A Critical Examination of Dialysis-Induced Hypotension

A Critical Examination of Dialysis-Induced Hypotension Prakash Keshaviah, Ph.D. and Fred L. Shapiro, M.D., F.A.C.P. Dialysis-induced hypotension has received considerable attention recently because of its high incidence of occurrence. Several factors have been proposed as etiologic mechanisms . They include hypovolemia, autonomic dysfunction , decreasing serum osmolality, vasodilation (or the inhibition of compensatory vasoconstriction) , efficiency of diffusive solute transport, depletion of vasoactive substances and blood gas and acid-base changes . The primary determinants of blood pressure being cardiac output and total peripheral resistance, the magnitude and direction of change of these two parameters determines the blood pressure response. If the rate of ultrafiltration exceeds the rate of vascular refilling, hypovolemia results. Intracellular fluid shifts secondary to preferential solute removal from the extracellular space may compromise vascular refilling and contribute to hypovolemia . If the hypovolemia is not compensated for by increases in heart rate or stroke volume , the cardiac output falls. Autonomic dysfunction , a previous history of myocardial infarction or impaired tissue oxygenation secondary to hypoxia may limit compensatory increases in heart rate and stroke volume. Even if the cardiac output falls , if compensatory vasoconstriction is elicited, blood pressure can be maintained . The experimental evidence suggests that the diffusive aspect of dialysis therapy plays an important role in inhibiting compensatory vasoconstriction. Such inhibition is not observed with hemofiltration, a therapy based on convective rather than diffusive solute removal . While autonomic dys-

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HE trend towards shorter, more efficient dialyses and the increasing age of the population on hemodialysis have accentuated the problem of symptomatic hypotension. This problem has received considerable attention in recent years and several different mechanisms have been postulated. At present, no consensus exists regarding the etiology of the hypotension other than it is probably multifactorial. The different factors that have been proposed as mechanisms are listed in Table 1. This list is not exhaustive but includes those factors that are supported by experimental data. Before examining these proposed mechanisms, the physiology of

From the Regional Kidney Disease Program at Hennepin County Medical Center, Minneapolis, Minn. Reprint requests should be addressed to Prakash Keshaviah. Ph.D ., Regional Kidney Disease Program, Hennepin County Medical C enter, 701 Park Avenue, Minn eapolis , Minn. 55415. © 1982 by The National Kidney Foundation , Inc . 0272 ·6386/82 /020290·12$02 .00/0

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function and the diffusive removal of vasoactive substances may play a role in inhibiting the vasoconstrictive response, the use of acetate as a buffer source and the decreasing serum osmolality seem to be of greater importance. Acetate produces vasodilation. It also has a positive inotropic effect . Studies suggest that the vasodilation produced by acetate is compensated for by a proportionate increase in cardiac output except during the early stages of the therapy when the fall in total peripheral resistance may overwhelm the increase in cardiac output. The substitution of bicarbonate for acetate results in a decrease in the incidence of symptomatic hypotension in some patients . This alleviation of symptoms appears to be significant only when the dialystate sodium concentration is relatively low ( 130~ 135 mM). At higher dialysate sodium concentrations (l40~ 145 mM), the blunting of the fall in serum osmolality seems to be of greater importance than the nature of the buffer source in reducing the incidence of symptomatic hypotension . It is not clear if blunting the fall in serum osmolality has a greater beneficial influence on the cardiac output or on the total peripheral resistance. While the etiology of dialysis-induced hypotension is complex, controversial, and multifactorial, amelioration of symptomatic hypotension with a higher dialysate sodium concentration offers a practical solution. The substitution of bicarbonate for acetate is a technically more complex and expensive alternative .

blood pressure maintenance will be reviewed briefly. The mean arterial pressure is the resultant product of the cardiac output and total peripheral resistance. The cardiac output in tum is the product of the stroke volume and the heart rate. The stroke volume is a function of myocardial contractility and vascular volume. The mean arterial pressure is therefore a function of the total peripheral resistance, vascular volume, heart rate and myocardial contractility. The dialytic process can influence all of these parameters and the direction and magnitude of change of these parameters together influence the blood pressure. The blood pressure and heart rate are readily measured whereas the measurement techniques for cardiac output, vascular volume and myocardial contractility are not readily adapted to the routine clinical setting. It is difficult to arrive at the etiology of dialysisinduced hypotension without knowing the time course and interaction of these various parameters .

American Journal of Kidney Diseases, Vol. It, No.2, September 1982

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Table 1. Mechanisms Postulated for Dialysis-Induced Hypotension 1. 2. 3. 4.

Hypovolemia Autonomic dysfunction Decreasing serum osmolality Vasodilatiorv'lnhibition of compensatory vasoconstriction 5. Efficiency of solute transport 6. Depletion of vasoactive substances 7. Blood gas and acid-base changes

Some of the confusion that exists in the literature is related to the fact that many of the studies purporting to elucidate the mechanisms responsible for hypotension do not include measurements of these various parameters, resulting in an incQmplete understanding of the problem. Further, hypotension is not always defined objectively or consistently. Also, in many experiments, more than one parameter is varied and important parameters such as the dialysate sodium concentration are not controlled, making interpretation of the results difficult. The factors listed in Table 1 have been proposed as mechanisms by various investigators. As has been pointed out by Kjellstrand,l the distinction between pathogenetic, mediating, underlying pathologic and pathophysiologic factors is not always made. If, for example, ultrafiltration produces hypovolemia and a decreased cardiac output which because of autonomic dysfunction is not compensated for by an increased total peripheral resistance, hypotension could result. In this example, ultrafiltration would be the pathogenetic factor, hypovolemia the mediating factor and autonomic dysfunction the underlying pathological factor. The decreased cardiac output not compensated for by vasoconstriction describes the pathophysiology of the observed hypotension. The relative importance of the factors listed in Table 1 depends on the role they play in terms of being pathogenetic, mediating, pathologic or pathophysiologic factors. As some or all of these factors may be involved in a given episode of hypotension, with varying degrees of involvement, the etiology of dialysis-induced hypotension is complex and a simple explaI\ation would not only be superficial but misleading as well. HYPOVOLEMIA

