Trends in Anaesthesia and Critical Care 3 (2013) 89e96

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Trends in Anaesthesia and Critical Care

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REVIEW

Organ dysfunction scores in ICU

C. Giannoni*, C. Chelazzi, G. Villa, A. Raffaele De Gaudio
Department of Health Sciences, Section of Anesthesiology and Intensive Care, University of Florence, Florence, Italy

s u m m a r y
Keywords: Organ dysfunction is common in ICU, and it is associated with high mortality rates, particularly among
Organ failure septic or complicated surgical patients. Scoring systems for organ dysfunction have a fourfold purpose:
Organ dysfunction scores
quantifying the entity and severity of organ dysfunction, stratifying and comparing patients as to
morbidity and risk of mortality, tracking progression of critical illness in ICU and identifying patients who
are unresponsive to therapies. The degree of organ dysfunction is strongly correlated with outcome,
though in general the performance of organ dysfunction scores in terms of outcome prediction is inferior
to that of classical severity scores, such as the Acute Physiology and Chronic Health Evaluation (APACHE)
II and Simplified Acute Physiology Score (SAPS) II. Scoring systems for organ dysfunction can be divided
into multiple organ dysfunction and single organ failure scores. The aim of this review is to summarize
and compare the most commonly used organ dysfunction scores.
Ó 2013 Elsevier Ltd. All rights reserved.

1. Introduction burns.1 In septic patients, Multiple organ dysfunction syndrome

Organ dysfunction is common in ICU, and it is associated with
high mortality rates, particularly among septic or complicated
surgical patients.1 Multiple organ dysfunction syndrome is defined
as a clinical syndrome characterized by development of progressive
and potentially reversible dysfunction in two or more organs or
organ systems.2 Tilney and Bailey described this syndrome in
19733; in 1975, Baue wrote an editorial titled “Multiple, Progressive,
or Sequential Systems Organ Failure: A Syndrome of the 1970s” in
which he postulated that a severe, local pathologic insult could
result in damage to distant organs.4 Following this principle, the
American College of Chest Physicians/Society of Critical Care
Medicine Consensus Conference (ACCP/SCCM) stated that the
detection of altered organ function in the acutely ill patient con-
stitutes a syndrome that should be called “multiple organ dys-
function syndrome” or MODS.5 The ACCP/SCCM proposed the
terminology “dysfunction” to identify this syndrome, a clinical
phenomenon in which organ homeostasis is lost throughout a
critical illness.5 According to the ACCP/SCCM definition, MODS is
defined as a continuum of cumulative organ dysfunctiondan
ongoing process rather than a dichotomous event that is either
present or absent, such as in single organ failure.6 MODS is induced
by a variety of acute insults, including sepsis, surgery, trauma, or
* Corresponding author.
E-mail address: claudiagiannoni@gmail.com (C. Giannoni).
constitutes the most severe zenith of the clinical spectrum, ranging
from sepsis to Multiple organ dysfunction syndrome itself. Many
patients who have suffered from Systemic inflammatory response
syndrome (SIRS) or Multiple organ dysfunction syndrome have
complex illnesses; often, they suffer from acute and chronic dis-
eases, with the nature of their disease presentation changing. In
this context, the rationale for using scoring systems is to ensure
that this evolving disease is properly represented in evaluations
and descriptions.5
Scoring systems for organ dysfunction have a fourfold purpose:
1) quantifying the entity and severity of organ dysfunction, 2)
stratifying and comparing patients as to morbidity and risk of
mortality, 3) tracking progression of critical illness in ICU, and 4)
identifying patients who are unresponsive to therapies.2 The
degree of organ dysfunction is strongly correlated with outcome,
though in general the performance of organ dysfunction scores in
terms of outcome prediction is inferior to that of classical severity
scores, such as the Acute Physiology and Chronic Health Evaluation
(APACHE) II and Simplified Acute Physiology Score (SAPS) II.2
Scoring systems for organ dysfunction can be divided into multi-
ple organ dysfunction scores (e.g. the Sequential Organ Failure
Assessment or SOFA score7) and single organ failure scores, which
describe single organ damage (for example, the Glasgow Coma
Scale for brain damage). The aim of this review is to summarize and
compare the most commonly used organ dysfunction scores.
Multiple organ dysfunction scores measure the total degree
of organ dysfunction in an attempt to estimate ongoing severity

2210-8440/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tacc.2013.01.008
90 C. Giannoni et al. / Trends in Anaesthesia and Critical Care 3 (2013) 89e96

Table 1
Characteristics of sequential organ failure assessment (SOFA), multiple organ dysfunction score (MODS), and logistic organ dysfunction score (LODS).

