CASI CLINICI

MINERVA ANESTESIOL 2006;72:87-96

A
T ® IC
Sepsis diagnosis and management:
work in progress

D
J. L. VINCENT, A. M. HABIB, C. VERDANT, A. BRUHN

GH E
M
Severe sepsis is a common disease process
in the critically ill and is associated with sub-
stantial morbidity and mortality. Continuing
Deparment of Intensive Care,
Erasme Hospital
Free University of Brussels, Brussels, Belgium
research has provided considerable insight
into the pathophysiology of sepsis over
recent years, enabling various aspects of the
A

sepsis response to be targeted. Discoveries

related to the link between coagulation and Definitions of sepsis
inflammation have been particularly excit-
PY V

ing, leading to the development of recombi- Sepsis vs infection

nant activated protein C. This review will dis-
cuss current definitions of sepsis, describe The words “sepsis“ and “infection“ are
new approaches to classification and diag- often used as synonyms, but they are dis-
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nosis of patients with sepsis, present rec-

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tinct entities. Infection is a microbiological

ommendations for management, and briefly
highlight areas of ongoing and future event, caused by bacteria, fungi, viruses etc.,
research. while sepsis is the host response to that infec-
CO E

Key words: Sepsis, diagnosis - Sepsis, therapy - tion, characterized by the release of many
Intensive care. mediators and by a constellation of clinical
and laboratory features (Table I), none of
IN

which are specific for sepsis. Whenever pos-

sible, infection should be defined by the
R ecent years have seen great advances in
our understanding of the pathophysiol-
ogy of sepsis and as a result new treatments
organ primarily infected and the type(s) of
microorganisms (e.g., a lung infection due
have become available and more are being to Pneumococcus or a urinary tract infection
due to E. coli). While the presence of infec-
M

developed.
In addition, progress has been made in
techniques to facilitate the diagnosis of sep-
sis.
In this article we will discuss the recent
advances in the diagnosis and management
of this important and common problem.
Address reprint requests to: Prof J. L. Vincent, Erasme
Hospital, Route de Lennik 808, 1070 Brussels, Belgium.
E-mail: jlvincen@ulb.ac.be
tion is essential for a diagnosis of sepsis,
sometimes the source of infection cannot be
identified, and sometimes the bacteriology
remains negative. In some patients with sep-
sis, the causative infection may never be iden-
tified at all; this does not mean the patient
does not have an infection, and hence can-
not have sepsis, just that we are unable to
locate or identify it. To help to rule out an
infection, an objective measure such as the

