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Acute renal failure in the cardiac care unit: Etiologies, outcomes, and prognostic factors
Kidney International, Vol. 56 (1999), pp. 238–243
Acute renal failure in the cardiac care unit: Etiologies, outcomes, and prognostic factors TERRY BEHREND and STEVEN B. MILLER George M. O’Brien Kidney and Urologic Diseases Center, Renal Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA
Acute renal failure in the cardiac care unit: Etiologies, outcomes, and prognostic factors. Background. Heart disease is a leading cause of hospitalizations, and its prevalence is expected to grow rapidly over the next few decades. The purpose of this study was to examine the incidence, etiologies, outcomes, and risk factors for mortality of acute renal failure (ARF) in cardiac care unit (CCU) patients. Methods. A retrospective, cohort study examining all patients who developed ARF while in the CCU at Barnes-Jewish Hospital over a 17-month time period was performed. Charts were reviewed to determine etiologies, hospital mortality rates, and risk factors for mortality. Results. Four percent of admissions to the CCU met criteria for ARF while in the unit. The etiologies of ARF were congestive heart failure (CHF; 35%), multifactorial (usually involving CHF; 26%), arrest/arrhythmia (13%), contrast (11%), volume depletion (6%), sepsis (6%) and obstruction (3%). The mortality rate was 50%. Oliguria, mechanical ventilation, and decreased cardiac function were statistically significant risk factors for mortality by univariate but not multivariate analysis. Thirty percent of patients with a cardiac index of less than 2.0 liter/ min/m2 survived to discharge. Conclusions. ARF occurs commonly in CCU patients and is associated with a high mortality rate. However, there are a significant number of survivors even among patients with severely depressed cardiac function.
tant so that treatment can be offered to patients likely to benefit, and withheld from those in whom it would only prolong suffering. Heart disease is the leading cause of mortality and the leading cause of hospitalization in patients over the age of 65 in the United States [5]. As the population ages and the treatment for ischemic heart disease improves, the number of patients with heart disease is expected to grow rapidly. These patients are at risk for ARF because of hemodynamic compromise, intravenous contrast, arterial catheterizations with the risk of atheroemboli, and the frequent use of angiotensin-converting enzyme inhibitors (ACEIs). As the number of patients with cardiac disease continues to grow, it is likely that we will see more of these patients develop ARF. Although many studies have evaluated the outcomes of ARF in various clinical settings, to our knowledge, no previous studies have specifically addressed ARF in cardiac care unit (CCU) patients. Accurately defining study populations is important because outcomes and prognostic factors can vary among different populations. Therefore, the purpose of this study was to define the incidence, etiologies, and outcomes and to examine risk factors for mortality of ARF in the CCU.
Acute renal failure (ARF) continues to be a common cause of morbidity and mortality in hospitalized patients, particularly in intensive care units (ICUs). Mortality rates range from 25 to 35% for hospital-acquired ARF [1, 2] to 46 to 88% for ARF in ICU patients requiring dialysis [3]. Despite advances in supportive care and dialysis, which is very expensive, mortality rates have not changed significantly over the past five decades [4]. Therefore, prognostic information is extremely impor-
METHODS The records of all patients admitted to the CCU at Barnes-Jewish Hospital, a tertiary care hospital in St. Louis, MO, USA, during the period from April 1996 to October 1997 were reviewed retrospectively. Patients were excluded if they were admitted to the CCU without any acute cardiac diagnosis. A computer database of patients’ laboratories was searched to identify those with a serum creatinine of greater than or equal to 2.0 mg/dl. A total of 404 patients were identified, and their charts were reviewed to determine if they met criteria for ARF. ARF was defined as an increase in serum creatinine of at least 0.9 to at least 2.0 mg/dl if the baseline value was less than 2.0 mg/dl or an increase of at least 1.5 mg/dl if
Key words: ICU, congestive heart failure, CCU, cardiac care unit, renal failure, dysrhythmia. Received for publication July 24, 1998 and in revised form February 2, 1999 Accepted for publication February 15, 1999
1999 by the International Society of Nephrology
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the baseline was 2.0 mg/dl or greater. These are the same criteria used previously by Shusterman et al [2]. The baseline creatinine was determined as the lower of the most recent creatinine measurements during the previous three months if available or the lowest value during the hospitalization. We identified 106 cases of ARF in the CCU during this time period. These charts were reviewed to determine the etiology of ARF and to obtain data to be evaluated as risk factors for mortality. The onset of ARF was classified as initial if the criteria for ARF were met on the day of admission. All others were labeled delayed ARF. Etiologic categories were predefined and included the following: hemodynamic causes subdivided into volume depletion, congestive heart failure (CHF), cardiac arrest/arrhythmia, or ACEI; sepsis; contrast; other toxins; cholesterol emboli; obstruction; other; and multifactorial. All charts were reviewed by a single reviewer (T.B.). The following criteria were used to define the etiologies of ARF. Volume depletion. Intravascular volume depletion was one criterion, as evidenced by history (decreased oral intake, vomiting, diarrhea, bleeding, diuresis, or weight loss) and/or physical exam (flat neck veins, tachycardia, postural hypotension), along with an improvement in renal function following volume replacement. Congestive heart failure. The diagnosis of CHF was made by physical exam findings including increased jugular venous pressure, rales, S3, and peripheral edema. CHF was determined to be the etiology of ARF if renal function improved with the treatment of CHF or if CHF was severe enough to cause a systolic blood pressure of less than 90 mm Hg or to require vasopressors. Cardiac arrest/arrhythmia. Any hemodynamically significant arrhythmia, defined as a fall in systolic blood pressure to less than 90 mm Hg, followed by an increase in serum creatinine within 24 hours, was included. Angiotensin-converting enzyme inhibitor. If there was a rise (or fall) in serum creatinine temporally related to the initiation (or discontinuation) of ACEI therapy in the absence of any other overriding clinical events, it was defined as an ARF etiology. Sepsis. Sepsis was the etiology of ARF if the systolic blood pressure was less than 90 mm Hg or if vasopressors were required in the presence of at least two of the following: temperature $38.38C, positive blood cultures, or a white blood cell count greater than 10,000/mm3. Contrast media. This included an increase in the serum creatinine to meet the definition of ARF within 48 hours following intravenous contrast. Cholesterol emboli. With biopsy-proven cholesterol emboli on either skin or renal biopsy, or at least three of the following criteria—arterial catheterization or manipulation prior to the ARF episode, livedo reticularis,
