Preface
The purpose of the 1st International Sepsis Forum on Sepsis in
Infants and Children
T he Pediatric Acute Lung In-
jury and Sepsis Investigator’s
(PALISI) Network is com-
prised of investigators at more
than 50 pediatric intensive care units
(ICU) across North America with links
to adult and pediatric research networks
in other countries (http://pedsccm.
wustl.edu/research/palisi/palisi.html).
Founded in 1999, PALISI has made con-
siderable progress in studying the epide-
miology and treatment of acute lung in-
jury, but investigation in the area of
sepsis has been more challenging. Al-
though sepsis is one of the top causes of
and contributors to mortality in the pe-
diatric ICU, there has never been a well-
defined, prospective epidemiologic study
of sepsis in infants and children, except in
the area of nosocomial infection surveil-
lance. The lack of understanding of the
disease process has hindered interven-
tions to improve outcomes in critically ill
neonates, infants, and children.
The mission of the International Sepsis
Forum (ISF) is to improve the understand-
ing and clinical management of patients
with severe sepsis (www.sepsisforum.org).
The ISF is headed by a steering committee
of international experts and opinion lead-
ers. One of the major goals of the ISF is to
develop an international consensus on the
latest understanding of key scientific and
clinical issues in the area of severe sepsis
and, in particular, septic shock. The Inter-
national Sepsis Forum on Sepsis in Infants
and Children was a joint initiative of the
PALISI Network and ISF. The goals of the
3-day consensus meeting were as follows:
1. To review and make recommendations
on current definitions of the systemic
This work was supported by the Mannion Family
Fund—Center for the Critically Ill Child, Division of
Critical Care Medicine at Children’s Hospital Boston,
the PALISI Network, and the ISF.
Copyright © 2005 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
DOI: 10.1097/01.PCC.0000161942.89304.0C
Pediatr Crit Care Med 2005 Vol. 6, No. 3 (Suppl.)
inflammatory response syndrome
(SIRS), sepsis, severe sepsis, septic
shock, and organ failure for neonates,
infants, and children.
2. To carefully define the most common
infections seen in critically ill neo-
nates, infants, and children from three
perspectives: a) identifying infection
early to enroll children in sepsis trials;
b) identifying infections for surveil-
lance and epidemiologic studies; and
c) identifying infections for diagnosis
and optimal therapy.
3. To review some of the most common
conditions predisposing infants and
children to sepsis including a compro-
mised immune system, age, gender,
burns and other traumatic injuries,
and genetic predisposition.
4. To debate whether predisposition and
type of infection should influence clin-
ical trials evaluating agents to prevent
or treat sepsis in infants and children.
5. To discuss non-mortality outcome
measures in clinical trials of therapies
to treat or prevent sepsis in children.
An extensive process of expert rec-
ommendations and thorough PubMed
searching took place to choose the
panel of international experts invited to
the meeting, with the goal of including
expertise in neonatal, pediatric, and
adult sepsis. The international panel
came from the United States, United
Kingdom, Canada, Australia, The Neth-
erlands, Switzerland, South Africa, and
Malaysia.
The conference started out with an
introduction to the scope and epidemi-
ology of pediatric sepsis by Drs. Scott
Watson and Joe Carcillo. They reported
that in the United States alone, there
were an estimated 4,400 pediatric
deaths from sepsis every year, with hos-
pital costs of $1.7 billion. They found
severe sepsis to be the fourth leading
cause of hospital admissions in the
United States. They described in detail
the characteristics of the population of
children with severe sepsis in the hos-
pital. The worldwide burden of sepsis in
children is even more tremendous, and
they reviewed these disturbing num-
bers. They encouraged ISF to develop
definitions that identify sepsis in its
earliest stages, when simple interven-
tions like antibiotics and intravenous or
enteral fluids can save the greatest
number of children worldwide.
When you ask pediatric residents if
a 5-yr-old with pneumonia, high fever,
elevated white blood count, tachypnea,
and tachycardia is septic, they will usu-
ally ask you whether the blood pressure is
stable. If you say yes, they will determine
that the patient is not yet septic. This
conclusion would be erroneous according
to the current definitions of sepsis in
infants and children in which SIRS plus
infection equals sepsis. To most pediatric
practitioners, however, the term sepsis in
infants and children is equated with sep-
tic shock. Calling a patient with straight-
forward pneumonia “septic” or a patient
with severe pneumonia who progresses to
respiratory failure requiring mechanical
ventilator support “severely septic” may
not add much to their understanding of
the disease process. Drs. Brilli and Gold-
stein presented the current definitions of
pediatric SIRS and sepsis, and a vigorous
discussion then ensued regarding the
utility of these definitions.