Score Year Development and collection of data Advantages Disadvantages

MODS 1995 - Systematic review - Simply to apply - Complexity of cardiovascular component
- Linear scale - No specificity of considered clinical parameters
- First value of each day
- Daily assessment
- Score of 0e4 given to each failing organ

SOFA 1996 - Consensus and tested in a prospective - Simple to apply - Evaluation of cardiovascular function depends
multicenter study - Routine laboratory parameters on the choice of vasoactive drugs
- Worst value in 24 h are considered
- Daily assessment
- Score of 0e4 given to each failing organ

LODS 1996 - Multivariate regression analysis - Routine laboratory parameters - Complexity

- Linear scale are considered - Despite increased complexity, no clear evidence
- Worst value at 24 h from ICU admission of better prognostic assessment
- Score of 0, 1, 3, or 5 given to each failing organ

Source: Adapted from Mendonca et al.2

of critical illness and predict outcome8. These scores may be
generaldthat is, they can apply to all critical patients (Table 1)dor
specific for single diseases, most notably sepsis.
2. General organ dysfunction scores
2.1. Multiple organ dysfunction score (MODS)
The Multiple Organ Dysfunction score (MODS) was developed in
1995 by Marshall et al. as a result of a systematic review of the
literature on multiple organ failure.9,10 Used as a measure of out-
come and of multiple organ dysfunction in studies on critically ill
patients, it strongly correlated with the final risk of mortality in ICU
and with hospital mortality. MODS was built considering simple
physiological measures of dysfunction, and the algorithm accounts
for six organ systems: respiratory, cardiovascular, hepatic, coagu-
lation, renal system and neurological (Table 2). The score ranges from
0 to 4 for each organ system, giving a total maximum score of 24;
the first value of each day is used6 to minimize artifactual varia-
bility and reflect a model of organ dysfunction as a
sustaineddrather than a transientdprocess. The maximum MODS
(the sum of the highest damage achieved in each organ system
during the ICU stay of the patient) provides an estimate of the
cumulative organ dysfunction, and it has been proposed as a
measure of outcome.9 The risk of death has a linear correlation with
total MODSs ranging between 0 (<5%) and 4 (>50%). The score
correlates not only with ICU mortality rate but also with in-hospital
mortality rate and ICUeLOS. MODS can also be used to describe
outcomes over time and stratify patients for clinical trials.10 The
main limitation of this score is that it has no relative specificity of
clinical parameters, such as hyperbilirubinaemia, increased serum
creatinine, low platelet count, or the GCS. Moreover, the pressure
corrected for heart rate (HR  MAP/CVP) includes assessment of
Table 2
Multiple organ dysfunction score (MODS).
Organ system 0 1 2 3
*
Cardiovascular (HR CVP/MAP) 0e10 10, 1e15 15, 1e20 20, 1e30 30,
1e300
Respiratory Pa02/Fi02 >300 226e300 151e225 76e150 75
Renal (creatinine, mmol/l) 100 101e200 201e350 351e500 >500
Central Nervous System (GCS) 15 13e14 10e12 7e9 6
Hepatic (total bilirubin, mmol/l) 20 21e60 61e120 121e240 >240
Haematologic (platelet >120 81e120 51e80 21e50 <20
count  103)
Source: Adapted from Cook et al.6
CVP, which is not always available in all patients in the ICU. In
addition, the circulatory system status may be conditioned by dose
of vasopressor agents, which alters these parameters and are not
considered by the score.9
2.2. Sequential organ failure assessment (SOFA) score
The Sequential Organ Failure Assessment (SOFA) score was
implemented in Paris in 1994 with the initial aim to describe
quantitatively and objectively the degree of organ dysfunction
during the course of sepsis-associated critical illness.7,11 Later, it
was applied to broader populations of critical patients and became
known by the acronym SOFA.8
As with MODS, evaluation of the score regularly and repeatedly
allows monitoring of patients’ clinical conditions and progression
of the critical illness in terms of ongoing organ failure.12 The score
evaluates six different systems (Table 3).
The function of each organ is scored from 0 (normal function)
to 4 (most abnormal), giving a possible score from 0 to 24.13 In
contrast to MODS, for the SOFA score, the worst value of each day
is recorded. In this score, cardiovascular dysfunction/failure is
based on the need of adrenergic support because the authors
could not find a better way to describe the cardiovascular system.7
The advantages of this score are that it is easily assessable and
utilizable, as it uses routine laboratory parameters. Further, it
allows for evaluating the damage of the single organ and its
evolution time.14 Although any assessment of morbidity can be
correlated to the risk of mortality, an SOFA score is not designed to
predict outcome but rather to describe a sequence of complica-
tions in critically ill patients. Moreno et al. showed that the total
maximum score has a very good correlation with outcomes and
that all the individual organ scores were higher in non-survivors.
Authors found that the best discriminative power was seen for the
cardiovascular score.15
SOFA score can predict long-term mortality in trauma patients,
in patients with peritonitis, and in patients with life-threatening
complications from cancer.16 Huang et al. extended these obser-
4 vations to evaluate the impact of organ dysfunction after acute
myocardial infarction (AMI) and found a correlation between SOFA
score and clinical outcome; they concluded that the SOFA score
provides potentially valuable prognostic information when applied
to patients with AMI.17,18 Finally, it was also found that the mean
SOFA score was more closely correlated with mortality than the
initial SOFA score, and it was also demonstrated that the trends of
SOFA score over the first 48 h may be clinically useful when they
decrease, in fact it was associated with a decrease in mortality.18
 C. Giannoni et al. / Trends in Anaesthesia and Critical Care 3 (2013) 89e96 91

