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Abstract
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Demographic Variables
Age
64-68
Gender
Male and female
Diagnosis
Sepsis or septic shock
Hypotension
Elevated lactate level
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Research Design
Specific design of study
Cohort Study
Interventions
Use and insertion of invasive monitoring equipment in ED
Monitoring of hemodynamic parameters such as:
central venous pressure (CVP)
arterial pressure (MAP)
continuous venous oxygen saturation (ScvO2)
Group
Completed protocol
Failed to complete protocol
Sample and Setting
Setting
Large urban tertiary-care hospital
Emergency Department (ED)
Medical Intensive Care Unit (MICU)
Inclusion criteria
Patients admitted to the ED with severe sepsis and hypotension or elevated lactate level
Exclusion criteria
Refusal of central line insertion
Documented contraindication to central line insertion
Did not survive long enough to undergo 6 h of EGDT
Patients not a candidate for aggressive treatment
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Sample and Setting (cont.)
Method used
Statistical method
Sample size
Independent-samples t test over both the 3-month and the 6-month period.
p value based on an independent-samples t test
Mortality rate
The eligible patients had an overall in-hospital mortality rate of 30.5% with a mean APACHE II score of 29.
Refusal to participate number and percentage
2 patient refused CVP
19 total did not meet criteria
Institutional review board
Rhode Island Hospital
Consent
Waived
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References
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References
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C R I T I C A L C A R E
Implementing a Collaborative Protocol in a Sepsis Intervention
Program: Lessons Learned
Brian Casserly • Michael Baram • Patricia Walsh •
Andrew Sucov • Nicholas S. Ward •
Mitchell M. Levy
Received: 6 April 2010 / Accepted: 27 October 2010 / Published online: 16 November 2010
� Springer Science+Business Media, LLC 2010
Abstract The objective of this prospective cohort study
was to see the effect of the implementation of a Sepsis
Intervention Program on the standard processes of patient
care using a collaborative approach between the Emer-
gency Department (ED) and Medical Intensive Care Unit
(MICU). This was performed in a large urban tertiary-care
hospital, with no previous experience utilizing a specific
intervention program as routine care for septic shock and
which has services and resources commonly available in
most hospitals. The study included 106 patients who
presented to the ED with severe sepsis or septic shock.
Eighty-seven of those patients met the inclusion criteria for
complete data analysis. The ED and MICU staff underwent
a 3-month training period followed by implementation of a
protocol for sepsis intervention program over 6 months. In
the first 6 months of the program’s implementation, 106
patients were admitted to the ED with severe sepsis and
septic shock. During this time, the ED attempted to initiate
the sepsis intervention protocol in 76% of the 87 septic
patients who met the inclusion criteria. This was assessed
by documentation of a central venous catheter insertion for
continuous SvO2 monitoring in a patient with sepsis or
septic shock. However, only 48% of the eligible patients
completed the early goal-directed therapy (EGDT) proto-
col. Our data showed that the in-hospital mortality rate was
30.5% for the 87 septic shock patients with a mean
APACHE II score of 29. This was very similar to a land-
mark study of EGDT (30.5% mortality with mean
APACHE II of 21.5). Data collected on processes of care
showed improvements in time to fluid administration,
central venous access insertion, antibiotic administration,
vasopressor administration, and time to MICU transfer
from ED arrival in our patients enrolled in the protocol
versus those who were not. Further review of our perfor-
mance data showed that processes of care improved stea-
dily the longer the protocol was in effect, although this was
not statistically significant. There was no improvement in
sec
ondary outcomes, including total length of hospital stay,
MICU days, and mortality. Implementation of a sepsis
intervention program as a standard of care in a typical
hospital protocol leads to improvements in processes of
care. However, despite a collaborative approach, the sepsis
intervention program was underutilized with only 48% of
the patients completing the sepsis intervention protocol.
