Acute postoperative renal failure in cardiac surgical patients

JOURNAL

Acute

OF SURGICAL

RESEARCH

Postoperative

20,

341-348 (1976)

Renal

Failure

in Cardiac

Surgical

Patients’

RONALD M. ABEL,M.D?, MORTIMER J. BUCKLEY, M.D., W. GERALD AUSTEN, M.D., G. OCTO BARNETT, M.D., CLYDE H. BECK, JR., M.D., AND JOSEF E. FISCHER, M.D. Surgical Cardiovascular and Hyperalimen tation Units, General Surgical Services, Department of Nephrology, Medical Service, and the Laboratory of Computer Sciences, Massachusetts General Hospital and the Harvard Medical School, Boston, Massachusetts 02114 Submitted for publication November 20,197s

The onset of acute renal failure (ARF) following any surgical procedure portends a poor prognosis not solely due to the loss of renal function per se, but also to lifethreatening complications of renal failure including sepsis, gastrointestinal hemorrhage, and central nervous system dysfunction [15, 181.The overall reported incidence of renal dysfunction following cardiac surgical operations varies from 0.1% for operations performed under hypothermia alone [13] to as high as 30.3% in patients undergoing open procedures but in whom the diagnosis of renal failure was made by a retrospective analysis of renal function studies [5]. There are many difficulties, however, in determining the incidence and etiology of renal failure in any retrospective analysis. Since the reported mortality of ARF following cardiac surgery is exceedingly high [B, 9, 16, 191 it is important to be able to predict those risk factors which might lead to the development of the acutely uremic state. The following study presents the results of a prospective analysis of patients operated upon consecutively at the Massachusetts General Hospital for a variety of cardiac diseases. A simplified clinical classification of the degree of renal dysfunction was applied

to characterize the incidence and degree of renal failure, common factors which might be able to predict future difficulties with renal function, and the results of treating renal failure following cardiac surgery. MATERIALS

AND METHODS

Patient Population

The intent of the study was to evaluate a consecutive series of 500 patients undergoing cardiac surgical procedures (either opened or closed). Patients who died either in the operating room or within the first postoperative day were excluded from the consecutive numbering. Claskjication

of Patients

For the purposes of data analysis and determining etiologic factors leading to the development of abnormal renal function following cardiac surgery, patients were segregated into four classes according to the following definitions: Class I, patients with normal renal function throughout the perioperative period. Serum creatinine concentrations never became greater than 1.5 mg/lOO ml and at no time required dialysis. Class II, patients with mild azeotemia but whose serum creatinine never became greater than 2.5 mg/lOO ml and in whom no ‘Supported in part by a grant from the McGaw Labo- dialysis was required. Class III, patients with ratories, Irvine, California. mild renal failure but in whom serum 2Address reprint requests to: Ronald M. Abel, M.D., creatinine never became greater than 5.0 Department of Surgery, The New York HospitalCornell Medical Center, 525 East 68th Street, New mg/ 100 ml and never required dialysis. Class York, New York 10021. IV included patients with severe acute renal 341

Copyright o 1976by Academic Press, Inc. All rights of reproduction in any form reserved.

342

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Mortality

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TABLE 1 and Renal Function

Class

Lived

Died

Total patients

I II III IV

360 93 13 2

3 11 4 16

363 104 17 18

% Mortality 0.8 10.6 23.5 88.8

failure (mostly ATN)3, in whom serum creatinine determinations peaked at greater than 5.0 mg/lOO ml or in whom dialysis became necessary for any indication.

