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Successful human kidney transplantation after six hours of cadaver organ preservation by mechanical ventricular assistance
Preliminary
SUCCESSFUL HUMAN AFTER SIX HOURS PRESERVATION VENTRICULAR
DAVID
B.
SKINNER, AND
G.
KIDNEY OF BY
M.D.,* MELVILLE
THE FOLLOWING CASE describes the use of mechanical ventricular assistance to preserve a human kidney in vivo for transplantation followed by immediate and satisfactory renal function.
METHOD The mechanical ventricular assistance device described by Anstadt, Schiff, and Baue consists of an outer cup and inner diaphragm bonded together at the apex and rim [2]. The cardiac ventricles are held within the cup by suction. Alternating positive and negative pneumatic pressures are delivered through a side-arm opening into the space between the outer shell and diaphragm to effect systole and diastole. The atria remain outside the device. From the Department of Surgery, The Johns Hopkins University School of Medicine, The Johns Hopkins Hospital, Baltimore, Maryland 21205. This research was supported by Grant HE-11831 ‘from the National Institutes of Health, Department of Health, Education, and Welfare. *John and Mary R. Markle Foundation Scholar in Medical Science. Submitted for publication Feb. 17, 1970.
Report
TRANSPLANTATION CADAVER ORGAN MECHANICAL ASSISTANCE
MARK WILLIAMS,
B.
ORRINGER,
M.D.,
M.D.*
CASE
REPORT
At 9:30 p.m., Jan. 18, 1970, a 32-year-old female was transferred to The Johns Hopkins Hospital having suffered a subarachnoid hemorrhage 24 hours previously. She had no history of renal disease, hypertension, or major illnesses. On arrival, she had no spontaneous respiration, and was maintained with a respirator. Despite vasopressors, systolic blood pressure was 46-60 mm. Hg, as it had been during the preceding day. Her pupils were fixed and dilated, and she had no response to noxious stimuli and no reflexes. Cardiac arrest occurred at lo:40 p.m. Despite closed chest cardiac massage, epinephrine, and sodium bicarbonate administration, no spontaneous cardiac action could be restored, and the patient was pronounced dead. Consent was obtained for renal transplantation, and the cadaver organ preservation team was notified. Closed chest cardiac massage was performed for 55 minutes during which there was no urine output. After the application of mechanical ventricular assistance (MVA), mean radial artery blood pressure ranged between 46-60 mm. Hg. Urine output was 85 cc. during the first hour of MVA, 185 cc. during the second 287
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hour, 77 cc. in the third hour, and 12 cc. in the fourth hour. Chemistries included a normal SUN and creatinine. Blood gases were monitored serially. The acidosis present when MVA was started, was initially corrected by sodium bicarbonate, and the pH was 7.48 2 hours later. The recipient, selected by tissue typing during #MVA, was a 46-year-old man who had received hemodialysis since October, 1968. He first experienced hematuria and the passage of calculi in 1963. A right nephrectomy was performed in Europe for a “tumor.” In 1968, the patient was hospitalized with uremia, anemia, and anasarca, and was treated with peritoneal dialysis and then with biweekly hemodialysis. In November, 1969, the polycystic left kidney was removed, and the patient was placed on the waiting list for a cadaver kidney transplant. He was called from his home and admitted to the hospital at 3:30 a.m. on Jan. 19. During the fifth hour of MVA, bilateral nephrectomies were performed in the donor,
6,
JUNE
1970
while the recipient was prepared for surgery. The device was removed from the donor at 4:30 a.m. In the standard fashion, the left donor kidney was transplanted to the right iliac fossa in the recipient. The total cold ischemit time was 2 hours. IMicroscopic evaluation of the donor’s right kidney which was not transplanted demonstrated good preservation, the only changes being reversible hydropic swelling in some tubules (Fig. 1). In the recovery room, the recipient’s hematocrit was 26%, serum creatinine 19 mg./lOO ml., and SUN 95 mg./lOO ml. He had an initial diuresis of 1000 cc. per hour for the first 3 hours, after which his urinary output stabilized at 70-100 cc. per hour. His postoperative course was entirely benign. By the fifth day, the serum creatinine was I.5 mg./lOO ml., and the SUN was 30 mg./lOO ml. These values remained constant (Fig. 2). Creatinine clearance 1 week after transplantation was 85 cc./ minute. The patient was maintained on immunosuppressive therapy using Imuran 150 mg. and prednisone 60 mg. a a day (3 mg./kg.)
