Comparison of Sustained Hemodiafiltration With Continuous Venovenous Hemodiafiltration for the Treatment of Critically Ill Patients With Acute Kidney Injury

Despite improvements in medical care, the mortality of critically ill patients with acute kidney injury (AKI) who require renal replacement therapy (RRT) remains high. We describe a new approach, sustained hemodiafiltration, to treat patients who suffered from acute kidney injury and were admitted to intensive care units (ICUs). In our study, 60 critically ill patients with AKI who required RRT were treated with either continuous venovenous hemodiafiltration (CVVHDF) or sustained hemodiafiltration (S‐HDF). The former was performed by administering a postfilter replacement fluid at an effluent rate of 35 mL/kg/h, and the latter was performed by administering a postfilter replacement fluid at a dialysate‐flow rate of 300–500 mL/min. The S‐HDF was delivered on a daily basis. The baseline characteristics of the patients in the two treatment groups were similar. The primary study outcome—survival until discharge from the ICU or survival for 30 days, whichever was earlier—did not significantly differ between the two groups: 70% after CVVHDF and 87% after S‐HDF. The hospital‐survival rate after CVVHDF was 63% and that after S‐HDF was 83% (P < 0.05). The number of patients who showed renal recovery at the time of discharge from the ICU and the hospital and the duration of the ICU stay significantly differed between the two treatments (P < 0.05). Although there was no significant difference between the mean number of treatments performed per patient, the mean duration of daily treatment in the S‐HDF group was 6.5 ± 1.0 h, which was significantly shorter. Although the total convective volumes—the sum of the replacement‐fluid and fluid‐removal volumes—did not differ significantly, the dialysate‐flow rate was higher in the S‐HDF group. Our results suggest that in comparison with conventional continuous RRT, including high‐dose CVVHDF, more intensive renal support in the form of postdilution S‐HDF will decrease the mortality and accelerate renal recovery in critically ill patients with AKI.     

Glutamine and Other Amino Acid Losses During Continuous Venovenous Hemodiafiltration

Abstract: Serum amino grams and daily losses of glutamine (Gin) and other amino acids (AAs) into diafiltrate were measured during the first 5 days of continuous venovenous hemodiafiltration (CVVHDF) in 6 ICU patients with acute renal failure (ARF). Four patients had ARF as a part of multiple organ failure (MOF) of septic origin, and 2 patients had isolated ARF because of primary renal disease. During the study, all the patients received defined total parenteral nutrition (TPN). The mean daily AA losses into dialysate were relatively low (0.61 ± 0.1 g N ) and reached 4.5% of the daily AA substitution. Gln represented 32.7 ± 5.9% of the total AA losses (0.19 ± 0.04 g N ). Serum levels of Gin (p = 0.002) and of most other AAs were significantly lower in the patients than in the control subjects (AA analysis in 16 healthy volunteers). Phenylalanine (Phe) was the only AA that was increased significantly (p < 0.01) in the patients. The mean patient serum concentrations of Phe and tyrosine were significantly higher (p < 0.03) than the correspondent concentrations in dialysate, but the lysine concentration was higher in dialysate (p < 0.03). The serum and dialysate concentrations of other AAs did not differ. Gin in serum decreased significantly (p < 0.03) on the second day of CVVHDF but returned to the baseline levels subsequently. Serum concentrations of Phe increased on the second day of CVVHDF (p < 0.05). Serum concentrations of other AAs remained stable during the whole study. We conclude that Gin losses into dialysate during CVVHDF are relatively low, but CVVHDF itself may induce changes in Gin metabolism and distribution that are reflected by a decrease of serum Gin levels at the institution of this treatment. Therefore, the need for Gin supplementation in ICU patients is even greater in the first days of CVVHDF.     

