Mortality after acute renal failure: models for prognostic stratification and risk adjustment.

To adjust adequately for comorbidity and severity of illness in quality improvement efforts and prospective clinical trials, predictors of death after acute renal failure (ARF) must be accurately identified. Most epidemiological studies of ARF in the critically ill have been based at single centers, or have examined exposures at single time points using discrete outcomes (e.g., in-hospital mortality). We analyzed data from the Program to Improve Care in Acute Renal Disease (PICARD), a multi-center observational study of ARF. We determined correlates of mortality in 618 patients with ARF in intensive care units using three distinct analytic approaches. The predictive power of models using information obtained on the day of ARF diagnosis was extremely low. At the time of consultation, advanced age, oliguria, hepatic failure, respiratory failure, sepsis, and thrombocytopenia were associated with mortality. Upon initiation of dialysis for ARF, advanced age, hepatic failure, respiratory failure, sepsis, and thrombocytopenia were associated with mortality; higher blood urea nitrogen and lower serum creatinine were also associated with mortality in logistic regression models. Models incorporating time-varying covariates enhanced predictive power by reducing misclassification and incorporating day-to-day changes in extra-renal organ system failure and the provision of dialysis during the course of ARF. Using data from the PICARD multi-center cohort study of ARF in critically ill patients, we developed several predictive models for prognostic stratification and risk-adjustment. By incorporating exposures over time, the discriminatory power of predictive models in ARF can be significantly improved.

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.

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.

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.

A fractional dialysate collection method to estimate solute removal in continuous venovenous hemodialysis.

BACKGROUND: Fractional direct dialysis quantification (fDDQ), whereby a known proportion of dialysate effluent is sampled, can reliably estimate total solute removal in intermittent hemodialysis (IHD). Our study aimed to develop and test the technique in continuous venovenous hemodialysis (CVVHD). METHODS: Twenty dialysate collections (mean duration 23.5 hours, range 17.25 to 26.6) were performed in 12 patients on CVVHD. An infusion pump diverted 10% of the total effluent volume to the fractional collection (fc), the remainder being channeled into the bulk collection (bc). Both fc and bc were collected on ice and assayed for urea nitrogen (UN) and creatinine (Cr). Actual solute removal (ASR) was calculated from the measured effluent volume and solute concentrations of the fc and bc. Estimated solute removal (ESR) was calculated from the product of the fc solute concentration and effluent volume. All fc/bc samples in 15 out of 20 collections underwent gram stain and aerobic/anaerobic culture. RESULTS: Bland-Altman analyses suggested good agreement between ASR and ESR [absolute values of percentage differences: 95% CI = 1.73, 5.17% (UN); 1.88, 4.31% (Cr)]. Favorable concordance correlation coefficients confirmed this [rc = 0.995 (UN), 0.997 (Cr)] and were apparently unaffected by heavy pseudomonal growths in 4 out of 7 culture positive collections [rc = 0.997 (UN), 0.997 (Cr); culture negative (N = 8), rc = 0.996 (UN), 0.997 Cr)]. CONCLUSION: fDDQ, using 24-hour, pump-assisted, cooled fractional dialysate sampling reliably estimates total solute removal and provides a practical alternative to total dialysate collection in assessing delivered dialysis dose.

Introduction of a switch that can reverse blood flow direction on-line during hemodialysis.

In several circumstances in hemodialysis, the regular direction of blood flow has to be reversed or changed, such as in access dysfunction or insufficient blood flow being obtained through the arterial port, as well as to measure actual access blood flow in fistulas or grafts by using the formula Qa = Qb((1-R)/R), where R represents recirculation in the reversed line configuration. We invented a disposable switch device made from standard blood line tubing that can be introduced into the dialysis circuit and allows for on-line reversal of lines, without needing to manually disconnect and reconnect tubing or interrupt the hemodialysis procedure. Over a period of eight months, 16 patients (8 arteriovenous fistula, 8 PTFE) underwent 193 hemodialysis sessions with the switch in place. Circuit pressures, pump, and actual blood flows measured with ultrasound dilution were monitored before and after reversing the lines. Switching was accomplished within 1-2 seconds. Arterial circuit (r = 0.99), venous circuit pressures (r = 0.6), and actual pump flow (364 +/- 56 vs. 350 +/- 57 ml/min; r = 0.73) correlated very well preswitching and postswitching (p < 0.0001). Dialysis circuit flow measured with an ultrasound dilution technique decreased from 364 +/- 56 (230-480) ml/min preswitching to 350 +/- 57 (220-490) ml/min postswitching (p < 0.001). No difficulties or complications were observed. This switch device is a useful addition to the technology of hemodialysis in that it greatly facilitates the procedure of reversing the lines in an extracorporeal circuit while not significantly interfering with circuit pressures and connections.

