JOURNAL OF DIALYSIS, 2(4). 325-345
(1978)
ULTRAFILTRATION FOLLOWED BY HAEMODIALYSIS. A LONGTERM TRIAL AND ACUTE STUDIES P i e r i d e s , S.B. K u r t z , W . J . Johnson D i v i s i o n of Nephrology, Mayo C l i n i c R o c h e s t e r , MN. 55901
A.M.
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ABSTRACT S e p a r a t e u l t r a f i l t r a t i o n f o l l o w e d by h a e m o d i a l y s i s (U.F.-H.D.) u s i n g Gambro Major o r Cordis-Dow h o l l o w - f i b e r d i a l y z e r s were e v a l u a t e d i n 10 d i a l y s i s p a t i e n t s o v e r a mean p e r i o d of 4 1 / 2 months and 4 5 5 U.F.-H.D. p r o c e d u r e s . F l u i d c o n t r o l was f a c i l i t a t e d i n oedemat o u s p a t i e n t s b u t t h e number of h y p o t e n s i v e e p i s o d e s d u r i n g t h e combined p r o c e d u r e r e q u i r i n g i n t r a v e n o u s 5% s a l i n e d i d n o t s i g n i f i c a n t l y d e c r e a s e . No s i g n i f i c a n t improvement in h y p e r t e n s i o n was noted. U l t r a f i l t r a t i o n (U.F.) a l o n e f o r a c u t e l y w a t e r o v e r l o a d e d , azotaemic p a t i e n t s proved v e r y u s e f u l . Two t o f i v e l i t e r s of oedema f l u i d could be removed a s y m p t o m a t i c a l l y i n one t o t h r e e h o u r s u s i n g transmembrane p r e s s u r e s of 250 t o 500 d g and U.F. r a t e s of 10 t o 4 2 ml/min. Two p a t i e n t s became a c u t e l y and s y m p t o m a t i c a l l y hypotens i v e . One was an i n s u l i n dependent d i a b e t i c i n whom 3800 m l were removed i n 7 5 minutes and t h e o t h e r a h y p e r t e n s i v e p a t i e n t undergoing t r e a t m e n t w i t h M i n o x i d i l and p r o p r a n o l o l . INTRODUCTION Diffusion i s the b a s i c p r i n c i p l e underlying the t r a n s f e r of s o l u t e s d u r i n g h a e m o d i a l y s i s u s i n g c o n v e n t i o n a l membranes such a s c e l l u l o s e a c e t a t e and cuprophan.
T h e r e f o r e s m a l l m o l e c u l e s such a s
sodium, potassium and u r e a a r e c l e a r e d p r e f e r e n t i a l l y w i t h t h e p o s s i b i l i t y t h a t l a r g e r and p o s s i b l y t o x i c m e t a b o l i t e s may accumulate i n t h e c i r c u l a t i o n (1,Z).
U.F.
during conventional d i a l y s i s
contributes l i t t l e t o small s o l u t e c l e a r a n c e but i t i s invaluable i n removing w a t e r from o v e r l o a d e d p a t i e n t s ( 2 , 3 , 4 ) . haemodialysis with U.F.
Combined
a s currently practiced is usually sufficient
t o c o n t r o l t h e a z o t a e m i a and o v e r h y d r a t i o n r e s u l t i n g from e n d - s t a g e 325 Copynght 0 1 9 7 8 by Marcel Dekker, Inc All Rights Reserved Neither this work nor any part may he reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying. microhlming, and recording. or by any information storage and retrieval system, without permission in writing from the publisher
326
PIERIDES, KURTZ, AND JOHNSON
r e n a l f a i l u r e b u t problems o c c a s i o n a l l y a r i s e i n p a t i e n t s xho gain f l u i d e x c e s s i v e l y betxeen d i a l y s e s o r become oedematous a f t e r an unsuccessful r e n a l t r a n s p l a n t , prolonged h y p e r a l i m e n t a t i o n o r a serious intercurrent illness.
In some of these p a t i e n t s a t t e m p t s t o u l t s a f i l t e r t h e excess
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f l u i d during standard haemodialysis may be complicated by troublesome hypotension, muscle cramps and vomiting.
S i m i l a r l y a minority of
oedema-free p a t i e n t s ( 5 , 6 , 7 ) a l s o become hypotensive during convent i o n a l haemodialysis r e q u i r i n g i n t r a v e n o u s s a l i n e i n o r d e r to maintain normal blood p r e s s u r e s d u r i n g t h e procedure.
The administra-
t i o n of s a l i n e obviously d e f e a t s t h e purpose of m a i n t a i n i n g optimal f l u i d balance. uncertain.
The pathogenesis of t h e s e hypotensive episodes remains
T r a d i t i o n a l l y they have been a s c r i b e d t o u l t r a f i l t r a t i o n -
induced hypovolemia ( 5 . 6 ) but i t i s l i k e l y t h a t i n some p a t i e n t s a d e f e c t i n vasomotor c o n t r o l p l a y s an important p a r t (7,8,9,10). Elegant experiments by Kersh and c o l l e a g u e s (8) aimed a t e v a l u a t i n g autonomic vasomotor f u n c t i o n i n t h e s e p a t i e n t s i n d i c a t e t h a t approximately 80 p e r c e n t of t h e p a t i e n t s who become hypotensive during haemodialysis appear t o have a s i g n i f i c a n t degree of autonomic i n s u f ficiency.
Work by L i l l e y and h i s c o l l e a g u e s ( 7 ) i n d i c a t e s t h a t the
f a u l t may be i n t h e a f f e r e n t l i m b of t h e b a r o r e c e p t o r r e f l e x .
Other
i n v e s t i g a t o r s have reported f i n d i n g s compatible with t h e s e conclus i o n s (11,12,13).
The p o s s i b i l i t y t h a t u l t r a f i l t r a t i o n - i n d u c e d
hypovolaemia may n o t be the primary and complete cause f o r the observed hypotension has r e c e n t l y received f u r t h e r support following the unexpected f i n d i n g t h a t c o n t r a r y t o popular b e l i e f t h e s e p a t i e n t s may t o l e r a t e l a r g e f l u i d losses i f these a r e produced by U.F. dialysis.
Although U.F.
alone without
had been used by s e v e r a l workers i n t h e p a s t
ULTRAFILTRATION FOLLOWED BY HAEMODIALYSIS
327
i n o r d e r t o d e a l w i t h oedematous p a t i e n t s ( 3 , 4 , 1 4 , 1 5 )
U.F.
t h e u s e of pure
b e f o r e h a e m o d i a l y s i s r e c e i v e d i t s main impetus from t h e work of
Bergstrom and c o l l e a g u e s ( 1 6 ) .
They i n d i c a t e d t h a t i f e x c e s s f l u i d
could be removed d u r i n g t h e f i r s t hour by U.F.
alone, haemodialysis
could be c a r r i e d o u t d u r i n g t h e l a t t e r p a r t of t h e " d i a l y s i s s e s s i o n ' '
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with minimal, i f any, symptoms o r i n c o n v e n i e n c e t o t h e p a t i e n t . This p r o j e c t w a s u n d e r t a k e n i n o r d e r t o d e f i n e c l i n i c a l s i t u a t i o n s where s e q u e n t i a l U.F.-Y.D. U.F.
a l o n e and U.F.-H.D.
m i g h t prove u s e f u l .
A t t h e same time,
were used i n t h e management of oedematous
azotaemic p a t i e n t s and j u v e n i l e d i a b e t i c s who were f l u i d o v e r l o a d e d .
METHODS
The s t u d y i n v o l v e d a ) a longterm s e q u e n t i a l U . F . - H . D .
t r i a l in
10 p a t i e n t s a l r e a d y s t a b i l i z e d on r e p e t i t i v e h a e m o d i a l y s i s , and b) 1 7 a c u t e U.F.
s t u d i e s i n 15 oedematous a z o t a e m i c p a t i e n t s .
Longterm s t u d y
Ten p a t i e n t s , 5 males and 5 f e m a l e s , aged 28-79, p r e v i o u s l y t r e a t e d by c o n v e n t i o n a l h a e m o d i a l y s i s u s i n g t h e Gambro Major o r Cordis-Dow hollow f i b e r kidney ( s u r f a c e a r e a ?.5 M2) were changed t o a program of one hour p u r e u l t r a f i l t r a t i o n followed by h a e m o d i a l y s i s u s i n g t h e same dialyzers.
The t o t a l U.F.-H.D.
i n m e d i c a t i o n were c a r r i e d o u t .
time remained unchanged and no changes F i v e p a t i e n t s were s e l e c t e d because of
r e c u r r e n t h y p o t e n s i v e e p i s o d e s o c c a s i o n a l l y accompanied by cramps and vomiting o c c u r r i n g d u r i n g o r immediately f o l l o w i n g d i a l y s i s .
Placement
i n t h e Trendelenburg p o s i t i o n and i n t r a v e n o u s 5% s a l i n e were used t o control these complications.
The need f o r a d m i n i s t e r i n g 5% s a l i n e was
taken a s an i n d i c a t i o n of a symptomatic h a e m o d i a l y s i s s e s s i o n .
F i v e more
PIERIDES, KURTZ, AM) JOHNSON
328
p a t i e n t s were included i n the study because of m i l d hypertension and occasional f l u i d overload.
During t h e i n i t i a l hour of pure U.F.,
each
p a t i e n t ' s blood l i n e s were connected t o t h e d i a l y z e r a s usual but the d i a l y s a t e f l u i d was n o t c i r c u l a t e d .
A clamp was used on t h e blood l i n e
r e t u r n i n g to t h e p a t i e n t (venous l i n e ) t o r a i s e the p r e s s u r e between
250 and 290 rraaHg.
The d i a l y z e r was h e l d i n a v e r t i c a l p o s i t i o n and the
u l t r a f i l t r a t e was c o l l e c t e d i n a measuring c y l i n d e r ( F i g u r e 1).
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the hour of U.F.
After
was completed, the venous clamp was removed allowing
the p r e s s u r e t o drop, t h e d i a l y s a t e l i n e s were reconnected t o the d i a l y z e r and pumping of d i a l y s a t e f l u i d was s t a r t e d . made t o keep U.F.
An attempt was
t o a minimum during t h e haemodialysis period avoiding
removal of any more f l u i d than was a b s o l u t e l y e s s e n t i a l t o r e s t o r e f l u i d balance.
\
\
Metallic screw clamp t o raise venous pressure -250 mm Hg
uu
Arterial blood pump
Measuring
Figure 1 Diagram t o i l l u s t r a t e the way U.F.
was c a r r i e d o u t
ULTRAFILTRATION FOLLOWED BY HAEMODIALYSIS
329
Serum u r e a , c r e a t i n i n e , phosphorus, c a l c i u m , potassium and haemoglobin were measured by s t a n d a r d a n a l y t i c a l t e c h n i q u e s a t t h e b e g i n n i n g and end of t h e t r i a l .
