Nephrology Dialysis Transplantation

Transcription

1 Nephrol Dial Transplant (1996) 11 [Suppl 2]: Nephrology Dialysis Transplantation Recirculation and the post-dialysis rebound J. E. Tattersall, P. Chamney, C. Aldridge and R. N. Greenwood Lister Hospital, Stevenage, UK Limitations to short haemodiaiysis It is now generally accepted that there is a significant risk of underdialysis if the treatment time is shortened towards 4 h or less. To avoid these risks, a return to longer dialysis times has been advocated, despite the increase in cost and inconvenience to the patient. An alternative strategy would be to understand the mechanism of reduced efficiency in short dialysis and specifically correct for it without resorting to long treatments. If it were possible to increase the rate of removal of fluid and solute mass in proportion to the reduction of dialysis time, without increasing the patient's fluid content, blood pressure or solute concentrations, then the short treatment would have equivalent efficacy to the long treatment. There are a number of factors which combine to reduce rate of fluid and solute removal in short dialysis. These include the relatively slow diffusion of middle and large molecular weight solutes, hypotension related to high ultrafiltration rates and the post-dialysis rebound. This paper will consider only the post-dialysis rebound, although it is accepted that other factors need to be considered when prescribing short dialysis. The rate at which solute can be removed from the patient is dependent on the dialyser clearance and on the rate at which solute can be conveyed from all parts of the body into the arterial needle. While the dialyser clearance rate is controllable and relatively easy to measure, the other factors are much more difficult to measure and are generally impossible to modify. For solute to travel from the intracellular compartment (which is the largest body water compartment) to the needle, it must cross the cell membrane, be carried into the central circulation by venous blood flow, be pumped into the aorta by the heart and carried to the needle by the fistula blood flow. Therefore the rate of transfer depends on the intra/extracellular mass transfer coefficient, regional bloodflowrates, cardiac output and fistula blood flow. The effect of these factors is to delay the rate at which solute is transferred into the fistula during Correspondence and offprint requests to: J. Tattersall, Renal Unit, Lister Hospital, Coreys Mill Lane, Stevenage SG1A KAB, UK. dialysis. The solute concentration in the fistula will, therefore, be lower than in the other compartments. This will reduce the rate at which solute is removed from the patient and results in an upward rebound in solute concentration after dialysis as the patient re-equilibrates. The multiple factors which delay solute transfer into the fistula from the patients are conveniently considered in different components, recirculation and inter-compartment transfer. Recirculation During haemodiaiysis, some of the blood entering the dialyser inlet has flowed from the dialyser outlet without passing through the peripheral capillaries. This flow of dialysed blood from dialyser outlet to inlet is termed recirculation and is quantified as the flow rate of recirculated blood entering the dialyser, expressed as a fraction of the extracorporeal blood flow rate. There are two types of recirculation, cardiopulmonary and access. Access recirculation 1996 European Dialysis and Transplant Association-European Renal Association Access recirculation does not normally occur during haemodiaiysis. It occurs when a proportion of the blood returning to the patient in the venous line is immediately drawn into the arterial needle and dialysed again without leaving the fistula (Figure 1). Access recirculation occurs only when the arterial needle is placed downstream of the venous needle or when the extracorporeal blood flow rate exceeds the blood flow rate in the fistula. In the case of incorrectly placed needles, the recirculated fraction will be the ratio of the extracorporeal blood flow rate to the fistula flow rate. Recirculation due to incorrectly placed needles commonly occurs in loop PTFE grafts where the direction of fistula flow is not obvious. Access recirculation due to limitations infistulaflow rate is relatively rare. Normally, fistula flow rates are well in excess of 700 ml/min and the extracorporeal blood flow rate is unlikely to exceed this. Recirculation of this kind is usually caused by a critical stenosis and is an indication that the fistula will soon clot. This kind of recirculation is critically dependent on the extfacorporeal blood flow rate; it is absent at low