Vol. 72, N. 3 MINERVA ANESTESIOLOGICA 87

VINCENT
TABLE I.—Common clinical and laboratory features of
sepsis.
— Fever/hypothermia
— Increased cardiac output/low systemic vascular resi-
stance
— Increased oxygen consumption
— Unexplained tachycardia
— Unexplained tachypnea/respiratory alkalosis
— Altered white blood cell count
— Increased C-reactive protein levels
— Increased procalcitonin levels
— Unexplained hyperglycemia
D
— Unexplained lactic acidosis
— Unexplained respiratory dysfunction (acute lung
injury)
— Thrombocytopenia/disseminated intravascular coa-
GH E
gulation
— Unexplained disorientation or confusion
— Unexplained alteration in liver function tests
— Unexplained alteration in renal function
M
— Capillary leak syndrome
T
infection probability score, which weights 6
variables [temperature, heart rate, respirato-
A
ry rate, white blood cell count, C-reactive
protein (CRP), sequential organ failure assess-
ment score (SOFA)] to make a composite
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score, may be useful.1
New concepts
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In the most recent International Sepsis
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Consensus Conference,2 the 29 experts
charged with providing “a conceptual and a
CO NE
practical framework to define the systemic
inflammatory response to infection” came to
the following conclusions: first, that the con-
cepts of sepsis (the host response to an infec-
tion), severe sepsis (sepsis associated with
organ dysfunction) and septic shock (sepsis
plus arterial hypotension despite adequate flu-
I
id resuscitation), as defined in the 1991 North
M
American Consensus Conference,3 remain use-
ful to clinicians and researchers, but that they
do not allow for precise staging or prognosti-
cation of the host response to infection.
Second, that while the concept of systemic
inflammatory response syndrome (SIRS)
remains useful as a concept, the diagnostic
criteria for SIRS published in 1992 3 are too
sensitive and non-specific, and an expanded
list of signs and symptoms of sepsis may bet-
ter reflect the clinical response to infection.
88 MINERVA ANESTESIOLOGICA
SEPSIS DIAGNOSIS AND MANAGEMENT
In view of these conclusions, the partici-
pants introduced the PIRO (predisposing
A
factors, infection, response, organ dysfunc-
tion) concept,2 a suggested means of staging
sepsis, rather like many cancers are staged
IC
using the tumor, nodes, metastases (TNM)
system. Using the emerging PIRO model
could aid physicians in better characteriz-
ing heterogeneous groups of septic patients,
providing insight into the continuum of sep-
sis, and improve the understanding and
management of severe sepsis and septic
shock.
PREDISPOSING FACTORS
Predisposing factors 4 include individual
®
characteristics, such as age, chronic diseases,
prolonged immunodepressant medications,
etc., that may influence a patient’s response
to infection and/or indicate which therapies
are likely to be most effective in that patient.
Increasingly, the role an individual’s genetic
make-up may have on the development of
sepsis and the severity of disease when it
develops are being explored and various
polymorphisms have been shown to influ-
ence the risk of infection and/or of mortali-
ty from sepsis.5 Single nucleotide polymor-
phisms, microsatellite, insertion and deletion
polymorphisms are all forms of genetic vari-
ation that can characterize an individual’s
risk for sepsis, organ dysfunction, or death.6
A polymorphism of the tumor necrosis factor-α
(TNF-α) gene, the TNF-2 allele, is associated
with increased serum levels of TNF and a
greater risk of mortality from septic shock.7 A
polymorphism within the intron 2 of the inter-
leukin-1 receptor antagonist (IL-1ra) gene
(IL-1RN*2) has been associated with reduced
IL-1ra production and increased mortality
rates.8 Polymorphisms in the Toll-like recep-
tor (TLR) and interferon-γ genes have also
been identified influencing susceptibility to
sepsis.9, 10 Advances in genetics technology
have now allowed investigators to design
glass slides (chips) with minute quantities of
short, gene-specific nucleotides. These gene-
specific probe nucleotides, ideally one for
each gene in the genome, are arrayed onto
the chip surface to produce a DNA microar-
Marzo 2006
SEPSIS DIAGNOSIS AND MANAGEMENT
ray. These can be used to generate an expres-
