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Hemodialysis in children
The Journal of Pediatrics VOL. 51
AUGUST, 1957
NO. 2
HEMODIALYSIS IN CHILDREN I~EPORT
OF
FIVE
CASES
FRANK II. CARTER,JR., M.D., ~ SHIGETO AOYA~A, M.D., ROBERT D . ~V[ERCEIr M.D., A~D WILLE1Vi J . K O L F F , M.D. CLEVELAND,
ITH
the development of safer and techniques for hemodialysis, there has been a growing interest in the use of the artificial kidney as an adjunct in the management of uremia. Several types of artificial kidneys now are in use1-4; however, only a few reports have mentioned their use for the treatment of renal failure in children. Mateer and co-workers ~ described hemodialysis used in five children, and Merrill and associates ~ mentioned the use of the artificial kidney for a 31/2-year-old child. This paper presents the findings in five children having renal failure treated with the artificial kidney and outlines other methods which have been helpful in management of that condition.
W materials
PRINCIPLE
AND
TECHNIQUE
OF
I-IEMODIALYSIS
In an artificial kidney, blood is circulated outside the body along a sysF r o m the Division of R e s e a r c h and the D e p a r t r n e n t of P e d i a t r i c s , The C l e v e l a n d Clinic Fo undation, a n d The F r a n k E. B u n t s Educational Institute. This w o r k w a s su pported b y a g r a n t from the Life Insurance
NIedical
Research
to Doctor I4olff. *Present address : San Diego General Hospital, San Diego, Calif.
Fund
County
0H[0
tern of membranes. Through the membranes dialysis takes place, which means that small molecules go through the membranes while large molecules are retained. This has a dual effect: first, retention products, such as urea, creatinine, uric and metabolic acids, sulfates, and phosphates, are removed from the blood and, second, plasma electrolytes are adjusted through equilibration with the rinsing fluid.
Types of Artificial Kidneys Used.The rotating type of artificial kidney 1 was used for only one patient (Case 1). The disposable coil kidney (Fig. 1) 4~' was utilized for the other four patients. The disposable coil kidney has proved to be an effective dialyzer that requires a minimum of time for preparation and is easily operated. Effective hemodialysis in children weighing less than 20 kilograms can be achieved with a single coil of the disposable kidney; in larger children both coils are used. To prime the single-coil system 400 ml. of blood is required, and 750 m]. to prime the twin-coil system. *Made by Travenol, subsidiary of Baxter Laboratories, Morton Grove, Ill.
]25
126
THE
JOURNAL
Rinsing Fluid Bath.--The composition of the rinsing fluid for the artificial kidney is given in Table I. The rinsing fluid is replaced every two hours to maintain a high gradient of retention products between the blood and the rinsing fluid. The amounts of sodium and potassium in the rinsing fluid can be varied. I n severe hyperkalemia, potassium chloride is withheld from the first rinsing flnid to permit a greater reduction in serum levels. However, some potassium (2.5
OF P E D I A T R I C S
the outflow tract by a screw clamp applied to the t r a c t and adjusted until a pressure of 250 ram. H g is obtained within the system. In this way 700 ml. of ultrafiltrate per hour may be removed. Heparin.--I-[eparin, 1 rag. per kilogram of body weight, is administered to the patient at the onset, and 25 rag. is added for each 500 ml. of blood used in priming the apparatus or used for transfusion during dialysis. In addition, during the first four hours of
l~ig. 1 . - - T h e d i s p o s a b l e coil o f t h e a r t i f i c i a l k i d n e y a n d i t s c o n t a i n e r a r e s h o w n in r i n s i n g fluid t a n k d u r i n g h e m o d i a l y s i s . T h e p a t i e n t ' s b l o o d e n t e r s t h e coil t h r o u g h t h e t u b e s l e a d i n g to t h e i n n e r p a r t a n d l e a v e s t h r o u g h t h e t w o t u b e s a t t h e p e r i p h e r y o f t h e T h e rinsing" fluid c i r c u l a t e s u p t h r o u g h a n d f l o w s o v e r t h e t o p of t h e coil a n d b a c k i n t o tank.
meq. per liter) is added to the next baths to prevent depletion of the serum potassium to dangerously low levels. Rate of Ultrafiltration.--With the disposable coil kidney, using two loops, the rate of ultrafiltration is 200 to 300 ml. per hour. When there is edema, it may be desirable to augment the rate of ultrafiltration. Resistance is offered to the flow of blood through
the two coil. the
dialysis, 5 to 10 rag. of heparin per hour is given. Clotting times are determined in Lee-White tubes; the first sign of clotting in the tubes is taken as the end point. The clotting time is maintained between 18 and 25 minutes. Cannuliza~ion.--The most satisfactory source of blood for hemodia]ysis in children has been the inferior vena cava. A small incision is made over
CARTER E T AL. :
HEiVfODIALYSIS I N
the saphenous vein near its termination (fossa ovalis). The vein is exposed and ligated, and a large-caliber polyvinyl eannula is introduced and passed through the femoral vein into the vena eava. This cannula remains indwelling throughout the uremic phase and is used for subsequent hemodialyses, intravenous infusions, and for the collection of blood samples for laboratory determinations. During hemodialysis, blood is returned through a similar eannula in a vein of the arm. With this technique, blood-flow rates usually range from 200 to 400 ml. per minute. 1 F, I . r]:ABL.
CO1VIPON-ENT
127
CHILDREN
status, repeatedly checks the cut-down sites to evaluate the extent of blood loss, if any, and continuously observes the extracorporeal system to ascertain the status of blood flow and of temperature, and whether there are blood leaks. CASE REPORTS
CASE 1.~-A 13-year-old boy was successfully operated upon for aortic stenosis by finger valvulotomy. During and after the operation he received 1,500 ml. of type B blood. H e was later found to have type O, with very weak anti-B agg]utinin titer. H e developed shock and jaundice, and the urine became dark.
T H E COMPOSITION OF THE RIN,SING I~LUID
AMOUNT (GiV[./]00 L.) "
Na +
K+
(]~EQ./L.) Ca ++ ~g++
Sodium chloride* 570 = 97 Sodium bicarbonate 300 = 36 5 Potassium ehloridef 40 -5 Calcium chloride 28 M a g n e s i u m chloride~ 15 -Total 133 I n v e r t s u g a r ( T r a v e r t ) 0.2 p e r c e n t . L a c t i c a c i d t o a d j u s t p H to 7.4. D u r i n g d i a l y s i s 10 p e r c e n t C Q i n O2 b u b b l e d t h r o u g h m a i n t a i n s
C]-
HC03-
97
i
3 l:t0
36
the pit.
* W h e n h i g h s e r u m s o d i u m l e v e l s a r e p r e s e n t , 600 Gin. /'q'aC1 (138 m e q . of N a *) is u s e d in t h e f i r s t b a t h , to p r e v e n t a r a p i d s h i f t in s e r u m s o d i u m c o n c e n t r a t i o n . t T w e n t y o r 30 Gin. K C I (2.5 to 3.7 m e q . of K +) m a y be used, d e p e n d i n g u p o n i n i t i a l s e r u m potassium levels. $ W h e n MgCI~.6H~O is u s e d , 30 Gin. is r e q u i r e d t o p r o v i d e 3 m e q . p e r l i t e r of M g ++ in t h e r i n s i n g fluid.
