Download Short-Term Prognosis in Critically Ill Patients With Cirrhosis

Short-Term Prognosis in Critically Ill Patients With Cirrhosis
Assessed by Prognostic Scoring Systems
MARKUS WEHLER,1 JUDITH KOKOSKA,1 UDO REULBACH,2 ECKHART GEORG HAHN,1 AND RICHARD STRAUSS1
The short-term prognosis of acutely ill patients with
cirrhosis is influenced by the degree of hepatic insufficiency and by dysfunction of extrahepatic organ systems.
The purpose of this study was to assess and compare the
prognostic accuracy of the Child-Pugh classification,
the Acute Physiology and Chronic Health Evaluation
(APACHE) II system and the Sequential Organ Failure
Assessment (SOFA) for predicting hospital mortality in
patients with cirrhosis when used 24 hours after admission to a medical intensive care unit (ICU). Prospective
data were recorded on 143 patients. Cumulative mortality rates were 36% in the ICU, 46% in the hospital, and
56% at 6-month follow-up. By using the area under receiver operating characteristic (AUROC) curves, the
SOFA showed an excellent discriminative power (AUROC 0.94), which was clearly superior to the APACHE II
(AUROC 0.79) and the Child-Pugh system (AUROC
0.74). Hospital mortality rates below and above a cutoff of
8 SOFA points were 4% and 88%, respectively (P <
.0005). The SOFA score also reflected resource use during the ICU treatment as measured by daily workload and
length of stay. The SOFA is an easily applied tool with
excellent prognostic abilities and can be used to enhance
clinical judgment of prognosis as well as providing
patients and families with objective information.
(HEPATOLOGY 2001;34:255-261.)
Chronic liver disease, including cirrhosis, was the tenth
most frequent cause of death in the United States in 1996.1
Because end-stage liver disease is characterized by episodes of liver decompensation and gastrointestinal hemorrhage, treatment in the intensive care unit (ICU) is often
needed in the management of these complications. In patients with cirrhosis who develop extrahepatic organ failure, hospital mortality rates of 63% to 100% have been
reported.2-7 For ethical reasons but also because of limited
resources and growing questions about the efficacy of intensive care treatment, physicians need early and reliable
Abbreviations: ICU, intensive care unit; APACHE, Acute Physiology and Chronic
Health Evaluation; SOFA, Sequential Organ Failure Assessment; TISS, therapeutic intervention scoring system; AUROC, area under receiver operating characteristic; 95% CI,
95% confidence interval.
From the 1Departments of Medicine I and 2Medical Informatics, Biometry, and Epidemiology of the University of Erlangen-Nuremberg, Germany.
Received February 26, 2001; accepted May 29, 2001.
Address reprint requests to: Markus Wehler, M.D., Department of Medicine I of the
University of Erlangen-Nuremberg, Krankenhausstrasse 12, 91054 Erlangen, Germany.
E-mail: [email protected]; fax: (49) 9131-853 6012.
Copyright © 2001 by the American Association for the Study of Liver Diseases.
0270-9139/01/3402-0007$35.00/0
doi:10.1053/jhep.2001.26522
outcome predictors to identify cases in which aggressive
treatment for cure or potential liver transplantation is merited, as well as those in which such care is likely to be
futile.8,9
The Child-Turcotte classification, and its subsequent modification by Pugh,10 is one of the most commonly used clinical
instruments to risk-stratify cirrhotic patients.11,12 The Acute
Physiology and Chronic Health Evaluation (APACHE) II,13 a
physiologically based prognostic system, is a widely used severity-of-illness scale to predict hospital mortality in all ICU
patients. More recently the Sequential Organ Failure Assessment (SOFA)14 has been developed and validated. Although
originally an instrument to classify various degrees of organ
dysfunction it has been shown that high SOFA scores for any
individual organ are associated with increased mortality.15,16
We analyzed and compared the prognostic accuracy of these 3
scoring systems in predicting hospital mortality of cirrhotic
patients when scores were measured 24 hours after admission
to a medical ICU.
