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J Thorac Cardiovasc Surg 1994;107:1489-1495
© 1994 Mosby, Inc.


CARDIOPULMONARY BYPASS,
MYOCARDIAL MANAGEMENT, AND SUPPORT TECHNIQUES

Acute renal failure in the patient undergoing cardiac operationPrevalence, mortality rate, and main risk factors

Giorgio Zanardo , MDa, Paolo Michielon , MDa, Agostino Paccagnella , MDa, Paolo Rosi , MDa, Mauro Caló , MDa, Valeria Salandin , MDa, Antonia Da Ros , MDa, Federica Michieletto , b, Giuseppe Simini , MDa


Treviso, Italy

Received for publication March 25, 1993. Accepted for publication Aug. 30, 1993. Address for reprints: Giorgio Zanardo, MD, 2° Servizio di Anestesia, Ospedale S. Maria dei Battuti, 31100 Treviso, Italy.

Abstract

A total of 775 consecutive patients who survived the first 24 hours after cardiac operation were prospectively studied to assess the prevalence, mortality rate, and main risk factors for development of new acute renal failure. Normal renal function before operation (serum creatinine level less than 1.5 mg/dl) was registered in 734 (94.7%) patients. Of these, 111 (15.1%) showed a postoperative renal complication including 84 (11.4%) classified as renal dysfunction (serum creatinine level between 1.5 and 2.5 mg/dl) and 27 (3.7%) as acute renal failure (serum creatinine level higher than 2.5 mg/dl). The mortality rate was 0.8% in normal patients, 9.5% in patients with renal dysfunction, and 44.4% when acute renal failure developed ( p < 0.0001). Indeed, the renal impairment proved to be an independent predictor of mortality ( p < 0.001), along with the infective ( p < 0.001), gastrointestinal ( p < 0.001), and cardiovascular ( p < 0.05) complications. Multivariate analysis identified the following variables as independent risk factors for postoperative renal impairment: use of intraaortic balloon pump ( p < 0.0001), need for deep hypothermic circulatory arrest ( p < 0.005), low-output syndrome ( p < 0.005), advanced age ( p < 0.005), need for emergency operation ( p < 0.025), and low urinary output during cardiopulmonary bypass ( p < 0.05). The 41 patients (5.3%) with preoperative renal failure showed a significantly higher morbidity and mortality rate than those without renal complications before operation. We conclude that in patients undergoing cardiac operation without preexisting renal dysfunction the likelihood of severe renal complications is reasonably low, but the associated mortality remains high. A prominent role in the development of postoperative acute renal failure must be recognized for preoperative, intraoperative, and postoperative hemodynamic factors, whereas cardiopulmonary bypass seems to be of lesser importance in this respect. (J THORAC CARDIOVASC SURG 1994;107:1489-95)

The patient undergoing a major surgical procedure is at risk for the development of postoperative acute renal failure (ARF). This is especially true for cardiac operations, which are considered to involve more risk than other types of operations because of the use of extracorporeal circulation and the higher likelihood of cardiovascular instability during and after the intervention.Go 1 The major concern is that the occurrence of postoperative ARF is still associated with a high mortality rate, ranging from 24% to 70%.Go Go 2-16 From the results of earlier epidemiologic investigations the multifactorial pathogenesis of ARF is evident.Go Go 2-7 Thus in the past years a number of studies, using multivariate statistical analysis, have been done to define the risk factors for ARF development, as well as the independent predictors of death in patients with renal complications.Go Go 8-16 Nevertheless, owing to the large number of different ARF classifications used, a comparative evaluation of the results (in terms of prevalence and mortality) is difficult and the clinical factors that have been found in correlation with ARF are often quite different from one study to another.

This study was undertaken to evaluate the prevalence, the mortality rate, and the main risk factors for ARF development in a surgical population without preoperative renal dysfunction.

METHODS

From January 1, 1989, to December 31, 1990, we studied prospectively 787 consecutive adult patients who underwent cardiac operation with total cardiopulmonary bypass (CPB). Patients who died within the first 24 hours after the operation (minimum time required for laboratory assessment of renal function) were excluded from the study. Because we were interested in new ARF (prevalence, mortality rate, and main risk factors) we performed a multivariate statistical analysis with data of patients with preoperative serum creatinine values of less than 1.5 mg/dl. Data for the remaining patients, that is, those with preoperative renal impairment, were analyzed univariately with regard to the outcome (morbidity and mortality rate).

