OUTCOMES AND APACHE II PREDICTIONS FOR CRITICALLY ILL PATIENTS WITH ACUTE RENAL FAILURE REQUIRING DIALYSIS

Abstract

Background:Despite the widespread availability of dialytic and intensive care unit technology, the probability of early mortality in critically ill patients with acute renal failure (ARF) is still high, and the evaluation of the patients' prognosis has been difficult. The Acute Physiology and Chronic Health Evaluation II (APACHE II) score is a reliable indicator of severity of illness and likelihood of survival in critically ill patients with ARF. We have attempted to determine whether the APACHE II scoring system can be used to predict prognosis. Methods: A retrospective cohort study evaluated the medical records of 100 consecutive patients in intensive care units with acute renal failure who required dialysis from January 1997 through December 1998. Results: Of the 100 patients studied, 65 were men and 35 were women. The mean age of survivors and nonsurvivors was 59.4 ± 20.3 years and 58.3 ± 20.0 years. The overall mortality rate was 71%. There were no significant differences between survivors and nonsurvivors in age, gender, or indication for dialysis. The cause of death in the majority of patients was related to higher APACHE II score during the 24 hours immediately preceding the initiation of acute hemodialysis, and carry mortality rates exceeding 85% with an APACHE II score of 24 or higher. Conclusion: We conclude that mortality rate for acute renal failure in intensive care unit patients continues to be high. The use of the APACHE II score determined at the time of initiation of dialysis for patients with ARF is a statistically significant predictor of patient survival. There is a significant trend with APACHE II score for outcome.

• Acute renal failure
• APACHE II
• Prognosis
• Critical care

INTRODUCTION

The mortality of patients with ARF in an intensive care unit (ICU) is still very high and has not improved over the last few years despite technical improvements [1-2]. Patients who develop ARF requiring dialysis often have multiple coexisting disease processes that contribute to the high morbidity and mortality. A number of investigators have suggested that the apparent failure to improve the outcome of ARF requiring dialysis results from a changing patient mix, with a steady increase in the severity of illness and multiple comorbid conditions [3-4]. Because ARF is a heterogeneous syndrome occurring in a wide range of patients with diverse disease etiologies, predicting outcome after the onset of ARF is difficult.

Numerous mortality prediction models have been developed in the past few years. Several general models were developed to predict the risk in multidisciplinary ICUs [5-10]. Other prediction models have been developed specifically for ARF patients [11-14], some of which were based on patients receiving dialysis [13-15]. The APACHE II scoring system has been among the most widely used source of prognostic information on the risk for death of patients admitted to ICUs. The APACHE II scoring system has the advantage of being easy to use, and has been used more frequently for risk stratification in ARF than other similar scoring systems. The APACHE II system has also been used to model outcomes other than survival [[16]]. Furthermore, the APACHE II score has traditionally been performed at the time of admission to the ICU, whereas the prognosis of patients with ARF requiring dialysis may best be determined on the day of dialysis initiation [[17]].

We therefore studied retrospectively the relations between APACHE II scores at the time of initiation of dialysis and mortality to define predisposing factors to ARF, and their relative influence on mortality in critically ill patients with ARF.