PATIENTS AND METHODS
This study was performed in a 12-bed noncoronary medical ICU
of a university hospital between October 1996 and December 1998. A
total of 143 consecutive patients with hepatic cirrhosis requiring
intensive monitoring and/or treatment that could not be provided
outside of the ICU were enrolled. Eight cirrhotic patients with
known end-stage cancer unresponsive to therapy were not admitted
to the ICU. Readmissions were also excluded.
Prospectively collected data included demographics, reason for
ICU admission, acute diagnosis, presence of comorbid disease,
severity of illness, organ function, therapeutic activity on all ICU
days, and length of ICU and hospital stay. Comorbid illnesses
were classified using the Charlson comorbidity index, which assigns weights for 19 major comorbid conditions affecting the patient⬘s prognosis.17 The severity of liver disease on ICU admission
was graded by the Child-Pugh system.10 The severity of illness
was assessed by the APACHE II system after the first 24 hours of
ICU admission. The APACHE II system is based on age, chronic
health status, and acute physiology score; the variables included
in the acute physiology scoring are mean arterial pressure, temperature, respiratory rate, heart rate, Glasgow Coma Score, hematocrit, white blood cell count, serum sodium, serum potassium, serum creatinine, serum bicarbonate or arterial pH, and
arterial oxygen tension or alveolar-arterial oxygen tension gradient (Appendix Table).13 Organ function was evaluated by the
SOFA.14 The SOFA is composed of scores from 6 organ systems
(respiratory, cardiovascular, hepatic, renal, coagulation, and neurologic) graded from 0 to 4 points according to normal function or
the degree of dysfunction (Table 1). In the first 24-hour period of
ICU admission the most abnormal value for each of the 6 organ
systems was recorded, and points were assigned for each organ
system. The SOFA score presents the sum of all 6 organ system
points. Organ failure was defined by a SOFA score of 3 or more
255
256 WEHLER ET AL.
HEPATOLOGY August 2001
TABLE 1. The Sequential Organ Failure Assessment (SOFA) Score
SOFA Score
Respiration
PaO2/FiO2
Coagulation
Platelets, ⫻103/mm3
Liver
Bilirubin, mg/dL
(␮mol/L)
Cardiovascular
Hypotension
CNS
Glasgow Coma Score
Renal
Creatinine, mg/dL
(␮mol/L)
or urine output
0
1
2
⬎400
301-400
201-300
⬎150
101-150
51-100
21-50
ⱕ20
⬍1.2
(⬍20)
1.2-1.9
(20-32)
2.0-5.9
(33-101)
6.0-11.9
(102-204)
⬎12.0
(⬎204)
MAP ⬍ 70
mm Hg
Dopamine ⱕ 5 or
dobutamine
(any dose)*
13-14
10-12
1.2-1.9
(110-170)
2.0-3.4
(171-299)
MAP ⱖ 70
mm Hg
15
⬍1.2
(⬍110)
3
101-200
with respiratory
support
Dopamine ⬎ 5 or
epi ⱕ 0.1 or
norepi ⱕ 0.1*
6-9
3.5-4.9
(300-440)
or ⬍500 mL/d
4
ⱕ100
with respiratory
support
Dopamine ⬎ 15 or
epi ⬎ 0.1 or
norepi ⬎ 0.1*
⬍6
⬎5.0
(⬎440)
or ⬍200 mL/d
Abbreviations: PaO2, arterial oxygen tension; FiO2, fractional inspired oxygen; MAP, mean arterial pressure; CNS, central nervous system; epi, epinephrine;
norepi, norepinephrine.
*Adrenergic agents administered for at least 1 hour (doses are given in ␮g/kg/min).
