Cytokine Patterns in Patients Who Undergo Hemofiltration for Treatment of Multiple Organ Failure

p < 0.05). Arterial interleukin-6 (IL-6) levels significantly decreased during CVVH from 1284.7 ng/ml to 557.9 ng/ml; IL-8 levels simultaneously decreased from an initial peak of up to 154.4 ng/ml at MP3 to 97.3 ng/ml at MP5. The drop in serum IL-6 and IL-8 levels closely correlated with clinical improvement. After 2 hours of CVVH the hemodynamic situation improved significantly, as revealed by a decrease in catecholamine expenditure, an increase in arterial pressure, and a decrease in pulmonary artery pressure. Moreover, 2 hours after the initiation of CVVH the oxygenation index rose significantly and correlated well with the drop in shunt fraction. The Murray score significantly fell to 1.86. The removal of IL-6 and IL-8 by CVVH after initial stimulation correlates with clinical improvement, which was demonstrated by significantly improved oxygenation and hemodynamics from 2 hours after the initiation of CVVH onward. The elimination of cytokines and several mediators by CVVH may contribute to the cardiopulmonary improvement of critically ill patients. In comparison with the clinical control group ( n = 7), which was comparable in terms of MOSF, no intervention led to a similar improvement in cardiorespiratory failure, and overall two of these patients died. Moreover, patients of the control group experienced a significant longer stay at in the intensive care unit.     

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.     

High clearance continuous renal replacement therapy with a modified dialysis machine

Recent studies suggest that the dialysis dose significantly affects survival in acute renal failure (ARF) patients and that bicarbonate dialysate improves acid-base balance during continuous renal replacement therapy (CRRT). These data inspired us to use slow continuous dialysis (SCD) in the treatment of ARF. SCD is defined by the following parameters: (a) blood flow (Q(B)) = 100 to 200 ml/min, (b) dialysate flow (Q(D)) = 100 to 300 ml/min, (c) the use of a modified hemodialysis machine with controlled ultrafiltration and online production of bicarbonate-based dialysate, and (d) continuous or extended daily treatment for 8 to 24 hours. SCD provides a urea clearance in the 70 to 80 ml/min range. Preliminary data from an ongoing clinical trial demonstrate the safety, efficiency, and simplicity of the treatment.     

Procalcitonin and proinflammatory cytokine clearance during continuous venovenous haemofiltration in septic patients

Procalcitonin (PCT), interleukin-6 (IL-6), tumour necrosis factor a (TNFalpha), and interleukin-1beta (IL-1beta) are important clinical prognostic markers in ICU septic patients. The goal of the study was to determine whether continuous venovenous haemofiltration (CWH), using an AN69 haemofilte, leads to elimination of PCT, TNFalpha, IL-6 and IL-1beta in 13 septic patients with multi-organ failure. At the start of haemofiltration (0), 6 and 12 hours the mean afferent plasma concentration +/- SD of PCT (10.1 +/- 9.1, 7 +/- 6, 5.9 +/- 5.7 ng/ml), IL-6 (804.6 +/- 847.6, 611.7 +/- 528.4, 575.2 +/- 539.2 pg/ml), and that of TNFalpha (4.5 +/- 2.6, 4 +/- 3.1, 3.8 +/- 2.9 pg/ml) significantly declined during CVVH. The efferent plasma concentrations were significantly lower than the corresponding afferent concentrations. PCT; IL-6 and TNFalpha were detectable in the ultrafiltrate of all patients. IL-1beta was only detectable in the plasma of eight patients and the ultrafiltrate of five patients. The plasma clearance of PCT, IL-6 and TNFalpha significantly decreased after 12 hours as a result of a decline in the adsorptive elimination of the mediators due to progressive membrane saturation. We demonstrated that if PCT, IL-6 and TNFalpha are used as clinical prognostic markers in septic patients who are treated with CWIH using an AN69 membrane, one should be aware that their plasma level could be modified by the therapy. In addition CWH could represent an appropriate tool to remove a broad spectrum of proinflammatory mediators, if such removal is required in septic patients.     

