In hemodialysis circuits, pulling large volumes of water across the semi-permeable membrane creates a convective current that "drags" additional solutes. While diffusion is effective at removing most small molecules, convection enhances the removal of small and mid-sized molecules.
Thus, convection can be added to hemodialysis therapy to enhance solute removal. To prevent hypovolemia, any water removed during hemofiltration must be returned to the blood before it reaches the patient. This is called "replacement" fluid. We set hemofiltration rates by adjusting replacement rates. Any fluid removed during hemofiltration is given back to maintain a net neutral fluid balance.
Replacement fluid must be sterile intravenous fluids with concentrations of electrolytes similar to plasma. For example, if the CRRT therapy includes a hemofiltration rate of 1 L per hour, and the fluid removal is set at ml per hour, ml will be pulled from the patient and introduced into the drainage collection bag each hour.
Because the 1 L of hemofiltration is replaced, the net fluid removed is ml. Whether hemofiltration is used or not, the net fluid removed is equal to the fluid removal setting. Replacement fluids can be returned either pre or post filter. This is referred to as predilution or post dilution sets. Predilution means that the replacement solution is returned to the blood before it reaches the filter, diluting the blood in the hollow fibers.
Postdilution means that the replacement fluid is returned to the blood after the filter but before the return side of the access catheter. Predilution dilutes the blood in the filter, reducing clotting. Postdilution concentrates the blood in the filter, enhancing clearance.
None of the filtered creatinine is reabsorbed from the tubules nor is any additional creatinine secreted into the tubule lumen post glomerulus. This makes it the best indicator of renal failure. Because it is completely eliminated during normal renal function, measurement of creatinine clearance is the best measure of glomerular filtration.
Urea is another byproduct of protein metabolism, however, it is a byproduct of all protein metabolism not just muscle protein metabolism. It is filtered into the glomerular filtrate. Unlike creatinine, a percentage of filtered urea is reabsorbed from the tubules. Consequently, urea levels can become increased in the presence of a normal creatinine level. For example, urea can increase due to increased urea production e.
Creatinine only increases when renal filtration decreases, or the production of creatinine becomes so high that it exceeds glomerular filtration capabilities. Excessive creatinine production can occur when significant muscle death has occurred, for example in rhabdomyolysis. Clearance is the rate at which solutes are cleared from the body. Clearance is abbreviated by the letter K. The clearance or K of a solute is the volume of blood from which the substance is completely removed per unit time Gambro training manual.
It is calculated as follows:. The remaining 30 ml will have the same concentration of urea as the blood entering the filter. The ml of blood being returned each minute to the systemic circuit will have significantly less urea than without dialysis, but will still have to mix in with the systemic volume.
Thus, blood must continually circulate through the filter before the total systemic level will begin to fall. To calculate the rate of clearance of a solute, the following formula can be used, where Q blood in is the flow of blood into the filter, Q blood out is the flow of blood out of the filter, C blood in is the concentration of the solute in the prefilter serum and C blood is the concentration of the solute in the post filter blood.
Q blood in and Q blood out are the same and equal to the blood flow rate. The optimal prescription dose has not been defined absolutely. Although there have been a number of attempts to evaluate higher effluent doses for example higher hemofiltration rates aimed at clearing septic cytokines , no studies have confirmed any outcome benefits. Effluent is calculated and reported by the CRRT machine and expressed as prescribed and delivered.
Weight in Kg. A dialysis membrane is a semi-permeable film that makes up the structural walls of the hollow fibers within a dialysis filter. A dialysis filter or dialyzer is collectively the dialysis membrane hollow fibers and the cannister that houses the membrane. Dialysis membranes need to be efficient at clearing wastes, but they must also be biocompatible with human blood.
Compatibility means that exposure of blood to the dialysis membrane produces minimal adverse effects. Filter permeability is influenced by pore size, the number of pores and the thickness of the membrane. Generally, high flux membranes which have more or larger pores allow more solutes and ultrafiltrate to move across the membrane.
Thinner membranes offer less resistance to solute movement by decreasing the distance the solute must travel across the membrane and also favours increased filtration. Solutes pass through the membrane according to solute size. Imagine taking a flour sieve and filling it with a mixture of sand, small rocks and debris.
Shaking up the contents would cause the smallest particles to move towards the bottom, passing easily through the openings.
Particles would be filtered through according to increasing size until you are left with the particles that are too large to fit through the sieve. Dialysis membranes act the same way, allowing small and mid sized molecules to pass across the membrane, without the loss of larger proteins.
High flux membranes that have a larger pore size increase the rate of clearance by allowing larger molecules to pass through the membrane, and by allowing more ultrafiltrate flow. Initially developed Sieving properties of a membrane describe the membrane's permeability to solutes during ultrafiltration.
