Etiology, incidence, and prognosis of renal failure following cardiac operations

Volume 71, Number 3

MttVCH

1 9 7 6

The Journal of T H O R A C I C A N D

CARDIOVASCULAR

SURGERY

Etiology, incidence, and prognosis of renal failure following cardiac operations Results of a prospective analysis of 500 consecutive patients A prospective study of 500 consecutive patients surviving the first 24 hours following cardiac surgical procedures was undertaken to determine the prevalence, etiology and results of therapy for postoperative acute renal failure (ARF). Thirty-five patients developed either moderate or severe ARF and an additional 102 developed mild prerenal azotemia. Positive risk factors noted in the development of postoperative renal failure included age, elevated preoperative concentrations of blood urea nitrogen (BUN), serum creatinine, and decreased 24 hour urine creatinine clearance. The duration of cardiopulmonary bypass (CPB), aortic cross-clamping, and the total duration of the operation also closely correlated with the incidence of ARF. In the early postoperative period, clinical assessment of hemodynamic change was most helpful in predicting postoperative ARF. Significant negative risk factors included type of operation performed, New York Heart Association classification, the use of preoperative diuretic therapy, and associated other chronic illnesses. During the operation itself, the lowest and mean blood pressures, flow rates on CPB and the presence of hemoglobinuria failed to correlate with subsequent ARF. The mortality rate for established ARF was extremely poor (88.8 per cent), and there were no survivors among those requiring dialysis. ARF following cardiac surgery is a highly lethal complication which arises in a setting of inadequate cardiac function and is associated with a multiple organ system failure. Therapy of this postoperative complication, therefore, appears to be better directed toward its prevention rather than treatment once established.

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., Boston, Mass.

From the Surgical Cardiovascular Unit and Hyperalimentation Unit, General Surgical Services, Massachusetts General Hospital, and the Harvard Medical School, Boston, Mass. 02114. Supported in part by a grant from the McGaw Laboratories, Irvine, Calif. Received for publication May 9, 1975. *Present address: Department of Surgery, The New York Hospital— Cornell Medical Center, 525 East 68th Street, New York, N. Y. 10021.

A he onset of acute renal failure (ARF) following any surgical procedure portends a poor prognosis, not solely because of a loss of renal function per se, but also because of life-threatening complications of renal failure including sepsis, gastrointestinal hemorrhage, and central nervous system dysfunction.1,2 The over-all reported incidence of renal dysfunction follow323

3 24

Abel et al.

ing cardiac surgical operations varies from 0.1 per cent for operations performed under hypothermia alone3 to as high as 30.3 per cent in patients who underwent open procedures but in whom the diagnosis of renal failure was made only from a retrospective analysis of renal function studies.4 There are many difficulties, however, in determining the incidence and the etiology of renal failure in any retrospective analysis. Since the reported mortality rate of ARF following cardiac surgery is exceedingly high, 5-8 it is important to be able to predict those risk factors which might lead to the development of the acute uremic state and, hopefully, prevent its occurrence. The following study is a prospective analysis of patients consecutively operated upon at the Massachusetts General Hospital with a variety of cardiac illnesses. A simplified clinical classification of renal dysfunction was applied to characterize the degree of renal failure. Materials and methods The intent of the study was to evaluate a consecutive series of 500 patients undergoing cardiac surgical procedures (either open or closed). Patients who died either in the operating room or within the first postoperative day were excluded from the consecutive numbering. Data collection and analysis. Data were collected by a specially trained research assistant and were divided as follows: 1. Preoperative evaluation. This included the baseline clinical, hemodynamic, renal, and epidemiologic information. 2. Intraoperative information. These data were obtained with the aid of the anesthesiology and cardiopulmonary technical staffs. 3. Postoperative daily assessment. This included biochemical, hemodynamic, clinical, and renal evaluations which were recorded each day for the first 7 postoperative days. In patients who became azotemic, however, data were collected at least every seventh day thereafter. 4. Summary and discharge data. This information included clinical diagnosis of renal failure, mortality statistics, and incidence of complications. Information was entered from data collection forms into an on-line computer system. All data manipulation, retrieval, and analyses were performed by utilizing the MUMPS programing language.9 Statistical analyses were performed by means of either Student's t test or chi-square analysis, and a one-tailed p value was assigned. General patient management. Patients undergoing

