Atypical electrolyte kinetics during an emergency dialysis session in a patient with Leriche syndrome.

A hemodialysis patient suffered from circulation failure due to a low output syndrome caused by a hyperkalemia (9.9 micromol/l) with typical ecg signs. An emergency hemodialysis was started. After 2 h ecg signs of hypokalemia (2.1 micromol/l) were detectable. Hemodialysis was stopped. 2 h later, serum potassium rose to 6.2 micromol/l. An obturation of the aorta and the inferior caval vein with perfusion through collateral vessels of the lower body side was obvious, resulting into a faster electrolyte correction in the upper and a delayed correction in the lower body side with a rebound in the upper compartment. Dialysis time and dialysate potassium (4.0 micromol/l) were increased. Furthermore no potassium problems occurred.

Prolonged survival of renal allograft in rats by methotrexate-albumin conjugates as immunosuppressive therapy.

Methothrexate (MTX) causes unwanted adverse events by affecting gastrointestinal and bone marrow cells when used as an immunosuppressant. Our aim was to reduce those side effects by covalent binding of methothrexate to human serum albumin (HSA) targeting rapidly proliferating lymphocytes, which are known to ingest albumin as an energy source. Twenty-one rats received a kidney transplant. Group A (n = 5) received standard immunosupression (free MTX); group B (n = 9), albumin-MTX conjugates; and group C (n = 7) albumin control. The primary endpoint of this animal study was transplant survival, which was evaluated as death due to uremia. The study was terminated on day 100. Placebo-treated rat recipients (group C) rejected their grafts at a median of 8 days, which was prolonged to 17 days in standard immunosuppressed rats (group A), resulting in doubling transplant survival compared to nonimmunosuppressed animals. However, the same dose given as HSA-conjugated MTX prolonged the median survival time to 43 days. (group B). Hence, the administration of conjugated methotrexate appeared to result in a doubling of transplant survival compared with standard immunosuppression. Moreover, two animals receiving MTX-HSA became long-term survivors without additional immunosuppression. Further studies should be performed to evaluate the significance of these findings in larger animals and possibly in clinical studies.

Reduced complications during hemodialysis by automatic blood volume controlled ultrafiltration.

BACKGROUND: Intradialytic morbid events (IMEs, mostly hypotension) are frequent complications during hemodialysis (HD). This study investigated whether automatic feedback control via adjustment of the ultrafiltration rate reduces IME frequency. METHODS: In this multi-center cross-over study, 56 hypotension-prone patients were treated both with standard HD (sHD, applying a constant ultrafiltration rate) and HD applying a blood volume controlled ultrafiltration rate (cHD). The relative blood volume (RBV) was continuously monitored. The individual relative blood volume limit (RBVcrit ) was determined from the measured RBV during initial sHD. During cHD, the ultrafiltration rate was automatically adjusted to keep the actual RBV above RBVcrit. RESULTS: In 3,081 HD treatments, slightly fewer IMEs were observed during cHD than during sHD (0.785+/-0.613 versus 0.695+/-0.547 per treatment, P=0.144). Less symptomatic events were seen during cHD: -13% for symptomatic hypotension (0.594 versus 0.685 per treatment, P=0.120), and -32% for cramps (0.049 versus 0.072 per treatment, P=0.009). Thirty-one patients with the highest IME rate (IME in at least every second treatment) especially benefited from cHD: 1.185+/-0.554 versus 0.979+/-0.543 IME per treatment (P=0.004). The reduction in blood pressure (BP) and the increase in heart rate were lower during the treatments with cHD than with sHD: systolic BP: -18.8+/-26.7 versus -22.2+/-28.9 mmHg (P=0.007), diastolic BP: -7.8+/-14.8 versus -9.1+/-15.3 mmHg (P=0.064), heart rate: 1.8+/-10.4 versus 2.3+/-11.6 per minute (P=0.014). Neither treatment duration nor ultrafiltration volume was significantly different between cHD and sHD. CONCLUSION: For cHD, less intradialytic morbid events were observed than for sHD, and pre- to post-dialytic changes in blood pressure and heart rate were less pronounced.