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hypocomplementemia, eosinophilia, or retinal lesions— the patient was defined as having ARF. Obstruction. This included hydronephrosis by any imaging modality or clinical evidence of urinary obstruction and a decrease of serum creatinine to or near baseline following relief of the obstruction. Risk factors to be evaluated were defined prospectively and included age, peak creatinine, oliguria (a urine output of less than 400 ml/24 hr), mechanical ventilation at the onset of ARF, chronic renal failure (a baseline creatinine of 2.0 mg/dl or more), admitting diagnosis, ejection fraction, cardiac index, nephrology consultation, and dialysis. The admitting diagnosis was categorized as either arrhythmia, CHF, or coronary artery disease (CAD), which included unstable angina and acute myocardial infarction. Ejection fraction was available in 99 patients and was determined by either echocardiography or ventriculography during cardiac catheterization. Ejection fraction was recorded as being less than or greater than 25%. In 67 patients who had a pulmonary artery catheter, the cardiac index was recorded as the lowest repeatable value. Dialysis therapy consisted of intermittent hemodialysis for 14 patients, continuous venovenous hemodialysis for 3 patients, and acute peritoneal dialysis for 1 patient. A polysulfone membrane (Fresenius F8) was used for all intermittent hemodialysis, and the membranes were not reused. Dialysis adequacy was measured at least once weekly by urea reduction ratio (URR) for patients on intermittent hemodialysis and treatments adjusted to maintain URR $65%. Univariate analysis of the predefined risk factors was performed by computing relative risks and 95% confidence intervals using the two-sided Fisher’s exact test. Statistical significance was defined as a two-sided P value of less than 0.05. Multiple logistic regression was used to analyze each of the predefined risk factors for mortality. Statistics were performed with the statistical program SPSS version 7.5 (SPSS Inc., Chicago, IL, USA). RESULTS There were 2392 admissions to the CCU during the 17-month period of the study. The serum creatinine was at least 2.0 mg/dl at some point in the hospital course of 624 patients (26%) and during the CCU stay for 404 patients (17%). One hundred six patients (4%) met the criteria for ARF while in the CCU. The characteristics of the patients with ARF are shown in Table 1. There was a wide distribution of ages, ranging from 22 to 90 years, with a mean of 69 years. Fifty-six (53%) patients were male. A significant number had underlying hypertension (58%), diabetes mellitus (52%), and chronic renal failure (21%). The etiologies of ARF are shown in Table 2. The
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Table 1. Clinical characteristics of 106 patients with acute renal failure in the cardiac care unit Age (mean 6 SD) (range) Male Hypertension Diabetes mellitus Chronic renal failure (baseline creatinine $2.0 mg/dl)
69 6 15 (22–90) 56 (53%) 61 (58%) 55 (52%) 22 (21%)
Mortality rates according to the etiology of ARF are shown in Table 4. CHF and arrest/arrhythmia as ARF etiologies had the highest mortality (59% and 79%, respectively). The lowest mortalities (17%) were in the volume depletion and contrast groups. The relative risks for mortality were statistically significant for arrest/ arrhythmia (1.72) and contrast (0.31).
Abbreviation is: SD, standard deviation.
most common etiology was CHF, accounting for 37 cases (35%). Twenty-eight cases (26%) were multifactorial, usually involving a low cardiac output state. Other etiologies included arrest/dysrhythmia (13%), contrast media (11%), volume depletion (6%), sepsis (6%), and obstruction (3%). ACEIs were not felt to be the primary etiology of any of the cases, but they were felt to contribute to three of the multifactorial cases. Fifty-three of the 106 patients (50%) survived the hospitalization. In addition, three of the hospital survivors were discharged to hospice care. In comparison, the hospital mortality for CCU patients without ARF was 8%. Twenty-five patients (24%) met the criteria for ARF on the day of admission. Fourteen of these patients (56%) survived the hospitalization, which was not significantly different from the 48% survival among the patients with delayed ARF. Nephrology consultation was obtained in 44 cases (42%), and there was no significant difference in mortality based on consultation. Eighteen patients (17%) received dialysis, and 9 (50%) survived the hospitalization. Four of these patients, or 44% of the patients who received dialysis and survived, were discharged on dialysis. Four patients recovered enough renal function to discontinue dialysis, and one chose not to undergo chronic dialysis and was discharged to hospice care. The relative risks for mortality based on the prospectively defined risk factors are shown in Table 3. Oliguria, mechanical ventilation, and decreased cardiac function, defined either as an ejection fraction of less than 25% or a cardiac index of less than 2.0, were associated with a statistically significant increased risk for hospital mortality. The relative risk with oliguria was 1.72 (P 5 0.01), with mechanical ventilation was 1.70 (P 5 0.01), with a decreased ejection fraction was 1.77 (P 5 0.009), and with a decreased cardiac index was 2.11 (P 5 0.003). Multivariate analysis did not find these factors to predict mortality. Because ejection fraction and cardiac index are likely to be related, they were combined as one variable (ejection fraction ,25% or confidence interval ,2.0 liter/min/m2) for the multivariate analysis and were still not found to be an independent predictor of mortality. Age, peak creatinine, chronic renal failure, admitting diagnosis, nephrology consult, or dialysis did not predict hospital mortality.