Vanadium in patients undergoing chronic haemodialysis

The relationships between serum vanadium and serum aluminium, beta 2-microglobulin, silicon, phosphate, red blood cell count, haemoglobin and systolic blood pressure were studied in 80 chronic haemodialysis patients. Vanadium transfer during haemodialysis was also examined. Serum vanadium in 80 patients before haemodialysis was 18.4 +/- 7.6 ng/ml (normal values: 0.4 +/- 0.2 ng/ml). Significant correlations between serum vanadium and serum aluminium, silicon, beta 2-microglobulin, phosphate, red blood cell count, haemoglobin, and systolic blood pressure were found. As ultrafiltrate vanadium was greater than vanadium in the dialysate, vanadium transfers from blood to dialysate. Therefore, serum vanadium before haemodialysis significantly decreased from 18.4 +/- 7.76 ng/ml to 13.0 +/- 5.30 ng/ml, during a 5-h haemodialysis.     

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.     

危重患者连续静脉-静脉血液滤过治疗中滤液蛋白丢失

目的 探讨危重患者连续静脉-静脉血液滤过治疗(CVVH)中滤液蛋白丢失及其主要影响因素.方法 对2008年9月至2009年9月收治的18例脓毒症或重症急性胰腺炎合并急性肾功能衰竭患者的临床资料进行分析.其中男性12例,女性6例,平均年龄45岁(39～62岁),均行24 h CVVH.置换液流速4000 mL/h,跨膜压(TMP)、血流量和超滤率分别为(173±48)mm Hg(1 mmHg=0.133 kPa)、(277±89)ml/h、(179±4)ml/min.采集滤前和滤后血液,连续收集24 h滤液,测定血浆和滤液总蛋白浓度,计算滤液蛋白丢失量并进行统计学分析.结果 滤液蛋白平均浓度(231±67)mg/L,滤液蛋白丢失量(22±6)g/d.CVVH治疗前后血浆蛋白水平差异无统计学意义[(56±6)g/L比(55±10)g/L,P＞0.05].滤液蛋白浓度和m浆蛋白平均浓度之间存在较弱相关性(r=0.481,P＜0.05),和TMP之间存在显著相关性(r=0.564,P＜0.01),多元逐步回归分析表明TMP和血浆蛋白浓度是影响滤液蛋白丢失的主要因素.结论 CVVH除了肾脏替代治疗作用外,也会引起血浆蛋白质经滤器丢失,其中,TMP和血浆蛋白浓度是影响滤液蛋白丢失的主要因素.在对接受CVVH治疗的危重患者制定营养方案时,必须考虑经滤器额外丢失的蛋白质.     

Drug Dosing During Continuous Renal Replacement Therapy

Continuous renal replacement therapy (CRRT) has given clinicians an important option in the care of critically ill patients. The slow and continuous dialysate and ultrafiltrate flow rates that are employed with CRRT can yield drug clearances similar to an analogous glomerular filtration rate of the native kidneys. Advantages such as superior volume control, excellent metabolic control, and hemodynamic tolerance by critically ill patients are well documented, but an understanding of drug dosing for CRRT is still a bit of a mystery. Although some pharmaceutical companies have dedicated postmarket research in this direction, many pharmaceutical companies have chosen not to pursue this information as it is not mandated and represents a relatively small part of their market. This lack of valuable information has created many challenges in the care of the critically ill patient as intermittent hemodialysis drug dosing recommendations cannot be extrapolated to CRRT. This drug dosing review will highlight factors that clinicians should consider when determining a pharmacotherapy regimen for a patient receiving CRRT.     