Immunoadsorption of sensitized kidney transplant candidates immediately prior to surgery.

Patients with anti-human leucocyte antigen (HLA) antibodies from previous transplantation, blood transfusion are highly sensitized and at risk to hyperacute renal graft loss. As these antibodies are identified to be of pathogenic importance, an effective removal may allow successful transplantation. Six 'high risk patients' [panel-reactive antibodies (PRA) >30% or retransplanted patients with an acutely rejected first graft within 6 months from surgery] were treated by protein A immunoadsorption (IA) immediately prior to transplantation. We treated the calculated plasma volume one to three times prior to surgery: mean 4600 mL (range 2100-10 200 mL). After transplantation we repeated the sessions according to antibody (Ab) recurrence, graft function and signs of rejection. The panel reactive Ab were reduced from mean 65% pre-IA (range 35-85) to lowest 15% (range 0-55). After the course they reappeared to 30% (range 0-90). Five of the six patients had no clinical signs of vascular rejection. At a follow-up of mean 54 months (+/-14) four grafts still function with a mean serum creatinine of 172 micromol/L (+/-57). Protein A IA is a safe and effective adjunct in the treatment of highly sensitized patients awaiting renal transplantation. The treatment immediately prior to operation can prevent hyperacute rejection and increases the graft survival in these patients.

Protein A immunoadsorption in a pregnant woman with habitual abortion.

The role of antibodies in the occurrence of recurrent spontaneous miscarriage is well known. However there are many controversial issues in the management of habitual abortion. This paper describes the effect of Protein A immunoadsorption on serum levels of these antibodies and its impact on a case of a successfully treated woman in a outpatient department without need for a central venous catheter. Given the favourable clinical results described in our paper we think it may be relevant for some worse cases in clinical practice and will interest your readers.

Prevention of haemodialysis-induced hypotension by biofeedback control of ultrafiltration and infusion.

BACKGROUND: Haemodialysis-induced hypotension is still a severe complication in spite of all the progress in haemodialysis treatment. Because of its multifactorial causes, haemodialysis-induced hypotension cannot be reliably prevented by conventional ultrafiltration and sodium profiling in open-loop systems, as they are unable to adapt themselves to actual decreases in blood pressure. METHODS: A blood-pressure-guided closed-loop system, for prevention of haemodialysis-induced hypotension by biofeedback-driven computer control of both ultrafiltration and saline infusion was clinically tested in 237 treatments of seven patients prone to hypotension. As medical knowledge on multifactorial causes of hypotension is characterized by a lack in deterministic knowledge, fuzzy logic and linguistic variables were used to involve clinical experience on hypotension phenomena in terms of fuzzy knowledge. Biofeedback control is based on frequent measurements of blood pressure at 5 min intervals. Blood pressure behaviour is described by linguistic variables and fuzzy sets. Adaptive rule bases were used for the simultaneous fuzzy control of both the ultrafiltration and infusion of hypertonic saline (20% NaCl). Proper adaptation of control features to patient's conditions was provided by the critical borderline pressure, which was set by the physician individually at the beginning of each treatment. During the initial and medium phases of the sessions, ultrafiltration rates up to 150% of the average rates were applied as long as decreases in blood pressure could be compensated by saline infusion. The surplus of ultrafiltrate volume was used for blood pressure stabilization in the final phase in most instances by low ultrafiltration rates. RESULTS: The advantages of biofeedback-controlled haemodialysis were demonstrated by both decreasing the frequency of hypotonic episodes and by increasing or maintaining constant levels of systolic blood pressure during the final phase in 88% of treatments. As saline infusion was applied mainly in the initial and medium phases, blood sodium levels were not significantly higher at the end of the sessions, and interdialytic weight gain was not elevated. CONCLUSION: The application of fuzzy logic in the blood-pressure-guided biofeedback control of ultrafiltration and sodium infusion during haemodialysis is able to minimize haemodialysis-induced hypotension.