DISCUSSION The incidence of ARF in patients with acute cardiac diagnoses in the CCU was 4%. This number likely underestimates the true incidence of ARF in this patient population, because we included only cases that met criteria for ARF during the CCU stay, which was often brief (the mean length of stay was 2.2 days). In fact, 220 (9% of CCU admissions) patients had an increase in serum creatinine from less than 2.0 mg/dl in the CCU to greater than 2.0 mg/dl during the rest of the hospital course. Compared with prior reports, this incidence is greater than that reported for community-acquired (1%) or hospital-acquired ARF in a mixed population of medical and surgical patients (2%) [2, 6]. Hou et al found a 5% incidence of hospital-acquired ARF but used much less stringent criteria to define ARF [1]. The incidence of ARF in other ICU populations has ranged from 3 to 30% [7–14]. In addition, the absolute numbers of patients with ARF concomitant with severe cardiac disease can be expected to rise sharply over the next few decades because of the rapidly escalating prevalence of heart disease. Preliminary evidence pointing to this trend already exists. In an analysis of ARF in ICU patients in two different time periods, McCarthy found a significant increase in the percentage of cases due to “cardiac prerenal” causes from 15% in 1977 through 1979 to 30% in 1991 through 1992 [15]. It is not surprising that the most common etiologies of ARF were hemodynamic causes related to the underlying cardiac disease. Thirty-five percent of cases were due primarily to severe CHF, and it also contributed to most of the multifactorial cases, which accounted for an additional 26% of all cases. Many of these patients have severely compromised cardiac function, and when ARF develops, questions regarding prognosis arise. Patients, families, and physicians would all like to know the prognosis in order to make decisions regarding further therapy. Previous studies have examined cardiac morbidity as a prognostic factor, but results have been contradictory. Some have found an association with mortality [7, 16–23], whereas others have not [24, 25]. It is difficult to compare these studies because of a wide variation in the definition of “cardiac failure,” including hypotension, CHF, infective endocarditis, myocarditis, arrhythmias, and myocardial infarction. Also, until now, no studies have specifically examined cardiac function as a prognostic factor in the CCU population.
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Behrend and Miller: ARF in the cardiac care unit Table 2. Etiologies of acute renal failure (ARF) in the cardiac care unit Etiology Hemodynamic Volume depletion CHF Arrest/dysrhythmia ACEI Contrast Sepsis Obstruction Multifactorial Total
Initial ARF 5 8 3 0 0 1 3 5
Delayed ARF
(20%) (32%) (12%)
1 29 11 0 12 5 0 23
(4%) (12%) (20%)
25 (24%)
Total
(1%) (36%) (14%)
6 37 14 0 12 6 3 28
(15%) (6%) (28%)
81 (76%)
P value
(6%) (35%) (13%)
0.003 0.81 1.00
(11%) (6%) (3%) (26%)
0.06 1.00 0.01 0.45
106 (100%)
Abbreviations are: CHF, congestive heart failure; ACEI, angiotensin-converting enzyme inhibitor.
Table 3. Risk factors for hospital mortality
Age (mean 6 SD) Peak creatinine $3.0 mg/dl Oliguria Mechanical ventilation CRF Admit diagnosis CHF CAD Dysrhythmia EF ,25% (N 5 99) CI ,2.0 liter/min/m2 (N 5 67) Nephrology consult Dialysis
Deaths N 5 53
Survivors N 5 53
Relative risk (95% confidence interval)
69 6 14 40 22 30 8
68 6 15 34 9 16 14
1.33 1.72a 1.70a 0.68
(0.83–2.13) (1.21–2.44) (1.16–2.50) (0.38–1.22)
18 23 12 28 26 21 9
21 25 7 17 11 23 9
0.88 0.93 1.34 1.77a 2.11a 0.92 1.00
(0.59–1.33) (0.63–1.36) (0.89–2.02) (1.15–2.71) (1.22–3.65) (0.62–1.37) (0.60–1.66)
Abbreviations are: SD, standard deviation; CRF, chronic renal failure; CHF, congestive heart failure; CAD, coronary artery disease; EF, ejection fraction; CI, cardiac index. a P # 0.01
Table 4. Hospital mortality according to ARF etiology Deaths
Survivors
Mortality
Relative risk (95% confidence interval)
Hemodynamic Volume depletion CHF Arrest/dysrhythmia ACEI Contrast Sepsis Obstruction Multifactorial
1 22 11 0 2 3 1 13
5 15 3 0 10 3 2 15
17% 59% 79%
0.32 (0.05–1.94) 1.32 (0.91–1.92) 1.72a (1.21–2.45)
17% 50% 33% 46%
0.31a 1.00 0.66 0.91
Total
53
53
50%
Etiology
a
(0.09–1.10) (0.44–2.28) (0.13–3.30) (0.58–1.42)
P , 0.05
At least three prior studies have found CHF specifically, rather than the broadly defined “cardiac failure,” to be a risk factor for hospital mortality in ARF. Lien and Chan evaluated 58 patients retrospectively and found CHF, not specifically defined, to be associated with increased mortality by univariate (RR 5 1.9), but not multivariate analysis [16]. Lohr, McFarlane, and Granthan retrospectively evaluated 126 patients with
ARF and found CHF, defined as characteristic radiographic appearance, rales, decreased cardiac output, or the presence of a third heart sound, to have a significantly increased risk of mortality (RR 5 1.3) [17]. In addition to CHF, Lohr, McFarlane, and Granthan found hypotension, assisted ventilation, gastrointestinal dysfunction, and sepsis to be prognostic factors and proposed a prognostic index based on the number of these factors pres-
