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Influence of antibiotic therapy on mortality of critical surgical illness caused or complicated by infection.

BACKGROUND: Conceptually, appropriateness of antibiotic therapy includes choice of agent relative to susceptibility of pathogens as well as dosing, timing of onset, and duration of therapy, but is most commonly considered in terms of choice of antibiotic. It has been suggested that inappropriate antibiotic selection can result in increased mortality. This study was performed to elucidate the role of scheduled, rotating antibiotic therapy in defining mortality among febrile, infected surgical ICU patients. METHODS: Prospective inception-cohort study of 356 patients during their initial episode of fever (temperature > 38.2 degrees C), caused by infection diagnosed by positive cultures or direct inspection (some cases of peritonitis). Collected data included age, gender, admission APACHE III score, peak temperature, microbial isolates and susceptibility, source of infection, multiple organ dysfunction score, mortality, and several time intervals (time that cultures were collected, time from collection to antibiotic prescription, time from collection to antibiotic administration, duration of therapy). RESULTS: The mean age was 63 +/- 1 years, the mean APACHE III score was 74 +/- 2 points, the mean multiple organ dysfunction score was 8 +/- 1 points, and overall mortality was 31%. Neither the source of infection nor the specific isolate influenced mortality. Antibiotic therapy was appropriate (covered the isolates) in 94% of cases, and did not influence mortality. Duration of therapy was identical between groups (5.1 +/- 0.3 vs. 5.4 +/- 0.3 days, p = 0.61). By logistic regression (dependent variable = mortality), APACHE III score OR 1.025, 95% C.I. 1.021-1.04) and delayed antibiotic administration (30-min intervals, OR 1.021, 95% C.I. 1.003-1.038) were independent predictors of mortality. CONCLUSIONS: The use of scheduled monthly antibiotic cycling in the surgical ICU is associated with a high rate of "appropriate" antibiotic therapy, and appears to maintain or improve resistance patterns. Because antibiotic therapy was mostly appropriate for isolates, initial inappropriate therapy could not be identified as a risk factor for mortality. However, in the setting of appropriate antibiotic choice, the prompt initial administration of antibiotics appears to be crucial for survival, but neither site of infection nor specific pathogen are influential.

APACHE↗

Explaining cost variations in clinical trials using severity of illness measures.

OBJECTIVE: To determine the usefulness of severity of illness measures in explaining the variation in costs observed in economic analyses of clinical trials. METHOD: Hospital costs and three severity of illness measures (Medical Illness Severity Grouping System [MedisGroups], Acute Physiology and Chronic Health Evaluation [APACHE] II, APACHE III) were calculated for patients undergoing surgical management of gastrointestinal malignancies. Regression models were developed to determine the predictive ability of the severity of illness measures on total costs and length of stay of surgical patients. RESULTS: There was not a significant reduction in the cost variance among patients after correcting for severity with use of the MedisGroups score. APACHE II scores were a better predictor of total costs, although this relationship did not reach statistical significance. As a continuous variable, APACHE III scores explained $326 of extra cost for each point on the scale, and as a categorical variable, identified those patients who were most expensive to care for and with long lengths of stay. CONCLUSION: Neither MedisGroups nor APACHE II were found to be useful in explaining cost variations in a clinical trial. The APACHE III system was more useful in discriminating resource intensive patients.

Clinical Trials as Topic↗

Should the pre-sedation Glasgow Coma Scale value be used when calculating Acute Physiology and Chronic Health Evaluation scores for sedated patients? Scottish Intensive Care Society Audit Group.

