Continuous renal replacement therapy (CRRT) or intermittent hemodialysis (IHD)--what is the procedure of choice in critically ill patients? A randomized clinical trial of continuous versus intermittent dialysis for acute renal failure. Biocompatible membranes preserve residual renal function in patients undergoing regular hemodialysis. Preservation of residual renal function in dialysis patients: effects of dialysis-technique-related factors. Intercurrent clinical events are predictive of plasma C-reactive protein levels in hemodialysis patients. Tolerance of hemodialysis: a randomized prospective trial of high-flux versus conventional high-efficiency hemodialysis. Randomized controlled trial of intraoperative goal-directed fluid therapy in aerobically fit and unfit patients having major colorectal surgery. Comparison of cellulose diacetate and polysulfone membranes in the outcome of acute renal failure. A prospective randomized study. Comparison of continuous and intermittent renal replacement therapy for acute renal failure. Cardiovascular response during hemodialysis and hemofiltration: thermal, membrane, and catecholamine influences. Are high flux dialysis and erythropoietin treatment in a collision course? A randomized cross-over comparison of the hemodynamic response to intermittent hemodialysis and continuous hemofiltration in ICU patients with acute renal failure.
Although at present there is no prospective randomized study which could show significantly better survival of patients on continuous procedures, the majority of intensivists advocate this technique of renal function replacement due to generally accepted opinion that it has less effect on circulation of already hemodynamically unstable patients. In our prospective randomized study with 104 patients, we also did not observe any difference in 28 days survival, in total survival, as well as in circulatory instability between two treatment modalities. Even in subgroup of 80 patients with sepsis and septic shock there were no difference in survival. Sepsis was the underlying disorder in 52 and septic shock in 28 patients out of 104 patients analyzed in this study. Our prospective randomized study did not show a statistically significant difference between the two methods of renal replacement therapy. Survival rates were not affected and neither was the occurrence of hemodynamic instability. We believe that both methods are complementary; IHD for faster elimination of electrolytes and waste products elimination, CRRT for regulation of higher calories requirements and for hemodynamically unstable patients. The expectations that one method is superior to the other in the term of better survival have not been corroborated by the current data available in the literature. The choice of the method should be individualized. ARF, which is an integral part of MOF, is a problem frequently encountered in critically ill patient treated in the ICU, but outcome of these patients depends closely on the control of basic event. Evaluation of each of the supportive procedures is therefore hindered by the fact that the underlying disease has the crucial effect on survival and the type of supportive procedure less so. Acute renal failure (ARF) requiring dialysis in critically ill patients is associated with an in-hospital mortality rate of 50 to 80%. The worldwide standard for renal replacement therapy is intermittent hemodialysis (IHD). Continuous hemodialysis and hemofiltration techniques have recently emerged as alternative modalities. These two therapies have not been directly compared.
                A multicenter, randomized, controlled trial was conducted comparing two dialysis modalities (IHD vs. continuous hemodiafiltration) for the treatment of ARF in the intensive care unit (ICU). One hundred sixty-six patients were randomized. Principal outcome measures were ICU and hospital mortality, length of stay, and recovery of renal function.
                Using intention-to-treat analysis, the overall ICU and in-hospital mortalities were 50.6 and 56.6%, respectively. Continuous therapy was associated with an increase in ICU (59.5 vs. 41.5%, P < 0.02) and in-hospital (65.5 vs. 47.6%, P < 0.02) mortality relative to intermittent dialysis. Median ICU length of stay from the time of nephrology consultation was 16.5 days, and complete recovery of renal function was observed in 34.9% of patients, with no significant group differences. Despite randomization, there were significant differences between the groups in several covariates independently associated with mortality, including gender, hepatic failure, APACHE II and III scores, and the number of failed organ systems, in each instance biased in favor of the intermittent dialysis group. Using logistic regression to adjust for the imbalances in group assignment, the odds of death associated with continuous therapy was 1.3 (95% CI, 0.6 to 2.7, P = NS). A detailed investigation of the randomization process failed to explain the marked differences in patient assignment.