P a i r e d "t" t e s t s were used t o a s s e s s
any s i g n i f i c a n t d i f f e r e n c e s .
Acute s t u d i e s
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Combined U.F.-H.D.
o r U.F.
w i t h o u t d i a l y s i s were performed i n
azotaemic p a t i e n t s on o c c a s i o n s when oedema was p r o m i n e n t . procedure was s i m i l a r t o t h a t used i n t h e l o n g t e r m U.F.-H.D. a p a r t from f i v e o c c a s i o n s when U.F.
The trial
a l o n e u s i n g h i g h e r venous p r e s s u r e s
( 4 5 0 - 5 0 0 n-nnHg) were used r e s u l t i n g i n more e f f i c i e n t
U.F.
Blood p r e s -
s u r e was monitored c l o s e l y e i t h e r w i t h a sphygmomanometer o r a Roche A r t e r i o s o n d manometer.
I n s e v e r a l p a t i e n t s s e r i a l serum o s m o l a l i t i e s
were r e c o r d e d by means of an Advanced I n s t r u m e n t s H i - p r e c i s i o n osmometer.
RESULTS
Longterm t r i a l
T a b l e 1 d e s c r i b e s t h e c l i n i c a l c h a r a c t e r i s t i c s of t h e 10 p a t i e n t s who p a r t i c i p a t e d i n t h i s t r i a l .
The f i n d i n g s d u r i n g t h e t r e a t m e n t
p e r i o d were compared t o t h o s e of an e q u a l p e r i o d p r e c e d i n g t h e s t u d y when p a t i e n t s were m a i n t a i n e d on s t a n d a r d h a e m o d i a l y s i s .
The number of
symptomatic h y p o t e n s i v e e p i s o d e s d i d n o t s i g n i f i c a n t l y d e c r e a s e i n f i v e p a t i e n t s who e x p e r i e n c e t h i s commonly, (84 i n c o n t r o l p e r i o d and 7 6 duri n g s e q u e n t i a l U.F.-H.D.
t = 0 . 6 6 , p = n . ~ . ) ; however a t l e a s t two
of
t h e f i v e p a t i e n t s f e l c t h a t t h e i r symptoms w e r e Less s e v e r e and e a s i e r t o reverse.
U.F.
r a t e s ranged from 1 3 t o 27 m l p e r m i n u t e , t h e mean f l u i d
loss d u r i n g t h e U.F.
hour b e i n g 1000 m l .
Thus, from 25 t o 100 p e r c e n t of
t h e f l u i d removed d u r i n g t h e combined U.F.-H.D.
procedure occurred during
Sex
Age
D u r a t i o n of Treatment
No of Procedures
3
Polycystic Disease
51
F
2
3 314
I n t e r s t i t i a l Nephritis
28
F
1
38
57
4 314
Lupus N e p h r i t i s
52
F
7
47
5
Myeloma Kidney
79
42
112
4
Nephrosclerosis
M
M
5
67
Reason for Entering the T r i a l
Hypotensive Symptoms 1
41
38
4 114
Nephrosclerosis
71
M
a
6
TABLE I
CLINICAL INFORMATION AND FINDINGS I N THE 10 PATIENTS WHO PARTICIPATED I N THE LONGTERM SEQUENTIAL UF-HD TRIAL AND ALSO THE 3 DIABETIC PATIENTS WHO STILL USE THIS PROCEDURE
Diagnosis
Symptomatic Hypotensive Runs Control
49
4 112
Lupus N e p h r i t i s
46
F
3
5 112
Chronic G . N .
69
M
9
42
4 314
Nephrosclerosis
48
Hypotensive Symptoms Hypotensive Symptoms Hypotensive Symptoms Hypotensive Symptoms
Trial
27
85/41
7
5
ib.a?a Diabetes Mellitus
Hypotensive Symptoms
70
Mean Supi Pre-dialy Blood P r e
117167
21
19
19
19
9
161190 154184
156178
163176
172174
Mild Oedema
~~
F
Control
20
27
14
158185
Mild Oedema Mild Oedema
146182
Mild Oedema
iiatiio
Hypertension a4
58
76 ~
i5.2+6 p=n. s
40 = 53%
7
11
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Case
(months)
---
53
4 112
Diabetes Mellitus
65
F
42
48
M
10
455
112
4
Total Mean
19 = 25% 29 = 23%
12 M 28 D i a b e t e s M e l l i t u s 6 76 Hypotensive Symptoms 42 F 65 D i a b e t e s M e l l i t u s 10 123 Hypotensive Symptoms 1 Hypotension ? muscle cramps f vomiting, r e q u i r i n g I V 5% s a l i n e 2 P a t i e n t p a r t i c i p a t e d i n t h e t r i a l and then c o n t i n u e d on t h e UF-HD procedure P a t i e n t s 11, 1 2 and 4 s t i l l use s e q u e n t i a l UF-HD
149178
p=
ULTRAFILTRATIOS FOLLOWED BY HAEMODIALYSIS t h e f i r s t hour of p u r e U.F.
U.F.
331
Hypotensive e p i s o d e s d u r i n g t h i s hour o f
were unusual b u t i n t h e f i v e s u s c e p t i b l e i n d i v i d u a l s t h e s e
symptoms r e c u r r e d when t h e p a t i e n t s resumed s t a n d a r d h a e m o d i a l y s i s . Because symptoms o c c u r r e d l a t e r on i n t h e p r o c e d u r e , b e t t e r f l u i d c o n t r o l was p o s s i b l e .
w a s t h e e a s e w i t h which f l u i d b a l a n c e c o u l d be
t i a l U.F.-H.D. restored.
Undoubtedly t h e g r e a t e s t a d v a n t a g e of sequen-
A s i n d i c a t e d by T a b l e I , no s i g n i f i c a n t changes i n hyper-
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t e n s i o n o c c u r r e d by t h e end of t h e t r i a l . A f t e r completion of t h e s t u d y , p a t i e n t 4 , a l o n g s t a n d i n g i n s u l i n - d e p e n d e n t d i a b e t i c who had been on c o n v e n t i o n a l h a e m o d i a l y s i s € o r a y e a r r e q u e s t e d c o n t i n u a t i o n of combined U.F.-H.D.
Two a d d i -
t i o n a l i n s u l i n dependent d i a b e t i c s have s i n c e e x p r e s s e d p r e f e r e n c e €or t h i s procedure.
Although a l l t h r e e of them show o c c a s i o n a l
h y p o t e n s i v e e p i s o d e s d u r i n g U.F.-H.D.,
symptoms a p p e a r more t o l e r a b l e ,
of s h o r t e r d u r a t i o n and e a s i e r t o r e v e r s e . Table I1 i l l u s t r a t e s t h e biochemical changes a t t h e end of t h e
trial.
There were no s i g n i f i c a n t d i f f e r e n c e s i n s e r u m u r e a , c r e a t i n i n e
calcium o r hemoglobin v a l u e s .
However, serum phosphorus and potassium
showed s m a l l b u t s i g n i f i c a n t i n c r e a s e s r e f l e c t i n g t h e f a c t t h a t o v e r a l l d i a l y s i s time was reduced by two t o t h r e e h o u r s p e r week. ed, U . F .
As anticipat-
d i d n o t improve s m a l l s o l u t e c l e a r a n c e s .
Acute p u r e U.F.
studies
F i f t e e n p a t i e n t s were t r e a t e d by U.F. a l o n e € o r oedema on
1 7 o c c a s i o n s , 2 p a t i e n t s h a v i n g two t r e a t m e n t s e a c h .
T a b l e 111
summarizes t h e volumes of f l u i d removed, t y p e of d i a l y z e r used, achieved U.F.
r a t e s and p r e s e n c e o r a b s e n c e of symptoms.
Of t h e 1 7 t r e a t m e n t s e s s i o n s , 1 3 were f r e e of any symptoms d e s p i t e removal of oedema f l u i d a t U.F.
r a t e s f a s t e r than p r e v i o u s l y
TABLE I1 BIOCHEMICAL CHANGES AT COMPLETION OF THE SEQUENTIAL UF-HD TRIAL
Serum Urea mg/100 m l
155
a
224
7
255
a7
6
184
20 2
5
134
145
4
202
126
3
270
2
190
1
118 204
169
159 185
Creatinine mg/100 ml
11.5 10.5 14.5 10.7 13.3 8.4
8.1
9.5
12.9
230
11.3
192
10.4 10.5
17.7 8.7
12.6 10.5 9.1 9.6
17.8 18.4
Potassium meq/L
4.7
6.1 4.8
4.9
4.2 3.1 4.2
4.2 4.5 4.7
5.1 6.1 6.4 5.7 4.6 5.3 5.2 4.5 5.4 5.2
Calcium mg/100 m l
9.1 10.1 10.3 8.8
9.5 8.7
8.7 8.6
8.2 8.0
9.4 9.5 9.7 8.9 9.4 8.4 9.4 8.3 8.0
8.6
Phosphorus mg/100 ml
3.3 4.3 4.3
6.9 4.6 3.1 4.8
5.2 4.3 3.1
5.1 5.9 4.1 9.0 6.0
7.5 3.5 5.4 6.3 4.5
Hemoglobin g/100 m l
6.0 7.9 4.8
5.5 7.9 6.4
6.3 8.6
5.8 7.9
6.1 9.7 7.2 6.0 6.6
6.6 7.8
8.4 6.9 8.7
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Case
Control T r i a l Control T r i a l Control T r i a l Control T r i a l Control T r i a l Control T r i a l
95
9
10
-
Mean t
P
166.3 186.3 f57 f41 ti-0.78 N.S.
11.07 12.53 t 2 . 0 8 f3.89 t=l.62 N.S.
4.5 5.3 t0.7 3.6 t=3.86 pq.005
9.0
9.0
f0.8 tO.6 t = O . 33 N.S.
4.4 5.7 t1.1 f1.6 t=2.75 pq.025
6.7 7.4 21.3 f1.2 t=2.03
N.S.
333
ULTRAFILTRATION FOLLOWED BY WENODIALYSIS possible during conventional haemodialysis.
I n t:io of f o u r r u n s ,
h y p o t e n s i v e e p i s o d e s \ ; e r e s e v e r e enough t o r e q u i r e t e r m i n a t i o n o f t r e a t m e n t , w h i l e i n t h e r e m a i n i n g two ( c a s e s 6 and 1 3 ) , t h e p r o c e d u r e was resumed a f t e r t h e i n t r a v e n o u s a d m i n i s t r a t i o n of 250 m l of proteinate. F i g u r e 2 i l l u s t r a t e s changes d u r i n g one of t h e s e symptomatic p r o c e d u r e s (Case l a ) .