Until recently hypotensive episodes were thought to be primarily related to hypovolemia in-

duced by ultrafiltration. This conVIctIOn was strengthened by the clinical observation that the hypotension was readily corrected by the infusion of fluids such as saline and albumin. Fluid is removed by ultrafiltration directly out of the vascular compartment. Hypovolemia can result if the rate of fluid removal exceeds the rate of vascular refilling from other body spaces. Some of the earliest measurements of plasma volume changes during hemodialysis were made by Kim et al. 2 who showed a progressive depletion of plasma volume, the rate of change being greatest in the early phase of the therapy. Kim and his coworkers quantitated the rate of vascular refilling from other body spaces and their measurements show that in the first hour of dialysis, plasma water contributed 64% of the ultrafiltered volume. In seven of the nine hypotensive episodes encountered in their study, blood volume fell below 50 ml/kg body weight. With decreasing durations of therapy, higher rates of ultrafiltration are necessary, thereby increasing the susceptibility to hypovolemia. If compensatory mechanisms, such as vasoconstriction, are not brought into play, hypotension can result. AUTONOMIC INSUFFICIENCY

Kersch , et al. 3 studied 8 patients who suffered severe hypotension during hemodialysis. They showed that based on the Valsalva maneuver and the amyl nitrite test, six of these eight patients had autonomic insufficiency, probably due to the generalized neuropathy of the uremic state. During dialysis-induced hypotensive episodes in these six patients, the total peripheral resistance fell and no increase in heart rate was noted despite a decline in central blood volume. The hypotension did not improve in these patients after volume expansion with 250 ml of saline but did respond to administration of norepinephrine. More recently, Nies et al. 4 subjected five patients with recurrent hypotension, and eight normotensive patients to a battery of tests of autonomic nervous system function. The response to the Val salva maneuver was generally abnormal and did not differentiate between the two groups. However, baroreceptor sensitivity, measured in terms of the response to a high pressure stimulus, was blunted only in the hypotensive subjects. The cause for this diminished sensitivity is unknown. Nies et al. conclude that autonomic dysfunction is not a sufficient explanation of dialysis-induced hypotension. The incidence of overt neuropathy in

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the dialysis population has decreased markedly in recent years, whereas the incidence of dialysis induced hypotension has not.

CONVENTIONAL THERAPY Ie

4

DECREASING SERUM OSMOLALITY

The observation that isolated ultrafiltration did not produce symptomatic hypotension was first reported by Kobayashi and coworkers in 1972 5 and later confirmed by Ing et al. in 1975. 6 Bergstrom, et al. in 1976 7 first demonstrated that ultrafiltration alone was well tolerated but not when combined with diffusion (using acetate as the buffer source). The potential benefit of separating and sequencing diffusion and ultrafiltration was also described by Shaldon in 1976. 8 These results have been confirmed by several other investigators, 9-13 and have led to a much better understanding of the problem of dialysis-induced hypotension. It has become clear that fluid removal does not, in itself, precipitate hypotension and that diffusive solute transport plays an important role. What aspect of diffusive solute transport is responsible for hypotension is as yet unclear. Bergstrom, in examining his data on the role of diffusive solute transport in inducing hypotension, suggested that serum osmolality was implicated. During isolated ultrafiltration, fluid removal was accomplished iso-osmotically, whereas in conventional hemodialysis, fluid was removed against a background of decreasing serum osmolality. Bergstrom speculated that the decreasing serum osmolality may influence baroreceptors, the vasomotor center, or the efferent sympathetic pathways and hence induce hypotension. Falls et al. 14 and Dh et al. 15 in some early studies showed that hemodialysis provokes a fluid shift of the order of 1 to 1.5 liter from the extracellular into the intracellular compartment, presumably as a consequence of preferential removal of solutes from the extracellular compartment and the resulting osmotic gradient between these compartments. These studies and Bergstrom's demonstration that diffusive solute transport may playa role in dialysis-induced hypotension, led us, in 1978,16 to formulate a model based on transcompartmental fluid shifts to explain the role of diffusive solute removal in the etiology of dialysisinduced hypotension. Figure 1 is a schematic representation of our fluid shift model. During conventional hemodialysis (panel a) preferential solute removal from the extracellular compart-

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Fig. 1. Schematic representation of transcompartmental fluid shifts in conventional therapy (top panel) and in the ultrafiltration phase (middle panel) and diffusive phase (bottom panel) of sequential therapy. The full and broken arrows represent shifts induced by osmotic and oncotic gradients respectively and the length of the arrow represents the approximate magnitude of the shift.

ment induces an intracellular fluid shift. Interstitial fluid is also mobilized for vascular refilling in response to the increased oncotic gradient across the capillary endothelium resulting from the ultrafiltration of a protein-free fluid from the vascular compartment. There is, hence, a two-way mobilization of interstitial fluid. During isolated ultrafiltraton (panel b), there is only one way mobilization of interstitial fluid (vascular refilling) as no osmotic gradients are established between the intra and extracellular compartments. Vascular refilling would therefore be more effective during isolated ultrafiltration, plasma volume depletion being less marked than in conventional hemodialysis.

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Table 2.

Changes in Body Fluid Spaces (Animal Studies) Conventional Dialysis Group" (n = 8)

Sequential UF and Diffusion Group III (n = 7)

Volume Untrafiltered (Vuf, ml) A Plasma Volume (mi) A Extraceliular Volume (ml) A ECV versus Vuf

Isolated UF

Diffusion With No UF

Total

700 180 ± 50 920 ± 170 NS

0 160 ± 10 260± 220

700 340± 50 1170± 150 P = 0.12

Total

684 330 ± 140 1190 ± 120 p = .002

Note: Values shown are Mean ±SEM; .UF: ultrafiltration; ECV: extraceliular volume.

