I. Baldwin

Myoglobin clearance by super high-flux hemofiltration in a case of severe rhabdomyolysis: a case report

ObjectiveTo test the ability of a novel super high-flux (SHF) membrane with a larger pore size to clear myoglobin from serum.SettingThe intensive care unit of a university teaching hospital.SubjectA patient with serotonin syndrome complicated by severe rhabodomyolysis and oliguric acute renal failureMethodInitially continuous veno-venous hemofiltration was performed at 2 l/hour ultrafiltration (UF) with a standard polysulphone 1.4 m2 membrane (cutoff point, 20 kDa), followed by continuous veno-venous hemofiltration with a SHF membrane (cutoff point, 100 kDa) at 2 l/hour UF, then at 3 l/hour UF and then at 4 l/hour UF, in an attempt to clear myoglobin.ResultsThe myoglobin concentration in the ultrafiltrate at 2 l/hour exchange was at least five times greater with the SHF membrane than with the conventional membrane (>100,000 μg/l versus 23,003 μg/l). The sieving coefficients with the SHF membrane at 3 l/hour UF and 4 l/hour UF were 72.2% and 68.8%, respectively. The amount of myoglobin removed with the conventional membrane was 1.1 g/day compared with 4.4–5.1 g/day for the SHF membrane. The SHF membrane achieved a clearance of up to 56.4 l/day, and achieved a reduction in serum myoglobin concentration from >100,000 μg/l to 16,542 μg/l in 48 hours.ConclusionsSHF hemofiltration achieved a much greater clearance of myoglobin than conventional hemofiltration, and it may provide a potential modality for the treatment of myoglobinuric acute renal failure.

High cut-off point membranes in septic acute renal failure: a systematic review.

Objectives To review the literature on the experimental, physiological and clinical effects of blood purification with high cut-off (HCO) point membranes in septic acute renal failure (ARF). Study Design MEDLINE and PubMed database search combining relevant terms and integrating data from studies on the use of HCO membranes. Setting and Population Ex vivo studies of endotoxemia, animal studies of bacteremia and clinical studies using HCO membranes in patients with septic ARF. Selection Criteria for Studies: Original data from primary publications. Interventions: HCO membrane-based hemodialysis, hemodiafiltration or hemofiltration. Outcomes: Plasma cytokine clearance, immunological and physiological effects and safety parameters of HCO membranes. Results HCO membranes effectively remove cytokines from blood. Treatment using HCO membranes has beneficial effects on immune cell function and increases survival in animal models of sepsis. Preliminary clinical studies show that HCO membranes decrease plasma cytokine levels and the need for vasopressor therapy. HCO membrane-based blood purification has now been applied in four pilot randomized controlled studies of 70 patients with septic ARF with no reports of serious adverse effects. Limitations Because of substantial heterogeneity, no formal quantitative analysis could be performed. Conclusions The available evidence on HCO blood purification justifies larger randomized controlled trials in patients with septic ARF.

Extracorporeal Blood Purification Therapy for Sepsis and Systemic Inflammation: Its Biological Rationale

EBPTs represent a promising new approach to the adjuvant treatment of severe sepsis, septic shock and MODS. Their technology is rapidly evolving and pilot animal and human studies are now taking place to prepare the territory for the first large randomized controlled trial. The rationale for EBPT is reasonable and the initial data are encouraging. The correct technology and molecular targeting, however, are still being explored. Once the best technology has been determined, it is likely that phase II and phase III trials will be performed to test the hypothesis that these therapies can indeed alter mortality in severe inflammatory multiorgan dysfunction.

Beta2-microglobulin removal and plasma albumin levels with high cut-off hemodialysis.

Purpose. β2-microglobulin (β2MG) is pivotal to the pathogenesis of dialysis-related amyloidosis. We compared the effects of high cut-off hemodialysis (HCO-HD) with those of standard high-flux hemodialysis (HF-HD) regarding the concentration and clearance of β2MG and albumin. Design. We enrolled ten patients with acute renal failure in a double-blind, cross-over, randomized controlled trial. Procedures Each patient received four hours of HCO-HD (estimated in vivo cutoff 50–60 kDa) and four hours of HF-HD (estimated in vivo cutoff 15–20 kDa) in random order. Statistical methods and outcome measures: As data lacked normal distribution, we used non-parametric statistical analysis. Plasma and dialysate concentrations of β2MG and albumin were measured at baseline and after four hours of each study treatment. Main findings. We found significantly greater diffusive β2MG clearances for HCO-HD compared to HF-HD (at the start: 71.8 ml/min vs. 5.1 ml/min; P=0.008 and at the end: 68.8 ml/min vs. 5.7 ml/min; P=0.008). We found a reduction in plasma β2MG concentrations of -31.6% during HCO-HD compared to an increase by 25.7% during HF-HD; P=0.008. At baseline (HCO-HD: 26.0 g/L vs. HF-HD: 26.5 g/L), and at the end of both treatments, plasma albumin concentrations were comparable (HCO-HD: 25.5 g/L vs. HF-HD: 26.5 g/L; P=0.25). During HCO-HD, albumin clearance was 1.9 ml/min at the start and decreased significantly to 0.8 ml/min at the end; P=0.008. HF-HD had an albumin clearance of 0.01 ml/min. Conclusions. HCO-HD was more effective in decreasing plasma β2MG concentrations than standard HF-HD and did not reduce plasma albumin levels. Further studies of HCO-HD in the treatment of dialysis-related β2MG accumulation appear warranted. (ClinicalTrials.gov number, NCT00333593 [ClinicalTrials.gov]) (Int J Artif Organs 2007; 30: 385–92)

Low-dose citrate continuous veno-venous hemofiltration (CVVH) and acid-base balance.