sion profile, the transcriptome, for the cell
or tissue of interest.6 Genomics and the
broader field of proteomics are likely to
become increasingly routinely used in patient
management.
INFECTION
Characteristics of the particular infection,
such as site (e.g., lung versus urinary tract),
D
responsible organism(s) (e.g., Gram-nega-
tive versus Gram positive, MRSA versus
MSSA), severity, can have an effect on the
GH E
host response and outcome, and may influ-
ence choice of treatment.11 However, while
few would argue that an E. coli urinary tract
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infection is likely to be less life-threatening
than a meningococcal meningitis, classify-
T
ing the relative importance of infections on
outcome is difficult. Using a systematic lit-
erature review and surveying 510 articles
A
describing the outcome of infections, cate-
gorized by microorganism and site of infec-
tion, Cohen et al.12 recently generated spe-
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cific risk codes for bacteremia, meningitis,
pneumonia, skin and soft tissue infections,
peritonitis, and urinary tract infections. For
R
each infection site and organism, a two-dig-
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it code was generated according to the mor-
tality rate associated with that infection (from
1: ≤5% to 4: >30%), and the level of evidence
CO NE
available to support the mortality risk (level
A representing evidence from more than 5
studies with more than 100 patients, through
to level E insufficient evidence from case
reports). They suggested this system be
termed the grading system for site and sever-
I
ity of infection (GSSSI) and although it needs
to be validated, this could be a useful means
M
of better characterizing the different risks
associated with infections caused by differ-
ent organisms in different sites.12 The tim-
ing of onset of infection may also influence
outcomes. A recent study showed that
patients who developed septic shock with-
in 24 h of ICU admission were more severe-
ly ill, but had better outcomes than patients
who developed septic shock later during
their ICU stay.13
Vol. 72, N. 3 MINERVA ANESTESIOLOGICA
VINCENT
RESPONSE
The degree of host response can be
A
assessed according to the presence or
absence of various clinical and laboratory
features and to the degree of elevation of,
IC
for example, white cell count, CRP, procalci-
tonin (PCT) etc.14 The host response will vary
between patients and over time in the same
patient. Volk et al. described an early hyper-
inflammatory phase followed by immuno-
paralysis based on the level of HLA-DR
monocyte surface expression in septic
patients.15 Improving our assessment of the
host response could help direct therapies
more appropriately.
®
ORGAN DYSFUNCTION
Organ dysfunction in severe sepsis is not
a simple present or not variable, but a con-
tinuous spectrum involving many organs and
varying with time and treatment.16 The degree
of organ involvement can be assessed with
various scoring systems, one of the most com-
monly used being the SOFA score.17
Diagnosis of sepsis
Sepsis represents a major diagnostic prob-
lem for the intensivist and considerable effort
is being concentrated on finding a sensitive
and specific diagnostic marker; many have
been suggested 18-22 and a non-exhaustive
list of proposed markers of sepsis is shown in
Table II. Studies have shown that early ther-
apy is critical in improving outcomes from
sepsis,23, 24 and the identification of a mark-
er that would allow a clear diagnosis of sep-
sis would certainly help improve outcomes in
these patients.
Procalcitonin (PCT) and CRP are 2 candi-
date markers of sepsis that have received a lot
of attention. CRP is an acute phase protein
that was first described in the early 1930s.
CRP levels are widely used as a relatively
non-specific marker of inflammation, and
many studies have demonstrated increased
CRP levels in patients with sepsis.25-27
Concentrations above 10 mg/dL on admis-
sion have been associated with particularly
89
VINCENT
TABLE II.—Some of the suggested markers of sepsis.
— White blood cell count
— C-reactive protein
— Procalcitonin
— Endotoxin
— Cytokines – IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, TNF,
IFN-γ, PAF
— TNF-receptors
— IL-1 receptor antagonist, IL-1 receptors
— Complement factors
— Endothelin-1
— ICAM-1, VCAM-1
D
— Phospholipase A2
— PGE2