Animal studies were undertaken to test this fluid shift hypothesis. 17 Two groups of acutely uremic dogs were studied, one group subjected to 4 hr of conventional hemodialysis and the other group to 1 hr of isolated ultrafiltration followed by 3 hr of diffusion with no further fluid removal. Dialysate sodium and acetate concentrations were 140 mM and 38 mM, respectively, in both groups . Plasma and extracellular fluid volumes were measured using 1251 RISA and 35S04 , respectively. The results are summarized in Table 2. The data indicate that in both sequential therapy and in conventional hemodialysis, the decrease of the extracellular fluid volume exceeds the volume ultrafiltered, this excess representing the intracellular fluid shift. During isolated ultrafiltration, such a shift is absent, the decrease in extracellular volume not being significantly different from the volume ultrafiltered. During diffusion, despite the absence of ultrafiltration, the extracellular and plasma volumes decrease implying an intracellular fluid shift induced by the diffusive therapy. Further, the data indicate a smaller decrease in plasma volume during isolated ultrafiltration compared to conventional hemodialysis for the same volume of fluid ultrafiltered, suggesting better vascular refilling during isolated ultrafiltration. The magnitude of the intracellular fluid shift was of the order of 500 ml in dogs with a mean body weight of 25 kg . Scaling this to the clinical setting, one would anticipate an intracellular fluid shift of the order of 1.5 liters, this being of the same order of magnitude as determined by Falls et al. 14 and Oh et al. 15 Cardiovascular measurements were also performed during these studies and will be referred to later. Blood pressure was maintained during isolated ultrafiltration but marked decreases were noted during conventional hemodialysis as well as during diffusion with no fluid removal. Van Stone and coworkers have recently studied the influence of dialysate sodium concentrations

on transcompartmental fluid shifts. 18 They measured the volumes of total body water, extracellular water and plasma in five patients subjected to three different levels of dialysate sodium equal to the serum sodium, 7% greater and 7% less than the serum sodium. Their data show that when the dialysate sodium concentration is equal to the serum sodium concentration , essentially all the water removed during dialysis is from the extracellular compartment. When the dialysate sodium concentration is below the serum sodium concentration , there is a fluid shift from the extracellular to the intracellular compartment. When the dialysate sodium concentration exceeds the serum sodium concentration, water is removed proportionately from both the intracellular and extracellular compartments . Plasma volume losses were disproportionately greater than losses from the other body compartments in all three cases , but the high dialysate sodium concentration minimized this effect. Symptomatic hypotension was noted in four of the five low dialysate sodium dialyses but in none of the normal and high sodium dialyses. Levine et al. 19 have also shown that increasing the dialysate sodium concentration from 126 to 135 mM decreased the frequency of hypotensive episodes from 1.4 to 0 .8 episodes/dialysis, despite a larger weight loss . The benefits of a high sodium dialysate in reducing intradialytic symptoms were reported by Stewart et al. in 1972. 20 They studied nine patients over a period of 15 mo divided into four phases. During phases 1 and 3 (3 mo each), the dialysate sodium concentration was 132.5 mM and in phases 2 and 4 (5 and 4 mo, respectively), the dialysate sodium concentration was 145 mM. There were fewer symptoms (headaches, vomiting, cramps) during the high sodium dialyses . Also , patients were less tired on the day following dialysis. There were no significant changes in predialysis diastolic blood pressures. Mean weight

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gains between dialyses were significantly greater during high sodium dialysis . However the increased weight gains were correctable by ultrafiltration with fewer intra-dialytic symptoms in the high sodium dialyses. These investigators concluded that the reduced symptoms noted during high sodium dialyses were probably related to smaller changes in extracellular volume and the absence of concomitant cellular overhydration . The influence of serum osmolality changes on intradialytic symptoms and EEG recordings was studied by Port et al . 21 in nine patients whose plasma osmolality was maintained constant during dialysis by the constant infusion of hypertonic saline into the dialysate. The control group consisted of eight patients studied during dialysis with a. dialysate sodium of 133 mM . The EEG recordings showed abnormalities in 10 of 13 control dialyses compared to two of nine experimental dialyses. Symptoms suggestive of the disequilibrium syndrome appeared in nine of the control and none of the experimental dialyses. Rodrigo et al. 22 used a high dialysate glucose concentration and intravenous mannitol to blunt the fall of serum osmolality during dialysis . The intravenous mannitol was more effective than the high dialysate glucose in promoting large changes in serum osmolality. The clinical signs of disequilibrium (headache , nausea , vomiting, and hypotension) declined in parallel with the decline in serum osmolality changes, being independent of the ultrafiltration rate. In a double blind crossover study comparing dialysate sodium concentrations of 131 and 146 mM, Ogden et al. 23 reported a decrease in disequilibrium symptoms, muscle cramps and hypotension during the high sodium dialyses . The incidence of disequilibrium symptoms were compiled based on patient questionnaires and the incidence of muscle cramps and hypotension compiled from questionnaires filled out by dialysis attendants. Van Stone and Cook24 have also shown, in a double blind study, that raising the dialysate sodium concentration (from 137 mM to 142 mM) increases the patient's state of well being postdialysis assessed by scoring patient responses. No significant differences were noted in the incidence or severity of intradialytic symptoms between the two dialysate concentrations. Mild increases were noted in the interdialytic weight gain and postdialysis systolic pressures with the high sodium dialyses. The studies of Port,

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Ogden, and Van Stone were all acute studies and do not permit conclusions concerning the longterm effects of using a high dialysate sodium in terms of increased thirst and hypertension. The Stewart study20 was of longer duration and indicates no apparent ill effects of raising the dialysate sodium concentration . VASODILATION/INHIBITION OF COMPENSATORY VASOCONSTRICTION

The benefits of blunting the fall in serum osmolality have been demonstrated in the various studies cited above. However, it is not clear if blunting the osmolality decrease has a beneficial influence on plasma volume alone or if it also influences any of the other determinants of blood pressure. Hemodynamic studies have shown that another determinant of blood pressure, namely total peripheral resistance , may be of pivotal importance in determining the blood pressure response. This finding has been confirmed by several investigators.9-12 These studies have shown that during isolated ultrafiltration there is a significant decrease in the cardiac output which is primarily related to a decrease in stroke volume associated with the fluid removal. However, blood pressure is maintained despite the fall in cardiac output by a marked increase in the total peripheral resistance . In other words, compensatory vasoconstriction plays an important role in preventing hypotension during isolated ultrafiltration. On the other hand, during pure diffusive therapy (with acetate as the buffer source and no fluid removal), there is an increase in cardiac output related mainly to an increased heart rate. Despite this increase in cardiac output, there is a fall in the blood pressure related to a marked decrease in the total peripheral resistance . In conventional hemodialysis (with simultaneous ultrafiltration and diffusion), the cardiac output falls as a consequence of a decreasing stroke volume which overwhelms the effect of the increased heart rate . No compensatory vasoconstriction is elicited, the total peripheral resistance remaining relatively constant. As a consequence the blood pressure falls. It appears that during conventional hemodialysis with acetate, the vasoconstrictive response to hypovolemia is masked by a vasodilatory tendency induced by the diffusive nature of the therapy . These opposing tendencies result in no net change in the total peripheral resistance thereby leading to hypo-