Strategies for the Treatment of Acute Renal Failure in Intensive Care Units: The Aspect of Dosing

Despite all the medical progress, the mortality rate in intensive care units for patients with acute renal failure (ARF) remains high, among specific patient populations, up to 88% [Letourneau I, Dorval M, Belanger R, Legare M, Fortier L, Leblanc M. Acute renal failure in bone marrow transplant patients admitted to the intensive care unit. Nephron Apr 2002; 90(4), 408–12.]. Recent trial results indicate that patient survival may be improved by adequate renal replacement therapy. In particular, the dose of intermittent and continuous renal replacement therapies has proved to be a significant factor affecting patient survival. Daily intermittent hemodialysis, e.g., is superior to alternate‐day intermittent hemodialysis, and with continuous therapies, survival is related to the filtration rate. Further relevant factors include early initiation of renal replacement therapy, choice of biocompatible membranes and the application of bicarbonate‐buffered replacement solutions for defined patient groups. The advantages offered by continuous techniques could be demonstrated for individual patient groups; in meta‐analyses, advantages were shown for the total population of patients with ARF. Other than for patients with chronic renal failure (NKF—DOQI. Clinical practice guidelines for hemodialysis adequacy. Am J Kid Dis 1997; Vol. 30, 515–566.), there are no current clinical guidelines for a standard treatment of intensive care patients with ARF. Therefore, such a treatment standard still needs to be determined.     

Hemodynamics and Survival of Patients with Acute Renal Failure Treated by Continuous Dialysis with Two Synthetic Membranes

Synthetic membranes are not identical and have specific interactions that may be harmful or beneficial. We have investigated the incidence of hypotension and the outcome of acute renal failure (ARF) in ventilated patients treated by continuous venovenous dialysis with 2 different synthetic membranes. In Study 1, the mean arterial pressure (MAP) and systemic vascular resistance (SVR) were monitored during the first 12 min of dialysis with polyacrylonitrile (PAN). In Study 2, the MAP and survival rates were compared in patients randomly assigned to either PAN or polysulfone. No subjects were receiving angiotensin converting enzyme inhibitors. In Study 1, the MAP decreased due to a reduction in the SVR during the first 6 min of dialysis but returned to the baseline value by 12 min in 22 patients during 27 dialysis treatments. In Study 2, the MAP was lower than the baseline value at 6 min during 233 dialysis treatments in 133 patients randomly assigned to PAN or polysulfone membranes (PAN group, 81.5 ± 15 to 78.7 ± 15.6 mm Hg, p =0.001; and polysulfone group, 81.3 ± 15.4 to 80.0 ± 15.7 mm Hg, p =0.06). Severe reductions in the MAP were seen during 13.2% of the PAN and 7.2% of the polysulfone treatments (χ², p =NS). The age, APACHE II score, MAP, inotrope requirement, and primary diagnosis did not differ according to membrane material in a total of 197 consecutive patients (PAN, n =97; polysulfone, n =100). Patient survival was 29% (PAN) and 27% (polysulfone). In multivariate analysis, APACHE II score, inotrope requirement, and liver failure were significant determinants of survival. In conclusion, PAN and polysulfone membranes were not different with respect to hypotensive reactions or survival in critically ill patients undergoing continuous venovenous hemodialysis.     

An Improvement in the Outcome of Acute Renal Failure

Background: Acute renal failure (ARF) requiring hemodialysis (HD) treatment is related to high mortality. The aim of this study was to analyze the influence of age, disease severity, and catabolism intensity on ARF outcome in patients requiring HD treatment during a 15‐year period (1987–2001). Methods: The retrospective, single‐center study included 583 patients, 428 male, 155 female, age 49 ± 15 years, treated by intermittent HD using cuprophane membranes with surface area of 1.3 m². Liano's Acute Tubular Necrosis Individual Severity Score (ATNISS) score and Hypercatabolism Depuration Score (HDS) score were calculated to estimate disease severity and catabolism intensity in ARF patients. Results: Average age of patients significantly increased during the 15‐year period for more than one decade (44 to 55 years; p = 0.0359), especially during the last five‐year period (47 ± 14.5 vs. 53 ± 14.7, p = 0.00015). Disease severity showed significant increase comparing periods 1992–1996 and 1997–2001 (ATNISS 0.385 ± 0.197 vs. 0.437 ± 0.208; p = 0.00137), while catabolism intensity during these periods was similar (HDS 0.569 ± 0.145 vs. 0.582 ± 0.127; p = 0.357). Despite the older and more severely ill population of ARF patients, mortality showed a sustained decrease during the 15‐year period. Mortality in the period from 1987 to 1991 (49/83; 59%) was similar with the period 1992–1996 (χ² = 0.44, p = 0.5081), but significantly higher than in the period 1997–2001 (114/250; 45.6%; χ² = 3.98, p = 0.0471). Conclusion: The results showed an improvement in the outcome of patients with ARF requiring HD treatment, despite increasing age, disease severity, and use of bioincompatible membranes.     