Keywords Early goal direct therapy (EGDT) �
Resuscitation �Sepsis �Medical intensive care unit (MICU) �
Emergency department (ED) � Implementation
Introduction
In recent years there have been several trials that have
demonstrated a survival benefit of new interventions for
severe sepsis and septic shock [1–3]. One of the most
dramatic studies was a trial of early goal-directed therapy
(EGDT) in patients with severe sepsis and evidence of
hypoperfusion who were admitted from the emergency
department (ED) [4]. In the original study, multiple inter-
ventions were coalesced into a protocol that focused on
therapy directed by specific physiologic goals and also on
B. Casserly and M. Baram contributed equally to this work.
B. Casserly (&)
Memorial Hospital of Rhode Island, Brown University,
111 Brewster Street, Pawtucket, RI 02860, USA
e-mail: brian_casserly@brown.edu
M. Baram � P. Walsh � A. Sucov � N. S. Ward � M. M. Levy
Rhode Island Hospital, Brown University, Providence, RI, USA
123
Lung (2011) 189:11–19
DOI 10.1007/s00408-010-9266-z
prompt attainment of those goals. In this landmark study, a
significant mortality benefit was found for patients treated
with this EGDT protocol when compared with patients who
received standard care.
In the years since the publication of these data many
institutions have recreated the protocols and treatments
used in that study with good success [5–9]. That study has
led many clinicians to suggest that early, aggressive
resuscitation should become the standard of care for
patients with severe sepsis and septic shock [10–14].
EGDT has become one of the cornerstones of the Surviving
Sepsis Campaign (SSC) guidelines that represent an
international collaboration to reduce mortality due to sepsis
[15, 16].
The purpose of our study was to see if a sepsis inter-
vention program based on the tenets of EGDT could be
established as the standard of care in a typical urban hos-
pital setting and assess how its implementation affects the
care of patients presenting to the ED with septic shock. The
introduction of a sepsis intervention program necessitated
the use and insertion of more invasive and sophisticated
monitoring equipment than is routinely utilized in our ED
for the care of patients with septic shock. This included the
monitoring of hemodynamic parameters such as central
venous pressure, arterial pressure, and continuous venous
oxygen saturation. We established a collaborative model
combining training and resources from the medical inten-
sive care unit (MICU) staff and the ED staff to adopt the
sepsis intervention program. Our model called for training
of the ED staff, use of central venous pressure (CVP)
monitoring, physiologic goal-directed treatment, and
enhanced communication between the ED and MICU staff
to monitor patients and speed up transfer to the MICU. For
a 6-month observation period we tracked the impact of our
sepsis intervention program on the processes of care such
as time to fluid administration, vasopressor administration,
catheter insertion, transfer to MICU, and time to initial
antibiotics, as well as traditional outcomes such as mor-
tality and length of stay in
the MICU.
Methods
Approval of
Study Design
This prospective cohort study was approved by the insti-
tutional review board of Rhode Island Hospital and con-
ducted under the auspices of an independent data and
safety monitor. Based on the previously published data, the
protocol was introduced as a change in the standard of care
offered to all patients admitted to the ED with severe sepsis
and/or hypotension. As a quality improvement study,
informed consent was waived.
Preimplementation
Prior to implementing the sepsis protocol, meetings were
held between the directors of all MICUs and ED. All
directors agreed that the treatments dictated by the proto-
cols were appropriate. Over a period of 3 months a pro-
gram of training sessions was begun that involved critical
care staff teaching ED residents, attendings, and nurses
how to identify sepsis and the rationale behind the resus-
citation protocol. In addition, a collaborative treatment
model was established between the critical care staff and
the ED that included the following: (1) early consultation
of the critical care staff, (2) enhanced communication
through a dedicated ‘‘sepsis beeper’’ carried by a member
of the on-call critical care team, and (3) improvement in
patient transfer by predetermining that all patients with
severe sepsis for whom the early resuscitation protocol is
initiated would be automatically admitted to the MICU.
Training in the physiologic concepts and practical logistics
of the resuscitation protocol was conducted in both the ED
and the MICU. Training sessions were held for both nurses
and physicians in both units. In addition, in the first
3 months of implementation of the sepsis intervention
protocol a dedicated MICU research fellow was available
to aid with central venous line insertion at the request of
the ED.
