Regional filter heparinization for continuous veno-venous hemofiltration in liver transplant recipients

AIM: To study safety, clinical and operative feasibility of continuous veno-venous hemofiltration (CVVH) with anticoagulation only of the filter in patients at risk for bleeding. METHODS: This prospective, comparative, non randomised study was completed at an intensive care unit of a teaching NHS hospital. Sixteen liver transplant (LT) recipients with acute renal failure needing CVVH were treated with a regional anticoagulation protocol (heparin and protamine were administered respectively pre- and post-filter) and compared to 11 critically ill subjects who received a standard low-heparin treatment. Activated coagulation time (ACT) monitoring was used to adjust anticoagulation and heparin neutralization. RESULTS: Mean circuit life was 35.8+/-13.6 hours (95% CI 28.5-43.1) in patients receiving regional anticoagulation and 34.4+/-14 hours in controls (95% CI 25.5-43.3; p=0.7). Fourty-eight circuits (47.5% of the total) in the heparin-protamine group had a life-span longer than 30 hours and other 22 (21.7%) were changed intentionally after 24 hours of use in absence of clots. None of the patients in both the studied groups had bleeding or hemodynamic complications and their azotemic control was always satisfactory. CONCLUSION: In LT recipients, regional anticoagulation can achieve a circuits life-span comparable to that from systemic anticoagulation with satisfactory safety and simplicity of use.     

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.     

Rapid removal of vancomycin by continuous veno-venous hemofiltration

We describe a 14-year-old girl with staphylococcal (coagulase-negative) ventriculo-peritoneal shunt infection, who developed oliguric acute renal failure and was found to have a serum vancomycin concentration of 250 microg/ml. Since only about 10%-50% of vancomycin is bound to protein in blood, we employed continuous veno-venous hemofiltration (CVVH) with a high ultrafiltration rate (1,800 ml/h) for increased convective clearance to remove vancomycin, which may have contributed to the acute renal failure. At the end of 38 h of CVVH, the vancomycin concentration had decreased in an exponential manner to 27 microg/ml. Over the subsequent 3-4 days, her renal function improved and the vancomycin concentration decreased further to <5 microg/ml. In conclusion, we believe that a high serum vancomycin concentration may be nephrotoxic and demonstrate that CVVH can be used effectively to remove vancomycin in children with acute renal failure.     

Prevention of tumor lysis syndrome using continuous veno-venous hemofiltration

Tumor lysis syndrome (TLS) and renal failure remain significant causes of morbidity and mortality in children with newly diagnosed Burkitt's lymphoma and high white blood cell count acute lymphocytic leukemia (ALL) despite conventional management with aggressive hydration, alkalinization, allopurinol, and the slow introduction of chemotherapy. A subgroup of patients at very high risk for TLS and renal failure can be identified based on the level of serum lactate dehydrogenase (LDH) and urine output. We evaluated the prospective use of continous veno-venous hemofiltration (CVVH), in addition to conventional management to prevent renal failure from tumor lysis, in three children with advanced abdominal Burkitt's lymphoma and in two children with high white blood cell count T-cel ALL who were at very high risk based on LDH and urine output. In this cohort of very highrisk patients, the LDH ratio (value at diagnosis/upper limit of normal) ranged from 0.88 to 10.3 and urine output from 0.13 to 4.7 ml/kg per hour. CVVH was begun at a mean time of 10.5 h before chemotherapy was initiated. Full-dose induction chemotherapy was begun within 24 h of diagnosis. After beginning CVVH, the uric acid levels decreased 46% prior to beginning chemotherapy and decreased to a mean of 4.2 mg/dl 24 h after chemotherapy was initiated. Four of the five patients had either no change or a drop in the serum creatinine. In patient one, blood urea nitrogen peaked at 58 mg/dl, and the creatinine at 4.7 mg/dl 6 days after beginning chemotherapy with a subsequent return to normal. Asymptomatic hypokalemia developed in all patients. After beginning chemotherapy, CVVH was continued for a mean of 85 h (range 70–91 h). No patient had complications secondary to CVVH. In summary, CVVH prevented renal failure secondary to TLS in 80% of these very high-risk patients. In the fifth patient, CVVH allowed full-dose chemotherapy to continue. The prospective use of CVVH could potentially decrease the morbidity and mortality associated with induction chemotherapy in very high-risk patients with a large tumor burden.     