Blood Pressure Guided Profiling of Ultrafiltration during Hemodialysis.

Hemodialysis-induced hypotension is still a common complication in spite of the progress achieved in hemodialysis (HD) treatment. Due to its multifactorial nature, dialysis-induced hypotension cannot be reliably prevented by conventional profiling of ultrafiltration in open-loop systems since they are unable to adapt themselves to actual decreases in blood pressure. A blood pressure guided closed-loop system for prevention of dialysis-induced hypotension by biofeedback-controlled profiling of ultrafiltration was clinically tested in 94 HD treatments of four patients prone to hypotension. Automatic profiling of ultrafiltration was based on frequent measurements of blood pressure at intervals of five minutes. Proper adaptation of control features to patients' conditions was provided by the lower limit of systolic pressure which was individually set by the physician at the beginning of each treatment. During the initial and medium phases of the HD sessions, ultrafiltration rates up to 200% of the average rates were applied as long as this was tolerated. The additional ultrafiltrate volume was used for blood pressure stabilization by lowering the ultrafiltration rates in the final phase of HD session. Biofeedback-controlled profiling of ultrafiltration provides reliable blood pressure stabilization in all phases of HD. During the first half of treatment, the frequency of hypotensive episodes remained below that with conventional therapy although ultrafiltration rates up to 200% were used. During the second half of treatment, blood pressure guided reduction of ultrafiltration rate provided a decreasing frequency of hypotensive episodes in contrast to the increasing trend during conventional therapy. Stable blood pressure trends during the last hour of HD were achieved in 91% of biofeedback-controlled treatments in comparison with only 32% of conventional treatments. Ultrafiltration rates of 150%-200% and blood pressure measurements at intervals of five minutes were well tolerated, since hypotension-prone patients were better monitored.

Improvement of multiple organ functions in hepatorenal syndrome during albumin dialysis with the molecular adsorbent recirculating system.

Recently, significant improvement of renal function and prolongation of survival were reported in hepatorenal syndrome (HRS) patients treated with the Molecular Adsorbent Recirculating System (MARS). As no impact on extrarenal organ function was documented, this trial looked into multiple organ function changes during MARS in HRS patients. Eight HRS patients (4 male, mean age 42.1 years, range 30-58, all United Network for Organ Sharing [UNOS] status 2A) were treated intermittendly 4-14 times (total 47, mean 5.9 +/- 3.4) between 4 and 8 h/single treatment. The following changes were observed pre- and posttreatment: bilirubin 466 +/- 146 to 284 +/- 134 micromol/L, creatinine 380 +/- 182 to 163 +/- 119 micromol/L, urea 26.4 +/- 10.3 to 12.9 +/- 4.9 mmol/L, plasma sodium 127.5 +/- 7.7 to 137.5 +/- 4.8 mmol/L (all p < 0.01). Mean arterial pressure (MAP) increased from 71.9 +/- 12.8 to 95.6 +/- 7.8 Torr (p < 0.001). Oliguria or anuria, present in all patients, was successfully reverted. Ascites, present in all patients, was not detectable after the treatment period. The hepatic encephalopathy grade decreased from 2.8 +/- 0.8 to 0.8 +/- 0.7 (p < 0.0001). Child-Index decreased from 13.25 +/- 1.3 to 9.4 +/- 1.8 (p < 0.001). The hospital survival rate was 62%. One man underwent successful liver transplantation 18 months after the treatment. We conclude that MARS can improve multiple organ functions in patients with HRS.

Liver support by extracorporeal blood purification: a clinical observation.

