Pharmacokinetics of ciprofloxacin and vancomycin in patients with acute renal failure treated by continuous haemodialysis.

To determine appropriate doses of ciprofloxacin and vancomycin for septic patients with acute renal failure (ARF) treated by continuous arteriovenous and venovenous haemodialysis, (CAVHD/CVVHD), we performed pharmacokinetic studies in patients receiving these antibiotics. All patients were treated by CAVHD/CVVHD using Hospal AN69S 0.43 m2 filters and Fresenius 1.5% peritoneal dialysis fluid at dialysate flow rates (Qd) of 1 and 2 l/h. Patients received ciprofloxacin 200 mg i.v. 12-hourly (n = 6) or 8-hourly (n = 5); vancomycin 1 g i.v. was administered to 10 patients approximately every 48 h to maintain therapeutic plasma levels. For ciprofloxacin, volume of distribution (Vdarea) was 136.5 +/- 9.81, terminal elimination half-life (t1/2) 6.4 +/- 0.8 h, and total body clearance (TBC) 264.3 +/- 22.9 ml/min (mean +/- SEM). Mean sieving coefficient (S/C) was 0.76 +/- 0.05 and filter clearances at Qd 1 and 2 l/h were 16.2 +/- 1.9 and 19.9 +/- 1.1 ml/min respectively. For vancomycin, Vdarea was 60.7 +/- 5.11, t1/2 24.7 +/- 2.6 h and TBC 31.0 +/- 4.6 ml/min. Mean S/C was 0.66 +/- 0.08 and filter clearances at Qd 1 and 2 l/h 12.1 +/- 2.0 and 16.6 +/- 2.0 ml/min. These data suggest that patients with ARF treated by CAVHD/CVVHD should be given ciprofloxacin 200 mg i.v. 8-12-hourly and vancomycin every 48 h.     

Trace element removal during in vitro and in vivo continuous haemodialysis.

BACKGROUND: Continuous renal replacement therapy (CRRT) increasingly is being used to treat critically ill patients with renal disease. CRRT removes waste products but also nutrients. Our understanding of trace element CRRT clearance has been limited by poor assay sensitivity. The development of inductively coupled plasma mass spectrometry (ICP-MS) allows for the measurement of CRRT trace element removal. METHODS: Continuous venovenous haemodialysis (CVVHD) transmembrane clearances of trace elements and urea were assessed using a bovine blood-based in vitro model using two different haemodialyser types. These findings were validated in 10 critically ill adult patients receiving continuous venovenous haemodiafiltration (CVVHDF). Calculated daily trace element loss was compared with a typical dose of daily trace element supplementation. RESULTS: The mean +/- SD in vitro CVVHD transmembrane clearances (ml/min) for the polysulfone haemodialyser were chromium 0.97 +/- 0.23, copper 0.47 +/- 0.18, manganese 4.6 +/- 3.6, selenium 1.2 +/- 0.63 and zinc 2.3 +/- 0.32 and for the cellulose diacetate haemodialyser chromium 1.54 +/- 0.91, copper 0.21 +/- 0.07, manganese 7.8 +/- 4.1, selenium 0.76 +/- 0.39 and zinc 2.7 +/- 0.37. The in vivo CVVHDF transmembrane clearances (ml/min) were chromium 5.4 +/- 2.4, copper 0.45 +/- 0.33, manganese 1.9 +/- 4.6, selenium 1.6 +/- 1.2, and zinc 4.0 +/- 1.3. CONCLUSION: ICP-MS assays detected the five trace elements in the effluent of CVVHDF patients. Trace element CVVHD transmembrane clearance estimates for our in vitro model were supported by the in vivo CVVHDF findings. Calculated daily trace element loss attributed to CVVHD and CVVHDF with dialysate flow rates of 33.3 ml/min is less than what is provided in a daily dose of a trace element supplementation product.     