Table 3
Sequential organ failure assessment (SOFA) score.

Systems/score 1 2 3 4
Central Nervous System (GCS) 13e14 10e12 6e9 <6
Respiratory Pa02/Fi02 <400 <300 <200 with respiratory support <100 with respiratory support
Cardiovascular hypotension MAP, <70 mmHg Dopa < 5 or Dobutamine Dopa > 5 or Epi < 0.1 or Norepi < 0.1 Dopa > 15, Epi > 0.1, Norepi > 0.1
Haematologic (platelet count  103) <150 <100 <50 <20
Hepatic (total bilirubin, mmol/l) 1.2e1.9 2.0e5.9 6e11.9 >12
Renal (creatinine, mmol/l) 1.2e1.9 2.0e3.4 3.5e4.9 or <500 ml/24 h >5.0, <200 ml/24 h

Source: Adapted from Huang et al.17

The Delta SOFA scoredthat is, the amount of organ dysfunction
occurring after ICU admissiondmeasures the progress of the
patient during the course of ICU stay and shows a good correlation
to outcomes in the Moreno series.15
2.3. Logistic organ dysfunction score (LODS)
The Logistic Organ Dysfunction Score (LODS) was developed by
Le Gall and colleagues in 1996.19,20 The developmental database for
this score was assembled as part of the European/North American
Study of Severity Systems (ENAS), which was used to develop the
Simplified Acute Physiology Score (SAPS) II for estimating the
probability of mortality among ICU patients. Authors collected data
on 14,745 patients admitted in 137 medical and surgical ICUs in 12
different countries.
LODS is calculated within the first 24 h, and 12 variables were
selected to study the function of six organ systems. All variables
must be measured at least once during the first day in ICU. If they
are not measured, they are considered normal for scoring pur-
poses.8 If the variables are measured more than once in the first
24 h, the most severe value is used for score calculation. The score is
based on six different systems: central nervous system, car-
diovascular system, renal system, respiratory system, haematologic
system and hepatic system (Table 4). LODS is calculated on the basis
of a logistic equation with the multiple logistic regression techni-
que and transformed into a model of mortality probability.21 LODS
is a weighted system: For neurological, cardiovascular, and renal
dysfunction, the maximum score allowed is 5; for respiratory and
coagulation systems, the maximum score allowed is 3; for liver
dysfunction, the maximum score is 1.8 The total number of points
provides an estimated risk of mortality. Four severity levels
are identified with scores ranging from 0 to 22 (0 indicates no
dysfunction, and 22 is the highest degree of severity). The additive
score correlates with the mortality rate. LODS also contains a
logistic regression equation that provides the probability of in-
hospital mortality.18 Thus, in contrast to SOFA and MODS, LODS
was implemented as a model of mortality prediction and not as a
solely descriptive model.12
LODS was developed to assess patient’s severity within the first
day of ICU admission22; however, it is possible to use it on a daily basis
because most values are routinely available for most ICU patients. This
is called delta-LODS, reflecting the degree of ongoing organ failure
during the course of ICU stay. Increases in delta-LODS are associated
with an increased ICU mortality.23 LODS was found to have an
excellent calibration (that is, the prognostic accuracy at different
levels of risk) and a very good discrimination (the ability of the model
to distinguish patients who will survive from patients who will
die).20,24 Chevret studied the daily accuracy of LODS in predicting the
mortality of critically ill patients, and the authors observed that the
daily LOD score accurately predicted ICU mortality at any time during
the first ICU week and it should be used to estimate the contribution of
the severity of the illness to the risk of death.25
2.4. Predisposition, infection, response, organ (PIRO) failure
Septic patients are significantly heterogeneous, and this makes
them difficult to stratify. A system for risk stratification emerged
from the Fifth Toronto Sepsis roundtable held in Toronto in October
2000 and this was the Insult, Response, and Organ dysfunction
system (IRO).26 In 2001, the International Sepsis Definitions Con-
ference expressed the need for a new, more sophisticated model for
staging the severity of sepsis and introduced the acronym
PIROdwith the addition of predisposition to IRO system.27 The
total score ranges from 0 to 13 and correlates with mortality at the
Pearson test.28 Williams et al.28 demonstrated that each compo-
nent of PIRO contributed to the overall risk of death with 30e50%
for any increase of each score entry. “P” (predisposition) includes
age, chronic liver disease, and congestive cardiomyopathy. An
increasing P corresponds to increasing mortality. “I” stands for
insult/infection and is adjusted for “P.” “R” stands as response to

