Continuous Hemofiltration/Hemodiafiltration in Critical Care

Abstract: Continuous hemofiltration and continuous hemodiafiltration (CHF/CHDF) were developed as continuous renal replacement therapy for patients with severe conditons and has come to be widely performed mainly in critical care, taking the place of intermittent hemodialysis. The membrane pore size of a hemofilter used for CHF/CHDF allows passage of substances ranging from 30,000 to 50,000 Da, and the method for solute removal in CHF/CHDF employs the principle of convection, which is advantageous for removing middle‐ to high‐molecular‐weight substances. As apheresis therapy to remove pathogenic substances in blood, CHF/CHDF is therefore being investigated for its possible effect on various morbid conditions. It has recently been found that CHF/CHDF removes humoral mediators including cytokines, particularly in severe systemic inflammatory response syndromes such as septic shock and severe acute pancreatitis. CHF/CHDF is thus beginning to be performed for the prevention and treatment of organ dysfunction secondary to septic shock, trauma, or acute pancreatitis. CHF/CHDF is also efficacious as artificial liver support in preventing adverse effects caused by plasma exchange (PE) and for continuous removal of hepatic coma‐inducing substances. CHF/CHDF is effective for various morbid conditions not only as renal replacement therapy, but also as apheresis therapy and is expected to be applied more widely in critical care in the future.     

Acute renal failure in the intensive care unit

Acute renal failure (ARF) is a common complication in critically ill patients, with ARF requiring renal replacement therapy (RRT) developing in approximately 5 to 10% of intensive care unit (ICU) patients. Epidemiological studies have demonstrated that ARF is an independent risk factor for mortality. Interventions to prevent the development of ARF are currently limited to a small number of settings, primarily radiocontrast nephropathy and rhabdomyolysis. There are no effective pharmacological agents for the treatment of established ARF. Renal replacement therapy remains the primary treatment for patients with severe ARF; however, the data guiding selection of modality of RRT and the optimal timing of initiation and dose of therapy are inconclusive. This review focuses on the epidemiology and diagnostic approach to ARF in the ICU and summarizes our current understanding of therapeutic approaches including RRT.     

Cytokine and endotoxin removal in critically Ill patients

Endotoxin and cytokine removal by blood purification is one of the most effective treatments for critical illness such as systemic inflammatory response syndrome (SIRS), sepsis and septic shock. SIRS and sepsis frequently associates with hepatic failure, renal failure, respiratory failure, cardiac failure, disseminated intravascular coagulation (DIC) and gastrointestinal bleeding. In these diseases endotoxin and several mediators such as inflammatory cytokines play important roles in clinical course and pathophysiology. The role of blood purification is to remove endotoxin and cytokines, to correct cytokine balance, and to modulate humoral conditions. We use 2 methods of blood purification. One is direct hemoperfusion using Toraymyxin developed by Kodama and Tani in Shiga University of Medical Science. Toraymyxin composed of a Polymyxin B immobilized, can remove endotoxin and can be applied to patients with endotoxemia or suspected bacteremia. The most impressive clinical effectiveness is the improvement of hemodynamic abnormalities. Blood pressure, cardiac index and oxygen consumption index improve after treatment by Toraymyxin. Furthermore inflammatory mediators such as TNF, IL‐6, IL‐10 and plasminogen activator inhibitor‐1 (PAI‐1) are significantly decreased either after 2 h or by the following day in survivors. An immediate mediator, endogenous cannabinoid which is generated by activated monocytes / macrophages and causes septic shock, is also reduced by Toraymyxin treatment. Another method of blood purification is continuous hemofiltration (CHF) and continuous hemodiafiltration (CHDF). CHF and CHDF have been applied only with renal indication, but recently it is widely applied with nonrenal indication for patients with critical illness. The main purpose of CHF and CHDF is to reduce humoral mediators level in blood. As in SIRS patients, inflammatory cytokines are continuously produced in inflammatory regions, the continuous therapy is recommended in ICU. Sometimes inflammatory cytokines are not so reduced in the blood level. The change in the blood level of cytokines depends on the balance between the generation rate and the removal rate of cytokines with continuous therapy. We have some successful results in patients with sepsis and SIRS, but further studies are required to make standardized strategy with blood purification and to have better survival rate.     