PATIENTS AND METHODS

Patient Information and Treatment

The charts of all patients with acute renal failure who required dialysis in the medical, general surgical, cardiac, cardiac surgical, trauma, and bone marrow transplant ICUs of Chang Gung Memorial Hospital in a two-year period (1997–1998) were reviewed. One hundred patients were identified. A retrospective analysis of the available clinical and laboratory data was performed. Case records were reviewed to identify patient sex, age, APACHE II scores on the first day of dialysis, length of stay, and outcome. Sepsis was defined as a microbiologically proven focus of infection and deterioration of the clinical state, as evidenced by at least two of the following: (a) temperature ≥38°C or <36°C; (b) leukocytosis >12 × 10⁹ L, <4 × 10⁹ L, or >10% immature form; (c) heart rate >90/min; (d) respiratory rate >20/min or PaCO₂ < 32 mmHg. Acute renal failure was defined as a serum creatinine level exceeding 3.2 mg/dL or a two-fold creatinine rise in chronic renal failure, after correcting prerenal causes and mechanical obstruction, or the acute need of renal replacement therapy [18-19]. The indication for dialysis included: volume overload with pulmonary edema inadequately controlled with diuretic therapy; hyperkalemia refractory to conservative measures; the need for hyperalimentation with insufficient urinary output; or a sign or symptom, such as encephalopathy, for which uremia could not be ruled out as a precipitating cause. We utilized continuous renal replacement therapy techniques in the hemodynamically unstable patients (systolic blood pressure <90 mmHg at the time of dialysis initiation). There were no strict laboratory criteria employed in the decision to initiate treatment. All cases of ARF requiring dialysis were included, with the exception of ARF after renal transplantation. The study included ARF attributed to acute tubular injury, acute glomerulonephritis, hepatorenal syndrome, and urinary tract obstruction. One hundred patients received renal replacement therapy; 90 were treated with intermittent hemodialysis (IHD), and 10 with continuous renal replacement therapy (CRRT).

APACHE II Scoring

The APACHE II score is the sum of three components: an acute physiology score, an age score, and a chronic health problems score, summarized in Table 1. Scores range from 0 to 71, with higher values having a worse prognosis. The acute physiology score is based on the worst physiological values (i.e., the values giving the greatest number of points) during the first 24 hours of admission for 12 acute physiological measurements routinely collected: temperature; mean arterial pressure; heart rate; respiratory rate; oxygenation; arterial pH; serum sodium, potassium, and creatinine levels; hematocrit; white blood cell count; and score on the Glasgow Coma Scale. In our study, the physiology component was calculated on the basis of the worst physiological measurement on the day of the initiation of dialytic treatment. For the coma score, patients were assessed without adjustment for medications that may influence neurological function.

Table 1. APACHE II Scoring System

Acute Physiology Score
Variable	+4	+3	+2	+1	0	+1	+2	+3	+4
Temperature (°C)	≥41	39∼40.9		38.5∼38.9	36∼38.4	34∼35.9	32∼33.9	30∼31.9	≤29.9;
Mean arterial BP (mmHg)	≥160	130∼150	110∼129		70∼109		50∼69		≤49
Heart rate	≥180	140∼179	110∼139		70∼109		55∼69	40∼54	≤39
Respiratory rate	≥50	35∼49		25∼34	12∼24	10∼11	6∼9		≤5
1. AaPO2 (mmHg)	≥500	350∼499	200∼349		<200	61∼70		55∼60	≤55
2. PaO2 (mmHg					>70
Arterial pH	≥7.7	7.6∼7.69		7.5∼7.59	7.33∼7.49		7.25∼7.32	7.15∼7.24	<7.15
3. Serum HCO3^−	≥52	41∼51.9		32∼40.9	23∼31.9		18∼21.9	15∼17.9	<15
Serum Na^+(meq/L)	≥180	160∼179	155∼159	150∼154	130∼149		120∼129	111∼119	≤110
Serum K^+(meq/L)	≥7	6∼6.9		5.5∼5.9	3.5∼5.4	3∼3.4	2.5∼2.9		<2.5
Serum Creatinine (mg/dL)	≥3.5	2∼3.4	1.5∼1.9		0.6∼1.4		<0.6
Hematocrit (%)	>60		50∼50.9	46∼49.9	30∼45		20∼29.9		<20
WBC count (cu/mm) × 1000	≥40		20∼39.9	15∼19.9	3∼14.9		1∼2.9		<1
4. Glascow coma
score
1. If FiO2 ≥50% record AaPO2
2. If FiO2 <50% record PaO2
3. Use only if no ABG
4. Score = 15 − actual GCS

Age score
Age(years)	<44	45∼54	55∼64	65∼74	>74
Scoring	0	2+	3+	5+	6+

Chronic Health Problems Score
Chronic health Adjustment	Biopsy Proven Cirrhosis	Heart Association Class IV	Severe COPD	Chronic Dialysis	Immune-Compromised
Scoring	5+	5+	5+	5+	5+

Statistical Analysis

Continuous variables are summarized by means and standard deviations and comparisons evaluated by Student's two-tailed t test for unequal variance. Univariate analysis of nonparametric factors between survivors and nonsurvivors was accomplished by using the Chi-square test. We used the Chi-square test of trend to analysize mortality rates associated with APACHE II scores among all patients. All analyses were two-tailed. p values less than 0.05 were considered statistically significant.