Anticoagulation with Low Molecular Weight Heparin (Fragmin) during Continuous Hemodialysis in the Intensive Care Unit

Abstract: A preparation of low molecular weight heparin (Fragmin) was administered to patients with multiorgan failure receiving continuous venovenous hemodialysis. Three patients received a high-dose regimen (35 IU/kg bolus followed by 13 IU/kg infusion), and 7 received a low-dose regimen (8 and 5 IU/kg, respectively) for 36 h. High-dose Fragmin was associated with minimal clotting in the extracorporeal circuit. Plasma fibrinopeptide A levels declined, and mean anti-Xa activity was in the range 0.47-0.79 IU/ml. The urea equilibration coefficient (UEC) (100% at initiation) remained above 90% throughout. All 3 patients had mild bleeding episodes, which led to discontinuation of Fragmin in 1. During all low-dose treatments, marked thrombus formation occurred in the extracorporeal circuit, and in 2, the circuit clotted within the study period. Fibrinopeptide A levels further increased in 4 patients, and mean anti-Xa activity was in the range 0.27-0.53 IU/ml. UEC declined appreciably in 3 treatments (including the 2 in which early circuit clotting occurred). One patient experienced a mild bleeding episode. The low-dose Fragmin regimen produced safer anticoagulation in patients at risk from bleeding and is suitable for prolonged renal support although the tendency to thrombosis may necessitate more frequent circuit changes.     

Acute Renal Failure During Eclampsia: Incidence Risks Factors and Outcome in Intensive Care Unit

Objective: To assess the incidence, risk factors and the outcome of acute renal failure (ARF) associated with eclampsia in intensive care unit (ICU). Design: Prospective and analytic study. Setting: A surgical ICU in a university hospital. Patients: 178 consecutive women with eclampsia admitted to an intensive care unit during seven years. ARF was defined by a serum creatinine concentration > 140 µmol/L. Results: The incidence of ARF was 25.8%. In univariate analysis the severity of patient illness, the complications associated with eclampsia (disseminated intravascular coagulation, Hellp syndrome, neurologic complications, abruptio placenta, aspiration pneumonia, delivery hemorrhage) were significantly associated with ARF. In a logistic regression model, risk factors for ARF included organ system failure (OSF) odds ratio (OR) = 1.81 confidence interval (CI) [1.08–3.05], bilirubin > 12 µmol/L OR = 4.42 CI [1.54–12.68], uric acid > 5.9 g/dL OR = 16.5 CI [3.09–87.94], abruptio placenta OR = 0.2 7 CI [0.08–0.99], and oliguria OR = 0.10 CI [0.03–0.44]. In contrast, severity of blood pressure or proteinuria on dipstick were not associated with ARF. However, in this series, 15 women required dialysis in the short term and one required long‐term dialysis. ARF associated with eclampsia was significantly associated with mortality (32.6% versus 9.1% p = 0.0001). Conclusion: ARF with eclampsia is a frequent situation that required intensive management when risks factors were present. The need for dialysis was a rare condition.     

Comparison of a Lactate- Versus Acetate-Based Hemofiltration Replacement Fluid in Patients with Acute Renal Failure