连续性血液净化在ICU多器官功能障碍综合征合并急性肾衰竭患者的应用及预后分析

目的探讨连续性血液净化治疗（CBPT）在ICU多器官功能障碍综合征（MODS）合并急性肾衰竭（APF）患者的疗效及影响预后的相关因素。方法回顾性分析2004年1月至2008年2月该院ICU中行连续性静-静脉血液滤过（CVVH）治疗的245例MODS合并ARF患者一般资料、血液生化检查、疾病严重程度评分等，对比分析CVVH治疗前后临床参数的变化及影响预后的因素。结果CVVH对容量负荷、溶质清除效果明显；反映疾病严重程度如氧合指数、APACHEⅡ评分、MODS评分、SOFA评分CVVH治疗前后比较无明显差异；全部患者死亡率为64．9％，病死率随着衰竭器官数目的增加而显著升高。多因素回归分析显示，患者CVVH治疗前衰竭器官数、医院获得性ARF、CVVH前APACHEⅡ评分、平均动脉压是独立危险因素。结论对于MODS合并ARF患者，CVVH治疗前患者疾病的严重程度是影响预后的重要因素，依据患者临床病情早期积极CBPT可能改善MODS合并ARF患者的预后。     

合并肾功能衰竭的肝移植患者接受肾脏替代治疗的价值

目的 回顾性分析合并急性肾功能衰竭的肝移植受体移植术前的危险因素,并探讨肾脏替代治疗(RRT)作为其移植前过渡治疗措施的价值. 方法收集2001年1月-2008年1月在卫生部移植医学工程技术研究中心由于急性肾功能衰竭而接受RRT的肝移植受体患者,依据不同预后对肝移植受体的临床特征进行分组对比分析;按接受不同RRT种类对肝移植受体的临床特征进行分组对比分析.用逻辑回归法分析能预测合并肾功能衰竭肝移植受体病死率的指标.对数据进行f检验、χ2检验、Logistic回归分析.结果 在接受RRT的患者中,有31.25%的患者因为肝移植而生存或者出院,68.75%的患者在等待移植期间死亡.死亡组患者与移植组相比,有更高的多器官功能障碍评分(4.98±2.32与4.45±2.02,P=0.008)、更低的平均动脉压[(56.5±7.1)mm Hg与(65.4±12.9)mm HgP=0.040;1 mm Hg=0.133 kPa].RRT的平均治疗天数在连续性肾脏替代治疗组和间歇血液透析组之间的差异没有统计学意义.与间歇血液透析组相比,连续性肾脏替代治疗组有更高的多器官功能障碍评分(4.82±2.12与3.45±1.91,P=0.040)、更低的平均动脉压[(56.0±14.2)mm Hg与(68.5±15.3)mm Hg,P=0.002]、更低的血清肌酐浓度[(320.12±185.15)μmol/L与(420.55±158.32)μmol/L,JP=0.008].肾功能衰竭受体术前平均动脉压越低,则死亡风险越高. 结论对患有急性肾功能衰竭的肝移植受体应用RRT是可取的.尽管病死率仍高,但可使部分患者得以肝移植而生存.     

A case report of acute renal failure and fulminant hepatitis associated with edaravone administration in a cerebral infarction patient

A 60-year-old male with cerebral infarction was admitted to our hospital and treated with edaravone. On day 12 of hospitalization, he suddenly lost consciousness and went into shock. Based on the laboratory findings, acute renal failure (ARF), fulminant hepatitis, and disseminated intravascular coagulation (DIC) were diagnosed. We immediately initiated continuous hemodiafiltration for three days and performed three sessions of plasma exchange. Following this, a gradual improvement was observed in the patient's general condition and laboratory values. On day 17 of hospitalization, intermittent hemodialysis (HD) was initiated. On day 20 of hospitalization, his renal function started to improve with an increase in urine volume. HD was successfully discontinued on the same day. Although the drug lymphocyte stimulation test for edaravone was negative, edaravone-induced fulminant hepatitis was suggested based on liver biopsy findings. We present a case of ARF, fulminant hepatitis, and DIC due to edaravone administration that was successfully treated with blood purification techniques. Since the use of edaravone treatment is expected to increase in the future, it is essential that clinicians consider the potential adverse effects of this treatment. It is suggested that blood purification is effective in inducing remission in patients with complications due to edaravone treatment.     