Table 4
Logistic organ dysfunction score (LODS).

Organ system Parameter 5 3 1 0 1 3 5

Cardiovascular HR <30 30e139 >140
Systolic blood pressure <40 40e69 70e89 90e239 240e269 270

Haematologic WBC (109/l) <1 1e2.4 2.5e49.9 50

Platelets (109/l) 0e49 50

Renal Urea nitrogen (g/l) 0.36e0.59 0e0.35 0.60e1.19 1.20

Creatinine (mg/dl) 1.20e1.59 0e1.19 1.60
Urine output <0.5 0.5e0.74 0.75e9.99 10

Neurologic GCS 3e5 6e8 9e13 14e15

Pulmonary PaO2 (mmHg)/FiO2 (on MV or CPAP) <150 150 No MV, no CPAP

PaO2 (kPa)/FiO2 <19.9 19.9 No IPAP

Hepatic Bilirubin (mg/dl) <2.0 2.0

PT time (s) 3 >3

Source: Adapted from Heldwein et al.21

92 C. Giannoni et al. / Trends in Anaesthesia and Critical Care 3 (2013) 89e96

Table 5
Predisposition, infection, response, organ (PIRO).

Criteria 0 1 2 3 4
Predisposition P0 age < 46 P1 age 46e64, no CLDa P2 age 64e85, no CLD and P3 age 46e64 with CLD P4 age 64e85 with CLD or age >85
no CCb or 64e85 with CC
c
Insult/infection I0 CA-UTI gram I1 CA-UTI not Gram-neg I2 CA infection except CA-UTI I3 nosocomial-acquired infection I4 nosocomial abdominal fungal
neg or nosocomial Gram-neg except Gram-pos or nosocomial infection
fungal nonabdominal infection
Response R0 no tachycardia R1 both tachycardia and
or tachypnoea tachypnoea
Organ failure O0 2OFd O1 3OF, 1 hepatic O2 3OF, none hepatic O3 4OF O4 5OF
a
CLD e chronic liver disease.
b
Chronic cardiomiopathy.
c
Community-acquired urinary tract infection.
d
Organ failure.
Source: Adapted from Williams et al.28