Management of the Patient.--During dialysis management is directed toward allaying apprehension and pain and providing general comfort. A 2year-old child who required sedation at the beginning of hemodia]ysis was given thiopental sodium rectally. Older children usually tolerated hemodialysis well with little o r no sedation. Throughout dialysis, a nurse reports on and records blood pressure, pulse, and respiratory rate. The physician examines the heart and lungs frequently for changes in cardiac or respiratory
The urine cleared in a few days. He did not develop anuria although the u r i n a r y volume (400 to 900 ml.) was inadequate (Fig. 2). Blood urea rose to 240 rag. per 100 rot., serum potassium to 5.7 meq. per liter, and COzcombining power was 10 meq. per liter. On the eighth day, on the basis of progressive acidosis, uremia, and clinical deterioration, he was treated with the rotating type of artificial kidney 1 for four and one-half hours. One pint of low-titer type O blood was used to prime the artificial kidney. The run was uneventful and no reactions occurred. The u r i n a r y output on the day of dialysis was 1,400 ml., whereas
128
THE
J O U R N A L OF P E D I A T R I C S
the previous day it had been only 890 ml. The day after dialysis the urinary output was 2,000 ml.; the boy had an uneventful recovery.
put may be confidently awaited without the likelihood that uremic complications will occur. CASE 2.--A previously healthy 5year-old girl developed acute glomerulonephritis with a convulsion, following otitis media. She first improved, as may be seen from Fig. 3; then oliguria and emesis reeurred. Early in the fourth week convulsions also recurred. Blood pressure was 164/100 mm. Hg. Blood urea increased to 279 mg. per 100 ml. On the twenty~sixth day the patient was
Comment.--If the boy's urinary output had continued to increase on the seventh day after the transfusion reaetion, we might have postponed or even not have performed the dialysis. However, the output was slightly less on the sixth day, and the clinical condition was deteriorating. It is by no means implied that this patient would not have lived had he not been treated "~
141
240
5.
4.8
4.1'
21,......~'co ;, ~
%/..__.:~.,."~ 4,ov.rg .............. %
,~8 '.9
,
"410 ~Dialysis 2100
1400Ji 450|.
685 ' J
I
I 3 I
740J I 5 ) Days
after
.89O] Urine, ml. I 7 I
I 1II'9 I
transfusian
540,
I 111
'
700 I
1|31
accident
Fig. 2 . - - C h a r t of c o u r s e ~n 1 3 - y e a r - o l d b o y w h o h a d a o r t i c v a l v u l o t o r n y , t r a n s f u s i o n a c c i d e n t , a n d o l i g u r i a ( n o a n u r i ~ ) t r e a t e d w i t h r o t a t i n g t y p e of a r t i ~ e i a l k i d n e y . C a s e l.
with the artificial kidney, tIowever, his elinieal management was greatly facilitated by the improvement that occurred the day after dialysis. It is impossible to predict the increase in urinary output in a patient with anuria. Even if diuresis increases rapidly, the uremic state will persist for a few more days. We believe that hemodialysis is indicated in order to bring about elinieal improvement, so that further increase in urinary out-
hemodialyzed for seven and one-half hours with the disposable single-coil (]0-meter) kidney. Thirty-nine grams of urea were removed. Blood urea was reduced from 279 to 99 rag. per I00 ml. There was a marked and immediate improvement in sensorium. Nausea and vomiting disappeared. Hypertension came down without medication. Urinary output was decreased on the day of hemodialysis but was mMntained above predia]ysis
CARTER E T AL. :
HE1RODIALYSIS I N
129
CHILDREN
litis. The clinical improvement after one dialysis, as expected, included cessation of vomiting and clearing of sensorium. Blood pressure decreased and convulsions ceased. Whether the eourse would have been altered by earlier hemodialysis is open to speculation. There is nothing to suggest it. C~SE 3.--A boy, aged 2 years, was in good health until Aug. 14, 1956, when he developed a skin rash on the neck and groin, anasarca, and vomiting. Temperature ascended to 104 ~ F.
levels on the following five days (Fig. 3). Thereafter, urinary output progressively decreased to complete anuria. Renal function seemed hopelessly impaired and only supportive therapy was nsed. Increasing uremia, eplstaxis, lethargy, recurring hypel~ension (170/120 mm. }Ig), failing vision, congestive heart failure, pleural effusion, and convulsions led to the patient's death on the thirty-ninth day of her illness. Necropsy findings included
279 2.
! 5.7
16B
9! Normal
/
5.T. e~
\
r
|
- - 4.~L%
,-"
%
"x
Dialysis
400 or,o..
~
13~ OIN 10
i
t
I '-I
I
15
!
I
I Days
I
!
20
I
I
after
--IN I
I
onset
I I Z5 of
I
I
I
t
30
I
I
I
I
1351
oliguria
~ i g . 3 . - - C h a r t of c o u r s e in g - y e a r - o l d g i r l w h o h a d w h a t a p p e a r e d to b e a c u t e g l o m e r u l o nephritis. Icier c o n d i t i o n i m p r o v e d t e m p o r a r i l y a f t e r one t r e a t m e n t w i t h t h e d i s p o s a b l e coil kidney, but renal function was not restored. She p r o v e d to h a v e c h r o n i c g l o m e r u l o n e p h r i t i s ~nd necrotizing arteriolitis, C a s e 2,
chronic glomerulonephritis with devastating necrotizing renal arteriolitis similar to that seen in malignant hypertension. Comment.--It is not clear why a condition that initially did not seem to differ from acute glomerulonephritis and even appeared to be on the way to recovery suddenly relapsed and beCame involved with necrotizing arterio-
The patient passed small amounts of poI~c-wine-colored urine, and then throughout tile following three days became anuric. There was a history of two small, slow-healing sores on the skin two to three weeks prior to the present illness. On the fifth anurie day he was brought to the Cleveland Clinic Hospital. Initial examination revealed a
130
THE
JOURNAL
OF PEDIATRICS
well-developed, apprehensive, irritable, pale child with minimal generalized and palpebral edema. Blood pressure was 130/80 ram. tIg, pulse rate was 78, and respirations were 30 per minute. Laboratory findings were as follows: serum sodium 125, potassium 6, chloride 102, and C02-eombining power 10.7 meq. per liter. Uric acid was 15.6 and blood urea 322 rag. per 100 ml. ]?Iemoglobin was 10.5 grams
the day after dialysis. Edema seemed less, and much of the central irritability was gone. He was maintained on 600 ml. of 10 per cent invert sugar in water given intravenously and 200 ml. of fluids and erythromyein given orally. U r i n a r y output slowly increased, the diuretic phase beginning on the third postdialysis day. A]bnminuria (trace to 1 plus) and microscopic hematuria persisted until the
I
II
$24
1010 n
_ .,,,'" ~ "
%.
Normal
i meq./L,
20
Dialysis 790
13.t' 230 il
13,1
Urine,
ml.
Days a f t e r onset of anuria Fig.
4.--Chart
of
course
in 2-year-old boy with acute improved after one dialysis.
per 100 ml. and the hematocrit reading 35 per cent. There was no urine available for examination. An electrocardiogram showed hyperkalemic changes. On the day of admission the patient was given rectal thiopental sodium anesthesia and was dialyzed for five hours with a single-coil disposable kidney. Thirty-six grams of urea were removed. Blood urea was reduced from 324 to 93 rag. per 100 ml. (Fig. 4). General improvement was noted on
glomerulonephritis, C a s e 3.
whose
condition
day of discharge. On the seventh postdialysis day he was inadvertently given a large solute load in the form of salted crackers, and generalized edema recurred. Edema was eontrolled by sodium restriction. The remainder of the hospitalization was uneventful. Six months after discharge he was reported to be well. Comment.--The diagnosis in this ease is not certain. The condition
CARTER E T AL. :
probably represented acute glomerulonephritis. In children, acute glomerulonephritis is not in itself an indication for hemodialysis; however, in the combination of rapidly progressing uremia, overhydration, acidosis, hyperkalemia, or clinical deterioration, hemodialysis may provide the time necessary for physiologic recovery. This ease report demonstrates the lack of a true diuretic phase, and the inability of the damaged kidney to adjust to an abnormal solute load. 353
154)
147
Dlolylil
Diolyl}l
I
sure was 130/50 ram. Hg. Ulcers and enerustations were present on the lips, the tongue, and the oral and nasal mucous membranes. Stools were tarry. There was no evidence of overhydration. His fever had subsided, but to make sure that the sepsis was under control he was given 4 million units of sodium penicillin daily during the anurie phase. Sodium penicillin was used instead of potassium penicillin to avoid administration of potassium during anuria. Initial lab-
366
V
6~0
Diolylls 204(
~
~
131
HEMODIALYSIS IN CHILDREN
i
{
t
110
I
1
I
I
Urine, rnl.
i lbi
Days a f t e r
i
onset
I
i
of
120i
}
t
i
I 25 {
{
I
onurio
F i g . 5 . - - C h a r t of c o u r s e in 1 4 - y e a r - o l d b o y w h o h a d f u l m i n a t i n g m e n i n g o c o c c a l sepsis, shock, a n d a c u t e t u b u l a r n e c r o s i s , H e r e c o v e r e d a f t e r t h r e e d i a l y s e s . C a s e 4.