Improving the delivery of continuous renal replacement therapy using regional citrate anticoagulation

AIMS: Regional citrate anticoagulation during acute renal replacement therapy (RRT) effectively prevents extracorporeal thrombosis and avoids bleeding risk. There have been a number of citrate anticoagulation protocols published; but a simple and predictable scheme with standardized components and procedures, as well as clearly defined citrate pharmacokinetics, is needed for continuous RRT (CRRT) that is now used frequently in the critical care setting. The present study sets forth methodology with standardized blood flow and dialysate composition, and with citrate and calcium infusions that are quantitatively linked to extracorporeal blood flow rate--a predictable and easily replicated CRRT paradigm. MATERIALS AND METHODS: CRRT using continuous venovenous hemofiltration with dialysis (CVVHD) was standardized using 150-200 ml/min blood flow, calcium-free dialysate with only moderate sodium (135 mEq/l) and bicarbonate (28 mEq/l) concentrations, and ultrafiltration limited to that needed for overall fluid balance in the intensive care unit. Citrate infusion (ACD-A solution) into the extracorporeal blood and calcium repletion in blood returned to the patient were proportional to blood flow. Anticoagulation was accomplished by keeping extracorporeal ionized calcium below 0.4 mM/l. Filter performance, citrate removal and changes in calcium, sodium and alkali were evaluated longitudinally. RESULTS: CVVHD using this protocol delivered urea clearance exceeding 2 l/h (48 l/d) when filter function was sustained. Filter longevity was markedly improved using citrate when compared with standard heparin anticoagulation, and nursing time spent on initiating and troubleshooting CRRT was approximately halved using this protocol. Sieving coefficients for urea, creatinine and citrate were approximately 0.9 and were sustained through nearly 3 days of filter use. Citrate clearance and removal were quantitatively linked to dialysate and ultrafiltration flow, resulting in 35-50% direct removal of the citrate-calcium chelate and reduced systemic citrate load. Serum tonicity and acid-base status were not problematic. The only notable side effect was modest calcium accumulation that necessitated reduction in calcium repletion rate. CONCLUSIONS: CVVHD is well suited to regional citrate anticoagulation. The present protocol is straightforward and predictable, with minor metabolic consequences that can be anticipated and adjusted. These results commend regional citrate anticoagulation to wider application.     

Use of continuous haemodiafiltration: an approach to the management of acute renal failure in the critically ill.

We have prospectively investigated the effect of a flexible approach to the management of acute renal failure in critically ill patients based on continuous haemodiafiltration (CHD). Fifty critically ill patients (mean APACHE II score 28.1, range 18-37), with a mean age of 59.5 years, were treated with continuous arteriovenous haemodiafiltration (CAVHD) and/or continuous venovenous haemodiafiltration (CVVHD). CHD achieved excellent haemodynamic stability and control of azotaemia in all patients and permitted aggressive parenteral nutrition. The mean blood urea concentration fell from 33.9 mmol/l (95% confidence interval, CI, 29.1-38.7) to a plateau of 17 mmol/l (95% CI 14.3-19.7) after 72 h of therapy despite persistent anuria and the parenteral administration of 0.3 g/kday of protein nitrogen (mean urea clearance: 24.2 ml/min; 95% CI 22.9-25.5). No supplemental dialytic therapy was required during the 9,485 h of treatment. All clinically significant complications related to vascular access (14%). Twenty-two patients (44%) survived to be discharged from the ICU. CHD is relatively safe and effective in the management of acute renal failure in the critically ill.     

Effects of lactate-buffered and lactate-free dialysate in CAVHD patients with and without liver dysfunction

BACKGROUND: Continuous modalities of renal replacement deplete patients of bicarbonate, which is traditionally replaced indirectly by lactate in dialysate or replacement fluids. We have compared a new lactate-free dialysate (unbuffered dialysate with separate bicarbonate replacement of dialytic bicarbonate loss) with standard lactate-buffered dialysate in terms of acid-base control, lactate accumulation, and hemodynamic stability in patients undergoing continuous renal replacement therapy in an intensive care unit. METHODS: A nonrandomized crossover cohort study involving 54 patients with multi-organ failure (of whom 19 had significant hepatic dysfunction) was performed. All patients completed 24-hour continuous hemodiafiltration against both lactate-buffered and lactate-free dialysate. Arterial pH, blood gases, bicarbonate, and lactate, venous sodium, blood pressure, and inotrope requirements were measured before and at six hourly intervals during the first 24 hours of dialysis against each dialysate. RESULTS: Lactate-free dialysate provided more rapid control of acidosis than lactate buffered with less total administration of buffer than that given during the lactate-buffered period (total mmol bicarbonate vs. total mmol lactate + bicarbonate). Lactate accumulation was slight in both periods, but was higher during lactate-buffered continuous venovenous hemodiafiltration (CVVHD). The mean arterial pressure rose during lactate-free dialysis with decreased inotrope doses and fell during lactate-buffered dialysis with increased inotrope requirement. Results in patients with liver dysfunction were not significantly different from those without it. CONCLUSIONS: Over the time scale of 24 hours, lactate derived from continuous dialysis circuits is efficiently cleared from the blood of most patients with multi-organ failure, but with less effect on systemic acidosis than is produced by equivalent amounts of bicarbonate.     