insult, and “O” stands for organ failure based on number of organ
failures (hepatic, cardiovascular, respiratory, haematologic, renal,
and metabolic acidosis) (Table 5).
The advantage of this score, compared with the MODS or SOFA
score, is that PIRO takes into account clinical variables that are more
specific for the septic patient rather than the generally critically
ill29. Although mortality in sepsis seems primarily associated with
the presence and degree of dysfunction/failure before or after ICU
admission, other factors have been shown to play important roles;
these include the nature of infection (nosocomial vs. community-
acquired) and the characteristics of the infection (site of infection,
presence of Gram-negative bacteria or fungi, and extent of
infection).29
3. Organ-specific dysfunction scores
3.1. Central nervous system: Glasgow coma scale (GCS)
The most frequent causes of central nervous system (CNS) fail-
ure are subarachnoid haemorrhage, spontaneous intracerebral
haemorrhage, ischaemic stroke, traumatic brain injury, anoxic
brain injury, status epilepticus, metabolic disorders, and infectious
disorders and sepsis.30 The kind of encephalopathy associated with
sepsis is related to the presence of microorganisms or their toxins
in the blood and in the brain; this is called “sepsis-associated
encephalopathy” (SAE).31 This term wants to define a diffuse cer-
ebral dysfunction induced by the systemic response to the infection
without clinical or laboratory evidence of direct infection in the
central nervous system.31
Cook et al. used the Glasgow Coma Scale to describe CNS
alterations in encephalopathy induced by sepsis,6 and Eidelman
and Sprung showed that a worsening of encephalopathy measured
by GCS is linked to an increase in mortality in septic patients.32 So,
even if it does not yield a proper score for SAE, GCS remains the
main score used for all the most frequent causes of CNS failure. The
Glasgow Coma Scale (GCS) was first implemented by Teasdale and
Jennett in 1974.33 Professor Jennet was involved in a 1970 multi-
arousal networks. Eyes opening to pain (score of 2), tested by a
stimulus on the limbs (supraorbital pressure may cause grimacing
and eye closure) indicate that this network is dysfunctional. No eye
opening (score of 1) stands for no response to speech or pain and
indicates absent arousal activity. One limit in this approach is the
persistent vegetative state, in which eye opening is not related to
arousal. The presence of verbal response indicates a higher level of
integration in the central nervous system. Other factors that may
influence verbal expression are tracheostomy, endotracheal tube,
or dysphasia. Oriented verbal response indicates that the patient is
aware of himself and the surrounding environment. Confused
verbal response indicates that the patient can converse but is
unable to answer questions about orientation. Inappropriate words
describe clear and comprehensible speech but using random or
repeated words. Incomprehensible sounds refer to moaning and
groaning without recognizable words, even if there is an attempt to
articulate. No sounds mean that the patient is unable to verbalize at
all. For motor response, a patient obeying to commands (score 6)
indicates an ability to process and integrate verbal stimuli; local-
ization to pain (score 5) indicates that the patient is able to identify
the location of a painful stimulus and attempts to remove it.
Withdrawal (score 4), or a normal flexor response, means the
patient attempts to move away from the noxious stimulus by rapid
withdrawal or abduction at the shoulder. A score of 6, 5, or 4
indicates integrity of cerebral cortex and integration networks. An
abnormal flexor response (score 3) implies a cerebral hemisphere
or internal capsule lesion. An abnormal flexor response is complex
but involves upper limb adduction, flexion of arms, wrists and
Table 6
Glasgow coma scale (GCS).
Activity Best response Score
Eye opening Spontaneous 4
To verbal stimuli 3
To painful stimuli 2
None 1

centre study to collect data on patients with severe traumatic head Verbal Oriented 5
injury. During the study, the authors found they were unable to Confused 4
uniquely identify “severe”; therefore, the score was created as a Inappropriate words 3
Nonspecific sounds 2
score initially intended as a research tool.34 The use of this score None 1
started to expand rapidly, and it has been successful because of its
Motor Follows commands 6
simplicity and reliability. The scale is composed of eye movement
Localizes pain 5
response, verbal response, and motor response. The three entries Withdraws to pain 4
are evaluated separately, and their sum is considered. The lowest Abnormal flexion to pain 3
possible GCS is 3 (deep coma or death), while the highest is 15 (fully Extension to pain 2
awake) (Table 6). Eyes opening can be spontaneous (score of 4) or to None 1

