Long-path second-harmonic interferometer with nanosecond time resolution: reliable diagnostic tool for electron density measurement in pulsed plasma devices.

We describe the performance of a second-harmonic interferometer (SHI) to measure, on an optical path exceeding 12 m, the electron plasma density of two plasmoids formed in separate theta-pinch chambers and then merged in a central compression chamber after undergoing acceleration and compression. The excellent mechanical stability and a time resolution better than 50 ns suggest the application of SHI, especially in pulsed plasma devices with limited optical accesses.

Dynamic formation of a hot field reversed configuration with improved confinement by supersonic merging of two colliding high-ß compact toroids.

A hot stable field-reversed configuration (FRC) has been produced in the C-2 experiment by colliding and merging two high-ß plasmoids preformed by the dynamic version of field-reversed θ-pinch technology. The merging process exhibits the highest poloidal flux amplification obtained in a magnetic confinement system (over tenfold increase). Most of the kinetic energy is converted into thermal energy with total temperature (T{i}+T{e}) exceeding 0.5 keV. The final FRC state exhibits a record FRC lifetime with flux confinement approaching classical values. These findings should have significant implications for fusion research and the physics of magnetic reconnection.

Fluid and volume monitoring.

BACKGROUND: Fluid resuscitation is not only used to prevent acute kidney injury (AKI) but fluid management is also a cornerstone of treatment for patients with established AKI and renal failure. Ultrafiltration removes volume initially from the intravascular compartment inducing a relative degree of hypovolemia. Normal reflex mechanisms attempt to sustain blood pressure constant despite marked changes in blood volume and cardiac output. Thus, compensated shock with a normal blood pressure is a major cause of AKI or exacerbations of AKI during ultrafiltration. METHODS: We undertook a systematic review of the literature using MEDLINE, Google Scholar and PubMed searches. We determined a list of key questions and convened a 2-day consensus conference to develop summary statements via a series of alternating breakout and plenary sessions. In these sessions, we identified supporting evidence and generated clinical practice recommendations and/or directions for future research. RESULTS: We defined three aspects of fluid monitoring: i) normal and pathophysiological cardiovascular mechanisms; ii) measures of volume responsiveness and impending cardiovascular collapse during volume removal, and; iii) measured indices of each using non-invasive and minimally invasive continuous and intermittent monitoring techniques. The evidence documents that AKI can occur in the setting of normotensive hypovolemia and that under-resuscitation represents a major cause of both AKI and mortality ion critically ill patients. Traditional measures of intravascular volume and ventricular filling do not predict volume responsiveness whereas dynamic functional hemodynamic markers, such as pulse pressure or stroke volume variation during positive pressure breathing or mean flow changes with passive leg raising are highly predictive of volume responsiveness. Numerous commercially-available devices exist that can acquire these signals. CONCLUSIONS: Prospective clinical trials using functional hemodynamic markers in the diagnosis and management of AKI and volume status during ultrafiltration need to be performed. More traditional measure of preload be abandoned as marked of volume responsiveness though still useful to assess overall volume status.

Treatment of patients with cardiac surgery associated-acute kidney injury.

Members of the Acute Dialysis Quality Initiative (ADQI) participated in a 3-day conference in Vicenza in May 2007 to evaluate the available literature on this topic and draft consensus recommendations for research studies in this area. This report summarizes the available evidence and describes the key questions that will need to be addressed with the goal of standardizing the care of patients with cardiac surgery-associated acute kidney injury (CSA-AKI) and improving outcomes.

Extracorporeal ultrafiltration for acute exacerbations of chronic heart failure: report from the Acute Dialysis Quality Initiative.

This report from a work group affiliated with the Acute Dialysis Quality Initiative is a critical assessment of the use of extracorporeal ultrafiltration (UF) in the management of acutely decompensated heart failure (HF). In addition to assessing UF in this setting, the report also provides background information on HF, including classification, pathophysiology, and the importance of concomitant renal failure. A summary of important results from clinical trials in this area is provided, along with a discussion of technical considerations. Finally, specific recommendations for future clinical evaluations are given.

A critical look at survival of diabetics with end-stage renal disease. Transplantation versus dialysis therapy.