Objective To evaluate the acid-base effect of low-dose regional citrate anticoagulation (RCA) during continuous veno-venous hemofiltration (CVVH). Design Prospective observational study. Setting ICUs of tertiary public and private hospitals. Subjects Thirty critically ill patients with acute renal failure at risk of bleeding or with a major contraindication to heparin-CVVH and/or short filter life. Methods We used a commercial citrate-based fluid (11 mmol/L, sodium: 140 mmol/L, chloride: 108 mmol/L and 1 mol/L of potassium) as pre-dilution replacement fluid during CVVH. Further potassium was added according to serum potassium levels. We measured all relevant variables for acid-base analysis according to the Stewart-Figge methodology. Results Before treatment, study patients had a slight metabolic acidosis, which worsened over 6 hours of RCA-CVVH (pH from 7.39 to 7.38, p<0.005; bicarbonate from 23.2 to 21.6 mmol/L, p<0.0001 and base excess from −2.0 to −3.0 mEq/L, p<0.0001) due to a significant increase in SIG (from 5.8 to 6.6 mEq/L, p<0.05) and a decrease in SIDa (from 37.5 to 36.6 mEq/L, p<0.05). These acidifying effects were attenuated by hypoalbuminemia and a decrease in lactate (from 1.48 to 1.34 mmol/L, p<0.005) and did not lead to progressive acidosis. On cessation of treatment, this acidifying effect rapidly self-corrected within six hours. Conclusions Low dose RCA-CVVH induces a mild acidosis secondary to an increased strong ion gap and decreased SIDa which fully self-corrects at cessation of therapy. Clinicians need to be aware of these effects to correctly interpret changes in acid-base status in such patients.

Beta2-microglobulin clearance with super high flux hemodialysis: an ex vivo study.

Background ß2m accumulation induces disease in patients with end-stage renal failure (ESRF). Thus, its removal from patients with ESRF appears desirable. Current dialysis technology, however, has limited effectiveness. Aims To measure ß2m clearance with a novel super high flux membrane. Design Ex vivo experimental study. Setting Intensive Care Laboratory of Tertiary institution. Subjects Six volunteers. Measurements and Results At a blood flow of 300 ml/min, the clearance of ß2-MG increased from 113.5 ± 38.5 ml/min with a dialysate flow rate of 200 ml/min to 184.8 ± 61.1 ml/min with a flow rate of 300 ml/min and 195.0 ± 60.0 ml/min with a 500 ml/min flow rate. The clearance of albumin was 4.5 ml/min with a dialysate flow rate of 200 ml/min, 5.2 ml/min for a flow rate of 300 ml/min and 5.8 ml/min for a flow rate of 500 ml/min. Conclusions High levels of ß2m clearance can be achieved with a super high flux membrane while albumin losses remain limited

High-volume hemofiltration.

The use of continuous hemofiltration has increased dramatically since its first description in 1977. It is now the dominant form of renal replacement therapy in Australia and is fast reaching a similar status in many European countries. Its growing use and the frequent observation of its beneficial effects in septic patients has directed the attention of researchers toward its application in the field of blood purification for sepsis. In this context, experimental studies have suggested that increasing the volume of ultrafiltrate produced may increase the beneficial effects of continuous hemofiltration. This so-called high-volume hemofiltration (HVHF) has now been demonstrated to have striking beneficial effects on hemodynamics in porcine septic shock. It has also been shown to attenuate gastrointestinal mucosal reperfusion injury in a model of gut ischemia. Furthermore, the infusion of ultrafiltrate obtained during HVHF into healthy pigs induces profound hypotension and myocardial depression, suggesting that vasodilatory and myocardial depressant substances may be removed during the procedure. Such animal experiments have led clinicians to conduct their first interventions with HVHF in humans with the multi-organ dysfunction syndrome and septic shock. The initial results are promising. They open up a new area for the investigation of HVHF as an adjuvant therapy in the management of severe sepsis, septic shock, and the multi-organ dysfunction syndrome.

An ex-vivo evaluation of vascular catheters for continuous hemofiltration.

Objectives: To measure outflow and inflow hydraulic resistance in double-lumen catheters used for hemofiltration under standardized laboratory conditions. Setting: ICU Laboratory of tertiary unit. Methods: Heparinized spent red cells diluted in polygeline solution to a constant hematocrit of 32% at 37°C were pumped using a standard Prisma M60 circuit through several hemofiltration catheters. Blood pump speed was increased and decreased in steps of 30 mL/min (30, 60, 90, 120, 150, and 180 mL/min) and catheter outflow and inflow pressures recorded and used to define the pressure flow relationship (line of hydraulic resistance) for each. Results: Double-lumen catheters posed different resistances to outflow or inflow. Among the <15 cm long catheters, the 11.5 Fr Quinton-Mahurkar (0.56 mmHg/mL/min) catheter offered the least resistance to outflow, while the Medcomp 11.5 Fr catheter offered the least resistance to inflow (0.78 mmHg/mL/min). Among the >19 cm long catheters, the 13.5 Fr Vascath Niagara catheter showed the lowest blood flow resistance to both outflow (0.63 mmHg/mL/min) and inflow (0.83 mmHg/mL/min). Longer catheters did not pose statistically greater resistance to both outflow and inflow. Resistance to inflow was consistently greater than resistance to outflow (p = 0.003). Overall, the Prisma M60 blood circuit alone accounted for 40% of the total extracorporeal circuit blood flow resistance. Conclusions: Proprietary hemofiltration catheters have variable resistance to blood flow under standard ex-vivo conditions. This ex-vivo information might be useful to clinicians in guiding their choice of catheters for clinical use.