连续性静脉-静脉血液滤过对内毒素休克羊血液动力学和炎性介质的影响

目的观察连续性静脉.静脉血液滤过(CVVH)对内毒素休克血液动力学和炎性介质的影响。方法 雄性绵羊12只,随机分为两组。对照组(A组,n=6),内毒素以1 mg·kg-1静脉泵注,30min内完成,同时静脉输注林格液15 ml·kg-1·h-1,持续6 h;血滤组(B组,n=6),于开始泵注内毒素后1 h给予CVVH治疗5 h,其余处理同A组。所有动物均给予气管插管、镇静、肌松、控制呼吸,行有创血液动力学监测;两组分别于内毒素泵注前(T0)、开始泵注后30、60、90、120、210、360 min(T1～T6)采静脉血及超滤液4ml,测定血浆及超滤液中内毒素、TNF-α、IL-6、IL-10的浓度。结果 血滤组CVVH治疗后(T1-T6)平均动脉压及体循环阻力指数明显上升、心率显著性下降。TNF-α于泵注内毒素后(T1-T6)两组均显著性增高,血滤组于CVVH治疗60 min(T4)时较治疗前(T2)虽无明显改变,但明显低于同时点对照组(P<0.01),CVVH治疗150～300 min(T5-T6)时TNF-α浓度较对照组及治疗前(T2)均显著性降低(P<0.05);IL-10虽呈增高趋势,但较治疗前和对照组无显著性变化;而两组IL-6水平则无明显差异。超滤液中可检测到TNF-α、IL-6、IL-10。结论 血滤治疗有利于纠正促炎细胞因子过度释放和抗炎细胞因子失衡,改善内毒素休克血液动力学。     

Dosage adjustment of drugs during continuous hemofiltration. Results and practical consequences of a prospective clinical study

In 43 ICU patients undergoing continuous volume constant hemofiltration (CVHF), the pharmacokinetics of 12 drugs were investigated to ensure correct dosage adjustments. Under conditions of CVHF, maximum doses were defined for cefotaxime, ceftazidime, digoxin, digitoxin, imipenem, metronidazole++, netilmicin, phenobarbital, phenytoin, theophylline, tobramycin, and vancomycin. For the estimation of sufficient doses without blood level measurements, sieving coefficients (S) were calculated by a new method. In addition, S was integrated as a CVHF-specific factor into a common equation for drug dose adjustment in patients with renal insufficiency. The regression of dosage received from kinetics on blood-level-independent equation adjustment was r = 0.9923. Since the volumes of distribution in ICU patients are variable, it is suggested that further drug monitoring is necessary for toxic drugs.     

Early and intensive continuous veno-venous hemofiltration for acute renal failure after cardiac surgery

Various forms of renal replacement therapies are available to treat acute renal failure (ARF) after cardiac surgery. The objective of this study was to assess the incidence of ARF developing postoperatively necessitating continuous veno-venous hemofiltration (CVVH) in adult patients requiring cardiopulmonary bypass (CPB), to determine the factors which influence the outcome in these patients and to assess the outcome following the use of early and intensive CVVH. During the study period, i.e. August 2000 to July 2002, 2355 adult patients underwent surgery under CPB, of whom 159 (6.7%) developed renal failure (creatinine >200 micromol/l) and 116 (5%) needed CVVH. Patients excluded were those who died within 24 h and those who underwent coronary artery bypass grafting without utilising CPB, thoracoabdominal aneurysm operations and pericardial surgery. Average age, Parsonnet score and Euroscore in the study population were 69.9 years, 21 and 7.70, respectively. Of the 116, 45 died in the intensive care unit (38.8% mortality). Relatively more non-survivors suffered from diabetes and preoperative renal dysfunction (P<0.05). Adverse outcome was also more likely if patient suffered from postoperative cardiac failure or had gastrointestinal complications or had more than two organ systems failing (P<0.05). Mortality was 100% if hepatic failure ensued.     

Hyperphosphatemia in tumor lysis syndrome: the role of hemodialysis and continuous veno-venous hemofiltration

We report a 4-year-old boy who developed tumor lysis syndrome complicated by severe hyperphosphatemia and acute renal failure, following chemotherapy for T-cell acute lymphoblastic leukemia. Despite successful treatment of hyperphosphatemia with hemodialysis, there was an immediate rebound in the high serum phosphorus level. The patient underwent a second treatment with hemodialysis which was then followed by continuous veno-venous hemofiltration (CVVH). CVVH maintained his serum phosphorus at a stable level until his renal function improved. CVVH can be used in conjunction with hemodialysis to successfully treat the hyperphosphatemia associated with tumor lysis syndrome.     