DIALYSIS-INDUCED HYPOTENSION

tension. In the light of these data, the previously held notion that autonomic insufficiency alone inhibits compensatory vasoconstriction seems incorrect. A given patient who is able to elicit vasoconstriction during isolated ultrafiltration is unable to do so during conventional hemodialysis, thereby implicating some aspect of the therapy rather than the compentency of the patient's nervous system. It is unclear if the inability to vasoconstrict during conventional hemodialysis is related to the fall in serum osmolality or to some other aspect of the therapy. The importance of preventing large decreases in serum osmolality have been demonstrated in several different ways. However, it is not known if the beneficial influence of blunting the fall in serum osmolality is related to preventing hypovolemia or facilitating compensatory vasoconstriction. Several investigators have shown that acetate can reduce total peripheral resistance. 25 -28 The studies of Kirkendol et al. 29 also indicate that acetate is a myocardial depressant. Kirkendol's early studies cannot, however, be extrapolated to the dialysis setting, as he infused bolus doses of acetate very rapidly into dogs and showed a decrease in myocardial contractility. Other animal and human studies 30-32 with rates of acetate infusion similar to those in dialysis show that acetate has a positive inotropic effect, cardiac output being actually increased. In most of these studies, the vasodilation produced by acetate did not result in a fall in the mean arterial pressure because of the proportionate increase in cardiac output. Aizawa and coworkers have studied the changes in hemodynamic parameters during acetate and bicarbonate dialysis 33 and during acetate infusions. 31 In acetate dialysis and during acetate infusion, they noted a significant increase in limb blood flow but no change in the mean arterial pressure. They, hence, deduced a decrease in vascular resistance. No changes in limb blood flow or vascular resistance were noted during. bicarbonate dialysis, but a significant fall in mean arterial blood pressure was noted. In contrast to the increased limb blood flow, Aizawa noted an increase in the ratio of the pre-injection period to the left ventricular ejection time with acetate suggesting depressed left ventricular function. A similar but smaller decrease was also noted during bicarbonate ~ialysis. Milutinovich et al. 34 have also reported

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depressed left ventricular function during acetate dialysis based on the measurement of systolic time intervals. They also noted a pronounced fall in blood pressure with acetate dialysis. Chen et al. 35 have shown that systolic time intervals are unreliable indicators of left ventricular function during dialysis. They report improved contractility and left ventricular function with a decrease in preload and after-load during hemodialysis with acetate-containing dialysate despite a fall in the arterial p02' We have recently reported on some detailed cardiovascular measurements in acutely uremic dogs during iso-osmotic dialysis. 36 Urea was added to dialysate to match the predialysis serum urea level and the dialysate sodium was adjusted to match the serum level. No fluid was ultrafiltered during the first half-hour. Despite the constant osmolality and the absence of fluid removal, we noted transient but significant changes in cardiovascular parameters within a few minutes of initiating dialysis. Mean blood pressure decreased markedly, being associated with an increased cardiac output and a drastic fall in total peripheral resistance. These changes were most pronounced during the phase of an increasing serum acetate level. As the serum acetate level began to plateau, the cardiovascular trends began to reverse but did not return to base-line levels. Unlike other studies, early, very frequent measurements were made allowing us to detect these rapid but transient changes. Such changes could easily be missed with less frequent measurements. In a follow-up study comparing sodium acetate, sodium bicarbonate and sodium chloride infusions in dogs, we were able to confirm that the marked but transient cardiovascular changes noted were related to acetate, not being seen during sodium bicarbonate and sodium chloride infusions. Based on these studies, we infer that the hypotensive episodes noted very early in dialysis are probably related to the acetate-induced decrease in total peripheral resistance, whereas those occurring later during the treatment may be related to hypovolemia and the inability to elicit compensatory vasoconstriction. This inference receives confirmation from the work of Posen and Mikhael 37 who divided patients into two groups based on the occurrence of hypotension within the first hour of dialysis. The group who had the early episodes of hypotension had a mean age greater than 65 and a

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previous history of myocardial infarction and congestive heart failure . In such patients, cardiac reserve is limited so that the marked decrease in total peripheral resistance noted early in treatment cannot be compensated for by an increased cardiac output. Hypotension therefore , results . The early episodes of hypotension were prevented when acetate was replaced by bicarbonate. Graefe et al. 38 compared ultrafiltration tolerance during high efficiency dialysis with acetate and bicarbonate containing dialysates . They noted fewer episodes of hypotension, considerably fewer symptoms (nausea, vomiting, headache, etc.) and an increased tolerance to fluid removal with bicarbonate dialysis . Iseki et al. 39 also noted improved blood pressure control with bicarbonate dialysis relative to acetate dialysis. However, predialysis blood pressures were quite different in the two groups making interpretation of their data difficult. Van Stone et aI. , 40 in a double blind study of acetate and bicarbonate dialyses, noted a lower incidence and severity of symptoms with bicarbonate dialyses but no difference in the blood pressure response. In contrast, Aizawa et al. 33 showed a significant fall in mean arterial blood pressure with bicarbonate dialysis but not with acetate dialysis . In trying to resolve the conflicting evidence from these various studies, one is confronted with the question of whether a higher dialysate sodium or the substitution of bicarbonate for acetate is a more effective way of alleviating dialysis-induced hypotension. Wehle and coworkers 41 addressed this problem by studying the blood pressure response in six patients subjected to isolated ultrafiltration and dialysis against sodium levels of 145 and 133 mM with both acetate (40 mM) and bicarbonate (25 mM) containing dialysates. There were no significant changes in systolic, diastolic or mean arterial pressure with isolated ultrafiltration. At a sodium level of 145 mM, there were no significant changes in systolic, diastolic or mean blood pressures whether acetate or bicarbonate was in the dialysate . At the lower sodium level of 133 mM, there were significant decreases in systolic and mean blood pressures with both bicarbonate and acetate, the decreases being more pronounced with acetate. Raja et al. 42 also found that with a decreasing serum osmolality during dialysis, bicarbonate produced less hypotension