Determinants of vancomycin clearance by continuous venovenous hemofiltration and continuous venovenous hemodialysis

The clearance of vancomycin is significantly reduced in patients with acute, as well as, chronic renal failure. Although multiple-dosage regimen adjustment techniques have been proposed for these patients, there is little quantitative data to guide the individualization of vancomycin therapy in acute renal failure patients who are receiving continuous renal replacement therapy (CRRT). To determine appropriate vancomycin dosing strategies for patients receiving continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodialysis (CVVHD), we performed controlled clearance studies in five stable hemodialysis patients with three hemofilters: an acrylonitrile copolymer 0.6 m2 (AN69), polymethylmethacrylate 2.1 m2 (PMMA), and polysulfone 0.65 m2 (PS). Patients received 500 mg of vancomycin intravenously at least 12 hours before the start of the clearance study. The concentration of vancomycin in multiple plasma and dialysate/ultrafiltrate samples was determined by EMIT (Syva, Palo Alto, CA). The diffusional clearance and sieving coefficient (SC) of vancomycin were compared by a mixed-model repeated-measures analysis of variance (ANOVA) with filter and blood (Q(B)), dialysate inflow (Q(DI)), or ultrafiltration rate (Q(UF)) as the main effects and patient as a random effect. Vancomycin was moderately protein bound in these patients; free fraction ranged from 49% to 83%. The SCs of the three filters were similar and significantly correlated with the free fraction of vancomycin (P = 0.01; r2 = 0.465). Significant linear relationships were observed between the diffusional clearance of vancomycin and Q(DI) for all three filters: AN69 (slope = 0.482; r2 = 0.880); PMMA (slope = 0.853; r2 = 0.966); and PS (slope = 0.658; r2 = 0.887). The slope of this relationship for the PMMA filter was significantly greater than that of the AN69 and PS filters. The clearance of vancomycin, urea, and creatinine, however, was essentially constant at all Q(B)s for all three filters. Thus, the clearance of vancomycin was not membrane dependent during CVVH. However, during CVVHD, membrane dependence of vancomycin clearance was noted at a Q(DI) greater than 16.7 mL/min; vancomycin clearance with PMMA at a Q(DI) of 25 mL/min was 66% and 43% greater than that with the AN69 and PS filters, respectively. CVVH (62% to 262%) and CVVHD (90% to 540%) can significantly augment the clearance of vancomycin in acute renal failure patients. Dosing strategies for individualization of vancomycin therapy in patients receiving CVVH and CVVHD are proposed.     

连续性肾脏替代治疗中滤器后加热法对患者体温的影响

目的探讨连续性肾脏替代治疗(CRRT)中滤器后加热法对患者体温的影响。方法将60例行CRRT治疗的患者随机分为对照组和观察组各30例,对照组按常规将加温装置连接到置换液的管路上,观察组将加温装置连接到滤器后静脉端血液回输管路上。两组均于CRRT治疗开始3h、6h、12h时测量患者体温及深静脉置管的动、静脉端的血液温度;比较两组治疗前后溶血反应相关检验结果。结果在CRRT治疗不同时段,两组深静脉置管的动、静脉端的血液温度比较,干预主效应均P<0.05;治疗12h时观察组低体温发生率显著低于对照组(P<0.05)。两组治疗前后溶血反应相关检验结果比较,差异无统计学意义(均P>0.05)。结论滤器后加热血液回输管路的方式可安全有效地补充CRRT治疗中循环热量,降低CRRT治疗中低体温发生率。     

Filter Adsorption of Anidulafungin to a Polysulfone‐Based Hemofilter During CVVHD In Vitro

