Solute mass balance during isovolaemic high volume haemofiltration

Objective To evaluate the effect of changing the amount of pre-dilution replacement fluid on the sieving coefficient (SC) and mass transfer of small solutes during isovolaemic high-volume haemofiltration (HVHF).Design and setting Prospective interventional study in the intensive care unit of a tertiary university hospital.Patients Eight patients with septic shock.Interventions Isovolaemic HVHF (6 l/h of replacement fluid) was performed. The proportion of replacement fluid delivered in pre-filter was altered to progressively decrease it from 6 to 0 l/h. Samples were simultaneously taken from the "pre-filter", "post-filter" and ultrafiltrate (UF) sampling ports.Measurements and results Sodium, potassium, chloride, total calcium, total magnesium, phosphate, total CO₂, urea, creatinine and glucose concentrations were measured in each sample. The sieving coefficients of chloride, total CO₂, phosphate, urea and glucose were higher than 1 in most pre-dilution states. The sieving coefficients of sodium, potassium, calcium, magnesium, total CO₂ and urea decreased significantly with decreasing pre-dilution fluid rate. The sieving coefficients of chloride and glucose increased with decreasing pre-dilution fluid rate. There was a significant mass gain of sodium and glucose under all pre-dilution conditions. Mass chloride gains decreased with decreasing pre-dilution rates and changed into chloride loss during 6 l/h of post-dilution. Decreasing pre-dilution improved urea and creatinine mass removal.Conclusions Small solute SC and mass transfer during isovolaemic HVHF are significantly affected by the proportion of replacement fluid administered pre-filter. Isovolaemic HVHF is neither isonatraemic nor isochloraemic.     

Heparin versus citrate for anticoagulation in critically ill patients treated with continuous renal replacement therapy

Background: Continuous renal replacement therapy (CRRT) is commonly used in the care of critically ill patients ( Gabutti et al., 2002 ). Critical illness increases the likelihood to both coagulation and bleeding, making anticoagulation for CRRT problematic. Aims: This mini‐review aims to examine the evidence that compares the use of systemic heparin and regional citrate as forms of anticoagulation for CRRT in critically ill patients. The primary outcome of interest was haemofilter circuit survival, and the secondary outcome was reduced risk of bleeding. Search strategy: A systematic literature search was undertaken to identify all studies comparing these drugs. The Cochrane Library , Medline and Embase databases were searched. Eighty‐nine articles were found. Included studies were randomized controlled trials (RCTs), which used a target population of critically ill adults. Studies were excluded if they had not been written in English and if they were not available through King’s College London. After applying the inclusion and exclusion criteria, three RCTs comparing the use of systemic heparin and regional citrate were included in the review. Results: Two studies showed significant differences in circuit survival time, with citrate prolonging survival time. All studies showed an increased risk of bleeding in the heparin group, resulting in a higher rate of transfusion while heparin was being used. Conclusions: The studies examined lacked reference to the power of the studies and strength in the presentation of the results. Because of the lack of reliability in the studies, it would be suggested that further research is needed on this topic in order to produce rigorous high‐quality reviews with limited bias. The use of citrate, as with all treatments in clinical practice, should be used with caution and assessed on an individual patient basis. Reviewing this evidence helps to gain an insight into different treatment options available, identifying some of the risks and benefits.     

ON‐LINE TECHNIQUE FOR PRODUCING SUBSTITUTION FLUID IN HAEMODIAFILTRATION AND HAEMOFILTRATION

When the kidneys are not able to fulfil their task anymore the individual reaches a situation known as End‐Stage Renal Disease (ESRD). Haemodialysis may be carried out. In order to have a more efficient dialysis the treatment modes haemodiafiltration and haemofiltration are also in use. In these modes a substitution fluid is added to the bloodstream and continuously removed by the dialyser. However, these modes require large volumes of sterile fluids, 10 to 30 litres for haemodiafiltration and 70 ? 100 litres for haemofiltration. This fact has made these treatment modes expensive. The fluids have traditionally been produced by the pharmaceutical industry in five litre bags, but in bags not all solutions are stable or possible to produce, for instance when sodium bicarbonate is used as a buffer. Today sodium bicarbonate is the absolute predominant buffer. An alternative way of producing the fluids has to be found. In 1978 LW Henderson (1) described a technique using filtration to produce substitution fluid on‐line i.e. preparing the fluid directly on site and giving it to the patient. Since then work has taken place in order to construct a system that is able to both mix, sterilise and administrate the substitution fluid in haemodiafiltration and haemofiltration. This work has resulted in dialysis machines with the feature to fulfil the task of producing sterile substitution fluid. On‐line haemodiafiltration is carried out in dialysis clinics. There are approximately 65 in Sweden, 1000 in Germany, 900 in Italy, 600 in France and 2500 in the US. The number of dialysis patients is around 1.000.000 worldwide and the increase is around 7 ? 9% annually.     

The haemodynamic effects of intermittent haemofiltration in critically ill patients

The haemodynamic effects of intermittent high volume venovenous haemofiltration were studied in 13 critically ill patients. The mean negative fluid balance during filtration was 1.2l and the mean duration of treatment 3 h 40 min. The cardiac index fell initially (4.5±0.2 to 3.8±0.2l/min/m²;p<0.05) but then remained stable throughout treatment before returning to baseline at the end of haemofiltration. The mean arterial pressure was unchanged with an increase in the systemic vascular resistance (651±33 to 765±65 dyne·s/cm⁵;p<0.05) suggesting that vascular responsiveness is maintained during haemofiltration.     