Reprinted with permission.14
points for the respective organ system.15 Therapeutic activity was
determined by the Therapeutic Intervention Scoring System
(TISS), a weighted score that quantitates the use of 76 diagnostic,
therapeutic, and monitoring procedures commonly performed in
the ICU.18
The principal study outcome was hospital mortality rate. Follow-up 6 months after hospital discharge was performed by telephone interview. If necessary, the registry office provided information as to patient survival or date of death. The diagnosis of
hepatic cirrhosis was made histologically (n ⫽ 37) or by clinical
evaluation (n ⫽ 106). The clincal diagnosis of cirrhosis was made
by a history of portal hypertension excluding other etiologies,
impaired liver function tests and clotting profile, and ultrasound
or computer tomography criteria.19 The Glasgow Coma Scale as
the neurologic component of the APACHE II and SOFA was
scored conservatively (for sedated patients normal function is
assumed unless there is evidence for intrinsically altered neurologic function). The criteria for diagnosing severe sepsis were as
previously defined.20 The Institutional Ethics Committee approved the study and because of the observational nature of the
study waived the need for informed consent.
Statistical Methods. Descriptive statistics are expressed as
mean ⫾ SD unless otherwise stated. The primary analysis compared hospital survivors with nonsurvivors. All variables were
tested for normal distribution by the Kolmogorov-Smirnov test.
Student⬘s t test was used for comparison of the means of continuous variables and normally distributed data. Mann-Whitney U
test was used otherwise. Categorical data were tested using the ␹2
statistic. Sensitivity, specificity, overall correctness, and positive
and negative predictive values were determined for the ChildPugh, APACHE II, and SOFA scores. Cutoff points giving the best
Youden index (sensitivity ⫹ specificity ⫺ 1) were calculated.21
Survival percentages of patients dichotomized by the SOFA score
with the best Youden index were described by the Kaplan-Meier
method.22 The ability of the scoring systems to discriminate between hospital survivors and nonsurvivors was assessed by using
the area under the receiver operating characteristic (AUROC)
curve.23 The effect of the various organ systems as assessed by
SOFA after the first 24 hours on the risk of hospital death was
evaluated using a Cox proportional hazards nonstepwise regression analysis.24
Resource use among patients with different numbers of organ
system failures was studied by examining the median TISS score of
all ICU days and ICU length of stay with the Kruskal-Wallis test. All
statistical tests were 2-tailed, and a significance level of P ⫽ .05 or less
was used. Data were analyzed using SPSS for Windows 10 (SPSS Inc.,
Chicago, IL).
RESULTS
A total of 143 patients with hepatic cirrhosis were enrolled
in the study. Fifty-two percent of the patients were admitted
from the ward, 38% from the emergency room, and 10% from
other hospitals. Demographic and clinical characteristics of
the study patients are shown in Table 2. The median age was
53 years, 62% were men, and all patients were white. Liver
disease was most commonly attributed to alcohol abuse, and
most patients had 2 or more other comorbid conditions. The
most common reason for ICU admission was upper gastrointestinal bleeding (42%) (Table 3). Management of the patients was time consuming and resource intensive (Table 2).
Seventy-four (52%) patients needed mechanical ventilation
(25% hospital survivors vs. 83% nonsurvivors, P ⬍ .0005), 70
(49%) were treated with vasopressors (22% vs. 80%, P ⬍
.0005), and 32 (22%) required renal replacement therapy (8%
vs. 40%, P ⬍ .0005). During the ICU stay 187 endoscopic
procedures (66% gastrointestinal) were performed and transfusion requirements were high (total 2,450 units of blood
products).
Follow-up to 180 days or time of death was complete for the
entire cohort. The cumulative incidence of death was 36% in
the ICU, 46% in the hospital, and 56% at 6 months. During the
first 24 hours of ICU admission 67% of the patients presented
with 1 or more organ system failures. The number of organ
systems failing was significantly related to hospital mortality,
with mortality rates ranging from 6.4% in patients without
any organ system failure to 96.7% in patients with 3 or more
organ system failures (Fig. 1).
To evaluate to what extent the applied scoring systems were
valid for prediction of hospital mortality; the sensitivity, spec-
HEPATOLOGY Vol. 34, No. 2, 2001
WEHLER ET AL.