KESHAVIAH AND SHAPIRO

than acetate. The differences between acetate and bicarbonate dialyses were less pronounced when the osmolality decrease was blunted with mannitol infusions. In a recent study, 43 Wehle et al. have readdressed the issue of relative importance of osmolality change versus the source of buffer (acetate versus bicarbonate). Hemodynamic measurements were performed during isovolemic dialyses with five different dialysate compositions which varied with regard to sodium, acetate, bicarbonate and urea. They found that low sodium dialysis (Na = 133 mM) induced a significant fall in blood pressure that was not prevented by the addition of urea to the dialysate . At a higher dialysate sodium (140 mM) , blood pressure was more stable with or without urea and irrespective of whether acetate or bicarbonate was in the dialysate. The use of acetate was associated with a fall in total peripheral resistance. However, the cardiac output increased proportionately resulting in a stable blood pressure. The authors conclude that for blood pressure stability, the change in tonicity produced by sodium is more important than changes in total osmolality or the source of buffer used in the dialysate. Borges et al. 44 compared acetate to bicarbonate dialysis during 120 dialyses in 30 patients with acute renal failure using a double blind protocol. The sodium concentration was 140 mM in both acetate and bicarbonate containing dialysates . Mannitol was infused in a dose of 0 . 5~ 1 g/kg during the first four dialyses , in a given patient. The urea nitrogen clearance was 1.5-2.0 mllmin/kg during the first two dialyses (4 hr duration) being increased to 3 mllmin/kg during the succeeding dialyses (5-6 hr duration) . There were no differences in blood chemistries, osmolality change, or weight loss between the two groups. No differences were noted between the predialysis and the last mean arterial pressure nor in the lowest and highest values during dialysis. There was also no statistical difference between the two groups in the number of dialyses associated with falls in mean arterial pressure less than 25% and greater than 25% of the initial value. The incidence of symptoms were also not statistically different in the acetate and bicarbonate dialyses. While this study is one of the largest acute studies comparing acetate and bicarbonate dialysis , the use of mannitol

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infusions, the lower urea nitrogen clearances in some of the dialyses and the acute dialysis setting cloud the interpretation of the data.

to the reduced rate of acetate influx from dialysate to blood. DEPLETION OF VASOACTIVE SUBSTANCES

EFFICIENCY OF SOLUTE TRANSPORT

An interesting study by Shaldon et al. 45 suggests that the efficiency of diffusive solute transport rather than the change in serum osmolality is more important in the etiology of dialysis-induced hypotension. Shaldon studied six patients with a high incidence of symptomatic hypotension. There were three study phases, each of a month's duration. In the first or control phase, the dialysate flow rate (QD) was 500 mllmin. In the second phase it was reduced to 300 mllmin, and in the final phase it was further reduced to 100 mllmin. All other parameters of the therapy were relatively unchanged during the three phases. A dialysate sodium concentration of 140 mM and an acetate concentration of 40 mM were used in all three phases, there being no glucose in the dialysate. The predialysis body weights were similar in the three phases and the mean loss averaged 2 kg. A 3-wk equilibration period was allowed in each phase and only the data of the last week was used to compare the three phases. As the dialysate flow rate was progressively reduced, the urea clearance was reduced and the predialysis serum urea levels increased, urea generation being unchanged. As a consequence, identical reductions in serum osmolality, pre- to postdialysis were noted in all three phases of the study. Despite similar decreases of serum osmolality, the incidence of symptomatic hypotension decreased from 67% in the control phase (QD = 500) to 50% in phase 2 (QD = 300) and further to 17% in phase 3 (QD = 100). The serum sodium concentration increased from 137 mM predialysis, to 139 mM postdialysis in the control phase. In phase 2, the serum sodium decreased from 139 mM to 137 mM; in phase three it was unchanged at 139 mM. These changes were considered insignificant and did not correlate with the incidence of symptomatic hypotension. No measurements were made of acetate transport during the three phases nor of serum acetate levels. The rate of acetate transport decreases with a decreasing dialysate flow rate. It could, therefore, be hypothesized that the reduced incidence of hypotension noted in Shaldon's study was related

Vasoactive substances such as epinephrine and norepinephrine, are easily removed by the dialysis membrane, being small solutes. There is evidence 46 •47 to suggest that depletion of norepinephrine occurs during dialysis which could be an etiologic factor in inducing hypotension. This hypothesis is consistent with Shaldon's finding of an inverse correlation between the efficiency of the dialytic process and the manifestation of symptomatic hypotension. It is also consistent with the finding that during isolated ultrafiltration, a process characterized by inefficient small solute removal, compensatory vasoconstriction is elicited, this ability being compromised during diffusive therapy. The evidence concerning the depletion of vasoactive substances is, however, controversial and it has been suggested 46 that the circulating concentrations of these amines are not as important as the concentrations at the site of release and action. BLOOD GAS AND ACID-BASE CHANGES

It has been known for a long time that the arterial p02 falls significantly very early in dialysis, and remains low over the remainder of the treatment. Several mechanisms have been formulated to explain the observed hypoxia. They include compromised oxygenation either because of microembolization 49 or from sequestration of leukocytes in pulmonary capillaries secondary to complement activation by the dialyzer membrane, 50 decreased hemoglobin affinity for oxygen with an increasing pH - the Bohr effect, 51 depressed ventilatory drive secondary to dissolved carbon dioxide and bicarbonate losses across the dialyzer membrane, 52 increased oxygen consumption from acetate metabolism and decreased respiratory quotients either secondary to carbon dioxide losses across the dialyzer membrane 52 .53 or as a direct consequence of acetate metabolism. 54 In examining the data from the above studies, it seems clear that the hypoxia can be explained in full by the observed decrease in respiratory quotient. Hypoxia is noted during acetate infusions in the absence of dialysis 55 and the studies of Oh 56

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also indicate a decrease in the respiratory quotient during acetate infusions. Nissenson, 57 and Eiser 58 indicate a blunting of the hypoxia when bicarbonate replaces acetate as the buffer source . Abu-Hamdan, et al. 59 could not, however, show differences in the arterial p02 in a study that alternated acetate and bicarbonate dialyses. Patients on dialysIs are usually anemic. A major adaption to the anemia is an increase in the 2,3DPG levels in red cells, thus facilitating tissue oxygenation . During dialysis, there is not only the early and sustained fall in arterial p02, but also a gradually increasing pH which increases the affinity of hemoglobin for oxygen. Torrance et al. 60 have shown that the fall in p02 together with the increase in pH could decrease oxygen delivery to an extent large enough to negate the influence of the increased 2,3-DPG. In patients with cardiac or respiratory insufficiency, the fall in p02 against the background of an increased pH could cause problems. Ahmad and coworkers 61 have shown that in patients dialyzed with high efficiency dialyzers against an acetate bath, subjective symptoms could be abolished by the administration of supplemental oxygen . Heneghan et al. 62 have also shown recently that the hypoxia induced by dialysis is related to the reduction of the respiratory quotient by acetate metabolism. They gave dialysis patients 200 g of glucose by mouth prior to dialysis, glucose being a substrate that can raise the respiratory quotient. In these patients, there was a blunting of the hypoxia. In another study, 63 Heneghan et al. confirmed the findings of Ahmad that supplemental oxygen can minimize the incidence of hypotensive episodes and the incidence and severity of intradialytic symptoms . This study was done in a double-blind protocol, five patients receiving nasal oxygen or compressed air. There were no significant differences in weight change, dialysate sodium or serum osmolality change between the two groups . HEMOFILTRATION VERSUS HEMODIALYSIS