The Journal of Thoracic and Cardiovascular Surgery

open operations usually received morphine anesthesia,10 moderate hemodilution, and hypothermia with the use of Ringer's lactate prime with bubble oxygenation. Diuretics were not routinely administered. Nearly all patients were monitored in the postoperative period with direct left atrial, intra-arterial, and central venous catheters. Pulmonary arterial catheters were employed when indicated. There was no specified protocol for the management of patients with incipient or established renal failure. Generally speaking, treatment of oliguria in the operating room was initiated by intravenous mannitol infusions. On occasion small doses of furosemide were also administered. No specific treatment for hemoglobinuria following cardiopulmonary bypass (CPB) was employed. The presence of oliguria in the immediate postoperative period was initially evaluated by determining urinary osmolarity and sodium and potassium concentrations. Cardiac output determinations by the indicator dye-dilution technique were obtained at regular intervals. Low cardiac output states in association with oliguria, hypotension, and/or acidosis were managed appropriately with cardiac pressor agents including isoproterenol, epinephrine, norepinephrine, or dopamine; use of intra-aortic balloon pumping (IABP) was dependent upon the specific hemodynamic insufficiency encountered. However, major emphasis in the management of patients with oliguria in the early postoperative period was placed on maintenance of cardiac output and, presumably, renal blood flow. This was done by maintaining left atrial filling pressures at an optimal level to produce a great enough cardiac output without the production of pulmonary edema to be reflected by a decrease in the alveolar-arterial oxygen gradient. In patients with postoperative systemic hypertension or with pronounced increases in systemic vascular resistance suggested by peripheral vasoconstriction and metabolic acidosis, intravenous infusions of nitroprusside were utilized. In patients with marked increases in pulmonary vascular resistance, vasodilating therapy was more often initiated with the use of phentolamine rather than nitroprusside. In cases of fixed oliguria or anuria which were unresponsive to augmentation of cardiac output, increased left atrial pressure, infusion of 50 mg. of mannitol intravenously, and the use of a "test" dose of furosemide of 100 to 200 mg. as a single bolus injection, a presumptive diagnosis of acute renal tubular necrosis (ATN) was entertained. Confirmatory evidence was hypothenuric urine and a high level of urinary sodium excretion. Although no definitive

Volume 71 Number 3 March, 1976

Renal failure after cardiac operations 3 2 5

Table I. Mortality rate as a function of renal failure following cardiac surgery Mortality rate Class

Lived

Died

(%)

I II III IV

360 93 13 2

3 11 4 16

0.8 10.6 23.5 88.8

than 2.5 mg. per 100 ml. and in whom no dialysis was required. Class III comprised patients with mild renal failure in whom serum creatinine never became greater than 5.0 mg. and who never required dialysis. Class IV included patients with severe acute renal failure (mostly ATN), in whom serum creatinine determinations peaked at greater than 5.0 mg. per 100 ml. or in whom dialysis became necessary for any indication noted previously. Results

treatment protocol was then applied in each instance of ATN, general treatment modalities included placement of a subclavian "lifeline" for the administration of intravenous essential 1-amino acids* and hypertonic dextrose as previously described11, 12. In the minority of patients able to take oral or nasogastric tube feedings, an oral preparation of essential 1-amino acids and adequate calories (Amin-Aid) was administered in isocaloric doses as would be given intravenously. In patients with good appetites who were willing to eat a modification of a normal hospital diet, a GiordanoGiovannetti type regimen13, u was administered limiting total protein intake to 40 Gm. per day. Additional supportive measures in patients with acute renal failure included the use of prophylaxis against complications of gastrointestinal hemorrhage by administration of aluminum-containing antacids and careful monitoring of the degree of gastrointestinal blood loss. Total fluid restriction was limited to the amount of nutritive solutions and to necessary antibiotics and cardioactive drugs. Indications for dialysis were individualized from patient to patient. The primary early indication for dialysis, however, was fluid overload and congestive heart failure. Late indications included an absolute level of blood urea nitrogen (BUN) from 125 to 150 mg. per milliliter with evidence of continued increases. No patient received dialysis because of hyperkalemia alone since this complication was not noted during adequate hyperalimentation therapy.15 Patient classification. For the purpose of data analysis, patients were segregated into four classes by degree of renal impairment: Class I included patients with normal renal function throughout the perioperative period. Serum creatinine concentrations never became greater than 1.5 mg. per 100 ml., and the patients never required dialysis. Class II comprised patients with mild azotemia whose serum creatinine never became greater *Kindly provided by the McGaw Laboratories, Irvine, Calif., as FreAmine E.

Within a 218 day period beginning Jan. 1, 1974, 538 major cardiac procedures were performed at the Massachusetts General Hospital. Thirty-five patients died either during the operative procedure or within the first 24 hours postoperatively. Three patients within this 7 month interval underwent a second cardiac procedure and, therefore, the list (Table I) of 500 patients includes 503 major procedures. There were 34 deaths in 500 patients for a mortality rate within this subgroup of 6.8 per cent. However, considering the entire consecutive series of 538 patients, the over-all mortality rate was 12.9 per cent. Of the 503 operations which constituted the study period, 474 (94.2 per cent) were performed with the aid of CPB. Patient distribution. The 500 patients included 296 men and 204 women with a mean age of 49.4 ± 0.74 (mean ± S.E.) years. Mortality differences in patients when classified by renal dysfunction were highly significant (p < 0.00025) (Table I). The types of surgical procedure performed segregated by postoperative renal dysfunction are presented in Table II. There are no significant differences in the over-all incidence of renal failure regardless of the type of operative procedure performed. Preoperative indicators. The exact cardiac diagnosis or New York Heart Association classification did not specifically correlate with postoperative renal failure other than by the obvious criteria: 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 did better-risk patients. For example, the differences in age relative to renal classification are more apparent when Classes II, III, and IV are compared to Class I (p < 0.0005) than when any other groupings are examined (Table III). Renal function as determined by the most immediate preoperative values of BUN, serum creatinine, and 24 hour urine creatinine clearance are presented in Table

The Journal of Thoracic and Cardiovascular Surgery

3 2 6 Abel et al.

Table II. Data on 503 consecutive operations by postoperative renal function Class (N o. ofpts.) Operation Aorta-coronary bypass graft operations Single graft Double grafts Three or more grafts Plus valve replacement Plus other procedures (VSD closure, LV aneurysm, 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.)