Liver failure associated with excretory insufficiency and jaundice results in an endogenous accumulation of toxins involved in the impairment of cardiovascular, kidney, and cerebral function. Moreover, these toxins have been shown to damage the liver itself by inducing hepatocellular apoptosis and necrosis, thus creating a vicious cycle of the disease. We report a retrospective cohort study of 26 patients with acute or chronic liver failure with intrahepatic cholestasis (bilirubin level > 20 mg/dL) who underwent a new extracorporeal blood purification treatment. A synthetic hydrophilic/hydrophobic domain-presenting semipermeable membrane (pore size < albumin size, 100-nm thick) was used for extracorporeal blood detoxification using dialysis equipment. The opposite side was rinsed with ligandin-like proteins as molecular adsorbents that were regenerated online using a chromatography-like recycling system (molecular adsorbent recirculating system [MARS]). Bile acid and bilirubin levels, representing the previously described toxins, were reduced by 16% to 53% and 10% to 90% of the initial concentration by a single treatment of 6 to 8 hours, respectively. Toxicity testing of patient plasma onto primary rat hepatocytes by live/dead fluorescence microscopy showed cell-damaging effects of jaundiced plasma that were not observed after treatment. Patients with a worsening of Child-Turcotte-Pugh (CTP) index before the treatments showed a significant improvement of this index during a period of 2 to 14 single treatments with an average of 14 days. After withdrawal of MARS treatment, this improvement was sustained in all long-term survivors. Ten patients represented a clinical status equivalent to the United Network for Organ Sharing (UNOS) status 2b (group A1), and all survived. Sixteen patients represented a clinical status equivalent to UNOS status 2a, and 7 of these patients survived (group A2), whereas 9 patients (group B) died. We conclude that in acute excretory failure caused by a chronic liver disease, this treatment provides a therapy option to remove toxins involved in multiorgan dysfunction secondary to liver failure.

Improvement of hepatorenal syndrome with extracorporeal albumin dialysis MARS: results of a prospective, randomized, controlled clinical trial.

In hepatorenal syndrome (HRS), renal insufficiency is often progressive, and the prognosis is extremely poor under standard medical therapy. The molecular adsorbent recirculating system (MARS) is a modified dialysis method using an albumin-containing dialysate that is recirculated and perfused online through charcoal and anion-exchanger columns. MARS enables the selective removal of albumin-bound substances. A prospective controlled trial was performed to determine the effect of MARS treatment on 30-day survival in patients with type I HRS at high risk (bilirubin level, > or =15 mg/dL) compared with standard treatment. Thirteen patients with cirrhosis with type I HRS were included from 1997 to 1999. All were Child's class C, with Child-Turcotte-Pugh scores of 12.4 +/- 1. 0, United Network for Organ Sharing status 2A, and total bilirubin values of 25.7 +/- 14.0 mg/dL. Eight patients were treated with the MARS method in addition to hemodiafiltration (HDF) and standard medical therapy, and 5 patients were in the control group (HDF and standard medical treatment alone). None of these patients underwent liver transplantation or received a transjugular intrahepatic portosystemic shunt or vasopressin analogues during the observation period. In the MARS group, 5.2 +/- 3.6 treatments (range, 1 to 10 treatments) were performed for 6 to 8 hours daily per patient. A significant decrease in bilirubin and creatinine levels (P <.01) and increase in serum sodium level and prothrombin activity (P <.01) were observed in the MARS group. Mortality rates were 100% in the control group at day 7 and 62.5% in the MARS group at day 7 and 75% at day 30, respectively (P <.01). We conclude that the removal of albumin-bound substances with the MARS method can contribute to the treatment of type I HRS.

Molecular adsorbent recycling system (MARS): clinical results of a new membrane-based blood purification system for bioartificial liver support.

The use of xenogenic or genetically engineered cell types in bioartificial liver support systems requires separation methods between the patients' blood and the liver support bioreactors that guarantee the sufficient transfer of pathophysiologically relevant substances but prevent complications. The present paper describes a new membrane separation system that is nearly impermeable to proteins but enables the exchange of water soluble and protein bound toxins by a special membrane and a recycled protein containing dialysate. Because the full range of toxins in hepatic failure has still not been identified, the value of this membrane separation method was evaluated clinically. Thirteen patients suffering from life threatening hepatic failure who had not responded to state of the art therapy were treated with this device, the molecular adsorbent recycling system (MARS). The overall survival rate was 69%. All patients showed positive response to the therapy, indicating that the presented membrane separator combines therapeutic effectivity with the highest safety criteria for the patient by cutting the exchange of substances below the level of proteins.

