role of hypovolemia in dialysis-induced hypotension

Artificial Organs 12(2):116-121, Raven Press, Ltd., New York 0 1988 International Society for Artificial Organs

Role of Hypovolemia in Dialysis-Induced Hypotension

*Kenji Maeda, "Hiroyuki Morita, *Takahiro Shinzato, *Benjamin Vazquez Vega, "Hiroyuki Kobayakawa, **Toshikazu Ishihara, **Hazime Inagaki, **Isemi Igarashi, and

**Tomoyuki Kitano

*Nagoya University Branch Hospital, Nagoya, and **Toyota Central R & D Labs, Japan

Abstract: Blood volume was measured continuously during hemodialysis using the authors' hematocrit continuous measurement system in an attempt to determine any relationship between dialysis-induced hypotension with acute onset and blood volume. Hypotension resulted approximately 3 h into dialysis in the present study. This point in time was that at which blood volume was more than 5% above the minimum level during the dialysis treatment, and in some patients it was more than 10%

over the minimum level of blood volume. At the time dialysis-induced hypotension occurred or before, there was no sharp decrease in blood volume nor any change in the plasma refilling rate. This suggested that this hy potension is caused by a sudden breakdown of the blood pressure support mechanism compensating for decreased blood volume. Key Words: Hypotension-Hemodialysis- Blood volume-Hypovolemia-Plasma refilling rate.

Several factors have been proposed as the etio- logic mechanism triggering dialysis-induced hypotension. They include hypovolemia (l), autonomic insufficiency (2,3), decreasing serum osmolality (4-6), inhibition of compensatory vasoconstriction (7,8), efficiency of diffusive solute transport (9), and depletion of vasoactive substances (10,ll). Still, all of the above factors taken together from various investigators fail to offer a consistent, co- hesive, and meaningful body of knowledge in relation to dialysis-induced hypotension. Perhaps the present consensus could only be that this type of hypotension is multifactorial. To elucidate the mechanism triggering dialysis-induced hypotension, close consideration must be given to the relation between each of the above-mentioned factor's variation over time and the dialysis-induced hypotension.

Hypovolemia is one of the first factors suggested to be a cause of dialysis-induced hypotension ( l ) , and it seems to have taken on the role of the main cause of hypotension in the minds of some. But

Received March 1987; revised September 1987. Address correspondence and reprint requests to Kenji Maeda,

M.D., Nagoya University Branch Hospital, 1-20, Daiko-minarni 1-chome, Higashi-ku, Nagoya, 461 Japan.

there is still no study to date that clarifies the relationship between changes in blood pressure and varying blood volume up to the time when dialysis- induced hypotension occurs, possibly because no method for continuous measurement of blood volume was available. The aim of the present study was therefore to determine whether or not there was any sudden decrease of blood volume at the time of dialysis-induced hypotension with acute onset, employing the authors' newly developed hematocrit continuous measurement system (12).

METHODS

Twenty-nine long-term dialysis patients who often had dialysis-induced hypotension with acute onset and who were not on any cardiotonic or anti- hypertensive drugs were selected as the subjects of this study. Changes in circulating blood volume were measured continuously, and blood pressure was obtained from these patients during 37 of their dialysis treatments. In the present study, dialysis- induced hypotension was defined as a drop in systolic blood pressure of more than 20 mm Hg within 10 min during hemodialysis, accompanied by symptom(s) such as vomiting, sweating, or lowered consciousness.

116

DIAL YSIS-INDUCED HYPOTENSION I17

Of the above-mentioned 37 dialyses, there were 19 in which dialysis-induced hypotension occurred a total of 23 times among 15 patients (6 men, 9 women), anywhere from 1 to 2 times per dialysis. For the present study, only the data from these 15 patients during their 19 dialyses were used. The average age of the 15 subjects was 52.3 t 2.6 years (? SD), their weight range 50.5 ? 2.2 kg (t SD), and their mean number of years on dialysis was 6.4 k 0.8 ( 5 SD). They were free of clinical symptoms of cardiac insufficiency and neuropathy. The heart rate and the mean blood pressure before hemodialysis were 82.5 t 20.3 beats/min (t SD) and 104.3 -+ 14.6 mm Hg ( t S D ) , respectively. These patients did not suffer from any type of arrhythmia. The renal disease was chronic glomerulonephritis. The residual renal function was less than 3 ml/min of calculated creatinine clearance. None of the patients were anephric or parathyroidectomized.