CASE 4.--A boy, aged 14 years, developed fulminating meningococcal sepsis with multiple peteehiae, ecchyraosis, hematuria, and shock. He was treated with intravenous infusions, hydrocortisone, antibiotics, and pressor agents. The blood pressure was restored, but anuria (40 to 75 ml. urinary output per day) developed and persisted, On the fifth anuric day the patient was transierred to the Cleveland Clinic Hospital. On entry the boy was critically ill but conscious. The blood pres-
oratory findings were serum sodium 131, potassium 4.7, chloride 87, and CQ-combining power 18.9 meq. per liter. Urea was 340 rag. per 100 ml. On the sixth day, despite active bleeding from the stomach and from one kidney, the patient was hemodialyzed for four hours with the twin-coil disposable kidney. One hundred eight grams of urea were removed. Blood pressure and pulse rate remained stable throughout the procedure. 0nly 85 rag. of heparin was needed to mainrain the clotting time between 16 and
132
THE
JOURNAL
20 minutes; there were no complications from heparinization and no increase of hemorrhage. The patient improved during and following the dialysis, t i e was able to take fluids by mouth, and to move about in bed. On the eighth anurie day he again became sleepy and appeared toxic. Urea was up to 261 rag. per 100 ml. Jie was redialyzed on the eighth and on the twelfth days (Fig. 5). During short periods of hypertension the boy became irritable and belligerent; after reduction of blood pressure his mental attitude improved. On the thirteenth day diuresis began; u r i n a r y output was 1,050 ml. and improvement was steady until his discharge twenty days later. I-Iydrocortisone was gradually withdrawn. During the anurie phase, fluid management consisted predominantly of 40 per cent invert sugar in water infused through an indwelling plastic eannula inse~ced through the saphenous vein into the inferior vena cava. This eannula functioned for fifteen days, and also was used for all three dialyses.
Comment.--When the sepsis had become controlled with antibioties and the adrenal insuffieieney (if present) with hydroeortisone, the results of shock and toxic damage became evident in the form of acute tubular neerosis and anuria. I n the ease of crush i n j u r y or severe infection, as seen here, early and frequent hemodialyses are mandatory to reverse rapidly progressing uremia, acidosis, and hyperkalemia that otherwise will lead to sudden death. The third hemodialysis was nndertaken at a time when the patient was remarkably improved and the diuretic phase appeared imminent. This procedure reflects our present attitude (see Case 1). When a patient is bleeding we must weigh the risks of heparinization; currently our experience is encouraging. Three or four extra units
OF
PEDIATRICS
of fresh blood is made available for immediate use, and the amount of heparin used is less than usual. The administration of 40 per cent invert sugar into the vena eava through a large indwelling eannula has ensured a high caloric intake. CASE 5 . - - A boy, aged 9 years, developed what appeared to be acute glomerulonephritis following an acute infection of the u p p e r respiratory tract. A few milliliters of urine obtained for analysis showed 1 plus albumin and abundant red blood cells. He became anurie and on the seventh anuric day was admitted to the Cleveland Clinic Hospital. Physical examination on entry revealed a well-developed, lethargic boy with generalized edema. Blood pressure was 130/85 ram. Jig, pulse rate was 90, and respirations were 34 per minute; temperature was 98.6 ~ F. The lung's were clear. An eleetrocardiogram demonstrated early hyperkalemic changes. Initial laboratory findings were hemoglobin 11.7 grams per 100 ml., blood urea 240 rag. per 100 ml., serum sodium 117, potassimn 6.9, and C02-combining power 7 meq. per liter. The patient was given an intravenous infusion of 500 ml. of 10 per cent invert sugar in water that contained 120 meq. of sodium lactate, 4 Gin. of calcium glueonate, and 500 rag. of erythromyein to curb the danger of acute potassium intoxication. The following morning, the eighth anuric day, there were some improvement in respiration and diminution in lethargy, but the child remained critically ill. Ite was dialyzed w i t h the twincoil disposable kidney for four hours (Fig. 6). Sixty-six grams of urea were removed. Blood urea decreased to 84 rag. per 100 ml., serum potassium to 4.2 meq. per liter, and the CQ-combining power increased to 22.3 meq. per liter. At the end of the hemodialysis, the child was moderately alert and demanded something to eat. A three-pound loss in weight occurred,
CARTER
ET
AL. :
133
I N CHILDICEN
IIEMODIALYSIS
tachycardia. He was transfused with 300 ml. of packed red blood cells. The following day the blood pressure rose to 220/120 ram. ttg, and a generalized convulsion began, which could not be controlled by sedative and ganglionblocking drugs. An intravenous infusion of s o d i u m n i t r o p r u s s i d e ~ brought about a rapid return of the blood pressure to 120/70 ram. Hg, and the. immediate cessation of convulsions. The infusion was continued with decreasing concentrations of nitroprusside over the next twelve hours without alteration in the blood pressure.
with a notable reduction in the generalized edema. Transient hypertension (160/90 ram. ]Jig) developed during the hemodialysis but was controlled with small doses of pentolinium bitartrate. The boy remained anuric throughout the next two days but continued to be hungry and appeared clinically improved. On the eleventh anurie day he became drowsy, febrile, and had a rise in blood pressure (170/90 mm. Hg). Edema was more pronounced. Again he was treated with the twincoil disposable kidney, this time for
Convulsion
1B6
Blood urea, rng, " I .
I~3
3,
9
s"
iS l ' ~rl
~
/
- ~
_
Normal
75
-
~o
-
~__
2 5.0
Diolysl$
Diolyl~l$ 2050
13~0
-"
1300
I 90
0
7
Urine,
125 I
10
I
I 1~5
I
I
I
Days
120
L
after
ml.
t
I
onset
L
125
I
t
t
I
I 3 ~lO
I
I
1
I 35 t
of o n u r i a
F i g . 6 . - - C h a r t of c o u r s e in 9 - y e a r - o l d b o y w i t h w h a t a p p e a r e d to b e a c u t e g l o m e r u l o n e p h r i tis. H i s c o n d i t i o n i m p r o v e d a f t e r t w o d i a t y s e s . L a t e r he d e v e l o p e d a c u t e h y p e r t e n s i o n a n d c o n v u l s i o n s . W h e n he w a s d i s c h a r g e d f r o m t h e h o s p i t a l , his c o n d i t i o n h a d i m p r o v e d b u t he h a d s l i g h t h e m a t u r i a . C a s e 5.
five hours. On the twelfth day urinary output began with 125 ml. and on the sixteenth day had increased to 1,560 nil. On the thirteenth day hypertension recurred, and continued throughout the next twelve days. Increasing doses of antipressor drugs were required to maintain the blood pressure at 150/90 ram. Itg. On the twenty-fourth day the hemoglobin was only 5.6 grams per 100 m]. It was believed that this anemia contributed to his dyspnea and
The ehild received no further antipressot medication. He remained normotensive (120/70 ram. Hg) throughout the remainder of his stay in the hospital. Following the convulsion the urine became grossly clear and the urinary output increased up to 2,000 ml. per day. The child continued to improve, and went home with slight residual hematuria. boy, upon initial examination, was in a fairly severe
Comment.--This
134
THE
JOURNAL
uremic state. To reverse the acidosis and to prevent the further development of hyperkalemia and its effects, he was given intravenously a combination of invert sugar, sodium lactate, and calcium gluconate. As anticipated, there was transient improvement, a respite that allowed preparation of the artificial kidney. A refractory convulsive state secondary to renal failure sometimes can be controlled by hemodialysis. In this instance, however, the convulsions were secondary to hypertension and were controlled only when the blood pressure was reduced. The intravenous use of sodium nitroprusside was lifesaving. Although the patient was discharged from the hospital in a normotensive state, a guarded prognosis must be made as to the ultimate outcome. DISCUSSION
General management of the uremic child is directed toward (1) establishmerit of fluid balance, (2) vigilance over the status of electrolytes, (3) maintenance of maximum caloric intake in the hope of reducing undue breakdown of protein and formation of retention products, and (4) prevention of infection. Dialysis, finally, is the most powerful means of overcoming and correcting the shortcomings of the conservative attempts.