The p a t i e n t ( c a s e 4 i n t h e longterm t r i a l ) was
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an i n s u l i n - d e p e n d e n t d i a b e t i c who a f t e r 75 m i n u t e s of U . F .
and l o s s o €
3,800 m l of f l u i d s u d d e n l y became h y p o t e n s i v e w i t h a slow i r r e g u l a r p u l s e r e q u i r i n g i n t r a v e n o u s i n f u s i o n of s a l i n e and d i s c o n t i n u a t i o n o f the procedure.
T h i s p a t i e n t usualLy remains asymptomatic when 900 t o
1800 m l a r e removed d u r i n g t h e i n i t i a l U.F. houi of a combined U . F . - H . D . procedure. F i g u r e 3 r e f e r s t o c a s e 1 5 , an a z o t a e m i c p a t i e n t n o t y e t on r e p e t i t i v e h a e m o d i a l y s i s , s u f f e r i n g from r e n a l f a i l u r e and s e v e r e n e p h r o t i c syndrome due t o m e m b r a n o p r o l i f e r a t i v e g l o m e r u l o n e p h r i t i s .
P r i o r to
t h e p r o c e d u r e , t h e p a t i e n t r e c e i v e d M i n o x i d i l , p r o p r a n o l o l and furosemide.
I m e d i a t e l y a f t e r p r i m i n g t h e Gambro Major d i a l y s e r x i t h t h e
p a t i e n t ' s own b l o o d , he became h y p o t e n s i v e and h i s p u l s e f e l l t o 37 b e a t s p e r m i n u t e .
The p r o c e d u r e was immediately t e r m i n a t e d and
t h e blood r e t u r n e d t o t h e p a t i e n t .
However, t h e blood p r e s s u r e d i d
n o t r i s e t o b a s e l i n e v a l u e s f o r two h o u r s .
I t is l i k e l y t h a t the
drug t h e r a p y i n t e r f e r e d w i t h t h e p a t i e n t ' s a b i l i t y t o respond t o hypovolemia, a f i n d i n g t h a t emphasizes t h e i m p o r t a n c e of c o n s i d e r i n g t h e p a t i e n t ' s d r u g s b e f o r e embarking on such a p r o c e d u r e .
Renal
f u n c t i o n d i d n o t change. F i g u r e s 4 and 5 i l l u s t r a t e two asymptomatic p r o c e d u r e s d u r i n g which 4 , 2 0 0 and 5,000 ml of oedema f l u i d were removed i n two and t h r e e h o u r s r e s p e c t i v e l y w i t h o u t a f a l l i n blood p r e s s u r e .
FINDINGS I N 17 U.F.
*
TABLE 111
RUNS CARRIED OUT ON 1 5 AZOTAEMIC PATIENTS
WITH OEDEMA AS A PROMINENT FINDING
Volume of Ultrafiltrate
Duration
2400
5
110
3000
4
120
4200
3
5000
2
3800
la
2140
1
90
75
180
Type o f Dialyser
Mean Venous Pressure mmHg
Gambro 1 . 5 Gambro 1 . 5 T r a v e n o l CF
250 450 450
U 1t r a Filtration Rate
Commen t s
ml/min 24 42
28
No symptoms
Sudden h y p o t e n s i o n & b r a d y c a r d i a
No symptoms
1500
Gambro 1 . 5 T r a v e n o l CF
450 400
35 27
No symptoms No symptoms
1500
120
Travenol CP
250
20
No symptoms
1500 180
T r a v e n o l CF 1500
250
14
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Case
(min)
2550
6
Asymptomatic s m a l l BP d r o p Had 250 m l of p r o t e i n a t e
335
ULTRAFILTRATION FOLLOWED BY HAEMODIALYSIS
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0
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5: .Y
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N
N
Ls
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0
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5 m
5 0
r u - O M 4
a u m
N
N
ir V
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V
Ls V
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3
3
3
3
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4
0
0
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m 0 0 N
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m
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3
4
3
4
3
336
PIERLDES, KURTZ, AND JOHNSON
Gambro major Venous resistance - 4 5 0 mm Hg Blood flow-166 ml/min Hemofiltration r a t e . 4 0 ml/min
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2
z 2'' -3
-
-4
80 60
Saline + take off hemofiltration 550 ml 0.9% saline given
60
0
Time, min
90
4% +
IHEMOFILTRATION)
DISCUSSION C l i n i c a l use of U.F. Removal of e x c e s s i v e e x t r a c e l l u l a r f l u i d remains t h e main indication for u l t r a f i l t r a t i o n .
Lunderquist used t h e Alwall d i a l y z e r -
u l t r a f i l t e r i n 1952 t o remove 7 . 4 kg from an azotaemic p a t i e n t i n pulmonary oedema over a course of n i n e hours ( 4 ) .
When r e p e t i t i v e
haemodialysis became e s t a b l i s h e d a decade l a t e r , U.F. i n t e g r a l p a r t of i t .
became an
Using t h e g e n e r a l l y a v a i l a b l e a r t i f i c i a l
kidneys, 500 t o 3000 m l s of f l u i d a r e u s u a l l y removed by U.F. over a four t o s i x hour long haemodialysis.
ULTRAFILTRATION FOLLOWED BY HAENODLALYSIS
337
lOOr
:v 80
I
Azatemic/nephrotic patient Membrano-proliferative GN Edema +++ Minoxidil, Inderal. Lasix
50
40 30
Needles in
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11 50 ml saline drained
Records of t h e two symptomatic and h y p o t e n s i v e runs i n a ) a n i n s u l i n - d e p e n d e n t d i a b e t i c p a t i e n t , b) a p a t i e n t on t r e a t m e n t w i t h M i n o x i d i l and p r o p r a n o l o l .
When t h e blood c h e m i s t r y v a l u e s o f t h e oedematous azotaemic p a t i e n t a r e s a t i s f a c t o r y and i n p a r t i c u l a r serum potassium i s normal, U.F.
o f f e r s th-o d i s t i n c t a d v a n t a g e s : prompt r e l i e f from t h e
e f f e c t s of oedema e s p e c i a l l y when t h e l u n g s a r e a f f e c t e d and absence of s i d e e f f e c t s d u r i n g t h e p r o c e d u r e .
Kopp ( 1 7 ) s t r e s s e d t h e i m -
p o r t a n c e of e n s u r i n g a normal serum p o t a s s i u m b e f o r e embarking on U.F. s i n c e t h i s procedure does n o t from t h e 17 pure U.F.
105-er
serum p o t a s s i u m .
The good r e s u l t s
t r e a t m e n t p e r i o d s i n o u r s t u d y confirm t h e
e f f i c a c y of t h i s p r o c e d u r e i n r e l i e v i n g oedema and o u r o b s e r v a t i o n s a r e i n agreement w i t h o t h e r p u b l i s h e d d a t a (3,14,15,16,18).
What i s
338
PIJIRIDES, KURTZ, AND JOHNSON
290
Gambro major Venous resistance-450 mm Hg Blood flow-170 ml/min Hernofiltration rate-35ml /min
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80
-3 -4
Time, min IHEMOFILTRATIONI
of i n t e r e s t however i s the general l a c k of hypotensive episodes during removal of f l u i d volumes which o c c a s i o n a l l y exceeded t h e p a t i e n t s ' own c i r c u l a t i n g blood volume.
Goss e t a 1 (19), K i m e t a1 ( 6 ) and Handt
e t a1 ( 2 0 ) have a l l demonstrated a f a l l i n c a r d i a c o u t p u t and blood volume d u r i n g standard haemodialysis and G o s s e t a1 ( 1 9 ) a l s o showed an increase i n t o t a l peripheral resistance. extended t h e s e f i n d i n g s t o pure U.F.
Hampl e t a1 (21) have s i n c e
I t would thus appear very l i k e l y t h a t
the key f a c t o r r e s p o n s i b l e f o r the usual absence of hypotensive episodes during haemodialysis is the p a t i e n t ' s a b i l i t y t o i n c r e a s e h i s o r her p e r i p h e r a l r e s i s t a n c e a p p r o p r i a t e l y so t h a t a normal blood pressure
i s maintained w h i l e oedema f l u i d l e a v e s the i n t e r s t i t i a l space t o e n t e r t h e v a s c u l a r compartment.
The importance of adequate p e r i -
ULTRAFILTRATION FOLLOWED 9Y HAFXODLALYSIS
3 39
%
330
320
90
8OL
Travenol HF 1500 Venous resistance-450 mm Hg Blood flow-190 ml/min Hemofiltration rate 2 7 m V min
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-
':E -5
200 r
I
90
0
I 180
Time, min lHEMOFlLTRATlON 1
Figures 4 & 5
Asymptomatic U.F. r u n s i l l u s t r a t i n g t h e removal o f 4 , 2 0 0 and 5,000 m l o f oedema f l u i d .
p h e r a l r e s i s t a n c e can be a p p r e c i a t e d by t h e f i n d i n g s i n two o f o u r p a t i e n t s ( F i g u r e s 2 & 3 ) who became a c u t e l y h y p o t e n s i v e .
Both had
good r e a s o n s f o r a compromized p e r i p h e r a l a r t e r i o l a r vasomotor control.
P a t i e n t 15 was on a n t i - h y p e r t e n s i v e t r e a t m e n t w i t h
p r o p r a n o l o l and M i n o x i d i l a p o t e n t p e r i p h e r a l v a s o d i l a t o r , w h i l e patient 1 was a longstanding insulin-dependent d i a b e t i c with a peripheral neuropathy.
The e x p e r i e n c e w i t h t h e l a t t e r p a t i e n t i s
340
PIERIDES, KURTZ, AND JOHNSON
instructive.
She has been undergoing U.F.-H.D.
f o r over a y e a r ,
r e g u l a r l y l o s i n g u p t o 1800 m l of f l u i d d u r i n g t h e U.F. minimal symptoms.
hour with
h t h e day she became a c u t e l y hypotensive,
U.F.
alone using a h i g h e r venous p r e s s u r e was being c a r r i e d o u t because of severe oedema.
Her blood p r e s s u r e dropped suddenly when 3,800 m l
had been removed and w h i l e t h e r e was s t i l l v i s i b l e a n k l e oedema. This would suggest t h a t t h e r e may be a l i m i t t o how much a p a t i e n t
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can compensate f o r r a p i d U.F.
losses.
Therefore pure U.F.
be considered a simple and always s a f e procedure.
should not
S e r i o u s hypoten-
s i v e episodes may occur i f e x c e s s i v e amounts of f l u i d a r e r a p i d l y removed e s p e c i a l l y i f t h e p a t i e n t ' s vasomotor c o n t r o l i s anatomic a l l y o r pharmacologically compromised.