Haemodynamic effects of arteriovenous and venovenous haemofiltration in piglets

The aim of this study was to compare the early haemodynamic effects of continuous arteriovenous haemofiltration (CAVH) with those of continuous venovenous haemofiltration(CVVH) in normal and endotoxic piglets, within the framework of a two-period cross-over trial. Sixteen domestic piglets (weight 6–18 kg) underwent 1 h of CAVH followed by 1 h of CVVH or 1 h of CVVH followed by 1 h of CAVH. Six were pre-treated with a graded endotoxin infusion to simulate clinical sepsis. The main measurements included: heart rate; mean arterial (MAP), pulmonary artery, central venous and pulmonary artery occlusion pressures; thermodilution cardiac output; and calculated systemic (SVRI) and pulmonary vascular resistance indexes. Each measurement was performed immediately before and 30 min after commencement of each technique of filtration. Commencement of haemofiltration in normal piglets caused minimal haemodynamic effects. In endotoxic piglets, commencement of filtration, whether CAVH or CVVH, caused a haemodynamic change which was significantly more pronounced in the first filter (SVRI –39%, MAP –32%) than the second filter (SVRI +22%, MAP +0.9%) (SVRI,P=0.01, first filter vs. second) (MAP,P=0.009 first filter vs. second). In conclusion, there were no significant differences between the early haemodynamic effects of CAVH and CVVH in normal or endotoxic piglets. The haemodynamic effects of either technique may become more significant in the presence of sepsis.     

Influence of continuous haemofiltration on haemodynamics and central blood volume in experimental endotoxic shock

In order to asses the influence of continuous haemofiltration (HF) on haemodynamics and central blood volume in endotoxic shock, endotoxinaemia was invoked in 20 swine (28–32 kg). 15 min after doubling the mean pulmonary pressure, the animals were randomly assigned to receive either a zero-balanced veno-venous HF with an ultrafiltration and replacement rate of 600 ml/h (HF group,n=10) or to observe the spontaneous course (E group,n=10) under a constant infusion of endotoxin for 4h. A trend to a higher survival rate in the HF group (6/10 vs. 3/10; group) during the observation period was evident, but not statistically significant. Early initiation of HF during endotoxic shock modifies the haemodynamic response, lowering the pulmonary artery pressure (PAP), PCWP, pulmonary (PVR) and systemic vascular resistance (SVR), compared to the spontaneous course, whereas the decrement of central blood volume was comparable in both groups. These changes cannot be explained by effects of the HF on the volume status, but supports and additional effect by the filtration of small and medium-sized molecules.     

Blood flow reductions during continuous renal replacement therapy and circuit life

Objective Reductions in blood flow rate may occur undetected during peristaltic pumping of blood through continuous renal replacement therapy circuits. We investigated whether undetected reductions in blood flow rate occur during continuous veno-venous haemofiltration, and whether they are correlated with filter life.Patients Twelve patients receiving continuous veno-venous haemofiltration in the intensive care unit of a tertiary hospital.Methods Extracorporeal circuit blood flow during haemofiltration was continuously monitored utilizing a miniature ultrasound Doppler device. Otherwise undetected blood flow reductions were identified at severity levels of between 20% and 100% less than the set diastolic flow rate (83 ml/min). Information on anticoagulation status was simultaneously obtained. The frequency and severity of blood flow reductions were recorded, and the correlation with filter life was determined.Measurements and results The duration of filter life ranged from 1.5 to 53 h, with a mean functional life of 19.62±16.32 h. There were 314 episodes of blood flow reduction during the 525 h of monitoring (0.59 episodes/h). There was a significant inverse relationship between the number of medium-level blood flow reductions and filter life. This correlation was much stronger than that between APTT and filter life.Conclusions Undetected blood flow reductions occur during continuous veno-venous haemofiltration. Such reductions are frequent, and when sufficiently severe appear to be correlated with filter life more strongly than the blood coagulation variables typically used to monitor adequacy of anticoagulation and promote filter longevity.     

Coupled plasma filtration adsorption

Background Severe sepsis and septic shock are perhaps the major cause of morbidity and mortality in Intensive Care. Their pathogenesis is only partly understood. Circulating peptides and lipid-derived substances (so-called mediators), however, appear to participate in the development of organ dysfunction. It might be possible to treat plasma in such a way that the injurious effect of mediators can be attenuated.Investigations Several ex vivo studies have shown that it is technically possible to adsorb mediators by means of specially developed sorbents. The application of these sorbents to the treatment of plasma in animals with experimental sepsis has shown that several markers of inflammation can be attenuated and that animal survival can be increased. We have recently transferred such technology to the treatment of human septic shock using a technique called Coupled Plasma Filtration Adsorption (CPFA). CPFA was found to attenuate the hypotension of septic shock and to dramatically alter the immuno-paralytic toxicity of septic plasma. Monocytes of patients treated with CPFA underwent a major improvement in their ability to respond to endotoxin.Conclusions CPFA represents a promising new approach to blood purification in sepsis. The findings associated with its application to humans highlight the importance of continuing to investigate blood purification as a possible approach to the treatment of septic shock, the potential usefulness of the humoral theory of sepsis, and the dominant state of immunosuppression associated with established septic shock.     

Arteriovenous haemofiltration: A new and simple method for treatment of over-hydrated patients resistant to diuretics

Summary Fluid withdrawal in over-hydrated patients resistant to diuretics was obtained by means of a capillary haemofilter, using the arterio-venous pressure gradient for blood perfusion at a rate of 100 ml/min. The ultrafiltration rate was 200–600 ml/h and could be maintained as long as 48 h without changing the haemofilter. This method, which needs no technical investment, is easy and simple to handle for the physician, bears only a very low risk for the patient, and ensures a negative fluid balance even at a mean blood pressure of only 60 mm Hg.Supported by the Deutsche Forschungsgemeinschaft SFB 89 Kardiologie Göttingen