In every patient the following variables, selected from the literature, were taken into account:

Before operation
Age, sex, hemodynamic status (cardiac catheterization), previous cardiac operation, emergency intervention, renal function (normal/altered, acute/chronic).

During operation
Type of intervention done, CPB duration, mean flow rates and blood pressures during CPB, use of deep hypothermic circulatory arrest (DHCA), level of hemodilution during CPB, need for diuretic therapy, CPB urinary volume, total intraoperative urinary output, and inotropic support requirement at the end of CPB or at the end of operation.

After operation
Need for inotropic therapy, use of intraaortic balloon pump (IABP), occurrence of complications, renal function, need for dialysis, duration of intensive care unit (ICU) stay, and survival or death after 24 hours from ICU admission.

During operation, electrocardiographic lead II and arterial pressure, via a radial artery catheter, were monitored continuously. After induction of anesthesia, a central vein catheter was inserted.

CPB was managed with nonpulsatile perfusion. A crystalloid priming solution (25 ml/kg) with mannitol supplementation (0.5 gm/kg) was used. Systemic flow was targeted at 2.2 L/min/m 2 and was varied according to the venous return to maintain a mean arterial pressure of about 60 ± 10 mm Hg. These variables were registered every 5 minutes during CPB.

During operation, diuretic therapy was administered when the urinary output fell below 0.5 ml/kg/hr, notwithstanding an adequate hemodynamic status. In the postoperative period patients with urinary output below 0.5 ml/kg/hr for at least 6 hours were considered to have oliguria. In such cases diuretic therapy followed optimization of cardiac output and filling pressures.

The adequacy of the hemodynamic status during operation and in the ICU was evaluated on the basis of inotropic drug administration: the patients who received dopamine or dobutamine, or both, in a dosage of more than 8 µg/kg/min, or epinephrine or isoproterenol were considered as having a low-output state (LOS). In the ICU this definition was accepted only when these therapies were required for longer than 4 hours.

IABP therapy was used when the pharmacologic treatment of the LOS failed to restore a satisfactory cardiac performance.

DHCA was done in 17 patients with type I dissecting aneurysm to allow aortic arch repair. The range of DHCA duration was 7 to 31 minutes (mean 21 ± 7 minutes). All these patients received dopamine 3 to 4 µg/kg/min before and after DHCA to minimize ischemic renal impairment.

Hemodilution was calculated as being the difference between the hemoglobin value before CPB and the value measured 10 minutes after the infusion of the first dose of cardioplegic solution.

Antibiotic prophylaxis was done in all patients: cefazolin 1 gm was administered intravenously every 6 hours, with the first dose given before skin incision. We considered as a septic complication the clinical situation in which further antimicrobial drugs were requested in addition to cefazolin or in substitution for it. The discontinuation of cefazolin because of allergic reactions or because of the development of renal complications was excluded from this definition.

Respiratory complications were considered as the necessity for prolonged postoperative mechanical ventilation (more than 24 hours) or the need for reintubation because of a primitive lung failure, that is, after exclusion of the main extrapulmonary complications that may potentially affect respiratory function or the ventilatory management (major arrhythmias, cardiac failure, central neurologic disorders, massive bleeding, reoperation).

Neurologic complications were defined as the occurrence of major cerebral damage causing hemiplegia or coma.

Enteric complications comprised clinical situations such as gastrointestinal bleeding, mesenteric infarction, or bowel occlusion diagnosed by means of endoscopic evaluation or abdominal operation.

Postoperative renal function was classified on the basis of the peak serum creatinine level as follows: class I, serum creatinine level less than 1.5 mg/dl, normal renal function; class II, serum creatinine level 1.5 to 2.5 mg/dl, renal dysfunction; and class III, serum creatinine level greater than 2.5 mg/dl, ARF.

In patients in class II, the diagnosis was confirmed by supporting criteria to avoid erroneous classifications, especially when the serum creatinine level was near to the normal limits. For this purpose we used the endogenous creatinine-clearance, water-reabsorption tests (urine/serum ratio of urea, creatinine, osmolality; free-water clearance) and the sodium-reabsorption tests (fractional excretion of sodium).Go 17 These diagnostic tests allowed us to validate in every patient the peak serum creatinine classification, so as to confirm its usefulness in a large epidemiologic trial. Indeed, such tests were also used to do a daily monitoring of the renal function in patients with postoperative renal impairment (classes II and III).