257
TABLE 2. Demographic and Clinical Characteristics of 143 Patients With Cirrhosis Admitted to a Medical ICU
Gender (F/M)
Age (years ⫾ SD)
Length of ICU stay (days ⫾ SD)
Length of hospital stay (days ⫾ SD)
Charlson Comorbidity Index
Child-Pugh category (A/B/C; n)
Child-Pugh points (mean ⫾ SD)
APACHE II (mean ⫾ SD), first 24 h
SOFA (mean ⫾ SD), first 24 h
Median TISS score (⫾SD)*
Mechanical ventilation (days ⫾ SD)
Renal replacement† (days ⫾ SD)
Vasopressor therapy‡ (days ⫾ SD)
Packed red blood cells
Single donor apheresis platelets
Fresh frozen plasma infused during ICU stay
(units ⫾ SD)
All Patients (n ⴝ 143)
Hospital Survivors
(n ⴝ 77)
Hospital
Nonsurvivors
(n ⴝ 66)
P
54/89
53 ⫾ 11.6
8.8 ⫾ 13.2 Median 5
26.6 ⫾ 28.5 Median 21
3.9 ⫾ 1.2
6/40/97
10.1 ⫾ 2
20.6 ⫾ 10.7
8.6 ⫾ 4.7
31 ⫾ 13
5.4 ⫾ 11.9
1.5 ⫾ 4.6
3.9 ⫾ 7.2
6.3 ⫾ 8.2
1.4 ⫾ 2.8
29/48
52 ⫾ 11.8
7.6 ⫾ 15.6 Median 4
31.7 ⫾ 34 Median 24
3.8 ⫾ 1.1
6/30/41
9.35 ⫾ 1.9
15.5 ⫾ 8
5.2 ⫾ 2.7
24 ⫾ 9
3.4 ⫾ 13.5
0.7 ⫾ 4.4
1.6 ⫾ 6.6
3.9 ⫾ 5.4
0.6 ⫾ 1.8
25/41
54 ⫾ 11.3
10.3 ⫾ 9.6 Median 8
20.6 ⫾ 19 Median 15
4.1 ⫾ 1.3
0/10/56
10.9 ⫾ 1.8
26.6 ⫾ 10.5
12.6 ⫾ 3.3
39 ⫾ 12
7.8 ⫾ 9.2
2.5 ⫾ 4.6
6.5 ⫾ 7.0
9 ⫾ 9.8
2.4 ⫾ 3.4
NS
NS
⬍.0005
.02
NS
⬍.0005
⬍.0005
⬍.0005
⬍.0005
⬍.0005
.025
.023
⬍.0005
⬍.0005
⬍.0005
16.7 ⫾ 21.1
⬍.0005
9.45 ⫾ 16.5
6.7 ⫾ 3.3
Abbreviation: NS, not significant.
*Median TISS score of all days the patient was treated in the ICU.
†Continuous veno-venous hemofiltration.
‡Intravenous epinephrine or norepinephrine.
ificity, overall correctness of prediction, and positive and negative predictive values were all determined. Table 4 shows
these data calculated at the cutoff point giving the best Youden
index. The best Youden index and highest overall correctness
of prediction was found for the SOFA score. ICU and hospital
mortality rates below and above a cutoff of 8 SOFA points
were 3% and 71%, and 4% and 88%, respectively (P ⬍ .0005
for both). Figure 2 shows the cumulative rates of survival
during hospitalization for the study group dichotomized by a
cutoff of 8 SOFA points.
Receiver operating characteristic curves were used to
evaluate the discriminative power of the scores. The SOFA
score calculated 24 hours after ICU admission was found to
be the most reliable scoring system to discriminate between
hospital survivors and nonsurvivors (AUROC 0.947, SE
0.02, 95% confidence interval [95% CI] 0.91-0.987) (Fig.