The Effects of Endotoxin–Contaminated Dialysate and Polysulfone or Cellulosic Membranes on the Release of TNFα during Simulated Dialysis

Abstract: Simulated dialysis of whole blood was used to determine whether membrane factors (biocompatibility), endotoxin (ET) membrane diffusion, or transmembrane monocyte–ET interactions would stimulate tumor necrosis factor (TNFα) release. Whole blood containing EDTA and aprotinin was recirculated in the blood compartment of hollow fiber dialyzers containing either regenerated cellulose or polysulfone membranes. ET–free and ET–spiked dialysate were recirculated consecutively in the dialysate compartment for 30 min each. Blood and dialysate samples were collected at t _o and after each 30 min of simulated dialysis for determination of TNFa and ET concentrations. TNFa was not detected in any blood samples collected after simulated dialysis with regenerated cellulose (RC) membranes and ET–free or ET–spiked dialysate. However, blood ET concentrations, as determined by the Limulus amebocyte lysate (LAL) assay, increased in RC dialyzers after each 30 min of simulated dialysis even with ET–free dialysate. Since TNFa was not detected in these blood samples, the material detected by the LAL assay probably was not ET but an LAL–reactive material. After simulated dialysis with polysulfone dialyzers and ET–free dialysate, TNFa and ET were not detected in blood samples. ET also was not detected in blood samples after dialysis with ET–spiked dialysate. However, TNFa was detected in 7 of 13 (54%) of the blood samples following the 500 ng/ml of ET dialysate spike. TNFα release during simulated dialysis with polysulfone membranes and ET–contaminated dialysate may be due to transmembrane stimulation of circulating mononuclear cells and not diffusion of ET across the membrane.     

Cytokine removal during continuous hemofiltration in septic patients

A potential application of the continuous renal replacement therapies is the extracorporeal removal of inflammatory mediators in septic patients. Cytokine elimination with continuous renal replacement therapies has been demonstrated in several clinical studies, but so far without important effects on their serum concentrations. Improved knowledge of the cytokine removal mechanisms could lead to the development of more efficient treatment strategies. In the present study, 15 patients with septic shock and acute renal failure were observed during the first 24 h of treatment with continuous venovenous hemofiltration (CVVH) with an AN69 membrane. After 12 h, the hemofilter was replaced and the blood flow rate (QB) was switched from 100 ml/min to 200 ml/min or vice versa. Pre- and postfilter plasma and ultrafiltrate concentrations of selected inflammatory and anti-inflammatory cytokines were measured at several time points allowing the calculation of a mass balance. Cytokine removal was highest 1 h after the start of CVVH and after the change of the membrane (ranging from 25 to 43% of the prefilter amount), corresponding with a significant fall in the serum concentration of all cytokines. The inhibitors of inflammation were removed to the same extent as the inflammatory cytokines. Adsorption to the AN69 membrane appeared to be the main clearance mechanism, being most pronounced immediately after installation of a new membrane and decreasing steadily thereafter, indicating rapid saturation of the membrane. A QB of 200 ml/min was associated with a 75% increase of the ultrafiltration rate and a significantly higher convective elimination and membrane adsorption than at a QB of 100 ml/min. The results indicate that optimal cytokine removal with CVVH with an AN69 membrane could be achieved with a combination of a high QB/ultrafiltration rate and frequent membrane changes.     

腹腔感染合并急性肾功能衰竭患者连续静脉-静脉血液滤过治疗前后血浆氨基酸水平变化

目的 探讨腹腔感染合并急性肾功能衰竭患者连续静脉-静脉血液滤过(CVVH)治疗前后血浆氨基酸水平变化和氨基酸丢失量.方法 回顾性分析2008年9月至2009年9月南京军区南京总医院收治的10例腹腔感染合并急性肾功能衰竭患者的临床资料.采用AV600S聚砜膜行24 h CVVH治疗,分别采集CVVH治疗前、治疗12 h和24 h血浆,连续收集24 h滤液.高压液相色谱测定血浆和滤液氨基酸浓度,并计算滤液氨基酸丢失量.采用配对t检验或Wilcoxon秩和检验,一元线性回归分析变量之间的关系.结果 10例患者中死亡6例,其中3例死于脓毒性休克,3例死于MODS.CVVH治疗24 h后血浆各种氨基酸水平显著下降,其中组氨酸、异亮氨酸、半胱氨酸和谷氨酰胺分别由(22.1±10.3)、(20.0±7.6)、(10.3±4.7)、(122.3±72.2)μmoL/L下降至(5.6±3.4)、(6.4±2.5)、(2.9±2.4)、(42.5±33.6)μmol/L.血浆总氨基酸水平呈下降趋势,CVVH治疗12 h和24 h分别下降52%和59%.滤液氨基酸24 h平均丢失量为(9631±1089)mg/d,其中非必需氨基酸和必需氨基酸丢失量分别为(5072±618)mg/d和(3747±654)mg/d,两者比较,差异有统计学意义(t=4.52,P＜0.05).CVVH治疗12 h后滤液氨基酸丢失量和血浆氨基酸水平之间呈正相关(r=0.68,P＜0.05).结论 腹腔感染患者接受CVVH治疗时,氨基酸可以经滤液丢失,因此,为CVVH患者制定营养方案时,滤液额外丢失的氨基酸需要考虑在内,尤其要适当增加非必需氨基酸的含量.     