Various investigators have shown that both preand postdilution hemofiltration are characterized by a lower incidence of hypotension and intradialytic symptoms than hemodialysis . Shaldon 64 and others ]],65 indicate that the primary difference between the therapies is the response of total peripheral resistance . In hemodialysis, total peripheral resistance is unchanged or decreases

KESHAVIAH AND SHAPIRO

slightly, so that a decreasing cardiac output associated with hypovolemia produces hypotension. In hemofiltration, however, the total peripheral resistance increases to compensate for the decreasing cardiac output, thereby maintaining blood pressure. These differences between hemofiltration and hemodialysis were noted by Shaldon whether acetate or bicarbonate was used as the buffer source and despite the use of a higher dialysate sodium (145 mM) in hemodialysis relative to the sodium concentration of 139 mM in the substitution fluid during hemofiltration. In hemodialysis with bicarbonate, the total peripheral resistance was unchanged whereas it declined slightly with acetate. In hemofiltration with bicarbonate, compensatory vasoconstriction was elicited early in the course of treatment. In hemofiltration with acetate, by contrast, there was an initial phase of vasodilation similar to that seen in hemodialysis with acetate. However, later in the course of the therapy , the trend was reversed, marked vasoconstriction being elicited. The differences between hemofiltration and hemodialysis in terms of blood pressure response are not well understood. There is evidence 65 to indicate that the inability to elicit compensatory vasoconstriction during hemodialysis may be due to an impaired sympathetic response. Plasma noradrenaline levels were found to increase during isolated ultrafiltration and hemofiltration but to remain relatively unchanged during hemodialysis. It has been speculated 64 that a vascular de stabilizer of middle to large molecular weight that is retained during conventional hemodialysis is effectively removed by hemofiltration. In isolated ultrafiltration, there is vascular stability despite inefficient solute removal. One can, therefore, invoke the destabilizer hypothesis only if one postulates that the destabilizer is produced during the diffusive phase of hemodialysis therapy. It has been suggested that vascular stability during hemofiltration is attributable to a lower sodium removal than in hemodialysis for the same sodium concentrations in substitution fluid and dialysate because of Donnan effects. 66 This view is still unproven and available measurements of sodium removal in the two therapies tend to dispute this hypothesis. 67 CONCLUSIONS

It is very difficult to synthesize all of the studies reviewed above into a consistent, cohesive and

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meaningful body of knowledge. Some investigators do not always make the distinction between associative and causative phenomena. The logical fallacy of "post hoc ergo propter hoc" (after this, therefore, because of this) is often committed. Further, a maneuver that is palliative IS otten misinterpreted as furnishing proof of etiology. As an example let us consider the following scenario: The infusion of mannitol blunts serum osmolality decrease during dialysis and also decreases the incidence of symptomatic hypotension. Let us assume that in this example, the observed hypotension is primarily related to the inability to elicit vasoconstriction to compensate for a decreasing cardiac output. The infusion of mannitol mobilizes intracellular fluid, increasing cardiac output and thereby preventing hypotension. The primary defect still lies in the vasoconstrictive ability. The mannitol is a palliative, in that it improves cardiac output. It does not playa role in the vasoconstrictive defect and is hence not an etiologic factor. The most direct way to analyze the problem of dialysis-induced hypotension is to look at the trends of cardiac output and total peripheral resistance, the determinants of blood pressure. Any dialysisassociated event that can influence these parameters can influence blood pressure control. Fluid removal and diffusive solute removal may both induce hypovolemia and a fall in cardiac output. If the fall in cardiac output is not compensated for by vasoconstriction, hypotension will ensue. Compensatory vasoconstriction may be compromised by serum osmolality changes, the vasodilatory properties of acetate, by autonomic dysfunction, by the dialytic removal of vasopressors, etc. The degree of hypovolemia induced by fluid removal and the extent to which the cardiac output falls may vary between patients and may be influenced by many factors in a given patient. If the patient can mobilize intracellular and interstitial fluid readily, plasma refilling can offset fluid removal by ultrafiltration, preventing hypovolemia. If plasma refilling cannot k.eep pace with ultrafiltration and hypovolemia results, the cardiac output may still remain unaffected if there are compensatory increases in myocardial contractility and heart rate. Myocardial contractility may be limited by a previous history of myocardial infarction or by decreased tissue oxygenation. The ability to increase the heart rate may be compromised by autonomic dysfunction. The decreasing

osmolality during dialysis may not only interfere with vascular refilling and hence lead to decreases in cardiac output but may also playa direct role in modulating baroreceptor sensitivity or vascular reactivity. Studies assessing the relative importance of the dialysate sodium concentration and the use of acetate as the buffer source suggest that at low dialysate sodium concentrations (130'-135 mM), the use of acetate is associated with a more marked fall of blood pressure than is bicarbonate. At higher dialysate sodium concentrations (140-145 mM) and with hemofiltration there seems to be little difference in blood pressure changes whether acetate or bicarbonate is used as the buffer source. Conversely, one might recommend that with acetate dialysis, a higher dialysate sodium concentration should be used than with bicarbonate dialysis. From a practical viewpoint, it is technically easier and more economical to perform acetate dialysis with a higher dialysate sodium than it is to perform bicarbonate dialysis. Long term trends of weight gain and predialysis blood pressure should, however, be watched more closely when using a higher dialysate sodium concentration. The etiology oCdialysis-induced hypotension is complex and no single, simple explanation can be formulated. There are many palliative maneuvers. If a particular maneuver works in a given patient, it should be used, but one should not be deluded into believing that this demonstrates the specific etiology of the problem.