Fig. 1. Photomicrograph of a biopsy from the kidney which was not transplanted. Hydropic SWelling of trlbules is the only abnormality noted in spite of the prolonged hypotension before death, closed chest card liac massage, 5 hours of MVA, and 2 hours of cold ischemia. (X145). 288
SKINNER
ET
AL:
HUMAN
KIDNEY
TRANSPLANTATION
SERUM CREATININE mg. %
URINARY PROTEIN mg. % 10,000 7
URINARY OUTPUT “‘24
HRS. Ol 0
I I
I 2
I 3
I 4 DAYS
I I I 5 6 7 POST-TRANSPLANT
I 8
I 9
1 IO
I II
I I2
Fig. 2. Parameters in the recipient in the first 12 days after transplantation. Good renal function is evidenced by the prompt fall in SUN and creatinine, and the steady level of urine output. Proteinuria, initially present in the transplanted kidney, cleared rapidly. day for the first week which was tapered a maintenance level of 30 mg. daily.
to
DISCUSSION The results in this case were much more satisfactory than those reported by Veith and colleagues who transplanted a human kidney preserved for 1% hours by closed chest massage and an additional 4 hours by MVA [7]. The kidney developed acute tubular necrosis and regained function slowly, This has been the only previous report describing MVA for cadaver organ preservation in humans. Although this initial clinical experience was not completely satisfactory, experimental evidence indicated that MVA was an effective means to preserve organs. Skinner, Anstadt, and Camp first demonstrated the use of MVA to preserve kidneys for transplantation in dog experiments [4]. Attai et al. employed this device to preserve dog kidneys, livers, and lungs for up to 8 hours prior to transplantation [3]. Tragus and colleagues reported satisfactory renal function during 4 hours of MVA in dogs [6].
Anstadt and Britz described successful maintenance of dogs for 24 and 36 hours by this method [ 11. Skinner, Newman, and Squire confirmed that MVA could support the entire organism for at least 24 hours in the majority of dog experiments, and offered anatomic and physiologic evidence that organs preserved for this period functioned well enough to warrant transplantation [S]. Microscopic study of kidneys preserved for 24 hours demonstrated no abnormalities in five of nine, and reversible hyaline droplet nephrosis in four kidneys. These findings were similar to those described in the preserved human kidney. In the case presented, the transplanted kidney was preserved for 6 hours in vivo using closed chest massage for the first four and mechanical ventricular assistance for 5 hours. After removal, it underwent 2 hours of cold ischemic time before transplantation. The use of MVA permitted tissue typing while blood flow to the kidney was maintained, permitted evaluation of urine function postmortem to ascertain renal viability, and allowed biochemical adjustments in the donor to insure optimal perfusion before kidney removal. 2%
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This approach was rewarded by prompt and excellent function of the transplanted kidney, and illustrated the effectiveness and applicability of this method in humans.
REFERENCES 1. Anstadt, G. L., and Britz, W. E., Jr. Continued studies in prolonged circulatory support by direct mechanical ventricular assistance. Trans. Amer. Sot. Artif. Intern. Organs 15:297-303, 1968. 2. Anstadt, G. L., Schiff, P., and Baue, A. E. Prolonged circulatory support by direct mechanical ventricular assistance. Trans. Amer. Sot. Artif. Intern. Organs 12:72, 1966. 3. Attai, L. A., Veith, F. J., Furman, S., Denize, A., Boley, S. J., Robinson, G., and Gliedman, M. L.
290
6,
JUNE
1970
Intracorporeal mechanical 19:202-203,
cadaver ventricular 1968.
organ preservation assistance. Surg. and Camp, ventricular 1967.
by Forum
4.
Skinner, D. B., Anstadt, G. L., Jr. Applications of mechanical tance. Ann. Surg. 166:500-512,
T. F., assis-
5.
Skinner, D. B., Newman, M. H., and Squire, R. A. Preservation and transplantation of dog organs maintained in vivo for 24 hours by mechanical ventricular assistance. J. Surg. Res. 10: 253-264, 1970. Tragus, E. T., Moore, J. R., Baue, A. E., and Blakemore, W. S. Mechanical cardiac massage for in vivo preservation of potential renal allografts. Trans. Amer. Sot. Artif. Intern. Organs 15:229-231, 1969. Veith, F. J., Dougherty, J. C., Attai, L., and Gliedman, M. L. Lung, liver and kidney preservation in transplantation. Transpl. Proc. 1:808-818, 1969.