Permeability of solutes decrease as the molecular size increases. The surface area of the membrane determines the available area for diffusion and ultrafiltration. The internal volume of the dialysis filter should be small enough to limit the amount of blood that is outside of the vascular compartment at any given time. This volume is important if the filter clots before blood can be returned to the patient. Larger filters have more membrane surface area for filtration and can tolerate higher blood flow rates.
For example:. ST 60 Filter: membrane surface area 0. ST Filter: membrane surface area of 1. The AN69 membrane was the first synthetic filter, developed in France in It has a strong negative charge, which adsorbs binds to the surface cytokines to their cationic residues.
It has a symmetric microporous architecture with a hydrogel structure. The hydrogel allows cytokines to be absorbed across the entire bulk of the membrane for enhanced adsorptive capacity.
One of the downsides of the standard AN69 membrane was that when blood came in contact with the membrane surface, it could induce bradykinin production and initiate an inflammatory response. When used in conjunction with an ACE Inhibitor, anaphylaxis could be induced.
PEI is a polymer with repeating units that consist of an amine group and two carbon aliphatic spacers. This reduces surface electronegativity, eliminating the production of bradykinin. PEI also provides antithrombogenic opportunities.
When the filter is primed with heparinized saline, the free positive charges of the PEI adsorb the negatively charged heparin molecules to the membrane surface. The heparin remains active on the membrane during treatment, even when the heparin is rinsed out with a second plain litre of saline.
Despite the surface treatment, the ST AN69 retains its cytokine adsorpting properties. A third generation AN69 membrane is available and indicated for use in sepsis. This membrane is called the oXirisTM filter. Improvements in the PEI surface treatment addition of positively charged amino acids to the PEI promote the absorption of negatively charged endotoxin as well as enhance adsoption of cytokines. Although ace inhibitors are usually held when patients develop acute kidney injury, if necessary, they can be administered when using an ST AN69 or oXirisTM membrane contraindicated when a basic AN69 membrane was in use.
Finally, adsorption is the ability of larger solutes to adhere to the surface of the dialysis membrane removal like being stuck to a sponger. Cytokine removal is non-specific it has the potential to remove both pro and antiinflammatory cytokines. All versions of the AN69 membrane have strong adsorptive properties. Adsorption of mid sized molecules including inflammatory mediators have been demonstrated by a drop in serum concentrations following initiation of a new filter.
The greatest benefit appears to occur in the first few hours; once the filter becomes saturated with proteins, further removal from the serum is limited. The optimal time to change a filter is unknown. It is not unusual to see filter life become more prolonged during sepsis as the patient begins to improve this may be an indication of filters being clogged with cytokines.
Although the goal is to try to get as long as possible from a filter to reduce treatment costs, replacement of the filter may reduce overall cytokine burden. The effect of filter duration on clinical outcomes is unknown. Filter loss can happen for many reasons. While clotting is an important problem that we manage with filter anticoagulation strategies, filters can also be loss due to "clogging" or "caking" by the adherence of cytokines or proteins to the membrane surface.
This will decrease the efficiency of the filter. In CCTC, we measure the ratio of serum to ultrafiltrate urea as marker of filter efficiency. Excessive fluid removal and intravascular dehydration may contribute to early clotting.
Blood flow rate, dehydration, hypercoagulable medical states, catheter size, access quality and pre versus post dilution may all influence clotting. Filters may also be lost due to machine malfunction or an inability to troubleshoot a situation quickly. CVVH is a convection based therapy.
Blood is pumped through the blood compartment of the filter and a significant filtrate flow is produced by action of the filtrate pump. This filtrate flow requires compensation by infusion of a substitution fluid to the blood flow pre- or post-filter. This way, high filtrate flows can be generated which enhances solute removal. The counter-current flow optimizes the diffusion gradient and, thus, the resulting diffusive clearances. In addition, a substitution fluid is infused into the blood flow either pre- or post-filter.
This is paralleled by filtration of plasma water across the membrane resulting in convective clearance. Renal replacement therapy RRT for the treatment of acute kidney injury AKI is mostly realized as extracorporeal blood purification.
Modality comparisons have failed to demonstrate any survival advantage for continuous versus intermittent therapies. Three recent multicenter randomized controlled trials have found similar results.
In the second study, Lins et al. Intention to treat analysis revealed a mortality of Mortality 14 days after discontinuation of RRT was Similarly, there was no difference in renal recovery. Three recent meta-analyses reached similar conclusions that the type of RRT does not have a major impact on survival or renal recovery. However, the validity of the data from the studies is dubious on account of issues related to study design, such as exclusion of patients with hemodynamic instability, improper randomization, differences in baseline characteristics between arms, and high crossover rates between modalities.