Pharmacokinetics of vancomycin in patients undergoing haemodialysis and haemofiltration

Vancomycin is widely used for the treatment of infections with Gram-positive bacteria in patients with end-stage renal disease. The concentration of vancomycin in serum, in ultrafiltrate, and in dialysate was measured during nine haemofiltration and seven haemodialysis procedures with high-permeability membranes. The t1/2 of vancomycin was 101 +/- 19 h in the interdialytic and interhaemofiltration period. There was no significant difference between the haemodialysis clearance (55.2 +/- 18.5 ml/min) and the haemofiltration clearance (66.8 +/- 13.6 ml/min). The redistribution phenomenon was about 25% in the post haemofiltration period and only 10% in the post haemodialysis period. Approximately 270 mg of vancomycin was recovered in dialysate or ultrafiltrate. With high-permeability membranes more commonly used in patients with end-stage renal disease, continuous monitoring of vancomycin therapy is recommended.     

Studies on dialysate mixing in the Genius single-pass batch system for hemodialysis therapy

BACKGROUND: The Genius single-pass batch system for hemodialysis contains a closed reservoir and dialysate circuit of 75 L dialysate. The unused dialysate is withdrawn at the top of the reservoir and the spent fluid is reintroduced into the container at the bottom. Although it has been claimed that both fractions remain unmixed during the dialysis session, no direct proof of this assumption has yet been provided. In the present study, we investigated whether contamination of the unused dialysate with uremic solutes occurred and at which time point it began. Two different dialysate temperatures were compared. METHODS: Ten chronic hemodialysis patients were dialyzed twice with the Genius system, with dialysate prepared at 37 degrees C and 38.5 degrees C, respectively. The sessions lasted 270 minutes with blood/dialysate flow set at 300 mL/min. Dialysate was sampled at 5, 60, 180, 210, 225, 230, 235, 240, 255, and 270 minutes both from the inlet and outlet dialysate line and blood was sampled from the arterial line predialysis, after 4 hours, and postdialysis. All samples were tested for osmolality, urea, creatinine, p-cresol, hippuric acid, and indoxyl sulfate. RESULTS: Uremic solutes appeared in the inlet dialysate line between 3 hours 50 minutes and 4 hours 10 minutes after the start of dialysis, corresponding to 68.6 and 74.7 L spent dialysate, respectively (37 degrees C vs. 38.5 degrees C; P = NS). No difference in the amount of removed solutes and in the serum levels was observed between 37 degrees C and 38.5 degrees C. A Kt/V of 1.17 +/- 0.20 and 1.18 +/- 0.26, respectively, was reached with the 37 degrees C and 38.5 degrees C dialysate temperature (P = NS). CONCLUSION: Contamination with uremic solutes occurred at the dialysate inlet only near the end of the session when small quantities of fresh dialysate were left in the container. Differences in dialysate temperature did not result in a different separation between used and unused dialysate, or in differences in removal of toxins or Kt/V.     