— Nitrates/nitrites
— Lactoferrin
GH E
— Elastase
— Neopterin
M must be started without delay. If the causative
high mortality rates, and increasing or per-
T
sistently high levels indicated a poor prog-
nosis, while declining values were associat-
ed with a more favorable prognosis.28 PCT
was described more recently as a potential
A
marker of infection and is not yet routinely
measured in many hospital laboratories. PCT
may be superior to CRP in discriminating
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infectious from other inflammatory diseases.
In addition, PCT has more rapid kinetics,
being produced and cleared more rapidly
R
than CRP, so may be better able to identify
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infection early and to follow disease
progress.29, 30 Indeed several studies have
CO NE
shown that PCT levels are correlated with
the severity of sepsis as measured by the
APACHE II or sequential organ failure assess-
ment scores.20, 29, 31, 32
Importantly, none of the markers current-
ly available is specific to sepsis, and a diag-
nosis of sepsis cannot conclusively be made
I
on the basis of the presence of any one item;
M
however, the presence of several features
can help increase the diagnostic likelihood in
a patient with a suggestive clinical picture.
The results of ongoing studies into markers
of sepsis, such as the The Genetic and
Inflammatory Markers of Sepsis (GenIMS)
study, are eagerly awaited. The rapid and
accurate identification of the nature of the
infection is also of critical importance. As an
example, identifying fungal or resistant organ-
ism more rapidly would notably improve the
90
SEPSIS DIAGNOSIS AND MANAGEMENT
appropriateness of antimicrobial treatment
strategies.
A
Management
IC
The management of sepsis can be consid-
ered in 3 sections: treatment of infection,
hemodynamic resuscitation and organ sup-
port, and modulation of the host response.
Treatment of infection
The source of infection must be identified
wherever possible and eliminated by surgical
removal of an infected focus when applica-
ble, and appropriate antimicrobial therapy
®
microorganism(s) is unknown, empiric antibi-
otics should be started based on the likely
culprit and local antibiotic patterns of preva-
lence and resistance. Patients who receive
appropriate antibiotics have a better outcome
than those who are initially treated with an
ineffective antibiotic,33-35 yet a recent study of
septic ICU patients found that in as many as
1/3 of patients the first line choice of antibi-
otic was inappropriate.36 Infectious disease
specialists who are familiar with local hospi-
tal and community pathogens and resistance
patterns should be involved in antimicrobial
selection decisions in all patients with severe
sepsis.34
Hemodynamic resuscitation
Another basic aspect of the management of
the patient with severe sepsis or septic shock
is optimal resuscitation, essentially involving
administration of sufficient fluids, and vasoac-
tive agents when required. Usually the crite-
ria for starting resuscitation include: mean
arterial pressure <65 mmHg, mixed venous
oxygen saturation (SvO2) <70%, urine out-
put <0.5 mL/kg/h, blood lactate concentration
>1.5 mEq/L, or a worsening of the peripher-
al capillary circulation. The choice of one
fluid type over another and the ideal end-
point of fluid resuscitation have generated
considerable debate and a discussion of these
aspects is beyond the remit of this paper.
MINERVA ANESTESIOLOGICA Marzo 2006
SEPSIS DIAGNOSIS AND MANAGEMENT
Fluid resuscitation should be commenced as
early as possible in the course of septic shock
(even before ICU admission).23 Requirements
for fluid infusion may be difficult to deter-
mine, and such decisions can be facilitated by
repeated fluid challenges. A fluid challenge
comprises 4 components: the type of fluid
to be administered (e.g., natural or artificial
colloids, crystalloids); the rate of fluid infusion
(e.g., 500 to 1 000 mL over 30 min); the end-
D
points (e.g., mean arterial pressure >70
mmHg, heart rate <110 beats/min); the safe-
ty limits (e.g., central venous pressure not
higher than 15 mmHg).
GH E
The choice of vasoactive agent has also
been the subject of considerable debate with
conflicting opinions in particular regarding
M
the supremacy of dopamine or norepineph-
rine.37, 38 Current guidelines recommend either
T
drug as a first-line agent,39, 40 and a random-