O u r encouraging experience with s e q u e n t i a l U.F.-H.D.
in diabetic
p a t i e n t s would s u g g e s t t h a t t h i s procedure may be of some b e n e f i t to them.
D i a b e t i c p a t i e n t s show an increased i n c i d e n c e of hypotensive
episodes d u r i n g conventional haemodialysis ( 2 2 ) and Ma e t a 1 ( 2 3 ) emphasized t h e i r unusually high weight g a i n s between d i a l y s e s n e c e s s i t a t i n g c o n s i d e r a b l e f l u i d removal d u r i n g haemodialysis. use of s e q u e n t i a l U.F.-H.D.
The
may indeed render haemodialysis less
s t r e s s f u l and symptomatic t o t h e s e p a t i e n t s . Why do c e r t a i n p a t i e n t s become hypotensive d u r i n g s t a n d a r d haemodialysis?
C l e a r l y t h i s m u s t be a m u l t i f a c t o r i a l problem a s only
small numbers of p a t i e n t s a r e a f f e c t e d , e s t i m a t e d by Maher and c o l leagues t o be 8 p e r c e n t ( 5 ) and by Graefe e t a 1 (24) 1 4 p e r c e n t of t h e i r haemodialysis populations. why pure U.F.
Equally important i s t h e question
i s n o t accompanied by hypotensive crises?
In the
i n i t i a l p r e s e n t a t i o n of t h e i r r e s u l t s , Bergstrom e t a1 ( 1 6 ) concluded t h a t s o l u t e s h i f t s brought about by d i f f u s i o n a c r o s s d i a l y s i s mem-
341
ULTRAFILTRATION FOLLOWED BY HAEMODIALYSIS b r a n e s f a c i l i t a t e d h y p o t e n s i o n i n s u s c e p t i b l e i n d i v i d u a l s b u t were u n a b l e t o d e t e r m i n e t h e i r e x a c t n a t u r e o r mode of a c t i o n .
As
e x p e c t e d , changes i n serum o s m o l a l i t y d u r i n g p u r e U.F. a r e minimal ( F i g u r e 4 & 5 ) , whereas d u r i n g r e g u l a r h a e m o d i a l y s i s t h e r e i s a d e f i n i t e d e c r e a s e i n serum o s m o l a l i t y which r e s u l t s i n a s i g n i f i c a n t s h i f t of e x t r a c e l l u l a r f l u i d i n t o t h e i n t r a c e l l u l a r s p a c e a s h a s been demonstrated by F a l l s e t a1 ( 2 5 ) .
However, i t i s u n l i k e l y t h a t t h i s
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i s t h e t r i g g e r i n g mechanism f o r t h e o b s e r v e d e p i s o d e s of h y p o t e n s i o n . Graefe e t a1 ( 2 4 ) r e f e r r e d to the myocardial depressing a c t i o n ( 2 6 ) and p e r i p h e r a l v a s o d i l a t i n g a c t i o n ( 2 7 ) o f sodium a c e t a t e , u n i f o r m l y employed d u r i n g s t a n d a r d h a e m o d i a l y s i s when they d e s c r i b e d e x p e r i m e n t s i n f i v e p a t i e n t s w i t h f r e q u e n t h y p o t e n s i v e e p i s o d e s t h a t showed f e w e r symptoms when d i a l y z e d w i t h sodium b i c a r b o n a t e r a t h e r than a c e t a t e . They p o s t u l a t e d t h a t t h e a b s e n c e of a c e t a t e d u r i n g p u r e U.F.
was
the explanation, a t l e a s t i n p a r t f o r the lack of hypotensive episodes.
T h i s does n o t however e x p l a i n why t h e s e h y p o t e n s i v e e p i s o d e s
a f f e c t o n l y a s m a l l m i n o r i t y of p a t i e n t s ( 5 , 2 4 ) , when sodium a c e t a t e i s u n i v e r s a l l y u s e d , u n l e s s i t c a n b e shown t h a t t h e s e i n d i v i d u a l s a r e i n c a p a b l e of m e t a b o l i z i n g a c e t a t e o r a r e p e c u l i a r l y susceptible to its effect.
I n t e r e s t i n g l y G r a e f e e t a 1 ( 2 4 ) used a
d i a l y s a t e p o t a s s i u m c o n c e n t r a t i o n of 3 meq/L i n t h e i r s t u d i e s . Henrich e t a 1 ( 2 8 ) n o t e d t h e p r e s e n c e o f i m p o r t a n t d i f f e r e n c e s between i s o k a l a e m i c and hypokalaemic d i a l y s e s .
I n a s e r i e s of c a r e -
f u l e x p e r i m e n t s , i s o k a l a e m i c h a e m o d i a l y s i s i n marked c o n t r a s t t o hypokalaemic d i a l y s i s r e s u l t e d i n a f a l l of plasma a l d o s t e r o n e , f a l l of plasma c a t e c h o l a m i n e s b u t no r i s e i n h e a r t r a t e d e s p i t e a f a l l i n blood p r e s s u r e and body w e i g h t .
It w a s t h o u g h t t h a t t h e f a l l i n
serum potassium c o u l d unmask a d e g r e e o f autonomic i n s u f f i c i e n c y
342
PIWIDES, KURTZ, AND JOHNSON
p r e s e n t i n some p a t i e n t s .
Recently serum dopamine-B-hydroxylase
l e v e l s have been shorn t o be low i n some p a t i e n t s on r e p e t i t i v e haemodialysis s u g g e s t i n g t h e presence of reduced sympathetic a c t i v i t y and autonomic dysfunction. potassium d u r i n g U.F.
The l a c k of changes i n serum
could prevent d i s t u r b a n c e s of autonomic
f u n c t i o n t h a t could t r i g g e r off a hypotensive episode. A t t h i s sizage one remains u n c e r t a i n a s t o how pure U.F.
protects
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s u s c e p t i b l e haemodialysis p a t i e n t s from hypotensive episodes but t h e l a c k of information should n o t be s u r p r i s i n g s i n c e as y e t we do n o t f u l l y understand t h e m u l t i p l e f a c t o r s t h a t f a c i l i t a t e t h e vasomotor i n s t a b i l i t y , f a l l in p e r i p h e r a l r e s i s t a n c e and hypotensive episodes during conventional haemodialysis i n t h e f i r s t p l a c e . The value of s e a u e n t i a l U.F.-H.D. L i t t l e information i s a v a i l a b l e on t h e longterm e f f e c t s of s e q u e n t i a l U.F.-H.D.
and t h e incidence of hypotensive episodes compared
to conventional haemodialysis.
In a w e l l c o n t r o l l e d b u t s h o r t B r i t i s h
study on seven p a t i e n t s and 30 d i a l y s e s i n each group, u s i n g t h e Rhodial 75 and f i l t e r s made of p o l y a c r y l o n i t r i l e membrane, no d i f f e r e n c e i n t h e i n c i d e n c e of headaches, nausea, hypotensive e p i s o d e s or cramps was noted between t h e two groups (18).
These r e s u l t s a r e i n good
agreement w i t h our f i n d i n g s over a much l o n g e r p e r i o d (Table I ) . There seems t o be no advantage i n s u b s t i t u t i n g s e q u e n t i a l U.F.-H.D. i n otherwise w e l l d i a l y z e d , non-fluid overloaded p a t i e n t s who r e g u l a r -
l y become hypotensive.
S e q u e n t i a l procedures i n t h e s e p a t i e n t s simply
delay t h e o n s e t of hypotensive symptoms t o t h e haemodialysis p o r t i o n of t h e procedure.
However, i t appears t h a t i n i n d i v i d u a l p a t i e n t s ,
e s p e c i a l l y d i a b e t i c s , symptoms may be m i l d e r and o f s h o r t e r d u r a t i o n .
343
ULTRAFILTRATION FOLLOWED BY HAEMODLALYSIS
The i n c i d e n c e of h y p o t e n s i v e e p i s o d e s i n o u r t h r e e d i a b e t i c p a t i e n t s d u r i n g 2 6 9 , p r o c e d u r e s ranged from 23 t o 53 p e r c e n t o c c u r r i n g a l m o s t uniformly d u r i n g t h e h a e m o d i a l y s i s p a r t . S i m i l a r t o t h e f a i l u r e of l o n g t e r m s e q u e n t i a l U.F.-H.D.
to
reduce t h e i n c i d e n c e of h y p o t e n s i v e e p i s o d e s i n s u s c e p t i b l e p a t i e n t s , t h e r e was no e v i d e n c e t h a t t h e m i l d m o s t l y s y s t o l i c h y p e r t e n s i o n p r e s e n t
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i n some of t h e p a t i e n t s improved ( T a b l e I ) .
These f i n d i n g s a r e n o t t o b e
compared w i t h t h e b e n e f i c i a l e f f e c t s of h a e m o f i l t r a t i o n a c r o s s a r t i f i c i a l kidneys l i k e t h e XM-50 Amicon d i a f i l t e r a s d e s c r i b e d by Henderson and colleagues (29,30).
T h e i r p r o c e d u r e i s e n t i r e l y d i f f e r e n t from t h e one
used h e r e , r e l y i n g m o s t l y on an a r t i f i c i a l k i d n e y w i t h an e x t r e m e l y h i g h u l t r a f i l t r a t i o n r a t e of t h e o r d e r of 60-80 ml/min and a m o l e c u l a r s i z e f i l t e r up t o 50,000 d a l t o n s , s o t h a t s m a l l and l a r g e s i z e uraemic t o x i n s a r e convected o u t of t h e blood w i t h t h e u l t r a f i l t r a t e . The e x p e r i e n c e g a i n e d i n t h e s e s t u d i e s c o n f i r m s t h a t t h e main b e n e f i t d e r i v e d from U.F.
i s f a c i l i t a t i o n of f l u i d removal.
The des-
c r i b e d r e s u l t s have h e l p e d t o demolish t h e t r a d i t i o n a l view t h a t u l t r a f i l t r a t i o n induced hypovolaemia i s t h e s o l e c a u s e of t h e h y p o t e n s i v e e p i s o d e s t h a t occur d u r i n g c o n v e n t i o n a l h a e m o d i a l y s i s , b u t a s y e t we do n o t know t h e i r t r i g g e r i n g mechanism, o t h e r t h a n a d i s t u r b a n c e i n autonomic vasomotor c o n t r o l may p l a y an i m p o r t a n t r o l e .
S e q u e n t i a l U.F.-H.D.
has l i t t l e
t o o f f e r i n t h e management of t h e uncomplicated d i a l y s i s p a t i e n t b u t may be of some u s e i n d i a b e t i c p a t i e n t s .