speech (score of 3), indicating integrity of brainstem and cortical Source: Adapted from Middleton et al.35
 C. Giannoni et al. / Trends in Anaesthesia and Critical Care 3 (2013) 89e96
fingers, extension for midbrain to upper pontine damage and
internal rotation of lower limbs and plantar flexion of feet. Extensor
posturing (score 2) is a hyperpronation of upper extremities,
extension of legs, plantar flexion of feet, progress to opisthotonus
(decerebration). None (score 1) means that the patient is flaccid
and makes no movement in response to a painful stimulus.35
GCS was originally described as a bedside repeated assessment.
It was used to objectively determine the severity of coma and
underlying brain dysfunction about 6 h after a traumatic brain
injury.34 This time period was chosen to avoid overestimation of
brain damage produced by temporary factors such as alcohol,
hypoxia, or hypotension. Indeed, GCS can be used in prehospital
trauma care and at the hospital admission as a predictor of outcome
in trauma populations, not only as a mortality predictor but also as
a predictor of functional outcome.36 The most important limi-
tations of GCS are the inability to obtain complete GCS data from
patients who are intubated or sedated. In addition, its use is
problematic outside the setting of trauma; for example, in epileptic
activity and in metabolic or drug-related CNS alterations, including
deep sedation.20 As a tool for the evaluation of CNS dysfunction, the
GCS has also been incorporated into more complex scores, such as
the Acute Physiology, Chronic Health Evaluation score (APACHE),
Trauma ScoreeInjury Severity Score (TRISS), SOFA score, MODS,
and LODS.20 Therefore, GCS is incorporated into all major scores
used in ICU to assess the neurological system. Even though one of
the main limitations of GCS is the use in sedated or intubated
patients, intensive care remains one of the settings for the appli-
cation of this score. In this scenario, its simplicity, and reproduci-
bility exceed this limit.37
3.2. Kidney
Acute kidney injury (AKI) is defined as a sudden and significant
decrease in kidney function.38 Acute renal failure (ARF) is a com-
mon complication of critical illness, and it is associated with high
mortality and has a separate independent effect on the risk of
death.39
3.2.1. Risk, injury, failure, end stage renal disease (RIFLE)
The Acute Dialysis Quality Initiative (ADQI) workgroup identi-
fied a definition/classification system for AKI. The group proposed a
multilevel classification in which the complete spectrum of acute
kidney injury could be included.38 The Risk, Injury, Failure, Loss,
and End stage Kidney (RIFLE) classification defines three pro-
gressive degrees of severity for AKI: risk (R), injury (I), and failure
(F) and the two outcome classes, loss of function (L) and end-stage
kidney disease (E) (Fig. 1). The RIFLE system is based on the severity
of modifications of serum creatinine or urine output from the
baseline conditions. The proposed timeframe for clinical
Fig. 1. Risk, injury, failure, end stage renal disease (RIFLE). Source: Adapted from Ronco
et al.40
93
application of RIFLE criteria is 1 week.39 RIFLE seeks to establish the
presence of AKI and to describe the severity of this syndrome; the
system is not intended to predict mortality or adverse outcome.
Since the publication of this score, many studies have been pub-
lished about the score’s utility. These studies are different from
each other and have different objectives to describe the epidemi-
ology of AKI or the association between the severity of AKI and
outcome.40 Among a total of 200,000 patients included in all these
studies, less than 2% were part of prospective studies; most studies
were retrospective and used only the creatinine/GFR (only 12% of
the studies used creatinine and urine output criteria together40,41).
Limitations of RIFLE classification are linked to relative non-
specificity of creatinine and urine output modifications. The
amount of lean body mass and the use of diuretics may alter RIFLE
criteria and interfere with patients’ stratification. Kellum noted that
patients in the Risk class, defined by creatinine, were more severely
ill than patients in the same class defined by urine output because
of the diuretic effects.38 A great limit of creatinine in evaluating
renal function is that it rises late and only for large amounts of lost
nephrons; baseline values are not always available. This makes
application of RIFLE criteria difficult because the system considers
changes from baseline. A possible solution could be to calculate a
theoretical baseline serum creatinine, assuming a normal glomer-
ular filtration rate.39 To overcome these limits, the use of
biomarkersdsuch as neutrophil gelatinase-associated lipocalin
(NGAL) or Cystatin Cdhas been suggested since they change sig-
nificantly earlier than does serum creatinine. Indeed, they seem to
reflect different aspects of renal injury; for example, NGAL reflects
tubular stress, and Cystatin C reflects changes in glomerular fil-
tration rate.42 However, currently, their routine use in clinical
practice is not supported. Moreover, changes in serum creatinine
smaller than those included under class Risk are associated with
poor outcomes.40 Further Kellum et al. showed that patients with
RIFLE class R are at high risk of progression to class I or class F, and
in patients with class I or F there was a significant increase in ICU
stay and of in-hospital mortality.38
3.2.2. Acute kidney injury network (AKIN) classification
AKIN was created by the Acute Kidney Injury Network working
group in 200743 as a modified version of the RIFLE classification.
Risk, injury, and failure were changed in AKIN stages 1, 2, and 3:
Patients who start renal replacement therapy were classified in
stage 3. The outcome categories were eliminated. The diagnostic
criteria for AKI proposed by AKIN are an abrupt (within 48 h)
reduction in kidney function defined as an absolute increase in
serum creatinine level of 26.4 mmol/l (0.3 mg/dl) or a percentage
increase in serum creatinine level of 50% (1.5-fold from baseline)
or a reduction in urine output (documented oliguria of <0.5 ml/kg/
h for >6 h) (Fig. 2). The fundamental aim of AKIN classification is to
Fig. 2. Acute kidney injury network (AKIN). Source: Adapted from Ronco et al.40
94 C. Giannoni et al. / Trends in Anaesthesia and Critical Care 3 (2013) 89e96