Effects of dermatan sulfate for anticoagulation in continuous renal replacement therapy

BACKGROUND: Dermatan sulfate (DS) is a natural glycosaminoglycan with a unique mechanism of action on the coagulation system. Unlike unfractionated heparin (UFH), DS selectively inhibits thrombin, does not inhibit factor Xa, is effective on both free and fibrin-bound thrombin and does not interfere with platelets. This study represents the first experience using DS as anticoagulant in patients on continuous renal replacement therapy (CRRT). METHODS: A total of 147 patients in our intensive care unit who developed acute renal failure after cardiovascular surgery were on CRRT according to the same protocol: machine, Gambro Prisma; filter, AN69, 0.9 m2; QB, 150 ml/min; QD, 2,000 ml/hour; and Q(Infusate), 500 ml/hour. In a retrospective cohort of 100 patients, anticoagulation was performed with UFH (UFH-CRRT): initial bolus of 530 +/- 363 IU, then i.v. infusion of 598 +/- 261 IU/hour. A prospective cohort of 47 patients received DS (DS-CRRT) as a 150-mg bolus followed by a 13.5 +/- 3 mg/hour infusion. Hematology tests were performed at baseline and during CRRT; filter lifetime was measured from the start to filter clotting. RESULTS: Median filter lifetime was 58 hours in DS-CRRT vs. 47 hours in UFH-CRRT (p<0.001). No differences emerged in basal hematology and hemostasis tests between groups. During CRRT, DS produced a smaller activated partial thromboplastin time increase than UFH (p<0.01). Platelet count exhibited a comparable small decline in both DS-CRRT and UFH-CRRT (p<0.01). No significant bleeding episodes occurred during DS-CRRT. In-hospital mortality was similar in the 2 cohorts. CONCLUSIONS: DS can be suggested as an anticoagulant for CRRT in patients who develop acute renal failure following major cardiovascular surgery.     

Sustained low-efficiency dialysis in the ICU: cost, anticoagulation, and solute removal

Hemodialysis (HD) for critically ill patients with acute renal failure has been provided as intermittent hemodialysis (IHD) or continuous renal replacement therapy (CRRT). IHD is often complicated by hypotension and inadequate fluid removal, and CRRT by high cost of solutions and problems with anticoagulation. Sustained low-efficiency daily dialysis (SLED) has been suggested as an alternative treatment. This is an observational, prospective pilot study describing the introduction of SLED at our institution. We compared SLED (23 patients, 165 treatments) with CRRT (11 patients, 209 days), focusing on cost, anticoagulation, and small solute removal. SLED consisted of 8 h of HD 6 days a week, with blood flow of 200 ml/min, dialysate flows of 350 ml/min, and hemofiltration with 1 l of saline/h. CRRT patients were anticoagulated with either heparin or citrate, and SLED patients with either heparin or saline flushes. The weekly costs to the hospital were $1431 for SLED, $2607 for CRRT with heparin, and $3089 for CRRT with citrate. Sixty-five percent of SLED treatments were heparin-free; filter clotting occurred in 18% of heparin treatments and 29% of heparin-free treatments (NS). Weekly Kt/V was significantly higher for SLED (8.4+/-1.8) and time-averaged serum creatinine was lower; equivalent renal clearance (EKRjc) was 29+/-6 ml/min for SLED, similar to that for CRRT. In summary, SLED may be routinely performed without anticoagulation; it provides solute removal equivalent to CRRT at significantly lower cost.     

Continuous venovenous hemofiltration: an alternative to continuous arteriovenous hemofiltration and hemodiafiltration in acute renal failure