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.     

连续性静脉-静脉血液滤过对全身炎症反应综合征患者白蛋白代谢率的影响

目的 探讨连续性静脉-静脉血液滤过（CVVH）对全身炎症反应综合征（SIRS）患者Alb代谢率的影响.方法 回顾性分析2010年12月至2011年12月南京军区南京总医院收治的28例SIRS患者的临床资料.其中8例患者仅常规抗感染、对症治疗（对照组）;10例患者行血液滤过治疗,血液滤过置换量为2 000 mL/h（低容量组）;10例患者行血液滤过治疗,血液滤过置换量为4 000 mL/h（高容量组）.采用稳定性同位素示踪技术,向患者同时静脉输注两种稳定性同位素标记的苯丙氨酸：[1-13C]苯丙氨酸和d5-苯丙氨酸.采用气相色谱质谱联用仪的选择离子检测模式检测质荷比为192、194、197、218和219片段的峰面积.采用数学模型计算Alb合成率（FSR）和分解率（FBR）.多组比较采用单因素方差分析,组间比较采用LSD或Dunnett＇s T3检验.结果 对照组、低容量组和高容量组患者治疗前Alb FSR分别为5.8％±0.9％、5.7％±1.1％、5.7％±1.0％,3组比较,差异无统计学意义（F=0.04,P＞0.05）;治疗后Alb FSR分别为5.9％±0.8％、7.3％±0.9％、7.8％±1.1％,3组比较,差异有统计学意义（F=9.15,P＜0.05）.治疗后低容量组和高容量组患者Alb FSR均显著高于对照组患者（=3.40,3.96,P＜0.05）;低容量组和高容量组患者Alb FSR比较,差异无统计学意义（t=1.02,P＞0.05）.对照组、低容量组和高容量组患者治疗前Alb FBR分别为7.0％±1.2％、6.5％±0.9％、7.2％±1.2％,3组比较,差异无统计学意义（F =0.88,P＞0.05）;治疗后3组患者Alb FBR分别为6.9％±1.1％、6.2％±0.9％、7.4％±1.0％,3组比较,差异无统计学意义（F=2.82,P＞0.05）.结论 CVVH可调节SIRS患者蛋白代谢,能够提高Alb FSR,但不能降低Alb FBR.     

无肝素连续性静脉-静脉血液滤过在高危出血患者中的应用

目的探讨对高危出血倾向患者行无肝素连续性静脉-静脉血液滤过（CVVH）治疗的可能性。方法37例患者共行CVVH治疗75例次,分为观察组和对照组。观察组43例次,有高危出血倾向,采用无肝素抗凝;对照组32例次,采用低分子量肝素钙抗凝。回顾性分析2组相关临床指标。结果2组治疗后血肌酐（SCr）、尿素氮（BUN）均降低,差异有统计学意义（P〈0．05）,2组SCr、BUN下降率均无统计学差异（P〉O．05）;观察组治疗前、后凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）差异无统计学意义（P〉0．05）,对照组治疗后PT、APTT较治疗前延长,差异有统计学意义（P〈0．05）;观察组有凝血功能障碍的患者管路和滤器使用寿命与对照组无统计学差异（P〉0．05）,观察组无凝血功能障碍的患者管路和滤器使用寿命短于对照组,差异有统计学意义（P〈0．01）。结论无肝素抗凝技术用于高危出血倾向患者的CVVH治疗疗效肯定,并无增加出血的风险。     

The impact of long-term haemofiltration (continuous veno-venous haemofiltration) on cell-mediated immunity during endotoxaemia