连续性肾脏替代治疗与间断性血液透析在重症肾综合征出血热治疗中的应用

目的回顾性观察连续性肾脏替代治疗(continuous renal replacement therapy,CRRT)与间断性血液透析(intermittent hemodialysis,IHD)在重症肾综合征出血热(hemorrhagic fever with renal syndrome,HFRS)患者中的应用。方法依据临床分型标准,将2008年1月—2012年8月在我中心行血液净化治疗的147例重症HFRS患者分为重型组和危重型组;参照中华医学会ICU血液净化指南,对纳入患者行CRRT或IHD治疗,比较2组行CRRT或IHD治疗的病死率、并发症发生率和急性期的实验室指标。结果重型组患者均存活;危重型组患者行CRRT与IHD后的病死率比较差异无统计学意义(P=0.124);危重型组行CRRT的比例明显高于重型组(P0.001)。病程中存在重叠期的重症患者,行CRRT初始治疗的例数明显多于行IHD的例数,但其生存率比较差异无统计学意义(P=1.000)。CRRT组患者病情较IHD组重,其疾病本身的肾外并发症也较IHD组常见。结论 CRRT可广泛应用于危重型HFRS患者的救治。CRRT可有效减轻水负荷,稳定机体的血流动力学状态,将有助于使危重患者平稳地渡过急性期。     

连续肾脏替代治疗在肝移植中的应用

目的探讨连续肾脏替代治疗(CRRT)在肝移植术后急性肾功能衰竭(ARF)合并多器官功能不全(MODS)治疗中的应用价值。方法分析连续静脉静脉血液滤过(CVVH)治疗7例肝移植术后ARF、成人呼吸窘迫综合征(ARDS)、急性心衰、全身炎症反应综合征(SIRS)等患者。3例合并ARDS患者同时进行呼吸机辅助呼吸治疗。结果4例治愈,另3例ARF合并MODS患者死亡。经CVVH治疗后,患者血清中的肌酐、尿素氮、血钾较治疗前降低(P<0.05),凝血酶原时间变化无意义。结论CVVH能有效控制氮质血症和高血钾等高分解状态,而不影响凝血功能。早期应用可以改善肝移植术后ARF、ARDS、充血性心力衰竭、SIRS等MODS患者的预后。     

On‐Line Hemodiafiltration in Critical Care

Abstract: On‐line products of substitution fluid permits virtually unlimited fluid volume exchange during continuous hemodiafiltration (CHDF) to critical care. In on‐line hemodiafiltration (HDF), endotoxin free dialysate obtained using pyrogen cut filters is infused into the blood circuit, and HDF is automatically performed using the closed‐loop balancing system of the dialysis machine. On‐line CHDF is the application of this on‐line HDF to continuous renal replacement therapy in the critical care field. We performed on‐line CHDF on 376 acute renal failure patients during a 5 year period, and the mean survival rate was 62.5%. We concluded that the on‐line CHDF system is safe and effective at maintaining acute renal failure patients.     