SUCCESSFUL HUMAN AFTER SIX HOURS PRESERVATION VENTRICULAR
DAVID
B.
SKINNER, AND
G.
KIDNEY OF BY
M.D.,* MELVILLE
THE FOLLOWING CASE describes the use of mechanical ventricular assistance to preserve a human kidney in vivo for transplantation followed by immediate and satisfactory renal function.
METHOD The mechanical ventricular assistance device described by Anstadt, Schiff, and Baue consists of an outer cup and inner diaphragm bonded together at the apex and rim [2]. The cardiac ventricles are held within the cup by suction. Alternating positive and negative pneumatic pressures are delivered through a side-arm opening into the space between the outer shell and diaphragm to effect systole and diastole. The atria remain outside the device. From the Department of Surgery, The Johns Hopkins University School of Medicine, The Johns Hopkins Hospital, Baltimore, Maryland 21205. This research was supported by Grant HE-11831 ‘from the National Institutes of Health, Department of Health, Education, and Welfare. *John and Mary R. Markle Foundation Scholar in Medical Science. Submitted for publication Feb. 17, 1970.
Report
TRANSPLANTATION CADAVER ORGAN MECHANICAL ASSISTANCE
MARK WILLIAMS,
B.
ORRINGER,
M.D.,
M.D.*
CASE
REPORT
At 9:30 p.m., Jan. 18, 1970, a 32-year-old female was transferred to The Johns Hopkins Hospital having suffered a subarachnoid hemorrhage 24 hours previously. She had no history of renal disease, hypertension, or major illnesses. On arrival, she had no spontaneous respiration, and was maintained with a respirator. Despite vasopressors, systolic blood pressure was 46-60 mm. Hg, as it had been during the preceding day. Her pupils were fixed and dilated, and she had no response to noxious stimuli and no reflexes. Cardiac arrest occurred at lo:40 p.m. Despite closed chest cardiac massage, epinephrine, and sodium bicarbonate administration, no spontaneous cardiac action could be restored, and the patient was pronounced dead. Consent was obtained for renal transplantation, and the cadaver organ preservation team was notified. Closed chest cardiac massage was performed for 55 minutes during which there was no urine output. After the application of mechanical ventricular assistance (MVA), mean radial artery blood pressure ranged between 46-60 mm. Hg. Urine output was 85 cc. during the first hour of MVA, 185 cc. during the second 287
JOURNAL
OF
SURGICAL
RESEARCH
VOL.
10
NO.
hour, 77 cc. in the third hour, and 12 cc. in the fourth hour. Chemistries included a normal SUN and creatinine. Blood gases were monitored serially. The acidosis present when MVA was started, was initially corrected by sodium bicarbonate, and the pH was 7.48 2 hours later. The recipient, selected by tissue typing during #MVA, was a 46-year-old man who had received hemodialysis since October, 1968. He first experienced hematuria and the passage of calculi in 1963. A right nephrectomy was performed in Europe for a “tumor.” In 1968, the patient was hospitalized with uremia, anemia, and anasarca, and was treated with peritoneal dialysis and then with biweekly hemodialysis. In November, 1969, the polycystic left kidney was removed, and the patient was placed on the waiting list for a cadaver kidney transplant. He was called from his home and admitted to the hospital at 3:30 a.m. on Jan. 19. During the fifth hour of MVA, bilateral nephrectomies were performed in the donor,
6,
JUNE
1970
while the recipient was prepared for surgery. The device was removed from the donor at 4:30 a.m. In the standard fashion, the left donor kidney was transplanted to the right iliac fossa in the recipient. The total cold ischemit time was 2 hours. IMicroscopic evaluation of the donor’s right kidney which was not transplanted demonstrated good preservation, the only changes being reversible hydropic swelling in some tubules (Fig. 1). In the recovery room, the recipient’s hematocrit was 26%, serum creatinine 19 mg./lOO ml., and SUN 95 mg./lOO ml. He had an initial diuresis of 1000 cc. per hour for the first 3 hours, after which his urinary output stabilized at 70-100 cc. per hour. His postoperative course was entirely benign. By the fifth day, the serum creatinine was I.5 mg./lOO ml., and the SUN was 30 mg./lOO ml. These values remained constant (Fig. 2). Creatinine clearance 1 week after transplantation was 85 cc./ minute. The patient was maintained on immunosuppressive therapy using Imuran 150 mg. and prednisone 60 mg. a a day (3 mg./kg.)