1. Fluid Balance.--During the anuric phase 20 to 30 ml. fluid intake per kilogram of body weight per day was sufficient to maintain fluid balance in our five cases. In normal children without fever the rate of insensible loss of water is about 500 ml. per square meter of body surface per day, but in anuric or edematous children we believe that it is less. Losses by sweating, vomiting, diarrhea, and by that small amount of urine that is produced should be considered. The best general guide is the daily weight of
OF P E D I A T R I C S
the patient. So long as a child is able to take something by mouth, intravenous administration of fluid should be avoided. During the early diuretic phase, the fluid lost must be replaced, but after the peak of diuresis has been reached careful curtailment of fluid intake should be undertaken, to prevent a prolongation of diuresis simply due to water loading.
Rarely Need Transfusion: Progressire anemia consistently follows the course of uremia, tlematoerit levels usually become stable between 25 and 30 ram. Generally the anemia is well tolerated, and attempts to restore hematocrit levels to normal are quite useless and even dangerous. Following transfusion there is a temporary rise in blood hemoglobin and then a decrease to pretransfusion levels. The addition of blood to an already expanded intravaseular compartment invites hypertension, congestive cardiac failure with pulmonary edema, and convulsions. When transfusion is unavoidable, multiple small infusions or, rather, exsanguinotransfusions (replacements) are better than one large transfusion. 2. Vigilance Over Status of Electrolytes.--Correction of electrolytes to a supposedly normal level is not our aim and may even be dangerous. We change electrolytes as little as possible.
During the anuric phase no sodium is given in any form unless it has been demonstrably lost in large quantities or a low alkali reserve (lower than 15 meq. per liter) induces us to give sodimn lactate (or sodium bicarbonate), 10 to 40 meq. per day. It rarely is necessary to give sodium chloride, since retained metabolic acids, such as SOs:,
CARTER
ET
AL. :
HEMODIALYSIS
will replace C1-. Potassium salts rarely. need be given.
During the diuretic phase sodium chloride sometimes must be provided. Two and one-half grams per liter of urinary output is only a rough guide, as it may be too much. In this phase potassium salts may have to be provided. (One glass of orange juice contains 20 meq. of potassium.) }Iypoealcemia, although often present, rarely produces the symptoms of twitching and convulsions erroneously attributed to it. 3. Caloric Intake.--By providing maximal daily calorie intake we t r y to encourage anabolie processes, diminish wasting of body protein, slow down the formation of retention products, and retard derangement of electrolytes. Calorie supplements in the form of fat emulsions, hard candy, and ginger ale help to boost the daily calorie intake. When anorexia precludes adequate oral intake and intestinal peristalsis still is present, occasionally a fluid homogenate delivered as a constant drip through a small plgstie gastric tube will maintain nutrition. The administration of 40 per cent invert sugar provides a large calorie intake in a small volume and has produced no demonstrable local or hemolytic effects when introduced into the vena cava. 4. Prevention of Infections.--The uremic child is extremely susceptible to infection. In addition to the danger produced by infection itself, the septic state increases catabolism which, in turn, increases the uremia. Adequate nursing care with particular emphasis on general bed care and oral hygiene is essential. Frequent physi-
IN
CHILDREN
135
cal examination for the early detection of septic loci must be made. Surgical care of cut-down sites minimizes complieation from this source. In addition, it has been our practice to give erythromyein prophylactically throughout the period of danger.
Indications for DiaIysis.--In severe uremia, a state is reached where conservative procedures become inadequate. With progression of the uremic process there begins a vicious cycle. Physical degeneration adds pathologic changes to an already delicate therapeutic problem. Vomiting, for example, makes calorie intake difficult and disturbs electrolyte balance. Coma prevents expectoration and promotes pulmonary infection. Insufficient calorie intake, electrolyte disturbance, and infection all enhance the uremia. We believe that dialysis should be undertaken before the patient enters the cycle. Indication for dialysis is both chemical and clinical. Chemical indications are a CO2-eombining power of less than 12 meq. per liter, a blood urea level of more than 200 mg. per 100 ml., and chemical and electrocardiographic evidence of hyperkalemia (usually a serum potassium level of more than 6.5 meq. per liter). Two clinical patterns of behavior should be a forewarning to the approach of more serious uremic complications. In the first there are lethargy, apathy, and somnolence. In the second there are irritability, restlessness, and psychosis. Either of these patterns frequently is associated with anorexia, nausea and vomiting, and alteration in cardiovascular status, especially with wide fluctuations in blood pressure.
136
THE JOURNAL OF PEDIATRICS
Early and frequent hemodialyses promote an improvement in sensorium, a return to the feeling of wellbeing, and a return of appetite. Catabolic retention products are reduced, a relative restoration of electrolyte equilibrium is obtained, and the total amount of body water is lessened. In all five patients here discussed clinical improvement after hemodialysis was evident and clinical management became easier. I t must be stated that each hemodialysis is undertaken at a calculated risk, but the risk is small. The fear of hemorrhage has hampered the application of hemodialysis, but, in general, uremic bleeding, such as eechymoses and bleeding from the gums or from the gastrointestinal tract, lessens after hemodialysis. Bleeding from wounds or ulcers must be evaluated for the individual patient. In the patient with meningococeemia there was a slight, transient increase in gastrointestinal and in genitourinary bleeding, but it was not serious. On occasion, hemodialysis has been maintained on as little heparin as was required for the blood used to prime the artificial kidney. Sudden changes in blood pressure might constitute a serious risk: an increase in blood pressure could lead to convulsions; a decrease, to sudden death. No alarming changes happened in the eight dialyses here discussed; but if they had occurred they would have been amenable to treatment. In the hands of a well-
trained team, hemodialysis is not only helpful in producing a smoother coarse in these children, but it may also be lifesaving. SUb{MARY
Eight hemodialyses were performed in five patients whose ages ranged from 2 to 14 years. Four patients surrived; one patient improved temporarily and then died. The etiologic factors that lead to renal failure were transfusion accident in one patient, shock secondary to meningocoeeal septicemia in one, chronic glomeru]onephritis with necrotizing arteriolitis in one (the patient who died), and what appeared to be acute glomerulonephritis in two patients. REFERENCES 1. Kolff, W. J.: and Berk, I-I. T. J . : Artificial K i d n e y : Dialyser With Great Area, Aeta reed. seandinav. 117: 121, 1944. 2. Alwall, N.: On ArtificiM Kidney. XI. Some Supplementary Constructional DetMls of DiMyser Intended for Rabbit and }Iomo, Acta rned. scandinav. (supp. 229) 133: 20, 1949. 3. Skeggs, L. T., Jr., Leonards, J. R., and }Ieisler, C. R.: Artificial Kidney. II. Construction and Operation of Improved Continuous Dialyzer, Prec. See. Exper. Biol. & Med. 72: 539, 1949. 4. Kolff, W. J., and Watsehlnger, :B.: ]~urther Development of Coil Kidney, J. Lab. & Clln. Med. 47: 969, 1956. 5. Mateer, F. M., Greenman, L., and Dan~ owski, T. S.: HemodiMysis of the Uremic Child, A. M. A. Am. J. Dis. Child. 89: 645, 1955. 6. Merrill, J. P., Smith, S., Callahan, E. J , I I I , and Thorn, G. W.: Vse of an Artificial Kidney; Clinical Experienee~ J. Clin. Invest. 29: 425, 1950. 7. :Page, I. H., Corcoran, A. C, Dustan, H. P., and Koppanyi, T.: Cardiovascular Actions of Sodium Nitroprusside in Animals and ~Iypertensive Patients, Circulation 11 : 188, 1955.