REFERENCES I. Kjellstrand c: Can hypotension during dialysis be avoided? Controversies in Nephrology 2:12-28, 1980 2. Kim KE, Neff M, Cohen B, et al: Blood volume changes and hypotension during hemodialysis. Trans Amer Soc Artif Int Organs 16:508-522, 1970 3. Kersch ES, Kronfield Sl, Unger A, et al: Autonomic insufficiency in uremia as a cause of hemodialysis-induced hypotension. N Engl 1 Med 290:650-653, 1974 4. Nies AS, Robertson D, Stone Wl: Hemodialysis hypotension is not the result of uremic peripheral autonomic neuropathy. 1 Lab Clin Med 94:395-402, 1979 5. Kobayashi K, Shibata M, Kato K, et al: Studies on the development of a new method of controlling the amount and contents of body fluids (extracorporeal ultrafiltration method: ECUM) and the application of this method for patients receiving long tenn hemodialysis. lap 1 NephroI14:1-15, 1972 6. Ing T, Ashbach DL, Kanter A, et al: Fluid removal and negative-pressure hydrostatic ultrafiltration using a partial vacuum. Nephron 14:451-455, 1975

300 7. Bergstrom J, Asaba H, Furst P, et al: Dialysis ultrafiltration and blood pressure. Proc Eur Dial Transpl Assoc 13:293-305, 1976 8. Shaldon S: Sequential ultrafiltration and dialysis. Proc Eur Dial Transpl Assoc 13:300, 1976 9. Keshaviah P, Ilstrup K, Constantini E, et al: The influence of ultrafiltration (UF) and diffusion (D) on cardiovascular parameters. Trans Amer Soc Artif Intern Organs 26:328333, 1980 10. Wehle B. Asaba H, Castenfors J , et al: Hemodynamic changes during sequential ultrafiltration and dialysis. Kidney Int 15:411-418, 1979 11. Hampl H, Paeprer H, Unger V, et al: Hemodynamic changes during hemodialysis , sequential ultrafiltration, and hemofiltration. Kidney Int 18:S83-S88, 1980 12. Jones EO, Ward MK, Hoenich NA, et al: Separation of dialysis and ultrafiltration - does it really help? Proc Eur Dial Transplant Assoc 14: 160-166, 1977 13. Rouby JJ, Rottembourg J, Durande J, et al: Hemodynamic changes induced by regular hemodialysis and sequential ultrafiltration hemodialysis: A comparative study. Kidney Int 17:801-810, 1980 14. Falls WF Jr , Stacy WK, Bear ES, et al: Dialysisinduced change of extracellular fluid volume in man. Proc Dial & Transpl Forum 2: 155- 160, 1972 15. Oh MS, Levison SP, Carroll HJ: Content and distribution of water and electrolutes in maintenance hemodialysis . Nephron 14:421-432, 1975 16. Keshaviah P, Berkseth RO , Shapiro FL, et al: Mechanisms and control of fluid removal by ultrafiltration. Proceedings of the lith Annual Contractor 's Conference (Artificial Kidney Program , National Institutes of Arthritis, MetaQolism and Digestive Diseases) p 124, 1978 17 . Keshaviah P, I1strup K, Berkseth R, et al: Transcompartmental fluid shifts induced by ultrafiltration (UF) and diffusion (D). Abstract, 11th Annual Meeting of the American Society of Nephrology , p 43A, J 978 18. Van Stone JC, Bauer J, Carey J: The effect of dialysate sodium concentration on body fluid distribution during hemodialysis. Trans Amer Soc Artif Intern Organs 26:383-386, 1980 19. Levine JB, Falk HM , Raja RM , et al: Effects of varying dialysate sodium using large surface area dialyzers. Trans Amer Soc Artif Intern Organs 24:139-141 , 1978 20. Steward WK, Fleming LW , Manuel MA: Benefits obtained by the use of high sodium dialysate during maintenance hemodialysis. Proc Eur Dial & Transpl Assoc 9: 111-118 , 1972 21. Port FK, Johnson WJ, Klass DW: Prevention of dialysis disequilibrium syndrome by use of high sodium concentration in the dialysate. Kidney Int 3:327-333, 1973 22. Rodrigo F, Shideman J, McHugh R, et al: Osmolality changes during hemodialysis: Natural history, clinical correlations, and influence of dialysate glucose and intravenous mannitol. Ann Intern Med 86:554- 561, 1977 23. Ogden DA: A double blind crossover comparison of high and low sodium dialysis. Proc Clin Dial & Transpl Forum 8: 157-165 , 1978 24. Van Stone JC , Cook J: Decreased postdialysis fatigue with increased dialysate sodium concentration. Proc Dial & Transpl Forum 8: 152-156, 1978

