buffered solutions in continuous extracorporeal renal replacement therapies

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é??ç¸?uffered solutions in continuous extracorporeal renal replacement therapies

Correspondence: Horst P.Background Continuous renal replacement therapies (CRRTs) are well accepted for critically ill patients with acute renal failure (ARF). Today, daily fluid exchange in CRRT reaches 30 to 40 liter and more. Therefore, the composition of the substitution/dialysate fluid, often primarily developed either for intermittent treatment or for peritoneal dialysis, becomes more relevant. Lactate (30 to 45 mmol/liter) is frequently used as the buffer because of the high stability of this substance. However, lactate is thought to have negative effects on metabolic and hemodynamic parameters.Methods Published data for different substitution fluids are presented with respect to acidosis and lactate concentration, uremia, and hemodynamic and metabolic alterations.Results Only a few studies compare substitution fluids with different buffers. Uremia and acidosis (pH, base excess) were sufficiently controlled during CRRT with an exchange volume of in average 30 liters using either buffer. If patients with severe liver failure and lactic acidosis were excluded, no difference in hemodynamic and metabolic parameters between the solutions occurred. The plasma lactate concentration was elevated during lactate use in some cases, but lactate levels remained within normal limits in patients without liver impairment. The bicarbonate concentration in the solutions should exceed 35 to 40 abercrombie and fitch mmol/liter, as in some cases the buffer capacity of the solutions was inadequate. In patients with severe liver failure or lactic acidosis, solutions with lactate buffer were shown not to be indicated.Conclusion In patients with reduced lactate metabolism, for example, concomitant severe liver failure, after liver transplantation or in lactic acidosis, bicarbonatebuffered solutions should be used. In nearly all other cases of critically ill patients with ARF, lactatebuffered solutions may be north face outlet used as well as bicarbonate solutions.Keywords: acute renal failure, continuous renal replacement therapy, dialysate, acidosisMany efforts have been made to reduce the high mortality of patients with acute renal failure (ARF). One of these is the development of continuous renal replacement therapies (CCRTs). CRRT, first published in 1977 by Kramer et al as continuous arteriovenous hemofiltration (CAVH), quickly gained ground because of its simplicity1. However, blood pressuredependent filtration could not adequately control azotemia in hemodynamically unstable patients with ARF. Therefore, a number of treatment methods aimed at combining the advantages of continuous therapy with a higher effectiveness have been developed since the beginning of the eighties2,3. Their common feature, for instance continuous arteriovenous hemodialysis and pumpassisted venovenous methods such as continuous venovenous hemofiltration (CVVH) or continuous venovenous hemodialysis (CVVHD), is that their greater efficacy enables them to satisfactorily maintain even hemodynamically unstable hypercatabolic patients with ARF and multiple organ dysfunction syndrome (MODS)3. In contrast to CAVH in these forms of treatment, daily fluid exchange reaches 30 to 40 liters and more, so that the composition of the substitution fluid becomes more relevant than in the early lowvolume CAVH method.Top of pageSOLUTIONS FOR FLUID REPLACEMENT: IMPORTANCE OF BUFFERRenal replacement therapy in ARF has three major aims4: detoxification, fluid elimination, and compensation of acidosis. In CRRT, the physical properties of hemofiltration, hemodialysis, or hemodiafiltration techniques are therefore used. In continuous treatment forms exclusively using hemofiltration, the ultrafiltrate is completely replaced by a sterile substitute solution. For sufficient control of azotemia also in MODS patients, CVVH treatment minimally requires a total of about 30 liters of hemofiltrate per day5. In techniques using hemodialysis, a defined quantity of dialysate passes on the outer side of the dialyzator as in intermittent hemodialysis. A certain quantity of ultrafiltrate is still produced so that the therapy represents a combination of dialysis and filtration, that is, of diffusive and convective transport6. For an effective treatment, a dialysate flow rate of 1 to 2 liters/hr (24 to 48 liters/day) is needed.Substitution fluids and dialysate used in CRRT have been primarily developed for intermittent hemofiltration or peritoneal dialysis. In CRRT techniques also including dialysis, any readytouse dialysis solution may be employed. In nearly all commercially available fluids, lactate (30 to 45 mmol/liter), which is converted to bicarbonate on an equimolar basis under physiological conditions, is used as the buffer to correct acidosis. The lactate buffer has the advantage of greater stability over a physiological bicarbonate buffer. However, lactate is thought to have negative effects on hemodynamic parameters7 and on metabolic parameters, for example, sciarpa burberry prezzo enhanced protein catabolism and decreased regeneration rate of adenosine 5'triphosphate (ATP) because of the fact that conversion from lactate to bicarbonate needs energy8. Lactatebuffered substitution solutions or dialysate according to the daily fluid exchange may lead to a daily lactate load