AUGUST, 1957
NO. 2
HEMODIALYSIS IN CHILDREN I~EPORT
OF
FIVE
CASES
FRANK II. CARTER,JR., M.D., ~ SHIGETO AOYA~A, M.D., ROBERT D . ~V[ERCEIr M.D., A~D WILLE1Vi J . K O L F F , M.D. CLEVELAND,
ITH
the development of safer and techniques for hemodialysis, there has been a growing interest in the use of the artificial kidney as an adjunct in the management of uremia. Several types of artificial kidneys now are in use1-4; however, only a few reports have mentioned their use for the treatment of renal failure in children. Mateer and co-workers ~ described hemodialysis used in five children, and Merrill and associates ~ mentioned the use of the artificial kidney for a 31/2-year-old child. This paper presents the findings in five children having renal failure treated with the artificial kidney and outlines other methods which have been helpful in management of that condition.
W materials
PRINCIPLE
AND
TECHNIQUE
OF
I-IEMODIALYSIS
In an artificial kidney, blood is circulated outside the body along a sysF r o m the Division of R e s e a r c h and the D e p a r t r n e n t of P e d i a t r i c s , The C l e v e l a n d Clinic Fo undation, a n d The F r a n k E. B u n t s Educational Institute. This w o r k w a s su pported b y a g r a n t from the Life Insurance
NIedical
Research
to Doctor I4olff. *Present address : San Diego General Hospital, San Diego, Calif.
Fund
County
0H[0
tern of membranes. Through the membranes dialysis takes place, which means that small molecules go through the membranes while large molecules are retained. This has a dual effect: first, retention products, such as urea, creatinine, uric and metabolic acids, sulfates, and phosphates, are removed from the blood and, second, plasma electrolytes are adjusted through equilibration with the rinsing fluid.
Types of Artificial Kidneys Used.The rotating type of artificial kidney 1 was used for only one patient (Case 1). The disposable coil kidney (Fig. 1) 4~' was utilized for the other four patients. The disposable coil kidney has proved to be an effective dialyzer that requires a minimum of time for preparation and is easily operated. Effective hemodialysis in children weighing less than 20 kilograms can be achieved with a single coil of the disposable kidney; in larger children both coils are used. To prime the single-coil system 400 ml. of blood is required, and 750 m]. to prime the twin-coil system. *Made by Travenol, subsidiary of Baxter Laboratories, Morton Grove, Ill.
]25
126
THE
JOURNAL
Rinsing Fluid Bath.--The composition of the rinsing fluid for the artificial kidney is given in Table I. The rinsing fluid is replaced every two hours to maintain a high gradient of retention products between the blood and the rinsing fluid. The amounts of sodium and potassium in the rinsing fluid can be varied. I n severe hyperkalemia, potassium chloride is withheld from the first rinsing flnid to permit a greater reduction in serum levels. However, some potassium (2.5
OF P E D I A T R I C S
the outflow tract by a screw clamp applied to the t r a c t and adjusted until a pressure of 250 ram. H g is obtained within the system. In this way 700 ml. of ultrafiltrate per hour may be removed. Heparin.--I-[eparin, 1 rag. per kilogram of body weight, is administered to the patient at the onset, and 25 rag. is added for each 500 ml. of blood used in priming the apparatus or used for transfusion during dialysis. In addition, during the first four hours of
l~ig. 1 . - - T h e d i s p o s a b l e coil o f t h e a r t i f i c i a l k i d n e y a n d i t s c o n t a i n e r a r e s h o w n in r i n s i n g fluid t a n k d u r i n g h e m o d i a l y s i s . T h e p a t i e n t ' s b l o o d e n t e r s t h e coil t h r o u g h t h e t u b e s l e a d i n g to t h e i n n e r p a r t a n d l e a v e s t h r o u g h t h e t w o t u b e s a t t h e p e r i p h e r y o f t h e T h e rinsing" fluid c i r c u l a t e s u p t h r o u g h a n d f l o w s o v e r t h e t o p of t h e coil a n d b a c k i n t o tank.
meq. per liter) is added to the next baths to prevent depletion of the serum potassium to dangerously low levels. Rate of Ultrafiltration.--With the disposable coil kidney, using two loops, the rate of ultrafiltration is 200 to 300 ml. per hour. When there is edema, it may be desirable to augment the rate of ultrafiltration. Resistance is offered to the flow of blood through
the two coil. the
dialysis, 5 to 10 rag. of heparin per hour is given. Clotting times are determined in Lee-White tubes; the first sign of clotting in the tubes is taken as the end point. The clotting time is maintained between 18 and 25 minutes. Cannuliza~ion.--The most satisfactory source of blood for hemodia]ysis in children has been the inferior vena cava. A small incision is made over
CARTER E T AL. :
HEiVfODIALYSIS I N
the saphenous vein near its termination (fossa ovalis). The vein is exposed and ligated, and a large-caliber polyvinyl eannula is introduced and passed through the femoral vein into the vena eava. This cannula remains indwelling throughout the uremic phase and is used for subsequent hemodialyses, intravenous infusions, and for the collection of blood samples for laboratory determinations. During hemodialysis, blood is returned through a similar eannula in a vein of the arm. With this technique, blood-flow rates usually range from 200 to 400 ml. per minute. 1 F, I . r]:ABL.
CO1VIPON-ENT
127
CHILDREN
status, repeatedly checks the cut-down sites to evaluate the extent of blood loss, if any, and continuously observes the extracorporeal system to ascertain the status of blood flow and of temperature, and whether there are blood leaks. CASE REPORTS
CASE 1.~-A 13-year-old boy was successfully operated upon for aortic stenosis by finger valvulotomy. During and after the operation he received 1,500 ml. of type B blood. H e was later found to have type O, with very weak anti-B agg]utinin titer. H e developed shock and jaundice, and the urine became dark.
T H E COMPOSITION OF THE RIN,SING I~LUID
AMOUNT (GiV[./]00 L.) "
Na +
K+
(]~EQ./L.) Ca ++ ~g++
Sodium chloride* 570 = 97 Sodium bicarbonate 300 = 36 5 Potassium ehloridef 40 -5 Calcium chloride 28 M a g n e s i u m chloride~ 15 -Total 133 I n v e r t s u g a r ( T r a v e r t ) 0.2 p e r c e n t . L a c t i c a c i d t o a d j u s t p H to 7.4. D u r i n g d i a l y s i s 10 p e r c e n t C Q i n O2 b u b b l e d t h r o u g h m a i n t a i n s
C]-
HC03-
97
i
3 l:t0
36
the pit.
* W h e n h i g h s e r u m s o d i u m l e v e l s a r e p r e s e n t , 600 Gin. /'q'aC1 (138 m e q . of N a *) is u s e d in t h e f i r s t b a t h , to p r e v e n t a r a p i d s h i f t in s e r u m s o d i u m c o n c e n t r a t i o n . t T w e n t y o r 30 Gin. K C I (2.5 to 3.7 m e q . of K +) m a y be used, d e p e n d i n g u p o n i n i t i a l s e r u m potassium levels. $ W h e n MgCI~.6H~O is u s e d , 30 Gin. is r e q u i r e d t o p r o v i d e 3 m e q . p e r l i t e r of M g ++ in t h e r i n s i n g fluid.