Candidemia is frequent in critically ill patients, especially in combination with an acute kidney injury (AKI). Echinocandins generally are recommended for therapy of such infections. Recent studies found no need for dosage adjustment in patients with end‐stage renal disease receiving hemodialysis, or patients with AKI receiving continuous venovenous hemofiltration. The aim of this in vitro study was to examine the adsorption of anidulafungin to the surface of the hemofilter during continuous venovenous hemodialysis (CVVHD) and its effect on anidulafungin concentrations. The concentration of anidulafungin in the dialyzed fluid, and the dialysate during CVVHD in vitro was examined using three different dialyzed fluids (saline; saline with 40 g/L human albumin; and a mixture of human erythrocytes and fresh frozen plasma). After the end of dialysis, the hemofilter was opened and portions of the filter capillaries were also analyzed to determine the amount of anidulafungin adsorbed. When dialyzing saline, about 99% of the anidulafungin used adsorbed to the hemofilter capillaries; in the experiments with saline with 40 g/L albumin, about 60% adsorbed to the hemofilter's surface, and when blood was dialyzed, 35% was found adsorbed after analyzing the filter capillaries. Anidulafungin was not detectable in the dialysate of any of the experiments, consequently the dialysis clearance was 0 mL/min. In conclusion, during CVVHD in vitro we found remarkable adsorption of anidulafungin to the hemofilter's surface, yet the effect on the tissue concentration needs further examination.     

Early continuous venovenous hemodialysis in dialysis-dependent patients after cardiac surgery: safety and efficacy

OBJECTIVES: The present study assessed the safety and efficacy of continuous venovenous hemodialysis (CVVHD) early after cardiac surgery. DESIGN: Retrospective database and medical record review. SETTING: University teaching hospital. PARTICIPANTS: Forty-five dialysis-dependent patients who underwent cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: CVVHD was begun postoperatively after confirmation of hemostasis, irrespective of circulatory status. In the last 5 patients, the ratio of extravascular lung water (EVLW) to intrathoracic blood volume (ITBV) was measured using a single-indicator thermodilution catheter and compared with patients of normal renal function undergoing cardiac surgery. MEASUREMENTS AND MAIN RESULTS: CVVHD was started at 4 hours after ICU admission. The maximum decrease in blood pressure within 60 minutes after initiation of CVVHD was 11 +/- 9 mmHg in the unstable hemodynamics group (defined as patients who required continuous intravenous adrenaline or intra-aortic balloon pump on admission to the ICU [n = 15]) and 7 +/- 8 mmHg in the stable hemodynamics group (n = 30, not significant). Circulatory status and oxygenation improved significantly 12 hours after CVVHD initiation in the unstable hemodynamics group. Blood volume from the chest tube did not increase after CVVHD. Early mortality (2.2%) was lower than that reported previously. The EVLW/ITBV ratio after ICU admission in dialysis-dependent patients was significantly higher than in patients with normal renal function. CONCLUSIONS: Early CVVHD after cardiac surgery in dialysis-dependent patients was safe and effective. There was no associated increased postoperative bleeding or hemodynamic instability. Fluid removal improved respiratory status, particularly in patients requiring circulatory assistance, and overall early morality rates were lower that those previously published.     

Continuous venovenous hemodialysis treatment in critically ill patients after liver transplantation

BACKGROUND: Acute renal failure (ARF) in critically ill patients is associated with a high mortality rate. Continuous renal replacement therapy (CRRT) is now widely used for the treatment of ARF in these critically ill patients. We retrospectively analyzed the role of CRRT as a prognostic parameter in patients receiving a cadaveric liver graft in 1998. METHODS: We reviewed the patient records of all adult recipients of a cadaveric liver graft (N = 54) in 1998 and compared those who underwent CRRT treatment (N = 19) to those without CRRT treatment (N = 35). RESULTS: Mortality was high in the continuous venovenous hemodialysis (CVVHD) group (58%). At the time of transplantation, creatinine (1.7+/-0.4 vs. 1.0+/-0.1 mg/dl), blood urea nitrogen (40+/-13 vs. 22+/-3 mg/dl), aspartate aminotransferase (ASAT; 585+/-420 vs. 242+/-97 U/liter), and bilirubin (11.6+/-4.1 vs. 6.5+/-1.9 mg/dl) were higher in the CVVHD group than in controls, whereas hemoglobin (10.3+/-0.6 vs. 10.8+/-0.4 g/dl), white blood cells (6.3+/-0.6 vs. 7.0+/-0.8/nl), and thrombocytes (110+/-18 vs. 90+/-10/nl) were similar. After transplantation, liver graft function was impaired in the CVVHD group as compared with controls. CONCLUSIONS: The necessity for CRRT in patients after liver transplantation correlates with a high risk of death. Thus, more efforts have to be made to prevent renal failure in patients after liver transplantation.     