of 800 to 1300 mmol. Case reports of a reduced lactate tolerance and a tendency to develop hyperlactatemia during treatment with lactatebuffered solutions also exist9. ARF patients with concomitant severe liver failure or hemodynamic instability in particular display an increased plasma lactate level as the conversion of lactate into bicarbonate is diminished10. There is some theoretical evidence that metabolic and hemodynamic disadvantages of lactate buffering can be avoided by the use of bicarbonatebuffered solutions. These solutions had been reported as early as 1985 as an alternative replacement fluid for CAVH11.Top of pageCLINICAL EXPERIENCE WITH SOLUTIONS USED IN CRRTTo date only a few <a href="http://www.photo2video.co.uk/tiffanyuk/">tiffany uk stores</a> studies have compared different buffers used in substitution fluids. From these data, there seems to be no controversy that acetatebuffered substitution fluids should be avoided, as a significantly reduced control of acidosis compared with a lactatebuffered solution has been recently reported during CVVH7, and lower hemodynamic stability is described in CRRT and intermittent dialysis <a href="http://www.photo2video.co.uk/northfaceoutlet/">north face outlet</a> procedures10,12,13. All critically ill patients with ARF were effectively treated by CRRT using either bicarbonate or lactatebuffered solutions. We could show that within 48 hours, uremia was well controlled using either buffer with a daily exchange volume of 30 liters and more, in accordance with data of other groups using lactatebuffered substitution solutions14,15,19.Top of pageHEMODYNAMIC PARAMETERSEspecially acetate, but also lactate buffer, has been shown to exert a negative influence on the mean arterial blood pressure and cardiac function in the critically ill7,18,20. Acetatebuffered substitution fluids should be avoided, as a significantly reduced control of acidosis compared with a lactatebuffered solution has been recently reported during CVVH21. We investigated the influence of a lactate and a bicarbonatebuffered substitution solution on hemodynamic and other parameters in patients with ARF and MODS who were undergoing CVVH in a crossover designed study15. The composition of the solutions used in that study is given in Table 1. There was no difference in hemodynamic parameters measured as mean arterial blood pressure (75.5 24.0 mm Hg for all patients) and blood pressure drop of more than 30%, or in the need of positive inotropic substances between the groups with different buffers. During hyperlactatemia (lactate > 5 mmol/liter), a reduced myocardial performance20 caused by an increased intracellular lactate concentration, leading to reduced cellular ATP production, has been reported. A correlation of mean arterial blood pressure to the degree of lactate intolerance has also been described20. In contrast to these data and pathophysiological reflections in our own study and some recently published articles (abstract; McLean et al, J Am Soc Nephrol 9:1413, 1996)16, there was no negative influence of lactate buffer. The hemodynamic status of the patients was comparable using either bicarbonate or lactatebuffered bottega veneta outlet on line solutions. In our own experience, this blood pressure stability is probably due to the fact that in these patients, despite significantly higher lactate levels during the substitution with lactate buffer, lactate levels never left the normal limits15. These findings had been impressively confirmed in the work of Thomas et al, who could show no differences in terms of cardiac index, left venticular stroke work index, and oxygen consumption for different buffers by right heart catheter measurements16. In contrast, patients in CRRT receive a maximum lactate load of 90 to 100 mmol/hr, even when fluid exchange in filtration or dialysate techniques increases to 2 liters/hr. The slower ultrafiltration in CRRT compared with intermittent hemofiltration may be the reason for the better lactate tolerance in critically ill patients, despite the same total quantity of substituted lactate (1000 to 1200 mmol/day). Lactate could be an effective bicarbonate generating base in patients with acute or chronic renal failure7,8. Under stable clinical conditions, 2000 mmol of lactate per day are metabolized to bicarbonate on an equimolar basis. Critically ill patients with ARF, especially with concomitant sepsis or circulatory shock, have been reported to display a reduced lactate tolerance9. In our study, which excluded patients with liver failure, the only sign of a possible lactate intolerance was the significantly higher lactate levels during lactate buffering (P = 0.001, but lactate levels never left the normal limits. In addition, lactate values decreased in both groups compared with baseline levels15. These results had been confirmed by Thomas et al, who also reported significantly higher lactate levels during lactate buffering without any clinical signs of hyperlactatemia16.Top of pageACIDOSISSufficient control of acidosis was reported by Hilton et al using a bicarbonate buffer17. In our own study, there was no difference in pH or base excess between the buffer solutions. Astonishingly, the bicarbonate concentration was significantly higher (P = 0.035) during the reception of the lactatebuffered solution compared with patients receiving the bicarbonate I solution Table 215. The same phenomena occurred in another study16. We explained this "mysterium" by the lower