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1976

the overall mortality was 12.9%. Of the 503 operations which constituted the study period, 445 (93.9%) were performed utilizing the cardiopulmonary bypass (CBP). Distribution

of Patients

The 500 patients included 296 males and 204 females. The mean age was 49.4hO.74 (mean&SE) years. The distribution of patients by classification of renal disease is shown in Table 1. The mortality differences by Chi-square analysis were highly significant (P
RESULTS During the 218 day interval reported, there were 538 major cardiac procedures performed at the Massachusetts General Hospital. Thirty-five patients succumbed either during the operative procedure or within the first 24 hr postoperatively. Three patients within this seven month interval underwent a second cardiac procedure and, therefore, the list of 503 operations was performed on 500 total patients. There were Preoperative Evaluation The exact cardiac diagnosis or New York 34 deaths in 500 patients for a mortality within this subgroup of 6.8%, but considering Heart Association classification did not the entire consecutive series of 538 patients, specifically correlate with postoperative Type of Operation Operation Aortocoronary bypass graft operations Single graft Double Graft Three or more grafts Plus valve replacement Plus other procedures (VSD closure, LV aneurysms, etc.) Closed mitral commissurotomy Open mitral commissurotomy MVR AVR MVR + AVR Other valve procedures Operations on thoracic aorta Total correction of congenital heart defect Miscellaneous (pericardial operations, left ventricular myotomy, etc.) 3ATN-Acute

tubular necrosis.

TABLE 2 by Renal Classification

(No. Patients)

I

II

III

IV

Total pts.

38 77 28 7

6 16 12 5

0 1 2 1

0 0 1 2

44 94 43 15

0 2 (2%) 3 (7%) 2 (13%)

3 6 11 59 55 17 5 3 42

3 1 1 21 22 3 6 1 4

0 1 0 3 5 0 2 0 2

1 0 0 3 5 1 3 0 0

7 8 12 86 87 21 16 4 48

1(14%) 0 0 9 (10%) 6 (7%) 1 (5%) 5 (31%) 0 1 (2%)

12

3

1

2

18

4 (22%)

Mortality

ABEL

ET AL.:

ACUTE

POSTOPERATIVE

TABLE 3 Age and Postoperative Renal Failure Class

No. Pts.

Age (yrs)

SD

SE

I II III IV

363 104 17 18

47.1 55.5 51.9 57.6

17.0 12.1 22.9 8.3

0.9 1.2 5.6 2.0

renal failure other than by the obvious: older patients, those with poorer preoperative hemodynamics, those with bona fide cardiovascular emergencies requiring immediate operations, and those with preoperative renal dysfunction tended to develop postoperative ARF at a higher prevalence than better risk patients. For example, the differences in age relative to renal classification are most apparent when comparing Classes II, III, and IV to Class I (P< O.OOOS), then when examining any other groupings (Table 3). Renal function as determined by the most immediate preoperative values of BUN, serum creatinine, and 24-hr urine creatinine clearance are presented in Table 4. The degree of preoperative renal dysfunction consistently predicted the onset of renal failure in the postoperative period. (The differences for BUN and serum creatinine by Student’ r-test were significant at the 0.0005 level and for creatinine clearance, significant at the 0.01 level or less). Of other clinical features in the preoperative history only the presence of chronic renal disease three of 35 patients in Classes III and IV compared to no patients in Classes I and II and the history of a previous cardiac operation (six of 35 patients in Classes III and IV) (17.1%) compared with 41 of 467 patients in Classes I and II (8.8%) were significantly different. Diabetes

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FAILURE

mellitus, significant systemic hypertension, arteriosclerotic peripheral vascular disease, old cerebral vascular accident or chronic obstructive pulmonary disease did not differ significantly in its prevalence among the four classesof renal dysfunction. The degree of hypothermia utilized, mean blood pressures during cardiopulmonary bypass, lowest blood pressure recorded during cardiopulmonary bypass and mean flow rates during perfusion did not correlate with the degree of renal dysfunction in the postoperative period (Tables 5, 6). The mean blood pressure recorded in the operating room immediately prior to transfer to the Intensive Care Unit did correlate, however, with the prevalence of renal dysfunction (Table 7). The latter changes were significant at least the 0.025 level but were more highly significant (P
TABLE 4 Preoperative Renal Function Class I II III IV