Abnormal electrical stimulus of an intra-aortic balloon pump with concurrent support with continuous veno-venous hemodialysis.

Malfunction of electronic medical support apparatus utilized in the ICU usually causes system failure. We report several occurrences of a potentially dangerous interaction between a continuous veno-venous hemodialysis (CVVHD) system and an intra-aortic balloon pump (IABP) counterpulsation device in four patients requiring both systems. The patients had acute renal failure in the face of multi-organ failure and were dependent upon the balloon pump for pressure support. Electrical interference created by the roller pump action of the CVVHD system was identified by the balloon pump as cardiac in origin, and it responded by inflation and deflation. As the blood pump rate was reduced, the interference reduced to the point of complete cessation when the blood pump was shut down. Whereas one patient transiently had a significant drop of mean arterial pressure (from 70 +/- 4 to 40 +/- 2 mm Hg) the other observed occurrences had no clinically significant sequelae. Electrocardiogram (ECG) tracings identified the abnormal stimulus and systematic review identified as potential sources for the creation of this interference static electricity buildup, piezoelectric properties of the polyvinyl chloride tubing, and, possibly but less likely, radiofrequency interference. A newer generation ECG cable and advanced cardiac rhythm recognition software (CardioSync) have been introduced with the Datascope System 98, and the ECG interference, although still occasionally present, does not cause erratic inflation and deflation of the intra-aortic balloon pump. Interference between different electrical support systems may occur, and we suggest that the systems be tested for compatibility before combined use and that older equipment be more rigorously tested for potential clinically significant interference.

Ultrafiltration method for measuring vascular access flow rates during hemodialysis.

BACKGROUND: The vascular access blood flow rate (QA) has been shown to be an important predictor of vascular access failure; therefore, the routine measurement of QA may prove to be a useful clinical method of vascular access assessment. METHODS: We have developed a new ultrafiltration (UF) method for determining QA during HD from changes in arterial hematocrit (H) after abrupt changes in the UF rate with the dialysis blood lines in the normal (DeltaHn) and reverse (DeltaHr) configurations. This method accounts for cardiopulmonary recirculation and requires neither intravenous saline injections nor accurate knowledge of the dialyzer blood flow rate. Clinical studies were conducted in 65 chronic HD patients from three different dialysis programs to compare QA determined by the UF method with that determined by saline dilution using an ultrasound flow sensor. RESULTS: Arterial H increased (P<0.0001) after abrupt increases in the UF rate when the lines were in the normal and reverse configurations. An increase in the UF rate from the minimum setting to 1.8 liter/hr resulted in a DeltaHn of 0.3+/-0.2 (mean +/- SD) H units and a DeltaHr of 1.6+/-1.0 H units. Q(A) values determined by the UF method (1050+/-460 ml/min) were 16+/-25% higher (P<0.001) than those determined by saline dilution (950+/-440 ml/min); the calculated QA values by the UF and saline dilution methods correlated highly with each other (R = 0.92, P<0.0001). The average coefficient of variation for duplicate measurements of QA determined by the UF method in a subset of these patients (N = 21) was approximately 10% when assessed in either the same dialysis session or consecutive sessions. CONCLUSIONS: The results from this study show that changes in arterial H after abrupt changes in the UF rate can be used to assess Q(A).

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.

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.

The move from dead to living membranes: bioartificial organ support of failing systems.