3). No differences were seen between the APACHE II (AUROC 0.79, SE 0.04, 95% CI 0.72-0.87) and the Child-Pugh
score (AUROC 0.74, SE 0.04, 95% CI 0.66-0.82). When
calculated for ICU outcome AUROC data did not change
significantly: SOFA (AUROC 0.92, SE 0.02, 95% CI 0.870.96), APACHE II (AUROC 0.79, SE 0.04, 95% CI 0.72-
TABLE 3. Causes of Cirrhosis and Reasons for Admission of 143 Patients
Admitted to the Medical ICU
All
Patients
n (%)
Cause of cirrhosis
Alcoholic
Posthepatitic
Cryptogenic
Other causes†
Primary ICU admission
cause
UGI bleeding
Severe sepsis
Acute renal failure
Hepatic coma
Pneumonia with
respiratory failure
Drug/alcohol
overdose
Acute pancreatitis
Hospital
Hospital
Survivors Nonsurvivors
n (%)*
n (%)*
P
108 (75)
20 (14)
5 (4)
10 (7)
52 (48)
15 (75)
4 (80)
6 (60)
56 (52)
5 (25)
1 (20)
4 (40)
.019
NS
NS
NS
60 (42)
20 (14)
19 (13)
18 (13)
41 (68)
3 (15)
11 (58)
7 (39)
19 (32)
17 (85)
8 (42)
11 (61)
.001
⬍.0005
NS
NS
17 (12)
6 (4)
7 (41)
6 (100)
10 (59)
0 (0)
NS
.03
3 (2)
2 (67)
1 (33)
NS
Abbreviations: UGI, upper gastrointestinal; NS, not significant.
*Number (%) of patients with the condition who survived or died.
†Primary biliary cirrhosis, secondary biliary cirrhosis, autoimmune hepatitis.
FIG. 1. Numbers of organ systems failing on the first day of ICU admission vs. hospital mortality in 143 patients with cirrhosis (␹2 test for trend ⫽
72, P ⬍ .0005). Organ failure defined by a SOFA score of 3 or more points for
the respective organ system.
258 WEHLER ET AL.
HEPATOLOGY August 2001
TABLE 4. Prediction of Subsequent Hospital Mortality in 143 Cirrhotic Patients After the First Day of ICU Admission
Scoring
System
Child-Pugh
APACHE II
SOFA
Cutoff
Point*
Youden
Index
Sensitivity
(%)
Specificity
(%)
Overall
Correctness
(%)
PPV
(%)
NPV
(%)
10
22
8
0.47
0.51
0.84
66
66
95
80
84
88
74
76
91
74
78
87
74
75
96
Abbreviations: PPV, positive predictive value; NPV, negative predictive value.
*Value giving the best Youden index.
0.87) and Child-Pugh score (AUROC 0.73, SE 0.04, 95% CI
0.64-0.82).
To evaluate the relative contribution to hospital outcome of
each of the 6 organ systems comprising the SOFA, a Cox
proportional hazards analysis was performed. The exponent
of the estimated coefficient ␤ for each organ represents the
factor by which the relative risk of hospital death changes
when the score for that particular organ increases 1 point.
This analysis showed that SOFA scores for the cardiovascular,
neurologic, renal, and hepatic system were significantly related to the risk of hospital death (Table 5). Results remained
unchanged when ICU mortality was used as the dependent
variable.
Resource use, as measured by median TISS of all ICU
days and median length of ICU stay, was directly proportional to the number of organ failures assessed by the SOFA
(Table 6). The total SOFA after the first 24 hours showed a
good correlation with median TISS of all ICU days (Pearson’s r ⫽ 0.7, P ⫽ .01). Moreover, because of the declining
survival with the increasing number of organ failures the
mean cumulative TISS points for patients discharged alive
increased 94-fold from 136 TISS points for patients with no
organ failure to 12,775 TISS points for patients with 3 or
more organ failures.
ically ill cirrhotic patients. The overall predictive accuracy of
the SOFA was 15% and 17% greater than that of the APACHE
II and Child-Pugh systems, respectively.
