- Email: [email protected]
The Artificial Kidney and Its Role in the Treatment of Renal Failure at the University Hospital
The Artificial Kidney and Its Role in the Treatment of Renal Failure at the University Hospital REED M. NESBIT, M.D., F.A.C.S. Professor of Surgery and Head, Section of Urology, University of Michigan Medical School, Ann Arbor
JOSEPH C. CERNY, M.D. Senior Clinical Instructor in Surgery (Urology), University of Michigan Medical School
ORGANIZATION
SINCE THE AUTUMN OF 1957 the maintenance and operation of a fully equipped hemodialysis unit has been a responsibility of the Department of Surgery, Section of Urology, at the University of Michigan Medical Center. Consultation in all phases of the problem of renal failure, its diagnosis, management, and assessment of indications for dialysis, is available. Referrals from the various departments, medical and pediatric as well as surgical, are answered, and consultation is offered to practitioners in Michigan and neighboring states. The hemodialysis unit is under the supervision of the urology staff and is operated by a urology resident during his period of assignment to research activities. While he is on this assignment, the resident has no other clinical responsibilities. Many of the men have had prior opportunity to spend six months with the cardiorenal group of Dr. John Merrill at the Peter Bent Brigham Hospital in Boston, Massachusetts. This association provides training in the techniques of hemodialysis and a delineation of its role in treating renal failure. An appreciation of the many types and clinical manifestations of renal diseases and a working knowledge of the various fluid and electrolyte aberrations are obtained. In many instances the association with Merrill's group has provided . opportunity for original investigative work in related areas. A modern, well equipped renal laboratory and the services of four technicians are closely allied with the hemodialysis unit. Determinations of all modalities of renal function and serum electrolytes are performed
1413
1414
REED
M.
NESBIT, JOSEPH C. CERNY
Fig. 1. Kolff twin coil hemodialyzer (right). A Harvard multispeed infusion-withdrawal pump (left) is used for regional heparinization of the dialyzer.
in the laboratory. Each technician is trained in the assembly and use of the artificial kidney, as well as in basic aspects of patient care, and actively assists the resident surgeon. A registered nurse is always present during dialysis. The resident and a technician are available on a 24 hour call basis. In the past two years 100 dialyses have been performed, approximately one per week. Necessity for the facilities of the artificial kidney is sporadic, however, and to prevent long periods of inactivity of the unit, and to maintain full efficiency of the operating team, trial runs are performed upon dogs at appropriate intervals. In general, if no patient has undergone dialysis within a given ten day period, a dog is run under the same closely monitored conditions. APPARATUS
Initially, the unit employed the Skeggs-Leonard parallel flow hemodialyzer. This apparatus has merit and was lifesaving in many cases, though disadvantages such as relatively low dialysance and difficult assembly led to its abandonment. The Kolff disposable, twin coil, artificial kidney is no~ used. This apparatus has the advantages of easy assembly, efficient dialysance and capability for ultrafiltration. These attributes have made the Kolff kidney popular in other laboratories as well as our own (Fig. 1). A MacNeill-Collins dialyzer has recently been acquired and is being evaluated. This device has certain advantages which are related to its
The Artificial Kidney in the Treatment of Renal Failure
1415
portability, small size and low internal resistance. The capacity of the dialyzer is 150 cc., and priming with blood is not necessary prior to use. Thus, during dialysis, only a small portion of the patient's circulating blood volume is extracorporeal. These features make this unit of particular value in pediatric dialysis. Ultrafiltration may be accomplished with the MacNeill-Collins dialyzer also. MANAGEMENT OF PATIENTS WITH RENAL FAILURE
Diagnosis
Patients with suspected renal failure must be carefully evaluated. An aecurate history is of paramount importance in assessing the kind and degree of renal damage. A knowledge of the patient's age, sex, occupation and familial history is necessary. Presence or absence of current symptomatology should be viewed in relation to previous medical or surgieal urinary tract disease. A thorough history must consider possible etiologic entities such as acute glomerulonephritis, recent surgery with marked blood loss, pregnancy complicated by eclampsia, acute dehydration, and gram-negative septicemia with hypotension. Renal failure resulting from ingestion or inhalation of toxins such as ethylene glycol, mercuric chloride or carbon tetrachloride is seen frequently. Marked allergic response to certain medications and hemolytic dyscrasias are known to cause renal damage and failure. Prolonged ingestion of phenacetin (acetophenetidin) containing compounds is thought to cause renal failure, and cases are being reported with increasing frequency, particularly in the European literature. Recently, a 60 year old man was admitted to the service with a history of having ingested many APC tablets daily for several years. Renal biopsy demonstrated the typical picture of phenacetin interstitial nephritis. Discontinuing the medication has resulted in a significant improvement of renal function. The obvious role of accurate physical diagnosis requires no reiteration. The physical manifestations of renal failure may be subtle and varied. Impairment of cerebral processes, abnormalities of hydration, pallor, hypertension, irregular respirations, eyeground changes, lesions of buccal mucosa indicating ingestion of toxins, cutaneous petechiae, pulmonary rales, cardiac enlargement, evidence of gastrointestinal hemorrhage, flank or abdominal masses indicating neoplasm, neurological aberrations and edema, are some of the physical findings which, while common to other diseases as well, may be seen in all degrees and combinations in renal failure. Laboratory studies frequently corroborate the diagnosis and are necessary in following the clinical course. Urinalysis, with measurement of specific gravity, pH, analysis for albumin and microscopic examination
1416
REED
M.