Recombinant hirudin (lepirudin) as anticoagulant in intensive care patients treated with continuous hemodialysis

BACKGROUND: Recombinant hirudin (lepirudin) is a potent direct thrombin inhibitor, which has been approved for the treatment of heparin-induced thrombocytopenia type II (HIT). Because the drug is mainly eliminated by the kidneys, a single loading dose of hirudin may induce therapeutic anticoagulation for up to one week in patients with renal insufficiency. Thus, the use of hirudin in critically ill patients with renal failure could markedly increase their bleeding risk. In this study, hirudin was used in critically ill patients with suspected HIT while on continuous venovenous hemodialysis (CVVHD). METHODS: Hirudin anticoagulation was performed in seven critically ill patients with suspected HIT. Four patients were initially anuric. Three patients had residual renal function. In all 64 CVVHD treatments (mean duration 12 hr), a polysulfone high-flux hemodialyzer (0.75 m2) with a dialysate flow rate of 1.5 liter/hr and an ultrafiltration rate of up to 200 ml/hr was used. Hirudin was given either as continuous intravenous infusion or as repetitive intravenous boli. Monitoring of anticoagulation was performed by measurements of the systemic activated partial thromboplastin time (aPTT). RESULTS: Hirudin dosage had to be individualized according to the risk of bleeding or clotting. During CVVHD, a continuous intravenous infusion (0.006 to 0.025 mg/kg body wt/hr, N = 2) or repetitive intravenous boli (0.007 to 0.04 mg/kg, N = 5) were given. Two patients required blood transfusions prior to and during hirudin treatment. In five patients without a high bleeding risk, the hirudin dose was adjusted to achieve the target aPTT (1.5 to 2.0 x baseline) in order to prevent thrombotic complications or frequent clotting in the extracorporal circuit. Hirudin dose requirements depended on residual renal function and extracorporal clearance. CONCLUSIONS: We conclude from these first clinical data that anticoagulation with hirudin in critically ill patients on continuous hemodialysis can be performed without excessive bleeding risk by combining close clinical and laboratory monitoring. The hirudin dose has to be reduced because of renal failure, and may require adjustment for residual or recovering renal function and extracorporal elimination.     

Veno-venous continuous renal replacement therapy for burned patients with acute renal failure

From 1995 to 1998, 12 burned patients with acute renal failure (ARF) were treated by veno-venous continuous renal replacement therapy (CRRT) at the Burn Unit of H?tel-Dieu de Montréal. Their mean (+/-SD) age was 51+/-12 years, and the mean burned surface covered 48.6+/-15.8% of total body surface area. All patients were mechanically ventilated and presented evidence of sepsis. The mean delay before occurrence of ARF was 15+/-6 days and ARF was mainly related to sepsis and hypotension. Main reasons for CRRT initiation were azotemia and fluid overload. A total of 15 CRRT modalities were applied (12 continuous veno-venous hemodiafiltration, CVVHDF; two continuous veno-venous hemofiltration, CVVH; and one continuous veno-venous hemodialysis, CVVHD) over 14+/-13 days. For CRRT, nine patients received heparin and three were not anticoagulated. Mean values for dialysate and reinjection flow rates were 1134+/-250 ml/h and 635+/-327 ml/h, respectively. Admission weight was 78.8+/-12.7 kg with a mean weight gain before CRRT initiation of 10.0+/-5.8 kg and a mean weight loss during CRRT of 8.9+/-5.5 kg. Nine patients received enteral plus parenteral nutrition, and three, parenteral nutrition only; the total caloric intake was 31.5+/-7.0 kcal/kg/day and protein intake, 1.8+/-0.4 g/kg/day. The normalized protein catabolic rate (nPCR) was evaluated at 2.28+/-0.78 g/kg/day during CRRT. The mortality rate was 50%. The six survivors all recovered normal renal function with four of them requiring intermittent hemodialysis for short periods. In conclusion, veno-venous CRRT is particularly well suited for this selected population allowing smooth fluid removal and aggressive nutritional support.     