BUN (mg/lOO ml) (+ SD k SE) 14.9 20.5 29.3 39.1

t + + +

4.9 12.5 21.7 34.5

+ f + f

0.3 1.2 5.3 8.1

Serum creatinine (mg/lOO ml f SD k SE) 1.08 1.31 1.38 2.03

* * + t

0.25 0.34 0.54 2.04

f f * +

0.01 0.03 0.13 0.48

Creatinine clearance (ml/24 * SD + SE) 105.8 84.8 79.2 74.1

?: 41.7 ? 34.6 t 43.4 t 36.4

f f + k

2.4 3.6 13.1 10.5

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1976

TABLE 5 Hemodynamic Measurements

Preoperative Pressure determination (mm Hg f SE) Class I II III IV

RA (mean) 4.6 5.0 8.8 7.3

PCW (mean)

PA (mean)

A 0.2 k 0.6 * 6.6 + 1.6

26.1 25.7 38.2 36.1

k f k k

1.0 2.0 7.1 3.8

16.5 17.6 21.0 21.0

f f f i

Cardiac index (liter/min/Mz r SE)

LVEDP

0.6 1.2 2.7 2.3

11.7 13.3 16.9 17.2

* f f i

0.5 0.9 2.6 2.3

2.62 2.45 2.18 2.09

+ i + i

Tricuspid regurgitation (#of patients)

0.06 0.11 0.35 0.15

1 2 0 3

*Severity judged as “4+” on scale l-4.

TABLE 6 Time and Renal Variables during 503 Operations

Hemodynamic,

Class

Duration of cardiopulmonary bypass (CPB) (mean min f SE)

I II III IV

Class I II III IV

93.5 r 120.2* 113.6 + 148.7 f

2.3 4.4 11.1 7

Lowest blood pressure recorded during CPB (mmHg ?: SE) 56.9 57.4 55.9 53.8

f f + *

Total duration of operation (mean min * SE)

.6 1.1 2.2 3.1

271.5 330.5 312 386.5

Mean flow rates during CPB (L/min/Ma f SE) 2.33 2.30 2.37 2.44

+ f c +

Class I II III IV

19.4 23.9 24.9 31.3

f + f f

0.3 0.6 1.6 1.6

4.7 10.3 27.7 34.6

122.5 122.3 112.1 105.6

A t t i

.9 1.8 6.3 4.2

21.6 25.6 29.6 31.9

f i f +

0.4 1.0 2.3 1.9

78.8 78.4 73.9 76.1

f .5 f 1.0 t 2.5 i 2.1

Urinary Volumes (ml * SE) prior to CPB 174.4 122.6 83.6 124

A 12.4 t 11.1 f 19.8 ?r 34.1

TABLE 7 Assessments during First Postoperative

Highest mean pulmonary capillary wedge pressure (mm Hg f SE)

Mean blood pressure during (CPB) (mean mmHg c SE)

29.2* 1.7 40.4 f 3.3 47.8 ?r 10.4 64.4 c 9.5

Last mean arterial blood pressure recorded in operating room (mmHg ?: SE)

.02 0.3 .07 .08

Hemodynamic Highest mean right atrial pressurea (mm Hg f SE)

f + + *

Duration aorta cross-clamped (mean min i SE)

during CPB 462.3 421.2 382.6 270.8

f * f r

0.08 0.08 0.31 0.18

26.3 36.6 90.8 57.3

368.5 393.4 306 256

CPB ?: 20.5 ?: 47.2 i 97.4 f 67.3

Week

Lowest cardiac index (liter/min/Ma t SE) 2.75 2.21 2.29 2.14

f r f f

following

Lowest systolic arterial blood pressure (mm Hg * SE) 87.4 77.1 69.3 62.9

f f + r

0.6 1.4 3.5 3.5

QFigures are derived as follows: Seven consecutive daily values for each patient for the first postoperative week were obtained and averaged. The group means representing the patient average per week are represented. The difference between Class I vs II, III, and IV, Classes I and II vs III and IV, Classes I, II, and III vs IV are all highly significant (F’ < 0.0005).