2 76 7/ V Fig. 1. Access recirculation. The top panel shows the normal situation when there is no access recirculation. The middle panel shows recirculation due to the arterial needle (A) being incorrectly placed upstream of the venous needle (V). The lower panel shows access recirculation in a stenosed fistula with flow rates lower than the extracorporeal blood flow rate. extracorporeal blood flow rates but increases rapidly as the extracorporeal blood flow rate increases above the fistula flow rate. After dialysis ceases, the recirculated blood is rapidly washed out of the fistula and the solute concentration rebounds upwards. The rebound due to access recirculation is complete within a few seconds. Cardiopulmonary recirculation Cardiopulmonary recirculation is inevitable when dialysis is performed using a fistula as access [1]. In cardiopulmonary recirculation, blood recirculates from venous needle, fistula, venous circulation, right heart, lungs, left heart, aorta, fistula and into the arterial needle (Figure 2). The recirculated fraction will be the ratio of the extracorporeal blood flow rate to the cardiac output. Cardiopulmonary recirculation also causes a post-dialysis rebound which takes about 1 min as the recirculated blood clears the pulmonary circulation. The effect of recirculation on dialysis efficiency The rate at which solute mass is removed from the patient by the dialyser (in mmol/min) is the dialyser clearance rate (in 1/min) multiplied by the concentration of solute at the dialyser inlet (inmmol/1). Recirculation effectively reduces the solute concentration in the blood entering the dialyser by diluting it with cleared blood. Dialyser clearance is calculated J. E. Tattersall et al. from the ratio of concentrations entering and leaving the dialyser and is unaffected by their absolute values. Therefore, recirculation does not affect the dialyser clearance rate. However, by reducing the concentration in the dialyser inlet, recirculation does reduce the mass of solute removed. The dose of dialysis delivered is usually calculated from the ratio of pre- and post-dialysis blood solute concentrations. If the post-dialysis sample is taken before the rebound, the concentration will be reduced by recirculation and the calculated dose significantly overestimated. Since access recirculation may be significant, the post-dialysis sample must be taken after the access-related rebound is complete. The post-dialysis sample is usually taken from a sample port in the arterial line after the blood pump has been slowed to 50ml/min for 30 s. This time allows the recirculated blood to clear the fistula and for the fistula blood to be drawn up to the sample port. Cardiopulmonary recirculation has a small and predictable effect on dialysis efficiency and does not need to be measured routinely. However, access recirculation, if present, may have a major effect on efficiency and may indicate imminentfistulafailure. It is therefore important to detect access recirculation. If the routine measurement of dialysis dose delivered reveals an unexpected fall-off in efficiency or if there are any doubts about fistula performance, recirculation should be measured. Measurement of recirculation The three-sample method Until recently, this method was considered to be the 'gold standard' for measuring fistula recirculation [2]. This is calculated from the urea concentration in samples taken simultaneously from the dialyser inlet and outlet and from a peripheral vein. This method assumes that the peripheral sample is representative of arterial blood. Any difference between urea concentrations at the dialyser inlet and the peripheral vein is assumed to be due to recirculation from the dialyser outlet directly into the arterial needle, i.e. access recirculation. This has now been shown to be false. Although, in steady-state, the urea concentration does not differ significantly between sample sites, during dialysis there is a disequilibrium between sites. Cardiopulmonary recirculation causes the central venous blood to have a greater concentration than the arterial blood. Also, the peripheral vein has a greater concentration still [3,4]. Relatively slow blood flow in the skin and resting muscles drained by the peripheral veins results in their solute concentration falling more slowly than the central blood compartment (Figure 2). Recirculation measured by the three-sample method detects a combination of cardiopulmonary and access recirculation and also the disequilibrium between body vascular compartments. Most studies have shown recir-