The objective of the study was to determine the impact of a lactate- and an acetate-based hemofiltration replacement fluid (HF) on the acid–base status in patients with acute renal failure (ARF) and continuous venovenous hemofiltration (CVVH). The prospective, cohort study was carried out in the intensive care unit of the Heinrich-Heine University Hospital, Düsseldorf, FRG. Subjects were 84 critically ill patients with ARF and CVVH. Fifty-two patients were subjected to lactate-based (group 1) and 32 to acetate-based hemofiltration (group 2). Thirty-eight patients had a septic, 46 a cardiovascular origin of the ARF. Creatinine, BUN, serum bicarbonate, arterial pH, lactate and APACHE II score were noted daily. Mean CVVH duration was 9.8 ± 8.1 days; mortality was 65%. The groups did not differ with regard to the main clinical parameters. Lacate-based hemofiltration led to significantly higher serum bicarbonate and arterial pH values as compared to the acetate-based hemofiltration. Baseline serum bicarbonate values were 23.3 ± 8.3 mmol/L in group 1 and 21.6 ± 4.3 mmol/L in group 2 (NS); values at 48 h after initiating CVVH treatment were 25.7 ± 3.8 mmol/L and 20.6 ± 3.1 mmol/L, respectively (p < 0.001). Arterial pH prior to CVVH treatment was 7.36 ± 0.1 in group 1 and 7.34 ± 0.1 in group 2 (NS), and 7.43 ± 0.07 versus 7.37 ± 0.06 (p < 0.001) on day 2. These findings were maintained throughout therapy. While a lack of increase in serum bicarbonate and arterial pH was correlated to a poor prognosis in lactate-based hemofiltration, no such observation could be made in acetate-based hemofiltration. Septic patients did not differ in their acid–base status from nonseptic patients. Lactic acidosis occurred in 8 septic patients irrespective of the substitution fluid. All 8 patients died. There was a significant increase in HCO₃ and arterial pH values in lactate-based as compared to acetate-based HF.     

Acute Renal Failure in Patients with Kidney Transplant: Continuous Versus Intermittent Renal Replacement Therapy

Mortality from acute renal failure in critically ill patients remains in excess of 50% despite decades of improvement in supportive care. It is not known whether replacement of other failing organs by non-renal organ transplantation affects mortality in acute renal failure. We retrospectively reviewed the course of 169 patients with acute renal failure managed at a single university medical center over a 1-year period. Measures of disease severity (need for renal replacement therapy, mechanical ventilation or parenteral nutrition, presence of oliguria and APACHE II scores) and final outcome were compared in 97 patients with acute renal failure who did not receive transplants and 72 patients with acute renal failure who underwent non-renal solid organ transplants. Overall mortality was 50.3% and directly correlated with APACHE II score. Compared to nontransplant patients, transplant recipients were younger, more frequently male, and less often oliguric; but the groups were similar in mean APACHE II scores and need for renal replacement therapy, prolonged mechanical ventilation, and parenteral nutrition. Overall, mortality was significantly lower for transplant patients compared to nontransplant patients (34.7% vs. 61.9%, p < 0.05). In nonoliguric acute renal failure and renal failure not requiring renal replacement therapy, mortality was low and similar in both transplant and nontransplant patients. Compared to nontransplant patients with similar risk factors and similar APACHE II scores, mortality was significantly lower for transplant patients who were oliguric, or who required renal replacement therapy, mechanical ventilation, or parenteral nutrition. Organ transplantation is associated with a survival advantage in acute renal failure when compared to the outcome of critically ill nontransplant patients. The relation between APACHE II scores and survival is altered by transplantation.     

Continuous Arteriovenous Haemofiltration and Haemodiafiltration in Acute Renal Failure

Continuous arteriovenous haemofiltration (CAVH) was employedin ten patients with acute renal failure using an AN-69 platefilter. Special measures were taken to improve the efficiencyof the technique, including the use of short, large-bore cathetersfor vascular access, predilution infusion of the substitutionfluid, and moderate vacuum suction to the ultrafiltrate compartment.In five patients continuous arteriovenous haemodiafiltrationwas performed by the addition of slow dialysis at a dialysateflow of 1 litre per hour. This technically simple manoeuvreenhanced solute clearances up to 20 ml/min and obviated theneed for standard intermittent dialysis sessions in all cases. Repeated measurements of transmembrane pressure and ultrafiltrationrate permitted calculation of the in vivo membrane permeabilityindex, which showed a reproducible decline with time. With relativelylow heparin requirements an adequate filter performance couldbe maintained for over 48 h. The encouraging clinical resultsindicate that CAVHD, in spite of the invasive nature of thistechnique, may be considered a first-choice treatment for patientswith acute renal failure in the intensive care unit.     