OBJECTIVE: To assess the effect on the performance of Acute Physiology and Chronic Health Evaluation (APACHE) II and APACHE III of two different approaches to scoring the Glasgow Coma Scale (GCS) in sedated patients. The first approach was to assume that the GCS score was normal, and the second was to use the GCS value recorded before the patient was sedated. DESIGN: Prospective cohort study over 2 yrs. SETTING: Twenty-two general adult intensive care units in Scotland. PATIENTS: 13,291 consecutive admissions to the participating intensive care units. MEASUREMENTS AND MAIN RESULTS: After exclusion of patients according to standard, predefined criteria, the Acute Physiology and Chronic Health Evaluation II and III systems were used to calculate the probability of hospital mortality for patients included in the study. In patients whose GCS scores could not be assessed accurately during the first 24 hrs, the APACHE II and III predictions were calculated twice: first, assuming that the GCS score was normal; and second, substituting the GCS score recorded before sedation. This generated two different databases for each system, and the predictions for both were compared with the observed hospital mortality rate. The effect of the two different approaches to the GCS on the performance of both APACHE II and APACHE III was assessed using measures of discrimination (area under the receiver operating characteristic curve) and goodness of fit (calibration curves and the Hosmer-Lemeshow statistic). Analysis was undertaken for both the entire cohort and for the group of patients whose APACHE scores were altered. There was a wide variation in the number of patients who had their scores altered between participating units. There were also differences between diagnostic groups. Overall, however, 50% of the patients were sedated and 22% had their scores altered. Using the presedation GCS score increased the discrimination of both APACHE II and APACHE III. The calibration of APACHE III was also improved but that of APACHE II deteriorated. The calibration improved, however, in those patients with altered scores, suggesting that the overall deterioration is attributable to other limitations in the fit of the model to these data. Although changes had the greatest effect in patients with a neurologic or trauma diagnosis, the changes were important in most diagnostic groups. CONCLUSIONS: The GCS is an important component of both APACHE II and APACHE III. It should be assessed directly whenever possible. When patients are sedated, using the GCS score recorded before sedation is preferable to the assumption of normality. The variations between different units and different diagnostic groups highlight the possible effects of case mix on the performance of prognostic scoring systems.

APACHE↗

Outcome of lung cancer patients with acute respiratory failure requiring mechanical ventilation.

To assess the weaning outcome of lung cancer patients with acute respiratory failure (ARF) requiring mechanical ventilation, we retrospectively analyzed the database of the respiratory intensive care unit at a university-affiliated tertiary care hospital. Charts were reviewed for cancer status, biochemistries before respiratory failure, causes of respiratory failure, acute physiology and chronic health evaluation (APACHE) III score, ventilatory settings, data recorded during spontaneous breathing, duration of ventilator days, and weaning outcome. Ninety-five consecutive respiratory failure events in 81 patients were recorded from January 1, 1995 through June 30, 1999. Twenty-six episodes ended with successful weaning (27.4%). Age, gender, and cancer status did not affect the weaning outcome. Serum albumin level, APACHE III score, highest fractional inspired O2 (FiO2) and highest positive end-expiratory pressure, organ failure, ability to shift to partial ventilatory support, and duration of mechanical ventilation could significantly influence the weaning outcome statistically. The overall hospital mortality rate was 85.2%. Our results suggested that lung cancer patients with ARF will have a better chance to wean if the initial APACHE III score was less than 70, use of FiO2 never exceeded 0.6, or less than 2 additional organ systems failed during the treatment course.

APACHE↗

Cost calculation and prediction in adult intensive care: a ground-up utilization study.

The ability of various proxy cost measures, including therapeutic activity scores (TISS and Omega) and cumulative daily severity of illness scores, to predict individual ICU patient costs was assessed in a prospective "ground-up" utilization costing study over a six month period in 1991. Daily activity (TISS and Omega scores) and utilization in consecutive admissions to three adult university associated ICUs was recorded by dedicated data collectors. Cost prediction used linear regression with determination (80%) and validation (20%) data sets. The cohort, 1333 patients, had a mean (SD) age 57.5 (19.4) years, (41% female) and admission APACHE III score of 58 (27). ICU length of stay and mortality were 3.9 (6.1) days and 17.6% respectively. Mean total TISS and Omega scores were 117 (157) and 72 (113) respectively. Mean patient costs per ICU episode (1991 dollar AUS) were dollar 6801 (dollar 10311), with median costs of dollar 2534, range dollar 106 to dollar 95,602. Dominant cost fractions were nursing 43.3% and overheads 16.9%. Inflation adjusted year 2002 (mean) costs were dollar 9343 (dollar AUS). Total costs in survivors were predicted by Omega score, summed APACHE III score and ICU length of stay; determination R2, 0.91; validation 0.88. Omega was the preferred activity score. Without the Omega score, predictors were age, summed APACHE III score and ICU length of stay; determination R2, 0.73; validation 0.73. In non-survivors, predictors were age and ICU length of stay (plus interaction), and Omega score (determination R2, 0.97; validation 0.91). Patient costs may be predicted by a combination of ICU activity indices and severity scores.