Management of the Patient.--During dialysis management is directed toward allaying apprehension and pain and providing general comfort. A 2year-old child who required sedation at the beginning of hemodia]ysis was given thiopental sodium rectally. Older children usually tolerated hemodialysis well with little o r no sedation. Throughout dialysis, a nurse reports on and records blood pressure, pulse, and respiratory rate. The physician examines the heart and lungs frequently for changes in cardiac or respiratory
The urine cleared in a few days. He did not develop anuria although the u r i n a r y volume (400 to 900 ml.) was inadequate (Fig. 2). Blood urea rose to 240 rag. per 100 rot., serum potassium to 5.7 meq. per liter, and COzcombining power was 10 meq. per liter. On the eighth day, on the basis of progressive acidosis, uremia, and clinical deterioration, he was treated with the rotating type of artificial kidney 1 for four and one-half hours. One pint of low-titer type O blood was used to prime the artificial kidney. The run was uneventful and no reactions occurred. The u r i n a r y output on the day of dialysis was 1,400 ml., whereas
128
THE
J O U R N A L OF P E D I A T R I C S
the previous day it had been only 890 ml. The day after dialysis the urinary output was 2,000 ml.; the boy had an uneventful recovery.
put may be confidently awaited without the likelihood that uremic complications will occur. CASE 2.--A previously healthy 5year-old girl developed acute glomerulonephritis with a convulsion, following otitis media. She first improved, as may be seen from Fig. 3; then oliguria and emesis reeurred. Early in the fourth week convulsions also recurred. Blood pressure was 164/100 mm. Hg. Blood urea increased to 279 mg. per 100 ml. On the twenty~sixth day the patient was
Comment.--If the boy's urinary output had continued to increase on the seventh day after the transfusion reaetion, we might have postponed or even not have performed the dialysis. However, the output was slightly less on the sixth day, and the clinical condition was deteriorating. It is by no means implied that this patient would not have lived had he not been treated "~
141
240
5.
4.8
4.1'
21,......~'co ;, ~
%/..__.:~.,."~ 4,ov.rg .............. %
,~8 '.9
,
"410 ~Dialysis 2100
1400Ji 450|.
685 ' J
I
I 3 I
740J I 5 ) Days
after
.89O] Urine, ml. I 7 I
I 1II'9 I
transfusian
540,
I 111
'
700 I
1|31
accident
Fig. 2 . - - C h a r t of c o u r s e ~n 1 3 - y e a r - o l d b o y w h o h a d a o r t i c v a l v u l o t o r n y , t r a n s f u s i o n a c c i d e n t , a n d o l i g u r i a ( n o a n u r i ~ ) t r e a t e d w i t h r o t a t i n g t y p e of a r t i ~ e i a l k i d n e y . C a s e l.
with the artificial kidney, tIowever, his elinieal management was greatly facilitated by the improvement that occurred the day after dialysis. It is impossible to predict the increase in urinary output in a patient with anuria. Even if diuresis increases rapidly, the uremic state will persist for a few more days. We believe that hemodialysis is indicated in order to bring about elinieal improvement, so that further increase in urinary out-
hemodialyzed for seven and one-half hours with the disposable single-coil (]0-meter) kidney. Thirty-nine grams of urea were removed. Blood urea was reduced from 279 to 99 rag. per I00 ml. There was a marked and immediate improvement in sensorium. Nausea and vomiting disappeared. Hypertension came down without medication. Urinary output was decreased on the day of hemodialysis but was mMntained above predia]ysis
CARTER E T AL. :
HE1RODIALYSIS I N
129
CHILDREN
litis. The clinical improvement after one dialysis, as expected, included cessation of vomiting and clearing of sensorium. Blood pressure decreased and convulsions ceased. Whether the eourse would have been altered by earlier hemodialysis is open to speculation. There is nothing to suggest it. C~SE 3.--A boy, aged 2 years, was in good health until Aug. 14, 1956, when he developed a skin rash on the neck and groin, anasarca, and vomiting. Temperature ascended to 104 ~ F.
levels on the following five days (Fig. 3). Thereafter, urinary output progressively decreased to complete anuria. Renal function seemed hopelessly impaired and only supportive therapy was nsed. Increasing uremia, eplstaxis, lethargy, recurring hypel~ension (170/120 mm. }Ig), failing vision, congestive heart failure, pleural effusion, and convulsions led to the patient's death on the thirty-ninth day of her illness. Necropsy findings included
279 2.
! 5.7
16B
9! Normal
/
5.T. e~
\
r
|
- - 4.~L%
,-"
%
"x
Dialysis
400 or,o..
~
13~ OIN 10
i
t
I '-I
I
15
!
I
I Days
I
!
20
I
I
after
--IN I
I
onset
I I Z5 of
I
I
I
t
30
I
I
I
I
1351
oliguria
~ i g . 3 . - - C h a r t of c o u r s e in g - y e a r - o l d g i r l w h o h a d w h a t a p p e a r e d to b e a c u t e g l o m e r u l o nephritis. Icier c o n d i t i o n i m p r o v e d t e m p o r a r i l y a f t e r one t r e a t m e n t w i t h t h e d i s p o s a b l e coil kidney, but renal function was not restored. She p r o v e d to h a v e c h r o n i c g l o m e r u l o n e p h r i t i s ~nd necrotizing arteriolitis, C a s e 2,
chronic glomerulonephritis with devastating necrotizing renal arteriolitis similar to that seen in malignant hypertension. Comment.--It is not clear why a condition that initially did not seem to differ from acute glomerulonephritis and even appeared to be on the way to recovery suddenly relapsed and beCame involved with necrotizing arterio-
The patient passed small amounts of poI~c-wine-colored urine, and then throughout tile following three days became anuric. There was a history of two small, slow-healing sores on the skin two to three weeks prior to the present illness. On the fifth anurie day he was brought to the Cleveland Clinic Hospital. Initial examination revealed a
130
THE
JOURNAL
OF PEDIATRICS
well-developed, apprehensive, irritable, pale child with minimal generalized and palpebral edema. Blood pressure was 130/80 ram. tIg, pulse rate was 78, and respirations were 30 per minute. Laboratory findings were as follows: serum sodium 125, potassium 6, chloride 102, and C02-eombining power 10.7 meq. per liter. Uric acid was 15.6 and blood urea 322 rag. per 100 ml. ]?Iemoglobin was 10.5 grams
the day after dialysis. Edema seemed less, and much of the central irritability was gone. He was maintained on 600 ml. of 10 per cent invert sugar in water given intravenously and 200 ml. of fluids and erythromyein given orally. U r i n a r y output slowly increased, the diuretic phase beginning on the third postdialysis day. A]bnminuria (trace to 1 plus) and microscopic hematuria persisted until the
I
II
$24
1010 n
_ .,,,'" ~ "
%.
Normal
i meq./L,
20
Dialysis 790
13.t' 230 il
13,1
Urine,
ml.
Days a f t e r onset of anuria Fig.
4.--Chart
of
course
in 2-year-old boy with acute improved after one dialysis.
per 100 ml. and the hematocrit reading 35 per cent. There was no urine available for examination. An electrocardiogram showed hyperkalemic changes. On the day of admission the patient was given rectal thiopental sodium anesthesia and was dialyzed for five hours with a single-coil disposable kidney. Thirty-six grams of urea were removed. Blood urea was reduced from 324 to 93 rag. per 100 ml. (Fig. 4). General improvement was noted on
glomerulonephritis, C a s e 3.
whose
condition
day of discharge. On the seventh postdialysis day he was inadvertently given a large solute load in the form of salted crackers, and generalized edema recurred. Edema was eontrolled by sodium restriction. The remainder of the hospitalization was uneventful. Six months after discharge he was reported to be well. Comment.--The diagnosis in this ease is not certain. The condition
CARTER E T AL. :
probably represented acute glomerulonephritis. In children, acute glomerulonephritis is not in itself an indication for hemodialysis; however, in the combination of rapidly progressing uremia, overhydration, acidosis, hyperkalemia, or clinical deterioration, hemodialysis may provide the time necessary for physiologic recovery. This ease report demonstrates the lack of a true diuretic phase, and the inability of the damaged kidney to adjust to an abnormal solute load. 353
154)
147
Dlolylil
Diolyl}l
I
sure was 130/50 ram. Hg. Ulcers and enerustations were present on the lips, the tongue, and the oral and nasal mucous membranes. Stools were tarry. There was no evidence of overhydration. His fever had subsided, but to make sure that the sepsis was under control he was given 4 million units of sodium penicillin daily during the anurie phase. Sodium penicillin was used instead of potassium penicillin to avoid administration of potassium during anuria. Initial lab-
366
V
6~0
Diolylls 204(
~
~
131
HEMODIALYSIS IN CHILDREN
i
{
t
110
I
1
I
I
Urine, rnl.
i lbi
Days a f t e r
i
onset
I
i
of
120i
}
t
i
I 25 {
{
I
onurio
F i g . 5 . - - C h a r t of c o u r s e in 1 4 - y e a r - o l d b o y w h o h a d f u l m i n a t i n g m e n i n g o c o c c a l sepsis, shock, a n d a c u t e t u b u l a r n e c r o s i s , H e r e c o v e r e d a f t e r t h r e e d i a l y s e s . C a s e 4.