ABEL ET AL.: ACUT ‘E POSTOPERATIVE

RENAL FAILURE

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1600 Z E

1500-

; $

1400

F : :

1300-

g

1200-

6 $

IIOO1000 -

Opemlton

I

2 Postoperallve

3

4

5

days

FIG. 1. Urinary output in the postoperative period following 503 cardiac procedures. There are no statistically significant differences between the four classifications of renal function at any time within the first five postoperative days.

failure (17.6%) received this potent, tubularactive diuretic (X2 = 21.64, P
Correlations

The mean 24-hr urinary volume when segregated by classes was not a determinant of the degree of renal dysfunction. (Fig. 1) In patients who remained normal (i.e., Class I), the maximum recorded BUN occurred on the fourth postoperative day (Table 8). The TABLE 8 Maximum Postoperative BUN Changes Following Cardiac Surgery

Class I II III IV

BUN (Mg/l OOmlf SE)

Postoperative day of peak BUN elevation (days * SE)

20.2 * 0.4 38.9 * 2.3

4.3 * 0.1 5.9 * 0.5

69.1 * 6.5 121.5 f 9.0

11.8 ?: 3.2 12.2 * 1.9

more severe the renal failure, the longer the duration of azotemia and this was even more marked in Class IV with true ARF (Table 8). Mannitol was infrequently used in the postoperative period. Only 18 patients received the drug within the first 24 hr postoperatively. There is a slightly higher incidence of usage of this drug in Class IV patients between the first and third postoperative days, but this was most often utilized as a “test” drug. The use of furosemide did differ from class to class when analyzed by either total dose given or by the absolute frequency of drug administration. The incidence of furosemide utilization is depicted in Fig. 2. The overall use of the drug appeared to peak by the first 24 to 48 hr postoperatively. In patients without renal failure drug usage continued at a somewhat decreasing frequency for thefirst postoperative week. The absolute incidence of drug usage in patients who eventually developed renal failure was significantly higher than those who remained with normal renal function (Fig. 2). Treatment ofRena

Failure

Fifteen patients (by definition, all Class IV) required dialysis. Twelve of these under-

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Postoperotlve

day5

FIG. 2. Furosemide administration in the postoperative period. Within the first two postoperative days furosemide usage varied directly with the degree of eventual renal dysfunction although a direct relationship could not be established.

perfusion by the administration of either mannitol or dextran [12] or of total renal blood flow by the use of intraoperative furosemide [lo]. More recent studies have denied the “protective” influences of these diuretic agents [ 191.Indeed, the use of these agents tended to correlate in an inverse way with the degree of renal failure in the postoperative period, although in many instances the drug was administered because of already-established oliguria in an attempt to “test” whether or not true acute renal failure was present. It is difficult to specifically incriminate the use of large doses of furosemide or other DISCUSSION potent diuretics as etiologic factors in causThe result of the present study parallels ing postoperative ARF. Although the pre and the observations of previous investigators immediate postoperative use of these drugs that the incidence of renal failure appears to was significantly greater in Classes III and correlate directly with the duration of cardio- IV, these are the very patients in whom two pulmonary bypass [16, 19, 201. We were not “usual” indications exist. In patients with able, however, to confirm whether hypoten- poor cardiac output and elevated left atria1 sion during cardiopulmonary bypass nor the pressures, a decrease in alveolar-arterial absolute flow rates on perfusion were im- oxygen gradient with increasing requireportant in predicting the degree of renal dys- ments for a higher inspired oxygen content function in the postoperative period as had despite positive end-expiratory pressure to been previously reported in groups reviewed maintain a PaO, within reasonable range retrospectively [7,8,9, 19,201. often requires the use of potent diuretic Diuretic therapy was not routine during or agents in order to decrease the amount of immediately after cardiopulmonary bypass. pulmonary interstitial water. Additionally, Other investigators had suggested with the onset of postoperative oliguria, maintenance of renal plasma flow during frequently large doses of furosemide had went peritoneal dialysis alone, one hemodialysis alone and two both modalities. There were no survivors amongst the 15 patients requiring dialysis. That is, the only two survivors in Class IV were those whose renal failure was not severe enough to require dialysis. A total of 48 patients received hyperalimentation therapy during the course of the postoperative period. All 18 Class IV patients received hyperalimentation therapy, 14 of which received the solution of essential l-amino acids and hypertonic dextrose as previously described [2,3,4].