Deaths

I

II

Ill

IV

Total pts.

38 77 28 7 3

6 16 12 5 3

0 1 2 1 0

0 0 1 2 1

44 94 43 15 7

0 2 3 2 1

6 11 59 55 17 5 3 42

1 1 21 22 3 6 1 4

1 0 3 5 0 2 0 2

0 0 3 5 1 3 0 0

8 12 86 87 21 16 4 48

0 0 9 6 1 5 0 1

10 7 5 31

12

3

1

2

18

4

22

No.

%

2 1 13 14

2

Legend: VSD, Ventricular septal defect. LV, Left ventricular. MVR, Mitral valve replacement. AVR, Aortic valve replacement.

Table III. Patient age and postoperative renal failure Class

No.

Age (yr.)

S.D.

S.E.

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

IV. By all methods of statistical comparison, the degree of preoperative renal dysfunction statistically predicted the onset of renal failure in the postoperative period: That is, the differences in BUN and serum creatinine changes by Student's t test were significant at the 0.0005 level; the creatinine clearance was significant at the 0.01 level or less. In only 6 patients had a cardiac arrest occurred prior to the day of operation. Although 3 of these developed Class IV and one Class III disease, the numbers are too small to make a definitive statement. Even so, these findings may suggest an important preoperative risk factor. Twenty-three (4.6 per cent) patients required IABP support in the preoperative period. Although a slightly higher percentage of those patients developing renal failure required IABP support preoperatively, the duration of IABP did not correlate with the incidence of renal failure (Table V). The degree of preoperative hemodynamic disability

as determined either by formal cardiac catheterization or by measurements in an intensive care unit were highly significant predictors of the postoperative renal failure (Table VI). In comparing either normal patients with all who developed some degree of renal dysfunction (Class I versus Classes II, III, and IV) or patients having developed ARF with all other patients (Class IV versus Classes I, II, and III) (vide supra), the results were highly significant. The changes in pulmonary capillary wedge and left ventricular end-diastolic pressures were less prominent than right-sided pressures or cardiac index itself. A history of preoperative intake of possible nephrotoxins did not correlate with the development of postoperative renal failure. That is, the use of radiographic contrast material, aminoglycoside or other potentially nephrotoxic antibiotics, and other commonly used potential nephrotoxins was not more common in Classes III and IV versus Classes I and II. Although diuretic therapy was utilized in all 35 patients developing either moderate or severe renal failure (Classes III and IV), only 239 of 467 patients (51.2 per cent) with no or little renal impairment postoperatively (Classes I and II) received any diuretics in the preoperative period. The most commonly used of the diuretics noted were the thiazides, either alone or in combination with spirolactone and furosemide. The history of chronic renal disease (3 of 35 patients in Classes III and IV compared to no patients in Classes

Volume 71 Number 3 March, 1976

Renal failure after cardiac operations 3 2 7

Table IV. Preoperative renal function: Influence on development of postoperative renal failure Class

BUN(mg.llOOml. ± S.D. ± S.E.)

I 11 HI IV

14.9 ± 4.9 ± 0.3 20.5 ± 12.5 ± 1.2 29.3 ±21.7 ± 5 . 3 39.1 ± 34.5 ± 8.1

Serum creatinine (mg. 1100 ml. ±S.D. ± S.E.) 1.08 1.31 1.38 2.03

±0.25 ±0.34 ±0.54 ± 2.04

±0.01 ±0.03 ±0.13 ± 0.48

Creatinine clearance (ml. 124 hr. ±S.D. ± S.E.) 105.8 84.8 79.2 74.1

±41.7 ± 34.6 ±43.4 ±36.4

±2.4 ± 3.6 ± 13.1 ± 10.5

Legend: BUN, Blood urea nitrogen.

Table V. Incidence and duration of preoperative intra-aortic balloon pumping (IABP) Class I II III IV

No. of patients

Per cent of total patients

11 7 2 3

3.0 6.7 11.8 16.7

Hours of IABP preop. {mean ± S.E.) 62A 79.4 11.8 31.5

± 19.6 ±31.7 ±6.8 ±21.2

I and II) and the history of a previous cardiac operation (6 of 35 patients in Classes III and IV [17.1 per cent] compared with 41 of 467 patients in Classes I and II [8.8 per cent]) were associated with a higher incidence of postoperative ARF. Diabetes mellitus, significant hypertension, arteriosclerotic peripheral vascular disease, old cerebral vascular accident, or chronic obstructive pulmonary diseases were not significant risk factors. Correlations based upon intraoperative data collection. Severe hypotension or an arrhythmia in the induction room or the operating room required emergency institution of cardiopulmonary bypass in 12 patients prior to the predicted "elective" timetable of performing the intended operation. Two of these procedures occurred in Class IV patients, but these differences were not significant because of the small numbers involved. In 38 of the 503 total procedures (7.6 per cent) the operation was classified as a true emergency. Fourteen of these emergency patients were in Class III and IV (40 per cent), compared to only 24 (5.1 per cent) of the remaining patients. There were no significant differences in the degree of renal dysfunction with regard to the anesthetic agent used (morphine, halothane, Penthrane, Innovar, or diazepam). The total duration of the operation and time of aortic cross-clamping correlated well with postoperative renal failure, as did several hemodynamic variables during CPB (Table VII). For example, comparing the mean duration of bypass of all Class I patients (93.5 ± 2.3 minutes) with the duration of bypass of all other