APACHE↗

Selenium in Intensive Care (SIC): results of a prospective randomized, placebo-controlled, multiple-center study in patients with severe systemic inflammatory response syndrome, sepsis, and septic shock.

OBJECTIVE: Sepsis is associated with an increase in reactive oxygen species and low endogenous antioxidative capacity. We postulated that high-dose supplementation of sodium-selenite would improve the outcome of patients with severe sepsis and septic shock. DESIGN: Prospective randomized, placebo-controlled, multiple-center trial. SETTING: Eleven intensive care units in Germany. PATIENTS: Patients were 249 patients with severe systemic inflammatory response syndrome, sepsis, and septic shock and an Acute Physiology and Chronic Health Evaluation (APACHE) III score >70. INTERVENTIONS: Patients received 1000 microg of sodium-selenite as a 30-min bolus injection, followed by 14 daily continuous infusions of 1000 microg intravenously, or placebo. MEASUREMENTS AND MAIN RESULTS: The primary end point was 28-day mortality; secondary end points were survival time and clinical course of APACHE III and logistic organ dysfunction system scores. In addition, selenium levels in serum, whole blood, and urine as well as serum glutathione-peroxidase-3 activity were measured. From 249 patients included, 11 patients had to be excluded. The intention-to-treat analysis of the remaining 238 patients revealed a mortality rate of 50.0% in the placebo group and 39.7% in the selenium-treated group (p = .109; odds ratio, 0.66; confidence interval, 0.39-1.1). A further 49 patients had to be excluded before the final analysis because of severe violations of the study protocol. In the remaining 92 patients of the study group, the 28-day mortality rate was significantly reduced to 42.4% compared with 56.7% in 97 patients of the placebo group (p = .049, odds ratio, 0.56; confidence interval, 0.32-1.00). In predefined subgroup analyses, the mortality rate was significantly reduced in patients with septic shock with disseminated intravascular coagulation (n = 82, p = .018) as well as in the most critically ill patients with an APACHE III score > or =102 (>75% quartile, n = 54, p = .040) or in patients with more than three organ dysfunctions (n = 83, p = .039). Whole blood selenium concentrations and glutathione peroxidase-3 activity were within the upper normal range during selenium treatment, whereas they remained significantly low in the placebo group. There were no side effects observed due to high-dose sodium-selenite treatment. CONCLUSIONS: The adjuvant treatment of patients with high-dose sodium-selenite reduces mortality rate in patients with severe sepsis or septic shock.

APACHE↗

Impact of exclusion criteria on case mix, outcome, and length of stay for the severity of disease scoring methods in common use in critical care.

OBJECTIVE: To identify the exclusion criteria for the major severity of disease scoring methods in critical care and to investigate the impact of the exclusion criteria on the case mix, outcomes and length of stay for admissions to intensive care units (ICUs) in England, Wales and Northern Ireland. DESIGN: Cohort study-analysis of prospectively collected data. SETTING: 127 adult, general (mixed medical/surgical) ICUs in England, Wales and Northern Ireland. PATIENTS: 120,503 admissions between 1995 and 2001. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirteen different exclusion criteria were identified from the original methodological/validation papers and data collection manuals for APACHE II, APACHE III, SAPS II and MPM II. Application of the original exclusion criteria for the four, major severity of disease scoring methods resulted in exclusion of between 11.5% and 14.6% of admissions. Hospital mortality for the overall cohort was 29.0% but ranged from 4.7% to 50.1% among those groups excluded. After application of the exclusion criteria for each scoring method, there was little difference in overall hospital mortality or median ICU and hospital length of stay for the included admissions when compared with the original cohort. At the level of individual ICUs, there were differences in hospital mortality before and after exclusions-minimum -3.1% to maximum 9.5% (APACHE II), minimum -2.8% to maximum 9.4% (APACHE III), minimum -3.1% to maximum 16.1% (SAPS II) and minimum -3.1% to maximum 16.5% (MPM II). The mean difference across individual ICUs was -0.5 % (95% CI -0.7% to -0.2%) for APACHE II, -0.2% (95% CI -0.2% to 0.1%) for APACHE III, 2.0% (95% CI 1.7% to 2.4%) for SAPS II and 2.1% (95% CI 1.7% to 2.5%) for MPM II. SAPS II and MPM II showed systematic variation. A survey of the literature found wide variation in the exclusion criteria reported in subsequent, published research using a single severity of disease scoring method (APACHE II). CONCLUSIONS: Exclusion criteria used in critical care research are often ill-defined and poorly reported. More attention to the choice of exclusion criteria and their effect on the reported results is essential. We hope this study will raise the need for both better reporting of exclusion criteria applied in studies and promote the need for a common set of explicit exclusion criteria for these methods.