                A randomized controlled trial of alternative dialysis modalities in ARF is feasible. Despite the potential advantages of continuous techniques, this study provides no evidence of a survival benefit of continuous hemodiafiltration compared with IHD. This study did not control for other major clinical decisions or other supportive management strategies that are widely variable (for example, nutrition support, hemodynamic support, timing of initiation, and dose of dialysis) and might materially influence outcomes in ARF. Standardization of several aspects of care or extremely large sample sizes will be required to answer optimally the questions originally posed by this investigation. Initiation of hemodialysis causes a further decrease of residual renal function (RRF). To assess the impact of the biocompatibility of the dialysis membrane, we performed a prospective randomized investigation in 20 normotensive patients with tubulointerstitial nephritis. The patients were randomly allocated to treatment with either a high-flux polysulfone or cellulose membrane over a period of 12 months. RRF, defined by creatinine clearance and daily urine volume, was found to decrease in both groups of patients after the initiation of hemodialysis. Of the two membranes used, however, the cellulose membrane caused an accelerated decrease of RRF (P < 0.05). The better maintenance of RRF in patients treated with polysulfone membranes was associated with higher Kt/V values and increased hematocrit values (P < 0.05). The pathophysiologic mechanism underlying the more rapid decline of RRF could not be explained by intradialytic hypotension, but may be related to the nephrotoxic effects of inflammatory mediators due to bioincompatibility. Therefore, the use of polysulfone membranes might be preferable in patients with relevant RRF. Residual renal function (RRF) is of paramount importance to dialysis adequacy, morbidity, and mortality, particularly for long-term continuous ambulatory peritoneal dialysis (CAPD) patients. Residual renal function seems to be better preserved in patients on CAPD than in hemodialysis (HD) patients. We analyzed RRF in 45 patients with end-stage renal disease (ESRD), commencing either CAPD or HD, to prospectively define the time course of the decline in RRF, and to evaluate dialysis-technique-related factors such as cardiovascular stability and bioincompatibility.
                Single-center prospective investigation in parallel design with matched pairs.
                Fifteen patients starting CAPD and 15 matched pairs of patients commencing HD were matched according to cause of renal failure and RRF. Hemodialysis patients were assigned to two dialyzer membranes differing markedly in their potential to activate complement and cells (bioincompatibility). Fifteen patients were treated exclusively with the cuprophane membrane (bioincompatible) and the other 15 patients received HD with the high-flux polysulfone membrane (biocompatible).
                Residual renal function was determined at initiation of dialytic therapy and after 6, 12, and 24 months. Dry weight (by chest x ray and diameter of the vena cava) was closely recorded throughout the study, and the number of hypotensive episodes counted.
                Residual renal function declined in both CAPD and HD patients, although this decline was faster in HD patients (2.8 mL/minute after 6 months and 3.7 mL/min after 12 months) than in CAPD patients (0.6 mL/min and 1.4 mL/min after 6 and 12 months respectively). It declined faster in patients with bioincompatible than with biocompatible HD membranes (3.6 mL/min vs 1.9 mL/min after 6 months). Eleven percent of the HD sessions were complicated by clinically relevant blood pressure reductions, but there were no differences between the two dialyzer membrane groups. None of the CAPD patients had documented hypotensive episodes. None of the study patients suffered severe illness or received nephrotoxic antibiotics or radiocontrast media.
                The better preservation of RRF in stable CAPD patients corresponded with greater cardiovascular stability compared to HD patients, independently of the membrane used. Furthermore, there was a significantly higher preservation of RRF in HD patients on polysulfone versus cuprophane membranes, indicating an additional effect of biocompatibility, such as less generation of nephrotoxic substances by the membrane. Thus, starting ESRD patients on HD prior to elective CAPD should be avoided for better preservation of RRF. In chronic hemodialysis (HD) patients, the repetitive induction of the acute phase response (APR) may induce a chronic micro-inflammatory state, leading to various long-term complications.
