1 Service de Réanimation Médicale Polyvalente and 2 Service de Néphrologie, Hôpital Gabriel Montpied and 3 Service d'Epidémiologie et Santé Publique, Hôtel-Dieu, Centre Hospitalier Universitaire de Clermont-Ferrand, France
Correspondence and offprint requests to: Bertrand Souweine, Service de Réanimation Médicale Polyvalente, Centre Hospitalier Universitaire Gabriel Montpied, BP 69, 63003 Clermont-Ferrand Cedex 1, France. Email: bsouweine{at}chu-clermontferrand.fr
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Abstract |
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Methods. All consecutive CD patients admitted to an adult, 10 bed medical/surgical ICU at a university hospital between January 1996 and December 1999 were included in this prospective observational study. Demographics, characteristics of the underlying renal disease, admission diagnosis, the number of organ system failures (OSFs) excluding renal failure and SAPS II, both calculated 24 h after admission, the duration of mechanical ventilation, ICU survival and survival status at hospital discharge and 6 months after discharge were recorded.
Results. A total of 92 CD patients, 16 on peritoneal dialysis and 76 on haemodialysis, were included. The main reason for ICU admission was sepsis and the mean ICU length of stay 6.2±9.9 days. ICU mortality was 26/92 (28.3%) and was associated in multivariate analysis with SAPS II (P<0.001), duration of mechanical ventilation (P<0.01) and abnormal values of serum phosphorus (high or low; P<0.05). Hospital mortality was 35/92 (38.0%) and was accurately predicted by SAPS II [receiver operating characteristics curve: 0.86±0.04; goodness-of-fit test: C = 6.86, 5 degrees of freedom (df), P = 0.23 and H = 4.78, 5 df, P = 0.44]. The 6 month survival rate was 48/92 (52.2%).
Conclusions. CD patients admitted to the ICU are a subgroup of patients with high mortality and SAPS II can be used to assess their probability of hospital mortality. The severity of the acute illness responsible for ICU admission and an abnormal value of serum phosphorus are determinants for ICU mortality.
Keywords: chronic dialysis; intensive care unit; outcome
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Introduction |
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The epidemiology of chronic dialysis (CD) patients shows growing numbers of patients who are getting older and sicker. These patients frequently develop cardiovascular complications, such as coronary artery disease, cerebrovascular disease, haematological abnormalities, gastrointestinal bleeding and bacterial infections, which are the principal cause of morbidity and a major cause of death in CD patients [1,3]. CD patients present a high risk of multiorgan dysfunction stemming from pre-existing medical problems and complications secondary to renal replacement therapy. Thus, as the number of older patients starting dialysis increases, so will that of patients requiring admission to the intensive care unit (ICU). In a recent study it was calculated that 2% of CD patients require ICU admission every year [4]. In addition, ESRD providers in the US [5] reported that an acute medical/surgical complication in CD patients is a listed cause of dialysis discontinuation prior to death. To describe the epidemiology and the outcome of ICU patients is of prime importance in helping CD patients and their family to plan what kind of care they would want in the event of critical illness. To date the few data available on the outcome of CD patients admitted to ICUs derive from studies comparing patients with ESRD and those with acute renal failure [4,6].
Different scoring systems have been designed to estimate the probability of hospital mortality and to compare the performance of different ICUs. The Simplified Acute Physiology Score II (SAPS II) was developed to grade the severity of individual ICU patients and to assess prognosis [7]. While most studies show a good SAPS II discrimination, several report calibration as disappointing [8]. Generic scores may fail to adequately predict outcome in ICU-admitted CD patients, since most allocate high points for several clinical and laboratory data that are usually out of the physiological range in CD patients, irrespective of the acute event leading to ICU admission. To our knowledge, only one case-control study, involving a relatively small number of CD patients, has investigated the adequacy of SAPS II to predict outcome [4]. However, calibration was not tested and, therefore, it is not known whether SAPS II is valid for this specific cohort.
The aim of the study was to describe the clinical features and outcome of CD patients admitted to an ICU and to confirm that SAPS II is able to predict their hospital mortality.
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Subjects and methods |
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CD patients
All consecutive CD patients, either on chronic haemodialysis or on chronic peritoneal dialysis, admitted to the ICU between January 1996 and December 1999 were enrolled in the study. For CD patients readmitted to the ICU during the study period, only the first ICU admission was taken into account. During their ICU stay, renal replacement therapy using intermittent haemodialysis was administered on average every other day. Haemodialysis was performed using bicarbonate dialysate and biocompatible membranes, essentially polyacrylonitrile membranes. The vascular accesses for haemodialysis procedures were the permanent arteriovenous fistula in the majority of patients and dialysis catheters in the others.
The Ethics Committee of the hospital was informed about the study design and raised no objections. Informed consent from patients was not requested, but patients were informed about the study.