Continuous venovenous hemofiltration (CVVH) has been used as an alternative to continuous arteriovenous hemofiltration (CAVH) and hemodiafiltration (CAVHD) in the management of critically ill patients with acute renal failure. This report describes our experience with the first 25 patients treated with CVVH at our institution. Vascular access was obtained through a single dual-lumen venous catheter. A blood pump was used to provide ultrafiltration pressure. An ultrafiltrate pump was incorporated to ensure predictable ultrafiltrate production rates. Safety features in the extracorporeal circuit included a venous drip chamber with bubble detector and an in-line pressure monitor. CVVH was initiated by a nephrologist and dialysis nurse and was maintained by the intensive care unit (ICU) nursing staff. Fifteen females and 10 males received CVVH therapy for a total of 193.5 days (average, 7.7 +/- 10.3 days; range, 0.5 to 48 days). Four of the 25 patients (16%) survived and were discharged from the hospital. Four additional patients (16%) survived the acute phase of their illness, but died from complications of their primary disease before discharge from the hospital. The mean weight change during CVVH was -7.9 +/- 7.0 kg (range, -26.5 to +2.9 kg). Metabolic waste products and electrolytes were adequately controlled by CVVH in all but one hypercatabolic patient. The mean heparin dose required was 6.5 +/- 4.2 U/kg/h and was adjusted to prevent filter clotting rather than to achieve a predetermined activated partial thromboplastin time (PTT). The median PTT was 35.8 seconds (range, 22.0 to 100; control, 19.5 to 29.5 seconds). Four episodes of volume-responsive hypotension occurred during the 193.5 treatment days. Only one patient experienced a hemorrhagic complication during CVVH. No patient experienced a complication related to vascular access. Twelve of 111 total hemofilters were changed because of clot formation. CVVH was well tolerated by patients and managed efficiently by the ICU nursing staff.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tailoring high-cut-off membranes and feasible application in sepsis-associated acute renal failure: in vitro studies.

BACKGROUND: As removal of pro-inflammatory cytokines is limited in conventional diffusive or convective extracorporeal therapies, we studied in two polysulphone membranes with an industrial albumin sieving coefficient of 0.05 (Type A) and 0.13 (Type B) cytokine (IL-6, IL-8, IL-1beta, IL-1ra, TNF-alpha) and plasma protein (albumin, cystatin C, total proteins) permeability profiles. Based on the convective membrane permeability, we evaluated in vitro the dialytic modality that could provide an acceptable balance between high cytokine and low albumin clearances. METHODS: Cytokine and plasma protein sieving coefficient (SC) and clearance were studied in (i) post-dilutional haemofiltration mode at 20% fixed ultrafiltration rate; (ii) haemodialysis mode (dialysate flow rate of 3 and 5 l/h); and (iii) haemodiafiltration mode (dialysate flow rate of 3 or 5 l/h with 0.5 l/h of ultrafiltrate). RESULTS: In haemofiltration mode both Type A and Type B haemodialysers at QB 150 ml/min exhibited similar median SC nearly up to 1 for IL-1beta and IL-1ra, at about 0.6 for IL-6, 0.4 for IL-8 and 0.7 for TNF-alpha, with clearance values ranging from 15 to 30 ml/min. SC were independent of blood flow and were stable throughout the whole experiment. Albumin SC was higher in Type B than in Type A and rapidly decreased from 0.2 to 0.02 and from 0.5 to 0.04 within 3 h for haemodialyser Types A and B, respectively. Cytokine SC was lower in haemodialysis than in haemodiafiltration and haemofiltration mode, and by increasing dialysate flow from 3 up to 5 l/h in both haemodialysis and haemodiafiltration mode, SC for all tested cytokines decreased. However, at 5 l/h clearances were not different or were higher, since increased amounts of dialysate outlet compensated for the decreased SC. Albumin clearances in haemodialysis and haemodiafiltration mode after 360 min at 5 l/h were 0.81 and 0.91 ml/min, respectively. CONCLUSIONS: Our studies show that a mixed convective and diffusive technique ensures high cytokine clearances with an acceptable loss of albumin.     

Haemostatic changes in systemic inflammatory response syndrome during continuous renal replacement therapy