                The present prospective study was designed to assess the alterations in the APR in 74 patients who were randomized to HD with a high-flux polysulfone (PS; F 60S), a super-flux PS (F 500S), or a super-flux cellulosic tri-acetate (CTA and CTA with filtered dialysate, CTA(f)) dialyzer. Blood samples collected at the start of the study and after twelve weeks were analyzed for interleukin-6 (IL-6) and C-reactive protein (CRP). In addition to the microbiological quality of the dialysate, the appearance of a "clinical event" was assessed.
                At baseline, mean IL-6 levels were within the reference range whereas mean CRP levels were slightly elevated. Mean values did not change after 12 weeks of HD with either modality. After subdividing the patients in quartiles with increasing change in plasma CRP, 23.0% of the patients showed a change of more than 8.0 mg/L. In a multiple regression analysis, CRP levels appeared to be independent of the degree of dialysate contamination, the material and the flux characteristics of the devices. In fact, the variable "clinical events" was the only significant predictor of the plasma CRP levels (P < 0.001).
                Based on these results, both PS and CTA super-flux dialyzers appear safe for clinical use. Whether changes in CRP values, which are associated with intercurrent clinical events, influence the long-term prognosis of chronic HD patients remains to be established. Hemodialysis is frequently complicated by hypotension and associated symptoms. It has been suggested that these symptoms may be related to the biochemical changes caused by cellulosic dialysis membranes. In this study, a prospective randomized crossover trial was conducted comparing the incidence of hypotension and acute symptoms during dialysis with large-surface-area (1.6 m2) cellulosic (cuprophane [CUP]) and noncellulosic (polyacrylonitrile [PAN], AN69) membranes. Dialyzers were used for a single use only. There was no difference in predialysis BUN, predialysis blood pressure, intradialytic weight gain, blood flow, dialysis efficiency (urea reduction), dialysis duration, hematocrit, or erythropoietin dose between the two study phases. When these clinical characteristics were matched, there was no difference in the number of episodes of hypotension (CUP, 19 +/- 3; PAN, 22 +/- 3; P = not significant [NS]). The incidence of symptomatic hypotension, as reflected by the number of episodes of hypotension requiring more than 100 mL of saline for correction, was also not different between study phases (CUP, 10 +/- 1; AN69, 11 +/- 2; P = NS). The incidence of intradialytic symptoms, including emesis, cramping, headache, angina, pruritus, and bronchospasm, was similar during the two study phases (CUP, 11 +/- 2; AN69, 10 +/- 1; P = NS). It was concluded that noncellulosic membranes do not offer any significant advantage over cellulosic membranes in reducing the acute complications of hemodialysis. Intraoperative fluid therapy regimens using oesophageal Doppler monitoring (ODM) to optimize stroke volume (SV) (goal-directed fluid therapy, GDT) have been associated with a reduction in length of stay (LOS) and complication rates after major surgery. We hypothesized that intraoperative GDT would reduce the time to surgical readiness for discharge (RfD) of patients having major elective colorectal surgery but that this effect might be less marked in aerobically fit patients.
                In this double-blinded controlled trial, 179 patients undergoing major open or laparoscopic colorectal surgery were characterized as aerobically 'fit' (n=123) or 'unfit' (n=56) on the basis of their performance during a cardiopulmonary exercise test. Within these fitness strata, patients were randomized to receive a standard fluid regimen with or without ODM-guided intraoperative GDT.
                GDT patients received an average of 1360 ml of additional intraoperative colloid. The mean cardiac index and SV at skin closure were significantly higher in the GDT group than in controls. Times to RfD and LOS were longer in GDT than control patients but did not reach statistical significance (median 6.8 vs 4.9 days, P=0.09, and median 8.8 vs 6.7 days, P=0.09, respectively). Fit GDT patients had an increased RfD (median 7.0 vs 4.7 days; P=0.01) and LOS (median 8.8 vs 6.0 days; P=0.01) compared with controls.
                Intraoperative SV optimization conferred no additional benefit over standard fluid therapy. In an aerobically fit subgroup of patients, GDT was associated with detrimental effects on the primary outcome.