Effects of Initiation of Continuous Renal Replacement Therapy on Hemodynamics in a Pediatric Animal Model

There are no studies analyzing the initial hemodynamic impact of continuous renal replacement therapy (CRRT) in children. We have performed a prospective observational study in 34 immature Maryland pigs to analyze the initial hemodynamic changes during venovenous CRRT. The heart rate, blood pressure, central venous pressure (CVP), pulmonary arterial occlusion pressure (PAOP), pulmonary capillary wedge pressure, temperature, and cardiac output (CO), simultaneously by pulmonary arterial thermodilution and femoral arterial thermodilution, were measured at 30-min intervals during 2 h. Venovenous CRRT induced an initial significant diminution of volemic hemodynamic parameters (intrathoracic blood volume, global end-diastolic volume, stroke volume index, PAOP, and CVP). Simultaneously, a significant increase in systemic vascular resistance index and left ventricular contractility, and a decrease in CO, was observed. We conclude that CRRT in a pediatric animal model induces initial hypovolemia, and a systemic cardiovascular response with vasoconstriction and increase in ventricular contractility.     

Extended daily veno-venous high-flux haemodialysis in patients with acute renal failure and multiple organ dysfunction syndrome using a single path batch dialysis system.

BACKGROUND: In the treatment of acute renal failure in patients with multiple organ dysfunction syndrome (MODS), continuous renal replacement therapies (CRRT) are increasingly used because of excellent volume control in the presence of improved cardiovascular stability. Patients with MODS, however, are frequently catabolic and have a high urea generation rate requiring either cost-intensive high-volume CRRT or additional intermittent haemodialysis to provide adequate clearance of small-molecular waste products. We tested the closed-loop batch haemodialysis system (called Genius((R))) for the treatment of acute renal failure in patients with MODS in the intensive care unit. METHODS: Blood flow and countercurrent dialysate flow were reduced to 70 ml/min. Thus the 75 l dialysate tank of the Genius((R)) system lasts for 18 h of extended single-path high-flux haemodialysis (18 h-HFD) using polysulphous F60 S((R)) dialysers. Blood pressure, body temperature, and venous blood temperature in the extracorporeal circuit (no heating of the dialysate), ultrafiltration rate, serum urea levels, dialyser urea clearance, and total urea removal were monitored. In addition we tested the bacteriological quality of the spent dialysate at the end of 18-h treatments. RESULTS: Twenty patients with acute renal failure and MODS were investigated. Averaged dialyser urea clearance was 59.8 ml/min (equal to 3.6 l/h or 64.8 l/day). Total removal of urea was 14.1+/-6.5 g/day keeping serum levels of urea below 13 mmol/l. Mean arterial pressure remained stable during the 18-h treatments with a mean ultrafiltration rate of 120 ml/h. The temperature in the venous blood tubing dropped by 5+/-0.5 degrees C during the 18-h treatment (0.28 degrees C/h) in the presence of unchanged core temperature in the patients. There was no bacterial growth in 2.5 l of spent dialysate (<0.0004 colony forming units/ml). CONCLUSIONS: Extended high-flux dialysis using the Genius((R)) system combines the benefits of CRRT (good cardiovascular stability, sterile dialysate) with the advantages of intermittent dialysis (high urea clearance, low treatment costs). High efficiency, simplicity and flexibility of the system offers the unique opportunity to use the same dialysis machine for extended time periods (18 h) as well as for shorter intermittent renal replacement therapy in critically ill patients.     

