CRITICALCARENURSE Vol 26, No. 3, JUNE 2006 43
sion of the bloodstream by micro
organisms. However, a subset of crit-
ically ill patients have features char-
acteristic of sepsis despite blood
cultures that are repeatedly negative
for microorganisms and no identified
source of bacterial, fungal, or viral
infection.5Trauma, surgery, burns,
and illnesses such as cancer and
pneumonia can trigger the onset of
sepsis. In 1991, the American College
of Chest Physicians/Society of Critical
Care Medicine Consensus Conference6
outlined definitions for systemic
inflammatory response syndrome,
sepsis, severe sepsis, septic shock,
and multiple organ dysfunction syn-
drome (Table 1). These definitions
have been widely adopted. They have
allowed greater consistency in diag-
nosis and treatment and in tracking
statistics on the incidence and occur-
rence of sepsis.
Patients vulnerable to sepsis may
have a number of risk factors7,8
(Table 2). Despite the wide variety of
patients who initially have systemic
inflammatory response syndrome, if
Kathy M. Picard, RN, MS, CCRN
Sharon C. O’Donoghue, RN, MS
Duane A. Young-Kershaw, RN, BSN
Kristin J. Russell, RN, BSN
Sepsis is a complex condition
acterized by hematological derange-
ments and a profound inflammatory
response to an infection or injury.
Despite recent advances in critical
care, sepsis affects more than 750000
patients and accounts for 215000
deaths in the United States each
year, at a cost of more than $16 bil-
that is often life threatening. It is char-
lion.1Mortality in septic shock has
decreasedonly slightly between
1970 and the late 1990s; it remains
the most frequent cause of death in
noncardiac intensive care units (ICUs).
Septicemia is currently ranked by
the Centers for Disease Control and
Prevention as the 10th leading cause
of death in the United States.2(p27)
Incredibly, and perhaps more dis-
turbing, severe sepsis is responsible
for the deaths of more Americans
than are colon, breast, prostate, and
pancreatic cancers combined, and
the mortality rate for sepsis is virtually
equal to the rate for acute myocar-
dial infarction (Figure 1).
Sepsis consists of a series of
inflammatoryand hemostatic alter-
ations presumably caused by inva-
Implementation of a
To receive CE credit for this article, visit
the American Association of Critical-Care
Nurses’ (AACN) Web site at http://www
.aacn.org, click on “Education” and select
“Continuing Education,” or call AACN’s Fax
on Demand at (800) 222-6329 and request
item No. 1125.
Kathy Picard is the clinical nurse specialist, Sharon O’Donoghue is a clinical nurse educa-
tor, and Kristin Russell is a nurse manager in the medical intensive care units and Duane
Young-Kershaw is the clinical nurse educator in the emergency department at Beth Israel
Deaconess Medical Center, Boston, Mass.
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the syndrome is not self-limiting and
progresses to sepsis, the disease pro-
gression is fairly homogeneous. Cel-
lular mediators are produced early
in the onset of sepsis and initiate a
cascade of events, including activa-
tion of the coagulation and comple-
ment pathways, vasodilation leading
to hypotension, endothelial dysfunc-
tion and fluid transudation, and
generalized inflammation. A triad
of events occurs, consisting of a pro-
processes that promote coagulation,
and impaired fibrinolysis. In healthy
persons, homeostasis is maintained
because these 3 mechanisms balance
one another (see Sidebar 1).
Background of the Protocol
Treatment of sepsis is largely
focused on supporting failing organ
systems. Interventions include fluid
replacement, airway management,
antibiotic therapy, use of vasoactive
medications, and hemodialysis. Var-
ious treatments used to improve
patients’ outcomes can paradoxically
contribute to organ dysfunction.