NESBIT, JOSEPH C. CERNY
of a stained sediment, is performed. A complete blood count is obtained. Estimates of renal function, particularly blood urea nitrogen, serum creatinine and phenolsulphonthalein excretion, are made. The status of the serum electrolytes, calcium and· phosphorus is determined. The electrocardiogram is a valuable adjunct in appraising the effect of elevated serum potassium upon the myocardium. The possibility of ureteral obstruction causing the oliguria must always be kept in mind. Excretory pyelograms will be useful in deciding this point when the oliguric patient is found to excrete 5 per cent of P.S.P. in 15 minutes, and 90 per cent Hypaque in such cases will usually provide acceptable pyelograms. In patients who are profoundly uremic and who excrete P.S.P. in less concentration than 5 per cent in 15 minutes, the use of excretory pyelography is futile, indeed it may be harmful, and retrograde pyelography is essential to differentiate obstructive from primary renal failure. Clinical Regimen
When oliguria with decreasing renal function signals the presence of frank renal failure, a specific program of clinical management is started: 1. Fluids are limited to a maintenance of 400 cc. per day. To this amount is added a volume equivalent to other measured fluid losses, such as urine output and loss from the gastrointestinal tract. 2. The patient is weighed daily. This is the simplest and most reliable method of following the clinical status of hydration. 3. Intake and output are accurately measured. 4. Protein intake is restricted. 5. Caloric requirements are given in the form of intravenous hypertonic glucose, or hard candy by mouth. 6. Determinations of serum electrolytes, urea nitrogen and creatinine are obtained daily. 7. Hyperkalemia, when it exists, is managed satisfactorily in most instances by the use of ion exchange resins administered orally or rectally. 8. Isolation precautions are strictly enforced. Patients in renal failure are extremely susceptible to infections of all kinds and must be isolated from the general hospital environment. Does this mean prophylactic antibiotics should be given? No, because antibiotics will not prevent infection from developing in these patients, and their use should therefore be limited to cases in which specific clinical indications exist. Furthermore, certain antibiotics are excreted primarily by the kidney and may accumulate to toxic levels in the presence of renal failure. 9. Marked electrolyte loss in the urine may occur during the diuretic phase of acute renal failure. Frequent determinations of urinary sodium and potassium are made, and replacement may be accurately achieved if loss is excessive.
The Artificial Kidney in the Treatment of Renal Failure
1417
DIALYSIS
Indications In spite of the program of conservative management as outlined, in our series 50 per cent of renal failure patients required hemodialysis at some time during their clinical course. The indications for dialysis are not specifically defined and must be individually appraised in each clinical situation. Progressive clinical deterioration, as evidenced by impaired cerebration, intractable nausea and vomiting, pulmonary edema, convulsions, severe electrolyte derangement or hyperkalemia, comprise indications for dialysis. In an otherwise satisfactory clinical course, elevation of nitrogen retention products above an arbitrary fixed point does not, in our opinion, constitute a valid criterion for dialysis. In view of the high mortality that has occurred in the renal failure cases that required dialysis in the past, most authorities are presently advocating earlier dialysis in the hope of stabilizing the patient's condition before irreversible deterioration has developed. Indeed, this concept has been carried to its ultimate by the daily or multiple dialysis regimen in early renal failure, advocated and practiced by Major Teschan and his group at Fort Sam Houston in San Antonio, Texas. l Advantages of this program are the greater latitude in intake of fluid and protein afforded the patient during the period of oliguria, and an apparent improvement in the mortality rate. Technique Surgical cutdowns for the placement of vascular cannulae are performed under local anesthesia in the dialysis room. Tapered polyethylene cannulae are introduced to as great a diameter as the individual vessel will allow. Radial artery and antecubital vein are the most frequently utilized vessels. When difficulties are encountered in cannulation of vessels because of previous trauma, anomaly or spasm, a double-lumen cannula placed in the inferior vena cava via the saphenous vein will provide an excellent blood flow rate. Some investigators have employed continuously heparinized indwelling cannulae for long periods of time in the treatment of renal failure by multiple dialysis. A permanent, subcutaneous, polyethylene, closed cycle, arteriovenous shunt is presently being evaluated. These techniques of vascular access are of particular value in conjunction with the MacNeill-Collins kidney, with which an extra corporeal pump is not needed and effective blood flow rates may often be maintained solely by the patient's arterial pressure. In our unit, however, in most cases separate vascular cutdowns have been performed for each dialysis. Prior to dialysis most patients are heparinized systemically to prevent blood from clotting in the apparatus. Certain patients have bleeding
1418
REED
M.
NESBIT, JOSEPH C. CERNY
tendencies as a complication of their renal failure, particularly gastrointestinal hemorrhage, which contraindicate systemic heparinization. In these individuals regional heparinization of the artificial kidney may be employed. Heparin is introduced into the arterial end of the dialyzer and protamine at the venous outlet. The rate of infusion of heparin and protamine is monitored by the Harvard Multispeed Infusion Pump (Fig. 1). The blood is thus adequately heparinized during its passage through the unit and is returned to the patient's circulation with normal clotting capability. Blood flow rates of 250 to 400 cc. per minute are considered optimal, though effective results can be obtained with flow rates as low as 100 cc. per minute. Maximum benefits of dialysis are obtained within four to six hours, except in barbiturate poisoning where longer dialysis is necessary. A transient period of hypotension, occurring immediately after dialysis has begun and lasting for from five to ten minutes, has been observed in some patients. This is felt to represent a period of adjustment of blood volume within the distensible cellophane coils of the dialyzer. In pediatric dialysis with the Kolff apparatus, a single coil has been used to minimize hypotension and reduce the amount of extracorporeal circulating blood volume. The dialyzing bath is prepared individually for each patient. The sodium, potassium, chloride, carbon dioxide, calcium, phosphorus, pH and