Eligibility and Resuscitation Protocol
Any patient presenting to the ED with a real or suspected
infection with either hypotension after 30 cc/kg resuscita-
tion with a crystalloid fluid or a lactate of more than
4 mmol/l was eligible for entry into the protocol. After
meeting the criteria for suspected sepsis, all patients had a
Presep (Edwards Lifescience, Irvine, CA), central venous
catheter inserted. This catheter enabled fluid replacement,
CVP monitoring, and continuous monitoring of central
venous oxygen saturation (ScvO2). The resuscitation pro-
tocol was similar to that published in the study by Rivers
et al. [4] (Fig. 1). The protocol was initiated in the ED by
the ED team and then continued during and after transfer to
the MICU.
Study Design
Over the course of the study period, all patients admitted to
the ED with severe sepsis and hypotension or elevated
lactate level were eligible for the protocol. Patients were
excluded if they (1) refused central line insertion or had a
documented contraindication to central line insertion (e.g.,
coagulopathy), (2) did not survive long enough to undergo
6 h of EGDT, or (3) were not candidates for aggressive
treatment (made comfort measures only, advance directive
12 Lung (2011) 189:11–19
123
or pre-existing diagnosis) (Fig. 2). The patients were sub-
sequently divided into two groups. (1) Completed protocol:
attempts to reach all the goals of the resuscitation protocol
(Fig. 1) were documented in the patient record, e.g., CVP,
MAP, and ScvO2 measurements had to be recorded where
appropriate according to the protocol (Fig. 1). Patients
were included in this group even if all the target goals were
not achieved within the 6-h window therapeutic of EGDT,
e.g., ScvO2 was still not greater than 70% despite receiving
adequate fluid resuscitation, transfusion, and inotropes.
This was not viewed as failure to complete. (2) Failed-to-
complete protocol: failure to either initiate or complete the
protocol. The reasons for no enrollment included ED
physician preference, catheter insertion but no protocol
started, or patient sent to the ICU without the catheter
placed despite the patient having no contraindication to
catheter insertion. Failure to complete also included no
documentation of CVP, MAP, or ScvO2 measurement
where appropriate according to the protocol. Adherence to
the protocol was assessed in an all-or-none fashion; that is,
if there was noncompliance with one element of the pro-
tocol, then there was noncompliance with the entire pro-
tocol. Therefore, a single violation of protocol was
assessed as failure to complete the protocol. This group of
patients served as a comparative group with the patients
who did complete the sepsis intervention protocol.
Any deficiencies regarding the implementation of the
sepsis intervention protocol were identified through
monthly audits and relayed to the ED/MICU as areas that
required improvement. Also, during the final 3 months the
ED were responsible for instituting the sepsis intervention
protocol without any assistance from the MICU research
fellow in central line insertion.
Outcome Variables
All patients enrolled in the sepsis intervention protocol
were tracked for resource utilization. Our primary outcome
variables were time from admission to the ED to catheter
insertion; time to fluid administration, vasopressors, and
antibiotics; and time to transfer from the ED to the MICU.
The baseline time (T0) for all measured outcomes was time
of arrival (registration) in the ED. A 6-month analysis was
performed to determine if the protocol group exhibited
diminishing times to therapeutic actions postintervention
and to see how this compared to the nonprotocol group.
There was a statistically significant increase in the differ-
ence of the APACHE II scores of the protocol and non-
protocol groups over 6 months (Table 1). As a
consequence of this confounder, the differences in sec-
ondary outcomes, including total length of hospital stay,
MICU days, and mortality, were not calculated between
these groups.
