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Cardiovascular response to hemodialysis: The effects of uremia and dialysate buffer

1998; Elsevier BV; Volume: 54; Linguagem: Inglês

10.1046/j.1523-1755.1998.06819.x

1523-1755

M. Jaraba, Alberto Rodríguez‐Benot, Rafael Guerrero, Domingo del Castillo, Alejandro Martín‐Malo, Mariano Rodríguez, Pedro Aljama,

Renal function and acid-base balance

Cardiovascular response to hemodialysis: The effects of uremia and dialysate buffer. Cardiovascular instability continues to be one of the primary clinical problems in hemodialysis. Acetate buffer in dialysate is one of the factors that may induce hypotension. Since uremia may have a direct effect on the regulation of the cardiovascular system, the present study was designed to investigate the separate effects of uremia and acetate hemodialysis on blood pressure in anesthesized dogs, as well as the hemodynamic parameters determined by invasive cardiovascular monitoring. Animals were separated into four groups: (1) group I, hemodialysis with acetate in controls; (2) group II, hemodialysis with acetate in uremic dogs; (3) group III, hemodialysis with bicarbonate in controls; and (4) group IV, hemodialysis with bicarbonate in uremic dogs. Acute uremia was induced by bilateral ureteral ligation and a 90-minute hemodialysis (acetate or bicarbonate) procedure was performed 72 hours later. The results obtained in this study show that, compared with dogs with normal renal function, acute uremia resulted in an elevation in mean arterial pressure (MAP; 178 ± 13 vs. 115 ± 23 mm Hg, P < 0.01), which was associated with an increase in cardiac index (CI) and left ventricular stroke work index (LVSWI). In these dogs, the pulmonary capillary wedge pressure (PCWP; preload) and the systemic vascular resistance index (SVRI; afterload) were not different than controls. In uremic dogs, hemodialysis with acetate, but not with bicarbonate, decreased the MAP to values similar to controls. The decrease in MAP induced by acetate hemodialysis in uremic dogs was associated with a decrease in SVRI and PCWP. These results suggest that in dogs with acute uremia, acetate hemodialysis (HD) decreases miocardial contractility that was previously increased by a direct effect of uremia. In controls, acetate produced a moderate decrease in MAP that was the result of a mild decrease in CI and SVR. Since PCWP was not significantly decreased after acetate HD, the decrease in CI can be attributed to a mild decrease in myocardial performance. In conclusion, this study in dogs suggests that uremia enhances myocardial contractility directly. Acetate hemodialysis reduces this elevated miocardial contractility to normal values. Cardiovascular response to hemodialysis: The effects of uremia and dialysate buffer. Cardiovascular instability continues to be one of the primary clinical problems in hemodialysis. Acetate buffer in dialysate is one of the factors that may induce hypotension. Since uremia may have a direct effect on the regulation of the cardiovascular system, the present study was designed to investigate the separate effects of uremia and acetate hemodialysis on blood pressure in anesthesized dogs, as well as the hemodynamic parameters determined by invasive cardiovascular monitoring. Animals were separated into four groups: (1) group I, hemodialysis with acetate in controls; (2) group II, hemodialysis with acetate in uremic dogs; (3) group III, hemodialysis with bicarbonate in controls; and (4) group IV, hemodialysis with bicarbonate in uremic dogs. Acute uremia was induced by bilateral ureteral ligation and a 90-minute hemodialysis (acetate or bicarbonate) procedure was performed 72 hours later. The results obtained in this study show that, compared with dogs with normal renal function, acute uremia resulted in an elevation in mean arterial pressure (MAP; 178 ± 13 vs. 115 ± 23 mm Hg, P < 0.01), which was associated with an increase in cardiac index (CI) and left ventricular stroke work index (LVSWI). In these dogs, the pulmonary capillary wedge pressure (PCWP; preload) and the systemic vascular resistance index (SVRI; afterload) were not