osmolar concentrations are calculated according to the patient's serum values and the desired gradient of correction. The bath is prepared anew and changed every two hours. Many patients with renal failure referred to this unit are overhydrated upon arrival and may also have pulmonary edema. Indeed, a common cause of death in such patients who have not been properly treated is pulmonary edema with drowning. The overhydration in these cases usually occurs because the physician treating the patient has misinterpreted oliguria as a manifestation of dehydration, and has given fluids in large amounts. Determination of urinary specific gravity can avert this error. If specific gravity is high, the patient is dehydrated, has adequate renal function, and may be given fluid. If specific gravity is low, however, the patient must be assumed to have impaired renal function and fluids should be withheld. In patients suffering from overhydration and pulmonary edema the ultrafiltration feature of the Kolff and MacNeill-Collins units has proved lifesaving. As much as 500 cc. of ultrafiltrate (water) per hour can be removed in this manner. The clinical and radiologic improvement in overhydrated patients following removal of several liters of fluid is a most dramatic event. Electrocardiographic monitoring is used, particularly in patients with abnormal T wave changes resulting from hyperkalemia, or in whom cardiac arrhythmia exists or is anticipated. Throughout the dialysis the
The Artificial Kidney in the Treatment of Renal Failure
1419
resident surgeon, the laboratory technician and the registered nurse are in constant attendance. At its termination, the cannulae are removed, the vessels ligated and a compression dressing applied. Patients who were heparinized systemically are given an appropriate dose of protamine to restore normal clotting time. RESULTS Acute Renal Failure
Approximately fifty patients a year are seen because of renal failure at the University Hospital. Many of them have chronic renal failure. It is chiefly in the group with acute renal failure, however, that hemodialysis makes its greatest contribution. During the past year 26 patients were treated for acute renal failure (Table 1). In 13 cases the condition was acute tubular necrosis; in six, oliguria resulted from operative or postoperative hypotension; in four, ingestion of ethylene glycol or mercuric chloride was the cause, while in the other three patients renal failure followed instances of gunshot trauma, eclampsia and perforated duodenal ulcer. Six patients were oliguric because of acute glomerulonephritis, and three suffered from renal artery occlusion. There were single cases of renal cortical necrosis, myoglobinuric nephrosclerosis, phenacetin interstitial nephritis and allergic glomerulitis. The latter case is that of a 50 year old man who was treated with para-aminosalicylic acid for a tuberculous arthritis. After receiving medication for three days, he developed urticarial cutaneous lesions, became oliguric, and exhibited the clinical and laboratory findings of acute renal failure. He subsequently recovered without requiring dialysis. SURVIVAL IN RELATION TO DIALYSIS, DURATION OF OLIGURIA, NITROGEN RETENTION AND AGE. Nineteen of the 26 patients with acute renal failure required dialysis. In the group which was dialyzed, the survival was 37 per cent, while in the nondialyzed group, 86 per cent survived. The single death in the latter group was that of a patient admitted to the hospital in terminal condition. Of the seven patients who required dialysis and survived, one was dialyzed twice, and the others were dialyzed one time each. Among those who died, three were dialyzed once, seven twice, one patient required dialysis three times, while another was dialyzed on four separate occasions. The average pre dialysis blood urea nitrogen level in patients who survived was 200 mg. per 100 mI., and duration of oliguria was 12 days. In patients who died, the average predialysis blood urea nitrogen was 280 mg. per 100 ml. and duration of oliguria was 14 days. One patient, a 44 year old man who suffered an acute tubular necrosis as a result of ethyl-
Table 1. AGE CASE
SEX
(yrs.)
M
35
2
M
55
3
M
49
4 5 6 7 8
M M M M F
65 38 44 57 65
ETIOLOGY
Acute tubular necrosis Postop. laparotomy Acute tubular necrosis Ethylene glycol ingestion Acute tubular necrosis Postop. gastrectomy Acute tubular necrosis Gunshot wound of abdomen Acute tubular necrosis Postop. laparotomy Acute tubular necrosis Ethylene glycol ingestion Acute tubular necrosis Ethylene glycol ingestion Acute tubular necrosis Perforated peptic ulcer Acute tubular necrosis Mercuric chloride ingestion Acute tubular necrosis Eclampsia Acute tubular necrosis Postop. laparotomy Acute tubular necrosis Postop. laparotomy
BLOOD UREA NITROGEN
12
249
8
Pulmonary edema
Survived
24
375
8, 11, 17, 21
Septicemia
Died
4
146
Moribund, terminal on admission
Died
4 15 15
15
440
6, 10
G.T. Bleeding
297
7
Pneumonia)
Died
171
9, 19
Perceptive deafness
8
255
5, 8
G.T. bleeding, obstruction
Died
8 15
15
144
3, 9
G.T. bleeding, pneumonia
Died
11
210
4
Anorectal ulceration, bleeding
Survived
18
11
F
72
12
F
62
13
M
67
Acute tubular necrosis Postop. aortic resection
14 15 16 17 18 19 20 21
M M
32 9 8 23 8 28 46
Acute glomerulonephritis Acute glomerulonephritis Acute glomerulonephritis Acute glomerulonephritis Acute glomerulonephritis Acute glomerulonephritis Bilateral renal infarct Bilateral renal cortical necrosis
9 14 9 20 8 2 2 26
192 200 210 231 226 125 225 423
9 6 3, 57, 76 8, 15 4
Myoglobinuric nephroglomerulosclerosis (R) Nephrectomy. (L) Renal infarct Bilateral renal artery occlusion Prolonged phenacetin ingestion Allergic response to P.A.S.
14 6 7 3 7
285 135 300 150 200
4, 7, 12 5 5
M M F
M M
Laryngitis, atelectasis
Survived
120
Oral moniliasis
Survived
165
G.T. bleeding
Survived
4
162
7 11
3
Pneumonia
129
11, 17
Pulmonary edema Anemia, hypertension Hypertension, nephrotic syndrome Anemia Anemia
Hypertension Myocardial infarction G.T. bleeding Hemolytic anemia Acute parotitis, tracheobronchitis Hypertension Convulsions Anemia Anemia
Died Died Died Survived Survived
~
~ to".! to".!
t:i
~
Z to".!
lfl
Survived Survived Survived Died Died Survived Survived Died Died
~
0
24
26
F
22 23 24 25 26
DEATH
Survived
10
4~
RESULT
15
47
mos. 40 57 66 60 51
COllPLICATIONS
Died
F
M M M M M
DAY OF
DAY OF DIALYSIS
DAYS OF OLIGURIA
9
F
,....
Acute Renal Failure
....t:d
~..,
c:....; 0
76 20
lfl
2 26
p
14 6 7
0
to".!
~
to".! ~
Z
~
The Artificial Kidney in the Treatment of Renal Failure
..
1421
ACUTE RENAL FAILURE ETHYLENE GLYCOL INGESTION A.V.D. 821183 43 yrs, wI, mole
.....
DIALYSIS
DIALYSIS
800 700 ~
.c
600
v
N
";) 500 u
400
7
• 350
iI" E
~
..J
300
\ ,,\" '1" /I" 'I \'1.. ,~II,I
z
:ll
250
~
0::
:;:)
!!i 200
I
0
0 0
..J III
50
o
0
;.
!
in
4'"
~
,
o
30..
...............................
::E
:;:)
r.
2 ..... BUN -URINE OUTPUT --SERUM K+
, 0
... '
ill
:;:)
,,,',\ ', ,I
'.............