Data collection
We recorded diagnosis on admission, the variables necessary to calculate SAPS II [7] and the number of organ system failures (OSFs), other than renal failure [9] during the first 24 h after ICU admission. SAPS II was calculated as indicated by its developers [7]. OSF was defined on the basis of the following features. Cardiovascular failure was defined by the presence of one or more of the following: heart rate 54/min, mean arterial blood pressure
49 mmHg, occurrence of ventricular tachycardia, occurrence of ventricular fibrillation and serum pH
7.24 with PaCO2 of
49 mmHg. Respiratory failure was defined by the presence of one or more of the following: respiratory rate
5/min or
49/min, PaCO2
50 mmHg, AaDO2
350 mmHg and need for mechanical ventilation (MV). Haematological failure was defined by one or more of the following: white blood cell count
1000/mm3, platelet count
20 000/mm3 and haematocrit
20%. Neurological failure was defined by a Glasgow coma score
6 in the absence of sedation. One point was given for each OSF and, thus, the number of OSFs per patient ranged from 0 to 4. Additional laboratory factors recorded on ICU admission were serum uric acid, serum phosphorus and serum cholesterol levels before a new dialysis. Severe sepsis was defined as reported previously by Bone et al. [10]. The following clinical and laboratory data related to ESRD were collected: cause of renal disease, prior duration of CD and mode of dialysis, either haemodialysis or peritoneal dialysis. Diabetes mellitus and cardiovascular disease (arterial hypertension, history of myocardial infarction or coronary revascularization procedure or angiographic evidence of coronary stenosis, peripheral vascular disease and prior vascular surgery for atherosclerosis and history of cerebral infarction) were recorded. We also noted the use and the duration of MV, the ICU length of stay and survival status at hospital discharge and 6 months after ICU discharge.
There was a standard procedure for collecting medical data, which were recorded by two physicians (A.E.H. and N.G.). All data gathered during the study period were systematically audited by a third physician (G.M.). In the event of disagreement, another physician (B.S.) was invited to give his opinion. The data included in the quality assessment were SAPS II variables, duration of hospitalization, outcomes at ICU and hospital discharge and use and duration of MV.
The SAPS II score, age, ICU length of stay and vital status at hospital discharge of all the non-CD patients admitted to the ICU during the same period were extracted from the general database of the Clermont-Ferrand Hospital registry.
Rationale and methodology of statistical analysis
It was decided to use univariate analysis to identify the variables to be included in a preliminary logistic regression model. All values were expressed as means±SD. The CD patients variables, including SAPS II score, were analysed by univariate analysis to compare survivors and non-survivors at ICU discharge. Univariate statistical analysis was performed by chi-square or Fisher tests when necessary to compare categorical variables and by MannWhitney U-test to compare continuous variables. Multivariate logistic regression analysis was performed, with survival at ICU discharge being the dependent variable and the variables found in the univariate analysis with a P-value of <0.15 for survivors and non-survivors being the independent variables. When the degree of correlation between the variables entered in the multiple regression equation is high, the regression model can produce incorrect variance estimates and may give a misleading interpretation of the model. To address the problem of multicolinearity, a correlation matrix was used to assess the overlap between the data. A high Spearman correlation (r>0.5) indicates that the data are highly correlated with each other [11]. One way of mitigating the harmful effect of multicolinearity is to delete offending variables from the regression model. This was done on the basis that one or more variables are redundant [11].
We then tested the performance of SAPS II in predicting hospital mortality. The individual specific probability of death derives from the SAPS II model. The following variables have been included in the equation: SAPsII, the number of OSF's, the duration of MV, serum phosphorus, and dialysis category. The probability of ICU death was calculated as follows:
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We calculated the predicted hospital death rates by summing predicted risks of dying for individual patients and dividing by the number of patients. The predicted and actual death rates were compared using the chi-square test. The ability of the model to discriminate between survivors and non-survivors was studied by receiver operating characteristic (ROC) curves. The ROC curves were constructed by plotting the true positive rate (sensitivity) against the false positive rate (100 specificity) at different risk thresholds. The ability of the standard SAPS II to accurately reflect the probability of hospital mortality was assessed using the HosmerLemeshow goodness-of-fit calibration test (H statistic and C statistic) and calibration curves [12]. Calibration evaluates the degree of correspondence between a model-estimated probability of mortality and the observed mortality rate. A low P-value suggests that the model does not correctly reflect the actual outcome [12].
Data analyses and statistics analysis were performed using SAS software (SAS Institute Inc). A P-value of <0.05 was considered statistically significant.
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Results |
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Discussion |
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Although this study was limited to one centre and the ICU-admitted CD population was small (n = 92), the characteristics of the CD patients according to mean age, mode of dialysis and mean primary renal disease were representative of a general CD population [13].