Effects of initiation of continuous renal replacement therapy on hemodynamics in a pediatric animal model

There are no studies analyzing the initial hemodynamic impact of continuous renal replacement therapy (CRRT) in children. We have performed a prospective observational study in 34 immature Maryland pigs to analyze the initial hemodynamic changes during venovenous CRRT. The heart rate, blood pressure, central venous pressure (CVP), pulmonary arterial occlusion pressure (PAOP), pulmonary capillary wedge pressure, temperature, and cardiac output (CO), simultaneously by pulmonary arterial thermodilution and femoral arterial thermodilution, were measured at 30-min intervals during 2 h. Venovenous CRRT induced an initial significant diminution of volemic hemodynamic parameters (intrathoracic blood volume, global end-diastolic volume, stroke volume index, PAOP, and CVP). Simultaneously, a significant increase in systemic vascular resistance index and left ventricular contractility, and a decrease in CO, was observed. We conclude that CRRT in a pediatric animal model induces initial hypovolemia, and a systemic cardiovascular response with vasoconstriction and increase in ventricular contractility.     

Catabolism in critical illness: estimation from urea nitrogen appearance and creatinine production during continuous renal replacement therapy

Thirty-eight intensive care unit (ICU) patients (26 men and 12 women with a mean age of 57.0 +/- 16.6 years) with acute renal failure (ARF) treated by venovenous continuous renal replacement therapy (CRRT) were evaluated while in relatively steady metabolic control. Twenty-seven were undergoing continuous venovenous hemodialysis, nine were undergoing continuous venovenous hemodiafiltration, and two were undergoing continuous venovenous hemofiltration. Periods of analysis varied between 24 and 408 hours (mean duration, 82.7 +/- 70.6 hours; median, 72 hours). Their mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score within 24 hours of admission to the ICU was 21.3 +/- 6.3 and survival rate was 31.6%. Urea nitrogen and creatinine concentrations were determined every 6 to 12 hours in both serum (Cun and Cc, respectively) and effluent (spent dialysate and/or ultrafiltrate). The mean effluent rate was 1,472 +/- 580 mL/h and blood flow rate, 166 +/- 32 mL/min. Urine was collected daily for urea nitrogen and creatinine measurement. Urea nitrogen appearance rate (UnA) and creatinine production rate (Pc), calculated from urea nitrogen (UnMR) and creatinine mass removal (CMR) from both the effluent and the urine, using Garred mass balance equations and the Forbes-Bruining formula, allowed normalized protein catabolic rate (nPCR) and estimates of lean body mass (LBM) to be derived. Creatinine metabolic degradation rate (Dc), estimated by the Mitch formula, was included in the calculation. The lowest body weight recorded during the study period was considered as dry weight (BW). The creatinine index (CI) was also obtained. For each parameter, the results are presented as mean, median, and range values: UnMRe (from effluent), 13.6 +/- 7.2, 12.5, 1.6 to 32.6 mg/min; UnMRu (from urine), 0.13 +/- 0.40, 0, 0 to 2.30 mg/min; UnA, 13.6 +/- 7.0, 12.5, 3.8 to 32.1 mg/min; nPCR, 1.75 +/- 0.82, 1.60, 0.61 to 4.23 g/kg/d; CMRe (from effluent), 942.0 +/- 362.3, 918.0, 211.2 to 1,641.6 mg/d; CMRu (from urine), 44.4 +/- 138.8, 0, 0 to 698.5 mg/d; Dc, 94.6 +/- 49.9, 81.9, 31.0 to 294.1 mg/d; Pc total, 1,067.1 +/- 409.7, 1,053.7, 261.5 to 1,988.2 mg/d; LBM, 38.3 +/- 11.9, 37.9, 15.0 to 65.0 kg; LBM/BW ratio, 49.5% +/- 14.0%, 50.3%, 22.5% to 86.0%; and CI, 13.7 +/- 4.7, 14.2, 4.1 to 25.8 mg/kg/d. When Pc was estimated from the Cockcroft-Gault equations (as Pc'), the mean value for Pc and Pc' was similar (1,067.1 +/- 409.7 v 1,284.9 +/- 484.1 mg/d), but there were relatively large differences for the majority of cases. A positive correlation was observed between UnA and Pc (R = 0.42). Serum albumin and LBM/BW correlated poorly (R = 0.20). Outcome was weakly related to UnA and to nPCR (R = 0.29 and R = 0.31, respectively). Urea nitrogen appearance appears widely variable in critically ill ARF patients. This simple approach can provide useful information for an easy estimate of net protein catabolism in critically ill patients with ARF undergoing CRRT.     