APACHE↗

[Analysis of costs of drug therapy in patients with acute respiratory insufficiency].

In a retrospective study, the authors analysed the clinical data of 38 patients who were admitted to a surgical intensive care unit (SICU) for mechanical ventilation lasted for at least 72 hours. The APACHE III score was calculated on the basis of clinical data documented during the first 24 hour of the treatment and the cost of drug administrations per patients per day was also determined by analysing all the drugs prescribed on the first 5 days of intensive care. The patients admitted to SICU with polytrauma or with abdominal septic focus required significantly higher cost of drug treatment than the patients after cardiopulmonary resuscitation or with bronchial asthma or pneumonia. The APACHE III score of the patients died at the SICU was significantly higher compared to the survivors who needed more expensive drug therapy than the non-survivors required. Antibiotic treatment, blood transfusions, and human plasma proteins caused the highest drug expenditure. There was no significant correlation between the APACHE III score and the cost of drug treatment.

Cardiopulmonary Resuscitation↗

Aerosolized surfactant in adults with sepsis-induced acute respiratory distress syndrome. Exosurf Acute Respiratory Distress Syndrome Sepsis Study Group.

BACKGROUND: Patients with acute respiratory distress syndrome (ARDS) have a deficiency of surfactant. Surfactant replacement improves physiologic function in such patients, and preliminary data suggest that it may improve survival. METHODS: We conducted a prospective, multicenter, double-blind, randomized, placebo-controlled trial involving 725 patients with sepsis-induced ARDS. Patients were stratified according to the risk of death at base line (indicated by their score on the Acute Physiological and Chronic Health Evaluation [APACHE III] index) and randomly assigned to receive either continuously administered synthetic surfactant (13.5 mg of dipalmitoylphosphatidylcholine per milliliter, 364 patients) or placebo (o.45 percent saline; 361 patients) in aerosolized form for up to five days. RESULTS: The demographic and physiologic characteristics of the two treatment groups were similar at base line. The mean (+/- SD) age was 50 +/- 17 years in the surfactant group and 53 +/- 18 years in the placebo group, and the mean APACHE III scores at randomization were 70.4 +/- 25 and 70.5 +/- 25, respectively. Hemodynamic measures, measures of oxygenation, duration of mechanical ventilation, and length of stay in intensive care unit did not differ significantly in the two groups. Survival at 30 days was 60 percent for both groups. Survival was similar in the groups when analyzed according to APACHE III score, cause of death, time of onset and severity of ARDS, presence or absence of documented sepsis, underlying disease, whether or not there was a do-not-resuscitate order, and medical center. Increased secretions were significantly more frequent in the surfactant group; the rates of other complications were similar in the two groups. CONCLUSIONS: The continuous administration of aerosolized synthetic surfactant to patients with sepsis-induced ARDS had no significant effect on 30-day survival, length of stay in the intensive care unit, duration of mechanical ventilation, or physiologic function.

Administration, Inhalation↗

Use and outcome of liver transplantation in acetaminophen-induced acute liver failure.