;
100
100
,,' '.." j ............. I"
c(
5 ~
,"I
,I
'v' I,
0::
..,z
..
6~ E
I,
... 400 0~ 200 ... .., 150 0300 :;:)
8
i
5
10
15
20
i
i
i
25
30
35
ffi
'"
0 40
DAYS
Fig. 2
ene glycol ingestion, survived after 26 days of oliguria and two dialyses (Fig. 2). Patients who were dialyzed and survived had an average age of 27 years. In those who succumbed, the average age was 45 years. COMPLICATIONS. The dominant role of complications in the clinical course of uremia was reaffirmed in this survey. Fifty per cent of the patients developed infection of some kind during their illness. In five patients the infection was major, e.g., pneumonia or septicemia, and contributed significantly to clinical morbidity. Two patients died as a direct result of infection. Other complications frequently seen were gastrointestinal bleeding, pulmonary edema, hypertension and anemia. DISCUSSION. The survival rate of 50 per cent in all cases of acute renal failure and 37 per cent in those which required dialysis parallels the experience reported by others.2 Duration of oliguria does not appear significa.nt in determining prognosis. The predialysis blood urea nitrogen was 40 per cent greater in patients who died, though prognosis did not in general appear related to the degree of nitrogen retention. Patients who died averaged 16 years older than those who survived, and the spectrum of distribution was broad in both groups.' The prognosis in acute tubular necrosis is related to the setting in which the disease develops. Cases which follow surgery or trauma have a poorer prognosis than those caused by eclampsia or ingestion of toxins. The survival was 50 per cent and 60 per cent in the two groups, a less marked difference than has been noted by others.3 The occurrence of infection as a complication in 50 per cent of patients is not as great as that in other series, and may be due in part to strict enforcement of isolation pre-
1422
REED
M.
NESBIT, JOSEPH C. CERNY
cautions. 4 The incidence of central nervous system complications and cardiac abnormalities is not of the magnitude described by others. Chronic Renal Failure Twenty-three patients were treated for chronic renal failure. Eight of them had chronic glomerulonephritis, five had ureteral obstruction, congenital or secondary to neoplasm, four suffered from chronic pyelonephritis and three had polycystic disease. There were single cases of bladder outlet obstruction with hydronephrosis, sclerosing pyelonephritis secondary to retrograde injection of sodium nitrite, and ureterosigmoid anastomosis for exstrophy of the bladder. Seventeen of the patients died in spite of treatment. DIALYSIS. Dialysis was performed in ten patients. Several received gratifying remission of clinical symptoms or electrolyte abnormalities. One patient is a 21 year old married woman with bilateral ureterosigmoid anastomosis who recently became pregnant and was delivered of a healthy infant, with no further deterioration of renal function; another is a 40 year old lawyer with polycystic disease who received prolonged remission of symptoms of hypertension following dialysis, and has subsequently returned to his practice. DISCUSSION. Indications for dialysis in this group of patients are less specific than in acute renal failure. To a great extent this is a matter of the philosophy of the individual physician. Patients in whom there exists the possibility of a superimposed acute process, either exacerbation of renal disease, infection or surgical disease, may be candidates for dialysis. In the latter instance, dialysis may be a valuable preoperative adjunct. Relief of intractable symptoms, such as nausea and vomiting, or recurrent convulsions, is often obtained. The hypertension and symptomatology of polycystic disease are sometimes markedly improved for prolonged periods of time. In centers where renal transplantation is performed, dialysis may be used to prepare the recipient optimally for operation. INVESTIGATIVE OPPORTUNITIES
The artificial kidney unit has provided an opportunity and stimulus for original investigation. Appraisal of the efficacy of indwelling vascular cannulae and of the subcutaneous arteriovenous shunt, particularly in reference to the MacNeill-Collins dialyzer, has been mentioned in previous paragraphs. Much of the initial laboratory and clinical evaluation of this dialyzer was carried out by members of our department in conjunction with Merrill's group in Boston. A similar appraisal of the Kolff apparatus was made four years ago. Recently, this combined effort has produced a commercially feasible pack for the MacNeill-Collins
The Artificial Kidney in the Treatment of Renal Failure
1423
kidney. We are presently evaluating the Fenwal ion exchange chamber in renal failure patients with uncontrollable hyperkalemia. Within the past year two infants, aged four months and one year, have been dialyzed using the Kolff apparatus and single coil. The four month infant was dialyzed twice, and is thought to be the youngest individual ever to undergo this procedure successfully. The necessary refinement of technique, particular problems encountered, and necessary precautions, have been described. SUMMARY
The successful development and management of an artificial kidney unit is an undertaking that imposes definite obligations and requirements upon those who are responsible for it. The mere acquisition of apparatus and pronouncement of willingness to perform hemodialysis is but a token beginning. This is a team project, headed by a physician especially trained in the problems of clinical renal disease, fluid and electrolyte therapy, and assessment of indications for hemodialysis. The team must include technical assistants who, like the physician, are available on a 24 hour basis. Closely allied laboratory facilities are necessary to appraise the many chemical aberrations of renal disease. Fully commensurate with the problems and obligations that accrue to a hemodialysis unit are the unique opportunities it provides for related investigative activity. The often lifesaving capabilities of this unit and its obvious contribution to the surrounding medical community are aspects which require no reiteration. Our experience with a series of cases of renal failure is presented, and a plan for clinical management described. The significance of age, duration of oliguria, nitrogen retention and complications in acute renal failure is discussed. The role of hemodialysis in both acute and chronic renal failure, its indications and results, has been outlined. REFERENCES 1. Bluemle, L. W., Webster, G. D. and Elkington, J. F.: Acute Tubular Necrosis. A.M.A. Arch. Int. Med. 104: 180-197 (Aug.) 1959.
2. Breakey, B., Reus, W. and Woodruff, M.: Technique for Dialysis of Infants. J. Urol. To be published. 3. Keleman, W. A. and Kolff, W. J.: Survey of Dialyses for Acute Renal Failure at Cleveland Clinic Hospital in 1958. Cleveland Clinic Quarterly 26: 227-234 (Oct.) 1959. 4. Kiley, J. E., Powers, S. and Beebe, R.: Acute Renal Failure. New England J. Med. 262: 481-486 (March) 1960. 5. Teschan, P. E., O'Brien, T. F. and Baxter, C. R.: Prophylactic Daily Hemodialysis in Treatment of Acute Renal Failure. Clin. Research 7: 280, 195H.