CASE 4.--A boy, aged 14 years, developed fulminating meningococcal sepsis with multiple peteehiae, ecchyraosis, hematuria, and shock. He was treated with intravenous infusions, hydrocortisone, antibiotics, and pressor agents. The blood pressure was restored, but anuria (40 to 75 ml. urinary output per day) developed and persisted, On the fifth anuric day the patient was transierred to the Cleveland Clinic Hospital. On entry the boy was critically ill but conscious. The blood pres-
oratory findings were serum sodium 131, potassium 4.7, chloride 87, and CQ-combining power 18.9 meq. per liter. Urea was 340 rag. per 100 ml. On the sixth day, despite active bleeding from the stomach and from one kidney, the patient was hemodialyzed for four hours with the twin-coil disposable kidney. One hundred eight grams of urea were removed. Blood pressure and pulse rate remained stable throughout the procedure. 0nly 85 rag. of heparin was needed to mainrain the clotting time between 16 and
132
THE
JOURNAL
20 minutes; there were no complications from heparinization and no increase of hemorrhage. The patient improved during and following the dialysis, t i e was able to take fluids by mouth, and to move about in bed. On the eighth anurie day he again became sleepy and appeared toxic. Urea was up to 261 rag. per 100 ml. Jie was redialyzed on the eighth and on the twelfth days (Fig. 5). During short periods of hypertension the boy became irritable and belligerent; after reduction of blood pressure his mental attitude improved. On the thirteenth day diuresis began; u r i n a r y output was 1,050 ml. and improvement was steady until his discharge twenty days later. I-Iydrocortisone was gradually withdrawn. During the anurie phase, fluid management consisted predominantly of 40 per cent invert sugar in water infused through an indwelling plastic eannula inse~ced through the saphenous vein into the inferior vena cava. This eannula functioned for fifteen days, and also was used for all three dialyses.
Comment.--When the sepsis had become controlled with antibioties and the adrenal insuffieieney (if present) with hydroeortisone, the results of shock and toxic damage became evident in the form of acute tubular neerosis and anuria. I n the ease of crush i n j u r y or severe infection, as seen here, early and frequent hemodialyses are mandatory to reverse rapidly progressing uremia, acidosis, and hyperkalemia that otherwise will lead to sudden death. The third hemodialysis was nndertaken at a time when the patient was remarkably improved and the diuretic phase appeared imminent. This procedure reflects our present attitude (see Case 1). When a patient is bleeding we must weigh the risks of heparinization; currently our experience is encouraging. Three or four extra units
OF
PEDIATRICS
of fresh blood is made available for immediate use, and the amount of heparin used is less than usual. The administration of 40 per cent invert sugar into the vena eava through a large indwelling eannula has ensured a high caloric intake. CASE 5 . - - A boy, aged 9 years, developed what appeared to be acute glomerulonephritis following an acute infection of the u p p e r respiratory tract. A few milliliters of urine obtained for analysis showed 1 plus albumin and abundant red blood cells. He became anurie and on the seventh anuric day was admitted to the Cleveland Clinic Hospital. Physical examination on entry revealed a well-developed, lethargic boy with generalized edema. Blood pressure was 130/85 ram. Jig, pulse rate was 90, and respirations were 34 per minute; temperature was 98.6 ~ F. The lung's were clear. An eleetrocardiogram demonstrated early hyperkalemic changes. Initial laboratory findings were hemoglobin 11.7 grams per 100 ml., blood urea 240 rag. per 100 ml., serum sodium 117, potassimn 6.9, and C02-combining power 7 meq. per liter. The patient was given an intravenous infusion of 500 ml. of 10 per cent invert sugar in water that contained 120 meq. of sodium lactate, 4 Gin. of calcium glueonate, and 500 rag. of erythromyein to curb the danger of acute potassium intoxication. The following morning, the eighth anuric day, there were some improvement in respiration and diminution in lethargy, but the child remained critically ill. Ite was dialyzed w i t h the twincoil disposable kidney for four hours (Fig. 6). Sixty-six grams of urea were removed. Blood urea decreased to 84 rag. per 100 ml., serum potassium to 4.2 meq. per liter, and the CQ-combining power increased to 22.3 meq. per liter. At the end of the hemodialysis, the child was moderately alert and demanded something to eat. A three-pound loss in weight occurred,
CARTER
ET
AL. :
133
I N CHILDICEN
IIEMODIALYSIS
tachycardia. He was transfused with 300 ml. of packed red blood cells. The following day the blood pressure rose to 220/120 ram. ttg, and a generalized convulsion began, which could not be controlled by sedative and ganglionblocking drugs. An intravenous infusion of s o d i u m n i t r o p r u s s i d e ~ brought about a rapid return of the blood pressure to 120/70 ram. Hg, and the. immediate cessation of convulsions. The infusion was continued with decreasing concentrations of nitroprusside over the next twelve hours without alteration in the blood pressure.
with a notable reduction in the generalized edema. Transient hypertension (160/90 ram. ]Jig) developed during the hemodialysis but was controlled with small doses of pentolinium bitartrate. The boy remained anuric throughout the next two days but continued to be hungry and appeared clinically improved. On the eleventh anurie day he became drowsy, febrile, and had a rise in blood pressure (170/90 mm. Hg). Edema was more pronounced. Again he was treated with the twincoil disposable kidney, this time for
Convulsion
1B6
Blood urea, rng, " I .
I~3
3,
9
s"
iS l ' ~rl
~
/
- ~
_
Normal
75
-
~o
-
~__
2 5.0
Diolysl$
Diolyl~l$ 2050
13~0
-"
1300
I 90
0
7
Urine,
125 I
10
I
I 1~5
I
I
I
Days
120
L
after
ml.
t
I
onset
L
125
I
t
t
I
I 3 ~lO
I
I
1
I 35 t
of o n u r i a
F i g . 6 . - - C h a r t of c o u r s e in 9 - y e a r - o l d b o y w i t h w h a t a p p e a r e d to b e a c u t e g l o m e r u l o n e p h r i tis. H i s c o n d i t i o n i m p r o v e d a f t e r t w o d i a t y s e s . L a t e r he d e v e l o p e d a c u t e h y p e r t e n s i o n a n d c o n v u l s i o n s . W h e n he w a s d i s c h a r g e d f r o m t h e h o s p i t a l , his c o n d i t i o n h a d i m p r o v e d b u t he h a d s l i g h t h e m a t u r i a . C a s e 5.
five hours. On the twelfth day urinary output began with 125 ml. and on the sixteenth day had increased to 1,560 nil. On the thirteenth day hypertension recurred, and continued throughout the next twelve days. Increasing doses of antipressor drugs were required to maintain the blood pressure at 150/90 ram. Itg. On the twenty-fourth day the hemoglobin was only 5.6 grams per 100 m]. It was believed that this anemia contributed to his dyspnea and
The ehild received no further antipressot medication. He remained normotensive (120/70 ram. Hg) throughout the remainder of his stay in the hospital. Following the convulsion the urine became grossly clear and the urinary output increased up to 2,000 ml. per day. The child continued to improve, and went home with slight residual hematuria. boy, upon initial examination, was in a fairly severe
Comment.--This
134
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uremic state. To reverse the acidosis and to prevent the further development of hyperkalemia and its effects, he was given intravenously a combination of invert sugar, sodium lactate, and calcium gluconate. As anticipated, there was transient improvement, a respite that allowed preparation of the artificial kidney. A refractory convulsive state secondary to renal failure sometimes can be controlled by hemodialysis. In this instance, however, the convulsions were secondary to hypertension and were controlled only when the blood pressure was reduced. The intravenous use of sodium nitroprusside was lifesaving. Although the patient was discharged from the hospital in a normotensive state, a guarded prognosis must be made as to the ultimate outcome. DISCUSSION
General management of the uremic child is directed toward (1) establishmerit of fluid balance, (2) vigilance over the status of electrolytes, (3) maintenance of maximum caloric intake in the hope of reducing undue breakdown of protein and formation of retention products, and (4) prevention of infection. Dialysis, finally, is the most powerful means of overcoming and correcting the shortcomings of the conservative attempts.
