A clinician attacks the three heads of sepsis (hypotension, hypoperfusion, and organ dysfunction).

Inspired by Hercules Kills Cerberus, Renato Pettinato,

2001, in Zuccaro Palace, Agira, Sicily, Italy. Printed with the permission of the artist and the Rubulotta family.

Crit Care Med 2004 Vol. 32, No. 11 (Suppl.) S445

Introduction
T he mortality of severe sepsis
(infection-induced organ dys-
function or hypoperfusion ab-
normalities) and septic shock
(hypotension not reversed with fluid re-
suscitation and associated with organ
dysfunction or hypoperfusion abnormali-
ties) in most centers remains unaccept-
ably high (1, 2). Similar to an acute myo-
cardial ischemic attack and an acute
brain attack, the speed and appropriate-
ness of therapy administered in the initial
hours after the syndrome develops likely
influence the outcome. In June 2003, a
group of international critical care and
infectious disease experts in the diagnosis
and management of infection and sepsis,
representing 11 organizations (Table 1),
gathered to develop guidelines that the
bedside clinician could use to improve
outcome in severe sepsis and septic
shock. Lead authors on recent positive
clinical trials were excluded from the pro-
cess to limit potential bias. This process
represented Phase II of the Surviving
Sepsis Campaign (SSC), an international
effort to increase awareness and to im-
prove outcome in severe sepsis. (Phase I
of the SSC was initiated in October 2002
with the Barcelona Declaration to im-
prove survival in severe sepsis, and Phase
III is dedicated to the use of the manage-
ment guidelines to evaluate the impact
on clinical outcome; see concluding arti-
cle in this supplement.) The meeting was
partially funded by unrestricted industry
grants. There were no industry members
on the committee. There was no industry
input into guidelines development and no
industry presence at any of the meetings.
Industry awareness or comment on the
recommendations was not allowed. The
sponsors of the educational grants did
not see the recommendations until the
manuscript was peer reviewed and ac-
cepted for publication in final form.
The recommendations from the con-
sensus conference were graded based
Copyright 2004 by the Society of Critical Care
Medicine and Lippincott Williams & Wilkins
DOI: 10.1097/01.CCM.0000147015.53607.1F
S446
on a modified Delphi methodology, and associated rationale were discussed
with categorization as previously de- and critiqued. When strong trial evi-
scribed (Table 2; adapted from refer- dence existed for outcome benefit in
ence 3). The methods for this document critically ill populations known to con-
build on a 2001 publication sponsored tain a larger number of sepsis patients,
by the International Sepsis Forum and these trials were considered in determi-
use the same method of grading recom- nation of recommendation grading. A
mendations (4). The 2001 publication, strict evidence-based methodology with
which was used as a starting point for a scoring system was not used. Each
the current process, included a MED- participant completed a conflict of in-
LINE search for clinical trials in the terest form, and individuals were not
preceding 10 yrs, supplemented by a assigned to a subgroup topic if they had
manual search of other relevant jour- a potential conflict of interest. Follow-
nals. Subtopics for each recommenda- ing the meeting, the process continued
tion were cross-referenced to sepsis, se- with further refinement of recommen-
vere sepsis, septic shock, sepsis dations through electronic communi-
syndrome, and infection. The SSC cation among committee members. A
guidelines considered the evidence in second meeting of core members of the
the 2001 publication (through 1999) committee occurred in early October
and repeated the process for 2000 2003. The executive summary of the
through 2003. The consensus commit- guidelines process with key recommen-
tee met in June 2003 with the first dations was finalized and approved by
presentations of data and recommenda- the consensus committee and by spon-
tions. At that time, recommendations soring organizations in December
Table 1. Eleven participating organizations
1. American Association of Critical-Care Nurses
2. American College of Chest Physicians
3. American College of Emergency Physicians
4. American Thoracic Society
5. Australian New Zealand Intensive Care Society
6. European Respiratory Society
7. European Society of Clinical Microbiology and Infectious Diseases
8. European Society of Intensive Care Medicine
9. International Sepsis Forum
10. Society of Critical Care Medicine
11. Surgical Infection Society
Table 2. Grading system
Grading of recommendations
A. Supported by at least two level I investigations
B. Supported by one level I investigation
C. Supported by level II investigations only
D. Supported by at least one level III investigation
E. Supported by level IV or V evidence
Grading of evidence:
I. Large, randomized trials with clearcut results; low risk of false-positive (alpha) error or false-
negative (beta) error
II. Small, randomized trials with uncertain results; moderate-to-high risk of false-positive
(alpha) and/or false-negative (beta) error
III. Nonrandomized, contemporaneous controls
IV. Nonrandomized, historical controls and expert opinion
V. Case series, uncontrolled studies, and expert opinion
Crit Care Med 2004 Vol. 32, No. 11 (Suppl.)
2003. That document was subsequently
published in both Critical Care Medi-
cine and Intensive Care Medicine (5, 6)
and represented an historic step for
critical care, worldwide. The guidelines
represent an international consensus
on the best available standard for the
management of sepsis.
This supplement represents the total
work of the consensus committee and
includes background material, questions
posed for recommendations, and addi-
tional recommendations not included in
the summary recommendations.
Evidence-based approaches are more
readily applied to data from therapeutic
trials. The evaluation of diagnostic
techniques is less well suited to this
approach. Readers will note the major-
ity of the recommendations are not
supported by high-level evidence. Many
are supported by expert opinion only.
Pediatric considerations are provided at
the end of the document for aspects of
management that differ from adults.
Recommendations are grouped by cat-
egory and not by hierarchy. These rec-
ommendations are intended to provide
Crit Care Med 2004 Vol. 32, No. 11 (Suppl.)
guidance for the clinician caring for a
patient with severe sepsis or septic
shock, but they are not applicable for
all patients. Recommendations from
these guidelines cannot replace the cli-
nicians decision-making capability
when he or she is provided with a pa-
tients unique set of clinical variables.
Although these recommendations are
written primarily for the patient in the
ICU setting, many recommendations
are appropriate targets for the pre-ICU
setting. It should be noted that valid
circumstances may sometimes prevent
physicians from accomplishing all rec-
ommendations in a specific patient, es-
pecially in the pre-ICU setting.
R. Phillip Dellinger, MD, FCCM
Section of Critical Care Medicine
Cooper University Hospital
Camden, NJ
Jean M. Carlet, MD
Service de la Ranimation
Polyvalente
Fondation Hpital Saint-Joseph
Paris, France
Henry Masur, MD
Critical Care Medicine
National Institutes of Health
Bethesda, MD
Herwig Gerlach, MD, PhD
Department for Anesthesiology
and Critical Care Medicine
Vivantes-Klinikum Neukoelln
Berlin, Germany
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