ized, controlled, double-blinded clinical trial
comparing the 2 drugs is currently under-
A
way in Europe.
Modulation of the host response
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DROTRECOGIN ALFA (ACTIVATED)
R
The development and licensing of
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drotrecogin α (activated), recombinant acti-
vated protein C, marked a turn-up on the
CO NE
rather downward sloping history of anti-sep-
sis therapeutics, in which multiple immuno-
modulatory agents have fallen to the way-
side as one after another clinical trial failed to
show that they had any beneficial effect on
outcome. With indications that the coagula-
tion system was keenly involved in the patho-
I
genesis of sepsis, the spotlight fell on medi-
ators of the coagulation pathway and their
M
potential ability to influence sepsis outcomes.
The Protein C Worldwide Evaluation in Severe
Sepsis (PROWESS) study was a multicenter,
randomized, controlled trial involving 1 690
patients from 164 centers in 11 countries.41
Given at a dose of 24 µg/kg of body weight/h
for 96 h, drotrecogin α (activated) reduced
mortality rates from 30.8% in the placebo
group to 24.7% in the treatment group, which
equated to one additional life saved for every
Vol. 72, N. 3 MINERVA ANESTESIOLOGICA
VINCENT
16 patients treated. Drotrecogin α (activat-
ed)-treated patients also showed significant-
A
ly faster resolution of cardiovascular and res-
piratory dysfunction and significantly slower
onset of hematological organ dysfunction
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than patients who received placebo.42 Apart
from an increased risk of bleeding, mostly
associated with invasive procedures, there
were no other safety concerns with drotreco-
gin α (activated) in the PROWESS study. A
further prospective study was conducted in
361 centers to confirm these findings and
provide additional safety data. This study,
ENHANCE, enrolled 2 375 adult patients and
treated them with the same dose of drotreco-
gin α (activated) as in the PROWESS study.24
The results confirmed the efficacy and safe-
®
ty of drotrecogin α (activated). A further
analysis of the safety profile of drotrecogin α
(activated) in more than 6 500 patients who
had received the drug in clinical trials or com-
mercially reported that 43% of bleeding
events that occurred in patients who received
drotrecogin α (activated) were procedure-
related, and that severe thrombocytopenia
and meningitis may be risk factors for serious
bleeding events in patients receiving the
drug.43 As a result of the inherent risk of
bleeding, drotrecogin α (activated) use is
contraindicated in patients with active inter-
nal bleeding, recent hemorrhagic stroke,
intracranial or intraspinal surgery, or severe
head trauma, trauma with an increased risk of
life-threatening bleeding, presence of an
epidural catheter, and intracranial neoplasm
or mass lesion or evidence of cerebral her-
niation. If a surgical procedure is necessary
during treatment, the infusion should be
stopped 2 h prior to the intervention and
restarted 12 h after adequate hemostasis has
been obtained. Drotrecogin α (activated) is
expensive, but in cost-effectiveness analy-
ses, it has been shown to be comparable to
other accepted ICU interventions.44, 45
Children were not included in the PROWESS
study, suggested that results from open label
studies and although drotrecogin α (activat-
ed) has the same pharmacokinetics, phar-
macodynamic effects, and safety profile in
the pediatric population,46 a phase III ran-
domized controlled trial in children with
91
VINCENT
severe sepsis has recently been discontinued
for lack of efficacy. Drotrecogin α (activated)
is currently licensed for use in adult patients
with severe sepsis and a high risk of mortal-
ity (e.g., as assessed by the APACHE II score).
This decision is supported by the recent
Administration of Drotrecogin alfa [activat-
ed] in Early Severe Sepsis (ADDRESS) study
that failed to show effectiveness of drotreco-
gin α (activated) in patients with less severe
disease.
D
STEROIDS
GH E
In a randomized controlled trial conduct-
ed in 19 ICUs across France and including
300 patients with septic shock, patients with
M
relative adrenal insufficiency (as assessed by
non-response to a corticotrophin test) were
treated with hydrocortisone (50 mg i.v. every
T
6 h) and fludrocortisone (50 µg per os daily)