BACKGROUND: Increased survival with high-volume continuous veno-venous haemofiltration (CVVH) has been demonstrated in critically ill patients. This may be the result of intensified blood purification or an effect on the immune system. We hypothesized that CVVH modifies the cell-mediated immunity. We investigated the effect of high-volume CVVH for 24 h on the cell-mediated immunity following endotoxin infusion. METHODS: Thirty pigs were divided into three groups. Ten pigs received 30 microg/kg of Escherichia coli endotoxin. These pigs were treated with CVVH (replacement 35 ml/kg/h) over the following 24 h. Ten pigs received the same bolus of endotoxin and ten pigs served as a control group. The adhesion molecules CD18, CD44 and CD62L and the ability to respond with an oxidative burst were measured. The number of neutrophils was counted in blood and lung tissue. The lymphoproliferative response and cytokines interleukin-6 and interleukin-10 were measured. RESULTS: The infusion of endotoxin was followed by initial granulocytopenia and, later, granulocytosis, activation of CD18 and CD62L, and increased oxidative burst. The cytokine level was increased. CVVH had no effect on the adhesion molecules or cytokine level and did not reduce the number of granulocytes in the lung significantly. CVVH, however, reduced the oxidative burst activity of neutrophils after 2 h of treatment. CONCLUSION: In the first few hours after endotoxaemia, high-volume CVVH reduced the oxidative burst activity of neutrophils. However, in the long term, CVVH was unable to modify the endotoxin-induced changes in cell-mediated immunity.     

Acid-base balance and substitution fluid during continuous hemofiltration

Critically ill patients with acute renal failure usually present with an unstable acid-base balance, often leading to cardiovascular complications and multi-organ failure. Therefore, to prevent metabolic acidosis, acid-base balance must be normalized and maintained; these patients are primarily treated with continuous hemofiltration techniques using different replacement fluids to influence the acid-base values. Dialysate solutions can be an acetate-based, lactate-based, citrate-based or bicarbonate-based buffer. This article discusses the strengths and weaknesses of each type of hemofiltration replacement fluid.     

19例原位肝移植术中凝血弹性图变化及与ACT相关性的临床研究

目的 探讨国人原位肝移植术中凝血弹性图（TEG）的变化及其与激活全血凝块形成时间（ACT）的相关性。方法 19例病人分为急性肝衰组（8例）与肝肿瘤组（11例）,接受原位肝移植术,无肝期采用体外静脉－静脉转流。两组病人分别于术前、无肝前（手术开始后120min,I 120)、无肝的30min（Ⅱ 30）、新肝前5min（Ⅲ－5）、新肝后5min（Ⅲ＋5）、30min（Ⅲ＋30）、60min（Ⅲ＋60）、120min（Ⅲ＋120）,8个时间点,分别观察硅燥土激活的全血TEG及ACT的变化。19例病人中有6例于新肝后5min同时观察肝素酶修正后的TEG与非肝素酶修正后的TEG及ACT的变化。结果 肝衰组TEG值（r、r k、αlpha角或α、MA）的变化主要在Ⅱ＋30min、Ⅲ－5min、Ⅲ＋5min,肝肿瘤组TEG值（r、r k、αMA）的变化均在新肝后5min、30min、60min。与术前值相比,两组TEG值的表现为r与r k延长,α与MA减小（P＜0．05、0．01）。相关研究表明,两组r k与ACT均呈正相关（r分别为0．743及0．634,P＜0．01）。其中6例于新肝后5min,有肝素酶与无肝毒酶的全血TEG值差异亦显著（P＜0．01）,后者经静注鱼精蛋白50－75mg后,两组TEG值差异无统计学意义（P＞0．05）。结论 TEG提示原位肝移植术中的凝血紊乱主要发生在无肝期及新肝早期,TEG指标r k与ACT有相关性。肝素酶修正后的全血TEG可提示新肝期体内存在肝素化效应,需用鱼精蛋白拮抗。     

Perioperative changes of blood coagulability evaluated by thromboelastography (TEG) in patients undergoing total knee and total hip arthroplasty

BACKGROUND : A large number of studies have examined the incidence of thromboembolic complications after orthopedic surgery of the lower extremity. We investigated the perioperative changes of coagulability following total knee arthroplasty (TKA) or total hip arthroplasty (THA) using thromboelastography (TEG), which could comprehensively assess the coagulation and fibrinolytic system. METHODS : Thirty patients scheduled for TKA (n= 10), THA (n= 10) and other lower extremity orthopedic surgery (control, n= 10) were studied. TEG was analyzed with K-value, MA-value and coagulation index (CI) before induction of anesthesia and 24 hours after surgery. RESULTS : K-values decreased significantly after TKA and THA compared with the values before the induction of anesthesia. MA-values and CI increased significantly after TKA and THA compared with the values before the induction. There were no significant changes in K-value, MA-value and CI in the control group during the perioperative period. CONCLUSIONS : The results suggest that TKA and THA lead blood coagulation to hypercoagulable state at the early postoperative stage.