A further analysis was performed using only the patients
in the final 3 months of the study, comparing the protocol
group with the nonprotocol group. This was motivated by
the fact that early in the study many patients were started
on the protocol but did not continue to receive care as per
protocol (e.g., continuous monitoring of ScvO2 was not
performed, CVP pressure measurements were not per-
formed). These ‘‘shortcuts’’ could have led to the conclu-
sion of falsely improved processes of care by reducing the
time spent managing the central line (a possible obstacle to
institution of a sepsis intervention program). After the first
3 months complete adherence to the sepsis intervention
protocol had improved. For this reason, analysis comparing
the median times of the protocol and nonprotocol groups in
the processes of care, namely, time to fluid administration,
central venous access insertion, antibiotic administration,
pressor administration, and time to MICU transfer from ED
arrival, was performed using the data of only those patients
in the final 3 months of the study. An analysis of the dif-
ferences in secondary outcomes of these two groups,
including total length of stay, MICU days, and mortality,
also was performed. We also measured rate of initiation of
sepsis intervention protocol and compliance with protocol
over the 6-month period of the study. Furthermore, we
Fig. 1 ED/MICU collaborative protocol for sepsis intervention
program for severe sepsis and septic shock patients
Lung (2011) 189:11–19 13
123
measured how many septic patients had lactate levels
drawn in the 6 months of sepsis
intervention protocol and
compared that number to that of the 6-month period prior
to sepsis intervention protocol.
Statistical Methods
We compared mean age, lactate level, and APACHE
II
score between the protocol and nonprotocol groups using
the independent-samples t test over both the 3-month and
the 6-month period. In the 6-month analysis we regres-
sed—separately for the protocol and nonprotocol groups—
each of the time-to-therapy variables (as listed above) on
the number of months postintervention to determine if the
protocol group exhibited diminishing times to therapeutic
actions postintervention. For these analyses we employed
median regression to address right-tail outliers. For com-
paring the protocol versus the nonprotocol group, we used
a p value based on an independent-samples t test to assess
if there was a statistically significant difference between
the two groups. In the analysis of the patients in the final
3 months of the study, we compared median time intervals
(time to fluid administration, vasopressor administration,
antibiotic administration, catheter insertion, and transfer to
MICU), length of stay, ICU days, and total hospital cost
between those groups using the Wilcoxon rank-sum test.
The v2 test was used to test for group differences in gender
and discharge disposition. We established an a value of
0.05 as indicating statistical significance in two-tailed
comparisons. All statistics were performed using Stata ver.
8 (Stata Corp., College Station, TX).
Results
One hundred six patients with sepsis or septic shock pre-
sented to the ED in the 6-month study period. Of the 106
patients, 87 met the inclusion criteria for further data
analysis. Overall, 82 (66%) of the patients who presented
to the ED had the sepsis intervention protocol initiated.
However, the sepsis intervention was only initiated in 66 of
87 (76%) patients with sepsis shock who were deemed
eligible for complete data analysis according to the a priori
exclusion criteria (Fig. 2). The eligible patients had an
overall in-hospital mortality rate of 30.5% with a mean
APACHE II score of 29. The overall compliance rate
compares favorably to that in the initial 3 months when
implementation rates were only (26/47) 55% of the eligible
population. However, only 42 of 87 patients (48%) com-
pletely complied with the protocol over the 6-month per-
iod. The compliance rate increased to 50% (20/40) in the
last 3 months compared to 42% (20/47) in the first
3 months.
There was a statistically significant increase in the
APACHE II score between the protocol and nonprotocol
Fig. 2 Patient allocations in 6-
month sepsis intervention
program implementation period
Table 1 Baseline characteristics of patients in 6-month analysis
No sepsis intervention
program but eligible
(n = 42)
Sepsis intervention
program (n = 45)
p
Age 64 68 0.3
Male 47% 49% 0.3
Apache
II
23 28 \0.048
Lactate 4.4 4.3 0.3
p value based on independent-samples t test
14 Lung (2011) 189:11–19
123
groups over 6 months (Table 1). As a consequence of this
confounder, the differences in secondary outcomes,
including total length of stay, MICU days, and mortality,
were not calculated between these groups. In the analysis
of the data of the 3-month period, there were no statisti-
cally significant differences between the protocol and
nonprotocol groups with respect to the baseline character-
istics tested, although we are underpowered to conclude
that there is no difference between the groups on gender
(Table 2).