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T h i s work w a s p r e s e n t e d in p a r t a t t h e 1 0 t h a n n u a l m e e t i n g of t h e American S o c i e t y of N e p h r o l o g y , W a s h i n g t o n , D . C . , O c t o b e r , 1 9 7 7 .
(1978)
ULTRAFILTRATION FOLLOWED BY HAEMODIALYSIS. A LONGTERM TRIAL AND ACUTE STUDIES P i e r i d e s , S.B. K u r t z , W . J . Johnson D i v i s i o n of Nephrology, Mayo C l i n i c R o c h e s t e r , MN. 55901
A.M.
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ABSTRACT S e p a r a t e u l t r a f i l t r a t i o n f o l l o w e d by h a e m o d i a l y s i s (U.F.-H.D.) u s i n g Gambro Major o r Cordis-Dow h o l l o w - f i b e r d i a l y z e r s were e v a l u a t e d i n 10 d i a l y s i s p a t i e n t s o v e r a mean p e r i o d of 4 1 / 2 months and 4 5 5 U.F.-H.D. p r o c e d u r e s . F l u i d c o n t r o l was f a c i l i t a t e d i n oedemat o u s p a t i e n t s b u t t h e number of h y p o t e n s i v e e p i s o d e s d u r i n g t h e combined p r o c e d u r e r e q u i r i n g i n t r a v e n o u s 5% s a l i n e d i d n o t s i g n i f i c a n t l y d e c r e a s e . No s i g n i f i c a n t improvement in h y p e r t e n s i o n was noted. U l t r a f i l t r a t i o n (U.F.) a l o n e f o r a c u t e l y w a t e r o v e r l o a d e d , azotaemic p a t i e n t s proved v e r y u s e f u l . Two t o f i v e l i t e r s of oedema f l u i d could be removed a s y m p t o m a t i c a l l y i n one t o t h r e e h o u r s u s i n g transmembrane p r e s s u r e s of 250 t o 500 d g and U.F. r a t e s of 10 t o 4 2 ml/min. Two p a t i e n t s became a c u t e l y and s y m p t o m a t i c a l l y hypotens i v e . One was an i n s u l i n dependent d i a b e t i c i n whom 3800 m l were removed i n 7 5 minutes and t h e o t h e r a h y p e r t e n s i v e p a t i e n t undergoing t r e a t m e n t w i t h M i n o x i d i l and p r o p r a n o l o l . INTRODUCTION Diffusion i s the b a s i c p r i n c i p l e underlying the t r a n s f e r of s o l u t e s d u r i n g h a e m o d i a l y s i s u s i n g c o n v e n t i o n a l membranes such a s c e l l u l o s e a c e t a t e and cuprophan.
T h e r e f o r e s m a l l m o l e c u l e s such a s
sodium, potassium and u r e a a r e c l e a r e d p r e f e r e n t i a l l y w i t h t h e p o s s i b i l i t y t h a t l a r g e r and p o s s i b l y t o x i c m e t a b o l i t e s may accumulate i n t h e c i r c u l a t i o n (1,Z).
U.F.
during conventional d i a l y s i s
contributes l i t t l e t o small s o l u t e c l e a r a n c e but i t i s invaluable i n removing w a t e r from o v e r l o a d e d p a t i e n t s ( 2 , 3 , 4 ) . haemodialysis with U.F.
Combined
a s currently practiced is usually sufficient
t o c o n t r o l t h e a z o t a e m i a and o v e r h y d r a t i o n r e s u l t i n g from e n d - s t a g e 325 Copynght 0 1 9 7 8 by Marcel Dekker, Inc All Rights Reserved Neither this work nor any part may he reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying. microhlming, and recording. or by any information storage and retrieval system, without permission in writing from the publisher
326
PIERIDES, KURTZ, AND JOHNSON
r e n a l f a i l u r e b u t problems o c c a s i o n a l l y a r i s e i n p a t i e n t s xho gain f l u i d e x c e s s i v e l y betxeen d i a l y s e s o r become oedematous a f t e r an unsuccessful r e n a l t r a n s p l a n t , prolonged h y p e r a l i m e n t a t i o n o r a serious intercurrent illness.
In some of these p a t i e n t s a t t e m p t s t o u l t s a f i l t e r t h e excess
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f l u i d during standard haemodialysis may be complicated by troublesome hypotension, muscle cramps and vomiting.
S i m i l a r l y a minority of
oedema-free p a t i e n t s ( 5 , 6 , 7 ) a l s o become hypotensive during convent i o n a l haemodialysis r e q u i r i n g i n t r a v e n o u s s a l i n e i n o r d e r to maintain normal blood p r e s s u r e s d u r i n g t h e procedure.
The administra-
t i o n of s a l i n e obviously d e f e a t s t h e purpose of m a i n t a i n i n g optimal f l u i d balance. uncertain.
The pathogenesis of t h e s e hypotensive episodes remains
T r a d i t i o n a l l y they have been a s c r i b e d t o u l t r a f i l t r a t i o n -
induced hypovolemia ( 5 . 6 ) but i t i s l i k e l y t h a t i n some p a t i e n t s a d e f e c t i n vasomotor c o n t r o l p l a y s an important p a r t (7,8,9,10). Elegant experiments by Kersh and c o l l e a g u e s (8) aimed a t e v a l u a t i n g autonomic vasomotor f u n c t i o n i n t h e s e p a t i e n t s i n d i c a t e t h a t approximately 80 p e r c e n t of t h e p a t i e n t s who become hypotensive during haemodialysis appear t o have a s i g n i f i c a n t degree of autonomic i n s u f ficiency.
Work by L i l l e y and h i s c o l l e a g u e s ( 7 ) i n d i c a t e s t h a t the
f a u l t may be i n t h e a f f e r e n t l i m b of t h e b a r o r e c e p t o r r e f l e x .
Other
i n v e s t i g a t o r s have reported f i n d i n g s compatible with t h e s e conclus i o n s (11,12,13).
The p o s s i b i l i t y t h a t u l t r a f i l t r a t i o n - i n d u c e d
hypovolaemia may n o t be the primary and complete cause f o r the observed hypotension has r e c e n t l y received f u r t h e r support following the unexpected f i n d i n g t h a t c o n t r a r y t o popular b e l i e f t h e s e p a t i e n t s may t o l e r a t e l a r g e f l u i d losses i f these a r e produced by U.F. dialysis.
Although U.F.
alone without
had been used by s e v e r a l workers i n t h e p a s t
ULTRAFILTRATION FOLLOWED BY HAEMODIALYSIS
327
i n o r d e r t o d e a l w i t h oedematous p a t i e n t s ( 3 , 4 , 1 4 , 1 5 )
U.F.
t h e u s e of pure
b e f o r e h a e m o d i a l y s i s r e c e i v e d i t s main impetus from t h e work of
Bergstrom and c o l l e a g u e s ( 1 6 ) .
They i n d i c a t e d t h a t i f e x c e s s f l u i d
could be removed d u r i n g t h e f i r s t hour by U.F.
alone, haemodialysis
could be c a r r i e d o u t d u r i n g t h e l a t t e r p a r t of t h e " d i a l y s i s s e s s i o n ' '
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with minimal, i f any, symptoms o r i n c o n v e n i e n c e t o t h e p a t i e n t . This p r o j e c t w a s u n d e r t a k e n i n o r d e r t o d e f i n e c l i n i c a l s i t u a t i o n s where s e q u e n t i a l U.F.-Y.D. U.F.
a l o n e and U.F.-H.D.
m i g h t prove u s e f u l .
A t t h e same time,
were used i n t h e management of oedematous
azotaemic p a t i e n t s and j u v e n i l e d i a b e t i c s who were f l u i d o v e r l o a d e d .
METHODS
The s t u d y i n v o l v e d a ) a longterm s e q u e n t i a l U . F . - H . D .
t r i a l in
10 p a t i e n t s a l r e a d y s t a b i l i z e d on r e p e t i t i v e h a e m o d i a l y s i s , and b) 1 7 a c u t e U.F.
s t u d i e s i n 15 oedematous a z o t a e m i c p a t i e n t s .
Longterm s t u d y
Ten p a t i e n t s , 5 males and 5 f e m a l e s , aged 28-79, p r e v i o u s l y t r e a t e d by c o n v e n t i o n a l h a e m o d i a l y s i s u s i n g t h e Gambro Major o r Cordis-Dow hollow f i b e r kidney ( s u r f a c e a r e a ?.5 M2) were changed t o a program of one hour p u r e u l t r a f i l t r a t i o n followed by h a e m o d i a l y s i s u s i n g t h e same dialyzers.
The t o t a l U.F.-H.D.
i n m e d i c a t i o n were c a r r i e d o u t .
time remained unchanged and no changes F i v e p a t i e n t s were s e l e c t e d because of
r e c u r r e n t h y p o t e n s i v e e p i s o d e s o c c a s i o n a l l y accompanied by cramps and vomiting o c c u r r i n g d u r i n g o r immediately f o l l o w i n g d i a l y s i s .
Placement
i n t h e Trendelenburg p o s i t i o n and i n t r a v e n o u s 5% s a l i n e were used t o control these complications.
The need f o r a d m i n i s t e r i n g 5% s a l i n e was
taken a s an i n d i c a t i o n of a symptomatic h a e m o d i a l y s i s s e s s i o n .
F i v e more
PIERIDES, KURTZ, AM) JOHNSON
328
p a t i e n t s were included i n the study because of m i l d hypertension and occasional f l u i d overload.
During t h e i n i t i a l hour of pure U.F.,
each
p a t i e n t ' s blood l i n e s were connected t o t h e d i a l y z e r a s usual but the d i a l y s a t e f l u i d was n o t c i r c u l a t e d .
A clamp was used on t h e blood l i n e
r e t u r n i n g to t h e p a t i e n t (venous l i n e ) t o r a i s e the p r e s s u r e between
250 and 290 rraaHg.
The d i a l y z e r was h e l d i n a v e r t i c a l p o s i t i o n and the
u l t r a f i l t r a t e was c o l l e c t e d i n a measuring c y l i n d e r ( F i g u r e 1).
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the hour of U.F.
After
was completed, the venous clamp was removed allowing
the p r e s s u r e t o drop, t h e d i a l y s a t e l i n e s were reconnected t o the d i a l y z e r and pumping of d i a l y s a t e f l u i d was s t a r t e d . made t o keep U.F.
An attempt was
t o a minimum during t h e haemodialysis period avoiding
removal of any more f l u i d than was a b s o l u t e l y e s s e n t i a l t o r e s t o r e f l u i d balance.
