Operating characteristics of pediatric continuous arteriovenous hemofiltration in an animal model

Continuous arteriovenous hemofiltration (CAVH) is an increasingly popular technique in the care of critically ill children. The operating characteristics of the available circuits are largely unknown. Prior to introducing CAVH into our pediatric intensive care unit, we investigated the performance of three CAVH circuits: CAVH with postfilter dilution, CAVH with prefilter dilution (CAVH_pre) and CAVH with dialysis counterflow. Using a neonatal lamb model, we measured filter blood flow (Q_B), ultrafiltrate rate (Q_U), arterial, venous and ultrafiltrate compartment pressure, oncotic pressure, plus urea levels in blood and ultrafiltrate fluid for the three CAVH circuit designs. Transmembrane pressure and urea clearance were calculated for various values of Q_B after varying a clamp on the arterial side of the circuit. The major finding, applicable to all circuits, was the wide variability of Q_B. Constant attention was required in order to obtain a consistent Q_B. Fluid clearance was effective with all three circuits. Urea clearance averaged 5–10 ml/min and was principally dependent on Q_U and independent of Q_B. The addition of dialysis counterflow did not increase urea clearance. The most convenient circuit we tested was CAVH_pre, but the problem of unstable Q_B is common to all unpumped arteriovenous filtrate circuits. It is a major limiting factor in the practical application of this technology to critically ill children.     

联合血液滤过、腹腔镜等治疗急性重症胰腺炎

目的探讨联合血液滤过、腹腔镜下置管引流和丹参治疗急性重症胰腺炎（SAP）的价值。方法30例SAP患者分为两组，A组20例行常规治疗，同时施行血液滤过、腹腔镜下置管引流。应用施他宁和丹参等扩张胰腺微循环药物；B组10例仅采用常规治疗（支持治疗，应用抑制胰腺分泌药，如施他宁、胰酶抑制剂及抗生素等），分别观察TNF、IL-6、IL-8、Balthazar CT积分、APAC职Ⅱ积分。结果A组TNF、IL-6、IL-8、Balthazar CT积分、APACHEⅡ积分较B组显著降低（P〈0．05）。病死率A组为15％，B组为30％。结论联合血液滤过、腹腔镜等方法治疗SAP可提高SAP的治愈率。     

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目的　观察持续高流量血液滤过 (HVHF)对重症急性胰腺炎 (SAP)伴多器官功能障碍综合征(MODS)的治疗作用。方法　 1997～ 2 0 0 2年 2 8例SAP伴MODS接受了HVHF治疗。APACHEⅡ评分为(14 36± 3 96 )分 ,BalthazarCT评分为 (8 5± 1 4 )分。从发病到开始HVHF时间 (6 0± 6 1)d ,HVHF治疗时间为 (4 0 4± 3 99)d。置换液以前稀释方式输入 ,流量为 4 0 0 0mL/h ,血流量 2 5 0～ 30 0mL/min ,连续 2 4h不间断。滤器为AN6 9膜 ,面积 1 2m2 ,每 2 4h更换 1次。采用低分子肝素抗凝。结果　 2 8例病人中 ,2 0例治愈出院 ,2例因经济原因放弃治疗 ,6例死亡 (2 1 4 % )。HVHF后体温、心率和呼吸频率显著降低 ;APACHEⅡ评分显著下降(14 4± 3 9vs 9 9± 4 3,P <0 0 1) ;动脉血氧分压显著提高 (6 8 5± 19 5vs 91 9± 2 5 0 ,P <0 0 1)。所有病人均良好耐受HVHF治疗 ,HVHF过程中血流动力学稳定 ,未发现明显的副作用。结论　对SAP伴MODS的病人 ,HVHF明显改善体温、心率、呼吸频率、APACHEⅡ评分和动脉血氧分压。HVHF过程中血流动力学稳定 ,可能成为重要的辅助治疗措施。     