                UK NIHR CRN 7285, ISRCTN 14680495. http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=7285. Whether the nature of haemodialysis (HD) membranes can influence the outcome of acute renal failure (ARF) remains debatable. Recent studies have suggested that dialysis with bioincompatible unsubstituted cellulosic membranes is associated with a less favourable patient outcome than dialysis with biocompatible synthetic membranes. Since we generally use a modified cellulosic membrane with substantially lower complement- and leukocyte-activating potential than cuprophane, for dialysis of patients with ARF, and because there are no data in the literature regarding the influence of modified cellulosic membranes on the outcome of patients with ARF, we compared the outcome of ARF patients dialysed either with cellulose diacetate or with a synthetic polysulfone membrane. We also investigated the potential role of permeability by comparing membranes with high-flux versus low-flux characteristics.
                This prospective, randomized, single centre study included 159 patients with ARF requiring HD. Patients were stratified according to age, gender, and APACHE II score and then randomized in chronological order to one of three dialysis membranes: low-flux polysulfone, high-flux polysulfone and meltspun cellulose diacetate.
                Aetiologies of ARF and the prevalence of oliguria were similarly distributed among the three groups. There was no significant difference between the three groups for survival (multivariate Cox's proportional hazards model, P=0.57), time necessary to recover renal function (P=0.82), and number of dialysis sessions required before recovery (P=0.86). Multivariate analysis showed that survival was significantly influenced only by the severity of the disease state (APACHE III score, P<0.0001), but not by the nature of the dialysis membrane (P=0.57) or the presence of oliguria (P=0.24).
                Among patients with ARF requiring HD survival and recovery time are not significantly influenced by the use of either meltspun cellulose diacetate or the more biocompatible high-flux or low-flux polysulfone. Dialysis using modified cellulose membranes is just as effective as dialysis using synthetic polysulfone membranes, but at a lower cost. In addition, the flux of the membrane did not influence patient outcome. Mortality rates of critically ill patients with acute renal failure (ARF) requiring renal replacement therapy (RRT) are high. Intermittent and continuous RRT are available for these patients on the intensive care units (ICUs). It is unknown which technique is superior with respect to patient outcome.
                We randomized 125 patients to treatment with either continuous venovenous haemodiafiltration (CVVHDF) or intermittent haemodialysis (IHD) from a total of 191 patients with ARF in a tertiary-care university hospital ICU. The primary end-point was ICU and in-hospital mortality, while recovery of renal function and hospital length of stay were secondary end-points.
                During 30 months, no patient escaped randomization for medical reasons. Sixty-six patients were not randomized for non-medical reasons. Of the 125 randomized patients, 70 were treated with CVVHDF and 55 with IHD. The two groups were comparable at the start of RRT with respect to age (62+/-15 vs 62+/-15 years, CVVHDF vs IHD), gender (66 vs 73% male sex), number of failed organ systems (2.4+/-1.5 vs 2.5+/-1.6), Simplified Acute Physiology Scores (57+/-17 vs 58+/-23), septicaemia (43 vs 51%), shock (59 vs 58%) or previous surgery (53 vs 45%). Mortality rates in the hospital (47 vs 51%, CVVHDF vs IHD, P = 0.72) or in the ICU (34 vs 38%, P = 0.71) were independent of the technique of RRT applied. Hospital length of stay in the survivors was comparable in patients on CVVHDF [median (range) 20 (6-71) days, n = 36] and in those on IHD [30 (2-89) days, n = 27, P = 0.25]. The duration of RRT required was the same in both groups.