The survival of 100 consecutive patients with diabetic nephropathy after treatment with hemodialysis, peritoneal dialysis, or renal transplantation was reviewed at our institution from 1976 to 1982. Standard actuarial survival analysis revealed an overall survival of 83% and 61% at one and two years, respectively. Coronary angiography was used as a screening procedure for renal transplantation. In the dialysis group, 27 patients were considered acceptable transplant candidates on the basis of the coronary angiography but were not transplanted for other reasons. When the survival analysis was limited to those "transplant candidates" the survival rates were 78%, 51%, and 8% at 1, 2, and 5 years, respectively. In comparison, survival after transplantation was 81%, 67%, and 45%, at 1, 2, and 5 years, respectively. In order to eliminate bias, survival comparisons were subsequently made using the Cox Proportional Hazard Model to take into account the time the transplant patients spent on dialysis prior to renal transplantation. When this analysis was performed, there was no significant difference in survival between transplantation and dialysis for the first two years, but overall survival after five years was significantly better after renal transplantation even when the comparison was limited to acceptable transplant candidates who remained on dialysis (P = .04). Survival for patients with significant coronary disease (greater than 70% stenosis of a coronary vessel or moderate to severe left ventricular dysfunction) was analyzed according to therapeutic modality. Although overall prognosis was poor in this group as a whole (1, 2, and 5 year survivals were 76%, 45%, and 19%, respectively), the cardiac patients had a trend to better survival after renal transplantation than when maintained on dialysis (P = .22). In addition to other factors such as quality of life, rehabilitation, and progression of other diabetic complications, the benefit of renal transplantation on patient survival must be considered when deciding between renal transplantation and maintenance dialysis therapy for diabetic patients with renal failure.

Role of the nephrologist in the intensive care unit.

Intensive care units (ICUs) are increasingly becoming a focal point for tension between medical specialists. In an extreme approach to this issue, some ICUs have become closed units managed by intensivists, with other specialists, such as nephrologists, having a restricted supportive role. The nephrologist, a subspecialist with broad skills in general internal medicine, has trained and appropriately can serve as the primary physician for patients with significant renal failure and end-stage renal disease in multiple hospital settings, including the ICU. Sick and complex hospitalized patients offer ample opportunity for a collaborative interaction between the nephrologist and intensivist in the ICU.

Cooling effect of continuous renal replacement therapy in critically ill patients.

Hypothermia is reported to increase intensive care unit (ICU) mortality. The heat loss that occurs during continuous renal replacement therapy (CRRT) favors the development of hypothermia. In an effort to assess the influence of CRRT on body temperature, we reviewed the records of 72 consecutive ICU patients treated with CRRT and further prospectively studied the temperature in the inlet and outlet lines for blood and dialysate of 27 other patients at various flow settings during continuous venovenous hemodialysis (CVVHD). Among the 72 retrospective cases, 36 episodes of hypothermia (core body temperature <35.5 degrees C) occurred and persisted for a mean of 2.6+/-1.8 days. It was more frequent during venovenous than arteriovenous modalities (31 of 67 v5 of 20, respectively); no patients developed hypothermia during arteriovenous slow continuous ultrafiltration (AVSCUS), whereas 48% of the patients undergoing CVVHD became hypothermic, occurring earlier in the therapy course (days 2 to 4). Mean arterial pressure (MAP) tended to increase after CRRT initiation, but absolute changes were not statistically significant. In the prospective arm, the CVVHD circuit temperatures were directly measured. Whereas no attempt was made to change body temperature, stepwise changes in blood (Qb) and dialysate flow rate (Qd) produced venous circuit temperature changes: the higher the Qb, the smaller the arteriovenous temperature differences independent of changes in Qd (P < 0.001). Also, venous circuit temperature varied directly with Qd at fixed Qb (P < 0.001). This relationship also held for temperature conversion to lost energy units per minute. Using room temperature dialysate, CRRT may significantly lower patients' core temperatures. Although the clinical significance of this effect is not clear at this point, energy loss during CVVHD may be important in hemodynamic stability or patient prognosis.

Overview of anemia associated with chronic renal disease: primary and secondary mechanisms.