or placebo for 7 days. Treated patients had a
reduced mortality compared to non-respon-
A
ders treated with placebo (53% vs 63%, haz-
ard ratio 0.67, 95% CI 0.47-0.95, P=0.02).48
In a recent meta-analysis of randomized stud-
PY V
ies in patients with severe sepsis or septic
shock treated with corticosteroids, overall
use of corticosteroids did not significantly
R
affect mortality.49 However, with longer cours-
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es (>5 days) of lower dose corticosteroids
(≤300 mg hydrocortisone or equivalent), mor-
CO NE
tality at 28 days and hospital mortality were
reduced.49 Another meta-analysis reached sim-
ilar conclusions.50 Nevertheless, some ques-
tions remain unanswered, including the opti-
mal test for adrenal insufficiency and whether
the results can be extrapolated to patients with
severe sepsis not in shock. It is not entirely
I
clear whether steroids treat sepsis per se, or
enhance hemodynamic support. Indeed, stud-
M
ies have indicated that steroids can increase the
response to adrenergic agents. At present,
steroid use in sepsis should be administered
only in the presence of shock.
The future
As our understanding of the pathophysi-
ology of sepsis improves, in particular the
92 MINERVA ANESTESIOLOGICA
SEPSIS DIAGNOSIS AND MANAGEMENT
mechanisms of cell-to-cell signaling and the
importance of apoptosis, more potential ther-
A
apeutic targets become apparent. Here we
will briefly mention just some of the many
agents under research, focusing on those
IC
that are, or are almost, at the clinical trial
stage.
New anti-endotoxin agents
Endotoxin (lipopolysaccharide, LPS) is a
component of the Gram-negative bacterial
cell wall and is a key initiator of sepsis. Once
in the circulation, endotoxin binds to LPS
binding protein (LBP), and the LPS-LPB com-
plex interacts with CD14 on the surface of
monocytes and macrophages resulting in cel-
®
lular activation. The LPS-LPB complex can
also interact with soluble CD14 and this can
then interact with another receptor on the
endothelial cell, which itself lacks surface
CD14. LPS can also form complexes with
serum lipoproteins, including low density
lipoproteins (LDL), high density lipoproteins
(HDL), and apolipoprotein A, which provide
a means of eliminating LPS from the circula-
tion.51 In acute illness, lipoprotein levels are
reduced,52, 53 this reducing LPS clearance.
Recent studies have indicated that intensive
insulin therapy to maintain blood glucose
levels less than 6.1 mmol/L improved out-
comes predominantly by reducing deaths
from sepsis-induced multiple organ failure.54
The incidence of nosocomial infections was
also reduced. A further study from Van den
Berghe et al. noted that intensive insulin ther-
apy also increases HDL and LDL levels and
multivariate analysis suggested that it was
this change in lipid levels, rather than an
effect on glucose levels, that contributed to
the beneficial effects of this approach on
mortality and morbidity.55 Replacing lipopro-
teins may therefore represent a novel method
of treating sepsis. Experimental studies in
human volunteers and animal models did
indeed show that HDL reduced flu-like symp-
toms during endotoxemia, and blocked the
endotoxin-induced release of TNF, IL-6 and
IL-8. Interestingly, HDL administration also
reduced CD14 expression on monocytes.56
In a porcine model of sepsis, an emulsion
Marzo 2006
SEPSIS DIAGNOSIS AND MANAGEMENT
of phospholipid, the predominant lipid in
HDL, lowered serum endotoxin and TNF-α
levels significantly, preserved cardiac output
and ejection fraction, and attenuated increas-
es in systemic and pulmonary vascular resis-
tances.57 A clinical trial with this phospho-
lipid emulsion is ongoing.
Other anti-endotoxin strategies currently
undergoing clinical testing include anti-CD14
antibodies,58 extracorporeal endotoxin ab-
D
sorption,59 and lipid A analogs.60
Macrophage migration inhibitory factor (MIF)
GH E
By modulating the expression of TLR4, the
signal-transducing molecule in the LPS recep-
tor complex, macrophage migration inhibito-
M
ry factor (MIF) induces the production of var-
ious pro-inflammatory mediators.61 MIF lev-
T
els are raised in patients with sepsis 62, 63 and
correlate with outcome,63 and animal studies
have demonstrated improved survival with
MIF neutralization.62, 64
A
High-mobility group B-1 protein