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ent. When applied to a different set of patients by a separate investigator, Lohr’s prognostic index did predict mortality [18]. These studies all exclusively examined patients treated with hemodialysis. Hemodynamic instability often complicates dialysis in patients with severely compromised cardiac function. Therefore, theoretically, the increased mortality in these studies could have been related to complications of hemodialysis. However, most of the patients in our study did not undergo dialysis, and we found a similar adverse prognostic effect by univariate but not multivariate analysis. Previous studies have noted that the timing of onset (community versus hospital acquired) is important in the prognosis of ARF. The proportion of cases with initial or community-acquired ARF was much lower in our study (24%) than has been reported previously (60%) [14, 26]. This may be related to the urgency and rapidity with which acute cardiac syndromes lead to hospitalization. In the CCU, we found no significant difference in the mortality of initial (44%) versus delayed ARF (52%). The discrepancy with other studies, which report a 20% absolute increase in mortality for patients with delayed ARF [14, 26], is likely due to the different etiologies of ARF. The decreased mortality in community-acquired ARF has been explained by an increased proportion of cases in this group due to etiologies with better prognoses. Specifically, 17 to 30% of these patients have been reported to have obstructive ARF [6, 26, 27]. Table 2 shows the different etiologies of ARF divided into initial and delayed ARF in our study. Although there were more obstructive cases in the initial group, they accounted for only 12% of the initial ARF cases and only 3% of the cases overall. Volume depletion, which had a low mortality, was also more common in the initial group. However, all of the contrast-induced ARF cases were in the delayed group, as expected, and also had a low mortality rate (17%), which tends to offset any survival advantage of the initial ARF group. Although the mortality was increased in patients with severely decreased cardiac function, there were still a significant number of survivors. Thirty percent of those with a cardiac index of less than 2.0 liter/min/m2 survived to discharge. The patient with the lowest recorded cardiac index in this study (1.1 liter/min/m2) survived. Although decreased ejection fraction or cardiac index was more common in the nonsurvivors, they were also present in one third of survivors (Fig. 1). Depressed cardiac function, therefore, cannot by itself be used as an indication to withhold treatment of ARF. However, considering cardiac function along with the overall clinical picture may be important in predicting prognosis. There has been a great deal of interest in developing prognostic scores to predict the outcome of ARF. Several scoring systems have been proposed; however, they are often
Fig. 1. Ejection fraction (EF; ; ,25%) and cardiac index (CI; j; ,2.0 liter/min/m2) in survivors and nonsurvivors. EF and CI were available in 99 and 67 patients, respectively. Among survivors, 33% had an EF ,25% and 35% had a CI ,2.0 liter/min/m2. Among nonsurvivors, 60% had an EF ,25%, and 72% had a CI ,2.0 liter/min/m2.
complicated and may not be valid outside of the population from which they were developed. Recently, Lian˜o has developed a prognostic index for acute tubular necrosis that is simple to calculate and was validated in a separate hospital [28]. The index was developed and tested in a diverse patient population, including medical, surgical, nephrotoxic, and septic etiologies of ARF, but does not include cardiac function as a prognostic factor. It would be interesting to test this index in a population of cardiac patients and to examine if cardiac function could improve its prognostic ability. Hospital survivors who required dialysis remained dependent on dialysis at the time of discharge more frequently than has been reported previously. Prior studies have reported a 17 to 33% incidence of dialysis dependency among hospital survivors who required hemodialysis for ARF in an ICU [15, 29], whereas 56% (5 out of 9) of such patients in our study remained dependent on dialysis at discharge. Possible explanations for this difference include the small number of patients requiring dialysis in this study or an earlier discharge. Alternatively, it is also plausible that CHF impairs renal recovery through impaired renal blood flow and altered glomerular hemodynamics. Because we had only nine patients survive after receiving dialysis, we could not adequately evaluate any differences that might have existed between patients that recovered renal function and those that remained dialysis dependent. Future studies should address this area. In summary, ARF is common in CCU patients, is most often hospital acquired and is due to hemodynamic causes. There may be a decreased rate of renal recovery, although a larger number of patients need to be exam-
Behrend and Miller: ARF in the cardiac care unit
ined to confirm this finding. Although there is a high mortality rate in these patients, there are a significant number of survivors, even among patients with severely depressed cardiac function. Future studies are needed to address the long-term survival of these patients, including both quantity and quality of life. Reprint requests to Steven B. Miller, M.D., Washington University School of Medicine, Renal Division Box 8126, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA. E-mail: [email protected]
REFERENCES 1. Hou SH, Bushinsky DA, Wish JB, Cohen JJ, Harrington JT: Hospital-acquired renal insufficiency: A prospective study. Am J Med 74:243–248, 1983 2. 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 83:65–71, 1987 3. MacKay K, Moss AH: To dialyze or not to dialyze: An ethical and evidence-based approach to the patient with acute renal failure in the intensive care unit. Adv Renal Replace Ther 4:288–296, 1997 4. Bywaters EGL: 50 years: The crush syndrome. BMJ 301:1412– 1415, 1990 5. Rich MW: Epidemiology, pathophysiology, and etiology of congestive heart failure in older adults. J Am Geriatr Soc 45:968–974, 1997 6. Kaufman J, Dhakal M, Patel B, Hamburger R: Communityacquired acute renal failure. Am J Kidney Dis 17:191–198, 1991 7. Groeneveld ABJ, Tran DD, van der Meulen J, Nauta JJP, Thijs LG: Acute renal failure in the medical intensive care unit: Predisposing, complicating factors and outcome. Nephron 59:602– 610, 1991 8. Kraman S, Khan F, Patel S, Seriff N: Renal failure in the respiratory intensive care unit. Crit Care Med 7:263–266, 1979 9. Werb R, Linton AL: Aetiology, diagnosis, treatment and prognosis of acute renal failure in an intensive care unit. Resuscitation 7:95–100, 1979 10. Sweet SJ, Glenney CU, Fitzgibbons JP, Friedmann P, Teres D: Synergistic effect of acute renal failure and respiratory failure in the surgical intensive care unit. Am J Surg 141:492– 496, 1981 11. Wilkins RG, Faragher EB: Acute renal failure in an intensive care unit: Incidence, prediction and outcome. Anaesthesia 38:628–634, 1983 12. Menashe PI, Ross SA, Gottlieb JE: Acquired renal insufficiency in critically ill patients. Crit Care Med 16:1106–1109, 1988