BACKGROUND: Endothelial damage and hemostatic imbalance play an important role in the evolution of the Systemic Inflammatory Response Syndrome (SIRS) into the Multiple Organ Dysfunction Syndrome (MODS). In Acute Renal Failure associated with SIRS, different types of Continuous Renal Replacement Therapies (CRRT) may give non-renal benefits by modifying the levels of some factors related to those disturbances. METHODS: Forty patients with SIRS-associated ARF were randomised to receive either continuous venovenous hemofiltration (CVVH) or continuous venovenous hemodiafiltration (CVVHDF) for the first 24 h. Afterwards the CRRT method was reversed. The group treated with CVVH moved to CVVHDF and that treated with CVVHDF to CVVH for the next 24 h. Plasma levels of: von Willebrand Factor (vWF), thrombomodulin, plasminogen activity inhibitor type 1 (PAI-1: antigen and activity), tissue type plasminogen activator (t-PA: antigen), prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin complexes (TAT) were measured previously to CRRT (base-line), and after 24 and 48 hours of therapy. Multivariate ANOVA was the statistical method used. RESULTS: In the MANOVA study a significant decrease in PAI-1 activity during the treatment procedure was observed (horizontality p <0.05). PAI-1 antigen showed a tendency to decrease although without statististical significance. There were no significantly different changes in the other factors analysed during either CRRT (parallelism p >0.05). At the base-line point, all the factors were higher than normal values in healthy adults. CONCLUSIONS: The present study suggests that CRRT, in patients with SIRS, may promote a decrease in PAI-1 and consequently, a better outcome. There were no differences between the CVVH and the CVVHDF methods regarding the factors analysed. The present data confirms that there is an important endothelial and hemostatic dysfunction in SIRS from the early phases.     

表皮生长因子对肿瘤坏死因子α致HaCaT细胞凋亡的抑制作用

目的了解肿瘤坏死因子α（TNF-α）导致HaCaT细胞凋亡过程中过氧化物酶体增殖物激活受体B（PPAR[3）的表达情况，探讨表皮生长因子（EGF）对HaCaT细胞的保护机制。方法将培养的HaCaT细胞分为正常对照组（不作任何处理）、TNF—α小剂量组（10ng／ml TNF-α处理）、TNF—α大剂量组（20ng／mlTNF-α处理）、EGF＋TNF—α小剂量组、EGF＋TNF—α大剂量组，后2组先用20ng／mlEGF培养4h后，再分别予以10、20ng／ml TNF—α处理。采用流式细胞仪检测细胞凋亡情况，半胱氨酸天冬氨酸蛋白酶3（easpase．3）荧光检测试剂盒测定caspase-3的活性，噻唑蓝比色法检测细胞存活率。以5、10、20、40ng／ml的EGF处理HaCaT细胞，采用反转录．PCR和蛋白质印迹法检测PPAR[3mRNA及其蛋白的表达。结果与TNF-α小剂量组[（32±6）％]、TNF-ct大剂量组[（57±6）％]比较，EGF＋TNF—α小剂量组、EGF＋TNF-α大剂量组细胞凋亡率[（20±3）％、（28±4）％]明显下降（P〈0．01），caspase-3活性降低、存活率上升（P〈0．01）。20ng／mlEGF处理细胞时，PPAR[3mRNA及其蛋白表达最强。结论EGF在抑制TNF-α导致的HaCaT细胞凋亡的同时，亦增强细胞中PPARβ的表达。     

Should Nicorandil Infusion Be Adapted in Dialysis‐Dependent Patients Undergoing Continuous Renal Replacement Therapy After Cardiac Surgery?

In this report, we studied whether plasma concentration of nicorandil is maintained effectively and safely in dialysis‐dependent patients with stage 5 chronic kidney disease (CKD5D) undergoing continuous renal replacement therapy (CRRT). Participants consisted of 10 patients undergoing CRRT after cardiac surgery. CRRT was performed with an effluent flow rate of either 600 mL/h (low‐flow group; n = 5) or 1800 mL/h (high‐flow group; n = 5). Nicorandil was infused intravenously at 0.1 mg/kg/h for more than 15 h starting 8 h before and 7 h after the start of CRRT. Plasma nicorandil concentrations were measured from arterial blood lines 1 h before and 7 h after CRRT initiation. Nicorandil clearance by CRRT was also calculated 1 h after CRRT initiation. Nicorandil plasma concentrations before and 7 h after CRRT initiation were 68.0 ng/mL and 74.6 ng/mL, respectively. Nicorandil clearance 1 h after CRRT initiation was 20.2 mL/min. Increasing the effluent flow rate from 600 mL/h to 1800 mL/h tended to increase nicorandil clearance. When nicorandil was infused intravenously during CRRT at 0.1 mg/kg/h in patients with CKD5D, plasma nicorandil concentrations were maintained within an effective concentration range.