KESHAVIAH AND SHAPIRO 25. Bauer W, Richards JW: A vasodilator action of acetate. J Physiol (London) 66:371-378 , 1928 26. Frohlich ED: Vascular effects of the Krebs intermediate metabolites. Am J Physiol 208:149-153 , 1965 27. Molnar JI, Scott JB , Frohlich ED , et al: Local effects of various anions and H+ on dog limb and coronary vascular resistances. Am J PhysioI203:125-132, 1%2 28. Olinger GN, Werner PH , Boncheck LI, et al: Vasodilator effects of the sodium acetate in pooled protein fraction . An Surg 190:305-311, 1979 29. Kirkendol PL, Devia CJ, Bower JD, et al: A comparison of the cardiovascular effects of sodium acetate, sodium bicarbonate and other potential sources of fixed base in hemodialysate solutions. Trans Amer Soc Artif Intern Organs 23: 399-405, 1977 30. Liang CS, Lowenstein JM: Metabolic control of the circulation: Effects of acetate and pyruvate. J Clin Invest 62: 1029-1038, 1978 31. Aizawa Y, Shibata A: Hemodynamic effects of acetate in man . J Dial 2:235-212, 1978 32. Kirkendol PL, Robie NW , Gonzalez FM , et al: Cardiac and vascular effects of infused sodium acetate in dogs . Trans Amer Soc Artif Intern Organs 24:714-718 , 1978 33 . Aizawa Y, Ohmori T , Imai K, et al: Depressant action of acetate upon the human cardiovascular system. Clin Nephrol 8:477-480, 1977 34. Milutinovic J, Bekheit S, Lapp L: Myocardial performance during dialysis with dialysate containing acetate, HCOa and sequential ultrafiltration dialysis. Amer Soc Nephrol (Abstr) p 47, 1980 35. Chen TS, Friedman HS, Del Monte M, et al: Hemodynamic changes during dialysis . Proc Clin Dial Transpl Forum 9:66-71, 1979 36. Keshaviah P, Himes M, I1strup K, et al: Hypotension during iso-osmotic dialysis. Am Soc Nephrol (Abstr) p 43A, 1981 37. Posen GA, Mikhael R: Dialysis-related hypotension: Etiology and prevention. Kidney Int (Abstr) 19: p 394, 1981 38. Graefe U, Milutinovich WC, Follette JE, et al: Less dialysis-induced morbidity and vascular instability with bicarbonate in dialysate. Ann Int Med 88:332-336, 1978 39. Iseki K, Onoyama K, Maeda T , et al: Comparison of hemodynamics induced by conventional acetate hemodialysis, bicarbonate hemodialysis and ultrafiltration . Clin Nephrol 14: 294-298, 1980 40. Van Stone JC, Cook J: The effect of replacing acetate with bicarbonate in the dialysate of stable chronic hemodialysis patients . Proc Clin Dial & Transpl Forum 9: 103-105 , 1978 41. Wehle B, Asaba H , Castenfors J , et al: The influence of dialysis fluid composition on the blood pressure response during dialysis . Clin Nephrol 10:62-66, 1978 42. Raja R, Kramer M, Rosenbaum JL, et al: Prevention of hypotension during iso-osmolar hemodi alysis with bicarbonate dialysate. Trans Amer Soc Artif Intern Organs 26:375-377, 1980 43. Wehle B, Asaba H, Castenfors J, et al: Influence of dialysate composition on cardiovascular function in iso-osmotic hemodialysis. Proc Eur Dial & Transpl Assoc 18: 153-158, 1981 44. Borges HF, Fryd DS , Rosa AA , et al: Hypotension during acetate and bicarbonate dialysi s in patients with acute renal failure. Am J Nephrol 1:24-30, 1981

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45. Shaldon S, Deschodt G, Beau MC, et al: The importance of serum osmotic changes in symptomatic hypotension during short hemodialysis. Proc Clin Dial & Transpl Forum 8:184-188, 1978 46. Cannella G. Picotti GB, Mioni G. et a1: Blood pressure behaviors during dialysis and ultrafiltration. A pathogenic hypothesis on hemodialysis-induced hypotension. Int J Artif Organs 1:69-75, 1978 47. Brecht HM. Ernst W, Koch KM: Plasma noradrenaline levels in regular hemodialysis patients. Proc Eur Dial Transpl Assoc 12:281- 290. 1976 48. Korchik WP, Brown DC, DeMaster EG: Hemodialysis induced hypotension. Int J Artif Organs l:p 151, 1978 49. Bischel MD, Scoles BG, Mohler TG: Evidence for pulmonary microembolization during hemodialysis. Chest 67: 335- 337, 1975 50. Craddock PR, Fehr J, Brigham KL, et al: Complement and leukocyte mediated pulmonary dysfunction in hemodialysis. N Engl J Med 296:769- 774, 1977 51. Wathen RL: The impact of acetate and bicarbonate containing dialysate on hydrogen ion balance. Proc Renal Physicians Assoc 1: 19-24, 1977 52. Sherlock J, Ledwith J, Letteri J: Hypoventilation and hypoxemia during hemodialysis: reflex response to removal of CO2 across dialyzer. Trans Amer Soc Artif Intern Organs 23:406-415, 1977 53. Aurigemma NM, Feldman NT, Gottlieb M, et al: Arterial oxygenation during hemodialysis. N Engl J Med 297: 871-873, 1977 54. Oh MS. Uribarri JV, Del Monte ML, et a1: Consumption of CO 2 in metabolism of acetate as an explanation for hypoventilation and hypoxemia during hemodialysis. Proc Clin Dial Transpl Forum 9:226-229, 1979 55. Wathen RL. Ward RA, Harding GB, et a1: Acid-base and metabolic responses to anion infusion in the anesthetized dog. Kidney Int 21:592-599, 1982 56. Oh MS, Heneghan WF, Kee CS, et al: Glucose ameliorates hypoxemia and reduction in respiratory quotient

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induced by infusion of sodium acetate. Amer Soc Nephrol (Abstr) p 48A, 1981 57. Nissenson AR: Prevention of dialysis-induced hypoxemia by bicarbonate dialysis. Trans Amer Soc Artif Intern Organs 26:339-342, 1980 58. Eiser AR, Jayamanne D, Koksong C. et al: Contrasting alterations in oxygen consumption (V0 2 ) and respiratory quotient (RQ) during acetate (A) and bicarbonate (B) hemodialysis (HD). Amer Soc Nephrol (Abstr) p 38, 1980 59. Abu-Hamdan DK, Mahajan SK, Desai S: Hypoxemia during bicarbonate dialysis. Am Soc Nephrol (Abstr) p 33, 1980 60. Torrance JD, Milne FJ, Hurwitz S, et al: Changes in oxygen delivery during hemodialysis. Clin NephroI3:54- 59. 1975 61. Ahmad S, Pabel M, Shen F, et al: The role of hypoxemia in the expression of acetate intolerance. Am Soc Nephrol (Abstr) p 33, 1980 62. Heneghan WF, Oh MS, Lnudin AP, et al: Glucose reduced hypoxemia during hemodialysis. 11th Annual Clinical Dialysis and Transplant Forum (Abstr) p 14, 1981 63. Heneghan WF, Brunswick JW, Oh MS, et al: Dialysis hypoxemia causes hypotension. Am Soc Nephrol (Abstr) p 42A, 1981 64. Shaldon S, Beau MC, Deschoft G, et al: Vascular stability during hemofiltration. Trans Am Soc Artif Intern Organs 26:391-393, 1980 65. Baldamus CA, Ernst W, Fassbinder W, et a1: Differing hemodynamic stability due to differing sympathetic response. Comparison of ultrafiltration, hemodialysis and hemofiltration. Proc Eur Dial Transpl Assoc 17:205-210, 1980 66. Gotch FA: Net sodium flux (1) in post-dilution hemofiltration (HF) and hemodialysis (HD). Am Soc Nephrol (Abstr) p 39A, 1980 67. Baldamus CA, Ernst W, Lysaght M, et a1: Is hemodynamic stability during hemofiltration (HF) a sodium (Na) balance related phenomenon. 11th Annual Clinical Dialysis & Transplant Forum (Abstr) p 5, 1981