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13. Jochimsen F, Schafer J-H, Maurer A, Distler A: Impairment of renal function in medical intensive care: Predictability of acute renal failure. Crit Care Med 18:480– 485, 1990 14. Brivet FG, Kleinknecht DJ, Loirat P, Landais PJM, French Study Group on Acute Renal Failure: Acute renal failure in intensive care units—causes, outcome and prognostic factors of hospital mortality: A prospective, multicenter study. Crit Care Med 24:192–198, 1996 15. McCarthy JT: Prognosis of patients with acute renal failure in the intensive care unit: A tale of two eras. Mayo Clin Proc 71:117– 126, 1996 16. Lien J, Chan V: Risk factors influencing survival in acute renal failure treated by hemodialysis. Arch Intern Med 145:2067–2069, 1985 17. Lohr JW, McFarlane MJ, Granthan JJ: A clinical index to predict survival in acute renal failure patients requiring dialysis. Am J Kidney Dis 11:254–259, 1988 18. Halstenberg WK, Goormastic M, Paganini EP: Validity of four models for predicting outcome in critically ill acute renal failure patients. Clin Nephrol 47:81–86, 1997 19. Cioffi WG, Ashikaga T, Gamelli RL: Probability of surviving postoperative acute renal failure. Ann Surg 200:205–211, 1984 20. Bullock ML, Umen AJ, Finkelstein M, Keane WF: The assessment of risk factors in 462 patients with acute renal failure. Am J Kidney Dis 5:97–103, 1985 21. Schaefer J-H, Jochimsen F, Keller F, Wegscheider K, Distler A: Outcome prediction of acute renal failure in medical intensive care. Intensive Care Med 17:19–24, 1991 22. Rasmussen HH, Pitt EA, Ibels LS, McNeil DR: Prediction of outcome in acute renal failure by discriminant analysis of clinical variables. Arch Intern Med 145:2015–2018, 1985 23. Cosentino F, Chaff C, Piedmonte M: Risk factors influencing survival in ICU acute renal failure. Nephrol Dial Transplant 9(Suppl 4):179–182, 1994 24. Corwin HL, Teplick RS, Schreiber MJ, Fang LST, Bonventre JV, Coggins CH: Prediction of outcome of acute renal failure. Am J Nephrol 7:8–12, 1987 25. Spiegel DM, Ullian ME, Zerbe GO, Berl T: Determinants of survival and recovery in acute renal failure patients dialyzed in intensive-care units. Am J Nephrol 11:44– 47, 1991 26. Lian˜o F, Pascual J, Madrid Acute Renal Failure Study Group: Epidemiology of acute renal failure: A prospective, multicenter, community-based study. Kidney Int 50:811–818, 1996 27. Feest TG, Round A, Hamad S: Incidence of severe acute renal failure in adults: Results of a community based study. BMJ 306:481– 483, 1993 28. Lian˜o F: Severity of acute renal failure: The need of measurement. Nephrol Dial Transplant 9(Suppl 4):229–238, 1994 29. Chertow GM, Christiansen CL, Cleary PD, Munro C, Lazarus JM: Prognostic stratification in critically ill patients with acute renal failure requiring dialysis. Arch Intern Med 155:1505–1511, 1995
Acute renal failure in the cardiac care unit: Etiologies, outcomes, and prognostic factors TERRY BEHREND and STEVEN B. MILLER George M. O’Brien Kidney and Urologic Diseases Center, Renal Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA
Acute renal failure in the cardiac care unit: Etiologies, outcomes, and prognostic factors. Background. Heart disease is a leading cause of hospitalizations, and its prevalence is expected to grow rapidly over the next few decades. The purpose of this study was to examine the incidence, etiologies, outcomes, and risk factors for mortality of acute renal failure (ARF) in cardiac care unit (CCU) patients. Methods. A retrospective, cohort study examining all patients who developed ARF while in the CCU at Barnes-Jewish Hospital over a 17-month time period was performed. Charts were reviewed to determine etiologies, hospital mortality rates, and risk factors for mortality. Results. Four percent of admissions to the CCU met criteria for ARF while in the unit. The etiologies of ARF were congestive heart failure (CHF; 35%), multifactorial (usually involving CHF; 26%), arrest/arrhythmia (13%), contrast (11%), volume depletion (6%), sepsis (6%) and obstruction (3%). The mortality rate was 50%. Oliguria, mechanical ventilation, and decreased cardiac function were statistically significant risk factors for mortality by univariate but not multivariate analysis. Thirty percent of patients with a cardiac index of less than 2.0 liter/ min/m2 survived to discharge. Conclusions. ARF occurs commonly in CCU patients and is associated with a high mortality rate. However, there are a significant number of survivors even among patients with severely depressed cardiac function.
tant so that treatment can be offered to patients likely to benefit, and withheld from those in whom it would only prolong suffering. Heart disease is the leading cause of mortality and the leading cause of hospitalization in patients over the age of 65 in the United States [5]. As the population ages and the treatment for ischemic heart disease improves, the number of patients with heart disease is expected to grow rapidly. These patients are at risk for ARF because of hemodynamic compromise, intravenous contrast, arterial catheterizations with the risk of atheroemboli, and the frequent use of angiotensin-converting enzyme inhibitors (ACEIs). As the number of patients with cardiac disease continues to grow, it is likely that we will see more of these patients develop ARF. Although many studies have evaluated the outcomes of ARF in various clinical settings, to our knowledge, no previous studies have specifically addressed ARF in cardiac care unit (CCU) patients. Accurately defining study populations is important because outcomes and prognostic factors can vary among different populations. Therefore, the purpose of this study was to define the incidence, etiologies, and outcomes and to examine risk factors for mortality of ARF in the CCU.