Once defined clinical criteria are fulfilled in acetaminophen-induced hepatotoxicity, prognosis without orthotopic liver transplantation (OLT) may be very poor. In the present study, we examined the application and outcome of OLT in 548 patients admitted to a single center between 1990 and 1996. Four hundred twenty-four (77%) of the patients studied did not fulfill transplantation criteria, and 396 of these (93%) survived. The majority of the 28 nonsurvivors (7%) in this group fulfilled two of three combined criteria, and the finding of a high APACHE III score could be used as an indicator for the need for OLT. Of the 56 patients (45%) not listed, in only a small proportion was this caused by psychiatric reasons, and in the majority, it was a consequence of the rapid development of multiple organ failure and cerebral edema. This also applied to 24 (35%) of the 68 listed patients in whom the rapidity of clinical deterioration, reflected in increasing APACHE III scores, was such that even with the prompt availability of donor organs, OLT was not possible. In the final event, only 44 (35%) of those who fulfilled criteria underwent OLT, of whom 33 (75%) survived to leave the hospital. Survival was greatest in those receiving unreduced grafts, and markers of early graft function differed significantly between survivors and nonsurvivors. Liver transplantation is an effective treatment in a relatively small number of patients with acetaminophen-induced hepatotoxicity, and for a substantial proportion, transplantation was never an option because of the rapidity of clinical deterioration. APACHE III scoring may be of value in decision making and in better defining patients in clinical trials.

Acetaminophen↗

Intensive care unit admissions with cirrhosis: risk-stratifying patient groups and predicting individual survival.

Prognosis for acutely ill patients with cirrhosis is influenced by the severity of hepatic abnormalities and by dysfunction of other organ systems. The purpose of this study was to examine the usefulness of the Acute Physiology, Age, and Chronic Health Evaluation (APACHE III) prognostic system for risk-stratifying groups of intensive care unit (ICU) patients with cirrhosis and in predicting individual survival. We used data for 17,440 ICU admissions at 40 American hospitals to select 117 of the 537 patients with a history of cirrhosis who were ventilated on ICU day 1, a group known to have a high mortality rate. We then calculated each patient's probability of hospital death on ICU days 1 through 7, using seven previously validated multivariate equations. Hospital mortality was 63% for the 117 study patients. The most important determinants of risk for hospital death on ICU day 1 were the acute physiology score of APACHE III, ICU admission diagnosis, and operative status. Daily changes in the acute physiology score caused a rise or fall in the probability of hospital mortality and was useful in assessing individual response to therapy. APACHE III accurately risk stratifies critically ill patients with cirrhosis because it accounts for many of the factors known to influence prognosis. This capability can be used to assess severity of illness and risk-stratify patients with cirrhosis during clinical trials. Daily prognostic estimates based on physiological changes over time reflect patient response and can help physicians to assess the incremental benefit of therapy.

Adult↗

Length of stay and mortality in neurocritically ill patients: impact of a specialized neurocritical care team.

OBJECTIVE: To determine predictors of in-hospital and long-term mortality and length of stay in patients admitted to the neurosciences critical care unit. DESIGN: Retrospective analysis of a prospectively collected database. SETTING: Neurosciences critical care unit of a large academic tertiary care hospital. PATIENTS: Adult patients (n = 2381) admitted to our neurosciences critical care unit from January 1997 to April 2000. INTERVENTIONS: Introduction of a specialized neurocritical care team. MEASUREMENTS AND MAIN RESULTS: Data obtained from the database included demographics, admission source, length of stay, neurosciences critical care unit and hospital disposition, admission Acute Physiology and Chronic Health Evaluation (APACHE) III score, and principal and secondary diagnoses. The introduction of a neurocritical care team in September 1998 was also collected, as was death at 1 yr after admission. Univariate analysis was carried out using Student's t-test, Mann-Whitney U test, or chi-square test (significance, p < .05). A logistic regression model was used to create a prediction model for in-hospital and long-term mortality. A general linear model was used to determine predictors of length of stay (after log transformation). Independent predictors of in-hospital mortality included APACHE III (odds ratio, 1.07 [1.06-1.08]) and admission from another intensive care unit (odds ratio, 2.9 [1.4-6.2]). The presence of a neurocritical care team was an independent predictor of decreased mortality (odds ratio, 0.7 [0.5-1.0], p = .044). Admission after the neurocritical care team was implemented was associated with reduced length of stay in both the neurosciences critical care unit (4.2 +/- 4.0 vs. 3.7 +/- 3.4, p < .001) and the hospital (9.9 +/- 8.0 vs. 8.4 +/- 6.9, p < .0001). There was no difference in readmission rates to the intensive care unit or discharge disposition to home before and after the neurocritical care team was established. The availability of the neurocritical care team was not associated with significant changes in long-term mortality. Factors independently associated with long-term mortality included female gender, admission from another intensive care unit, APACHE III score, and being moderately disabled before admission. CONCLUSION: Introduction of a neurocritical care team, including a full-time neurointensivist who coordinated care, was associated with significantly reduced in-hospital mortality and length of stay without changes in readmission rates or long-term mortality.