Effectiveness of Combining Plasma Exchange and Continuous Hemodiafiltration (Combined Modality Therapy in a Parallel Circuit) in the Treatment of Patients with Acute Hepatic Failure

Abstract: Plasma exchange has gained widespread acceptance as an effective mode of blood purification in patients suffering from acute hepatic failure. However, it is still undetermined whether a single use of plasma exchange is capable of removing inflammatory cytokines completely or of preventing the development of citrate toxicity inherent with fresh frozen plasma. To clarify these issues we developed combined plasma exchange and continuous hemodiafiltration (CHDF) modality in which CHDF is performed in an opposite direction to plasma exchange. This study was designed to assess the effectiveness of combined modality therapy. Fifteen patients with acute hepatic failure were treated with plasma exchange (plasma exchange group) or plasma exchange and CHDF (plasma exchange + CHDF group), and various biochemical parameters were determined before and after treatment. Although citrate levels increased significantly after treatment compared with pretreatment levels in both the plasma exchange group and the plasma exchange + CHDF group, the percentage of the increase in citrate levels was significantly higher in the plasma exchange group than in the plasma exchange + CHDF group. Bilirubin levels were significantly lower after treatment in both the plasma exchange and plasma exchange + CHDF groups. There were no significant differences in tumor necrosis factor‐α levels before and after treatment in the plasma exchange group, but they were significantly lower after treatment in the plasma exchange + CHDF group. Interleukin‐6 (IL‐6) levels increased significantly after treatment in the plasma exchange group, but there were no significant differences in the IL‐6 levels before and after treatment in the plasma exchange + CHDF group. Interleukin‐8 levels increased significantly after treatment in the plasma exchange group while decreasing significantly after treatment in the plasma exchange + CHDF group. These results indicate that combining plasma exchange and CHDF in a parallel circuit is an effective modality for suppressing the elevation of blood citrate levels and for removing inflammatory cytokines. This finding may have important implications for the development of an effective treatment for patients with acute hepatic failure.     

连续性肾脏替代疗法在重症急性肾功能衰竭治疗中的应用

目的 回顾分析连续性肾脏替代疗法（ＣＲＲＴ）在重症急性肾功能衰竭（ＡＲＦ）治疗中的应用和影响预后的因素。方法 １９８６年５月至１９９９年１月用ＣＲＲＴ治疗重症ＡＲＦ患者１０１例,回顾性分析了患者临床特点、ＣＲＲＴ方法和预后。结果 １０１例患者中６０例（５９．４％）度过疾病的急性期（存活组）,４１例（４０．６％）在急性期死亡（死亡组）,对两组患者的临床统计学资料、肾功能衰竭的特点、疾病严重程度（ＡＰ     

持续静脉滴注速尿治疗充血性心力衰竭随机对照研究

目的　探讨持续静脉滴注速尿治疗充血性心力衰竭 (CHF)的药效学及对生理平衡的影响是否优于一次性注射治疗。方法　采用随机对照方法将 70例 NYHA心功能 — 级 CHF患者分为持续静脉滴注组 (静滴组 ,35例 )和一次性静脉注射组 (静注组 ,35例 ) ,静滴组在注射 10 mg负荷剂量速尿后持续静滴 30 m g,静注组一次性注射 4 0 mg,均持续 3日。治疗前后分别评价心功能及血生化指标 ,并计算每日尿量和尿 K+、Na+、Cl-排泄量。结果　静滴组每日尿量及尿K+、Na+、Cl-排泄量均明显大于静注组 ,尤其在治疗的第二日、第三日 ,治疗后静注组除血脂浓度升高比静滴组更显著外 ,其他生化指标两组无显著差异。结论　持续静脉滴注速尿治疗 CHF在药效学方面明显优于静脉注射方式 ,并可提高肾脏对速尿的敏感性 ,延缓耐受性的产生。对生理平衡的影响也可能优于一次性静脉注射 ,值得进一步探讨。     

The dose of nafamostat mesilate during plasma exchange with continuous hemodiafiltration in the series-parallel circuit