Use of IHD has been associated with progressively positive fluid balance whereas CRRT permits a better management of volume overload patients with AKI and also allows adequate volume of nutrition without compromising fluid balance. Removal of fluid in order to get a neutral fluid balance with IHD short sessions can precipitate intra-dialytic hypotension, which is an important contributing factor for an increased risk of recurrent kidney injury and non-recovery of renal function.
Observational studies suggest initial treatment with CRRT may be associated with higher rates of renal recovery. IHD has some advantages over CRRT, among which include practicality and flexibility of application, limitation of expenses, and fewer bleeding complications. It is now recognized that more than one therapy can be utilized for managing patients with AKI. Transitions in therapy are common and reflect the changing needs of patients during their hospital course.
Each modality has a role in the management of patients with AKI and should be tailored for each patient based on the dynamic need. Since the year , multiple studies in intermittent and in continuous therapies have suggested that higher doses of renal replacement therapy are associated with improved outcomes.
Nevertheless, one important aspect which needs to be considered, is that the ATN study and RENAL trial did not measure actual solute removal, and that measured effluent volume normalized for effective treatment time significantly overestimates delivered dose of small solutes in CRRT.
It appears that the relationship between dose administered by RRT and survival has two regions: a dosage-dependent region where increases in intensity of dose are associated with improved survival and a dosage-independent region where after a threshold is reached; further increment on the intensity dose is not associated with better outcomes.
The influence on solute clearance of some operational characteristics of CRRT, such as clotting, use of pre-dilution versus post-dilution replacement fluids, convective versus diffusive modalities, and concentration polarization of the filter, affect delivering a prescribed dose; that is why simply prescribing a target dose and adjusting for treatment interruptions is insufficient as to representing actual solute clearance.
Originally, dose quantification was restricted to the measurement of blood urea nitrogen BUN and creatinine levels. However, total effluent volume overestimates the actual delivered dose of dialysis in CRRT; that is why the sieving coefficient small solute ultrafiltrate to blood ratio should be continuously monitored at least daily.
There are several methods for quantifying different RRT in a manner that makes dose expressions comparable. Solute removal index SRI is another dose expression that could be used to compare different modalities of RRT, which uses dialysate-side measurements for its calculation. Equivalent renal urea clearance EKR , which appears to be a better alternative for dose quantification across different modalities; since it is calculated using time average urea concentrations TAC as opposed to peak urea concentrations.
EKR has a limitation, it assumes that G is equal to the urea removal rate, an assumption that cannot be made during hypercatabolic states like AKI. Dose quantification and expression in AKI patients should not only be limited to the assessment of small solute clearance.
Fluid balance is a critical component of the care of critically ill patients with AKI and one of the main goals of any RRT should be achieving it. Overall fluid balance depends on the amount of fluid intake, which is countered by the amount removed by urine output and ultrafiltration.
When balance is not achieved, fluid accumulation and fluid overload develop and contribute to increase mortality and non-renal recovery in critically ill patients with AKI. Among dialyzed patients, survivors had significantly lower fluid accumulation when dialysis was initiated compared to non-survivors after adjustments for dialysis modality and severity score.
In non-dialyzed patients, survivors had significantly less fluid accumulation at the peak of their serum creatinine. Other observational studies have since then reported similar findings. RRT is continued until the patient manifests evidence of recovery of kidney function, ultrafiltration goal is met or correction of metabolic abnormality occurs. Renal recovery ensues in the setting of increasing urine output. Further assessment of renal recovery can be obtained by measurement of a timed urine collection for creatinine clearance CrCl.
Despite improvement in the management of critically ill patients and developments made in renal replacement techniques, the mortality of patients with AKI in the ICU continues to be high as has been shown in recent studies.
In a prospective cohort study, Aldawood et al. Multivariate analysis showed that mechanical ventilation requirement was independently associated with an increased mortality risk. In another population-based cohort study, Yasuda et al. Of these patients, The in-hospital mortality rate was Treatment conditions e. In general high-efficiency hemofilters containing synthetic membrane material are used during CRRT as this membrane material presents the characteristics to match the above requirements.
Please feel free to send us any questions you may have about our products and support. Japanese Top of page. Top of page. Ideal function for such equipment include: Ease of use Accurate control of each pump Flexibility to adapt to different treatment modalities CVVH, CVVHD, CVVHDF, SCUF, pre- or post dilution Flexibility to individualize the blood flow, filtrate, replacement fluid and dialysate flow Control of replacement and dialysate fluid to temperature to allow patient temperature management Mobile to be used in different locations in the hospital Low extracorporeal volume to minimize the risk for hemodynamic instability Back-up battery for blood recovery and for maintaining the data in memory in case of power failure Ideally be able to perform other types of extracorporeal treatment like therapeutic apheresis e.
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