RESULTS

Subject Characteristics

From January 1997 to December 1998 one hundred patients received dialytic therapy for ARF in the ICUs. Sixty-five (65%) were men and 35 (35%) were women. Overall, the in-hospital mortality for the entire group was 71%. The age of survivors and nonsurvivors was not statistically significantly different (mean ± SD: 59.4 ± 20.3 years vs. 58.3 ± 20.0 years, p = 0.806). No gender distinction was noted, 27% (18/65) of men survived, compared to 31% (11/35) of women (p = 0.167). Infective episodes occurred while on the ICUs in 69 patients; 17 of these (24.6%) left the hospital alive. For all patients, the median APACHE II score on the first day of dialysis was 22 (range, 17–27; 25th to 75th percentiles). Table 2 shows the patient characteristics for the survivors and nonsurvivors. There were no significant differences in the number of days from time of ICU admission to dialysis initiation between the two groups.

Table 2. Patient Characteristics

	Survivors	Non-Survivors	p-Value
Outcome	29	71
Age	59.4 ± 20.3	58.3 ± 20.0	0.806
Gender (M:F)	18 : 11	47 : 24	0.167
Duration of ICU stay (days)	39.6 ± 40.5	21.9 ± 20.3	0.032
Admission days	81.2 ± 61.7	27.3 ± 24.5	<0.001
Interval from ICU admission to the start of H/D (days)	10.8 ± 20.5	10.2 ± 14.9	0.891
APACHE II scores	17.72 ± 4.74	23.79 ± 6.92	<0.001

The majority of all patients were thought to have acute tubular necrosis on the basis of clinical history, examination of urinary sediment, and the urinary chemistry profile. The remaining presumptive diagnoses of underlying kidney disease are shown in Table 3. No patient underwent renal biopsy. Those patients who developed ARF secondary to acute pancreatitis (n = 6), rhabdomyolysis (n = 6), or obstructive uropathy (n = 3) tended to have a better prognosis compared to other patients.

Table 3. Presumptive Causes of Acute Renal Failure

	n	Survivors	Survival Rates (%)
Acute tubular necrosis, associated with
Sepsis syndrome	69	17	24.6
Cardiogenic shock or cardiac arrest	15	2	13.3
Hypovolemic shock	46	9	19.6
Nephrotoxin exposure	24	4	16.7
Acute pancreatitis	6	4	66.7
Rhabdomyolysis	6	4	66.7
Hepatorenal syndrome	5	0	0.0
Obstructive uropathy	3	2	66.7
Uncertain	2	1	50.0

Renal Replacement Therapy

All patients received some form of dialytic intervention for ARF according to usual clinical criteria. A total of 90 patients received IHD, and CRRT was performed in 10 patients. Patients that underwent CRRT had a greater mortality rate (90%) compared to those undergoing IHD (68.9%) (p < 0.001). This is probably because, in general, more unstable, sicker patients are chosen for CRRT.

Mortality and APACHE II Scoring

Data to calculate APACHE II scores on the day of the initiation of dialytic treatment were available for 100 patients. The mean APACHE II score for all patients was 22.03 ± 6.92 (range 6–37). The mean APACHE II score on the first day of dialysis was significantly higher in nonsurvivors than survivors, 23.79 ± 6.92 vs. 17.72 ± 4.74, respectively (p < 0.001). APACHE II scores stratified according to hospital mortality are shown in Figure 1. As can be seen in Figure 2, as the APACHE II score increases, the percentage of patients dying also increases. There was a progressive and significant increase in mortality associated with an increase in the APACHE II score among all patients (χ² for trend p = 0.022, Fig. 2).

Figure 1. Box plots depicting the APACHE II scores for patients according to their outcome. Boxes represent 25th to 75th percentiles, with 50th percentile (solid line) value shown within the boxes. The minimum and maximum are shown as capped bars.

Figure 2. Mortality in APACHE II scoring system patients with acute renal failure requiring dialysis (χ² for trend p < 0.05).