Renal Protective Effects of Early Continuous Venovenous Hemofiltration in Rhabdomyolysis: Improved Renal Mitochondrial Dysfunction and Inhibited Apoptosis

Rhabdomyolysis (RM) and subsequent myoglobin (Mb) deposition can lead to acute kidney injury. Continuous venovenous hemofiltration (CVVH) can remove Mb, but direct renal protection is unclear. We hypothesized that CVVH can improve renal mitochondrial dysfunction in its early stage. Twenty‐four mongrel dogs were randomly divided into four groups: (A) control; (B) model; (C) model + CVVH (50 mL/kg/h); and (D) model + CVVH (30 mL/kg/h). RM was induced by glycerol via intramuscular injection. The dogs were closely monitored for urine flow and renal function. Mb, plasma tumor necrosis factor‐α (TNF‐α), and interleukin (IL)‐6 were measured by enzyme‐linked immunosorbent assay. After 8 h of CVVH, the morphological changes of renal mitochondria were observed and mitochondrial function indicators (reactive oxygen species, malondialdehyde, and respiratory control index) were detected. Western blot analysis was used to detect the expression of Mb, TNF‐α, and IL‐6 in renal tubules. The terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin nick end labeling assay method and Western blot analysis were used to detect apoptosis and apoptosis‐related proteins. In group B, the dog urine output gradually decreased with increased blood creatinine. In groups C and D, the urine output was normal and stable. CVVH effectively eliminated Mb. High‐dose CVVH was significantly better for removal efficiency than low‐dose CVVH. CVVH significantly reduced the deposition of circulating Mb in the kidney in a dose‐dependent manner. The impact of CVVH on TNF‐α and IL‐6 were not observed. The morphological changes of mitochondria and function indicators were significantly improved in group C compared with groups D and B. Compared with group B, renal apoptosis and apoptosis‐related protein expression were inhibited in groups C and D. Group C was significantly better for mitochondrial improvement and apoptosis inhibition than group D. At the cellular and molecular level, CVVH can improve renal mitochondrial function and inhibit cell apoptosis. Early CVVH can protect from RM‐caused renal injuries in a dose‐dependent manner.     

急性肾衰竭三种治疗方法的疗效对比观察

目的 :回顾性探讨治疗急性肾衰竭较理想的透析方法。方法 :对 2 3例HD患者和 2 0例PD患者及 17例CRRT患者进行比较 ,观察其治愈率、死亡率及透析后的主要并发症。结果 :HD组、PD组、CRRT组的治愈率分别为 82 .6 %、85 %、76 .5 % ;死亡率分别为 8.7%、0、17.6 %。腹膜透析并发症少。结论 :急性肾衰竭在缺少CRRT条件 ,病情允许情况下可首选腹膜透析治疗 ,严重病例、多器官衰竭还是选择CRRT为宜     

Outcomes of Acute Renal Failure Patients Requiring Intermittent Hemodialysis

The published studies on the prognosis of patients requiring intermittent hemodialysis (IHD) are scarce and have some conflicts. In this study, we retrospectively analyzed our data on ARF patients who were treated with IHD. A total of 192 (female: 85, 44.3%; male: 107, 55.7%) patients were included in the study. The mean age was 56.3 ± 17.1 years. In all, 48.9% of the patients were older than 60 years. The mean number of IHD sessions was 7.8 ± 8.0 per patient; 12.4% was due to prerenal causes, 76.8% was due to intrarenal causes, and 10.8% was due to postrenal causes. The leading indication of the IHD was uremic symptoms (46.8%). With the exclusion of hypertension, 72.4% of the patients had at least one systemic comorbidity. After treatment, 75.5% of the patients recovered, in contrast to 9.4% of patients who were transferred to chronic renal replacement programs and 15.1% who died during IHD period. Pre-dialytic serum creatinine (p?=?0.003) and albumin levels (p?=?0.016), total IHD session number per patient (p?=?0.003), and age (p?=?0.034) were the parameters that were related to high mortality in statistical analysis. Mortality was higher if the leading indication of IHD was biochemical disturbances (p?=?0.013). Diabetes mellitus did not influence mortality. Consequently, predialytic serum creatinine and albumin levels may be very important predictors of mortality. Patients in high-risk groups (older age, female sex, and low pre-dialytic creatinine and albumin levels) should be considered to be treated with slow continuous renal replacement methods.     