For each of the five time-to-therapy variables tested as
our primary outcomes, the median interval was shorter in
the protocol group than the nonprotocol group, and the
difference was statistically significant for the time to fluid
administration and the time to catheter insertion (all other
p values were less than 0.2) (Table 3). There were no
significant group differences exhibited for our secondary
outcomes (Table 3). The coefficients of each of the five
time-to-therapy (dependent) variables for the protocol
group, though not statistically significant, were negative,
providing further evidence that the sepsis intervention
program was effective in reducing therapy intervals
(Table 4). Coefficients were positive for all but one (time
to catheter insertion) of the time variables for the nonpro-
tocol group, which suggests that factors other than the
intervention were not at play in explaining the diminished
times exhibited for the protocol subjects (Table 4). This is
supported by the fact that the coefficients of the five time-
to-therapy (dependent) variables for the protocol group
were statistically improved compared to those of the non-
protocol group (Table 4). Over the 6-month period, the
introduction of this protocol led to an increase of 32% in
the rate at which lactate levels were obtained in patients
with sepsis who presented to the ED, suggesting increasing
awareness of the protocol. Lactate levels were measured in
90 of the 106 patients (85%) during the 6 months of sepsis
intervention protocol. This represents an absolute increase
of 32% compared to the preceding observational 6 months
where it was measured in 60 of 113 patients (53%).
Discussion
The physiologic rationale for the use of early, aggressive
resuscitation of patients with severe sepsis or septic shock
is based on earlier studies in which increased oxygen
delivery was found to be associated with improved survival
[17, 18]. In the original trial that evaluated the impact of
early goal-directed therapy on patients with severe sepsis
or septic shock, Rivers et al. [4] conducted the protocol
over a 6-h period, entirely in the ED. This protocol led to
an absolute mortality reduction of 16%. Several observa-
tional studies have validated the effectiveness of protocol-
directed resuscitation [19–23] and its use has been
advocated in practice-based guidelines for sepsis manage-
ment [15, 16]. More institutions have adopted a formal
Table 2 Comparisons of patient characteristics between the sepsis
intervention protocol and nonprotocol (did not complete protocol)
groups in final 3 months
Protocol (n = 20) Nonprotocol (n = 20) p
Age 64.1 (17.9) 63.4 (18.7) 0.9
a
Percent female 65.0 40.0 0.11
b
Lactate 4.0 (2.5) 3.9 (2.2) 0.96
a
Apache score 25.4 (9.0) 23.2 (5.8) 0.36
a
Values for age, lactate, and Apache score are means (±SD)
a p value based on independent-samples t test
b p value based on v2 test
Table 3 Comparisons of
primary and secondary outcome
variables between the sepsis
intervention protocol and
nonprotocol (no protocol)
groups
Except for percents, all values
are medians (1st and 3rd
quartiles)
a
p value based on Wilcoxon
rank-sum test
b
p value based on 2 9 3 v2 test
Protocol (n = 20) Nonprotocol (n = 20) p
a
Primary outcomes; time (min) to
Fluid administration 24 (1, 67) 54 (21, 152) 0.02
a
Pressor administration 121 (82, 177) 274 (110, 353) 0.15
a
Antibiotic administration 97 (60, 178) 121 (84, 185) 0.13
a
Catheter insertion 142 (90, 211) 262 (158, 429) 0.01
a
Transfer to MICU 282 (214, 320) 320 (220, 471) 0.16
a
Secondary outcomes
Total length of stay 7 (4, 7) 5.5 (2.5, 13.5) 0.83
a
ICU days 3 (2, 7) 2 (1, 4) 0.24
a
Total hospital cost 11801 (9084, 22940) 11568 (6486, 26607) 0.71
a
Discharge disposition (%)
Home 26.3 50.0 0.20
b
Nursing home 36.8 15.0
Death 36.8 35.0
Lung (2011) 189:11–19 15
123
protocol for the delivery of sepsis therapy [24–26]. Despite
accumulating clinical evidence of the value of a standard-
ized approach to the treatment of sepsis, these interventions
remain underutilized [27–29]. The failure to translate evi-
dence into practice has been identified as one of the great
challenges of modern medicine [30–32]. In institutions that
have adopted protocol-based resuscitation, compliance
ranges from 50 to 60% [20, 33, 34]. Difficulty in recog-
nizing patients with early severe sepsis in busy EDs, the
complex nature of the intervention, and resource utilization
may partly account for the slow rate at which this important
intervention for septic patients has been adopted into routine
clinical practice [27, 35]. Because there is no physiologic
reason why a sepsis intervention protocol must be con-
ducted solely in the ED, the purpose of this trial was to
evaluate whether a collaborative protocol between the ED
and MICU could be developed that would facilitate the
initiation of sepsis intervention program in the ED.