APACHE↗

Intensive care unit prognostic scoring systems to predict death: a cost-effectiveness analysis.

OBJECTIVE: To evaluate the cost-effectiveness, using the technique of decision analysis, of withdrawing care from patients in the intensive care unit (ICU) who are predicted to have a high probability of death (>90%) after 48 hrs using a mortality risk estimate based on daily Acute Physiology and Chronic Health Evaluation (APACHE) III scores. MATERIALS AND METHODS: A decision tree model was constructed to compare the cost-effectiveness of two clinical strategies. In the first strategy, patients receive ICU care until they were discharged, died, or had care withdrawn based on subjective clinical criteria. In the second strategy, patients remained in the ICU until they were either discharged, died, or had life-sustaining care withdrawn based on subjective criteria or if they were predicted to have a >90% risk of mortality after 48 hrs by a prognostic scoring system. Transition probabilities were based on a retrospective data analysis of 4,106 noncardiac ICU patients admitted to a tertiary surgical ICU over a 9-yr period. Cost estimates were based on daily Therapeutic Intervention Scoring System (TISS) scores from our database and using published data on the estimated production cost for a TISS point. The sensitivity (16.6%) and specificity (99.6%) of the mortality risk estimate at 48 hrs (using the >90% decision point) based on daily APACHE III scores were derived from published data. RESULTS: In the base case analysis, we assumed that the sensitivity and specificity of the prognostic risk estimate are unchanged when exported to a new environment. Not using a prognostic scoring system as the basis for withdrawing care resulted in a slightly higher survival rate (87.2% vs. 86.85%) at a cost-per-death prevented (CPDP) of $263,700. Since prognostic scoring systems have not been shown to retain the same predictive power when exported to new databases, we chose to explore the effect of varying the specificity of the scoring system on CPDP. Decreasing the specificity from .996 (baseline) to .98 causes the CPDP to drop to $53,300. Changing the specificity to .95 results in a CPDP prevented of $21,700. Using one-way sensitivity analysis, the CPDP is shown to be relatively insensitive to delaying the decision point from ICU day 3 to day 7. Sensitivity analysis also indicates that CPDP increases rapidly with hospital death rate. For a death rate of 30%, the CPDP increases to $768,600 (in the base case, the death rate is 12.8%); when the specificity is decreased to .95, the CPDP drops to $62,100. CONCLUSION: Unless daily mortality risk estimates based on APACHE III can be shown to retain the same level of predictive power in ICUs outside the development database, it is unlikely that the incremental cost-effectiveness gained by using them as the basis to withdraw care is sufficient to justify their use in this manner.

APACHE↗

Renal failure in the ICU: comparison of the impact of acute renal failure and end-stage renal disease on ICU outcomes.