Several past studies analyzed the predictive abilities
of prognostic systems on the short-term mortality of cirrhotic patients. Zimmerman et al.5 showed that the
APACHE III system accurately risk stratifies critically ill
cirrhotic patients requiring mechanical ventilation. Zauner
et al.25 retrospectively compared the prognostic abilities
of liver-specific and general scoring systems in 198 ICU
patients with cirrhosis. They found that the APACHE III
system was the most accurate prognostic system (AUROC
at admission 0.78, after 48 hours 0.8) and that a cutoff
point of 80 had an overall correct prediction of 70%.25
The prognostic value of the APACHE II system (AUROC
at admission 0.69, after 48 hours 0.78) was as good as
the liver-specific scoring systems (i.e. Mayo Risk Score AUROC at admission 0.72, after 48 hours 0.66, Composite
Clinical and Laboratory Index Scoring AUROC at admission 0.68, after 48 hours 0.68). Cooper et al.26 analyzed
a cohort of 538 patients with decompensated end-stage
liver disease enrolled in the Study to Understand Prognoses
and Preferences for Outcomes and Risks of Treatments
(SUPPORT). They developed a multivariable prognostic
DISCUSSION
In this study we have shown that the SOFA is an excellent
prognostic system for predicting in-hospital mortality in crit-
FIG. 2. Cumulative survival in 143 patients with cirrhosis according to
their SOFA (solid curve, SOFA ⱕ8 points, n ⫽ 71; dashed curve, SOFA ⱖ9
points, n ⫽ 72) after the first day of admission to a medical intensive care unit.
Day 0 is the day of intensive care unit admission.
FIG. 3. Receiver operating characteristic curves for SOFA (■, AUROC
0.94), APACHE II (䊐, AUROC 0.79), and Child-Pugh points (Œ, AUROC
0.74) recorded after the first day of intensive care unit admission.
HEPATOLOGY Vol. 34, No. 2, 2001
WEHLER ET AL.
TABLE 5. Cox Proportional Hazards Regression Analysis Showing the
Effect of Different Organ Systems on the Risk of Hospital Death
Variable
␤
SE
P
Risk Ratio
(95% CI)
Cardiovascular
Neurologic
Renal
Hepatic
Respiratory
Coagulation
0.53
0.37
0.32
0.27
0.08
0.06
0.13
0.11
0.11
0.1
0.11
0.1
⬍.0005
.001
.004
.01
.45
.57
1.69 (1.31-2.17)
1.45 (1.16-1.82)
1.38 (1.1-1.71)
1.3 (1.06-1.6)
1.09 (0.87-1.35)
1.06 (0.87-1.29)
NOTE. Organ systems assessed by SOFA 24 hours after ICU admission. ␤,
coefficient. Risk ratios are presented for a 1-point change in the scores for
each organ.
model, which included renal insufficiency, Glasgow Coma
Score, ventilatory insufficiency, age 65 years, and prolonged prothrombin time, that had a AUROC of 0.76 and
0.74 for death at 30 and 180 days, respectively.26 Butt et
al.27 prospectively compared the prognostic accuracy of the
Child-Pugh and the APACHE III systems in predicting hospital mortality in 282 general ward patients with cirrhosis.
The overall correctness of prediction values were 75% and
67% for the APACHE III and Child-Pugh systems, respectively. Afessa and Kubilis28 compared the prognostic performances of APACHE II and Child-Pugh score in 111 cirrhotic patients hospitalized for upper gastrointestinal
bleeding and did not find significant differences between
the 2 scoring systems (APACHE II AUROC at admission
0.78; Child-Pugh 0.76). Recently Zauner et al.7 developed a
new scoring system for predicting hospital mortality in
critically ill cirrhotic patients. Their Intensive Care Cirrhosis Outcome score is based on a multiple logistic regression
analysis including bilirubin, cholesterol, creatinine clearance, and lactate. In a study group of 70 cirrhotic patients
the Intensive Care Cirrhosis Outcome score showed a high
discriminative ability in predicting hospital mortality (AUROC 0.90) and had an overall correctness of prediction of
83%.7
The predictive accuracies we found for the APACHE II
and Child-Pugh systems in our sample compare well with
data reported by Zauner et al.25 and Afessa and Kubilis.27
The discriminatory power of the SOFA score seems to be
superior to previously evaluated prognostic systems in cirrhotic patients.
The SOFA score also reflected resource use during the ICU
treatment as measured by daily TISS and ICU length of stay.