\
\
Metallic screw clamp t o raise venous pressure -250 mm Hg
uu
Arterial blood pump
Measuring
Figure 1 Diagram t o i l l u s t r a t e the way U.F.
was c a r r i e d o u t
ULTRAFILTRATION FOLLOWED BY HAEMODIALYSIS
329
Serum u r e a , c r e a t i n i n e , phosphorus, c a l c i u m , potassium and haemoglobin were measured by s t a n d a r d a n a l y t i c a l t e c h n i q u e s a t t h e b e g i n n i n g and end of t h e t r i a l .
P a i r e d "t" t e s t s were used t o a s s e s s
any s i g n i f i c a n t d i f f e r e n c e s .
Acute s t u d i e s
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Combined U.F.-H.D.
o r U.F.
w i t h o u t d i a l y s i s were performed i n
azotaemic p a t i e n t s on o c c a s i o n s when oedema was p r o m i n e n t . procedure was s i m i l a r t o t h a t used i n t h e l o n g t e r m U.F.-H.D. a p a r t from f i v e o c c a s i o n s when U.F.
The trial
a l o n e u s i n g h i g h e r venous p r e s s u r e s
( 4 5 0 - 5 0 0 n-nnHg) were used r e s u l t i n g i n more e f f i c i e n t
U.F.
Blood p r e s -
s u r e was monitored c l o s e l y e i t h e r w i t h a sphygmomanometer o r a Roche A r t e r i o s o n d manometer.
I n s e v e r a l p a t i e n t s s e r i a l serum o s m o l a l i t i e s
were r e c o r d e d by means of an Advanced I n s t r u m e n t s H i - p r e c i s i o n osmometer.
RESULTS
Longterm t r i a l
T a b l e 1 d e s c r i b e s t h e c l i n i c a l c h a r a c t e r i s t i c s of t h e 10 p a t i e n t s who p a r t i c i p a t e d i n t h i s t r i a l .
The f i n d i n g s d u r i n g t h e t r e a t m e n t
p e r i o d were compared t o t h o s e of an e q u a l p e r i o d p r e c e d i n g t h e s t u d y when p a t i e n t s were m a i n t a i n e d on s t a n d a r d h a e m o d i a l y s i s .
The number of
symptomatic h y p o t e n s i v e e p i s o d e s d i d n o t s i g n i f i c a n t l y d e c r e a s e i n f i v e p a t i e n t s who e x p e r i e n c e t h i s commonly, (84 i n c o n t r o l p e r i o d and 7 6 duri n g s e q u e n t i a l U.F.-H.D.
t = 0 . 6 6 , p = n . ~ . ) ; however a t l e a s t two
of
t h e f i v e p a t i e n t s f e l c t h a t t h e i r symptoms w e r e Less s e v e r e and e a s i e r t o reverse.
U.F.
r a t e s ranged from 1 3 t o 27 m l p e r m i n u t e , t h e mean f l u i d
loss d u r i n g t h e U.F.
hour b e i n g 1000 m l .
Thus, from 25 t o 100 p e r c e n t of
t h e f l u i d removed d u r i n g t h e combined U.F.-H.D.
procedure occurred during
Sex
Age
D u r a t i o n of Treatment
No of Procedures
3
Polycystic Disease
51
F
2
3 314
I n t e r s t i t i a l Nephritis
28
F
1
38
57
4 314
Lupus N e p h r i t i s
52
F
7
47
5
Myeloma Kidney
79
42
112
4
Nephrosclerosis
M
M
5
67
Reason for Entering the T r i a l
Hypotensive Symptoms 1
41
38
4 114
Nephrosclerosis
71
M
a
6
TABLE I
CLINICAL INFORMATION AND FINDINGS I N THE 10 PATIENTS WHO PARTICIPATED I N THE LONGTERM SEQUENTIAL UF-HD TRIAL AND ALSO THE 3 DIABETIC PATIENTS WHO STILL USE THIS PROCEDURE
Diagnosis
Symptomatic Hypotensive Runs Control
49
4 112
Lupus N e p h r i t i s
46
F
3
5 112
Chronic G . N .
69
M
9
42
4 314
Nephrosclerosis
48
Hypotensive Symptoms Hypotensive Symptoms Hypotensive Symptoms Hypotensive Symptoms
Trial
27
85/41
7
5
ib.a?a Diabetes Mellitus
Hypotensive Symptoms
70
Mean Supi Pre-dialy Blood P r e
117167
21
19
19
19
9
161190 154184
156178
163176
172174
Mild Oedema
~~
F
Control
20
27
14
158185
Mild Oedema Mild Oedema
146182
Mild Oedema
iiatiio
Hypertension a4
58
76 ~
i5.2+6 p=n. s
40 = 53%
7
11
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Case
(months)
---
53
4 112
Diabetes Mellitus
65
F
42
48
M
10
455
112
4
Total Mean
19 = 25% 29 = 23%
12 M 28 D i a b e t e s M e l l i t u s 6 76 Hypotensive Symptoms 42 F 65 D i a b e t e s M e l l i t u s 10 123 Hypotensive Symptoms 1 Hypotension ? muscle cramps f vomiting, r e q u i r i n g I V 5% s a l i n e 2 P a t i e n t p a r t i c i p a t e d i n t h e t r i a l and then c o n t i n u e d on t h e UF-HD procedure P a t i e n t s 11, 1 2 and 4 s t i l l use s e q u e n t i a l UF-HD
149178
p=
ULTRAFILTRATIOS FOLLOWED BY HAEMODIALYSIS t h e f i r s t hour of p u r e U.F.
U.F.
331
Hypotensive e p i s o d e s d u r i n g t h i s hour o f
were unusual b u t i n t h e f i v e s u s c e p t i b l e i n d i v i d u a l s t h e s e
symptoms r e c u r r e d when t h e p a t i e n t s resumed s t a n d a r d h a e m o d i a l y s i s . Because symptoms o c c u r r e d l a t e r on i n t h e p r o c e d u r e , b e t t e r f l u i d c o n t r o l was p o s s i b l e .
w a s t h e e a s e w i t h which f l u i d b a l a n c e c o u l d be
t i a l U.F.-H.D. restored.
Undoubtedly t h e g r e a t e s t a d v a n t a g e of sequen-
A s i n d i c a t e d by T a b l e I , no s i g n i f i c a n t changes i n hyper-
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t e n s i o n o c c u r r e d by t h e end of t h e t r i a l . A f t e r completion of t h e s t u d y , p a t i e n t 4 , a l o n g s t a n d i n g i n s u l i n - d e p e n d e n t d i a b e t i c who had been on c o n v e n t i o n a l h a e m o d i a l y s i s € o r a y e a r r e q u e s t e d c o n t i n u a t i o n of combined U.F.-H.D.
Two a d d i -
t i o n a l i n s u l i n dependent d i a b e t i c s have s i n c e e x p r e s s e d p r e f e r e n c e €or t h i s procedure.
Although a l l t h r e e of them show o c c a s i o n a l
h y p o t e n s i v e e p i s o d e s d u r i n g U.F.-H.D.,
symptoms a p p e a r more t o l e r a b l e ,
of s h o r t e r d u r a t i o n and e a s i e r t o r e v e r s e . Table I1 i l l u s t r a t e s t h e biochemical changes a t t h e end of t h e
trial.
There were no s i g n i f i c a n t d i f f e r e n c e s i n s e r u m u r e a , c r e a t i n i n e
calcium o r hemoglobin v a l u e s .
However, serum phosphorus and potassium
showed s m a l l b u t s i g n i f i c a n t i n c r e a s e s r e f l e c t i n g t h e f a c t t h a t o v e r a l l d i a l y s i s time was reduced by two t o t h r e e h o u r s p e r week. ed, U . F .
As anticipat-
d i d n o t improve s m a l l s o l u t e c l e a r a n c e s .
Acute p u r e U.F.
studies
F i f t e e n p a t i e n t s were t r e a t e d by U.F. a l o n e € o r oedema on
1 7 o c c a s i o n s , 2 p a t i e n t s h a v i n g two t r e a t m e n t s e a c h .
T a b l e 111
summarizes t h e volumes of f l u i d removed, t y p e of d i a l y z e r used, achieved U.F.
r a t e s and p r e s e n c e o r a b s e n c e of symptoms.
Of t h e 1 7 t r e a t m e n t s e s s i o n s , 1 3 were f r e e of any symptoms d e s p i t e removal of oedema f l u i d a t U.F.
r a t e s f a s t e r than p r e v i o u s l y
TABLE I1 BIOCHEMICAL CHANGES AT COMPLETION OF THE SEQUENTIAL UF-HD TRIAL
Serum Urea mg/100 m l
155
a
224
7
255
a7
6
184
20 2
5
134
145
4
202
126
3
270
2
190
1
118 204
169
159 185
Creatinine mg/100 ml
11.5 10.5 14.5 10.7 13.3 8.4
8.1
9.5
12.9
230
11.3
192
10.4 10.5
17.7 8.7
12.6 10.5 9.1 9.6
17.8 18.4
Potassium meq/L
4.7
6.1 4.8
4.9
4.2 3.1 4.2
4.2 4.5 4.7
5.1 6.1 6.4 5.7 4.6 5.3 5.2 4.5 5.4 5.2
Calcium mg/100 m l
9.1 10.1 10.3 8.8
9.5 8.7
8.7 8.6
8.2 8.0
9.4 9.5 9.7 8.9 9.4 8.4 9.4 8.3 8.0
8.6
Phosphorus mg/100 ml
3.3 4.3 4.3
6.9 4.6 3.1 4.8
5.2 4.3 3.1
5.1 5.9 4.1 9.0 6.0
7.5 3.5 5.4 6.3 4.5
Hemoglobin g/100 m l
6.0 7.9 4.8
5.5 7.9 6.4
6.3 8.6
5.8 7.9
6.1 9.7 7.2 6.0 6.6
6.6 7.8
8.4 6.9 8.7
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Case
Control T r i a l Control T r i a l Control T r i a l Control T r i a l Control T r i a l Control T r i a l
95
9
10
-
Mean t
P
166.3 186.3 f57 f41 ti-0.78 N.S.
11.07 12.53 t 2 . 0 8 f3.89 t=l.62 N.S.
4.5 5.3 t0.7 3.6 t=3.86 pq.005
9.0
9.0
f0.8 tO.6 t = O . 33 N.S.
4.4 5.7 t1.1 f1.6 t=2.75 pq.025
6.7 7.4 21.3 f1.2 t=2.03
N.S.
333
ULTRAFILTRATION FOLLOWED BY WENODIALYSIS possible during conventional haemodialysis.