The development of hypoproliferative anemia with generally normocytic red blood cells in most patients with chronic renal failure impairs the success of maintenance dialysis therapy, particularly hemodialysis. Anemia can be a complication of the hemodialysis procedure itself, with its associated blood losses and mild effect on oxygen transport functioning. However, the primary cause of anemia in the chronic dialysis patient is decreased erythropoiesis. The most important mechanism leading to decreased erythropoiesis involves the production of subnormal levels of erythropoietin (EPO). Insufficient nephric output of EPO or, possibly, suppression of the effect of EPO by uremic inhibitors may cause this decreased erythropoiesis. Other factors, such as iron deficiency, hyperparathyroidism, systemic infections, and aluminum toxicity may contribute to anemia in some patients. Increased hemolysis, a comparatively mild factor in the anemia of chronic dialysis patients, may be related to retention of protein metabolism products, hypersplenism, hypophosphatemia, drugs, or other conditions in affected patients. There are several traditional treatment options for anemia: transfusions; iron, vitamin B12, or folic acid supplementation when indicated; a change to peritoneal dialysis; parathyroidectomy; and administration of androgens. None of these treatments have proved satisfactory, and some, such as transfusions and androgen therapy, pose risks and have serious side effects. A comparatively new approach, administration of genetically engineered erythropoietin (r-HuEPO; EPOGEN, AMGEN inc, Thousand Oaks, CA), has been found effective in treating anemia in clinical trials. Patients have shown improved cardiac performance as well as enhanced quality of life, and hypertension appears to be the most serious side effect of r-HuEPO therapy.

Acute dialysis and continuous renal replacement: the emergence of new technology involving the nephrologist in the intensive care setting.

The emergence of dialytic support for patients with reversible renal failure was one of the most significant advances in critical care medicine. Supporting a patient with a failed organ till organ recovery has not had the same success with other organ failures. Despite the indispensable nature of the support, dialysis was intermittent at best, and carried its own morbidity. The emergence of a "continuous" dialysis delivery system, originally through an arteriovenous access and later through veno-venous methodology, began to simulate the continuity of the natural kidney, and lifted much of the fluid and drug restrictions imposed by the intermittent nature of standard dialytic therapies. Components of the system were next reviewed for improvement and biocompatability. Differences in patient outcome were documented with various component comparisons, and disparate patient tolerance of delivery modality was also clearly proven. The hemodynamic stability of continuous treatment created utilization to be focused on the more unstable, the more severely compromised patient group. In this context, comparative studies with intermittent delivery methods showed improved hemodynamic stability among patients treated with continuous renal replacement therapies (CRRT), but no clear difference in patient mortality. Patient characteristics and severity scoring have recently been undertaken to better describe the population, and attempts at dialysis dosing is currently being developed for ARF dialysis recipients. Early results seem to point toward a dialysis dose effect on mortality in certain groups of ICU acute renal failure patients. However, the dialytic process is only depurative and artificial. Plastic membrane bio-incompatibility, human physiological responses to foreign material exposure, either in the circuit material itself or introduced from therapy methodology, pose practical and theoretical problems. Recent advances in the field of bio-artificial technology have allowed the development of functioning hybrid "blood processors," which function as a renal tubule and may be able to not only "clean" blood, but also allow for other cellular functions not currently possible with dead membrane technology. Combining living cells with a continuous delivery method may be the next significant step toward a fully functional renal replacement therapy.

The end-stage renal disease program. Experience with a chronic disease capitated health plan.

The ESRD program has demonstrated the potential for a capitated, disease-oriented, total care method of patient support. Given both the increasing age and complexity of the patient population, not only has the cost per patient decreased over the life of the program, but the standardized mortality rates have also declined. Technology has bridged the gap and made the relative cost per treatment more affordable and science has developed medications and techniques that have enhanced both patient comfort and longevity. As more complex patients enter the fold of the ESRD program, an increased awareness of enhanced coordination of care needs to be recognized.

Comparison of renal transplantation and dialysis in rehabilitation of diabetic end-stage renal disease patients.

We have reviewed the outcome of replacement therapy for end-stage renal disease (ESRD) in 100 diabetic patients with emphasis on late complications, extrarenal diabetic manifestations, and overall patient rehabilitation. Long-term complications, other than myocardial infarction, were not different after renal transplantation compared with chronic dialysis. Overall rehabilitation was better after renal transplantation compared with chronic dialysis (p less than 0.05). Retinopathy and neuropathy were more stable with renal transplantation and peritoneal dialysis compared with hemodialysis (p less than 0.05). These factors should be considered along with expected patient survival when deciding between different treatment modalities for diabetic ESRD.