                The present investigation provides no evidence for a survival benefit of continuous vs intermittent RRT in ICU patients with ARF. Nine patients on regular dialysis were studied, in a cross-over format comparing hemodialysis (HD) and hemofiltration (HF), to identify potential mechanisms of the disparate hemodynamic responses. Dialysis and substitution fluid composition (high sodium, acetate), treatment time, fluid loss rate, and membrane type (AN 69) were matched. Cardiac output was determined by changes in thoracic electrical bioimpedance. Cardiac output remained stable during HF but increased during HD (p < 0.001, HD vs. HF), despite a parallel reduction in stroke volume. The heart rate response was significantly greater during HD relative to HF (p < 0.01). Systemic vascular resistance remained stable during HF but decreased significantly during HD (p < 0.05). Although there was a modest fall during HD, the difference in blood pressure at the end of treatment between HD and HF was not significant. Comparable increases in body temperature were observed during both treatments. Plasma catecholamines increased in parallel during HD and HF and following orthostatic stimulation at the end of treatment, and extracorporeal catecholamine clearances were similar. The values for serum sodium, total CO2, anion gap, potassium, and hematocrit at the end of treatment were similar, whereas total serum calcium was significantly greater following HD. There were no significant differences in indices of myocardial contractility or central blood volume. These results suggest that the disparate hemodynamic responses to fluid and solute removal during HD and HF can be dissociated from changes in osmolality or venous tone, membrane bioincompatibility, thermal stress, or differences in acetate delivery or catecholamine release. The explanation for the disparate hemodynamic responses between these two treatment modalities remains unclear. A role for an as yet unidentified vasodilatory substance generated during dialysate exposure, or convectively removed during hemofiltration, remain intriguing possibilities. Twenty patients treated with human recombinant erythropoietin (EPO) for 9 months were studied. The patients were randomly allocated to high flux (HF) or conventional dialysis (CD). Patients on HF used the F-60 or F-80 dialyzer, with a polysulfone membrane; QB: 470 ml/min; QD: 800 ml/min; t: 127 min; Kt/V: 1.01. Conventional dialysis patients used regenerated cellulosic membranes; QB: 297 ml/min; QD: 500 ml/min; t: 193 min; Kt/V: 1.05. Mean dose of EPO was 103 U/kg for HF patients and 112.4 U/kg for patients on CD. At 9 months, no significant differences were observed in HCT (HF 33.6% vs. CD 33.2%), BUN, serum creatinine, potassium, or phosphorus. Hemoconcentration during dialysis was 12% for HF and 17% for CD. Urea clearance decreased 7% for HF and 9% for CD, while clearance of creatinine, potassium, and phosphorus decreased between 14 and 18% with both treatments. Heparin requirements increased 10% in HF and 16% in CD. Hypertension was similar in both groups. One HF patient withdrew from the study because of hypertension and one HF patient had seizures related to hypertension. Vascular access clotting or hospitalizations were no different. High flux dialysis patients on EPO over a 9 month period did not have any catastrophic complications when HCT was maintained between 30 and 35%. To compare the hemodynamic response of ICU patients with acute renal failure of a 24-h continuous arteriovenous hemofiltration (CAVH) and that of patients with a 4-h intermittent hemodialysis (HD).
                Cross-over randomized clinical trial. The two periods to be compared were a 24-h CAVH and the 24-h encompassing a 4-h HD. These two periods were separated by a 24-h wash-out period.
                Ten bed medicosurgical ICU of a tertiary care center in Paris, France.
                Inclusion criterion was the requirement of replacement therapy for acute renal failure in patients already submitted to mechanical ventilation.
                CAVH was performed with Ringers' lactate used for restitution and infused before the hemofilter. The ultrafiltrate output was maintained at around 15 ml/min. HD was performed with a bicarbonate-buffered dialysate.
                Mean arterial pressure (MAP), use of adrenergic drugs, and change in body weight during each period.
                Twenty-seven consecutive patients were included, 15 CAVH-HD and 12HD-CAVH. CAVH and HD allowed the same metabolic efficacy. No hemodynamic parameter (MAP, amount of adrenergic drugs, change in body weight) differed between the two methods.
                CAVH is equivalent to HD in terms of MAP and the use of vasopressive drugs and fluids. Establishing the superiority of CAVH would require carefully controlled studies assessing either outcome or changes in tissue oxygenation.
In patients who are haemodynamically stable, the RRT modality does not appear to influence important patient outcomes, and therefore the preference for CRRT over IRRT in such patients does not appear justified in the light of available evidence. CRRT was shown to achieve better haemodynamic parameters such as MAP. Future research should focus on factors such as the dose of dialysis and evaluation of newer promising hybrid technologies such as SLED. Triallists should follow the recommendations regarding clinical endpoints assessment in RCTs in ARF made by the Working Group of the Acute Dialysis Quality Initiative Working Group.