Acute renal failure (ARF) continues to be a common cause of morbidity and mortality in hospitalized patients, particularly in intensive care units (ICUs). Mortality rates range from 25 to 35% for hospital-acquired ARF [1, 2] to 46 to 88% for ARF in ICU patients requiring dialysis [3]. Despite advances in supportive care and dialysis, which is very expensive, mortality rates have not changed significantly over the past five decades [4]. Therefore, prognostic information is extremely impor-
METHODS The records of all patients admitted to the CCU at Barnes-Jewish Hospital, a tertiary care hospital in St. Louis, MO, USA, during the period from April 1996 to October 1997 were reviewed retrospectively. Patients were excluded if they were admitted to the CCU without any acute cardiac diagnosis. A computer database of patients’ laboratories was searched to identify those with a serum creatinine of greater than or equal to 2.0 mg/dl. A total of 404 patients were identified, and their charts were reviewed to determine if they met criteria for ARF. ARF was defined as an increase in serum creatinine of at least 0.9 to at least 2.0 mg/dl if the baseline value was less than 2.0 mg/dl or an increase of at least 1.5 mg/dl if
Key words: ICU, congestive heart failure, CCU, cardiac care unit, renal failure, dysrhythmia. Received for publication July 24, 1998 and in revised form February 2, 1999 Accepted for publication February 15, 1999
1999 by the International Society of Nephrology
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the baseline was 2.0 mg/dl or greater. These are the same criteria used previously by Shusterman et al [2]. The baseline creatinine was determined as the lower of the most recent creatinine measurements during the previous three months if available or the lowest value during the hospitalization. We identified 106 cases of ARF in the CCU during this time period. These charts were reviewed to determine the etiology of ARF and to obtain data to be evaluated as risk factors for mortality. The onset of ARF was classified as initial if the criteria for ARF were met on the day of admission. All others were labeled delayed ARF. Etiologic categories were predefined and included the following: hemodynamic causes subdivided into volume depletion, congestive heart failure (CHF), cardiac arrest/arrhythmia, or ACEI; sepsis; contrast; other toxins; cholesterol emboli; obstruction; other; and multifactorial. All charts were reviewed by a single reviewer (T.B.). The following criteria were used to define the etiologies of ARF. Volume depletion. Intravascular volume depletion was one criterion, as evidenced by history (decreased oral intake, vomiting, diarrhea, bleeding, diuresis, or weight loss) and/or physical exam (flat neck veins, tachycardia, postural hypotension), along with an improvement in renal function following volume replacement. Congestive heart failure. The diagnosis of CHF was made by physical exam findings including increased jugular venous pressure, rales, S3, and peripheral edema. CHF was determined to be the etiology of ARF if renal function improved with the treatment of CHF or if CHF was severe enough to cause a systolic blood pressure of less than 90 mm Hg or to require vasopressors. Cardiac arrest/arrhythmia. Any hemodynamically significant arrhythmia, defined as a fall in systolic blood pressure to less than 90 mm Hg, followed by an increase in serum creatinine within 24 hours, was included. Angiotensin-converting enzyme inhibitor. If there was a rise (or fall) in serum creatinine temporally related to the initiation (or discontinuation) of ACEI therapy in the absence of any other overriding clinical events, it was defined as an ARF etiology. Sepsis. Sepsis was the etiology of ARF if the systolic blood pressure was less than 90 mm Hg or if vasopressors were required in the presence of at least two of the following: temperature $38.38C, positive blood cultures, or a white blood cell count greater than 10,000/mm3. Contrast media. This included an increase in the serum creatinine to meet the definition of ARF within 48 hours following intravenous contrast. Cholesterol emboli. With biopsy-proven cholesterol emboli on either skin or renal biopsy, or at least three of the following criteria—arterial catheterization or manipulation prior to the ARF episode, livedo reticularis,
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hypocomplementemia, eosinophilia, or retinal lesions— the patient was defined as having ARF. Obstruction. This included hydronephrosis by any imaging modality or clinical evidence of urinary obstruction and a decrease of serum creatinine to or near baseline following relief of the obstruction. Risk factors to be evaluated were defined prospectively and included age, peak creatinine, oliguria (a urine output of less than 400 ml/24 hr), mechanical ventilation at the onset of ARF, chronic renal failure (a baseline creatinine of 2.0 mg/dl or more), admitting diagnosis, ejection fraction, cardiac index, nephrology consultation, and dialysis. The admitting diagnosis was categorized as either arrhythmia, CHF, or coronary artery disease (CAD), which included unstable angina and acute myocardial infarction. Ejection fraction was available in 99 patients and was determined by either echocardiography or ventriculography during cardiac catheterization. Ejection fraction was recorded as being less than or greater than 25%. In 67 patients who had a pulmonary artery catheter, the cardiac index was recorded as the lowest repeatable value. Dialysis therapy consisted of intermittent hemodialysis for 14 patients, continuous venovenous hemodialysis for 3 patients, and acute peritoneal dialysis for 1 patient. A polysulfone membrane (Fresenius F8) was used for all intermittent hemodialysis, and the membranes were not reused. Dialysis adequacy was measured at least once weekly by urea reduction ratio (URR) for patients on intermittent hemodialysis and treatments adjusted to maintain URR $65%. Univariate analysis of the predefined risk factors was performed by computing relative risks and 95% confidence intervals using the two-sided Fisher’s exact test. Statistical significance was defined as a two-sided P value of less than 0.05. Multiple logistic regression was used to analyze each of the predefined risk factors for mortality. Statistics were performed with the statistical program SPSS version 7.5 (SPSS Inc., Chicago, IL, USA). RESULTS There were 2392 admissions to the CCU during the 17-month period of the study. The serum creatinine was at least 2.0 mg/dl at some point in the hospital course of 624 patients (26%) and during the CCU stay for 404 patients (17%). One hundred six patients (4%) met the criteria for ARF while in the CCU. The characteristics of the patients with ARF are shown in Table 1. There was a wide distribution of ages, ranging from 22 to 90 years, with a mean of 69 years. Fifty-six (53%) patients were male. A significant number had underlying hypertension (58%), diabetes mellitus (52%), and chronic renal failure (21%). The etiologies of ARF are shown in Table 2. The
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Table 1. Clinical characteristics of 106 patients with acute renal failure in the cardiac care unit Age (mean 6 SD) (range) Male Hypertension Diabetes mellitus Chronic renal failure (baseline creatinine $2.0 mg/dl)
69 6 15 (22–90) 56 (53%) 61 (58%) 55 (52%) 22 (21%)
Mortality rates according to the etiology of ARF are shown in Table 4. CHF and arrest/arrhythmia as ARF etiologies had the highest mortality (59% and 79%, respectively). The lowest mortalities (17%) were in the volume depletion and contrast groups. The relative risks for mortality were statistically significant for arrest/ arrhythmia (1.72) and contrast (0.31).