different than controls. In uremic dogs, hemodialysis with acetate, but not with bicarbonate, decreased the MAP to values similar to controls. The decrease in MAP induced by acetate hemodialysis in uremic dogs was associated with a decrease in SVRI and PCWP. These results suggest that in dogs with acute uremia, acetate hemodialysis (HD) decreases miocardial contractility that was previously increased by a direct effect of uremia. In controls, acetate produced a moderate decrease in MAP that was the result of a mild decrease in CI and SVR. Since PCWP was not significantly decreased after acetate HD, the decrease in CI can be attributed to a mild decrease in myocardial performance. In conclusion, this study in dogs suggests that uremia enhances myocardial contractility directly. Acetate hemodialysis reduces this elevated miocardial contractility to normal values. mean arterial pressure pulmonary capillary wedge pressure central venous pressure heart rate cardiac output cardiac index left ventricular stroke work index systemic vascular resistance index positive end-expiratory pressure arterial O2 partial pressure hemodialysis Cardiovascular instability continues to be one of the main clinical problems in hemodialysis1.Henrich W.L. Hemodynamic instability during hemodialysis.Kidney Int. 1986; 30: 605-612Abstract Full Text PDF PubMed Scopus (125) Google Scholar. Hypotension during hemodialysis has been attributed to a combination of factors: a decrease in plasma osmolality2.Henrich W.L. Woodard T.D. Blachley J.D. Gomez-Sanchez C. Plettinger W. Cronnin R.E. Role of osmolality in blood pressure stability after dialysis and ultrafiltration.Kidney Int. 1980; 18: 480-488Abstract Full Text PDF PubMed Scopus (88) Google Scholar, volume depletion3.Vantone J.C. Bauer J. Carey J. The effect of dialysate sodium concentration on body fluid distribution during hemodialysis.Trans Am Soc Artif Intern Organs. 1980; 26: 383-386Google Scholar, impairment of sympathetic autonomic response4.Daul A.E. Wang X.L. Michel M.C. Brodde O.E. Arterial hypotension in chronic hemodialyzed patients.Kidney Int. 1987; 32: 728-735Abstract Full Text PDF PubMed Scopus (69) Google Scholar,5.Daugirdas J.T. Dialysis hypotension: A hemodynamic analysis.Kidney Int. 1991; 39: 233-246Abstract Full Text PDF PubMed Scopus (298) Google Scholar, myocardial diastolic dysfunction6.Ritz E. Ruffmann K. Rambausek M. Mall G. Schmidli M. Dialysis hypotension–Is it related to diastolic left ventricular malfunction?.Nephrol Dial Transplant. 1987; 2: 293-297PubMed Google Scholar and the use of acetate1.Henrich W.L. Hemodynamic instability during hemodialysis.Kidney Int. 1986; 30: 605-612Abstract Full Text PDF PubMed Scopus (125) Google Scholar,5.Daugirdas J.T. Dialysis hypotension: A hemodynamic analysis.Kidney Int. 1991; 39: 233-246Abstract Full Text PDF PubMed Scopus (298) Google Scholar. Acetate-induced hypotension has been explained by vasodilation due to a direct effect on vascular smooth muscle7.Daugirdas J.T. Nawab Z.M. Acetate relaxation of isolated vascular smooth muscle.Kidney Int. 1987; 32: 39-46Abstract Full Text PDF PubMed Scopus (30) Google Scholar,8.Daugirdas J.T. Swanson V. Islam S. Nutting C. Kim D.D. Wang X. Fiscus R.R. Acetate causes endothelium-independent increases in cyclic AMP, but has no effect on cyclic GMP, in the rat caudal artery.Am J Physiol. 1988; 225: H1378-H1383Google Scholar and by a decreasing myocardial contractility9.Kirkendol P.L. Devia C.J. Bower J.D. Holbert R.D. A comparison of the cardiovascular effects of sodium acetate, sodium bicarbonate and other potential sources of fixed base in hemodialysate solutions.Trans Am Soc Artif Intern Organs. 1977; 23: 399-405Crossref PubMed Scopus (78) Google Scholar, 10.Aizawa Y. Ohmori T. Imak K. Depressant action of acetate upon the human cardiovascular system.Clin Nephrol. 