guarantee the best outcomes for patients with, and those at risk of Table 7
developing, AKI. This definition was based on evidence that even Lung injury score (LIS).
small changes in serum creatinine are associated with adverse
Test Result Score
outcome. The time for diagnosis is 48 h, and that was proposed to
Chest radiogram No alveolar consolidation 0
guarantee a rapid diagnosis for an acute condition. The AKIN clas- Alveolar consolidation 1
sification emphasizes the concept that small alterations in renal confined to 1 quadrant
function contribute to adverse outcomes. The AKIN classification Alveolar consolidation 2
excludes easily reversible causes of decreased urine output as confined to 2 quadrants
Alveolar consolidation 3
urinary tract obstructions or volume depletion. These factors are
confined to 3 quadrants
virtually impossible to verify in retrospective studies, which makes Alveolar consolidation 4
it impossible to apply this classification in this kind of study. The confined to 4 quadrants
AKIN classification is based on changes in creatinine within 48 h, a
Hypoxaemia score PaO2/FiO2 >300 0
measure not always available in hospital wards. AKIN requires two PAO2/FiO2 225e299 1
consecutive serum creatinine for the diagnosis; therefore, this PaO2/FiO2 175e224 2
obviates the problem of unavailable baseline creatinine. The largest PaO2/FiO2 100e174 3
PaO2/FiO2 <100 4
study that used the AKIN classification was a retrospective rean-
alysis in which the authors compared RIFLE and AKIN on the first PEEP score (when mechanically <5 cm H2O 0
day in ICU; mortality and prevalence were very similar between ventilated) 6e8 cm H2O 1
9e11 cm H2O 2
AKIN and RIFLE.44 They concluded that the AKIN criteria did not
12e14 cm H2O 3
materially improve the sensitivity or the ability of the definition >15 cm H2O 4
and classification of AKI in the first 24 h after admission to ICU.44 In
Respiratory system compliance >80 ml/cm H2O 0
another large retrospective study involving 22,303 patients, the score (when available) 60e79 ml/cm H2O 1
authors concluded that the 48-h window for AKI diagnosis may 40e59 ml/cm H2O 2
miss patients with a slow but significant decline in renal function.45 20e39 ml/cm H2O 3
The limitations of AKIN are similar to RIFLE; in fact, the diagnosis <19 ml/cm H2O 4
based on clinical parameters can be late, so it can be difficult to Source: Adapted from Matthay et al.49
apply these criteria to patients without creatinine daily measure-
ments or to patients admitted with a high creatinine that then
decreases.40 3.4. Liver: ChildePugh