Fig. 1. Photomicrograph of a biopsy from the kidney which was not transplanted. Hydropic SWelling of trlbules is the only abnormality noted in spite of the prolonged hypotension before death, closed chest card liac massage, 5 hours of MVA, and 2 hours of cold ischemia. (X145). 288
SKINNER
ET
AL:
HUMAN
KIDNEY
TRANSPLANTATION
SERUM CREATININE mg. %
URINARY PROTEIN mg. % 10,000 7
URINARY OUTPUT “‘24
HRS. Ol 0
I I
I 2
I 3
I 4 DAYS
I I I 5 6 7 POST-TRANSPLANT
I 8
I 9
1 IO
I II
I I2
Fig. 2. Parameters in the recipient in the first 12 days after transplantation. Good renal function is evidenced by the prompt fall in SUN and creatinine, and the steady level of urine output. Proteinuria, initially present in the transplanted kidney, cleared rapidly. day for the first week which was tapered a maintenance level of 30 mg. daily.
to
DISCUSSION The results in this case were much more satisfactory than those reported by Veith and colleagues who transplanted a human kidney preserved for 1% hours by closed chest massage and an additional 4 hours by MVA [7]. The kidney developed acute tubular necrosis and regained function slowly, This has been the only previous report describing MVA for cadaver organ preservation in humans. Although this initial clinical experience was not completely satisfactory, experimental evidence indicated that MVA was an effective means to preserve organs. Skinner, Anstadt, and Camp first demonstrated the use of MVA to preserve kidneys for transplantation in dog experiments [4]. Attai et al. employed this device to preserve dog kidneys, livers, and lungs for up to 8 hours prior to transplantation [3]. Tragus and colleagues reported satisfactory renal function during 4 hours of MVA in dogs [6].
Anstadt and Britz described successful maintenance of dogs for 24 and 36 hours by this method [ 11. Skinner, Newman, and Squire confirmed that MVA could support the entire organism for at least 24 hours in the majority of dog experiments, and offered anatomic and physiologic evidence that organs preserved for this period functioned well enough to warrant transplantation [S]. Microscopic study of kidneys preserved for 24 hours demonstrated no abnormalities in five of nine, and reversible hyaline droplet nephrosis in four kidneys. These findings were similar to those described in the preserved human kidney. In the case presented, the transplanted kidney was preserved for 6 hours in vivo using closed chest massage for the first four and mechanical ventricular assistance for 5 hours. After removal, it underwent 2 hours of cold ischemic time before transplantation. The use of MVA permitted tissue typing while blood flow to the kidney was maintained, permitted evaluation of urine function postmortem to ascertain renal viability, and allowed biochemical adjustments in the donor to insure optimal perfusion before kidney removal. 2%
JOURNAL
OF
SURGICAL
RESEARCH
VOL.
10
NO.
This approach was rewarded by prompt and excellent function of the transplanted kidney, and illustrated the effectiveness and applicability of this method in humans.
REFERENCES 1. Anstadt, G. L., and Britz, W. E., Jr. Continued studies in prolonged circulatory support by direct mechanical ventricular assistance. Trans. Amer. Sot. Artif. Intern. Organs 15:297-303, 1968. 2. Anstadt, G. L., Schiff, P., and Baue, A. E. Prolonged circulatory support by direct mechanical ventricular assistance. Trans. Amer. Sot. Artif. Intern. Organs 12:72, 1966. 3. Attai, L. A., Veith, F. J., Furman, S., Denize, A., Boley, S. J., Robinson, G., and Gliedman, M. L.
290
6,
JUNE
1970
Intracorporeal mechanical 19:202-203,
cadaver ventricular 1968.
organ preservation assistance. Surg. and Camp, ventricular 1967.
by Forum
4.
Skinner, D. B., Anstadt, G. L., Jr. Applications of mechanical tance. Ann. Surg. 166:500-512,
T. F., assis-
5.
Skinner, D. B., Newman, M. H., and Squire, R. A. Preservation and transplantation of dog organs maintained in vivo for 24 hours by mechanical ventricular assistance. J. Surg. Res. 10: 253-264, 1970. Tragus, E. T., Moore, J. R., Baue, A. E., and Blakemore, W. S. Mechanical cardiac massage for in vivo preservation of potential renal allografts. Trans. Amer. Sot. Artif. Intern. Organs 15:229-231, 1969. Veith, F. J., Dougherty, J. C., Attai, L., and Gliedman, M. L. Lung, liver and kidney preservation in transplantation. Transpl. Proc. 1:808-818, 1969.