Six patients used a Gambro Plate Dialyzer (Cu- prophan, 1.0 m2) and another 9 an Asahi AM Neo Dialyzer (Cuprammonium rayon, 1.0 or 1.5 m2). A volumetric ultrafiltration controller (DBB-22@, Nikkiso Co., Ltd., Tokyo, Japan) was used for the dialysate supply and control of the ultrafiltration rate. During the hemodialyses, the ultrafiltration rate was kept constant at 9.23 * 0.99 ml/min ( _C SD). The dialysate consisted of Na 135 mEq/L, K 2.0 mEq/L, Ca 3.5 mEq/L, Mg 1.5 mEq/L, C1 105 mEq/L, acetate 37 mEq/L, and glucose 200 mg/dl.

To measure the circulating blood volume, the authors employed their own hematocrit continuous measurement system (12), which works off the principle of increasing blood electrical resistance in terms of increasing hematocrit and, conversely, allows the hematocrit value to be obtained from the electrical resistance of the circulating blood. In the system under study here, a minifilter (Asahi PAN 60P, polyacrylonitrile, 0.6 m2) was placed in series just upstream of the dialyzer to obtain ultrafiltration at a rate of 10 ml/min. Downstream of the minifilter, as well as at a point upstream of the dialyzer, the fluid was replaced at the same rate. The replacement fluid composition was Na 140 mEq/L, K 2.0 mEq/L, Ca 3.5 mEq/L, Mg 1.5 mEq/L, C1 107 mEqlL, and acetate 40 mEq/L. The plasma electrolyte composition downstream of the dialyzer showed no difference when fluid replacement was performed either at 10 mlfmin or not at all in the minifilter. Using the ultrafiltrate resistivity, the ef- fect of the electrolyte concentration upon blood electrical resistivity could be cancelled. During dialysis, this system indicated the hematocrit level every 5 s, recording the mean value every 30 s.

From the stature and the weight at the end of the dialysis, the standard blood volume was estimated using the formula of Hidalgo et al. (13). Then, from this standard value and the variations in the hematocrit (mean value every 30 s) during the hemodialysis, the circulating blood volume was estimated at each point.

Using such 21 blood volumes determined every 30 s beginning with the 10 rnin before hypotension was induced until it in fact occurred, a linear re- gression equation was calculated, and the slope was taken for the rate of decrease in the blood volume at the time of the dialysis-induced hypotension. Using the same method, the same diminution rate was estimated for 10, 20, and 30 rnin before hypotension developed (i.e., the slope of the linear re- gression equation between 20 to 10 min before hypotension, 30 to 20; and 40 to 30 rnin before the same, respectively). Also, basing upon the rate of blood volume decrease and the water removal rate, the plasma refilling rate was obtained at the time of the hypotension and at 10, 20, and 30 rnin before the same.

Two milliliters of the ultrafiltrate developing in the minifilter was sampled every 5 min, and both its sodium and potassium concentrations were measured by autoanalyzer. From pretesting it was found that the sodium and potassium concentrations of the ultrafiltrate were approximately equiva- lent to those of the plasma at 45 s beforehand. Then the electrolyte level of the ultrafiltrate obtained in this way in place of the 45-s earlier electrolyte level of the plasma was used.

Blood pressure was measured at the time of dialysis-induced hypotension as well as at every 5 rnin during dialysis with an auto-sphygmomanometer. It is often difficult to measure diastolic blood pressure noninvasively when hypotension develops. Thus, only the systolic blood pressure was observed in this investigation.

Hereafter, all data were expressed as the mean * SE, and paired Student’s t test was used for the statistical processing.

RESULTS

Figure 1 shows the changes with time in blood volume during 19 hemodialyses in 15 patients. Blood volume rapidly diminished immediately after dialysis was begun, and this rate of decrease tapered off as treatment progressed. This phenomenon corresponds with the blood volume variation pattern projected by Kimura et al. (14) with a math-

Artif Organs. Vol. 12, No. 2, 1988

118

n =? E

W

E P 3 -

rn 0 0 - m

K . MAEDA ET AL.

I T

I I I Dialysis Start of 1st hour 2nd hour 3rd hour dialysis

FIG. 1. Changes over time in blood volume during hemodialysis.

ematical model and also corroborates the results of Kim et al. (1).