ABEL

ET AL.: ACUTE

POSTOPERATIVE

been given to “test” whether or not renal tubular function was present. Based upon the observation that the use of furosemide neither statistically altered the overall urinary volume in any group of patients intraoperatively or postoperatively nor did it appear to have any beneficial effects, we must conclude that the routine use of this agent put in the postoperative period to treat oliguria alone is not indicated. Furthermore, since there is evidence that the administration of the drug in the presence of established ATN may result in a worsening state of renal failure [14] there appears to be no justification for its use in the perioperative period for the purposes of augmenting urinary volume alone. This recommendation is notwithstanding the known increases in renal blood flow which can be recorded following furosemide administration [lo]. That is, despite an apparent increase in renal blood flow or redistribution of renal blood flow towards the cortex [6], there appears to be little or no beneficial clinical manifestations particularly during low cardiac output states following cardiac surgery. The dismal results of treatment of patients with established acute tubular necrosis following cardiac surgery are disappointing but not unexpected [5]. They parallel similar results reported from this institution [l], and elsewhere [17] for patients with anuria following ruptured abdominal aortic aneurysms. Although all of the patients were treated with the most aggressive forms of therapy for ARF currently used, including early dialysis when indicated, total parenteral nutrition [2, 3, 41 none of the patients with renal failure severe enough to require dialysis survived. Indeed, the only two survivors in Class IV were amongst the three who did not require dialysis and presumably had a milder form of acute renal failure. The extremely high mortality rates in Class III and IV are primarily due to multiple organ failure as a consequence of inadequate cardiac function. Germane to this issue is the additional fact that in only two of

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347

the 35 deaths was acute renal failure incriminated as a direct cause of death, whereas the majority were cardiac, respiratory, or septic etiologies. SUMMARY AND CONCLUSION A prospective study of 500 consecutive patients surviving the first 24 hr following cardiac surgical procedures was undertaken to determine the prevalence, etiology and results of therapy of acute postoperative renal failure. Thirty-five patients developed either moderate or severe renal failure and an additional 104 developed mild prerenal azotemia. Positive risk factors in the ultimate development of postoperative renal failure included age, operations involving the tricuspid valve, elevated preoperative concentrations of BUN and serum creatinine and decreased 24 hour urine creatinine clearance. Additionally, patients who had sustained preoperative cardiac arrest and those with poorer hemodynamics had a higher incidence of postoperative renal failure. During the operation itself, the total duration of perfusion and of aortic crossclamping and the duration of the operation correlated well with the development of postoperative renal failure. In the early postoperative period, the hemodynamic state of the patients was the most important single predictor of postoperative renal failure. The use of furosemide in the early postoperative period also correlated with the subsequent development of renal failure, although a cause and effect relationship could not be established. Significant negative risk factors included type of operation performed independent of the duration noted above, New York Heart Association classification, the use of diuretic therapy, and associated other chronic illnesses. During the operation the lowest and mean blood pressures and the flow rates on cardiopulmonary bypass did not correlate with subsequent renal failure nor did the incidence or degree of hemoglobinuria. The use of furosemide in the early postoperative period for the single indication