JOSEPH C. CERNY, M.D. Senior Clinical Instructor in Surgery (Urology), University of Michigan Medical School
ORGANIZATION
SINCE THE AUTUMN OF 1957 the maintenance and operation of a fully equipped hemodialysis unit has been a responsibility of the Department of Surgery, Section of Urology, at the University of Michigan Medical Center. Consultation in all phases of the problem of renal failure, its diagnosis, management, and assessment of indications for dialysis, is available. Referrals from the various departments, medical and pediatric as well as surgical, are answered, and consultation is offered to practitioners in Michigan and neighboring states. The hemodialysis unit is under the supervision of the urology staff and is operated by a urology resident during his period of assignment to research activities. While he is on this assignment, the resident has no other clinical responsibilities. Many of the men have had prior opportunity to spend six months with the cardiorenal group of Dr. John Merrill at the Peter Bent Brigham Hospital in Boston, Massachusetts. This association provides training in the techniques of hemodialysis and a delineation of its role in treating renal failure. An appreciation of the many types and clinical manifestations of renal diseases and a working knowledge of the various fluid and electrolyte aberrations are obtained. In many instances the association with Merrill's group has provided . opportunity for original investigative work in related areas. A modern, well equipped renal laboratory and the services of four technicians are closely allied with the hemodialysis unit. Determinations of all modalities of renal function and serum electrolytes are performed
1413
1414
REED
M.
NESBIT, JOSEPH C. CERNY
Fig. 1. Kolff twin coil hemodialyzer (right). A Harvard multispeed infusion-withdrawal pump (left) is used for regional heparinization of the dialyzer.
in the laboratory. Each technician is trained in the assembly and use of the artificial kidney, as well as in basic aspects of patient care, and actively assists the resident surgeon. A registered nurse is always present during dialysis. The resident and a technician are available on a 24 hour call basis. In the past two years 100 dialyses have been performed, approximately one per week. Necessity for the facilities of the artificial kidney is sporadic, however, and to prevent long periods of inactivity of the unit, and to maintain full efficiency of the operating team, trial runs are performed upon dogs at appropriate intervals. In general, if no patient has undergone dialysis within a given ten day period, a dog is run under the same closely monitored conditions. APPARATUS
Initially, the unit employed the Skeggs-Leonard parallel flow hemodialyzer. This apparatus has merit and was lifesaving in many cases, though disadvantages such as relatively low dialysance and difficult assembly led to its abandonment. The Kolff disposable, twin coil, artificial kidney is no~ used. This apparatus has the advantages of easy assembly, efficient dialysance and capability for ultrafiltration. These attributes have made the Kolff kidney popular in other laboratories as well as our own (Fig. 1). A MacNeill-Collins dialyzer has recently been acquired and is being evaluated. This device has certain advantages which are related to its
The Artificial Kidney in the Treatment of Renal Failure
1415
portability, small size and low internal resistance. The capacity of the dialyzer is 150 cc., and priming with blood is not necessary prior to use. Thus, during dialysis, only a small portion of the patient's circulating blood volume is extracorporeal. These features make this unit of particular value in pediatric dialysis. Ultrafiltration may be accomplished with the MacNeill-Collins dialyzer also. MANAGEMENT OF PATIENTS WITH RENAL FAILURE
Diagnosis
Patients with suspected renal failure must be carefully evaluated. An aecurate history is of paramount importance in assessing the kind and degree of renal damage. A knowledge of the patient's age, sex, occupation and familial history is necessary. Presence or absence of current symptomatology should be viewed in relation to previous medical or surgieal urinary tract disease. A thorough history must consider possible etiologic entities such as acute glomerulonephritis, recent surgery with marked blood loss, pregnancy complicated by eclampsia, acute dehydration, and gram-negative septicemia with hypotension. Renal failure resulting from ingestion or inhalation of toxins such as ethylene glycol, mercuric chloride or carbon tetrachloride is seen frequently. Marked allergic response to certain medications and hemolytic dyscrasias are known to cause renal damage and failure. Prolonged ingestion of phenacetin (acetophenetidin) containing compounds is thought to cause renal failure, and cases are being reported with increasing frequency, particularly in the European literature. Recently, a 60 year old man was admitted to the service with a history of having ingested many APC tablets daily for several years. Renal biopsy demonstrated the typical picture of phenacetin interstitial nephritis. Discontinuing the medication has resulted in a significant improvement of renal function. The obvious role of accurate physical diagnosis requires no reiteration. The physical manifestations of renal failure may be subtle and varied. Impairment of cerebral processes, abnormalities of hydration, pallor, hypertension, irregular respirations, eyeground changes, lesions of buccal mucosa indicating ingestion of toxins, cutaneous petechiae, pulmonary rales, cardiac enlargement, evidence of gastrointestinal hemorrhage, flank or abdominal masses indicating neoplasm, neurological aberrations and edema, are some of the physical findings which, while common to other diseases as well, may be seen in all degrees and combinations in renal failure. Laboratory studies frequently corroborate the diagnosis and are necessary in following the clinical course. Urinalysis, with measurement of specific gravity, pH, analysis for albumin and microscopic examination
1416
REED
M.