quantity of buffer substances in the bicarbonatebuffered solution (34.5 mmol/liter bicarbonate and 3 mmol/liter lactate) compared with the lactatebuffered solution (44.5 mmol/liter lactate). In a recently published study, a bicarbonatebuffered substitution solution with a higher amount of bicarbonate (40 mmol/liter) showed a better control of acidosis than a lactatebuffered solution (abstract; McLean et al, J Am Soc Nephrol 9:1413, 1996). Additionally, there was also a clear trend to higher serum bicarbonate concentrations in the group with the bicarbonatebuffered solution (abstract; McLean et al, ibid). According to the results of our own study, we composed a bicarbonatebuffered solution with a higher bicarbonate concentration Table 1. Comparing this solution (bicarbonate II solution) against a lactatebuffered solution, the bicarbonate concentration of the patients in this group was significantly increased as compared with the lactate group and the bicarbonate I group Table 2. Azotemia was well controlled with this solution, and no difference according to hemodynamic parameters compared with the lactate solution occurred. In our own studies, no differences between the groups were found for ammonia and glucose. Nitrogen excretion differed significantly between the lactate group and the bicarbonate I group for days 1 through 4 (P = 0.0035), whereas there was no difference when we compared the bicarbonate II <a href="http://www.photo2video.co.uk/abercrombie/">abercrombie and fitch</a> solution with the lactate solution Table 215. Lactate infusions have been reported to induce a higher degree of protein catabolism than bicarbonate8. In our first experience, nitrogen excretion was significantly increased in patients receiving lactatebuffer on days 1 through 415, whereas in a second part of the study on days 5 through 8, there was no significant difference. This is probably due to the higher protein catabolic rate in critically ill patients on the first three to five days12, but may also be of no or minor relevance because when we used the bicarbonate II solution with a higher content of bicarbonate, there was no statistical difference in nitrogen excretion compared with the lactate buffer. Protein catabolism may also be due to the blockade of the conversion of pyruvate to oxaloacetic acid, a mechanism that prevents intracellular gluconeogenesis20. Despite this, we and others could not show any difference in carbohydrate metabolism between the two buffers Table 215,16,17,21.Top of pageELECTROLYTESBicarbonate solutions must be stable for a 24hour period without precipitation of calcium carbonate or magnesium carbonate13. Therefore, the magnesium and calcium concentration is reduced compared with the lactatebuffered solution. To adjust ionic strength, the chloride concentration must be increased. Possible precipitation does not allow a higher phosphate concentration in one of the solutions, and thus, phosphate must be separately substituted to avoid phosphate depletion, as MODS patients with ARF tend to develop hypophosphatemia leading to decreased respiratory and cardiac function. In our study, no differences between the groups in phosphate, potassium, chloride, or sodium concentration occurred. Differences in chloride, calcium, and magnesium were released by the composition of the bicarbonate buffer determined by the chemical properties of the compound15.Top of pagePROBLEMS IN DAILY USE OF BICARBONATEBUFFERED SOLUTIONSThree major problems may occur in daily use of bicarbonatesolutions.(a) The solution has to be mixed immediately before use from a bufferfree electrolyte solution and the bicarbonate buffer. It must be realized that the administration of the bufferfree electrolyte solution may endanger the patients, and crucial to remember that the lone application of either the buffer or the bufferfree solution is impossible.(b) The readily mixed bicarbonatebuffered solution has to be prepared in <a href="http://www.biennalecarrara.it/burberryoutlet/">sciarpa burberry prezzo</a> bags made of special plastic sheeting to prevent evaporation of carbon <a href="http://www.barrioroma.it/bottegavenetaoutlet/">bottega veneta outlet on line</a> dioxide. The solution must be stable for at least 24 hours without precipitation of calcium carbonate or magnesium carbonate13.(c) To avoid precipitation of calcium carbonate and magnesium carbonate, the concentration of these electrolytes is reduced. Additionally, phosphate is not included in the solution. The patients' serum concentration of these electrolytes must therefore be carefully monitored, and electrolytes must be added if necessary. Especially the magnesium concentration in bicarbonate solutions may be insufficient in patients with arrhythmia or depleted cardiac function.Top of pageCONCLUSIONIn conclusion, in patients with reduced lactate metabolism, for example, concomitant hepatic failure, after liver transplantation or lactic acidosis, bicarbonatebuffered solutions should be used as the replacement fluid. In nearly all other critically ill patients, the physiological capacity of lactate metabolism allows the use of lactatebuffered solutions. Acetatebuffered solutions and solutions containing high amounts of glucose should be avoided. It must be realized that the bicarbonate solution has to tiffany uk stores be mixed immediately before use from a bufferfree electrolyte solution and the buffer. The administration of the bufferfree electrolyte solution may endanger the patients.