Mortality rate refers to death in the ICU after postoperative hour 24.

The patients were informed about the purpose of the study and gave oral consent. The study was approved by the Human Investigation Committee of our institution.

Each preoperative, intraoperative, and postoperative variable listed earlier herein was compared among the three classes of renal function by the {chi} 2 test for homogeneity and the one-way analysis of variance, with significance at p = 0.05. Only the variables that attained significance were included in the further analysis.

The second step in analysis consisted of fitting a logit model to relate the probability of ARF occurrence to the other attributes of the patients, in a regression-like way. The stepwise procedure was used to select the significant attributes, with p = 0.05.

Furthermore, a separate multiple linear regression analysis was done to investigate the relative influence of each postoperative complication on mortality rate.

RESULTS

Twelve patients died within the first 24 hours after the operation and were excluded. LOS occurred in six of these, ventricular fibrillation in two, and massive bleeding in four. Of the remaining 775 patients, 734 (94.7%) showed a normal renal function before operation and 41 (5.3%) had a preexisting renal impairment (GoTable I).


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Table I. General characteristics of the patients
 
Among the patients without preoperative renal dysfunction, 111 (15.1%) had a postoperative renal complication: 84 (11.4%) were assigned to class II and 27 (3.7%) to class III (GoTable II). The overall mortality rate was 3.4% and ranged from 0.8% for the patients without renal complications (class I) to 18% for those with postoperative renal impairment (classes II and III). Furthermore, the mortality rate increased progressively with the degree of the renal impairment, with rates of 0.8%, 9.5%, and 44.4% in classes I, II, and III, respectively (p < 0.0001). A direct relationship between the prevalence of complications and the postoperative renal function was registered (GoTable II). Indeed, ARF was found to be an independent predictor of mortality after 24 hours, along with LOS and the infective and gastrointestinal complications (GoTable III).


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Table II. Preoperative, intraoperative, and postoperative clinical variables versus postoperative renal function: results of univariate analysis on 734 patients without preexisting renal disease
 

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Table III. Effect of postoperative complications on mortality after 24 hours: results of multivariate analysis
 
The ICU stay was longer than 72 hours in 10.1% of patients in class I, 57.3% of those in class II, and 85.1% of those in class III (p < 0.001). Four patients (0.54%) underwent dialytic therapy.

In stepwise multiple logistic regression the occurrence of ARF was significantly predicted by the following set of independent variables: age, emergency intervention, CPB diuresis, DHCA, LOS, and IABP support (GoTable IV).


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Table IV. Multivariate analysis of risk factors for postoperative renal impairment Standard
 
The patients with preexisting renal dysfunction had the characteristic of having an older mean age than those without preoperative impairment (62.8 versus 57.07 years, p < 0.001). As shown in GoTable I, in this group there was both a higher prevalence of postoperative complications and a higher mortality rate (17.1% versus 3.4%, p < 0.001).

DISCUSSION

In the present study, the ARF prevalence and mortality rate were not different from those previously reported in the cardiac surgery field in which the prevalence of ARF is said to vary from 2.5% to 7%, with a mortality rate ranging between 24% and 70%.Go Go 2-16

Renal impairment was shown to be the most frequent complication, after LOS: a postoperative serum creatinine level exceeding 1.5 mg/dl was registered in 15.1% of our patients, but only 3.7% had a serum creatinine level higher than 2.5 mg/dl (ARF).

The mortality rate was significantly affected by the postoperative renal function and increased progressively with the rise of serum creatinine peak level, up to 44% in patients with ARF. Multivariate analysis confirmed that a renal complication was an independent risk factor for death (GoTable III). This result suggests that ARF occurrence might increase the mortality rate after 24 hours independently from any other organ dysfunction, even though it is frequently noted in a context of multiple organ failure. This is consistent with the conclusion previously reported by Shusterman and associatesGo 13 but seems to be in contrast with the current opinion, which relates the so-called late mortality of patients with ARF to the large number of unavoidable complications secondary to renal impairment.Go 1 More recently, the risk factors for mortality in a medical ICU population with ARF were investigated to better understand the relative influence on mortality exerted by clinical situations predisposing or complicating ARF.Go 16 To achieve this goal the time of appearance of each organ system failure with respect to the time of ARF development was registered. It was concluded that mortality in ARF is mainly influenced by factors occurring before rather than after ARF.