Effective diffusion volume flow rates (Qe) for urea, creatinine, and inorganic phosphorous (Qeu, Qecr, QeiP) during hemodialysis

In vivo solute clearances can be estimated from dialyzer blood (Qb) and dialysate (Qd) flow rates and a solute- and dialyzer-specific overall permeability membrane area product (KoA). However, these calculations require knowledge of the flow rate of the effective solute distribution volume in the flowing bloodstream (Qe) in order to calculate in vivo clearances and KoAs. We have determined Qe for urea, creatinine, and inorganic phosphorus from changes in concentrations across the blood compartment and mass balance between the blood and dialysate streams. We made four serial measurements over one dialysis in 23 patients and found that Qeu equals the total blood water flow rate, Qecr equals the plasma water flow rate plus 61% of red cell water flow rate, and QeiP is limited to the plasma water flow rate. Equations are derived to calculate Qe for each of these solutes from Qb and hematocrit and in vivo KoAs for each solute were calculated.     

The Acute Dialysis Quality Initiative--part V: operational characteristics of CRRT

This report represents the consensus statement of the ADQI workgroup addressing the operational characteristics of continuous renal replacement therapy (CRRT). Issues addressed included the specific operational characteristics of continuous hemofiltration (HF), continuous hemodialysis (HD), and continuous hemodiafiltration (HDF) and the impact of these different modalities on solute removal. The relative roles of arteriovenous (AV) and venovenous (VV) modalities of therapy were also evaluated. The workgroup also addressed the optimal components of a CRRT system from an operational standpoint.     

Citrate clearance in children receiving continuous venovenous renal replacement therapy

Anticoagulation is usually indicated in patients receiving continuous renal replacement therapy (CRRT) to prevent clotting of the extra-corporeal circuit. While heparin is the most frequently used anticoagulant, regional citrate anticoagulation is becoming the preferred choice in those patients at high risk for bleeding. However, it has been widely claimed that to avoid citrate toxicity, CRRT with citrate anticoagulation should utilize diffusive clearance (e.g., continuous venovenous hemodialysis). We studied citrate clearance in five children who received citrate anticoagulation during CRRT with a COBE PRISMA machine and an M-60 (AN-69) filter. The blood flow rate ranged from 50 to 150 ml/min (2.1-8.0 ml/kg per min). Citrate was infused in the circuit circulation as an acid citrate dextrose (ACD) solution at a rate of 1.6-3.7% of the blood flow rate to maintain the circuit ionized calcium (iCa) <0.5 mmol/l. Calcium-free replacement fluid with reduced alkali (NaHCO3 20 mEq/l) was infused in pre-filter mode at a rate of 1,800-2,000 ml/h per 1.73 m(2). In a separate central line, CaCl2 (0.8%) was infused (rate 25-50% of ACD infusion) to maintain systemic iCa between 1.0 and 1.3 mmol/l. Citrate concentration was measured using an enzymatic assay. Total CRRT duration was 1,224 h. Twenty-four filters were changed due to clotting, with a mean filter life of 51 h. Mean (range) citrate levels (mmol/l) were (1) before initiating CRRT ( n=2): patient baseline 0.13 (0.1-0.15), (2) during CRRT ( n=7): circuit 4.54 (3.95-6.25), effluent 4.31 (3.95-5.46), and patient 0.69 (0.30-1.13). Sieving coefficients for urea and citrate were 0.88-0.97 and 0.88-1.0, respectively. Citrate clearance (31-38 ml/min per 1.73 m(2)) was similar to that of urea (31-38 ml/min per 1.73 m(2)), and when evaluated in two patients, remained unchanged after substituting half of the convective clearance [continuous venovenous hemofiltration (CVVH)] by diffusive clearance [continuous venovenous hemodiafiltration (CVVHDF)]. The post-filter citrate load (mean+/-SD) delivered to the five patients during CRRT was 1.06+/-0.62 mmol/kg per hour. With the exception of alkalosis in one patient, no other complications were observed. Renal function recovered in all patients. We conclude that citrate anticoagulation in children is feasible, effective, and safe. Sufficient citrate clearance to prevent its toxic accumulation is achieved by convective clearance (CVVH) alone and diffusive clearance (CVVHDF) does not appear to be mandatory when utilizing citrate anticoagulation during CRRT.     

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.