Several studies show that the diagnosis of acute renal failure still is predictive of high mortality. The reasons for this dismal prognosis despite improvements in dialytic methodologies and critical care are not entirely clear. Continuous renal replacement therapies have to date not shown improved outcome. Dialysis is conceptually not truly a "renal replacement therapy," because the many reabsorptive, metabolic, synthetic, and endocrine functions that occur in the kidney are not duplicated. This dilemma is applicable in varying degrees to other failing organs. Another therapeutic approach to a variety of organ failure conditions could be the transplantation of specific cell types to replace specific functions in the diseased host. The phenomenon of bioencapsulation with synthetic semipermeable membranes offers the possibility of allowing transplanted cells to function while sequestering them from the host's immune system. At this time, a bioartificial kidney is being developed that can be placed in series with a hemofilter and consists of proximal tubular cells layered on the surface of the hollow fibers of a dialyzer. Metabolic and transport functions appear to be intact. Further testing and refinement of this model will occur, which represents a potentially revolutionary form of therapy for renal disease.

Predictors of mortality and the provision of dialysis in patients with acute tubular necrosis. The Auriculin Anaritide Acute Renal Failure Study Group.

To explore the natural history of critically ill patients with acute renal failure due to acute tubular necrosis, we evaluated 256 patients enrolled in the placebo arm of a randomized clinical trial. Death and the composite outcome, death or the provision of dialysis, were determined with follow-up to 60 d. The relative risks (RR) and 95% confidence intervals (95% CI) associated with routinely available demographic, clinical, and laboratory variables were estimated using proportional hazards regression. Ninety-three (36%) deaths were documented; an additional 52 (20%) patients who survived received dialysis. Predictors of mortality included male gender (RR, 2.01; 95% CI, 1.21 to 3.36), oliguria (RR, 2.25; 95% CI, 1.43 to 3.55), mechanical ventilation (RR, 1.86; 95% CI, 1.18 to 2.93), acute myocardial infarction (RR, 3.14; 95% CI, 1.85 to 5.31), acute stroke or seizure (RR, 3.08; 95% CI, 1.56 to 6.06), chronic immunosuppression (RR, 2.37; 95% CI, 1.16 to 4.88), hyperbilirubinemia (RR, 1.06; 95% CI, 1.03 to 1.08 per 1 mg/dl increase in total bilirubin) and metabolic acidosis (RR, 0.95; 95% CI, 0.90 to 0.99 per 1 mEq/L increase in serum bicarbonate concentration). Predictors of death or the provision of dialysis were oliguria (RR, 5.95; 95% CI, 3.96 to 8.95), mechanical ventilation (RR, 1.53; 95% CI, 1.07 to 2.21), acute myocardial infarction (RR, 1.95; 95% CI, 1.24 to 3.07), arrhythmia (RR, 1.51; 95% CI, 1.04 to 2.19), and hypoalbuminemia (RR, 0.56; 95% CI, 0.42 to 0.74 per 1 g/dl increase in serum albumin concentration). Neither mortality nor the provision of dialysis was related to patient age. These observations can be used to estimate risk early in the course of acute tubular necrosis. Furthermore, these and related models may be used to adjust for case-mix variation in quality improvement efforts, and to objectively stratify patients in future intervention trials aimed at favorably altering the course of hospital-acquired acute renal failure.

A protocol for coadministration of i.v. iron dextran and heparin in chronic hemodialysis patients.

The coadministration of intravenous iron dextran and heparin as a continuous infusion during hemodialysis (HD) is a safe and effective method used in maintaining and/or increasing iron stores and hematocrit levels in patients with end stage renal disease (ESRD). The technique of mixing iron dextran in low doses with heparin and infusing this mixture via the heparin syringe pump on the dialysis machine has shown to be cost effective, as well as instrumental in reducing the risk of adverse reactions due to rapid infusion or large dose infusion of iron dextran. At the Cleveland Clinic Foundation, we developed a protocol based on this methodology. A total of more than 1,000 doses of intravenous iron dextran and heparin have been administered to our HD patients using this technique, and no adverse reactions have been reported or observed.