The high mortality of patients with ARF is not surprising, but that of the renal dysfunction group needs to be briefly discussed. In fact, a rise of serum creatinine levels above normal limits but not exceeding 2.5 mg/dl was associated with a 10-fold increase in mortality rate in comparison with that of the normal patients (GoTable II). Because in this group of patients the renal function is not so impaired as to represent per se an important risk factor of death, a prominent role in the determination of mortality in these patients may be played by the same clinical factors that are responsible for the initial development of the renal impairment, namely LOS.

From the analysis of the risk factors the following variables emerged as independent predictors of ARF: advanced age, emergency intervention, CPB diuresis, use of DHCA, need for IABP supports and LOS development in the postoperative period (GoTable IV).

Most of these variables are considered as markers of renal hypoperfusion occurring before, during, or after operation. In fact, in our patients the need for emergency intervention is a better indicator of a poor preoperative hemodynamic profile than the angiographic data, which are often collected several weeks before the operation. Similarly, the use of DHCA during CPB and the need for IABP or inotropic support (LOS) in the ICU are indexes of a poor hemodynamic situation during and after operation.

The relationship between CPB diuresis and postoperative ARF is remarkable because it is a new concept, which was also confirmed after exclusion of the patients who received diuretic treatment during CPB. In a study of patients undergoing aortic operation without CPB no correlation between intraoperative diuresis and postoperative ARF development was found.Go 18 The intraoperative urinary output has been taken into consideration only in a minority of the studies on ARF after cardiac operation. Abel and colleaguesGo 3 registered a lower diuresis before CPB in patients with postoperative renal impairment, whereas urinary output during and after CPB was not different. Slogoff and associatesGo 15 evaluated the incidence of oliguria (urinary output less than 0.5 ml/kg/hr) during CPB, and Corwin and associatesGo 14 considered the total intraoperative diuresis: they failed to demonstrate any statistical correlation with the postoperative renal outcome. In the present study, lower diuresis during CPB was one of the earliest perioperative clinical markers of patients at high risk for postoperative ARF development. It is conceivable that during CPB the relative renal hypoperfusion may have unmasked situations of impaired renal reserve that were not detectable by means of the currently used laboratory screening methods.

The other CPB characteristics were not significant as independent predictors of postoperative ARF development. CPB time was univariately correlated with renal complication, but its importance as a risk factor was not confirmed by the multivariate analysis, as recently observed by other authors.Go Go 14,15 Neither CPB flows nor CPB pressures were related to postoperative ARF development, as previously reported.Go Go 5,15 In particular, Slogoff and associatesGo 15 did a careful analysis of the CPB variables with the use of a stepwise linear regression and excluded any correlation with postoperative renal dysfunction.

It is still controversial whether age is important or not in predisposing to ARF. Although a reduced functional capacity of the kidney in the older patient is documented,Go 19 a number of previous studies failed to demonstrate any statistical correlation between advanced age and the incidence of renal complications,Go Go 10,15 whereas some others reported that ARF is more likely to develop in older patients.Go Go Go Go Go 3,4,9,14,16 To explain the positive correlation it has been suggested that older patients may have a reduced ability to cope with a critical circulationGo 9 or that they more frequently undergo high-risk procedures.Go 14 In the present study, the probability of ARF development was only slightly increased by the age of the patient (coefficient 0.07), but this effect was evident in almost all patients (standard error 0.02) (GoTable IV). If the role played by age should be confirmed, this variable would represent an even more important handicap when attempting to reduce ARF incidence, inasmuch as the surgical patient is becoming increasingly more elderly.

With regard to the patients with preoperative renal impairment, we registered a higher incidence of complications and deaths with respect to those without preexisting renal dysfunction (GoTable I). Unfortunately, our data are inadequate to clarify whether the observed outcome may have been influenced by preexisting renal failure or not. In fact, the small number of these patients makes it difficult to do a reliable analysis of the independent variables that can significantly affect morbidity and mortality. However, the few studies in which this problem was specifically investigated concluded that mortality rate was not increased by the presence of renal failure before the intervention.Go Go Go 7,8,16

To summarize, in the present study the incidence of new ARF was reasonably low, but the associated mortality was still very high. The results of our investigation on the risk factors for renal impairment are in good agreement with the current opinions regarding the pathogenesis of ARF after cardiac operation: a prominent role has been attributed to the hemodynamic status, whereas the CPB variables seem to be of lesser importance. In fact, standardized controlled trials reported that although hypothermic nonpulsatile CPB might be associated with a certain degree of renal ischemia, ARF occurs only when the perioperative insult is prolonged or worsened by other injuries, such as LOS in the early postoperative period.Go Go 20,21 Otherwise there will be a prompt recovery of the renal function without clinical manifestations of kidney failure.