patients (Classes II, III, and IV) (123.2 ± 4.3 minutes) shows that these changes are statistically significant (p < 0.0005). The 335.5 ± 9.6 minutes of total operating time in patients in Classes II, III, and IV as compared with that in Class I patients is also significant (p < 0.0005). For procedures requiring aortic cross-clamping, a mean of 47.0 ± 2.0 minutes was required in Class I patients as compared with 57.4 ± 3.0 minutes in Class II, III, and IV patients (p < 0.0025). These figures presumably suggest that more complicated intracardiac procedures and those with associated technical difficulties requiring a longer total duration of operating time were associated with the development of ARF. The degree of hypothermia utilized, mean blood pressure during CPB, lowest blood pressure recorded on CPB, and mean flow rates during perfusion did not correlate, however, with the degree of renal dysfunction in the postoperative period. The mean blood pressure recorded in the operating room immediately prior to transfer to the intensive care unit was a significant predictor of renal dysfunction (Table VII). The latter changes were significant at least at the 0.025 level, but they were more highly significant (p < 0.0005) when the Class IV patients were compared with all others. The volume of urine measured in the operating room either during CPB or for the duration of the operation from bypass to skin closure did not correlate with the incidence of postoperative ARF. When comparing Class I patients (i.e., normal) to all other patients, however, the pre-CPB urinary volumes were substantially greater than those in all other patients. That is, the mean urinary volume in Class I was 174.4 ± 12.4 ml. compared with 119.1 ± 9.8 ml. in Classes II, III and IV (p < 0.005). No other group comparison for pre-CPB urinary volumes were statistically significant. Of the 474 patients operated upon with the aid of CPB, 35 (7.4 per cent) required IABP in order to be weaned from bypass, as has previously been described.16 Seven of these 35 patients developed Class IV and 3 developed Class III disease. The requirement

The Journal of Thoracic and Cardiovascular Surgery

3 2 8 Abel et al.

Table VI. Preoperative hemodynamic measurements and postoperative renal failure Pressure determination (mm. Hg ± S.E.) Class I II III IV

Mean RAP

Mean PAP

4.6 5.0 8.8 7.3

26.1 25.7 38.2 36.1

± ± ± ±

0.2 0.6 6.6 1.6

± ± ± ±

1.0 2.0 7.1 3.8

Mean PCWP 16.5 17.6 21.0 21.0

± ± ± ±

0.6 1.2 2.7 2.3

Cardiac index (L.lmin.lsq.

LVEDP 11.7 13.3 16.9 17.2

± ± ± ±

0.5 0.9 2.6 2.3

2.62 2.45 2.18 2.09

± ± ± ±

M. ± S.E.)

0.06 0.11 0.35 0.15

Legend: RAP, Right atrial pressure. PAP. Pulmonary artery pressure. PCWP. Pulmonary capillary wedge pressure. LVEDP. Left ventricular end-diastolic pressure.

for IABP in the operating room was significantly greater, therefore, in patients who developed postoperative failure (p < 0.005). The occurrence of hemoglobinuria following open cardiac operations was infrequent. In only 24 did instances of either "moderate" or "marked" hemoglobinuria occur, and these did not correlate with the development of postoperative ARF. The frequency of mannitol and furosemide usage intraoperatively was compared with postoperative renal dysfunction. There was a significantly higher incidence of furosemide administration in patients in Classes III and IV compared to Classes I and II. Sixteen of 35 patients developing moderate or severe ARF (45.7 per cent) compared with only 82 of the remaining patients with little or no renal failure (17.6 per cent) received this potent, tubular-active diuretic (x2 = 21.64, p < 0.0005). However, analysis of mannitol usage demonstrated no significant differences. Administration of the three most commonly used cardiac pressor agents (isoproterenol, norepinephrine, and epinephrine) was evaluated to determine any relationship with subsequent renal failure. On the other hand, 4 patients in Classes HI and IV received high doses of epinephrine (greater than 3 mm. per minute). Only 11 and 6 patients, respectively, received these doses in the much larger Classes I and II. Daily hemodynamic, metabolic and pharmacologic assessments. Twenty-nine patients sustained a cardiac arrest within the first postoperative week. This event was noted more frequently in patients with postoperative ARF than in patients with normal renal function—8 of 18 patients in Class IV (44 per cent) compared with only 7 of 364 Class I patients (2 per cent) who had sustained a cardiac arrest and were successfully resuscitated. Daily hemodynamic variables continued to correlate with renal dysfunction as they had in the preoperative period. There was a direct relationship between the