1977; 8: 477-480PubMed Google Scholar, 11.Vincent J.L. Vanherwedhem J.L. Degaute J.P. Berré J. Dufaye P. Kahn J. Acetate-induced myocardial depression during hemodialysis for acute renal failure.Kidney Int. 1982; 22: 653-657Abstract Full Text PDF PubMed Scopus (62) Google Scholar, 12.Ruder M.A. Alpert M.A. Vantone J. Selmon M.R. Kelly D.L. Haynie J.D. Perkins S.K. Comparative effects of acetate and bicarbonate hemodialysis on left ventricular function.Kidney Int. 1985; 27: 768-773Abstract Full Text PDF PubMed Scopus (33) Google Scholar. However, the results reported on the myocardial depressant effects of acetate have not been consistent; some authors have found no myocardial impairment during hemodialysis using acetate as compared to bicarbonate13.Anderson L.E. Nixon J.V. Henrich W.L. Effects of acetate and bicarbonate dialysate on left ventricular performance.Am J Kidney Dis. 1987; 5: 350-355Abstract Full Text PDF Scopus (8) Google Scholar,14.Metha B.R. Fisher D. Ahmad M. Dubose T.D. Effects of acetate and bicarbonate hemodialysis on cardiac function in chronic dialysis patients.Kidney Int. 1983; 24: 782-787Abstract Full Text PDF Scopus (38) Google Scholar. Since uremia may have a direct effect in the regulation of the cardiovascular system, the role of acetate as a factor inducing cardiovascular instability must be analyzed in the setting of uremia. We consider that the effect of acetate on a cardiovascular system may not be the same in an uremic environment as in normal renal function. The aim of this study was to investigate in anesthesized dogs the separate effects of uremia and acetate hemodialysis on blood pressure and the hemodynamic parameters that can be determined by invasive cardiovascular monitoring. The experiments were performed in 28 adult mongrel dogs (20 to 32 kg). Half of the animals underwent bilateral ureteral ligation and the other half were sham-operated. Seventy-two hours later the animals were assigned to four groups of seven dogs each: (1) group I, hemodialysis with acetate in controls; (2) group II, hemodialysis with acetate in uremic dogs; (3) group III, hemodialysis with bicarbonate in controls; and (4) group IV, hemodialysis with bicarbonate in uremic dogs. The animals were allowed free access to water but not food during the 12 hours preceding the experiment. Anesthesia was induced by intravenous administration of sodium penthobarbital (15 mg/kg body wt) and maintained with a combination of pancuronium bromide (0.1 mg/kg body wt), fentanyl (0.05 mg/kg body wt), and midazolam (0.2 mg/kg body wt). An endotracheal tube was placed and ventilation was maintained using a volumetric respirator (MA-2 Puritan Bennett, Los Angeles, CA, USA). The ventilatory parameters were: tidal volume, 15 ml/kg/body wt; FiO2= 0.5, PEEP= 5 cm H2O; respiratory rate between 12 to 15 rpm to maintain the PaCO2 at 32 to 35 mm Hg. The femoral artery and vein were used as vascular access for hemodialysis. Blood and dialysate flow rates were 100 and 500 ml/min, respectively. The hemodialysis period was 90 minutes, there was no ultrafiltration, and the membrane used was cuprophan 0.7 m2. Anticoagulation was achieved with a pre-hemodialysis i.v. bolus of sodium heparin 100 IU/kg. The composition (mEq/liter) of the dialysate was: sodium 138, potasium 4 and acetate 35 for the acetate dialysate; and the same sodium and potassium concentration, with bicarbonate 35 and acetate 2.75, for the bicarbonate dialysate. An indwelling catheter was inserted into the contralateral femoral artery for blood pressure monitoring and blood sampling. A triple lumen Thermodilution Swan-Ganz catheter (Edwards Laboratories AHS, Añasco, Puerto Rico, USA) was inserted through an upper limb vein and advanced into the main pulmonary artery. Both the Swan-Ganz and the arterial catheters were connected to pressure transducers (model 21080A; Hewlett-Packard, Palo Alto, CA) previously placed at the level of the middle right atrium. Pressure measurements and ECG were recorded using a four-channel amplifier (model 7754B; Hewlett-Packard). Cardiac output (CO) was measured by a thermodilution technique (Cardiac output computer model 9520; Edwards Laboratories). Each value represented the mean of three consecutive measurements. The following parameters were measured at baseline and at 15 minute intervals: blood pressure, heart rate (HR), pulmonary capillary wedge pressure (PCWP), cardiac output (CO) and central venous presssure (CVP). The following