Abbreviation is: SD, standard deviation.
most common etiology was CHF, accounting for 37 cases (35%). Twenty-eight cases (26%) were multifactorial, usually involving a low cardiac output state. Other etiologies included arrest/dysrhythmia (13%), contrast media (11%), volume depletion (6%), sepsis (6%), and obstruction (3%). ACEIs were not felt to be the primary etiology of any of the cases, but they were felt to contribute to three of the multifactorial cases. Fifty-three of the 106 patients (50%) survived the hospitalization. In addition, three of the hospital survivors were discharged to hospice care. In comparison, the hospital mortality for CCU patients without ARF was 8%. Twenty-five patients (24%) met the criteria for ARF on the day of admission. Fourteen of these patients (56%) survived the hospitalization, which was not significantly different from the 48% survival among the patients with delayed ARF. Nephrology consultation was obtained in 44 cases (42%), and there was no significant difference in mortality based on consultation. Eighteen patients (17%) received dialysis, and 9 (50%) survived the hospitalization. Four of these patients, or 44% of the patients who received dialysis and survived, were discharged on dialysis. Four patients recovered enough renal function to discontinue dialysis, and one chose not to undergo chronic dialysis and was discharged to hospice care. The relative risks for mortality based on the prospectively defined risk factors are shown in Table 3. Oliguria, mechanical ventilation, and decreased cardiac function, defined either as an ejection fraction of less than 25% or a cardiac index of less than 2.0, were associated with a statistically significant increased risk for hospital mortality. The relative risk with oliguria was 1.72 (P 5 0.01), with mechanical ventilation was 1.70 (P 5 0.01), with a decreased ejection fraction was 1.77 (P 5 0.009), and with a decreased cardiac index was 2.11 (P 5 0.003). Multivariate analysis did not find these factors to predict mortality. Because ejection fraction and cardiac index are likely to be related, they were combined as one variable (ejection fraction ,25% or confidence interval ,2.0 liter/min/m2) for the multivariate analysis and were still not found to be an independent predictor of mortality. Age, peak creatinine, chronic renal failure, admitting diagnosis, nephrology consult, or dialysis did not predict hospital mortality.
DISCUSSION The incidence of ARF in patients with acute cardiac diagnoses in the CCU was 4%. This number likely underestimates the true incidence of ARF in this patient population, because we included only cases that met criteria for ARF during the CCU stay, which was often brief (the mean length of stay was 2.2 days). In fact, 220 (9% of CCU admissions) patients had an increase in serum creatinine from less than 2.0 mg/dl in the CCU to greater than 2.0 mg/dl during the rest of the hospital course. Compared with prior reports, this incidence is greater than that reported for community-acquired (1%) or hospital-acquired ARF in a mixed population of medical and surgical patients (2%) [2, 6]. Hou et al found a 5% incidence of hospital-acquired ARF but used much less stringent criteria to define ARF [1]. The incidence of ARF in other ICU populations has ranged from 3 to 30% [7–14]. In addition, the absolute numbers of patients with ARF concomitant with severe cardiac disease can be expected to rise sharply over the next few decades because of the rapidly escalating prevalence of heart disease. Preliminary evidence pointing to this trend already exists. In an analysis of ARF in ICU patients in two different time periods, McCarthy found a significant increase in the percentage of cases due to “cardiac prerenal” causes from 15% in 1977 through 1979 to 30% in 1991 through 1992 [15]. It is not surprising that the most common etiologies of ARF were hemodynamic causes related to the underlying cardiac disease. Thirty-five percent of cases were due primarily to severe CHF, and it also contributed to most of the multifactorial cases, which accounted for an additional 26% of all cases. Many of these patients have severely compromised cardiac function, and when ARF develops, questions regarding prognosis arise. Patients, families, and physicians would all like to know the prognosis in order to make decisions regarding further therapy. Previous studies have examined cardiac morbidity as a prognostic factor, but results have been contradictory. Some have found an association with mortality [7, 16–23], whereas others have not [24, 25]. It is difficult to compare these studies because of a wide variation in the definition of “cardiac failure,” including hypotension, CHF, infective endocarditis, myocarditis, arrhythmias, and myocardial infarction. Also, until now, no studies have specifically examined cardiac function as a prognostic factor in the CCU population.
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Behrend and Miller: ARF in the cardiac care unit Table 2. Etiologies of acute renal failure (ARF) in the cardiac care unit Etiology Hemodynamic Volume depletion CHF Arrest/dysrhythmia ACEI Contrast Sepsis Obstruction Multifactorial Total
Initial ARF 5 8 3 0 0 1 3 5
Delayed ARF
(20%) (32%) (12%)
1 29 11 0 12 5 0 23
(4%) (12%) (20%)
25 (24%)
Total
(1%) (36%) (14%)
6 37 14 0 12 6 3 28
(15%) (6%) (28%)
81 (76%)
P value
(6%) (35%) (13%)
0.003 0.81 1.00
(11%) (6%) (3%) (26%)
0.06 1.00 0.01 0.45
106 (100%)
Abbreviations are: CHF, congestive heart failure; ACEI, angiotensin-converting enzyme inhibitor.