1. Fluid Balance.--During the anuric phase 20 to 30 ml. fluid intake per kilogram of body weight per day was sufficient to maintain fluid balance in our five cases. In normal children without fever the rate of insensible loss of water is about 500 ml. per square meter of body surface per day, but in anuric or edematous children we believe that it is less. Losses by sweating, vomiting, diarrhea, and by that small amount of urine that is produced should be considered. The best general guide is the daily weight of
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the patient. So long as a child is able to take something by mouth, intravenous administration of fluid should be avoided. During the early diuretic phase, the fluid lost must be replaced, but after the peak of diuresis has been reached careful curtailment of fluid intake should be undertaken, to prevent a prolongation of diuresis simply due to water loading.
Rarely Need Transfusion: Progressire anemia consistently follows the course of uremia, tlematoerit levels usually become stable between 25 and 30 ram. Generally the anemia is well tolerated, and attempts to restore hematocrit levels to normal are quite useless and even dangerous. Following transfusion there is a temporary rise in blood hemoglobin and then a decrease to pretransfusion levels. The addition of blood to an already expanded intravaseular compartment invites hypertension, congestive cardiac failure with pulmonary edema, and convulsions. When transfusion is unavoidable, multiple small infusions or, rather, exsanguinotransfusions (replacements) are better than one large transfusion. 2. Vigilance Over Status of Electrolytes.--Correction of electrolytes to a supposedly normal level is not our aim and may even be dangerous. We change electrolytes as little as possible.
During the anuric phase no sodium is given in any form unless it has been demonstrably lost in large quantities or a low alkali reserve (lower than 15 meq. per liter) induces us to give sodimn lactate (or sodium bicarbonate), 10 to 40 meq. per day. It rarely is necessary to give sodium chloride, since retained metabolic acids, such as SOs:,
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will replace C1-. Potassium salts rarely. need be given.
During the diuretic phase sodium chloride sometimes must be provided. Two and one-half grams per liter of urinary output is only a rough guide, as it may be too much. In this phase potassium salts may have to be provided. (One glass of orange juice contains 20 meq. of potassium.) }Iypoealcemia, although often present, rarely produces the symptoms of twitching and convulsions erroneously attributed to it. 3. Caloric Intake.--By providing maximal daily calorie intake we t r y to encourage anabolie processes, diminish wasting of body protein, slow down the formation of retention products, and retard derangement of electrolytes. Calorie supplements in the form of fat emulsions, hard candy, and ginger ale help to boost the daily calorie intake. When anorexia precludes adequate oral intake and intestinal peristalsis still is present, occasionally a fluid homogenate delivered as a constant drip through a small plgstie gastric tube will maintain nutrition. The administration of 40 per cent invert sugar provides a large calorie intake in a small volume and has produced no demonstrable local or hemolytic effects when introduced into the vena cava. 4. Prevention of Infections.--The uremic child is extremely susceptible to infection. In addition to the danger produced by infection itself, the septic state increases catabolism which, in turn, increases the uremia. Adequate nursing care with particular emphasis on general bed care and oral hygiene is essential. Frequent physi-
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cal examination for the early detection of septic loci must be made. Surgical care of cut-down sites minimizes complieation from this source. In addition, it has been our practice to give erythromyein prophylactically throughout the period of danger.
Indications for DiaIysis.--In severe uremia, a state is reached where conservative procedures become inadequate. With progression of the uremic process there begins a vicious cycle. Physical degeneration adds pathologic changes to an already delicate therapeutic problem. Vomiting, for example, makes calorie intake difficult and disturbs electrolyte balance. Coma prevents expectoration and promotes pulmonary infection. Insufficient calorie intake, electrolyte disturbance, and infection all enhance the uremia. We believe that dialysis should be undertaken before the patient enters the cycle. Indication for dialysis is both chemical and clinical. Chemical indications are a CO2-eombining power of less than 12 meq. per liter, a blood urea level of more than 200 mg. per 100 ml., and chemical and electrocardiographic evidence of hyperkalemia (usually a serum potassium level of more than 6.5 meq. per liter). Two clinical patterns of behavior should be a forewarning to the approach of more serious uremic complications. In the first there are lethargy, apathy, and somnolence. In the second there are irritability, restlessness, and psychosis. Either of these patterns frequently is associated with anorexia, nausea and vomiting, and alteration in cardiovascular status, especially with wide fluctuations in blood pressure.
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Early and frequent hemodialyses promote an improvement in sensorium, a return to the feeling of wellbeing, and a return of appetite. Catabolic retention products are reduced, a relative restoration of electrolyte equilibrium is obtained, and the total amount of body water is lessened. In all five patients here discussed clinical improvement after hemodialysis was evident and clinical management became easier. I t must be stated that each hemodialysis is undertaken at a calculated risk, but the risk is small. The fear of hemorrhage has hampered the application of hemodialysis, but, in general, uremic bleeding, such as eechymoses and bleeding from the gums or from the gastrointestinal tract, lessens after hemodialysis. Bleeding from wounds or ulcers must be evaluated for the individual patient. In the patient with meningococeemia there was a slight, transient increase in gastrointestinal and in genitourinary bleeding, but it was not serious. On occasion, hemodialysis has been maintained on as little heparin as was required for the blood used to prime the artificial kidney. Sudden changes in blood pressure might constitute a serious risk: an increase in blood pressure could lead to convulsions; a decrease, to sudden death. No alarming changes happened in the eight dialyses here discussed; but if they had occurred they would have been amenable to treatment. In the hands of a well-
trained team, hemodialysis is not only helpful in producing a smoother coarse in these children, but it may also be lifesaving. SUb{MARY
Eight hemodialyses were performed in five patients whose ages ranged from 2 to 14 years. Four patients surrived; one patient improved temporarily and then died. The etiologic factors that lead to renal failure were transfusion accident in one patient, shock secondary to meningocoeeal septicemia in one, chronic glomeru]onephritis with necrotizing arteriolitis in one (the patient who died), and what appeared to be acute glomerulonephritis in two patients. REFERENCES 1. Kolff, W. J.: and Berk, I-I. T. J . : Artificial K i d n e y : Dialyser With Great Area, Aeta reed. seandinav. 117: 121, 1944. 2. Alwall, N.: On ArtificiM Kidney. XI. Some Supplementary Constructional DetMls of DiMyser Intended for Rabbit and }Iomo, Acta rned. scandinav. (supp. 229) 133: 20, 1949. 3. Skeggs, L. T., Jr., Leonards, J. R., and }Ieisler, C. R.: Artificial Kidney. II. Construction and Operation of Improved Continuous Dialyzer, Prec. See. Exper. Biol. & Med. 72: 539, 1949. 4. Kolff, W. J., and Watsehlnger, :B.: ]~urther Development of Coil Kidney, J. Lab. & Clln. Med. 47: 969, 1956. 5. Mateer, F. M., Greenman, L., and Dan~ owski, T. S.: HemodiMysis of the Uremic Child, A. M. A. Am. J. Dis. Child. 89: 645, 1955. 6. Merrill, J. P., Smith, S., Callahan, E. J , I I I , and Thorn, G. W.: Vse of an Artificial Kidney; Clinical Experienee~ J. Clin. Invest. 29: 425, 1950. 7. :Page, I. H., Corcoran, A. C, Dustan, H. P., and Koppanyi, T.: Cardiovascular Actions of Sodium Nitroprusside in Animals and ~Iypertensive Patients, Circulation 11 : 188, 1955.