Our primary goal was to assess whether it would be
possible to develop a collaborative approach (ED/MICU)
in the implementation of a sepsis intervention program in a
large ED (approximately 100,000 visits/year) of a teaching
hospital that had no previous experience with the routine
use of a treatment protocol for septic patients. Our aim was
to develop a protocol that would allow one to identify
septic patients in the ED, obtain the necessary physiologic
measurements, start a sepsis intervention protocol, and
facilitate transfer to the MICU. This protocol involved
early communication between ED and MICU personnel
and early identification of patients with severe sepsis and
hypoperfusion as evidenced by hypotension or elevated
lactate levels. Overall, 66% (82 patients) of our 106
patients with sepsis or septic shock had the sepsis inter-
vention protocol initiated. This represents 76% of the eli-
gible patients according to the a priori exclusion criteria.
This number is difficult to interpret as sepsis care was not
administered systematically prior to the initiation of the
protocol. However, this compares favorably to the initial
3 months the when implementation rate in eligible patients
was only 55%. This is also supported by the reduction in
catheter insertion times that occurred over the 6 months,
suggesting an effect of increasing experience on the use of
sepsis intervention protocol. Furthermore, over the 6-
month period, the introduction of this protocol led to an
increase of 32% in the rate at which lactate levels were
obtained in patients who presented with sepsis in the ED,
suggesting increasing awareness of the protocol.
In this study we chose to analyze separately the patients
enrolled in the final 3 months of our protocol in order to
better compare the group of patients who were eligible for
the sepsis intervention program and those who actually
received the therapy. Early in the study, many patients
were started on the protocol after 6 h or had the catheter
inserted but did not adhere to the initial phase of the pro-
tocol, e.g., continuous ScvO2 monitoring was not initiated.
Therefore, the population chosen for analysis included the
patients in the final 3 months of the study with the hope
that the formal feedback mechanisms would limit similar
types of training effects.
The patients who received the sepsis intervention pro-
tocol were compared to a group of patients with severe
sepsis who were eligible for the protocol but did not
receive the therapy. This concurrently collected group of
patients, while not a prospectively identified nonprotocol
group, consisted of patients who were not started on the
protocol for unclear reasons. It should be acknowledged
that this comparison is, in fact, the very essence of a
selection bias or ‘‘confounding by indication.’’ This is a
fundamental flaw of all retrospective studies and any pro-
spective study that does not undergo randomization [36].