3.3. Lung: lung injury score (LIS) Decompensated cirrhosis has a poor prognosis with a mortality
rate of 79%, which becomes higher when cirrhotic patients require
According to the Berlin definition of Acute Respiratory Distress admission to ICU.50
Syndrome (ARDS),46 ARDS is an acute diffuse, inflammatory lung The Child and Turcotte classification (1964) and the Pugh’s
injury that leads to an increase of pulmonary vascular permeability, modification (1973) have been widely used for the assessment of
an increase of lung weight, and loss of aerated lung tissue. The the severity of decompensated chronic liver disease. The Childe
clinical hallmarks are hypoxaemia and bilateral radiographic Pugh score can stratify patients into prognostic groups: patients
opacities, associated with increased venous admixture, increased who need surgical treatment, sclerotherapy, or transjugular intra-
physiological dead space, and decreased lung compliance. The hepatic portosystemic shunt (TIPS). The ChildePugh score includes
morphological hallmark of the acute phase is diffuse alveolar three different classes, each of which is associated with a pro-
damage (i.e., oedema, inflammation, hyaline membrane, or hae- gressively less favourable prognosis (Table 8). The points for each
morrhage).46 The Berlin definition proposed a definition with three parameter can be calculated by the sum of the individual scores. CP
mutually exclusive severity categories of ARDSdmild, moderate, score was initially proposed for portal hypertension surgery, but its
and severedand proposed some variables to characterize severe prognostic value has been demonstrated in many other situations,
ARDS: timing, chest imaging, origin of oedema, and oxygenation such as ascites, ruptured esophageal varices, subclinical encephal-
plus additional physiologic measurements as the compliance.46 opathy, hepatocellular carcinoma, liver surgery, alcoholic cirrhosis,
Murray et al. developed the Lung Injury Score (LIS) to charac- decompensated HCV-related cirrhosis, primary sclerosing chol-
terize the presence and extent of acute pulmonary damage.47 LIS angitis, primary biliary cirrhosis, and BuddeChiari syndrome.51
quantifies the severity of lung injury and respiratory failure from Though commonly used to assess hepatic dysfunction and prog-
the degree of arterial hypoxaemia, the level of PEEP, the respiratory nosis in ICU patients with acute and acute-on-chronic hepatic
compliance and the radiographic abnormalities (Table 7).46 Patients failure, a study by Burroughs et al. demonstrated that for cirrhotic
with severe lung injury have LIS of more than 2.5, those with mild patients admitted to ICU, SOFA was a better predictor than the
lung injury LIS of 1e2.5. LIS has been used to assess the improve- ChildePugh scores.50 Moreover, some important clinical
ment or worsening of the severity of lung injury. Gas exchange aspectsdsuch as age or presence of varicesdwere not included.52
abnormalities are expressed as the ratio between arterial oxygen
tension and the fractional concentration of inspired oxygen.
Radiographic abnormalities are useful to evaluate the presence of Table 8
oedema and the severity of increased pulmonary permeability. ChildePugh.
PEEP is an added value that takes into account that some patients Points 1 2 3
are already ventilated when their pulmonary parenchymal injury
Encephalopathy None Minimal Advanced (coma)
occurs; in this case, a better PaO2/FiO2 ratio may be influenced by Ascites Absent Controlled Refractory
ventilation therapy. Compliance measures give additional infor- Bilirubin (mmol/l) <34 34e51 >51
mation about the severity and the course of parenchymal lung Albumin (g/l) >35 28e35 <28
injury.48 The main limitations of the score are linked to variability Prothrombin (s) <4 4e6 >6

in chest radiogram interpretation and measure of compliances.49 Source: Adapted from Valla.51
 C. Giannoni et al. / Trends in Anaesthesia and Critical Care 3 (2013) 89e96
Finally, ascites and hepatic encephalopathy have some subjective
components, and these variables may alter between observers.
3.5. Cardiovascular system
Acute cardiovascular failure and shock are common in critical
patients. Common alterations may include reduced venous return
from fluid shift and increased venous capacity, reduced or
increased peripheral vascular resistance, and depressed cardiac
contractility.53 The net result is usually a reduction of organ per-
fusion and delivery of oxygen to tissues and a state of “global
hypoxia,” which contributes to organ dysfunction.54 During shock,
when fluid administration fails to restore adequate arterial
pressure and organ perfusion, therapy with vasopressors is
initiateddincluding norepinephrine, dopamine, epinephrine,
phenylephrine, or vasopressin.55 The “vasopressor score” is calcu-
lated as dopamine dose (mg/kg/min  1) plus dobutamine dose
(mg/kg/min  1) plus epinephrine dose (mg/kg/min  100) plus
norepinephrine dose (mg/kg/min  100) plus phenylephrine dose
(mg/kg/min  100).56 This is an indirect measure of the degree of
cardiocirculatory failure in the critically ill. This score was first used
to quantify the impact of a thyroid hormone infusion (T4) on the
vasopressor requirements in a group of children with cessation of
neurologic function.56 Despite not being validated as a severity
score in the critically ill, its use has been proposed to quantify the
degree and severity of circulatory shock.
4. Conclusions
Single organ failure of multiple organ dysfunction is common in
critically ill patients. The number of failing organs and the degree of
failure is linked to the severity of the disease and outcome. Many
scoring systems are available to quantify organ failure and assess
the outcome and risk of mortality. Of those, SOFA, MODS, and LODS
are the most validated. Single organ scores are less reliable in
predicting the outcome, although in some clinical scenarios, they
may be more relevant than general scores in quantifying the
process underlying critical illness, such as the GCS in traumatic
brain injury.
Conflict of interest
All of the authors declare they have no conflicts of interest.
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