3 Recirculation and the post-dialysis rebound artery Peripheral Circulation 400 ml/min peripheral vein 4 l/min central vein Fig. 2. Simple plan of the circulation. Cardiopulmonary recirculation occurs as some of the dialysed blood from the venous needle (V) flows through heart (RV, LV) and lungs back to the arterial needle (A) without passing through the capillary beds in the central and peripheral circulation. Intracellular solute must diffuse from the cells into the circulation (solid arrows) and is then carried by the blood flow into the fistula. This takes time and the delay reduces dialysis efficiency and causes the rebound. During dialysis, solute concentration will be higher in the peripheral veins than in the central veins and lowest in the arteries. This diagram shows only two of the many circulation compartments. culation fractions around 12% using the three-sample method [5]. method returns recirculation rates in the region of 5-15% due to this rebound artefact even when there is no fistula recirculation. The slowflowmethod This is a modification of the three-sample method. The peripheral sample is replaced by a sample from the dialyser inlet taken after the blood pump has been slowed to 50 ml/min for 30 s [6]. Under these conditions, the sample should reflect the arterial urea concentration and the method should detect only fistula recirculation. However, the timing of the slow flow sample is critical. If the sample is taken too soon, there will be insufficient time for dialysed blood to clear the fistula and for arterial blood to have been drawn up to the sample port. In this case the slow flow sample will be identical to the dialyser inlet sample and the recirculation fraction calculated will be zero whatever the true fraction may be. If, on the other hand, the slowflowsample is taken too late, the solute concentrations in thefistulawill have started to rebound upwards as dialysed blood clears the central circulation and solute re-equilibrates within the patient. Delays of more than 30 s in sampling at low flow will be affected unpredictably by this rebound and the calculated recirculation rates will be overestimates. In practice, this Saline dilution methods A bolus of saline is injected into the venous line during dialysis and is detected in the arterial line a short time later [7]. By comparing the size of the saline bolus detected in the arterial line with its original size as it enters the fistula, the recirculated fraction may be calculated. If there is access recirculation, a saline bolus will be detected in the arterial line within seconds of its passage into the fistula. The cardiopulmonary recirculation will result in a saline bolus being detected approximately 1 min after its passage into the fistula, as the saline will have passed around the pulmonary circulation. Therefore, this method may distinguish between fistula and cardiopulmonary recirculation and calculate their fractions separately. The blood temperature module This method uses the same principle as the saline dilution method, but a thermal bolus replaces the saline [8]. A bolus of blood at about 35 C is produced

4 78 by reducing the temperature of the dialysate for about 2 min. This cool blood is detected and quantified by a temperature sensor on the venous line. Recirculation of the cool blood bolus into the arterial line is detected by another sensor. Since the duration of the cool bolus is about 2 min, this method cannot distinguish between fistula and cardiopulmonary recirculation and its precision is relatively low at approximately 50-10%. However, this method is much less invasive than the other methods as no injections or samples are required. Also, this method is the simplest to operate as the module is part of the dialysis machine, the temperature sensors operate from outside unmodified blood lines and the entire system is under automatic control. The operator simply presses a button and the module displays the recirculated fraction approximately 2 min later. The occlusion method The fistula is occluded between the arterial and venous needles by finger pressure. If there is access recirculation, the pressure in the arterial line will fall rapidly and the dialysis machine will alarm. This is because part of the flow into the arterial line was recirculated blood from the venous line and was stopped by the finger pressure. This method does not detect cardiopulmonary recirculation and is very easy to perform. However, if the fistula needles are very close together or the fistula is a deep prosthetic graft, it may be difficult or impossible to occlude by finger pressure. Interpreting the recirculated fraction Since access recirculation is critically dependent on the extracorporeal blood flow rate, recirculation should always be measured at the highest extracorporeal blood flow rate likely to be used during dialysis. Methods which detect a combination of cardiopulmonary and access recirculation (blood temperature module, slow flow method) will generally return a value of up to 15% due to cardiopulmonary recirculation. If the recirculation fraction is much greater than 15% then access recirculation is likely. If access recirculation is detected and needle