degree of hemodynamic impairment and renal function (Table VIII). IABP was employed in 50 patients, and this frequency was significantly greater in Class IV patients than in the others (Table VIII). However, the over-all duration of postoperative IABP usage was not significantly different from group to group. Mean 24 hour urinary volumes, when segregated by classes, were not significant determinants of renal dysfunction (Fig. 1). That is, the degree of oliguria did not correlate with either the serum creatinine or the BUN changes. In patients who remained normal (i.e., Class I), the maximum recorded BUN occurred on the fourth postoperative day (Table IX). The more severe the renal failure, the longer the duration of azotemia. Mannitol was infrequently used in the postoperative period. Only 18 patients received the drug within the first 24 hours and, although there was a slightly higher use of this drug in Class IV patients between the first and third postoperative days, this was most often utilized as a "test" drug. The use of furosemide, however, did significantly differ from class to class when analyzed by either total dose given or by the absolute frequency of drug administration (Fig. 2). The over-all use of the drug appeared to peak by the first 24 to 48 hours postoperatively. Thereafter, in patients with moderate or severe renal failure (Classes III and IV), furosemide was rarely given. In patients without renal failure, however, furosemide usage in low doses continued at a somewhat decreasing frequency for the first postoperative week. The absolute incidence of drug usage in patients who eventually developed renal failure was significantly higher than in those who continued to have normal renal function. Norepinephrine was infrequently used in the postoperative period (24 patients on the first postoperative day in the entire group of patients). There did not appear to be a significant correlation between the use of

Volume 71 Number 3 March, 1976

Renal failure after cardiac operations 3 2 9

\ Uj

1400

?>

1300


1200

3 1000

OPERATION

2 3 TIME (days)

o

OPERATION

1 TIME

(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 5 postoperative days.

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

this agent and the subsequent development of renal failure. Epinephrine, on the other hand, did receive wide utilization (94 patients on the first postoperative day). A higher percentage of Class III and IV patients received epinephrine during the first 3 postoperative days, and this incidence bore an inverse relationship to the differences in cardiac index and pulmonary capillary wedge pressure noted above. For example, 12 of the 18 Class IV patients (66.7 per cent) received epinephrine within the first 24 hours following operation, compared with only 33 of 365 Class I patients (9.0 per cent). The use of isoproterenol paralleled the use of norepinephrine and epinephrine, since patients in both Class III and Class IV appeared to have a slightly higher drug usage, particularly between the first and third postoperative days. Therefore, no specific catecholamine agent could be incriminated as having a direct causative influence on the development of renal failure, as opposed to its need for cardiovascular support in patients with already established poor hemodynamic states. Postoperative complications and results of therapy. Postoperative complications occurred at a relatively greater frequency in patients with poorer renal function (Table X). Specifically, respiratory insufficiency, pulmonary infection, and gastrointestinal hemorrhage occurred more commonly in patients in Classes III and IV. Six of 18 Class IV patients (33 per

cent) sustained excessive postoperative hemorrhage requiring re-exploration, compared to an over-all incidence of 30 patients with this complication in the entire group of 500 patients (6.0 per cent) and an incidence of only 15 patients (4.1 per cent) in Class I (Table XI). Treatment of renal failure. Fifteen patients (by definition, all Class IV) required dialysis. Twelve of these underwent peritoneal dialysis alone, one had hemodialysis alone, and 2 were treated by both modalities. There were no survivors among the 15 patients requiring dialysis. That is, the only 2 survivors in Class IV were these whose renal failure was not severe enough to require dialysis. A total of 40 patients received hyperalimentation therapy during the course of the postoperative period. Fourteen of 18 Class IV patients received hyperalimentation therapy with the solution of essential 1-amino acids and hypertonic dextrose. There were no complications directly attributable to hyperalimentation therapy. Discussion Much of the interest and controversy surrounding the problem of ARF following cardiac surgery has centered upon the influences of CPB itself in altering renal function. The problem of ARF following closed cardiac procedures differs little from that noted in general surgical patients. 17-19 That is, acute renal

The Journal of Thoracic and Cardiovascular Surgery

3 3 0 Abel et al.

Table VII. Hemodynamic, time, and renal variables during 503 operations: Correlations with postoperative renal failure

Class I II III IV

Duration of CPB (mean min. ± S.E.)

Total duration of operation (mean min. ± S.E.)

93.5 120.2 113.6 148.7

271.5 330.5 312 386.5

± 2.3 ± 4.4 ± 11.1 ± 7

Duration aorta cross-clamped (mean min. ± S.E.)

± 4.7 ± 10.3 ±27.7 ± 34.6

29.2 40.4 47.8 64.4

Mean blood pressure during (mm. Hg ± mean ± S.E.)

± 1.7 ± 3.3 ± 10.4 ± 9.5

76.8 78.4 73.9 76.1

± ± ± ±

0.5 1.0 2.5 2.1

Lowest blood pressure recorded during CPB (mm. Hg ± S.E.) 56.9 57.4 55.9 53.8

± ± ± ±

0.6 1.1 2.2 3.1

Mean flow rates during CPB (L.lmin.l sq. M. ± S.E.) 2.33 2.30 2.37 2.44

± ± ± ±

Last mean arterial blood pressure recorded in operating room (mm. Hg ± S.E.)

0.02 0.3 0.07 0.08

122.5 122.3 112.1 105.6

± 0.9 ± 1.8 ± 6.3 ±4.2

Legend: CPB. Cardiopulmonary bypass.