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des akuten Nierenversagens nach Herz-Lungenof maintenance of urinary volume appeared Maschinen-Operationen. Thoruxchirurgie 20:26-37, not to be beneficial and potentially harmful. 1972. The mortality rate for established severe 8. Cameron, J. S., Trounce, J. R. Acute renal failure renal failure was extremely poor (88.8%) and after surgery using cardiopulmonary bypass. Dethere were no survivors amongst those partment of Medicine, Guy’s Hospital, London, pp. 7-9. requiring dialysis. Acute renal failure occuring in the post- 9. Doberneck, R. C., Reiser, M. P., Lillehei, C. W. Acute renal failure after open-heart surgery utilizoperative period is a highly lethal complicaing extracorporeal circulation and total body perfution which arises in a setting of inadequate sion. J. Thorac. & Cardiovas. Surg. 43:44&452, cardiac function and is associated with a 1962. multiple organ system failure. The proper 10. Engelman, R. M., Gouge, T. H., Smith, S. J., Stahl, W. M., Gombos, E. A., Boyd, A. D. The effect of role of treatment of this post-operative comdiuretics on renal hemodynamics during plication appears to be better directed cardiopulmonary bypass. J. Surg. Res. 16:268-279, towards prevention of low flow states result1974. ing in acute tubular necrosis rather than 11. Grismer, J. T., Levy, M. J., Lillehei, R. C., Indeglia, R. Renal function in acquired valvular heart disease treatment of the complication once it is esand effects of extracorporeal circulation. Surgery tablished.

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3. Abel, R. M., Beck, C. H., Jr., Abbott, W. M., Ryan, J. A., Jr., Barnett, G. O., Fischer, J. E. Improved survival from acute renal failure after treatment with intravenous essential l-amino acids and glucose: results of a prospective double-blind study. N. Engl. J. Med. 288:695-699, 1973. 4. Abel, R. M., Abbott, W. M., Beck, C. H., Jr., Ryan, J. A., Fischer, J. E. Essential l-amino acids for hyperalimentation in patients with disordered nitrogen metabolism. American J. Surg. 128: 317-323,1974.

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55:24-41,1964. 12. Kahn, D. R., Cerny, J. C., Lee, R. W. S., Sloan, H. The effect of dextran and mannitol on renal function during open-heart surgery. Surgery 57:676-679, 1964. 13. Krian, A., Bircks, W., Wetzela, W. Das akute Nierenversagen nach operationen am Herzen und an den groben thorakalen GefaRen. Thorax-chirurgia 20:199-217, 1972. 14. Lawson, D. H., Macadam, R. F., Singh, H., Gavras, H., Hartz, S., Turnbull, D. and Linta, A. L. Effect of furosemide on antibiotic induced renal damage in rats. J. Infectious Dis. 126:593, 1972. 15. Montgomerie, J. Z., Kalmanson, G. M., Guze, L. B. Renal failure and infection. Medicine, (Baltimore) 47:1-32, 1968. 16. Porter, G. A., Kloster, F. E., Herr, R. J., Starr, A., Griswold, H. E., Kimsey, J. Renal complications associated with valve replacement surgery. J. Thorac. & Cardiovasc. Surg. 53:145-152, 1967. 17. Tilney, N. L., Bailey, G. L., Morgan, A. P. Sequential system failure after rupture of abdominal aneurysm. An unsolved problem in postoperative care. Ann. Surg. 178:117, 1973. 18. Stott, R. B., Ogg, C. S., Cameron, J. S., et al. Why the persistently high mortality in acute renal failure. Lance12:75-79,1972.

19. Yeboah, E. D., Petrie, A., Pead, J. D. Acute renal failure and open heart surgery. British Med. J. 1:415-418, 1972.

20. Yeh, T. J., Brackney, E. L., Hall, D. P., Ellison, R. G. Renal complications of open-heart surgery: predisposing factors, prevention, and management. J. Thorac. & Cardiovasc. Surg. 47~79-97, 1964.