position errors have been excluded, then it is helpful to determine thefistulaflow rate. This is achieved by measuring recirculation at different blood flows and determining the maximum blood flow at which no access recirculation occurs. If the method detects both cardiopulmonary and access recirculation, than the fistula flow rate may be determined by analysing the relationship between blood flow and recirculation (Figure 3). Dialysis should not be performed using blood flow rates in excess of the fistula flow rate and the dialysis time should be increased to compensate for the reduction in blood flow rate. Since access recirculation is usually due to critical stenosis and may precede complete failure, further investigation of the fistula is needed. RF(%) Qb (ml/min) J. E. Tattersall et al Fig. 3. The relationship between the recirculated fraction (RF) and extracorporeal blood flow rate (Qb). The data points represent measurements in a patient. In this case, the fistula flow rate was limited to 370 ml/min by stenosis. So long as the extracorporeal blood flow rate is less than the fistula flow rate (Qf) then the recirculated fraction is Qb/CO, where CO is the cardiac output. When Qb>Qf, the recirculated fraction is 1 -Qf(CO-Qf )/CO/Qb. Intercompartment solute transfer The major component of the post-dialysis rebound is due to solute transfer between compartments [9]. The body can be considered to be made up of multiple aqueous compartments which contain solute. These compartments include the cells, gut, regions of the body where there is relatively low blood flow, the main blood circulation and the fistula. The dialyser clears only the fistula directly. Solute in all other compartments will transfer into the fistula at finite and variable rates. The mechanism of solute transfer between compartments may be diffusion, for example across cell membranes, or it may be flow, for example from poorly perfused areas into the main circulation. The solute concentration in the fistula depends not only on the dialyser clearance but also on the rate at which solute is transferred into the fistula from other compartments. The slower the intercompartment transfer relative to the dialyser clearance the lower the solute concentration in the fistula. Intercompartment solute transfer has the same effect on dialysis efficiency as does recirculation. It reduces the solute concentration in the fistula and, therefore, dialyser inlet which has the effect of reducing the rate at which solute is removed from the patient without affecting the dialyser clearance. After dialysis the solute concentration rebounds upwards as the patient re-equilibrates, taking about 30 min to complete. Taking the rebound into consideration in planning dialysis Both cardiopulmonary recirculation and intercompartment transfer become more important as the dialyser

5 Recirculation and the post-dialysis rebound clearance rate increases. In short, high clearance dialysis, the solute concentrations at the dialyser inlet are lower throughout dialysis than in a longer, slower dialysis. This is due to the greater degree of recirculation and intercompartment disequilibrium and results in a lower mass of solute removed despite similar clearances and Kt/V. These effects also result in the post-dialysis rebound which is, again, relatively greater after short, rapid dialyses (Figure 4). If dialysis is quantified using pre- and immediate post-dialysis blood solute concentrations, the dose of dialysis will be overestimated, particularly in short, rapid dialysis. In prescribing dialyses, it is necessary to add extra dialysis dose to compensate for the recirculation and intercompartment transfer effects. This extra dose will be relatively greater in rapid dialyses. In the measurement of dialysis dose actually delivered, the mass of solute actually removed during dialysis must be measured in a total or partial dialysate collection. Alternatively, if the dialysis is quantified using pre- and post-dialysis blood solute concentrations, the post-dialysis sample must be drawn after the rebound is complete at least 30 min post-dialysis. The patient clearance time Dialysis efficiency can be considered to be limited by the rate at which urea can be delivered from the different compartments of the body into the fistula. This rate depends on cardiac output, blood flow in the different regions of the body, and the rate of diffusion across cell membranes. The mathematics describing these effects are similar and surprisingly simple [10], reducing to a single time constant the patient clearance time. This is the time needed to clear the peripheral compartments of the body and is, in effect, the urea concentration (mm) ! 