Table VIII. Hemodynamic assessments in first postoperative week versus renal classification IABP

Class I II III IV

Highest mean RAP* (mm. Hg ± S.E.) 19.4 23.9 24.9 31.3

± ± ± ±

0.3 0.6 1.6 1.6

Highest mean PCWP* (mm. Hg ± S.E.) 21.6 25.6 29.6 31.9

± ± ± ±

0.4 1.0 2.3 1.9

Lowest cardiac index* (L.lmin.l sq. M. ± S.E.) 2.75 2.21 2.29 2.14

± ± ± ±

0.08 0.08 0.31 0.18

Lowest systolic arterial blood pressure* (mm. Hg. ± S.E.) 87.4 77.1 69.3 62.9

± ± ± ±

0.6 1.4 3'.5 3.5

No. of patients 17 20 4 9

Duration postop. (days) 3.4 5.0 4.0 5.7

± 0.5 ± 0.4 ± 1.4 ±0.8

* Figures were derived as follows: Seven consecutive daily values for each patient in the first postoperative week were averaged. The group means representing the patient average per week are represented. All differences between Class I versus II, III. and IV and between Classes I and II versus III and IV are highly significant (p < 0.0005).

tubular necrosis usually occurs following a period of prolonged hypotension with resulting nephron ischemia and a diminution in renal cortical blood flow.20 Prerenal etiologies such as renal vascular disease (either embolic or thrombotic) and postrenal causes (including obstructive disease) account for a much smaller percentage of patients seen on a cardiac surgical service. The over-all incidence in patients undergoing closed cardiac procedures, either for congenital or acquired heart disease, is extremely small in this and in other series reported. The effects of extracorporeal circulation on renal hemodynamics and urinary output have been well studied. 21-23 A gradual reduction in para-amino hippurate (PAH) extraction, noted in dogs subjected to periods of long and short perfusion, correlated with diminution of renal blood flow to as great as 65 per cent of pre-perfusion levels.21 Renal blood flow and PAH extraction decreased in a linear relationship with time and then became more markedly diminished beyond 120 minutes. The results of the present report parallel these observations, since the incidence of renal failure appears to correlate directly with the duration of CPB, as had also been previously reported from retrospective studies. 5 ' 6 * 24 In the present report, however, we were

unable to confirm statistically that hypotension during CPB or the magnitude of perfusion flow rates were significant in predicting the degree of renal dysfunction in the postoperative period, as had been reported from large retrospective series. 6-8 ' 24, 25 Although Grismer and colleagues26 concluded from a prospective analysis of 37 patients that neither perfusion rates nor length of perfusion were directly related to renal dysfunction, data specifically relating perfusion hemodynamics to postoperative renal function were not available. Although previous investigators reported maintenance of renal plasma flow during perfusion with either mannitol or dextran27 or maintenance of total renal blood flow with intraoperative furosemide,28 other recent studies have denied the "protective" influences of these diuretic agents.6 Indeed, the use of these agents tended to correlate directly with the degree of renal failure in the postoperate period, although in many instances the drug was administered because of already established oliguria in an attempt to "test" whether true ARF was present. There was little significant hemoglobinuria in the present series of patients. This is undoubtedly due to the shorter perfusion times currently required to

Renal failure after cardiac operations 3 3 1

Urinary volumes (ml. ± S.E.)

Prior to CPB

During CPB

174.4 122.6 83.6 124

462.3 421.2 382.6 270.8

± 12.4 ±11.1 ± 19.8 ±34.1

± 26.3 ±36.6 ± 90.8 ± 57.3

Following CPB 368.5 393.4 306 256

± 20.5 ± 47.2 ± 97.4 ±67.3

perform corrective open-heart surgery in this era and due to alterations and improvements in the technical management of CPB. Unlike previous investigators,3' 24, 25 we were unable to relate the degree of hemoglobinuria to the subsequent development of renal failure. Therefore, we do not support the suggestion of others that "prophylactic" mannitol therapy in highrisk patients is indicated because of the possibility that the drug will promote a diuresis of hemoglobinuric urine.5 Doberneck,8 Yeboah,6 and their associates reported an increased incidence of ARF with more complex intraoperative procedures, including repair of tetralogy of Fallot and multiple valve replacement. Although diagnosis and specific type of procedure did not correlate with postoperative ARF, our results are more in line with the retrospective analysis reported by Yeh and co-workers24 in concluding that the common factor of importance was total length of perfusion rather than the type of operation itself. Regarding other preoperative predictors of ARF, the most significant correlative features were age, preoperative renal failure, and poorer hemodynamics on preoperative catheterization. That these features are significant is not surprising, since the final common influence is similar: a lower than normal glomerular filtration rate, even prior to operation, either as a result of pre-existing renal disease or because of an absolute decrease in cardiac index, which would result in a prerenal etiology of a decrease in glomerular filtration rate. No patient was operated upon in a state of already established ARF. The fact that even mild preoperative chronic renal failure was associated with an exceedingly high incidence of postoperative ARF and that the over-all mortality rate for patients developing ARF following cardiac surgery was exceedingly high suggest that the presence of severe renal dysfunction,