Successful Treatment of Six Patients with Neuroleptic Malignant Syndrome Associated with Myoglobulinemic Acute Renal Failure

Neuroleptic malignant syndrome is a rare but potentially lethal, rare reaction to neuroleptics which is characterized by altered levels of consciousness, extrapyramidal effects, autonomic instability, hyperthermia, and elevated serum creatine phosphokinase levels. The most serious complication of neuroleptic malignant syndrome is acute renal failure.

We investigated six cases of neuroleptic malignant syndrome associated with myoglobulinemic acute renal failure due to rhabdomyolysis and effect of hemodialysis or hemodiafiltration.

The patients were five males and one female with a mean age of 43.5 yr. All of the patients, who developed acute renal failure induced from rhabdomyolysis, had previously received butyrophenone (haloperidol), phenothiazine, benzamide, iminomide, benzisoxazole, antidepressants, and hypnotics (benzodiazepine and barbiturate) for the treatment of schizophrenia. The clinical manifestations of neuroleptic malignant syndrome were characterized by altered consciousness, muscle rigidity and weakness, fever, and excessive perspiration. The peak laboratory data were blood urea nitrogen 102 ± 26 (mean ± SD) mg/dL, serum creatinine 9.1 ± 2.1 mg/dL, serum creatine phosphokinase 229,720 ± 289,940 IU/L, and all of them developed oliguric acute renal failure. Dantrolene sodium administration was given to five cases and hemodialysis or hemodiafiltration was performed in all of them. The serum creatinine level after hemodialysis or hemodiafiltration was 1.4 ± 1.0 mg/dL. All patients were successfully cured of acute renal failure by hemodialysis or hemodiafiltration.

As a result, myoglobulinemic acute renal failure associated with neuroleptic malignant syndrome was successfully treated by hemodialysis or hemodiafiltration.     

Treatment of acute renal failure in an infant by continuous arteriovenous hemodialysis

Continuous arteriovenous hemodialysis (CAVHD) was performed in a critically ill, oliguric infant with progressive uremia using a miniature Amicon hemofilter. Modification was made in the filter system by circulating 2.5% Dianeal peritoneal dialysis fluid into the second port of the ultrafiltrate compartment to enable the filter to function by dialysis too (CAVHD). In comparison with continuous arteriovenous hemofiltration (CAVH), CAVHD provided superior urea clearance and adequate fluid removal, allowing the simultaneous administration of parenteral nutrition. The higher solute clearances in CAVHD make the technique superior to CAVH for renal replacement therapy in critically ill infants.     

Adequacy Indices for Dialysis in Acute Renal Failure: Kinetic Modeling

Many aspects of the management of renal replacement therapy in acute renal failure (ARF), including the appropriate assessment of dialysis adequacy, remain unresolved, because ARF patients often are not in a metabolic steady state. The aim of this study was to evaluate a system of adequacy indices for dialysis in ARF patients using urea and creatinine kinetic modeling. Kinetic modeling was performed for two different fictitious patients (A and B) with characteristics described by the average parameters for two patient groups and for two blood purification treatments: sustained low efficiency daily dialysis (SLEDD) in Patient A and continuous venovenous hemofiltration (CVVH) in Patient B, based on data from a clinical report. Urea and creatinine generation rates were estimated according to the clinical data on the solute concentrations in blood. Then, using estimated generation rates, two hypothetical treatments were simulated, CVVH in Patient A and SLEDD in Patient B. KT/V, fractional solute removal (FSR) and equivalent renal clearance (EKR) were calculated according to the definitions developed for metabolically unstable patients. CVVH appeared as being more effective than SLEDD because KT/V, FSR, and EKR were higher for CVVH than SLEDD in Patients A and B. Creatinine KT/V, FSR, and EKR were lower and well correlated to the respective indices for urea. Urea and creatinine generation rates were overestimated more than twice in Patient A and by 30–40% in Patient B if calculated assuming the metabolically stable state than if estimated by kinetic modeling. Adequacy indices and solute generation rates for ARF patients should be estimated using the definition for unsteady metabolic state. EKR and FSR were higher for urea and creatinine with CVVH than with SLEDD, because of higher K·T and minimized compartmental effects for CVVH.