Acknowledgments

We acknowledge Professor S. Rigatti Luchini, Department of Statistics, Padova University, for statistical assistance.

Footnotes

From St. Maria dei Battuti General Hospital, Treviso; the Second Service of Anesthesia and Intensive Care Medicine, a Treviso General Hospital, Treviso; and the Department of Statistics, b Padova University, Padova, Italy. Back

References

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  2. Yeboah ED, Petrie A, Pead JL. Acute renal failure and open heart surgery. BMJ 1972;11:415-8.
  3. Abel RM, Buckley MJ, Austen WG, Barnett GO, Beck CHD, Fisher JE. Etiology, incidence and prognosis of renal failure following cardiac operations: results of a prospective analysis of 500 consecutive patients. J THORAC CARDIOVASC SURG 1976;71:323-33. [Abstract]
  4. Bhat JG, Gluck MC, Lowenstein J, Baldwin DS. Renal failure after open heart surgery. Ann Intern Med 1976;84:677-82.
  5. Hilberman M, Myers BD, Carrie BJ, Derby G, Jamison RL, Stinson EB. Acute renal failure following cardiac surgery. J THORAC CARDIOVASC SURG 1979;77:880-8. [Abstract]
  6. Gailiunas P, Chawla R, Lazarus M, Cohn L, Sanders J, Merril JP. Acute renal failure following cardiac operations. J THORAC CARDIOVASC SURG 1980;79:241-3. [Abstract]
  7. Hou SH, Bushinsky DA, Wish JB, Cohen JJ, Harrington JT. Hospital-acquired renal insufficiency: a prospective study. Am J Med 1983;74:243-8. [Medline]
  8. Rasmussen HH, Ibels LS. Acute renal failure: multivariate analysis of causes and risk factors. Am J Med 1982;73:211-8. [Medline]
  9. Koning HM, Koning AJ, Leusink JA. Serious acute renal failure following open heart surgery. Thorac Cardiovasc Surg 1985;33:283-7. [Medline]
  10. Rasmussen HH, Pitt EA, Ibels LS, McNeil DR. Predic tion of outcome in acute renal failure by discriminant analysis of clinical variables. Arch Intern Med 1985;145:2015-8. [Abstract/Free Full Text]
  11. Lien J, Chan V. Risk factors influencing survival in acute renal failure treated by hemodialysis. Arch Intern Med 1985;145:2067-9. [Abstract/Free Full Text]
  12. Lange HW, Aeppli DM, Brown DC. Survival of patients with acute renal failure requiring dialysis after open heart surgery: early prognostic indicators. Am Heart J 1987;113:1138-43. [Medline]
  13. Shusterman N, Strom BL, Murray TG, Morrison G, West SL, Maislin G. Risk factors and outcome of hospital-acquired acute renal failure. Am J Med 1987;83:65-71. [Medline]
  14. Corwin HL, Sprague SM, DeLaria GA, Norusis MJ. Acute renal failure associated with cardiac operations: a case-control study. J THORAC CARDIOVASC SURG 1989;98:1107-12. [Abstract]
  15. Slogoff S, Reul GJ, Keats AS, et al. Role of perfusion pressure and flow in major organ dysfunction after cardiopulmonary bypass. Ann Thorac Surg 1990;50:911-8. [Abstract]
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Renal Dysfunction in High-Risk Patients After On-Pump and Off-Pump Coronary Artery Bypass Surgery: A Propensity Score Analysis
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K. R. Pai, I. R. Ramnarine, A. D. Grayson, and N. K. Mediratta
The effect of chronic steroid therapy on outcomes following cardiac surgery: a propensity-matched analysis
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G. Asimakopoulos, A. P. Karagounis, O. Valencia, N. Alexander, M. Howlader, M. A. Sarsam, and V. Chandrasekaran
Renal Function After Cardiac Surgery Off- Versus On-Pump Coronary Artery Bypass: Analysis Using the Cockroft-Gault Formula for Estimating Creatinine Clearance
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C. S. Rinder, M. Fontes, J. P. Mathew, H. M. Rinder, and B. R. Smith
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