Resource use increased tremendously with growing organ
dysfunction, and intense therapy was not associated with improved outcome. Similar findings were noted by Cooper et al.
in their group of patients with decompensated end-stage liver
disease.26
For any predictive model to be clinically useful, it must
show ease of use, accuracy, acceptance by the data collecting
staff, and reproducibility.29 The SOFA system has already
been used sucessfully in large numbers of critically ill patients.15,16,30,31 The variables needed to record the SOFA are
derived from standard monitoring of critically ill patients and
calculation at the bedside takes 3 minutes.31 Although the
SOFA was not developed to predict outcome but to describe
the degree of organ dysfunction in critically ill patients, several recent studies showed its predictive ability not only in
259
patients with sepsis but also in trauma patients and in medical
cardiovascular patients.14,15,30,31
However, there are some limitations of the SOFA
that should be addressed. Serum bilirubin as the descriptor of liver function lacks specificity, it has limited ability
to reflect the full spectrum of liver dysfunction in critical
illness and cannot differentiate acute liver dysfunction
from the effects of preexisting chronic disease.32 The Glasgow Coma Scale as the variable reflecting neurologic dysfunction also has shortcomings. Its clinical evaluation is
subject to expectation bias and random error and it is affected by sedative and analgesic drugs frequently used in
critically ill patients. Nevertheless, besides the cardiovascular and renal organ systems, the hepatic and neurologic
systems of the SOFA were also associated with an increased
risk of death. These findings are in agreement with those of
previous studies on the SOFA, which implicated the cardiovascular, the neurologic, and the renal systems in increasing the risk of death.15,16,31 In these investigations no
effect of the hepatic system was noted, but only a minority
of their study patients had severe hyperbilirubinemia during the first ICU day. Interestingly, several recent studies
analyzing the effect of different organ systems on outcome
find no15,31,33 or little effect (risk ratio 1.17)16 associated
with pulmonary dysfunction. Maybe this finding is related
to improvements in respiratory support and the observation that refractory hypoxemia is an unusual cause of
death.33,34
Potential limitations of our study should also be mentioned. First, it was performed at an academic referral hospital, therefore our results may not be applicable to institutions
with different patient populations. Second, it should be noted,
that we tested the prognostic instruments in patients already
admitted to intensive care and not as a preadmission screening tool.8 Finally, we would like to stress that all prognostic
systems are not readily applicable to individual patients because of the fact that scoring systems are developed to predict
group outcomes.35
In conclusion, our data show that the discriminatory
power of the SOFA to predict short-term mortality in critically ill patients with cirrhosis is clearly superior to the
APACHE II and Child-Pugh systems. SOFA also seems to
be superior to previously evaluated prognostic systems.
Prognostic scoring systems cannot replace the clinical evaluation of the patient, which includes an appreciation not
only of the overall prognosis but also of the patient⬘s views.
However, we believe that the SOFA may improve the phy-
TABLE 6. Resource Use for 143 Patients With Cirrhosis According to the
Number of Organ Failures Assessed After the First Day
of ICU Admission
Number of organ failures
Number of patients
Patients alive at hospital discharge/
6-month follow-up (%)
Median SOFA score
Median TISS score*†
Median length of ICU stay (days)†
0
47
94/72
4
22
3
1
36
2
30
67/67
7
28
5.5
27/13
11
38
7.5
ⱖ3
30
3/3
15.5
45
7.5
NOTE. Organ failure is defined as 3 or more SOFA points for the respective
organ system.
*Median TISS points of all days treated on the ICU.
†P ⬍ .0005 by Kruskal-Wallis test.