hemodynamic and pulmonary function parameters were calculated based on previously published formulas15.Yang S.S. Bentivoglio L.G. Maranhao V. Goldberg H. From Cardiac Catheterization Data to Hemodynamic Parameters. F.A. Davis Company, New York1972: 332Google Scholar,16.Nunn J.F. Applied Respiratory Physiology. Butterwort & Co. Ltd., London1979: 524Google Scholar: mean arterial pressure (MAP), cardiac index (CI), systolic index (SI), left ventricular stroke work index (LVSWI), systemic vascular resistance index (SVRI). Body surface area (BSA) was calculated using the formula: BSA = 0.112 ×3√(weight)217.Lacroix E. Leusen I. La circulation hépatique et splacnique.J Physiol. 1965; 57: 115-122Google Scholar. Blood samples were drawn from the femoral artery at baseline and at 15 minute intervals to test the following: total protein, creatinine, BUN, sodium and potassium by autoanalyzer; acetate concentration by an enzymatic technique using a kit from Boehringer Manheim, Germany; osmolality by freezing point depression (Fiske Os Osmometer; Beckman, Germany); and blood gases (Radiometer, ABL-2, Copenhagen, Denmark). Plasma volume was measured before and after completing hemodialysis using 131I-albumin from Sorin Biomedica (Mirandola, Italy). All animals received humane care in compliance with the "Principles of Laboratory Animal Care," formulated by the National Society for Medical Research and the "Guide for the Care and Use of Laboratory Animals," prepared by the National Academy of Science and published by the National Institutes of Health (NIH publication No 86-23, revised 1985). The results are expressed as the mean ±se. Comparisons between two means were made by a non-paired t-test. ANOVA followed by Scheffé's test was used for multiple comparisons. Statistical significance was defined as P < 0.05. Compared to controls, uremic dogs showed significantly higher values of serum creatinine, osmolality, potassium and total protein. The serum bicarbonate levels were lower in uremic than in control dogs (Table 1). The weight was similar in both groups, and the measured plasma volume was moderately decreased in uremic as compared to control dogs, although the difference was not statistically significant.Table 1Basal parameters in control and uremic dogs Open table in a new tab Baseline hemodynamic parameters for control and uremic dogs are given in Figure 1. MAP was markedly increased in uremic dogs as compared to controls (178 ± 13 vs. 115 ± 23 mm Hg, P < 0.01). This increase in MAP in uremic dogs was associated to a significant elevation of CI (2.75 ± 0.51 vs. 4.09 ± 0.82 liter/min/m2P < 0.05), with no differences in PCWP. The LVSWI was greater in uremic than in control dogs (70.4 ± 17 vs. 33.3 ± 11 g/m/m2P < 0.05) and the SVRI did not significantly differ in both groups (3674 ± 869 vs. 4194 ± 648 dyn × sec/cm5, NS in control and uremic dogs, respectively). Changes in MAP, CI and SI during acetate and bicarbonate hemodialysis in control and uremic dogs are shown in Figure 2A. Bicarbonate hemodialysis did not result in a significant change in MAP in control dogs. In uremic dogs, bicarbonate hemodialysis caused a moderate decrease in blood pressure, but the MAP values at the end of HD were still high (167 ± 7 mm Hg). By contrast, acetate HD resulted in a marked decrease in MAP in uremic dogs (from 174 ± 15 to 98 ± 29 mm Hg, P < 0.01). In controls, acetate HD also led to a significant decrease in MAP (from 120 ± 18 to 92 ± 27 mm Hg, P < 0.01). The MAP decrease induced by acetate HD was greater in uremic than control dogs, and at the end of the HD procedure MAP values in uremic and control dogs were similar. As seen for MAP, bicarbonate HD did not induce a significant change in CI in control dogs, while in uremic dogs it caused only a moderate decrease in CI that did not reach statistical significance. In uremic dogs that had high baseline CI values acetate HD decreased CI to almost half compared to baseline; however, these values of CI after acetate HD were similar in uremic and control dogs. In controls, acetate HD caused a moderate increase in CI at 15 minutes that did not reach statistical significance, and at the