‘view into the future’, especially concerning the
major impact of this disease for the economic
burden as well as for the medical threats
worldwide.
immature neutrophils) are fulfilled.
Merely ten years after the consensus
conference hosted by Bone et al, 5 several
experts then met in Washington to discuss
a new definition of sepsis. A classification system
allowing stratification of septic patients, termed
PIRO (today called Sepsis-2), was developed at this
conference in 2001. 6 (P stands for predisposition;
I, for type and extent of the primary insult (in the
case of sepsis, primary infection); R, for type and
extent of host response; and O, for extent of
organ dysfunction). The introduction of a PIRO
model, however, remained theoretical, even
though there have been several attempts to
introduce a system that enables scoring of septic
patients. 7
In an approximately two-year process with
extended and complex biometric evaluations,
a new approach called Sepsis-3 was developed,
which is based on patient data from several
validated sources, and which was published in the
form of three papers in 2016. 8–10 A key element of
this concept is the omission of SIRS as a factor in
the definition of sepsis. The new Sepsis-3 defines
sepsis as: “a life-threatening organ dysfunction
caused by a dysregulated host response to
infection”. 8 Therefore, if no organ dysfunction is
seen, one may only speak of an infection, not of
sepsis. The term severe sepsis is superfluous as its
criteria (organ failure) are already included in the
new definition of sepsis. The term septic shock
remained but now includes an elevated lactate
level >2mmol/l as an additional factor.
This short overview, which is far from being
fully comprehensive, demonstrates that it is not
easy to compare epidemiological data of sepsis.
In the following, this dilemma should be kept in
mind, and simple comparisons of large data sets,
that are based on different definitions and/or
selection criteria for sepsis, should be performed
with care.
100 years of varying definitions
A teleological definition was proposed by Hugo
Schottmüller in 1914: “Sepsis is present if a focus
has developed from which pathogenic bacteria
constantly or periodically, invade the bloodstream
in such a way that this causes subjective and
objective symptoms”. 4 This definition is
problematic and increasingly being dismissed,
as it is based on subjective clinical observations.
In addition, it insinuates an incorrect
pathophysiological rationale as it assumes that
bacteria themselves spread. However, today
one assumes that the body produces its own
transmitters as a response to the infection and
that these spread systemically, thus affecting
peripheral organs. 3
Partly due to these arguments, a US surgeon,
Roger Bone, organised a conference in which
consensus was reached that sepsis should be
defined with tangible criteria and should,
therefore, include the aspect of host response.
Here, the term systemic inflammatory response
syndrome (SIRS), which is still commonly used,
was defined. 5 If SIRS occurs without infection
(for example, burns, pancreatitis, post-operative
setting, etc), the condition is only defined as SIRS;
similarly, an infection without SIRS does not
equal sepsis. Only when infection in combination
with SIRS are observed may one speak of sepsis.
Therefore, sepsis was defined as “a systemic
inflammatory response syndrome to infection”
that may be seen when two or more of the four
SIRS criteria (heart rate >90/min; core
temperature >38°C or <36°C; respiratory rate
>20/min or PaCO 2 <32mmHg; white blood
cell count >12,000/ml or <4000/ml or >10%
Research versus administration
At first glance, it might be simpler to gather data
from administrative hospital files than trying to
obtain prospective data from research protocols.
However, both ways contain tricks and traps that
must be considered.
Example 1 (research)
In a prospective, multicentre, longitudinal
observational study, a total of 11,883 patients
from 133 ICUs at 95 German hospitals over four
weeks were included. The patients were followed
up for the occurrence of severe sepsis or septic
shock (Sepsis-1 definitions) during their ICU stay. 11
A total of 1503 patients (12.6%) with severe sepsis
or septic shock were diagnosed. The calculated
incidence rate of severe sepsis or septic shock was
11.64 per 1000 ICU days. ICU mortality in patients
with severe sepsis/septic shock was 34.3%,
compared with 6% in those without sepsis. Total
hospital mortality of patients with severe sepsis
or septic shock was 40.4%. Classification of the
septic shock patients using the new Sepsis-3
definitions showed higher ICU and hospital
mortality (44.3 and 50.9%, respectively). 11
Example 2 (administration)
To determine the incidence and mortality of
sepsis and septic shock, German case-related
8
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