Examples of these treatments include
the use of high-tidal-volume ventila-
tion to improve oxygenation, which
may cause barotrauma or damage of
the lung parenchyma; use of antimi-
crobial agents that cause nephrotoxic
effects; and hemodialysis in renal
dysfunction, which may worsen a
Recent studies have shown that
early goal-directed therapy is benefi-
cial to patients with sepsis.10Advances
in the management of severe sepsis
and septic shock have resulted in
improved survival for these critically
ill patients. Current management
includes early goal-directed therapy,10
activated protein C for severe sepsis,11
intensive insulin therapy,12steroids
for patients with adrenal suppres-
sion,13and protective lung ventila-
tion.14Rivers et al10reported the use
of early goal-directed therapy in
patients entering the emergency
department with sepsis or septic
shock. The therapy, which included
manipulating preload by using fluids
and blood transfusions and manipu-
lating oxygen delivery by using vaso-
pressors, inotropic agents, and blood
44 CRITICALCARENURSE Vol 26, No. 3, JUNE 2006
Figure 1 Comparison of mortality in the United States, by cause.
*Data from Angus et al.1
†Data from the Centers for Disease Control and Prevention, 2003.3
‡Data from the American Cancer Society, 2001.4
Thousands of deaths/year
Cause of death
Table 1 American College of Chest Physicians/Society of Critical Care Medicine
consensus panel definitions6
Systemic inflammatory response syndrome (SIRS): SIRS is a widespread inflamma-
tory response to a variety of severe clinical injuries. This syndrome is clinically indi-
cated by the presence of 2 or more of the following:
• Temperature >38ºC or <36ºC
• Heart rate >90/min
• Respiratory rate >20/min or PaCO2<32 mm Hg
• White blood cell count >12 x 109/L or <4 x 109/L, or with >10% immature
Sepsis: In sepsis, the clinical signs of SIRS are present together with definitive
evidence of infection.
Severe sepsis: Sepsis is considered severe when it is associated with organ dysfunc-
tion, hypoperfusion, or hypotension. The manifestations of hypoperfusion may
include, but are not limited to, lactic acidosis, oliguria, and an acute alteration in
Septic shock: Septic shock is sepsis with hypotension despite adequate fluid replace-
ment combined with perfusion abnormalities that may include, but are not limited to,
lactic acidosis, oliguria, and an acute alteration in mental status. Patients who
require inotropic or vasopressor support despite adequate fluid replacement are in
Multiple organ dysfunction syndrome: Multiple organ failure refers to the presence of
altered organ function in an acutely ill patient such that homeostasis cannot be
maintained without intervention.
CRITICALCARENURSE Vol 26, No. 3, JUNE 2006 53
The ICU nurses received “on-shift
training.” The nurse educator devel-
oped a short program that was pre-
sented on a small-group basis; the
program covered the nuances of the
protocol, the new catheter, and ScvO2.
ICU in-service training was provided
during regularly scheduled work
hours. Individual support was pro-
vided as needed by members of the
sepsis team to ensure that the pro-
tocol became a part of practice at
BIDMC. Nursing competency with
the protocol will be verified with a
mandatory annual competency test.
Education of physicians was
accomplished through grand rounds,
in-service training during morning
rounds, and continual online train-
ing. The sepsis order set in the sys-
tem for entering physicians’ orders
also introduced the physicians to the
nuances of the protocol. All treat-
ments, including fluid therapy, med-
ications and dosing, and antimicrobial
therapy, are contained in a template
that is tailored to individual patients.
Challenges During Implementation
Some of the difficulties encoun-
tered during the implementation of
the MUST Protocol included educat-
ing the large number of staff work-
ing various shifts, transferring
patients treated by using the MUST
Protocol from the emergency
department to the ICU in a timely
fashion, expediting placement of the
ScvO2catheter; and dealing with
problems with equipment.
The team also discovered that the
healthcare staff had not been edu-
cated on exactly how long a patient
was expected to be treated by using
the protocol. The team regrouped
and decided that for each patient,
termination of treatment based on
the protocol would be explored daily
during rounds. Now, if treatment is
still required, the patient remains in
the protocol. An order from a physi-
cian is required to terminate the pro-
tocol. This information was quickly
disseminated to the staff.