I n t:io of f o u r r u n s ,
h y p o t e n s i v e e p i s o d e s \ ; e r e s e v e r e enough t o r e q u i r e t e r m i n a t i o n o f t r e a t m e n t , w h i l e i n t h e r e m a i n i n g two ( c a s e s 6 and 1 3 ) , t h e p r o c e d u r e was resumed a f t e r t h e i n t r a v e n o u s a d m i n i s t r a t i o n of 250 m l of proteinate. F i g u r e 2 i l l u s t r a t e s changes d u r i n g one of t h e s e symptomatic p r o c e d u r e s (Case l a ) .
The p a t i e n t ( c a s e 4 i n t h e longterm t r i a l ) was
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an i n s u l i n - d e p e n d e n t d i a b e t i c who a f t e r 75 m i n u t e s of U . F .
and l o s s o €
3,800 m l of f l u i d s u d d e n l y became h y p o t e n s i v e w i t h a slow i r r e g u l a r p u l s e r e q u i r i n g i n t r a v e n o u s i n f u s i o n of s a l i n e and d i s c o n t i n u a t i o n o f the procedure.
T h i s p a t i e n t usualLy remains asymptomatic when 900 t o
1800 m l a r e removed d u r i n g t h e i n i t i a l U.F. houi of a combined U . F . - H . D . procedure. F i g u r e 3 r e f e r s t o c a s e 1 5 , an a z o t a e m i c p a t i e n t n o t y e t on r e p e t i t i v e h a e m o d i a l y s i s , s u f f e r i n g from r e n a l f a i l u r e and s e v e r e n e p h r o t i c syndrome due t o m e m b r a n o p r o l i f e r a t i v e g l o m e r u l o n e p h r i t i s .
P r i o r to
t h e p r o c e d u r e , t h e p a t i e n t r e c e i v e d M i n o x i d i l , p r o p r a n o l o l and furosemide.
I m e d i a t e l y a f t e r p r i m i n g t h e Gambro Major d i a l y s e r x i t h t h e
p a t i e n t ' s own b l o o d , he became h y p o t e n s i v e and h i s p u l s e f e l l t o 37 b e a t s p e r m i n u t e .
The p r o c e d u r e was immediately t e r m i n a t e d and
t h e blood r e t u r n e d t o t h e p a t i e n t .
However, t h e blood p r e s s u r e d i d
n o t r i s e t o b a s e l i n e v a l u e s f o r two h o u r s .
I t is l i k e l y t h a t the
drug t h e r a p y i n t e r f e r e d w i t h t h e p a t i e n t ' s a b i l i t y t o respond t o hypovolemia, a f i n d i n g t h a t emphasizes t h e i m p o r t a n c e of c o n s i d e r i n g t h e p a t i e n t ' s d r u g s b e f o r e embarking on such a p r o c e d u r e .
Renal
f u n c t i o n d i d n o t change. F i g u r e s 4 and 5 i l l u s t r a t e two asymptomatic p r o c e d u r e s d u r i n g which 4 , 2 0 0 and 5,000 ml of oedema f l u i d were removed i n two and t h r e e h o u r s r e s p e c t i v e l y w i t h o u t a f a l l i n blood p r e s s u r e .
FINDINGS I N 17 U.F.
*
TABLE 111
RUNS CARRIED OUT ON 1 5 AZOTAEMIC PATIENTS
WITH OEDEMA AS A PROMINENT FINDING
Volume of Ultrafiltrate
Duration
2400
5
110
3000
4
120
4200
3
5000
2
3800
la
2140
1
90
75
180
Type o f Dialyser
Mean Venous Pressure mmHg
Gambro 1 . 5 Gambro 1 . 5 T r a v e n o l CF
250 450 450
U 1t r a Filtration Rate
Commen t s
ml/min 24 42
28
No symptoms
Sudden h y p o t e n s i o n & b r a d y c a r d i a
No symptoms
1500
Gambro 1 . 5 T r a v e n o l CF
450 400
35 27
No symptoms No symptoms
1500
120
Travenol CP
250
20
No symptoms
1500 180
T r a v e n o l CF 1500
250
14
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Case
(min)
2550
6
Asymptomatic s m a l l BP d r o p Had 250 m l of p r o t e i n a t e
335
ULTRAFILTRATION FOLLOWED BY HAEMODIALYSIS
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336
PIERLDES, KURTZ, AND JOHNSON
Gambro major Venous resistance - 4 5 0 mm Hg Blood flow-166 ml/min Hemofiltration r a t e . 4 0 ml/min
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2
z 2'' -3
-
-4
80 60
Saline + take off hemofiltration 550 ml 0.9% saline given
60
0
Time, min
90
4% +
IHEMOFILTRATION)
DISCUSSION C l i n i c a l use of U.F. Removal of e x c e s s i v e e x t r a c e l l u l a r f l u i d remains t h e main indication for u l t r a f i l t r a t i o n .
Lunderquist used t h e Alwall d i a l y z e r -
u l t r a f i l t e r i n 1952 t o remove 7 . 4 kg from an azotaemic p a t i e n t i n pulmonary oedema over a course of n i n e hours ( 4 ) .
When r e p e t i t i v e
haemodialysis became e s t a b l i s h e d a decade l a t e r , U.F. i n t e g r a l p a r t of i t .
became an
Using t h e g e n e r a l l y a v a i l a b l e a r t i f i c i a l
kidneys, 500 t o 3000 m l s of f l u i d a r e u s u a l l y removed by U.F. over a four t o s i x hour long haemodialysis.
ULTRAFILTRATION FOLLOWED BY HAENODLALYSIS
337
lOOr
:v 80
I
Azatemic/nephrotic patient Membrano-proliferative GN Edema +++ Minoxidil, Inderal. Lasix
50
40 30
Needles in
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11 50 ml saline drained
Records of t h e two symptomatic and h y p o t e n s i v e runs i n a ) a n i n s u l i n - d e p e n d e n t d i a b e t i c p a t i e n t , b) a p a t i e n t on t r e a t m e n t w i t h M i n o x i d i l and p r o p r a n o l o l .
When t h e blood c h e m i s t r y v a l u e s o f t h e oedematous azotaemic p a t i e n t a r e s a t i s f a c t o r y and i n p a r t i c u l a r serum potassium i s normal, U.F.
o f f e r s th-o d i s t i n c t a d v a n t a g e s : prompt r e l i e f from t h e
e f f e c t s of oedema e s p e c i a l l y when t h e l u n g s a r e a f f e c t e d and absence of s i d e e f f e c t s d u r i n g t h e p r o c e d u r e .
Kopp ( 1 7 ) s t r e s s e d t h e i m -
p o r t a n c e of e n s u r i n g a normal serum p o t a s s i u m b e f o r e embarking on U.F. s i n c e t h i s procedure does n o t from t h e 17 pure U.F.
105-er
serum p o t a s s i u m .
The good r e s u l t s
t r e a t m e n t p e r i o d s i n o u r s t u d y confirm t h e
e f f i c a c y of t h i s p r o c e d u r e i n r e l i e v i n g oedema and o u r o b s e r v a t i o n s a r e i n agreement w i t h o t h e r p u b l i s h e d d a t a (3,14,15,16,18).
What i s
338
PIJIRIDES, KURTZ, AND JOHNSON
290
Gambro major Venous resistance-450 mm Hg Blood flow-170 ml/min Hernofiltration rate-35ml /min
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80
-3 -4
Time, min IHEMOFILTRATIONI
of i n t e r e s t however i s the general l a c k of hypotensive episodes during removal of f l u i d volumes which o c c a s i o n a l l y exceeded t h e p a t i e n t s ' own c i r c u l a t i n g blood volume.
Goss e t a 1 (19), K i m e t a1 ( 6 ) and Handt
e t a1 ( 2 0 ) have a l l demonstrated a f a l l i n c a r d i a c o u t p u t and blood volume d u r i n g standard haemodialysis and G o s s e t a1 ( 1 9 ) a l s o showed an increase i n t o t a l peripheral resistance. extended t h e s e f i n d i n g s t o pure U.F.
Hampl e t a1 (21) have s i n c e
I t would thus appear very l i k e l y t h a t
the key f a c t o r r e s p o n s i b l e f o r the usual absence of hypotensive episodes during haemodialysis is the p a t i e n t ' s a b i l i t y t o i n c r e a s e h i s o r her p e r i p h e r a l r e s i s t a n c e a p p r o p r i a t e l y so t h a t a normal blood pressure
i s maintained w h i l e oedema f l u i d l e a v e s the i n t e r s t i t i a l space t o e n t e r t h e v a s c u l a r compartment.
The importance of adequate p e r i -
ULTRAFILTRATION FOLLOWED 9Y HAFXODLALYSIS
3 39
%
330
320
90
8OL
Travenol HF 1500 Venous resistance-450 mm Hg Blood flow-190 ml/min Hemofiltration rate 2 7 m V min
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-
':E -5
200 r
I
90
0
I 180
Time, min lHEMOFlLTRATlON 1
Figures 4 & 5
Asymptomatic U.F. r u n s i l l u s t r a t i n g t h e removal o f 4 , 2 0 0 and 5,000 m l o f oedema f l u i d .
p h e r a l r e s i s t a n c e can be a p p r e c i a t e d by t h e f i n d i n g s i n two o f o u r p a t i e n t s ( F i g u r e s 2 & 3 ) who became a c u t e l y h y p o t e n s i v e .
Both had
good r e a s o n s f o r a compromized p e r i p h e r a l a r t e r i o l a r vasomotor control.
P a t i e n t 15 was on a n t i - h y p e r t e n s i v e t r e a t m e n t w i t h
p r o p r a n o l o l and M i n o x i d i l a p o t e n t p e r i p h e r a l v a s o d i l a t o r , w h i l e patient 1 was a longstanding insulin-dependent d i a b e t i c with a peripheral neuropathy.
The e x p e r i e n c e w i t h t h e l a t t e r p a t i e n t i s
340
PIERIDES, KURTZ, AND JOHNSON
instructive.
She has been undergoing U.F.-H.D.
f o r over a y e a r ,
r e g u l a r l y l o s i n g u p t o 1800 m l of f l u i d d u r i n g t h e U.F. minimal symptoms.
hour with
h t h e day she became a c u t e l y hypotensive,
U.F.
alone using a h i g h e r venous p r e s s u r e was being c a r r i e d o u t because of severe oedema.
Her blood p r e s s u r e dropped suddenly when 3,800 m l
had been removed and w h i l e t h e r e was s t i l l v i s i b l e a n k l e oedema. This would suggest t h a t t h e r e may be a l i m i t t o how much a p a t i e n t
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can compensate f o r r a p i d U.F.
losses.
Therefore pure U.F.
be considered a simple and always s a f e procedure.
should not
S e r i o u s hypoten-
s i v e episodes may occur i f e x c e s s i v e amounts of f l u i d a r e r a p i d l y removed e s p e c i a l l y i f t h e p a t i e n t ' s vasomotor c o n t r o l i s anatomic a l l y o r pharmacologically compromised.