We studied nafamostat mesilate (NM) and interleukin (IL)-18 levels to determine whether the dose of NM is reduced during plasma exchange (PE) with continuous hemodiafiltration (CHDF) when the series-parallel circuit is used. The subjects of the current study included four patients with acute hepatic failure who underwent PE with CHDF. The four patients underwent a total 15 PE + CHDF procedures, and for each procedure, they were randomized to receive either a half-dose of NM or no NM in the CHDF circuit. Eight procedures were carried out with NM administration, and seven were carried out without NM administration. The dose of NM in the NM group was significantly higher than that in the non-NM group (P = 0.040). No significant differences were observed between the two groups in the inlet NM concentration, the outlet NM concentration, or the rate of IL-18 removal. No statistical correlation was observed between the IL-18 level and the NM dose, the inlet NM concentration, or the outlet NM concentration. There was no blood access difficulty such as catheter failure or clotting of the filter. Thus, it might be possible to carry out PE and CHDF with the series-parallel method without administration of NM in the CHDF circuit.     

连续性静脉静脉血液滤过在心脏手术后急性肾功能衰竭中的疗效及应用时机

目的 探讨连续性静脉静脉血液滤过(CVVH)在心脏手术后急性肾功能衰竭中的疗效及应用时机.方法 回顾性分析48 例心脏术后并发急性肾功能衰竭(ARF)患者的临床资料,按出现尿量减少(<0.5 ml·kg-1·h-1)至开始CVVH 治疗的时间间隔分为两组:A 组<4 h(27 例),B 组>4 h(21 例).分别对两组患者治疗前后的血尿素氮(BUN)、血肌酐(Cr)、胱抑素C(Cysc),以及CVVH 治疗时间、呼吸机使用时间、ICU 住院时间等指标进行比较.结果 两组患者经过CVVH 治疗后,BUN、Cr、Cysc 等指标均明显改善,两组间差异无统计学意义(P>0.05);A 组的CVVH 治疗时间、呼吸机使用时间、ICU 住院时间较B 组患者短,死亡率亦较B 组低,两组间比较差异有统计学意义(P<0.01).结论 CVVH 是治疗心脏术后急性肾功能衰竭的有效方法.及时诊断,尽早(出现少尿4 h 内)行CVVH 治疗,可明显加快ARF 患者肾功能恢复,减少并发症,减少住院时间,降低死亡率.     

End-stage renal failure patients requiring renal replacement therapy in the intensive care unit: incidence,clinical features,and outcome

AIMS: To study incidence, clinical features, and outcome of critically ill patients with end-stage renal failure (ESRF) requiring renal replacement therapy (RRT) in the intensive care unit (ICU) and to test the validity of severity scoring systems for these patients. METHODS: Data for ESRF patients treated with RRT were collected from 81 Australian adult ICUs providing RRT. They were compared with matched controls with acute renal failure. RESULTS: Thirty-eight ESRF patients received RRT in the ICU over 3 months. The mean APACHE II score was 21.8 (predicted mortality: 37%) and the SAPS II score 44.7 (predicted mortality: 37%). The hospital mortality was 34%. Receiver operating characteristic curves showed good discrimination ability for hospital mortality for these two scores (AUC: 0.81 for APACHE II and 0.84 for SAPS II). Using admission diagnosis and SAPS II scores, 32 ESRF patients treated with continuous RRT (CRRT) were matched to 32 acute renal failure patients also treated with CRRT. ICU mortality (22 vs. 38%) and hospital mortality (38 vs. 38%) were comparable between the two groups. CONCLUSIONS: ESRF patients requiring RRT in the ICU were relatively frequent. Severity scores could be used to predict the hospital outcome for these patients. Their mortality, when treated with CRRT, was similar to that of diagnosis- and severity-score-matched patients with acute renal failure.     

Common places on clinical management of acute renal failure

Acute renal failure (ARF) is an abrupt decline of renal function, and acute tubular necrosis (ATN) is its more frequent expression. Recent contributions in physiopathological knowledge, specially in post-ischemic ARF, are scarcelly reflected in therapy. Morbidity and mortality due to ARF are very high, mainly in critically ill patients. Prevention and treatment of ATN are based in avoiding nephrotoxicity and renal ischemia. An adequate evaluation of renal risk factors in hospitalized patients is important. Maintaining euvolemia, effective cardiac output and adequate renal perfussion pressure are three paramount factors in ischemia prevention. The best dialytic schedule is not universally accepted. ARF replacement therapy must be flexible, tailoring techniques (IHD, SLED, CRRT) to the clinical situation of patients. There is not a consensus in dialysis dose in ARF. Nevertheless, despite a robust scientific evidence is lacking, some data suggest that a delivered minimum dose of sKtV >1 in IHD or >35 ml/kg/h in CRRT would be beneficial for patient survival.     