Protein A immunoadsorption (i.a.) in renal transplantation patients with vascular rejection.

Vascular rejection after renal transplantation is connected with a higher frequency of allograft dysfunction or graft loss. Plasmapheresis as an adjunctive therapy in the treatment of humoral mediated acute graft rejection was compared with protein A immunoadsorption. Eleven patients with acute graft rejection and high titers of cytotoxic HLA-Ab and/or signs of vascular rejection at graft biopsy (performed in 9 patients) have been treated. Six of them have a stable graft function, the longest graft survival until now is 41 months, four are back on haemodialysis and one patient died from CMV-pneumonia with a stable graft function 9 months after transplantation. We conclude that IA is a useful adjunctive therapy in the treatment of vascular rejection after renal transplantation. Further investigations are necessary to optimize criteria for inclusion.

Pharmacokinetics of mezlocillin and sulbactam under continuous veno-venous hemodialysis (CVVHD) in intensive care patients with acute renal failure.

OBJECTIVE: In intensive care medicine, continuous detoxication methods, such as continuous veno-venous hemodialysis (CVVHD), are used for treating acute renal failure. However, in contrast to conventional hemodialysis, little is known about the pharmacokinetics of many drugs administered in this setting and guidelines for dosages of drugs often do not exist. This holds particularly true for broad-spectrum antibiotics, which are often required during intensive care. METHODS: In this study, we investigated the pharmacokinetics of the acylureidopenicillin mezlocillin and the beta-lactamase inhibitor sulbactam during CVVHD and deduced dosage recommendations from the kinetic parameters with the goal of maintaining trough levels of above 10 mg.l-1 for mezlocillin and 5 mg.l-1 for sulbactam. Six intensive care patients with acute renal failure, receiving mezlocillin (n = 5) and/or sulbactam (n = 4), were examined during CVVHD and during intervals between CVVHD. The serum concentrations and the amounts of the drugs excreted into the dialyzate and into the urine within one dosage interval were measured using high performance liquid chromatography (HPLC). Three of the patients were jaundiced, indicating functional impairment of the liver. RESULTS: The clearances by CVVHD (CLCVVHD) for mezlocillin ranged between 11.0 and 44.9 ml.min-1 and the half lives ranged between 1.12 and 8.84 h. Low CL and long half lives were observed in the patients with jaundice. For sulbactam, CLCVVHD ranged between 10.1 and 22.8 ml.min-1 and serum half lives were 4.25-6.11 h, independent of liver function. CONCLUSION: Due to high hepatobiliary clearance of mezlocillin, dosage adjustments in patients with acute renal failure, treated by CVVHD, are needed only with concurrent impaired liver function. For sulbactam, the optimal dose was found to be 0.5 g, administered every 12 h, regardless of liver function.

A new procedure for the removal of protein bound drugs and toxins.

To extend the applicability of dialysis to the removal of albumin bound toxins, a new dialysis procedure was developed. A double sided albumin impregnated high-flux polysulfon dialyzer was used together with a closed loop dialysate compartment with an albumin containing dialysate solution, that was purified on line in a three step process with a charcoal and resin adsorbent, and another dialyzer for a normal dialysis or filtration of the albumin containing dialysate that was then recycled to the albumin impregnated dialyzer. The system effectively removed strongly albumin bound toxins like unconjugated bilirubin or free fatty acids from plasma and blood in vitro and in vivo and therefore could be considered a possible therapeutic means for the treatment of acute liver failure or acute and chronic intoxications with albumin bound toxins, e.g., in drug overdose or chronic renal failure.