Acute renal failure in the intensive care unit. Therapy overview, patient risk stratification, complications of renal replacement, and special circumstances.

This article provides a basic definition of severity scoring among patients with acute renal failure and extends the definition into the types of dialysis support that are generally used in intensive care unit acute renal failure. Acute dialysis dosing and the problems that create a difference between chronic renal failure and acute renal failure support are described, the dialytic techniques and side effects and complications of each are compared, and nonrenal-based special situations in which extracorporeal therapy has been found to be helpful are defined.

The use of iron in patients on chronic dialysis: mistake and misconceptions.

Anemia is the most common hematologic abnormality in patients with chronic renal failure. The reasons for anemia in chronic renal failure are many and include erythropoietin and iron deficiencies, inflammation, infection, aluminum toxicity, and hyperparathyroidism. Iron deficiency alone affects more than 50% of patients on dialysis, and the estimated iron loss for these patients is 1.5 to 3 grams per year. The use of erythropoietin has also uncovered iron deficiency in a multitude of patients. Iron and erythropoietin supplementation has often restored normal or near-normal levels of hematocrit in these patients and has therefore improved some of the symptoms classically connected with chronic renal failure, such as fatigue, cold intolerance, and mental sluggishness, among others. Resistance to erythropoietin is frequently observed in the maintenance care for dialysis patients, and the most common reason is iron deficiency. It is important to understand the physiology of renal anemia, erythropoiesis and iron metabolism in order to avoid mistakes and misconceptions in the management of iron in chronic dialysis patients. In this article, we review several mistakes, misconceptions, practices, and guidelines in iron supplementation therapy. We also review the physiology of anemia in renal disease and the importance of erythropoietin and iron in causing anemia and discuss recent Dialysis Outcomes Quality Initiative (DOQI) guidelines on the topic.

Risk modeling in acute renal failure requiring dialysis: the introduction of a new model.

Predicting patient outcome in acute renal failure has become increasingly important as technology advances and ethical questions arise concerning life supporting therapies. We propose a new model which uses mortality as an endpoint and may be applied to the acute renal failure patient in the ICU setting who requires dialysis. This model is based on our ICU acute renal failure registry and has been prospectively validated for our institution. Our registry for the purposes of developing this model consists of data from 512 ICU patients requiring acute dialysis from 1988 until 1992. The model was developed by testing a variety of potential risk factors for mortality in a univariate analysis (Student's t-test and Chi square), and those factors found to be significant (p < 0.05) were subsequently tested in a multivariate fashion. The factors found significant included male gender, respiratory failure requiring intubation, hematologic dysfunction (platelet count < 50,000, leukocyte count < 2,500, or bleeding diathesis), bilirubin < 2.0 mg/dl, the absence of surgery, serum creatinine on the first dialysis treatment day, an increasing number of failed organ systems, and an increased BUN from the time of admission. Weights are assigned to each variable based on the odds ratio, and a score is generated with a range of 0 to 20. The initial data for the registry demonstrates good fit using the Hosmer and Lemeshow goodness-of-fit table. The model is next validated in 88 patients from 1993 through February 1994, then prospectively tested in 35 additional patients using a standard data collection form, and the model continues to demonstrate good fit. Although this model has been prospectively validated at our institution, this model or any such predictive model should be used with caution if not independently validated at any institution which proposes its use.

Validity of four models for predicting outcome in critically ill acute renal failure patients.