High Shear Rate Hemofiltration: Influence of Fiber Dimensions and Shear Rates

The variation of ultrafiltration flow rate (QF) at high transmembrane pressure with inlet wall shear rate (gamma w) was found to be proportional to gamma wn, with n ranging from 0.45 to 0.55, when gamma w increases up to 4,500 s-1. To test whether long filters operated at high shear rates were more efficient than shorter ones for the same inlet blood flow, we made experiments with 10- and 20-cm filters with same number of fibers (550) at various shear rates from 700 to 3,000 s-1. The filtration rates provided by the 20-cm filter were found to be 5-15% larger than those provided by two 10-cm filters arranged in parallel and 10-20% smaller than those provided by two 10-cm filters arranged in a series. The explanation lies in the rapid decay of QF with distance from the inlet due to the developing concentration boundary layer. When pulsations are imposed on the inlet blood flow, the filtration rate was seen to increase by 10-20%, and the effect of plugging was seen to decrease in small-area hemofilters.     

Hemofiltration in severe high microvascular permeability pulmonary edema secondary to rickettsial spotted fever

Two patients, affected by spotted fever, developed low pulmonary capillary wedge pressure (PCWP) pulmonary edema with severe hypoxemia. Conventional specific and supportive therapy, including mechanical ventilation, failed to induce significant respiratory and hemodynamic improvement which was dramatically reached by means of hemofiltration. Removal of circulating middle molecular weight peptides by the convective mass transfer, characteristic of hemofiltration, offers a new and effective therapeutic approach for the adult respiratory distress syndrome secondary to rickettsial diseases.     

Effect of Plasma Proteins on the Sieving Spectra of Hemofilters

qoffxture of neutral maltodextrins with a continuous molecular weight distribution from 340 to 120,000 daltons has been used alone or in the presence of plasma to determine solute rejection by four hemofilters and the effect of plasma on such rejection. High pressure liquid chromatographic analyses were utilized to establish concentration ratios of feed and filtrate solutions over a wide molecular weight range. At equal transmembrane velocities, the boundary layer-corrected rejection of each hemofilter was determined as a function of molecular weight. The presence of plasma increased rejection by the Amicon Diafilter 30, the Hospal RP-6, and the Gambro FH202 hemofilters , but the Fresenius D-6 was virtually unaffected.     

Plasma and tissue levels of neuropeptide y in experimental septic shock: relation to hemodynamics, inflammation, oxidative stress, and hemofiltration

Neuropeptide Y (NPY), a potent vasoconstrictor released from the sympathetic nerves, has been suggested to counterbalance sepsis-induced vasodilation. Thus, the changes in plasma and tissue NPY concentrations in relation to hemodynamic variables and inflammatory markers in a porcine model of moderate septic shock were investigated. Susceptibility of NPY to be removed by continuous hemofiltration in two settings has been also studied. Thirty-four domestic pigs were divided into five groups: (i) control group; (ii) control group with conventional hemofiltration; (iii) septic group; (iv) septic group with conventional hemofiltration; and (v) septic group with high-volume hemofiltration. Sepsis induced by fecal peritonitis continued for 22 h. Hemofiltration was applied for the last 10 h. Hemodynamic and inflammatory parameters (heart rate, mean arterial pressure, cardiac output, systemic vascular resistance, plasma concentrations of tumor necrosis factor-α, interleukin-6, and NPY) were measured before and at 12 and 22 h of peritonitis. NPY tissue levels were determined in the left ventricle and mesenteric and coronary arteries. Sepsis induced long-lasting increases in the systemic NPY levels without affecting its tissue concentrations. Continuous hemofiltration at any dose did not reduce sepsis-induced elevations in NPY plasma concentrations, nor did it affect the peptide tissue levels. The increases in NPY systemic levels were significantly correlated with changes in the systemic vascular resistance. The results support the hypothesis of NPY implication in the regulation of the vascular resistance under septic conditions and indicate that NPY clearance rate during hemofiltration does not exceed the capacity of perivascular nerves to release it.     