The hypotension induced by dialysis occurred 2.95 t 0.17 h into dialysis. As can be seen from Figure 1, at this point the rate of blood volume decrease was very much diminished. With each of the patients, the results also indicated that there was no sharp decrease in the blood volume either before or at the actual onset of hypotension induced by dialysis treatment. Thus, there was no statistically significant difference in the rate of blood volume decrease at 30, 20, and 10 rnin before hypotension or at the time of same (Table 1). The plasma refilling rate, which is obtained from the water removal rate and the rate of blood volume decrease, also showed no significant variation at 30, 20, and 10 rnin before or when hypotension developed.

As indicated in Figure 2, the circulating blood volume in the patients under study at the start of

TABLE 1. Rate of blood volume decrease, piasma refilling rate, and heart rate before and at the time of

dialysis-induced hypotension

Blood volume Plasma

Systolic Diminution Refilling

(mm Hg) (beaumin) (mVmin) (rnlhin) blood pressure Heart rate rate rate

V, 128 2 5 83.6 2 5.2 3.56 ? 0.70 6.57 5 0.95 V, 134 k 6 88.1 5 6.1 3.17 2 0.66 6.90 2 0.86 V, 118 2 6" 87.3 t 5.8 2.98 % 0.68 7.02 % 0.81 V, 76 i 4b 80.1 I 5.6 3.25 0.84 6.88 % 0.84

V,, V,, and V, represent values at 30, 20, and 10 min before hypotension developed, respectively, and V, indicates values at the time of hypotension.

(p < 0.05) and b(p < 0.001) denote values that were significantly different from the preceding value (V,-V,, V,-V,, V,-V,).

hemodialysis was 4,245 5 201 ml, against 3,440 t 160 ml at the end of dialysis, and 3,338 ? 138 ml as the minimum blood volume. However, when hypotension resulted from dialysis, the blood volume was 3,506 2 138 ml. A comparison of the blood volume when hypotension occurred with the minimum value during the course of dialysis shows that of 23 hypotensive episodes, the dialysis-induced hypotension occurred when the blood volume was 10% over the minimum blood volume in four in- stances; on the overall, hypotension developed when the level was 5.26 k 0.92% above the rnin- imum blood volume.

Also, whereas the hypotension occurred at an average of 2.95 ? 0.17 h after dialysis was begun, the minimum blood volume was attained 3.80 t 0.12 h after the treatment was initiated.

As seen in Table 2, the plasma sodium cuincentra- tion began to fall very slowly following the start of dialysis; it fell from 137.8 _t 0.4 mEq/L, immediately following the start of dialysis to 136.3 & 0.3 mEq/L (p < 0.05) at 30 rnin before the dialysis-induced hypotension occurred. However, for 30 rnin immediately before hypotension developed, the plasma sodium level obtained every 5 rnin failed to display any significant decrease in relation to either the value at 30 rnin before the hypotension resulted or its respective preceding values.

On the other hand, the plasma potassium level fell rapidly immediately following the start of dialysis, but gradually tapered off so as to attain, at 30 rnin before dialysis-induced hypotension developed, a level no different from that obtained at 5 min before the hypotension. However, as shown in Table 2 when the hypotension developed, there was a rapid rise in the plasma potassium level; with fast

Artif Organs, Vol. 12, No. 2, 1988

DIAL YSIS-IND UCED HYPOTENSION 119

4 5 0 0 1 T n 9) E

W

E 8 3 -

TI 0 0 z

T T

Initial Blood Volume Minimum Blood Volume Blood Volume during Blood Volume at

Dialysis induced End Hypotension

FIG. 2. Blood volume at beginning and end of hemodialysis as well as when dialysis-induced hypotension occurs, together with minimum blood volume during hemodialysis.

administration of saline solution, the blood pressure recovered, and at the same time the plasma potassium level reverted to the pre-hypotension level. The plasma potassium concentration then gradually resumed its moderate decline,

DISCUSSION

Clinically, dialysis-induced hypotension presents as gradually decreasing blood pressure with even- tual symptom(s), or as a sudden drop with

TABLE 2. Plasma sodium and potassium concentvations before and at the time of

dialysis-induced hypotension

Systolic Sodium Potassium blood pressure concentration concentration

(mm Hg) (mEqiL) (mEqiL)

At start of hernodial ysis

30 min before hypotension



IS min before hypotension

10 rnin before hypotension


At time of hypotension

5 rnin after hypotension

10 min after hypotension

At the end of hemodialys is

144 t 7

128 t 5b

Not measured

134 i 6

Not measured

118 -t 6"

Not measured

76 i 4b

120 ? l b

122 i 6

117 i 6'