NESBIT, JOSEPH C. CERNY
of a stained sediment, is performed. A complete blood count is obtained. Estimates of renal function, particularly blood urea nitrogen, serum creatinine and phenolsulphonthalein excretion, are made. The status of the serum electrolytes, calcium and· phosphorus is determined. The electrocardiogram is a valuable adjunct in appraising the effect of elevated serum potassium upon the myocardium. The possibility of ureteral obstruction causing the oliguria must always be kept in mind. Excretory pyelograms will be useful in deciding this point when the oliguric patient is found to excrete 5 per cent of P.S.P. in 15 minutes, and 90 per cent Hypaque in such cases will usually provide acceptable pyelograms. In patients who are profoundly uremic and who excrete P.S.P. in less concentration than 5 per cent in 15 minutes, the use of excretory pyelography is futile, indeed it may be harmful, and retrograde pyelography is essential to differentiate obstructive from primary renal failure. Clinical Regimen
When oliguria with decreasing renal function signals the presence of frank renal failure, a specific program of clinical management is started: 1. Fluids are limited to a maintenance of 400 cc. per day. To this amount is added a volume equivalent to other measured fluid losses, such as urine output and loss from the gastrointestinal tract. 2. The patient is weighed daily. This is the simplest and most reliable method of following the clinical status of hydration. 3. Intake and output are accurately measured. 4. Protein intake is restricted. 5. Caloric requirements are given in the form of intravenous hypertonic glucose, or hard candy by mouth. 6. Determinations of serum electrolytes, urea nitrogen and creatinine are obtained daily. 7. Hyperkalemia, when it exists, is managed satisfactorily in most instances by the use of ion exchange resins administered orally or rectally. 8. Isolation precautions are strictly enforced. Patients in renal failure are extremely susceptible to infections of all kinds and must be isolated from the general hospital environment. Does this mean prophylactic antibiotics should be given? No, because antibiotics will not prevent infection from developing in these patients, and their use should therefore be limited to cases in which specific clinical indications exist. Furthermore, certain antibiotics are excreted primarily by the kidney and may accumulate to toxic levels in the presence of renal failure. 9. Marked electrolyte loss in the urine may occur during the diuretic phase of acute renal failure. Frequent determinations of urinary sodium and potassium are made, and replacement may be accurately achieved if loss is excessive.
The Artificial Kidney in the Treatment of Renal Failure
1417
DIALYSIS
Indications In spite of the program of conservative management as outlined, in our series 50 per cent of renal failure patients required hemodialysis at some time during their clinical course. The indications for dialysis are not specifically defined and must be individually appraised in each clinical situation. Progressive clinical deterioration, as evidenced by impaired cerebration, intractable nausea and vomiting, pulmonary edema, convulsions, severe electrolyte derangement or hyperkalemia, comprise indications for dialysis. In an otherwise satisfactory clinical course, elevation of nitrogen retention products above an arbitrary fixed point does not, in our opinion, constitute a valid criterion for dialysis. In view of the high mortality that has occurred in the renal failure cases that required dialysis in the past, most authorities are presently advocating earlier dialysis in the hope of stabilizing the patient's condition before irreversible deterioration has developed. Indeed, this concept has been carried to its ultimate by the daily or multiple dialysis regimen in early renal failure, advocated and practiced by Major Teschan and his group at Fort Sam Houston in San Antonio, Texas. l Advantages of this program are the greater latitude in intake of fluid and protein afforded the patient during the period of oliguria, and an apparent improvement in the mortality rate. Technique Surgical cutdowns for the placement of vascular cannulae are performed under local anesthesia in the dialysis room. Tapered polyethylene cannulae are introduced to as great a diameter as the individual vessel will allow. Radial artery and antecubital vein are the most frequently utilized vessels. When difficulties are encountered in cannulation of vessels because of previous trauma, anomaly or spasm, a double-lumen cannula placed in the inferior vena cava via the saphenous vein will provide an excellent blood flow rate. Some investigators have employed continuously heparinized indwelling cannulae for long periods of time in the treatment of renal failure by multiple dialysis. A permanent, subcutaneous, polyethylene, closed cycle, arteriovenous shunt is presently being evaluated. These techniques of vascular access are of particular value in conjunction with the MacNeill-Collins kidney, with which an extra corporeal pump is not needed and effective blood flow rates may often be maintained solely by the patient's arterial pressure. In our unit, however, in most cases separate vascular cutdowns have been performed for each dialysis. Prior to dialysis most patients are heparinized systemically to prevent blood from clotting in the apparatus. Certain patients have bleeding
1418
REED
M.
NESBIT, JOSEPH C. CERNY
tendencies as a complication of their renal failure, particularly gastrointestinal hemorrhage, which contraindicate systemic heparinization. In these individuals regional heparinization of the artificial kidney may be employed. Heparin is introduced into the arterial end of the dialyzer and protamine at the venous outlet. The rate of infusion of heparin and protamine is monitored by the Harvard Multispeed Infusion Pump (Fig. 1). The blood is thus adequately heparinized during its passage through the unit and is returned to the patient's circulation with normal clotting capability. Blood flow rates of 250 to 400 cc. per minute are considered optimal, though effective results can be obtained with flow rates as low as 100 cc. per minute. Maximum benefits of dialysis are obtained within four to six hours, except in barbiturate poisoning where longer dialysis is necessary. A transient period of hypotension, occurring immediately after dialysis has begun and lasting for from five to ten minutes, has been observed in some patients. This is felt to represent a period of adjustment of blood volume within the distensible cellophane coils of the dialyzer. In pediatric dialysis with the Kolff apparatus, a single coil has been used to minimize hypotension and reduce the amount of extracorporeal circulating blood volume. The dialyzing bath is prepared individually for each patient. The sodium, potassium, chloride, carbon dioxide, calcium, phosphorus, pH and osmolar concentrations are calculated