particularly anuric ARF, should contraindicate cardiac surgical intervention. It is difficult to incriminate specifically the use of large doses of furosemide or other potent diuretics as etiologic factors in causing postoperative ARF. Although the pre- and immediate postoperative use of these drugs was significantly greater in Classes III and IV, these are the very patients in whom two usual indications exist. In patients with poor cardiac output and elevated left atrial pressures, a decrease in alveolar-arterial oxygen gradient with increasing requirements for a higher inspired oxygen content, despite use of positive end-expiratory pressure to maintain a Pao2 within reasonable range, often requires the use of potent diuretic agents in order to decrease the amount of pulmonary interstitial water. Additionally, with the onset of postoperative oliguria, frequently large doses of furosemide had been given to "test" whether or not renal tubular function was present. The use of furosemide neither statistically altered the over-all urinary volume in any group of patients intraoperatively or postoperatively nor appeared to have any beneficial effects. Thus we must conclude that the routine use of this agent in the postoperative period to treat oliguria alone is not indicated. Furthermore, since there is evidence that furosemide administration may be associated with accelerated renal failure in the presence of contracted blood volume28 and that the administration of the drug in combination with potentially nephrotoxic antibiotics may result in a worsening state of renal failure,29 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.30 That is, despite an apparent increase in renal blood flow or redistribution of renal blood flow toward the cortex,31 there appears to be little or no beneficial clinical manifestation, particularly during low cardiac output states following cardiac surgery. It is interesting that the rate of urinary flow did not correlate with the degree of renal dysfunction in the first postoperative week. BUN and serum creatinine, rather than urinary volume, appeared to be more important predictors of renal dysfunction. The use of cardiac pressor agents did not adversely influence renal function other than by the obvious indirect relationship by which patients with low cardiac output states and, therefore, poor renal blood flow have a greater requirement for these agents for circulatory support. Similarly, the isolated use of IABP did not appear to be

332

The Journal of Thoracic and Cardiovascular Surgery

Abel et al.

Table IX. Maximum postoperative BUN following cardiac surgery

Class I II

in

IV

BUN (mg. 1100 ml. 20.2 38.9 69.1 121.5

± ± ± ±

changes in

Table XI. Secondary (noncardiac) required in postoperative period

Postoperative day of peak BUN elevation (days ±S.E.)

±S.E.) 0.4 2.3 6.5 9.0

4.3 5.9 11.8 12.2

procedures

Class

±0.1 ± 0.5 ± 3.2 ± 1.9

Table X. Late postoperative complications following 503 cardiac surgical procedures Class Complication

/

II

///

IV

Total

Respiratory insufficiency Pulmonary sepsis Wound infection Wound dehiscence Mediastinitis Gastrointestinal hemorrhage Urinary tract infection Cerebrovascular accident Major psychiatric disturbances Major arrhythmias (excluding atrial fibrillation) Complete heart block Bacteremia

3 8 8 1 1 1 31 9 11 60

7 15 4 0 0 1 17 8 7 35

1 5 1 0 0 1 6 0 3 6

13 9 1 0 2 9 2 2 1 8

24 38 14 1 3 12 56 19 22 109

3 2

5 3

2 0

1 7

11 12

an etiologic factor with regard to renal failure. However, since so many of the patients who eventually developed renal failure had low cardiac output states requiring IABP, a much higher percentage of these patients developed Class III or IV disease. The dismal results of treatment of patients with established acute tubular necrosis following cardiac surgery are disappointing but not unexpected. They are similar in many respects to those for anuric patients following ruptured abdominal aortic aneurysms. 12, 33 Although all patients were treated with the most aggressive therapy available for ARF, including early dialysis when indicated and total parenteral nutrition, 11, 12 15 ' none of the patients with renal failure severe enough to require dialysis survived. The extremely high mortality rates in Classes 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 the thirty-five deaths was ARF incriminated as a direct cause of death. The majority were cardiac, respiratory, or septic etiologies.

Operation

I

II

III

IV

Total

Exploration for hemorrhage Tracheostomy Laparotomy (usually for gastrostomy)

15

7

2

6

30

3 2

7 6

4 4

14 6

28 18

We would like to express appreciation to Mrs. Cynthia Franklin, Research Assistant of the Hyperalimentation Unit, for her diligent data collection and analysis; to the members of the Resident and Visiting Staff of the Department of Anesthesiology for aiding in data collection; to Eric Skinner and Penny Prather of the Laboratory of Computer Sciences for data programming; and to Doris Clarke of the Cornell Medical College for aid in manuscript preparation.

REFERENCES

1 Montgomerie, J. Z., Kalmanson, G. M., and Guze, L. B.: Renal Failure and Infection, Medicine (Baltimore) 47: 1, 1968. 2 Stott, R. B., Ogg, C. S, Cameron, J. S., et al.: Why the Persistently High Mortality in Acute Renal Failure, Lancet 2: 75, 1972. 3 Krian, A., Bircks, W., and Wetzels, E.: Das akute Nierenversagen nach operationen am Herzen und an den groben thorakalen GefaBen, Thoraxchirugie 20: 199, 1972. 4 Abel,R. M., Wick, J., Beck, C. H., Jr., Buckley, M. J., and Austen, W. G.: Renal Dysfunction Following Open Heart Operations, Arch. Surg. 108: 175, 1974. 5 Porter, G. A., Kloster, F. E., Herr, R. J., Starr, A., Griswold, H. E., and Kimsey, J.: Renal Complications Associated With Valve Replacement Surgery, J. THORAC. CARDIOVASC. SURG. 53: 145,

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Volume 71 Number 3 March, 1976