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High-mobility group B-1 protein (HMGB1)
acts as a late mediator of systemic inflamma-
tion, and is released from endotoxin-stimu-
R
lated macrophages some 8-12 h after the
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release of the early cytokines. HMGB1 induces
the activation of transcription factors and the
release of pro-inflammatory mediators by
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monocytes and endothelial cells.65, 66 In animal
models of sepsis, anti-HMGB1 antibodies,
even when given late after sepsis induction,
improved survival and reduced sepsis-induced
organ injury.67 Ethyl pyruvate, which inhibits
HMGB1 production in vivo, also improved
I
survival in a mouse model of sepsis.68 Unlike
many animal models when the onset of sep-
M
sis is determined artificially, in patients the
onset is often difficult to define and many
patients will be diagnosed relatively late, mak-
ing the longer time-frame of HMGB1 of par-
ticular interest as it may be effective even
when targeted later in the sepsis process.
Hemoperfusion strategies
Blood purification systems have been pro-
posed for the treatment of sepsis based on the
Vol. 72, N. 3 MINERVA ANESTESIOLOGICA
VINCENT
rationale that by removing inflammatory
mediators, this strategy could improve out-
A
comes. However, hemoperfusion per se
removes all mediators both good and bad
and may not be beneficial in all patients at all
times. Some studies have suggested that cou-
IC
pled plasma filtration adsorption (CPFA)
improves blood pressure and restores
immune function in patients with septic
shock 69, 70 However, further study is needed
to determine which technique may be most
beneficial, and at present hemofiltration is
not recommended unless there is co-exist-
ing renal failure.39
®
Conclusions
Severe sepsis and septic shock are still
associated with high mortality rates, but
progress is being made. Early diagnosis is
vital in improving outcomes and develop-
ment of more effective markers of sepsis
will help in allowing treatments to be insti-
tuted as early as possible in the disease
process. Appropriate infection control strate-
gies and adequate haemodynamic stabi-
lization remain essential, but must now be
combined with drotrecogin alfa (activated)
if there is no contraindication, and other
immunomodulatory strategies as they
become available. It is unlikely that one
agent will ever be discovered to cure all
patients with sepsis, just as one antibiotic
cannot treat all infections, and one
chemotherapy drug is not active against all
cancers. Sepsis treatment must be seen as a
package, with different patients requiring
different packages, and the package con-
tents varying with time in the same patient.
Attempts to characterize patients, such as
the PIRO system, will help in identifying
which therapies are best given to which
patients and when, and as new interven-
tions undergo clinical testing, treatment pro-
tocols must be adapted accordingly. This is
a rapidly moving field, very much a work in
progress, and the success of drotrecogin α
(activated) has given new impetus to the
search for effective diagnostic and thera-
peutic strategies in patients with sepsis.
93
VINCENT
Riassunto
Diagnosi di sepsi e sua gestione: attuali progressi
La sepsi grave è un processo patologico comune
nel paziente criticamente ammalato ed è associata
ad una sostanziale morbidità e mortalità. In questi
ultimi anni la continua ricerca ha fornito notevoli dati
sulla fisiopatologia della sepsi, evidenziando vari
aspetti della risposta alla sepsi che devono essere
colpiti. Le scoperte relative alla correlazione tra coa-
gulazione e infiammazione sono state particolarmente
eccitanti, consentendo lo sviluppo della proteina C
D
attivata ricombinante. Questa revisione discuterà le
attuali definizioni di sepsi, descriverà i nuovi approc-
ci alla classificazione e alla diagnosi dei pazienti con
sepsi e presenterà le raccomandazioni per la gestio-
GH E
ne, inoltre discuterà brevemente le attuali aree di
ricerca e quelle future.
Parole chiave: Sepsi, diagnosi - Sepsi, terapia - Terapia
intensiva.
M with multiple organ failure of septic and nonseptic ori-
T References
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A
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Knaus WA et al. Definition for sepsis and organ failure
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