according to the patient's serum values and the desired gradient of correction. The bath is prepared anew and changed every two hours. Many patients with renal failure referred to this unit are overhydrated upon arrival and may also have pulmonary edema. Indeed, a common cause of death in such patients who have not been properly treated is pulmonary edema with drowning. The overhydration in these cases usually occurs because the physician treating the patient has misinterpreted oliguria as a manifestation of dehydration, and has given fluids in large amounts. Determination of urinary specific gravity can avert this error. If specific gravity is high, the patient is dehydrated, has adequate renal function, and may be given fluid. If specific gravity is low, however, the patient must be assumed to have impaired renal function and fluids should be withheld. In patients suffering from overhydration and pulmonary edema the ultrafiltration feature of the Kolff and MacNeill-Collins units has proved lifesaving. As much as 500 cc. of ultrafiltrate (water) per hour can be removed in this manner. The clinical and radiologic improvement in overhydrated patients following removal of several liters of fluid is a most dramatic event. Electrocardiographic monitoring is used, particularly in patients with abnormal T wave changes resulting from hyperkalemia, or in whom cardiac arrhythmia exists or is anticipated. Throughout the dialysis the
The Artificial Kidney in the Treatment of Renal Failure
1419
resident surgeon, the laboratory technician and the registered nurse are in constant attendance. At its termination, the cannulae are removed, the vessels ligated and a compression dressing applied. Patients who were heparinized systemically are given an appropriate dose of protamine to restore normal clotting time. RESULTS Acute Renal Failure
Approximately fifty patients a year are seen because of renal failure at the University Hospital. Many of them have chronic renal failure. It is chiefly in the group with acute renal failure, however, that hemodialysis makes its greatest contribution. During the past year 26 patients were treated for acute renal failure (Table 1). In 13 cases the condition was acute tubular necrosis; in six, oliguria resulted from operative or postoperative hypotension; in four, ingestion of ethylene glycol or mercuric chloride was the cause, while in the other three patients renal failure followed instances of gunshot trauma, eclampsia and perforated duodenal ulcer. Six patients were oliguric because of acute glomerulonephritis, and three suffered from renal artery occlusion. There were single cases of renal cortical necrosis, myoglobinuric nephrosclerosis, phenacetin interstitial nephritis and allergic glomerulitis. The latter case is that of a 50 year old man who was treated with para-aminosalicylic acid for a tuberculous arthritis. After receiving medication for three days, he developed urticarial cutaneous lesions, became oliguric, and exhibited the clinical and laboratory findings of acute renal failure. He subsequently recovered without requiring dialysis. SURVIVAL IN RELATION TO DIALYSIS, DURATION OF OLIGURIA, NITROGEN RETENTION AND AGE. Nineteen of the 26 patients with acute renal failure required dialysis. In the group which was dialyzed, the survival was 37 per cent, while in the nondialyzed group, 86 per cent survived. The single death in the latter group was that of a patient admitted to the hospital in terminal condition. Of the seven patients who required dialysis and survived, one was dialyzed twice, and the others were dialyzed one time each. Among those who died, three were dialyzed once, seven twice, one patient required dialysis three times, while another was dialyzed on four separate occasions. The average pre dialysis blood urea nitrogen level in patients who survived was 200 mg. per 100 mI., and duration of oliguria was 12 days. In patients who died, the average predialysis blood urea nitrogen was 280 mg. per 100 ml. and duration of oliguria was 14 days. One patient, a 44 year old man who suffered an acute tubular necrosis as a result of ethyl-
Table 1. AGE CASE
SEX
(yrs.)
M
35
2
M
55
3
M
49
4 5 6 7 8
M M M M F
65 38 44 57 65
ETIOLOGY
Acute tubular necrosis Postop. laparotomy Acute tubular necrosis Ethylene glycol ingestion Acute tubular necrosis Postop. gastrectomy Acute tubular necrosis Gunshot wound of abdomen Acute tubular necrosis Postop. laparotomy Acute tubular necrosis Ethylene glycol ingestion Acute tubular necrosis Ethylene glycol ingestion Acute tubular necrosis Perforated peptic ulcer Acute tubular necrosis Mercuric chloride ingestion Acute tubular necrosis Eclampsia Acute tubular necrosis Postop. laparotomy Acute tubular necrosis Postop. laparotomy
BLOOD UREA NITROGEN
12
249
8
Pulmonary edema
Survived
24
375
8, 11, 17, 21
Septicemia
Died
4
146
Moribund, terminal on admission
Died
4 15 15
15
440
6, 10
G.T. Bleeding
297
7
Pneumonia)
Died
171
9, 19
Perceptive deafness
8
255
5, 8
G.T. bleeding, obstruction
Died
8 15
15
144
3, 9
G.T. bleeding, pneumonia
Died
11
210
4
Anorectal ulceration, bleeding
Survived
18
11
F
72
12
F
62
13
M
67
Acute tubular necrosis Postop. aortic resection
14 15 16 17 18 19 20 21
M M
32 9 8 23 8 28 46
Acute glomerulonephritis Acute glomerulonephritis Acute glomerulonephritis Acute glomerulonephritis Acute glomerulonephritis Acute glomerulonephritis Bilateral renal infarct Bilateral renal cortical necrosis
9 14 9 20 8 2 2 26
192 200 210 231 226 125 225 423
9 6 3, 57, 76 8, 15 4
Myoglobinuric nephroglomerulosclerosis (R) Nephrectomy. (L) Renal infarct Bilateral renal artery occlusion Prolonged phenacetin ingestion Allergic response to P.A.S.
14 6 7 3 7
285 135 300 150 200
4, 7, 12 5 5
M M F
M M
Laryngitis, atelectasis
Survived
120
Oral moniliasis
Survived
165
G.T. bleeding
Survived
4
162
7 11
3
Pneumonia
129
11, 17
Pulmonary edema Anemia, hypertension Hypertension, nephrotic syndrome Anemia Anemia
Hypertension Myocardial infarction G.T. bleeding Hemolytic anemia Acute parotitis, tracheobronchitis Hypertension Convulsions Anemia Anemia
Died Died Died Survived Survived
~
~ to".! to".!
t:i
~
Z to".!
lfl
Survived Survived Survived Died Died Survived Survived Died Died
~
0
24
26
F
22 23 24 25 26
DEATH
Survived
10
4~
RESULT
15
47
mos. 40 57 66 60 51
COllPLICATIONS
Died
F
M M M M M
DAY OF
DAY OF DIALYSIS
DAYS OF OLIGURIA
9
F
,....
Acute Renal Failure
....t:d
~..,
c:....; 0
76 20
lfl
2 26
p
14 6 7
0
to".!
~
to".! ~
Z
~
The Artificial Kidney in the Treatment of Renal Failure
..
1421
ACUTE RENAL FAILURE ETHYLENE GLYCOL INGESTION A.V.D. 821183 43 yrs, wI, mole
.....
DIALYSIS
DIALYSIS
800 700 ~
.c
600
v
N
";) 500 u
400
7
• 350
iI" E
~
..J
300
\ ,,\" '1" /I" 'I \'1.. ,~II,I
z
:ll
250
~
0::
:;:)
!!i 200
I
0
0 0
..J III
50
o
0
;.
!
in
4'"
~
,
o
30..
...............................
::E
:;:)
r.
2 ..... BUN -URINE OUTPUT --SERUM K+
, 0
... '
ill
:;:)
,,,',\ ', ,I
'.............
;
100
100
,,' '.." j ............. I"
c(
5 ~
,"I
,I
'v' I,
0::
..,z
..