end of hemodialysis the values were similar to baseline. Bicarbonate HD did not significantly change SI in control and uremic animals. Acetate HD caused changes in SI similar to those observed in CI, while in uremic dogs acetate HD decreased the SI to half the initial values. In controls, acetate HD resulted in a moderate increase in SI at 15 minutes, followed by a progressive decrease until the end of HD, at which time values were not different from baseline. SI values after acetate HD were lower in uremic than in control dogs, but the difference was not statistically significant. Changes in SVR, PCWP, and LVSWI during acetate and bicarbonate hemodialysis in controls and uremic dogs are shown in Figure 2B. During bicarbonate HD, the SVRI did not change in uremic and control dogs. Acetate HD induced an initial (15 min) fall in SVRI in the control group that was not statistically significant by one-way ANOVA. In uremic animals, the SVRI did not significantly change during acetate HD. During bicarbonate HD, the PCWP remained unchanged in the control and uremic groups. In control dogs undergoing acetate HD, the PCWP tended to remain moderately elevated, but the difference was not statistically significant compared to baseline values. However, by the end of the procedure the values were similar to those seen at baseline, and in uremic animals PCWP did not change with acetate HD. Bicarbonate HD did not cause a significant change in LVSWI controls. In uremic dogs, bicarbonate HD led to a moderate decrease in LVSWI that was not statistically significant until the end of the bicarbonate HD. Nevertheless, in uremic dogs LVSWI was still higher than in controls at the end of bicarbonate HD (P < 0.01). By contrast, in uremic dogs acetate HD induced a relatively rapid decrease in LVSWI, and the values and the end of the procedure were similar to those of controls treated with bicarbonate HD. In controls treated with acetate HD, the LVSWI did not change significantly. The left ventricular work relative to the corresponding cardiac filling pressure is a measure of myocardial contractility. Therefore, the relationship between LVSWI and PCWP in each group of dogs before and after bicarbonate and acetate HD is shown in Figure 3. For a mean baseline PCWP within a relatively narrow range (7 to 11 mm Hg), the LVSWI was greater in uremic than in control dogs. The acetate HD caused a marked decrease in LVSWI that was not associated to a commensurate decrease in PCWP. At the end of acetate HD, the LVSWI values in uremic and control dogs were similar. In uremic dogs, bicarbonate HD caused a very modest decrease in LVSWI compared to the LVSWI decline induced by acetate HD despite a similar PCWP. In controls, bicarbonate HD did not induce a significant change in LVSWI and PCWP, while acetate HD caused a mild drop in LVSWI despite no significant change in PCWP. Therefore, in uremic dogs myocardial contractility was increased compared with controls, and after acetate HD myocardial contractility decreased to values that were not different from those of controls after acetate HD. In control dogs, acetate HD resulted in a modest decrease in myocardial contractility. Bicarbonate HD has no significant effect on myocardial contractility. As expected, serum acetate increased after acetate HD in control and uremic dogs. Blood pH and serum bicarbonate were decreased after acetate HD as compared with bicarbonate HD (Table 2). In uremic dogs, serum creatinine and osmolality decreased with both bicarbonate and acetate HD. The degree of change of these parameters was similar with both types of HD. Both types of HD caused no significant changes in plasma volume.Table 2Acetate hemodialysis in control and uremic dogs Open table in a new tab This study was designed to evaluate in dogs the independent effects of uremia and HD with acetate on MAP and invasive hemodynamic parameters. Uremia was induced by bilateral ureteral ligation, and the animals were evaluated 72 hours later. Both uremic and control (non-uremic) animals underwent hemodialysis with acetate, and different dogs were hemodialyzed with bicarbonate. The results obtained in this study