Una visión nefrológica del tratamiento sustitutivo renal en el paciente crítico con fracaso renal agudo: horizonte 2020

Renal replacement therapies (RRT) as support for acute kidney injury in critically ill patients have become a routine and essential practice in their management, resulting in the widespread use of various techniques among these patients, such as intermittent hemodialysis (IHD), extended hemodialysis and continuous RRT (CRRT).In this review we aim to summarize current evidence of indication, choice of modality, timing of initiation, dosing and technical aspects of RRT. We carried out a narrative review based on guidelines, consensus documents by main working groups and the latest relevant clinical trials on RRT in the critically ill.We did not find enough evidence of any RRT modality having superior benefits in terms of patient survival, length of intensive care unit/hospital stay or renal outcomes among critically ill patients, in spite of optimization of clinical indication, modality, timing of initiation and intensity of initial therapy. This is still a controverted matter, since only early start of high-flux CRRT has been proven beneficial over IHD among hemodynamically unstable postoperative patients.Our objective is to portrait current RRT practices in multidisciplinary management of critically ill patients by intensive care and nephrology professionals. Implication of a nephrologist in the assessment of hemodynamic status, coexisting medical conditions, renal outcome expectations and management of resources could potentially have benefits at the time of RRT selection and troubleshooting.     

Acute renal failure in patients with hematologic neoplasms

The retrospective study of acute renal failure (ARF) in patients with hematologic neoplasms was carried out. ARF occurred in 32 (6.1%) of 526 patients with hematologic neoplasms. Twenty-one (66%) patients recovered from ARF, but only 7 (22%) survived and were discharged from the hospital and 25 (78%) died of ARF or other complications. In 17 patients with leukemia or malignant histiocytosis, sepsis and/or disseminated intravascular coagulation were the most common causes of ARF, and all 17 patients died. In 11 patients with multiple myeloma, ARF was always attributable to the underlying disease, and the clinical course improved with the initiation of blood purification therapy (hemodialysis, plasma exchange) and chemotherapy. Five patients in blast crisis of chronic myelogenous leukemia or non-Hodgkin's lymphoma developed ARF as a result of tumor lysis syndrome. In this group, renal function improved with hemodialysis but only 2 patients survived. Patients with oliguria had worse outcomes than those without oliguria. Survival appeared to depend not on renal function but on the underlying disease, the cause of ARF, and other complications. These findings suggest that, in patients with hematologic neoplasms complicated by ARF, early initiation of blood purification therapy will improve the prognosis.     

Partial blood recirculation: a new trial for prolonging filter life during continuous hemodiafiltration

Although continuous hemodiafiltration (CHDF) has been widely accepted in the management of complicated acute renal failure, the requirement for prolonged continuous systemic anticoagulation appears to be a major drawback. We herein describe the case of a patient who developed postoperative multiple organ failure and received CHDF therapy with partial blood recirculation (PBR). PBR is a mode of extracorporeal circulation used as an anticoagulation modality. The technique accelerates the blood flow rate with the goal of extending filter life, and it was performed because the filter life had been significantly shortened (10.5 +/- 5.1 h) during the CHDF process in this case. Despite increasing the dose of the anticoagulant, changing the hemofilter and changing the mode from postdilution to predilution, we did not obtain amelioration of filter life. The filter life was significantly improved (41.5 +/- 1.4 h) when we performed PBR. It is difficult to minimize the bleeding risk and maintain filter life during CHDF. Our success in prolonging the filter life during this case therefore suggests that PBR might resolve one of the main problems related to CHDF, although more study is needed to clarify the advantages of this system.