6~ E
I,
... 400 0~ 200 ... .., 150 0300 :;:)
8
i
5
10
15
20
i
i
i
25
30
35
ffi
'"
0 40
DAYS
Fig. 2
ene glycol ingestion, survived after 26 days of oliguria and two dialyses (Fig. 2). Patients who were dialyzed and survived had an average age of 27 years. In those who succumbed, the average age was 45 years. COMPLICATIONS. The dominant role of complications in the clinical course of uremia was reaffirmed in this survey. Fifty per cent of the patients developed infection of some kind during their illness. In five patients the infection was major, e.g., pneumonia or septicemia, and contributed significantly to clinical morbidity. Two patients died as a direct result of infection. Other complications frequently seen were gastrointestinal bleeding, pulmonary edema, hypertension and anemia. DISCUSSION. The survival rate of 50 per cent in all cases of acute renal failure and 37 per cent in those which required dialysis parallels the experience reported by others.2 Duration of oliguria does not appear significa.nt in determining prognosis. The predialysis blood urea nitrogen was 40 per cent greater in patients who died, though prognosis did not in general appear related to the degree of nitrogen retention. Patients who died averaged 16 years older than those who survived, and the spectrum of distribution was broad in both groups.' The prognosis in acute tubular necrosis is related to the setting in which the disease develops. Cases which follow surgery or trauma have a poorer prognosis than those caused by eclampsia or ingestion of toxins. The survival was 50 per cent and 60 per cent in the two groups, a less marked difference than has been noted by others.3 The occurrence of infection as a complication in 50 per cent of patients is not as great as that in other series, and may be due in part to strict enforcement of isolation pre-
1422
REED
M.
NESBIT, JOSEPH C. CERNY
cautions. 4 The incidence of central nervous system complications and cardiac abnormalities is not of the magnitude described by others. Chronic Renal Failure Twenty-three patients were treated for chronic renal failure. Eight of them had chronic glomerulonephritis, five had ureteral obstruction, congenital or secondary to neoplasm, four suffered from chronic pyelonephritis and three had polycystic disease. There were single cases of bladder outlet obstruction with hydronephrosis, sclerosing pyelonephritis secondary to retrograde injection of sodium nitrite, and ureterosigmoid anastomosis for exstrophy of the bladder. Seventeen of the patients died in spite of treatment. DIALYSIS. Dialysis was performed in ten patients. Several received gratifying remission of clinical symptoms or electrolyte abnormalities. One patient is a 21 year old married woman with bilateral ureterosigmoid anastomosis who recently became pregnant and was delivered of a healthy infant, with no further deterioration of renal function; another is a 40 year old lawyer with polycystic disease who received prolonged remission of symptoms of hypertension following dialysis, and has subsequently returned to his practice. DISCUSSION. Indications for dialysis in this group of patients are less specific than in acute renal failure. To a great extent this is a matter of the philosophy of the individual physician. Patients in whom there exists the possibility of a superimposed acute process, either exacerbation of renal disease, infection or surgical disease, may be candidates for dialysis. In the latter instance, dialysis may be a valuable preoperative adjunct. Relief of intractable symptoms, such as nausea and vomiting, or recurrent convulsions, is often obtained. The hypertension and symptomatology of polycystic disease are sometimes markedly improved for prolonged periods of time. In centers where renal transplantation is performed, dialysis may be used to prepare the recipient optimally for operation. INVESTIGATIVE OPPORTUNITIES
The artificial kidney unit has provided an opportunity and stimulus for original investigation. Appraisal of the efficacy of indwelling vascular cannulae and of the subcutaneous arteriovenous shunt, particularly in reference to the MacNeill-Collins dialyzer, has been mentioned in previous paragraphs. Much of the initial laboratory and clinical evaluation of this dialyzer was carried out by members of our department in conjunction with Merrill's group in Boston. A similar appraisal of the Kolff apparatus was made four years ago. Recently, this combined effort has produced a commercially feasible pack for the MacNeill-Collins
The Artificial Kidney in the Treatment of Renal Failure
1423
kidney. We are presently evaluating the Fenwal ion exchange chamber in renal failure patients with uncontrollable hyperkalemia. Within the past year two infants, aged four months and one year, have been dialyzed using the Kolff apparatus and single coil. The four month infant was dialyzed twice, and is thought to be the youngest individual ever to undergo this procedure successfully. The necessary refinement of technique, particular problems encountered, and necessary precautions, have been described. SUMMARY
The successful development and management of an artificial kidney unit is an undertaking that imposes definite obligations and requirements upon those who are responsible for it. The mere acquisition of apparatus and pronouncement of willingness to perform hemodialysis is but a token beginning. This is a team project, headed by a physician especially trained in the problems of clinical renal disease, fluid and electrolyte therapy, and assessment of indications for hemodialysis. The team must include technical assistants who, like the physician, are available on a 24 hour basis. Closely allied laboratory facilities are necessary to appraise the many chemical aberrations of renal disease. Fully commensurate with the problems and obligations that accrue to a hemodialysis unit are the unique opportunities it provides for related investigative activity. The often lifesaving capabilities of this unit and its obvious contribution to the surrounding medical community are aspects which require no reiteration. Our experience with a series of cases of renal failure is presented, and a plan for clinical management described. The significance of age, duration of oliguria, nitrogen retention and complications in acute renal failure is discussed. The role of hemodialysis in both acute and chronic renal failure, its indications and results, has been outlined. REFERENCES 1. Bluemle, L. W., Webster, G. D. and Elkington, J. F.: Acute Tubular Necrosis. A.M.A. Arch. Int. Med. 104: 180-197 (Aug.) 1959.
2. Breakey, B., Reus, W. and Woodruff, M.: Technique for Dialysis of Infants. J. Urol. To be published. 3. Keleman, W. A. and Kolff, W. J.: Survey of Dialyses for Acute Renal Failure at Cleveland Clinic Hospital in 1958. Cleveland Clinic Quarterly 26: 227-234 (Oct.) 1959. 4. Kiley, J. E., Powers, S. and Beebe, R.: Acute Renal Failure. New England J. Med. 262: 481-486 (March) 1960. 5. Teschan, P. E., O'Brien, T. F. and Baxter, C. R.: Prophylactic Daily Hemodialysis in Treatment of Acute Renal Failure. Clin. Research 7: 280, 195H.