O u r encouraging experience with s e q u e n t i a l U.F.-H.D.
in diabetic
p a t i e n t s would s u g g e s t t h a t t h i s procedure may be of some b e n e f i t to them.
D i a b e t i c p a t i e n t s show an increased i n c i d e n c e of hypotensive
episodes d u r i n g conventional haemodialysis ( 2 2 ) and Ma e t a 1 ( 2 3 ) emphasized t h e i r unusually high weight g a i n s between d i a l y s e s n e c e s s i t a t i n g c o n s i d e r a b l e f l u i d removal d u r i n g haemodialysis. use of s e q u e n t i a l U.F.-H.D.
The
may indeed render haemodialysis less
s t r e s s f u l and symptomatic t o t h e s e p a t i e n t s . Why do c e r t a i n p a t i e n t s become hypotensive d u r i n g s t a n d a r d haemodialysis?
C l e a r l y t h i s m u s t be a m u l t i f a c t o r i a l problem a s only
small numbers of p a t i e n t s a r e a f f e c t e d , e s t i m a t e d by Maher and c o l leagues t o be 8 p e r c e n t ( 5 ) and by Graefe e t a 1 (24) 1 4 p e r c e n t of t h e i r haemodialysis populations. why pure U.F.
Equally important i s t h e question
i s n o t accompanied by hypotensive crises?
In the
i n i t i a l p r e s e n t a t i o n of t h e i r r e s u l t s , Bergstrom e t a1 ( 1 6 ) concluded t h a t s o l u t e s h i f t s brought about by d i f f u s i o n a c r o s s d i a l y s i s mem-
341
ULTRAFILTRATION FOLLOWED BY HAEMODIALYSIS b r a n e s f a c i l i t a t e d h y p o t e n s i o n i n s u s c e p t i b l e i n d i v i d u a l s b u t were u n a b l e t o d e t e r m i n e t h e i r e x a c t n a t u r e o r mode of a c t i o n .
As
e x p e c t e d , changes i n serum o s m o l a l i t y d u r i n g p u r e U.F. a r e minimal ( F i g u r e 4 & 5 ) , whereas d u r i n g r e g u l a r h a e m o d i a l y s i s t h e r e i s a d e f i n i t e d e c r e a s e i n serum o s m o l a l i t y which r e s u l t s i n a s i g n i f i c a n t s h i f t of e x t r a c e l l u l a r f l u i d i n t o t h e i n t r a c e l l u l a r s p a c e a s h a s been demonstrated by F a l l s e t a1 ( 2 5 ) .
However, i t i s u n l i k e l y t h a t t h i s
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i s t h e t r i g g e r i n g mechanism f o r t h e o b s e r v e d e p i s o d e s of h y p o t e n s i o n . Graefe e t a1 ( 2 4 ) r e f e r r e d to the myocardial depressing a c t i o n ( 2 6 ) and p e r i p h e r a l v a s o d i l a t i n g a c t i o n ( 2 7 ) o f sodium a c e t a t e , u n i f o r m l y employed d u r i n g s t a n d a r d h a e m o d i a l y s i s when they d e s c r i b e d e x p e r i m e n t s i n f i v e p a t i e n t s w i t h f r e q u e n t h y p o t e n s i v e e p i s o d e s t h a t showed f e w e r symptoms when d i a l y z e d w i t h sodium b i c a r b o n a t e r a t h e r than a c e t a t e . They p o s t u l a t e d t h a t t h e a b s e n c e of a c e t a t e d u r i n g p u r e U.F.
was
the explanation, a t l e a s t i n p a r t f o r the lack of hypotensive episodes.
T h i s does n o t however e x p l a i n why t h e s e h y p o t e n s i v e e p i s o d e s
a f f e c t o n l y a s m a l l m i n o r i t y of p a t i e n t s ( 5 , 2 4 ) , when sodium a c e t a t e i s u n i v e r s a l l y u s e d , u n l e s s i t c a n b e shown t h a t t h e s e i n d i v i d u a l s a r e i n c a p a b l e of m e t a b o l i z i n g a c e t a t e o r a r e p e c u l i a r l y susceptible to its effect.
I n t e r e s t i n g l y G r a e f e e t a 1 ( 2 4 ) used a
d i a l y s a t e p o t a s s i u m c o n c e n t r a t i o n of 3 meq/L i n t h e i r s t u d i e s . Henrich e t a 1 ( 2 8 ) n o t e d t h e p r e s e n c e o f i m p o r t a n t d i f f e r e n c e s between i s o k a l a e m i c and hypokalaemic d i a l y s e s .
I n a s e r i e s of c a r e -
f u l e x p e r i m e n t s , i s o k a l a e m i c h a e m o d i a l y s i s i n marked c o n t r a s t t o hypokalaemic d i a l y s i s r e s u l t e d i n a f a l l of plasma a l d o s t e r o n e , f a l l of plasma c a t e c h o l a m i n e s b u t no r i s e i n h e a r t r a t e d e s p i t e a f a l l i n blood p r e s s u r e and body w e i g h t .
It w a s t h o u g h t t h a t t h e f a l l i n
serum potassium c o u l d unmask a d e g r e e o f autonomic i n s u f f i c i e n c y
342
PIWIDES, KURTZ, AND JOHNSON
p r e s e n t i n some p a t i e n t s .
Recently serum dopamine-B-hydroxylase
l e v e l s have been shorn t o be low i n some p a t i e n t s on r e p e t i t i v e haemodialysis s u g g e s t i n g t h e presence of reduced sympathetic a c t i v i t y and autonomic dysfunction. potassium d u r i n g U.F.
The l a c k of changes i n serum
could prevent d i s t u r b a n c e s of autonomic
f u n c t i o n t h a t could t r i g g e r off a hypotensive episode. A t t h i s sizage one remains u n c e r t a i n a s t o how pure U.F.
protects
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s u s c e p t i b l e haemodialysis p a t i e n t s from hypotensive episodes but t h e l a c k of information should n o t be s u r p r i s i n g s i n c e as y e t we do n o t f u l l y understand t h e m u l t i p l e f a c t o r s t h a t f a c i l i t a t e t h e vasomotor i n s t a b i l i t y , f a l l in p e r i p h e r a l r e s i s t a n c e and hypotensive episodes during conventional haemodialysis i n t h e f i r s t p l a c e . The value of s e a u e n t i a l U.F.-H.D. L i t t l e information i s a v a i l a b l e on t h e longterm e f f e c t s of s e q u e n t i a l U.F.-H.D.
and t h e incidence of hypotensive episodes compared
to conventional haemodialysis.
In a w e l l c o n t r o l l e d b u t s h o r t B r i t i s h
study on seven p a t i e n t s and 30 d i a l y s e s i n each group, u s i n g t h e Rhodial 75 and f i l t e r s made of p o l y a c r y l o n i t r i l e membrane, no d i f f e r e n c e i n t h e i n c i d e n c e of headaches, nausea, hypotensive e p i s o d e s or cramps was noted between t h e two groups (18).
These r e s u l t s a r e i n good
agreement w i t h our f i n d i n g s over a much l o n g e r p e r i o d (Table I ) . There seems t o be no advantage i n s u b s t i t u t i n g s e q u e n t i a l U.F.-H.D. i n otherwise w e l l d i a l y z e d , non-fluid overloaded p a t i e n t s who r e g u l a r -
l y become hypotensive.
S e q u e n t i a l procedures i n t h e s e p a t i e n t s simply
delay t h e o n s e t of hypotensive symptoms t o t h e haemodialysis p o r t i o n of t h e procedure.
However, i t appears t h a t i n i n d i v i d u a l p a t i e n t s ,
e s p e c i a l l y d i a b e t i c s , symptoms may be m i l d e r and o f s h o r t e r d u r a t i o n .
343
ULTRAFILTRATION FOLLOWED BY HAEMODLALYSIS
The i n c i d e n c e of h y p o t e n s i v e e p i s o d e s i n o u r t h r e e d i a b e t i c p a t i e n t s d u r i n g 2 6 9 , p r o c e d u r e s ranged from 23 t o 53 p e r c e n t o c c u r r i n g a l m o s t uniformly d u r i n g t h e h a e m o d i a l y s i s p a r t . S i m i l a r t o t h e f a i l u r e of l o n g t e r m s e q u e n t i a l U.F.-H.D.
to
reduce t h e i n c i d e n c e of h y p o t e n s i v e e p i s o d e s i n s u s c e p t i b l e p a t i e n t s , t h e r e was no e v i d e n c e t h a t t h e m i l d m o s t l y s y s t o l i c h y p e r t e n s i o n p r e s e n t
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i n some of t h e p a t i e n t s improved ( T a b l e I ) .
These f i n d i n g s a r e n o t t o b e
compared w i t h t h e b e n e f i c i a l e f f e c t s of h a e m o f i l t r a t i o n a c r o s s a r t i f i c i a l kidneys l i k e t h e XM-50 Amicon d i a f i l t e r a s d e s c r i b e d by Henderson and colleagues (29,30).
T h e i r p r o c e d u r e i s e n t i r e l y d i f f e r e n t from t h e one
used h e r e , r e l y i n g m o s t l y on an a r t i f i c i a l k i d n e y w i t h an e x t r e m e l y h i g h u l t r a f i l t r a t i o n r a t e of t h e o r d e r of 60-80 ml/min and a m o l e c u l a r s i z e f i l t e r up t o 50,000 d a l t o n s , s o t h a t s m a l l and l a r g e s i z e uraemic t o x i n s a r e convected o u t of t h e blood w i t h t h e u l t r a f i l t r a t e . The e x p e r i e n c e g a i n e d i n t h e s e s t u d i e s c o n f i r m s t h a t t h e main b e n e f i t d e r i v e d from U.F.
i s f a c i l i t a t i o n of f l u i d removal.
The des-
c r i b e d r e s u l t s have h e l p e d t o demolish t h e t r a d i t i o n a l view t h a t u l t r a f i l t r a t i o n induced hypovolaemia i s t h e s o l e c a u s e of t h e h y p o t e n s i v e e p i s o d e s t h a t occur d u r i n g c o n v e n t i o n a l h a e m o d i a l y s i s , b u t a s y e t we do n o t know t h e i r t r i g g e r i n g mechanism, o t h e r t h a n a d i s t u r b a n c e i n autonomic vasomotor c o n t r o l may p l a y an i m p o r t a n t r o l e .
S e q u e n t i a l U.F.-H.D.
has l i t t l e
t o o f f e r i n t h e management of t h e uncomplicated d i a l y s i s p a t i e n t b u t may be of some u s e i n d i a b e t i c p a t i e n t s .
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