OBJECTIVE: Several mathematical models are used to predict the survival of patients in renal failure and have become standards. Few of these models have been sufficiently validated, however, and their applicability at other institutions has been established. DESIGN: We attempted to validate four models used to predict mortality in the setting of acute renal failure (Lohr, Bullock, Cioffi, APACHE II) with a registry of 512 ICU patients who received acute dialysis at our institution between 1988 and 1992. Using mortality as an endpoint, we applied each model as described by the original authors and compared the predicted results against the actual outcomes recorded in the registry. RESULTS: The Lohr Model is based on five risk factors thought to predict mortality or survival. Although we found these five factors were strongly associated with mortality (p < 0.001), more than 20% of the highest-risk group survived. The Bullock Model predicted only 20% of the mortality of our data. For the Cioffi Model, the original study found a clear discrimination score (survivors: 1.76, non-survivors: -0.423); however, we found no significant difference in the score discriminating survivors and non-survivors (survivors: 0.70, non-survivors: 0.71, p = 0.96). APACHE II is a risk model consisting of a premorbid assessment of chronic health and 12 physiologic variables taken during ICU admission. We applied APACHE II to both our cardiac and non-cardiac patients, and found that this score did not discriminate between survivors and non-survivors (p values ranged from 0.37 to 0.62) in acute renal failure in either case: the original APACHE II system was not applied to cardiac surgery patients. CONCLUSIONS: We conclude that models with good performance in their institutions of origin may not be valid in other institutions. Before using a predictive model, validity testing at the specific institution should be undertaken.

Blood recirculation in temporary central catheters for acute hemodialysis.

The low-flow method has been shown as a reliable evaluation of access recirculation. Few data is available on temporary central catheter blood recirculation; results of 2% and 4% have been reported in subclavian, 10% in 24 cm long femoral, and 18% in 15 cm long femoral catheters, mostly in indwelling catheters for chronic hemodialysis. The purpose of this prospective study was to evaluate blood recirculation in a larger number of recently inserted temporary intravenous catheters for acute hemodialysis, comparing subclavian and femoral sites. Fifty blood recirculation measurements were performed in 38 different temporary central venous dialysis catheters inserted in thirty-one critically ill patients from medical and surgical intensive care units presenting acute renal failure supported by intermittent hemodialysis. All the catheters used were well-functioning 11.5 French dual lumen Quinton of 13.5 or 19.5 cm length. Catheters presenting mechanical dysfunction, which did not allow a blood flow rate of 300 ml/min or for which lines had to be reversed were excluded from the analysis. Access blood recirculation was measured shortly after catheter insertion according to the low flow method applied after the first 30 minutes of hemodialysis at a blood flow rate of 300 ml/min. Mean blood recirculation for the 50 measurements was 10.3 +/- 9.2%. It was significantly higher in the 26 femoral catheters than in the 24 subclavian catheters, reaching respective means of 16.1 +/- 9.1% and 4.1 +/- 3.6% (p = 0.0001). Blood recirculation rate was not different between 13.5 cm and 19.5 cm long subclavian catheters (3.0 +/- 2.6%, n = 13, versus 5.4 +/- 4.3%, n = 11, respectively), but was significantly higher in 13.5 cm long femoral catheters (22.8 +/- 9.1%, n = 9, versus 12.6 +/- 6.9%, n = 17) (p = 0.004). Blood recirculation was measured on two separate occasions in 12 catheters randomly selected (5 femoral and 7 subclavian catheters); the obtained results were reproducible with a mean difference of only 2.1 +/- 1.8% between the two measurements and a correlation of 0.96. The mean time elapsed between catheter insertion and recirculation assessment was 2.2 +/- 3.1 days and was similar for femoral and subclavian catheters. No correlation was found between the percentage of recirculation and the arterial and venous resistances recorded during dialysis session or with the time from catheter insertion. Mean urea reduction ratio (URR) for the 50 dialysis sessions was 57.8 +/- 13.0%. It was significantly higher for sessions performed with subclavian than with femoral catheters (62.5 +/- 10.9%, n = 24, versus 54.5 +/- 14.2%, n = 26) (p = 0.03). In conclusion, the expected blood recirculation in well-functioning and recently inserted temporary dialysis catheters is under 5% for subclavian, over 12% in 19.5 cm femoral, and over 22% in shorter 13.5 cm femoral catheters at a blood flow rate of 300 ml/min. The consequently reduced dialysis efficiency with femoral catheters is another factor to be considered in the choice of a site for temporary dialysis catheter insertion in acute renal failure patients, particularly when dialysis dose delivery is a priority, such as intoxication cases treated by extracorporeal therapy.

A preliminary survey of bacterial contamination of the dialysate circuit in continuous veno-venous hemodialysis.