260 WEHLER ET AL.
HEPATOLOGY August 2001
APPENDIX
The APACHE II Severity of Disease Classification System
High Abnormal Range
Physiologic Variable
ⴙ4
ⴙ3
ⴙ2
Temperature—rectal (°C)
Mean arterial pressure (mm Hg)
Heart rate (ventricular response)
Respiratory rate (nonventilated or ventilated)
Oxygenation
AaDO2 or PaO2 (mm Hg)
FiO2 ⱖ 0.5 record
AaDO2
FiO2 ⬍ 0.5 record only
PaO2
Arterial pH
Serum sodium (mmol/L)
Serum potassium (mmol/L)
Serum creatinine (mg/100 mL) (Double point
score for acute renal failure)
Hematocrit (%)
White blood count (total/mm3) (in 1,000s)
Glasgow Coma Score (GCS), score ⫽ 15
minus actual GCS
ⱖ41
ⱖ160
ⱖ180
ⱖ50
39-40.9
130-159
140-179
35-49
110-129
110-139
ⱖ500
350-499
200-349
ⱖ7.7
ⱖ180
ⱖ7
ⱖ3.5
7.6-7.69
160-179
6-6.9
2-3.4
ⱖ60
ⱖ40
Low Abnormal Range
ⴙ1
38.5-38.9
25-34
155-159
36-38.4
70-109
70-109
12-24
ⴙ1
34-35.9
10-11
ⴙ2
32-33.9
50-69
55-69
6-9
ⴙ3
30-31.9
40-54
ⴙ4
ⱕ29.9
ⱕ49
ⱕ39
ⱕ5
⬍200
7.5-7.59
150-154
5.5-5.9
1.5-1.9
50-59.9
20-39.9
0
PO2
⬎70
7.33-7.49
130-149
3.5-5.4
0.6-1.4
PO2
61-70
3-3.4
7.25-7.32
120-129
2.5-2.9
⬍0.6
46-49.9
15-19.9
30-45.9
3-14.9
20-29.9
1-2.9
32-40.9
22-31.9
18-21.9
PO2
55-60
7.15-7.24
111-119
PO2
⬍55
⬍7.15
ⱕ110
⬍2.5
⬍20
⬍1
A Total Acute Physiology Score (APS)
䊐
Sum of the 12 individual variable points
Serum HCO3 (venous mmol/L) (Not
preferred, use if no ABGs)
ⱖ52
41-51.9
15-17.9
⬍15
B Age points
䊐
Assign points to age as follows:
Age (years)
ⱕ44
45-54
55-64
65-74
ⱖ75
Points
0
2
3
5
6
C Chronic Health Points
䊐
If the patient has a history of severe organ system insufficiency or is immunocompromised assign points as follows: (a) for nonoperative or emergency
postoperative patients, 5 points; (b) for elective postoperative patients, 2 points.
Definitions
Organ insufficiency or an immunocompromised state must have been evident prior to this hospital admission and conform to the following criteria:
Liver: Biopsy-proven and documented portal hypertension; episodes of past upper GI bleeding attributed to portal hypertension; or prior episodes of
hepatic failure/encephalopathy/coma.
Cardiovascular: New York Heart Association Class IV.
Respiratory: Chronic restrictive, obstructive, or vascular disease resulting in severe exercise restriction, i.e., unable to climb stairs or perform household
duties; or documented chronic hypoxia, hypercapnia, secondary polycythemia, severe pulmonary hypertension (⬎40 mm Hg), respirator dependency.
Renal: Receiving chronic dialysis
Immunocompromised: The patient has received therapy that suppresses resistance to infection, e.g., immunosuppression, chemotherapy, radiation, longterm or recent high-dose steroids, or has a disease that is sufficiently advanced to suppress resistance to infection, e.g., leukemia, lymphoma, AIDS.
Aⴙ䊐
Bⴙ䊐
C
APACHE II Score ⫽ Sum of 䊐
A APS points
䊐
B Age points
䊐
C Chronic health points
䊐
Abbreviations: AaDO2, alveolar-arterial oxygen tension gradient; PaO2, arterial oxygen tension; FiO2, fractional inspired oxygen; APS, acute physiology
score; ABG, arterial blood gas; GI, gastrointestinal; AIDS, acquired immunodeficiency syndrome.
Reprinted with permission.13
HEPATOLOGY Vol. 34, No. 2, 2001
sician’s estimate of prognosis and, therefore be useful in
clinical decision making aimed at using medical resources
appropriately as well as providing patients and families
with objective information.
WEHLER ET AL.
17.
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