BACKGROUND: Acute renal failure (ARF) is associated with a persistent high mortality in critically ill patients in intensive care units (ICUs). Most studies to date have focused on patients with established, intrinsic ARF or relatively severe ARF due to multiple factors. None have examined outcomes of dialysis-dependent chronic renal failure [end-stage renal disease (ESRD)] patients in the ICU. We examined the incidence and outcomes of ARF in the ICU using a standard definition and compared these to outcomes of ICU patients with either ESRD or no renal failure. We sought to determine the impact of renal dysfunction and/or loss of organ function on outcome. METHODS: We prospectively scored 1530 admissions to eight ICUs over a 10-month period for illness severity at ICU admission using the Acute Physiological and Chronic Health Evaluation (APACHE III) evaluation tool. Patients were defined as having ARF based on the definition of Hou et al (Am J Med 74:243-248,1983) designed to detect significant measurable declines in renal function based on serum creatinine. ESRD patients were identified as being chronically dialysis-dependent prior to ICU admission and the remainder had no renal failure. Clinical characteristics at ICU admission and ICU and hospital outcomes were compared between the three groups. RESULTS: We identified 254 cases of ARF, 57 cases of ESRD and 1219 cases of no renal failure for an incidence of ARF of 17%. Roughly half the ARF patients had ARF at ICU admission and the remainder developed ARF during their ICU stay. Only 11% of ARF patients required dialysis support. ARF patients had significantly higher acute illness severity scores than those with no renal failure, whereas patients with ESRD had intermediate severity scores. ICU mortality was 23% for patients with ARF, 11% for those with ESRD, and 5% for those with no renal failure. There was no difference in outcome between patients who had ARF at ICU admission and those who developed ARF in the ICU. Patients with ARF severe enough to require dialysis had a mortality of 57%. APACHE III predicted outcome very well in patients with no renal failure and patients with ARF at the time of scoring but underpredicted mortality in those who developed ARF after ICU admission and overestimated mortality in patients with ESRD. CONCLUSIONS: ARF is common in ICU patients and has a persistent negative impact on outcomes, although the majority of ARF is not severe enough to require dialysis support. The mortality of patients with ARF from all causes is almost exactly similar to that noted using the same criteria two decades ago. More profound ARF requiring dialysis continues to have an even greater mortality. Nevertheless, acute declines in renal function are associated with a mortality that is not well explained simply by loss of organ function. The majority of ARF patients who did not require dialysis still had a considerably higher mortality than the ESRD patients, all of whom required dialysis; while ARF patients who did require dialysis had a much higher morality than ESRD patients. APACHE III performs well and captures the mortality of patients with ARF at the time of scoring. Development of ARF after scoring has a profound effect on standardized mortality. We were unable to identify a unique mortality associated with ARF, but the presence of measurable renal insufficiency continues to be a sensitive marker for poor outcome.

APACHE↗

Death in two Canadian intensive care units: institutional difference and changes over time.

OBJECTIVE: To study and compare the mode of death in two different institutions' intensive care units (ICUs) for the two time periods, 1988 and 1993. DESIGN: Retrospective chart review. SETTING: Medical/surgical/trauma ICUs in two tertiary care teaching hospitals. PATIENTS: Patients dying in the medical/surgical/trauma ICUs between January 1, 1988 and December 31, 1988; and January 1, 1993 and December 31, 1993. Data collection included demographics, origin of admission, date of ICU admission, date of death, Acute Physiology and Chronic Health Evaluation (APACHE) III diagnostic categories, APACHE II physiologic variables, organ system failures present at the time of admission and 24 hrs before death, and mode of dying. APACHE II scores and mortality risk were calculated. Data analysis included a multiple analysis of variance to assess overall effect, with subsequent analyses of variance to assess the effect of institution and year on each individual dependent variable. All results are reported as mean +/- SEM values. RESULTS: A total of 439 charts were reviewed. Gender, age, and origin of admission were not different between the 2 yrs or the two institutions. Mean APACHE II scores and organ system failures were lower at Hospital A in 1998 vs. Hospital B, as was predicted mortality. These factors increased at Hospital A in 1993 and were similar to those at Hospital B. Withdrawal of support was much more common in 1993 than 1988 at both institutions (43% at Hospital A and 46% at Hospital B in 1988 vs. 66% at A and 80% at B in 1993), increasing to a greater extent in 1993 at Hospital B (p<.05). Length of stay in the ICU was significantly longer at Hospital A than at Hospital B in 1988 (9.4+/-1.4 vs. 4.3+/-0.6 days; p<.05) and in 1993 (8.2+/-2.9 vs. 3.8+/-0.5 days; p < .05). CONCLUSIONS: There has been an increase in withdrawal of life support, in recent years, at both the institutions studied. Differences exist between institutions with respect to end-of-life decisions in the ICU. These differences are likely representative of widely prevalent regional differences and are the result of many factors.

APACHE↗

Acute Physiology and Chronic Health Evaluation (APACHE) IV: hospital mortality assessment for today's critically ill patients.