AIMS: The problem of dialysate bacterial contamination has not been defined in continuous renal replacement therapy. We assessed the bacterial integrity of source bicarbonate dialysate (study 1) and the continuous veno-venous HD (CVVHD) bicarbonate dialysate circuit (study 2). METHODS: Study 1: 50 ml dialysate were collected from 41 bags randomly selected from 150 consecutively made dialysate bags, immediately after manufacture or after 24, 48 or 72 h. Study 2: 10 ml dialysate were drawn from 4 sample points ranged along the dialysate circuit in 18 therapies (mean duration 119.5 +/- 72.0 h). All points were sampled at therapy start then daily, bar the proximal point which was sampled after each dialysate bag change. All dialysate samples underwent Gram stain and aerobic/anaerobic culture. Samples over 10 ml were cultured after centrifugation (15 min, 4,000 rpm). A disseminated contamination (DC) involved > or = 1 sample point at a time and/or was sustained over time. RESULTS: Study 1: One bag was culture-positive (staphylococcal/diphtheroid growths; 48-h sample). Study 2: Six DCs developed in 6 therapies (1 at therapy end, 5 sustained to therapy end (duration 57.25 +/- 45.95 h), 5 with Gram-negative bacilli, all involving reported growths of > or = 1,000 cfu). Dialyzer-inclusive dialysate circuit changes were more frequent in non-DC therapies (change rate: DC, 0.08 +/- 0.12/day, non-DC, 0.34 +/- 0.23, p = 0.02, permutation tests with general scores) but did not entirely prevent DC or alter it once underway. CONCLUSIONS: Sustained bacterial contamination of bicarbonate-based CVVHD is common and could relate to the completeness of dialysate circuit change. The importance of technique and regular quality control is highlighted.

Continuous renal prosthetic therapy in acute renal failure: an overview.

The technology surrounding the treatment of acute renal failure has been traditionally left in the realm of dialysis. The use of peritoneal dialysis for the neonate or small infant and the often difficult use of hemodialysis in larger children and adolescents have been the mainstay of support. Not infrequently, however, the multisystem nature of the failure demonstrated by these patients made either form of therapy at best inadequate. The morbidity of the procedure would add to the already high morbidity of the disease and the patient would either be unable to receive the needed medications because of necessary fluid restrictions, or be subjected to severe hemodynamic or respiratory embarrassment due to the treatment methods themselves. It is precisely toward this patient population that the continuous forms of renal replacement therapy, reviewed herein, are directed.

Growth kinetics and structure of fibrin gels.

The structure and kinetics of fibrin gels grown from fibrinogen solutions under quasiphysiological conditions, but in absence of Ca++, were investigated by means of elastic light scattering. By combining classical light scattering and low-angle elastic light scattering, an overall wave-vector range of about three decades was spanned, from q approximately 3 x 10(2) to q approximately 3 x 10(5) cm(-1). The scattered intensity distribution of the gels was measured in absolute units and fitted to a single function, which was able to reproduce accurately the data over the entire wave-vector range. From the fitting, it was possible to estimate the average diameter d of the fibrin fibers, the average crossover length xi of the gel, and establish the fractal nature of the gel structure, with a measure of its fractal dimension D(m). The measure of the intensity in absolute units also allowed the estimate of the density rho of the fibrin fibers and provided an independent measure of their size. The kinetics of formation of the gel was described in terms of a simple growth model: the scaffold of the network is formed very early in the course of the gelation process, at a "networking time," t(n), which is much smaller than the time required to form the final gel. At times t>t(n), the gel structure remains substantially unchanged and the successive growth consists only in a thickening of the gel fibers. Gels prepared under the same physical-chemical conditions, but at different fibrinogen concentrations, exhibited rather similar structures and kinetics, showing that the modalities of the gelation process are mainly governed by the solution conditions, and only secondarily by the fibrinogen concentration. For gels at fibrinogen concentration of approximately 0.24 mg/ml, the gel parameters were d approximately 130 nm, xi approximately 27 microm, D(m) approximately 1.3, and rho approximately 0.4 g/cm(3). Our d and rho values are in very good agreement with electron microscopy- and turbidity-derived literature data, respectively, while xi seems to be related to the mesh size of the initial scaffold formed at t(n), rather than to the mesh size of the final aged gel.