22 P IIffiffr^ I time (min) Fig. 4. Plot of urea concentration against time. The data points represent the mean of 29 measurements in 29 different patients treated by long and short dialysis on consecutive weeks. The lines represent concentrations predicted by single (dotted) and double pool (solid lines) UKMs with Kt/V=\. The addition of 30min to the dialysis time (shaded area) corrects for the effect of the rebound in both long and short dialyses. mean of the ratios of intercompartment mass transfer rate (flow rate or diffusion coefficient) to the volumes of the peripheral compartments. The patient clearance time is approximately 30 min and comprises F/cardiac output (approximately 6 min) for cardiopulmonary recirculation and 24 min for intercompartment transfer. The patient clearance time (tp) may be calculated from the observed post-dialysis solute rebound in individual patients from the equation tp = td{ktvi/ktvr-l) where Ktvi and Ktvr are the Kt/V calculated by singlepool UKM using immediate and 1 h post-dialysis urea concentrations. This time is independent of the dialyser clearance and is reproducible. The patient clearance time is also relatively constant between patients. Assuming a clearance time of 30 min for all patients may be an acceptable approximation and avoids the need to measure it individually. The patient clearance time can be used to correct for the effects of the rebound on dialysis efficiency. In the prescription of dialysis time, the patient clearance time should be added for each unit of Kt/V prescribed. Whereas dialysis time is normally prescribed using the formula t = [desired Kt/V]V/K the 30 min patient constant should be included thus: = [desired Kt/V](V/K + 30) This will have the effect of increasing a 4 h dialysis by 12% and a 2 h dialysis by 25% (Figure 4). In the measurement of dialysis dose delivered, the 30 min constant can be used to correct the Kt/V calculated conventionally from pre- and immediate post-dialysis solute concentrations by multiplying it by td/(td+30). This will effectively reduce the Kt/V calculated by 10-25% depending on the dialysis time. Conclusion The mass of solute removed by dialysis is reduced by recirculation and intercompartment transfer effects. These effects are relatively greater in short, rapid dialyses and must be taken into account. Access recirculation should be avoided altogether. The quantification of dialysis using pre- and post dialysis urea will effectively take access recirculation into account if the post-dialysis sample is taken at least 30 s after dialysis has effectively stopped. This allows recirculated blood to clear the fistula and arterial blood to be drawn up to the sample port. If access recirculation is suspected then it should be measured at different blood flow rates to determine the maximum blood flow rate possible without access recirculation. The effects of cardiopulmonary recirculation and intercompartment transfer on dialysis quantification may be taken into account by using the dialysate collection method or the pre- and post-dialysis blood 79

6 80 sample method, provided the post-dialysis sample is taken at least 30min after the dialysis has ended to allow the rebound to complete. Alternatively, pre- and immediate post-dialysis samples may be used but the resulting Kt/V corrected by multiplying by td/(td+30). When prescribing dialysis, an extra 30 min per unit of Kt/V prescribed should be added to allow for intercompartment transfer and cardiopulmonary recirculation. References 1. Schneditz D, Polaschegg HD, Levin NW, Cu GA, Morris AT, Kramer M, Daugirdas JT, Kaufman AM. Cardio-pulmonary recirculation in dialysis. An underrecognized phenomenon. ASAIO J 1992; 38: M Gibson SM, Von Albertini B, Bosch JP. Reproducible measurement of recirculation without peripheral venipuncture. Kidney Int 1990; 37: 297 (abstract) J. E. Tattersall et al. 3. Sherman RA. Recirculation revisited. Semin Dial 1991; 4: Buur T, Will EJ. Haemodialysis recirculation using a femoral artery sample. Nephrol Dial Transplant 1994; 9: Tattersall JE, Farrington K, Raniga PD, Thompson H, Tomlinson C, Aldridge C, Greenwood RN. Haemodialysis recirculation detected by the three-sample method is an artefact. Nephrol Dial Transplant 1993; 8: Sherman RA, Levy SS. Assessment of a two-needle technique for the measurement of recirculation during hemodialysis. Am J Kidney Dis 1991; 18: Aldridge C, Greenwood RN, Frampton CF, Wilkinson JS, Cattell WR. Instrument design for the bedside assessment of arteriovenous fistulae in haemodialysis patients. Proc EDTNA- ERCA 1985; 14: Kramer M, Polaschegg HD. Automated measurement of recirculation. EDTNA-ERCA J 1993; 19: Pendrini PR, Zereik S, Rasmy S. Causes, kinetics and clinical implications of post-hemodialysis urea rebound. Kidney Int 1988; 34: Tattersall JE, Greenwood RN, Farrington K. Intercompartment diffusion and cardio-pulmonary recirculation in long and short dialyses. J Am Soc Nephrol 1994; 5: 530