A Messori

A. M. E. Spoelstra - de Man

A. R. J. Girbes

AM Korinek

C Brun-Buisson

CP Stoutenbeek

D Cook

DC Bergmans

DF Zandstra

DJ Cook

E Abraham

E Jonge de

E Maury

FM Brunkhorst

G Berghe Van den

HM Schardey

I Kantorova

J Pugin

JC Stothert Jr

JM Hammond

JM Kahn

L Silvestri

M Leone

M Viviani

MA Cal de la

MH Poleski

MJ Bonten

N Basso

P Reusser

PH Voort van der

RE Sarginson

RP Dellinger

RS Bresalier

T Ben Menachem

UK Misra

W Lingnau

English

PubMed

Springer - Publisher Connector

Intensive Care Med (2008) 34:1160–1162
DOI 10.1007/s00134-008-1089-5 C O R R E S P O N D E N C E
A. M. E. Spoelstra - de Man
A. R. J. Girbes
Comment on “Surviving Sepsis
Campaign: International
guidelines for management of
severe sepsis and septic shock:
2008” by Dellinger et al.
Accepted: 27 February 2008
Published online: 16 April 2008
© The Author(s) 2008
An author’s reply to this comment is
available at: http://dx.doi.org/
10.1007/s00134-008-1090-z.
Sir: We read with interest the recent
revision of the Surviving Sepsis Cam-
paign (SSC) guidelines by Dellinger
et al. [1]. The use of the GRADE
system to classify the strength of
the recommendations has certainly
improved the guidelines. However,
we regret that not all guidelines were
adjusted according to the current
literature.
First of all, the absence of a rec-
ommendation regarding selective
digestive tract decontamination
(SDD) is striking. The guidelines
group was evenly split, with equal
numbers weakly in favor and against
recommending the use of SDD. This
is remarkable, since SDD is one of
the best ever evaluated therapies in
intensive care medicine, with more
than 50 randomized controlled trials
and 10 meta-analyses showing that
SDD reduces pneumonia by 65% and
mortality by 22% [2].
The authors gave several reasons
why they chose not to recommend
SDD in their guidelines. They argue
that no studies regarding SDD specif-
ically focused on septic patients.
However, several other guidelines
based on general ICU populations
(i.e., stress ulcer prophylaxis, deep
vein thrombosis prophylaxis, glucose
control and bicarbonate therapy)
received strong recommendations.
Furthermore, the authors state
that studies comparing SDD with
non-antimicrobial interventions, such
as ventilator bundles, are needed. Are
they seriously suggesting that until
these studies have been performed
a therapy with proven high efficiency
should be withheld from patients with
severe sepsis? It seems that no scien-
tific arguments, no study whatsoever
could change the apparently biased
authors.
The main argument against the
use of SDD is the persistent concern
regarding emergence of antimi-
crobial resistance in critically ill
patients. Antimicrobial resistance
was not a clinical problem in 10
SDD studies monitoring resistance
for 2–9 years [3–11]. SDD even
seemed to reduce the resistance of
aerobic Gram-negative bacilli, the
target microorganisms of SDD [12,
13], possibly because the addition of
enteral to parenteral antimicrobials
prevents spontaneous mutation of
target bacteria and eradicates mutants.
In their “rationale” the authors are es-
pecially concerned about emergence
of resistant Gram-positive infec-
tions. The SDD prophylaxis is not
active against vancomycin-resistant
enterococci (VRE) and methicillin-
resistant S. aureus (MRSA) and
may promote gut overgrowth of
these intrinsically resistant bacteria.
Therefore, in ICUs with endemic
MRSA enteral vancomycin is re-
quired as a component of SDD.
VRE did not emerge in any of the
studies using enteral vancomycin, and
there is no evidence that SDD pro-
motes infection due to Gram-positive
bacteria [14–19]. On the contrary,
the continued use of only systemic
antibiotics may lead to a further
rise in drug-resistant Gram-positive
bacteria. We propose, therefore, that
the authors of the SSC guidelines
use the available literature instead of
their bias.
Secondly, the strong recommen-
dation in favor of the use of stress
ulcer prophylaxis is not, in our view,
in line with currently available ev-
idence. This recommendation is,
like that in the guidelines of 2004,
still mainly based on ancient studies
performed in the 1980s [20–23],
a meta-analysis from 1991 [24], and
a large trial in 1998 [25] without
a control arm. However, the most