OBJECTIVE: To improve the accuracy of the Acute Physiology and Chronic Health Evaluation (APACHE) method for predicting hospital mortality among critically ill adults and to evaluate changes in the accuracy of earlier APACHE models. DESIGN: : Observational cohort study. SETTING: A total of 104 intensive care units (ICUs) in 45 U.S. hospitals. PATIENTS: A total of 131,618 consecutive ICU admissions during 2002 and 2003, of which 110,558 met inclusion criteria and had complete data. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We developed APACHE IV using ICU day 1 information and a multivariate logistic regression procedure to estimate the probability of hospital death for randomly selected patients who comprised 60% of the database. Predictor variables were similar to those in APACHE III, but new variables were added and different statistical modeling used. We assessed the accuracy of APACHE IV predictions by comparing observed and predicted hospital mortality for the excluded patients (validation set). We tested discrimination and used multiple tests of calibration in aggregate and for patient subgroups. APACHE IV had good discrimination (area under the receiver operating characteristic curve = 0.88) and calibration (Hosmer-Lemeshow C statistic = 16.9, p = .08). For 90% of 116 ICU admission diagnoses, the ratio of observed to predicted mortality was not significantly different from 1.0. We also used the validation data set to compare the accuracy of APACHE IV predictions to those using APACHE III versions developed 7 and 14 yrs previously. There was little change in discrimination, but aggregate mortality was systematically overestimated as model age increased. When examined across disease, predictive accuracy was maintained for some diagnoses but for others seemed to reflect changes in practice or therapy. CONCLUSIONS: APACHE IV predictions of hospital mortality have good discrimination and calibration and should be useful for benchmarking performance in U.S. ICUs. The accuracy of predictive models is dynamic and should be periodically retested. When accuracy deteriorates they should be revised and updated.

APACHE↗

Identifying potentially ineffective care in a community hospital.

OBJECTIVES: To develop a formula to predict mortality for intensive care unit patients between day 5 in an intensive care unit and 100 days after hospital discharge from a community hospital. DESIGN: Retrospective 1-yr derivation study with validation on a subsequent year's intensive care unit population. SETTING: An 850-bed, not-for-profit community hospital with three adult intensive care units, including medical-surgical, cardiac-medical, and cardiac-surgical units. PATIENTS: The development patient set included 4045 consecutive adult admissions to the intensive care unit between July 1995 and June 1996. The validation sample consisted of 4084 admissions between July 1996 and June 1997. RESULTS: During the first year, 100-day posthospital discharge mortality was predicted by the combination Acute Physiology and Chronic Health Evaluation (APACHE) III predicted mortality on day 5 of >0.92 or the product of day 1 and day 5 APACHE predicted mortality of >0.40, with an increase in the APACHE predicted mortality from day 1 to day 5 of >0.10. Specificity in the development cohort was 0.99, sensitivity was 0.30, and positive predictive value was 0.95. The second-year validation study demonstrated a specificity, sensitivity, and positive predictive value of 0.98, 0.29, and 0.91, respectively, when applying the model to the validation sample. CONCLUSIONS: By using readily available APACHE III data, we were able to identify patients at high risk of dying between intensive care unit day 5 and 100 days after discharge. Although the low sensitivity limits the number of patients for whom death at 100 days is predicted, the high specificity and positive predictive value suggests this information may provide useful information for families and physicians. If these formulas can be validated in diverse institutional settings, decisions regarding short- and long-term outcomes may be improved by using objective survival predictions from two time points.

APACHE↗

[Risk predictors, scoring systems and prognostic models in anesthesia and intensive care. Part II. Intensive Care].

The aim of the second part of this review article was to describe common scoring systems in intensive care, and to point out their possible benefits and limitations. Intensive care medicine multipurpose scoring-systems are currently used to estimate severity of illness, mortality and the amount of treatment required. Costs (only commercial available scores e.g. Acute Physiology and Chronic Health Evaluation [APACHE] III) and time needed for calculation have to be taken into consideration. Prognostic models of the third generation (APACHE III, Simplified Acute Physiology Score [SAPS] II, Mortality Prediction Model [MPM] II) should be preferred having better prognostic performance compared to scoring systems of prior generations. Although no prospective study exists comparing these three common scoring systems, it appears that all three systems are able to provide useful information to the clinician and researcher. These scoring systems were designed to classify severity of illness or the course of diagnostic and therapeutic interventions and to perform a risk stratification for scientific studies in a standardized way. In quality management and cost control, scoring systems and predictors are used for risk adjustment and evaluation of care performance.

APACHE↗