Renal failure after cardiac operations

11 Abel, R. M., Beck, C. H., Jr., Abbott, W. M., Ryan, J. A., Jr., Barnett, G. O., and Fischer, J. E.: Improved Survival From Acute Renal Failure After Treatment With Intravenous Essential 1-Amino Acids and Glucose: Results of a Prospective Double-Blind Study, N. Engl. J. Med. 288: 695, 1973. 12 Abel, R. M., Abbott, W. M., Beck, C. H., Jr., Ryan, J. A., and Fischer, J. E.: Essential 1-Amino Acids for Hyperalimentation in Patients With Disordered Nitrogen Metabolism, Am. J. Surg. 128: 317, 1974. 13 Giordano, C : Use of Exogenous and Endogenous Urea for Protein Synthesis in Normal and Uremic Subjects, J. Lab. Clin. Med. 63: 231, 1963. 14 Giovannetti, S., and Maggiore, Q.: A Low Nitrogen Diet With Proteins of High Biological Value for Severe Chronic Uraemia, Lancet 1: 1000, 1964. 15 Abel, R. M., Abbott, W. M., and Fischer, J. E.: Intravenous Essential 1-Amino Acids and Hypertonic Dextrose in Patients With Acute Renal Failure: Effects on Serum Potassium, Phosphate and Magnesium, Am. J. Surg. 123: 632, 1972. 16 Buckley, M. J., Craver, J. M., Gold, H. K., Mundth, E. D., Daggett, W. M., and Austen, W. G.: Intra-aortic Balloon Assist for Cardiogenic Shock After Cardiopulmonary Bypass, Circulation V. 47, 48: 90, 1973 (Suppl. III). 17 Berne, T. V., and Barbour, B. H.: Acute Renal Failure in General Surgical Patients, Arch. Surg. 102: 594, 1971. 18 Marshall, V. C : Acute Renal Failure in Surgical Patients, Br. J. Surg. 58: 17, 1971. 19 Hollenberg, N. K., Adams, D. F., Oken, D. E., Abrams, H. L., and Merrill, J. P.: Acute Renal Failure Due to Nephrotoxins, N. Engl. J. Med. 282: 1329, 1970. 20 Dobrin, R. S.: Management of Acute Renal Failure, Drug Ther. 2: 39, 1972. 21 Moghissi, K., Machell, E. S., and Munday, K. A.: Changes in Renal Blood Flow and PAH Extraction During Extracorporeal Circulation of Short and Long Duration: Experimental Study in Dogs, Cardiovasc. Res. 3: 37, 1969. 22 Connolly, J. E., Kountz, S. L., Guernsey, J. M., and Stemmer, E. A.: Acidosis as a Cause of Renal Shutdown During Extracorporeal Circulation: Its Correction by the Use of THAM, J. THORAC. CARDIOVASC. SURG. 46:

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23 Porter, G. A., Kloster, F. E., Herr, R. J., Starr, A., Griswold, H. E., Kimsey, J., and Lenertz, H.: Relationship Between Alterations in Renal Hemodynamics During Cardiopulmonary Bypass and Postoperative Renal Function, Circulation 34: 1005, 1966. 24 Yeh, T. J., Brackney, E. L., Hall, D. P., and Ellison, R. G.: Renal Complications of Open-Heart Surgery: Predisposing Factors, Prevention, and Management, J. THORAC. CARDIOVASC. SURG. 47: 79,

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25 Brunner, L., Heisig, B., Scheler, F., Stapenhorst, K., Tauschke, D., Baumgarten, C , Hoffmeister, H. E., Kirchhoff, P. G., Rastan, H., Regensburger, D., Stunkat, R., de Vivie, R., and Koncz, J.: Die Ursachen des akuten Nierenversagens nach Herz-LungenMaschinen-Operationen, Thoraxchirurgie 20: 26, 1972. 26 Grismer, J. T., Levy, M. J., Lillehei, R. C , Indeglia, R., and Lillehei, C. W.: Renal Function in Acquired Valvular Heart Disease and Effects of Extracorporeal Circulation, Surgery 55: 24, 1964. 27 Kahn, D. R., Cerny, J. C , Lee, R. W. S., and Sloan, H.: The Effect of Dextran and Mannitol on Renal Function During Open-Heart Surgery, Surgery 57: 676, 1965. 28 Ufferman, R. C , Jaenike, J. R., Freeman, R. B., Pabico, R. C , and Drikstein, C. D.: Effects of Furosemide in Experimental Acute Renal Failure, Clin. Res. 21: 711, 1973. 29 Lawson, D. H., Macadam, R. F., Singer, H., Gavras, H., Harty, S., Turnbull, A., and Linton A. H.: Effect of Furosemide on Antibiotic-Induced Renal Damage in Rats, J. Infect. Dis. 126: 593, 1972. 30 Engelman, R. M., Gouge, T. H., Smith, S. J., Stahl, W. M., Gombos, E. A., and Boyd, A. D.: The Effect of Diuretics on Renal Hemodynamics During Cardiopulmonary Bypass, J. Surg. Res. 16: 268, 1974. 31 Birtch, A. J., Zakheim, R. M., Jones, L. G., and Barger, A. C : Redistribution of Renal Blood Flow Produced by Furosemide and Ethacrynic Acid, Circ. Res. 21: 869, 1967. 32 Tilney, N. L., Bailey, G. L., and Morgan, A. P.: Sequential System Failure After Rupture of Abdominal Aortic Aneurysms, An Unsolved Problem in Postoperative Care, Ann. Surg. 178: 117, 1973. 33 Abbott, W. M., Abel, R. M., Beck, C. H., Jr., and Fischer, J. E.: Renal Failure After Ruptured Aneurysm, Arch. Surg. 110: 1110, 1975.