137.8 5 0.4 5.4 i 0.1

136.3 t 0.3" 3.9 i 0.2b

136.2 2 0.3 3.9 ? 0.2

136.4 t 0.3 3.8 f 0.1

136.3 t 0.3 3.9 i 0.1

136.2 lr 0.2 3.9 * 0.1

136.3 5 0.2 3.9 5 0.1

136.2 t 0.2 4.3 i 0.1"

136.3 5 0.2 3.8 F 0.1"

136.2 5 0.2

136.0 5 0.2

3.9 ? 0.1

3.6 -c 0.1"

a p < 0.05 and bp < 0.001 denote values that were significantly different from the preceding measured value.

symptom(s) in an otherwise rather stable blood pressure. No consensus is found as to the mechanism triggering either, other than to indicate that it must be multifactorial. To pinpoint what triggers these types of dialysis-induced hypotension, we must first observe any variation over time in each factor thus far proposed and consider the relationship between changes in the factor during hemodialysis with the drop in blood pressure.

Among the factors, hypovolemia has been taken for a key factor causing hypotension. However, no research has elucidated the role of hypovolemia in dialysis-induced hypotension. The authors attribute this to the unavailability of any continuous method for measuring blood volume, a problem resolved by the recently developed hematocrit continuous measurement system (12). It was used to investigate changes over time in blood volume during hemodialysis and its possible correlation with variations in blood pressure at the time of dialysis-induced hypotension. The dialysis-induced hypotension in which there is a sudden drop in blood pressure was studied because it seemed a good type for empha- sizing the relation between blood volume and hypotension.

Dialysis-induced hypotension and its connection with hypovolemia can be conceived in terms of the following two pictures. In one, a sharp or excessive decrease in blood volume exceeds the compensatory capacity of the chronically impaired blood pressure support mechanisms (15- 18), and dialysis-induced hypotension results. In the other picture, there is some abrupt breakdown of the blood pressure support mechanism compensating for the loss of blood volume.


120 K . MAEDA ET AL.

In the present investigation, the dialysis-induced hypotension occurred when the blood volume was 5% over its lowest level during hemodialysis; and in some patients, it developed when blood volume was 10% over the minimum level. Also, there was no sudden loss of blood volume at the time the hypotension occurred. This finding, of course, does not corroborate our first picture. Hence, the suddenly induced hypotension during dialysis is con- sidered to be due to a sudden breakdown of the blood pressure support mechanism compensating for loss of blood volume which is ascribable either to the ultrafiltrate or water transfer into cells

There is still no explanation for what triggers the breakdown of the blood pressure support system.

In the present study, it was discovered that there was no change in the plasma sodium level for a con- siderable time before any hypotension was induced by the dialysis. In this way, the fact that there was no abrupt drop in the plasma sodium level, either before or at the time of acute hypotension, un- dercuts any argument that the sudden drop in plasma osmolality of itself could have caused the abrupt breakdown in the blood pressure support mechanism.

Nevertheless, in hemodialysis using low sodium dialysate, dialysis-induced hypotension frequently occurs. In hemodialysis with a high sodium dialysate, or in sequential ultrafiltration (4-6), the low incidence of dialysis-induced hypotension is an ac- knowledged fact. When a low sodium dialysate is used, there is a shift of fluid to within the cells as the plasma osmolality decreases (14,2 1,22); this phenomenon may also result in the cells that make up the blood pressure support system. The edema of these cells, along with numerous other factors such as ischemia in this system due to hypovolemia, elevation in the plasma acetate level and the like, may create a predisposition to acute vasculo- pathy or autonomic neuropathy.

In the present study, it was found that there was a rapid rise in the plasma potassium level when hypotension developed. During a hemodialysis in which potassium is continuously removed, the potassium is consecutively eliminated from within cells to the outside thereof. If the extracorporeal circulation is suddenly stopped, according to sepa- rately conducted experiments by the present authors, the plasma potassium level suddenly climbs. However, in the present study, no attempt was made to stop the extracorporeally circulating blood flow either before or at the actual time when dialysis-induced hypotension occurred. This phenom-

( 14,19 -22).

enon may result from the ischemia of the tissue caused by impaired microcirculation occurring at the time when the hypotension was induced by the dialysis; ischemia of the tissue would have led to a decrease in the Na-K ATPase activity in the cell membranes, and then a decrease in the actrve transport of potassium within the cells.

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Art$ Organs, Vol. 12, No. 2, 1988

role of hypovolemia in dialysis-induced hypotension

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