A large portion of the meeting was de-
voted to defining infections in critically ill
children. The experts were asked to define
infections from the three perspectives listed
above. Diagnoses were also to be catego-
rized according to certainty, using the cat-
egories of definite, probable, and possible.
The following types of infections were re-
viewed: pneumonia, meningitis, and other
central nervous system infections, central
venous catheter-related infections, urinary
tract infections, intraabdominal infections,
surgical wound infections, and other skin
and soft tissue infections, bloodstream in-
fections, and meningococcemia. Working
groups were held to review current defini-
tions and to make revisions specific to ne-
onates, infants, and children when indi-
S1
cated. This information was then presented
to the entire group for discussion. After the
conference, manuscripts with the proposed
definitions were sent to all members of the
group for comment before arriving at the
final definitions. We realize that these def-
initions are only a beginning. Our goal is
for epidemiologic studies to be designed to
test these definitions with feedback and on-
going refinement.
The next portion of the conference
was devoted to predisposition to sepsis in
neonates, infants, and children. Dr.
Steven Opal presented the PIRO (predis-
position, infection, response, and organ
dysfunction) concept of understanding
sepsis that is being continually refined by
adult sepsis experts. Dr. Michael Quasney
then presented an overview of what is
known about genetic predisposition to
sepsis, and Dr. Sally Vitali reviewed the
limitations of these studies. A large por-
tion of the predisposition section was de-
voted to the immunocompromised host.
Dr. Greg Preibe’s editorial describes this
in detail. Cancer, acquired immunodefi-
ciencies, HIV, and congenital immunode-
ficiencies were reviewed regarding how
they predispose children to sepsis. This
section of the proceedings provides fasci-
nating insights into those children we
care for in the ICU who have the highest
mortality from sepsis. Other factors that
predispose to sepsis, such as trauma and
burns, were then reviewed by Drs. Jeffrey
Upperman and Robert Sheridan, respec-
S2
tively. Dr. Sheridan was also able to posit
definitions for infectious processes that
occur exclusively in burn patients who
are included with the surgical wound in-
fection portion in the skin and soft tissue
infection definitions article in these pro-
ceedings.
The final portion of the meeting was
devoted to issues relevant to the design of
sepsis studies. Dr. Joachim Fischer pre-
sented a fascinating overview of issues
hindering a physician’s ability to diag-
nose sepsis in children. Drs. Jacques La-
croix and Jacques Cotting reviewed the
state of the art for severity of illness and
organ dysfunction scoring in children.
Dr. William Tarnow-Mordi described the
use of severity of illness and organ dys-
function scoring in neonatal clinical tri-
als. A general discussion was then held on
the role that these scores should have in
clinical trials in neonates, infants, and
children. Dr. Tarnow-Mordi then re-
viewed what has been learned from de-
signing sepsis studies in neonatal inten-
sive care. He discussed the need for very
large, simple, randomized, controlled tri-
als and the benefit of preplanned prospec-
tive meta-analysis. Mortality in pediatric
sepsis in the developed world is mark-
edly lower than for adult sepsis. This
makes mortality infeasible as an out-
come measure for most clinical trials
because the largest trials in pediatric
critical care to date enrolled fewer than
350 children, and even then, obtaining
Pediatr Crit Care Med 2005 Vol. 6, No. 3 (Suppl.)
that number of subjects was extremely
challenging and took years. Drs. Martha
Curley and Jerry Zimmerman reviewed
in great depth the pros and cons of
non-mortality outcome measures for
clinical trials. Finally, Dr. Joe Carcillo
concluded the meeting by facilitating
an invigorating discussion on what the
next ISF on sepsis in infants and chil-
dren topic should be. His article on
future directions addresses the global
burden of sepsis and provides fascinat-
ing insights into sepsis in the develop-
ing world.
This consensus conference was funded
through a generous donation from the
Mannion Family Fund—Center for the
Critically Ill Child, Division of Critical Care
Medicine at Children’s Hospital Boston,
with additional support from the PALISI
Network and ISF. This funding has allowed
us to publish the full proceedings of the
conference and to allow free access to these
articles from anywhere in the world
through internet links through Pediatric
Critical Care Medicine or the ISF Web sites.
Our hope is that investigators and clini-
cians will put these definitions and ideas
through rigorous testing so that the fur-
ther revision, which we know is needed, is
performed expeditiously.
Adrienne G. Randolph, MD, MSc
Children’s Hospital of Boston
Boston, MA