Table 3. Risk factors for hospital mortality
Age (mean 6 SD) Peak creatinine $3.0 mg/dl Oliguria Mechanical ventilation CRF Admit diagnosis CHF CAD Dysrhythmia EF ,25% (N 5 99) CI ,2.0 liter/min/m2 (N 5 67) Nephrology consult Dialysis
Deaths N 5 53
Survivors N 5 53
Relative risk (95% confidence interval)
69 6 14 40 22 30 8
68 6 15 34 9 16 14
1.33 1.72a 1.70a 0.68
(0.83–2.13) (1.21–2.44) (1.16–2.50) (0.38–1.22)
18 23 12 28 26 21 9
21 25 7 17 11 23 9
0.88 0.93 1.34 1.77a 2.11a 0.92 1.00
(0.59–1.33) (0.63–1.36) (0.89–2.02) (1.15–2.71) (1.22–3.65) (0.62–1.37) (0.60–1.66)
Abbreviations are: SD, standard deviation; CRF, chronic renal failure; CHF, congestive heart failure; CAD, coronary artery disease; EF, ejection fraction; CI, cardiac index. a P # 0.01
Table 4. Hospital mortality according to ARF etiology Deaths
Survivors
Mortality
Relative risk (95% confidence interval)
Hemodynamic Volume depletion CHF Arrest/dysrhythmia ACEI Contrast Sepsis Obstruction Multifactorial
1 22 11 0 2 3 1 13
5 15 3 0 10 3 2 15
17% 59% 79%
0.32 (0.05–1.94) 1.32 (0.91–1.92) 1.72a (1.21–2.45)
17% 50% 33% 46%
0.31a 1.00 0.66 0.91
Total
53
53
50%
Etiology
a
(0.09–1.10) (0.44–2.28) (0.13–3.30) (0.58–1.42)
P , 0.05
At least three prior studies have found CHF specifically, rather than the broadly defined “cardiac failure,” to be a risk factor for hospital mortality in ARF. Lien and Chan evaluated 58 patients retrospectively and found CHF, not specifically defined, to be associated with increased mortality by univariate (RR 5 1.9), but not multivariate analysis [16]. Lohr, McFarlane, and Granthan retrospectively evaluated 126 patients with
ARF and found CHF, defined as characteristic radiographic appearance, rales, decreased cardiac output, or the presence of a third heart sound, to have a significantly increased risk of mortality (RR 5 1.3) [17]. In addition to CHF, Lohr, McFarlane, and Granthan found hypotension, assisted ventilation, gastrointestinal dysfunction, and sepsis to be prognostic factors and proposed a prognostic index based on the number of these factors pres-
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ent. When applied to a different set of patients by a separate investigator, Lohr’s prognostic index did predict mortality [18]. These studies all exclusively examined patients treated with hemodialysis. Hemodynamic instability often complicates dialysis in patients with severely compromised cardiac function. Therefore, theoretically, the increased mortality in these studies could have been related to complications of hemodialysis. However, most of the patients in our study did not undergo dialysis, and we found a similar adverse prognostic effect by univariate but not multivariate analysis. Previous studies have noted that the timing of onset (community versus hospital acquired) is important in the prognosis of ARF. The proportion of cases with initial or community-acquired ARF was much lower in our study (24%) than has been reported previously (60%) [14, 26]. This may be related to the urgency and rapidity with which acute cardiac syndromes lead to hospitalization. In the CCU, we found no significant difference in the mortality of initial (44%) versus delayed ARF (52%). The discrepancy with other studies, which report a 20% absolute increase in mortality for patients with delayed ARF [14, 26], is likely due to the different etiologies of ARF. The decreased mortality in community-acquired ARF has been explained by an increased proportion of cases in this group due to etiologies with better prognoses. Specifically, 17 to 30% of these patients have been reported to have obstructive ARF [6, 26, 27]. Table 2 shows the different etiologies of ARF divided into initial and delayed ARF in our study. Although there were more obstructive cases in the initial group, they accounted for only 12% of the initial ARF cases and only 3% of the cases overall. Volume depletion, which had a low mortality, was also more common in the initial group. However, all of the contrast-induced ARF cases were in the delayed group, as expected, and also had a low mortality rate (17%), which tends to offset any survival advantage of the initial ARF group. Although the mortality was increased in patients with severely decreased cardiac function, there were still a significant number of survivors. Thirty percent of those with a cardiac index of less than 2.0 liter/min/m2 survived to discharge. The patient with the lowest recorded cardiac index in this study (1.1 liter/min/m2) survived. Although decreased ejection fraction or cardiac index was more common in the nonsurvivors, they were also present in one third of survivors (Fig. 1). Depressed cardiac function, therefore, cannot by itself be used as an indication to withhold treatment of ARF. However, considering cardiac function along with the overall clinical picture may be important in predicting prognosis. There has been a great deal of interest in developing prognostic scores to predict the outcome of ARF. Several scoring systems have been proposed; however, they are often
Fig. 1. Ejection fraction (EF; ; ,25%) and cardiac index (CI; j; ,2.0 liter/min/m2) in survivors and nonsurvivors. EF and CI were available in 99 and 67 patients, respectively. Among survivors, 33% had an EF ,25% and 35% had a CI ,2.0 liter/min/m2. Among nonsurvivors, 60% had an EF ,25%, and 72% had a CI ,2.0 liter/min/m2.
complicated and may not be valid outside of the population from which they were developed. Recently, Lian˜o has developed a prognostic index for acute tubular necrosis that is simple to calculate and was validated in a separate hospital [28]. The index was developed and tested in a diverse patient population, including medical, surgical, nephrotoxic, and septic etiologies of ARF, but does not include cardiac function as a prognostic factor. It would be interesting to test this index in a population of cardiac patients and to examine if cardiac function could improve its prognostic ability. Hospital survivors who required dialysis remained dependent on dialysis at the time of discharge more frequently than has been reported previously. Prior studies have reported a 17 to 33% incidence of dialysis dependency among hospital survivors who required hemodialysis for ARF in an ICU [15, 29], whereas 56% (5 out of 9) of such patients in our study remained dependent on dialysis at discharge. Possible explanations for this difference include the small number of patients requiring dialysis in this study or an earlier discharge. Alternatively, it is also plausible that CHF impairs renal recovery through impaired renal blood flow and altered glomerular hemodynamics. Because we had only nine patients survive after receiving dialysis, we could not adequately evaluate any differences that might have existed between patients that recovered renal function and those that remained dialysis dependent. Future studies should address this area. In summary, ARF is common in CCU patients, is most often hospital acquired and is due to hemodynamic causes. There may be a decreased rate of renal recovery, although a larger number of patients need to be exam-
Behrend and Miller: ARF in the cardiac care unit
ined to confirm this finding. Although there is a high mortality rate in these patients, there are a significant number of survivors, even among patients with severely depressed cardiac function. Future studies are needed to address the long-term survival of these patients, including both quantity and quality of life. Reprint requests to Steven B. Miller, M.D., Washington University School of Medicine, Renal Division Box 8126, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA. E-mail: [email protected]
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