show that compared with dogs with normal renal function, those with acute uremia show an increased MAP that is associated with an increase in CI and LVSWI. In these dogs, PCWP (preload) and SVRI (afterload) did not differ from the control values. The mechanism by which acute uremia increases LVSWI is not clear, because neither preload nor afterload changes explain the increase in LVSWI. Thus, based on our results, uremia has a direct positive inotropic effect. It is important to emphasize that dogs used in the present study had acute uremia, so that hemodynamic findings may not be comparable to those seen in chronic uremia. Patients with chronic renal failure on maintenance dialysis have end organ damage, which is absent in our dog model of acute uremia. Therefore, we consider that the specific effect of uremic toxic products on cardiovascular function should be evaluated in the setting of acute uremia. In uremic dogs, hemodialysis with acetate, but not with bicarbonate, decreased MAP to values similar to those of control dogs. The decrease in MAP induced by acetate hemodialysis in uremic dogs was associated with a decrease in CI and LVSWI and with no significant changes in SVRI and PCWP. These results suggest that in dogs with acute uremia, acetate HD decreases myocardial contractility that was previously increased by a direct effect of uremia. Thus, the drop in MAP can be explained by a decreased CI with little or no influence of SVRI. There were some differences between the effect of acetate hemodialysis in control and uremic dogs. In controls, acetate caused a slight decrease in MAP, resulting from a mild decrease in CI and SVR. Since PCWP was not significantly decreased after acetate HD, the decrease in CI can be attributed to a slight decrease in myocardial performance. In controls, acetate HD caused transient changes in hemodynamic parameters at 15 minutes that are worth discussing. Compared to baseline, CI and LVSWI were increased after 15 minutes, and SVRI was decreased. From this time point until the end of the procedure, CI and LVSWI tended to decrease, while SVRI remained unchanged. These results show that in non-uremic animals the short-term increase in serum acetate concentration may cause both a decrease in SVR and an increase in CI, the latter being secondary to the decrease in afterload. Both effects have been reported by different authors14.Metha B.R. Fisher D. Ahmad M. Dubose T.D. Effects of acetate and bicarbonate hemodialysis on cardiac function in chronic dialysis patients.Kidney Int. 1983; 24: 782-787Abstract Full Text PDF Scopus (38) Google Scholar, 18.Nixon J.V. Mitchell J.H. McPhaul JR, J.J. Henrich W.L. Effect of hemodialysis on left ventricular function. Dissociation of changes in filling volume and in contractile state.J Clin Invest. 1983; 71: 377-384Crossref PubMed Scopus (83) Google Scholar, 19.Nitenberg A. Huyghebaert M.F. Blanchet F. Amiel C. Analysis of increased myocardial contractility during sodium acetate infusion in humans.Kidney Int. 1984; 26: 744-751Abstract Full Text PDF PubMed Scopus (17) Google Scholar, 20.Nutting C.W. Islam S. Ye M. Batlle D. Daugirdas T. The vasorelaxant effect of acetate: Role of adenosine, glycolysis, and lyotropism, and pHi and Cai2+.Kidney Int. 1992; 41: 166-174Abstract Full Text PDF PubMed Scopus (22) Google Scholar. Bicarbonate HD induced basically no change in the hemodynamic parameters tested, thus demonstrating that the hemodialysis procedure per se was not the main cause of the hemodynamic changes observed. Plasma volume and osmolality were similar after both types of hemodialyses; however, pH and serum bicarbonate levels were lower after acetate than bicarbonate hemodialysis. It is unlikely that this mild decrease in pH induced by acetate hemodialysis could explain the marked differences in hemodynamic parameters. In conclusion, the results of the present study in dogs with acute uremia suggest that uremia enhances myocardial contractility directly, and that acetate hemodialysis reduces the resulting increased myocardial contractility to normal values. This work was supported in part by Fundación Hospital Reina Sofía-CajaSur.