Norepinephrine and hospital mortality in critically ill patients undergoing continuous renal replacement therapy

High-dose vasopressor use is associated with increasing mortality in patients with septic shock. We conducted this study to determine if the high-dose of vasopressor used before the initiation of continuous renal replacement therapy (CRRT) is associated with increasing mortality in critically ill patients. We retrospectively reviewed all patients who underwent CRRT in the medical intensive care unit of China Medical University Hospital between 2003 and 2007. The association between mortality and highest vasopressors (dopamine and norepinephrine [NE]) dose used were analyzed using Kaplan-Meier analysis and multivariate Cox regression. A total of 279 patients (170 men and 109 women) treated with CRRT in medical intensive care were reviewed and 237 (84.9%) died. In Kaplan-Meier analysis with log-rank test, dopamine dose of ≥20 μg/kg/min and NE dose of ≥0.3 μg/kg/min were significantly linked to mortality (P = 0.007 and <0.001). In multivariate Cox proportional hazards regression, NE dose of ≥0.3 μg/kg/min, Acute Physiology and Chronic Health Evaluation II score, and low platelet count were independently linked to mortality. The hazard ratios and 95% confidence interval (CI) were 1.771 (95% CI: 1.247-2.516, P = 0.001), 1.035 (95% CI: 1.012-1.058, P = 0.003), and 0.997 (95% CI: 0.996-0.999, P = 0.003), respectively. Critically ill patients treated with very high dose of NE before the initiation of CRRT have a very high mortality rate regardless of the acute kidney injury stage.     

Experimental high-volume hemofiltration with predilutional tris-hydroxymethylaminomethane for correction of low tidal volume ventilation-induced acidosis

The most common method of controlling acidemia during lung‐protective ventilation is CO₂ removal with an extracorporeal lung assist (ECLA) system. Another possibility to prevent acidemia is based on intravenous (i.v.) application of tris‐hydroxymethyl‐aminomethane (3 mol/L, THAM) buffer, which can bind hydrogen protons and which can be removed from the body via renal replacement therapy (RRT). We investigated whether RRT combined with predilutional (prefilter) THAM‐application provides an alternative to ECLA for a rescue situation. For this, anesthetized pigs, 40 kg of body weight, six animals per group, underwent 5 h of acidemia (pH 7.19–7.24) induced by acid infusion and permissive hypercapnia (low tidal volume ventilation, PaCO₂ 80–90 mm Hg). Isovolemic, high‐volume hemofiltration (HVHF) was operated with predilutional THAM‐infusion for treatment. To evaluate adverse effects of this approach, we set up further groups: HVHF with postdilutional (post‐filter) THAM‐application; i.v.‐THAM without HVHF; normal pH homeostasis with HVHF. Acid‐base parameters, hemodynamics, renal function, and lung morphology were investigated. HVHF with predilutional THAM‐infusion of 8 mmol/kg/h allowed fast pH normalization, significant reduction in PaCO₂ to 56 mm Hg and tolerable hemodynamics. HVHF alone or lower dose i.v. THAM (2 mmol/kg/h) failed to produce a comparable result. A postdilutional THAM infusion reduced hemodynamic tolerability and increased lung edema formation. HVHF in pigs with normal acid‐base status resulted in a decreased base excess and urine acidification. In conclusion, predilutional THAM‐application and HVHF corrected the acid‐base disorder and improved pulmonary hemodynamics. Further studies are necessary to optimize the protocol including the dosage.     

A novel plasma filtration therapy for hepatic failure: preclinical studies

There is a need to develop artificial means of liver replacement and/or assistance with the aim of either supporting patients with borderline functional liver cell mass until their liver regenerates, or until a donor liver becomes available for transplantation. Selective plasma filtration is a novel approach to blood purification therapy designed to reduce the level of circulating toxins of hepatic and renal failure, mediators of inflammation and inhibitors of hepatic regeneration. The results of preclinical studies indicate that treatment of pigs with experimentally-induced fulminant hepatic failure is safe and effective in extending survival time and arresting brain swelling. In addition, the amount of ammonia, aromatic amino acids, IL6, TNFalpha and C3a removed during the 6-h treatment in the present study was higher by 34% to 175% than the total plasma content of those substances at the start of therapy.