To our knowledge, only two studies have reported the outcome of CD patients admitted to an ICU. The first study evaluated the impact of acute renal failure with regard to the total loss of renal function on outcome [6]. The CD and acute renal failure patients had similar APACHE III scores with no difference between the observed and predicted hospital mortality. Despite this similarity in APACHE III scores, the observed hospital mortality was significantly higher in acute renal failure patients than in CD patients. The study involved 57 CD patients with an 11% ICU mortality and a 14% hospital mortality. These lower ICU and hospital mortality rates may be related to differences in case mix and in admission diagnoses, but any explanations remain speculative because of the lack of information on ERSD patients and on their ICU admission characteristics. The other study involved 38 acutely ill CD patients with a mean age of 44.9 years [4]. The first reason for ICU admission was sepsis. As reported by the authors, many CD patients were referred to ICU for post-operative care. This study did not report factors associated with ICU mortality. The mean SAPS II score of CD patients was 44.7 with an observed hospital mortality of 34.2%. In our study, CD patients were older with a slightly higher mean SAPS II and hospital mortality. Most CD patients were admitted because they required life-sustaining support. Sepsis was the leading cause for ICU admission and the observed ICU mortality in CD patients admitted for severe sepsis (37.5%) was comparable to reported ICU mortality for this type of admission [8].
In our study, the CD patients formed a subgroup of patients with a greater illness severity and a higher mortality than that observed in the non-CD ICU patients. This higher severity may be related to the frequency of associated comorbidity, especially cardiovascular comorbidity, which is recorded in almost all of this population. However, half of the CD patients were 6 month survivors, which shows that intensive care can be successful and should not be dismissed out of hand. As far as we know, no previous study has reported long-term survival after ICU discharge of CD patients.
Prognostic analysis at ICU discharge
In our study, univariate analysis identified four variables related to ICU mortality: SAPS II, the number of OSFs, MV duration and high or low serum phosphorus concentration. We found no significant differences in CD patient characteristics between survivors and non-survivors with regard to the distribution of primary renal disease and the prior dialysis duration. Given the sample size, ICU mortality did not seem to be related to the type of dialysis. However, since we did not evaluate all the important predictors of long-term mortality in CD patients, such as nutritional status and serum albumin concentration [14,15], we cannot exclude that some of them may have had an impact on ICU mortality. In addition, formal analysis efficiency either by measurement of dialysis dose (Kt/V) or by urea reduction ratios was not performed and, thus, the impact of dialysis modality and dose per se on the ICU outcome of these patients cannot be determined from our data.
When SAPS II, the number of OSFs and MV duration were included in the multivariate analysis, their significance level decreased sharply, suggesting an overlap between the variables. A high degree of correlation between data entered in a multivariate analysis may distort the relationship between outcome and vital explanatory variables. This is probably why in the first multivariate model SAPS II and an abnormal value of serum phosphorus level were not identified as prognostic factors. Given the need to address multicolinearity, we used Spearman correlation to diagnose redundant data. Matrix analysis revealed a high correlation between the number of OSFs and both SAPS II and MV duration. The number of OSFs was, therefore, withdrawn from the multivariate model [11]. The second multivariate model, taking into account multicolinearity, retained the following predictive variables: SAPS II, MV duration and abnormal value of serum phosphorus level.
The severity of the critical illness as defined by the generic prognostic scores, the number of acute organ dysfunctions and MV are classically reported as important adverse prognostic factors in the overall population. Similar results have been reported after ICU admission of patient groups with chronic diseases [16,17]. The impact of abnormal (high or low) serum phosphorus levels on ICU survival needs to be highlighted. Hypophosphataemia is a multifactorial event and may be related to the severity of acute illness [18]. In addition, it often reflects severe malnutrition, which affects up to half of CD patients, and malnutrition is a well-known factor of morbidity and mortality in this population [14]. In contrast, elevated serum phosphorus is of poor prognostic value in CD patients and preventing hyperphosphataemia appears to reduce morbidity and mortality from cardiovascular disease, which is the leading cause of death in CD patients [19]. According to new recommendations, the control of serum phosphorus levels is one of the targets set for the management of mineral homeostasis in ESRD patients [20]. Thus, the results of the multivariate analysis suggest that both the severity of the acute illness that motivated ICU admission and the underlying renal disease and its treatment are predictive of ICU mortality in CD patients.
Validity of SAPS II
This report demonstrates that SAPS II is a reliable predictor of hospital mortality for CD patients, although it includes several variables that are usually abnormal in non-critically ill CD patients, i.e. urinary output, serum urea level, serum potassium level and serum bicarbonate level. These variables can count for up to 30 points in the calculation of SAPS II and in our CD patients accounted for an average of 19.1 points, which corresponds to 38.7% of the overall score. Calibration measures how closely mortality prognosis fits the observed mortality. We found that observed and predicted mortality agreed well over the whole range of SAPS II and, hence, SAPS II adequately estimates the severity of ICU-admitted CD patients. However, we must point out that the use of goodness-of-fit is generally more reliable for calibration when the number of patients included is higher than in our sample. Thus, given the small size of the population, we cannot exclude that the goodness-of-fit test failed to show a difference between observed and estimated hospital mortality.
In summary, this study provides evidence that in ICU-admitted CD patients the severity of the acute illness, the duration of MV and abnormal values (high or low) of serum phosphorus are reliable prognostic markers for ICU mortality. Our findings suggest that the appropriateness of intensive care for these patients should be discussed on the same basis as for the general population.
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Acknowledgments |
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Conflict of interest statement. None declared.
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References |
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