DISCUSSION

In our experience, only 29% of critically ill patients with acute renal failure requiring renal replacement therapy will survive to leave the hospital. The prognosis of critically ill patients with ARF requiring dialysis is poor. Although dialysis can be lifesaving in some circumstances, it may be unhelpful in others, probably because of the uncontrollable underlying nonrenal disease [[20]]. Survival of patients with ARF does not appear to have improved over the past several decades [[2]], [[21]]. However, comparisons between various studies may be difficult because of differences in patient populations, such as age, severity of illness, associated premorbid medical conditions, and other acute complications. A recent report by Cosentino and colleagues evaluated survival in the ARF patients in the ICU [[22]]. Mortality of patients in their study was 79.1%, which is very similar to our studies (71%) as well as to other reports [[20]], [23-24]. Their reports also evaluated critically ill patients requiring dialysis for ARF and found mortality ranging from 67.3 to 81%.

Two earlier editorials, in 1972 [[25]] and 1983 [[2]] elegantly asked why the mortality rate associated with ARF had remained so high, despite technological improvements. This interrogation persists. Some investigators have concluded that ICU patients deemed appropriate for the initiation of dialysis in recent years have been more critically ill. Patient age has increased, illness severity has worsened, and the causes of renal failure in young adults associated with a good outcome (predominantly obstetric complications and trauma) have become progressively less common. Previous health, comorbid disease, patient age, and the number of failed organ systems influence outcome, regardless of the modality of renal support [[26]].

Renal replacement therapy has evolved in the pursuit of improved survival, with the development of continuous rather than intermittent treatment. Possible benefits of continuous therapy include improved hemodynamic stability, predictable and gradual control of metabolic disturbance with the subsequent maintenance of a stable metabolic environment, the ability to titrate fluid balance for “unlimited” volumes of nutrition and/or drugs. Despite these advantages, there are few data to indicate a survival advantage from continuous treatment [[26]]. In our study, patients dialysed with CRRT had a greater risk of death than those dialysed with IHD. However, no definite conclusions can be made, since the sicker, more unstable patients are managed with CRRT. In order to determine which type of dialytic intervention may be more beneficial for ICU patients with ARF, a prospective, randomized trial would have to be conducted.

APACHE II scores are already widely used to quantify risk factors in patients admitted to ICUs. The widespread adoption of the APACHE II scoring system in the assessment of patients with ARF would enable a more meaningful comparison of different modes of medical and dialysis treatment, and would provide valuable information on the changing epidemiology of ARF. The APACHE II had originally been designed to predict outcomes on admission; some investigators used the APACHE II score obtained within 24 hours of initiation of dialysis, as we did in our study. Because nephrologists frequently do not see patients in the ICU before the need for dialysis, scores determined at this time are also likely to be more readily available to nephrologists for help in predicting outcome [[17]].

The APACHE II score calculated at the time of dialysis initiation was significantly higher for the nonsurvivors in our report (p < 0.001). In our study, an APACHE II score over 27 was invariably associated with a fatal outcome, however, too few patients were studied in this group to conclude that renal replacement therapy is futile. We observed a trend for a significant rise in mortality rates associated with higher APACHE II scores among all patients. The mortality rates increased to a large extent when APACHE II scores above 23 were noted in our study. Many factors can influence outcomes in an ICU patient population, including case mix, severity of illness, and quality of care. Compared to other reports, our population (mean age of 58.60 ± 20.01 years) appeared older, and this may be a factor for relatively higher mortality rates to match the similar APACHE II scores. Furthermore, perhaps infection is a contributory cause of death due to high incidence rates of sepsis (69%) in our patients. The existence of sepsis was a very poor prognostic factor during our study, consistent with the findings of other investigators. It is generally accepted that the underlying disease plays a major part in the prognosis of ARF [[14]], [[27]].

In summary, 71% of critically ill patients with ARF requiring dialysis died in the hospital. Our studies showed that the risk of patients with ARF in the ICUs is increased when APACHE II scores are higher at the time of initiation of dialysis. In addition, mortality rates increase as the APACHE II score on the first day of dialysis increases.