The education rollout was com-
plicated by the large number of nurses
and physicians typically involved in
the care of a patient with sepsis. The
team planned to initiate the in-service
programs 2 weeks before the first
anticipated use of the protocol so
that caregivers would be able to
quickly use the knowledge gained.
As in most healthcare education, the
requirement for staffing 7 days a
week, 24 hours a day presented the
challenge of trying to reach personnel
on all shifts within the short 2-week
time frame. During the first months
of implementation of the protocol,
nurses caring for patients being
treated according to the protocol
had questions. Members of the sep-
sis team made themselves available
via pager to provide the support
needed. This support was considered
imperative for successful implemen-
tation of the protocol within the
specified time line. Support provided
included fielding telephone calls,
directing staff to online resources or
MUST protocol binders, and work-
ing side-by-side with nurses at the
bedside as patients were admitted.
Currently, team members are
exploring possible solutions to
improve the time to initiation of
treatment. For example, shifting the
responsibility for the placement of
catheters (currently the responsibil-
ity of the emergency department
team) to whoever can get it done
quickly is being considered. BIDMC
opened an additional 7-bed ICU to
increase the total number of critical
care beds in an attempt to have
“sepsis code beds” readily available.
Emergency department nurses have
continued to administer antibiotics
and the initial fluid bolus immediately
by using a peripheral intravenous
catheter rather than delay treatment
until the central catheter is placed.
Equipment challenges centered
on tracking cables and monitors used
for assessment of ScvO2as patients
were transferred from the emergency
department to multiple ICUs. For
each patient, the central venous
catheter is connected to the patient’s
monitor via a fiber-optic cable that
enables continuous display of ScvO2
values. This cable travels with the
patient to the ICUs because calibra-
tion data is stored in the cable. Some
difficulties have been experienced
with returning cables to the emer-
gency department for use on subse-
quent patients. This problem is
complicated by the fact that BIDMC
has ICUs on 2 separate campuses,
requiring that some patients be trans-
portedvia ambulance. To fix this
problem, we adopted a system in
which an extra cable is swapped out
by the emergency department and
ICU teams during transfer to the ICU.
Additional cables were purchased to
help alleviate this problem.
Sepsis continues to be common
in patients and is associated with a
high mortality rate despite advances
in critical care in the past 2 decades.
According to predictions, the inci-
dence of sepsis and septic shock will
increase dramatically in the years to
come because of the so-called graying
of America and the increased occur-
rence of chronic disease and HIV
infection.1These factors, coupled
with the improved ability to diagnose
and identify sepsis, will lead to an
even greater challenge for caregivers.
The multidisciplinary sepsis team
at BIDMC has taken proven thera-
pies for the treatment of sepsis and
incorporated them into an evidence-
based clinical pathway that is used
by nurses. The team’s goals were to
expedite detection of patients at risk
for sepsis and to initiate early goal-
directed therapy for these patients.
Collaborative efforts and institutional
acceptance of the MUST protocol
led to the successful development
and implementation of the protocol.
The multidisciplinary sepsis team
met bimonthly to implement the
protocol and now meets on a periodic
basis. The agenda includes an update
on the number of patients treated by
using the protocol and any issues or
challenges, for example, the need to
provide education on the protocol as
the ICUs and emergency department
acquire new staff members. The team
also discusses future directions. Team
members are currently looking at the
feasibility of early recognition of sep-
sis in patients in the medical-surgical
As advances occur in the treat-
ment of patients with severe sepsis
and new interventions are proved
effective, members of the sepsis team
at BIDMC expect to modify the MUST
Protocol accordingly. We hope that
this new protocol, as it exists today
and as it evolves, will improve sur-
vivability for patients with sepsis
and decrease related healthcare costs.
We thank Nathan Shapiro, MD, MPH, J. Woodrow
Weiss, MD, and Michael Howell, MD, for their on-
going assistance and guidance with this project.
We also thank the dedicated nurses and staff of
the emergency department and intensive care
units at Beth Israel Deaconess Medical Center for
their role in the development, implementation,
and maintenance of the protocol. This project
was funded in part by a grant from Edwards Life-
sciences, Irvine, Calif.
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