recent meta-analysis [26] shows no
reduction of clinical important bleed-
ing – but is somehow completely
ignored. Whether the results of these
older trials are applicable nowadays
is questionable, since the incidence
of stress ulcer-related bleeding has
significantly decreased over recent
decades due to improved ICU treat-
ment [27, 28]. This definitely affects
the balance between the benefit
of prevention of gastro-intestinal
bleeding and the increased risk of
ventilator-associated pneumonia due
to higher stomach pH [29]. Several
recent trials show comparable rates
of bleeding and endoscopic evidence
of stress-related injury between treat-
ment and placebo groups [30–33].
These results are pathophysiologi-
cally plausible, since stress ulcers
are caused not by increased secretion
of gastric acid, but by splanchnic
hypoperfusion. Unfortunately, many
recent trials only compare H2 block-
ers with proton pump inhibitors,
without a placebo group. Altogether,
according to the most recent meta-
analysis and the more recent trials,
a strong recommendation not to use
stress ulcer prophylaxis would be
more appropriate.
Thirdly, we disagree with the
strength of the recommendation
to reduce blood glucose levels in
patients with severe sepsis. On the
current evidence, this should be at
most a weak recommendation. The
beneficial effect of intensive insulin
therapy has been demonstrated only
in surgical patients, not in septic
patients [34–36]. The benefit versus
1161
harm balance of intensive insulin
therapy may be quite different for
patients with severe sepsis than for
the investigated surgical patients. It
is not unreasonable to assume that
septic patients may be more at risk
for hypoglycemia, because sepsis
may be associated with a deficiency
of counterregulatory hormones. In
the study of medical patients by
van den Berghe [36], as well as the
VISEP study [35] and the Glucontrol
study [34], the risk of hypoglycemia
was substantially increased, and
hypoglycemia was an independent
risk factor for mortality. None of
these studies followed up the patients
with hypoglycemia for neurocogni-
tive impairment. Furthermore, the
target glucose level of <150 mg/dl
recommended in the guidelines is
based solely on expert opinion and is
not supported by data from any trial.
Therefore, the beneficial effect, the
harmlessness, and the target glucose
level of intensive insulin therapy
remain to be demonstrated in septic
patients.
In conclusion, the revised SSC
guidelines have certainly been im-
proved by the use of the GRADE
system to classify the strength of the
recommendations. However, a strong
recommendation in favor of the use of
SDD should have been implemented.
The strong recommendations in fa-
vor of stress ulcer prophylaxis and
glucose control are not in line with
current evidence.
Open Access. This article is distributed
under the terms of the Creative Commons
Attribution Noncommercial License which
permits any noncommercial use, distri-
bution, and reproduction in any medium,
provided the original author(s) and source
are credited.
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A. M. E. Spoelstra - de Man () ·
A. R. J. Girbes
VU University Medical Centre,
Department of Intensive Care,
7057, 1007 MB Amsterdam,
The Netherlands
e-mail: apspoel@xs4all.nl


Comment on “Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008” by Dellinger et al.

Crossref

A before–after study of multi-resistance and cost of selective decontamination of the digestive tract.

Bleeding and pneumonia in intensive care patients given ranitidine and sucralfate for prevention of stress ulcer: meta-analysis of randomised controlled trials. BMJ 321:1103–1106 27. Zandstra DF, Stoutenbeek CP

Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of death.

Gullo A

MB Amsterdam, The Netherlands e-mail: apspoel@xs4all.nl

Prevention of ventilator-associated pneumonia by oral decontamination: a prospective, randomized, double-blind, placebocontrolled study. Am J Respir Crit Care Med 164:382–388 17. Korinek

Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock:

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2480487

Comment on “Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008” by Dellinger et al.

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