency. Also described are potential problems, tests that indicate the severity of these problems, and monitors and algorithms to detect or avoid these problems in clinical use of the system. The results of the treatment of two patients with acute hepatic failure and coma using the BioLogic-DTPF System are reviewed.

Bedside peritoneoscopic peritoneal catheter placement of Tenckhoff and newer peritoneal catheters.

The success of Tenckhoff chronic peritoneal dialysis catheters depends more upon the skill of the physician in placing catheters and on the technique of placement than it does on the exact design of the peritoneal catheter. In this summary article, the existing types of peritoneal catheters are reviewed, including two recent alternative designs: Tenckhoff catheters with larger internal diameters, and the T-fluted catheter with grooved limbs adjacent to the parietal peritoneum. The three types of placement procedures for catheters (peritoneoscopy, surgical or dissective, and blind techniques) are described, and the complications of Tenckhoff catheters are compared according to placement technique.