Even propensity matching cannot account for unseen bia-
ses [37]. In its essence, ‘‘confounding by indication’’ is
based on the assumption that no physician would withhold
a therapy that was thought to be beneficial for a patient
[38]. This bias needs to be considered when evaluating our
results. Certainly this selection bias may have influenced
the secondary outcomes, i.e., total length of stay, ICU days,
and mortality. However, we feel that processes of care such
as time to fluid administration, vasopressor administration,
catheter insertion, transfer to MICU, and time to initial
antibiotics should be not be influenced by physician
selection bias if the fundamental assumption of
Table 4 Coefficients from median regression analyses regressing each of five time-to-therapy variables (min) on months postintervention for the
sepsis intervention protocol and nonprotocol (no protocol) groups
Protocol Nonprotocol p value
Fluid administration -4.3 (n = 42; p = 0.54) 8.5 (n = 45; p = 0.57) \0.048a
Pressor administration -26.8 (n = 21; p = 0.08) 40.0 (n = 23; p = 0.24) \0.03a
Antibiotic administration -15.0 (n = 40; p = 0.18) 16.6 (n = 45; p = 0.23) \0.046a
Catheter insertion -15.2 (n = 42; p = 0.22) -75.5 (n = 28; p = 0.29) \0.03a
Transfer to MICU -12.3 (n = 42; p = 0.30) 14.8 (n = 45; p = 0.54) \0.04a
a p value based on independent-samples t test for comparing protocol versus nonprotocol group
16 Lung (2011) 189:11–19
123
‘‘confounding by indication’’ holds true, that is, no physi-
cian would withhold beneficial therapy. This is particularly
relevant considering that we applied stringent criteria to
ensure that patients not appropriate for aggressive mea-
sures were excluded from receiving the sepsis intervention
program (Fig. 1).
Our data suggest that the use of a collaborative protocol
for sepsis intervention may decrease the time to initiation
of resuscitation for patients admitted to the ED with severe
sepsis and decrease the time to transfer to the MICU. In the
last 3 months of the protocol study, there was a statistically
significant decrease in time to initial fluid administration
and time to catheter insertion in the ED. In addition, there
were trends toward decreased time for administration of
vasopressors and antibiotics and transfer time to the MICU.
While not statistically significant, by regression analysis,
all time variables—fluids, vasopressors, antibiotics, and
transfer to the MICU—showed negative coefficients,
indicating decreased time for all variables over the 6-month
study period. Also, adherence to the protocol over the
6 months significantly improved for four of the five pro-
cesses of care compared to patients in which the protocol
was not completed, namely, central venous access, antibi-
otics, vasopressor administration, and time to MICU
transfer from ED arrival. Transfer from the ED to the
MICU is particularly important since our data suggest that
introducing a collaborative protocol between the ED and
the MICU decreases the amount of time that these patients
with severe sepsis and evidence of hypoperfusion spend in
the ED. This is an important benefit of a standard approach
to sepsis care as it may encourage clinicians to adopt a
strategy that has already been proven to confer a survival
benefit on this critically ill population [31].
Another important and interesting aspect of our data is
the impact of the collaborative protocol on the timing of
initiating antibiotic therapy. Our sepsis intervention pro-
tocol did not mention antibiotic administration. The pro-
tocol addressed only initial resuscitation efforts with fluids
and the possible use of red blood cell transfusions and the
administration of inotropic therapy (dobutamine), as per
the initial Rivers et al. trial [4]. It appears that as a result of
the protocol, greater emphasis was placed on identifying
and treating patients with sepsis and hypoperfusion in the
ED. It is interesting to note that by simply increasing the
attention paid to these critically ill patients, the time to
antibiotic administration was reduced and thus the overall
quality of care for these patients was improved. Our data
lend support to the suggestions in the literature that specific
efforts at quality improvement in patients with sepsis and
septic shock may lead to general improvement in care [26,
39, 40].
There are several weaknesses of this study. First, the
number of patients enrolled was small and the period of
evaluation was short. The small number of patients meant
that the likelihood of an effect of the protocol on any of the
secondary outcomes, especially mortality, was very unli-
kely. It also needs to be reiterated that patients in this study
were not randomized. However, we feel that the consistent
outcomes seen in the regression analysis demonstrate a
clear impact of the collaborative protocol, over the 6-
month study period, on the timing of resuscitation in the
ED and transfer to the MICU. We believe that these results
support the benefit of making operational a sepsis inter-
vention program with an ED/ICU collaborative approach.
Despite the obvious benefits to patients of a protocolized
approach to sepsis care, many institutions have low com-
pliance rates, suggesting that making a sepsis intervention
protocol operational presents difficulties [28, 33, 41]. One
possibility is that physicians are unduly influenced by the
concern that the amount of time required to treat these
patients in the ED will be increased [29]. Our data suggest
that through collaboration between the ED and the MICU,
the use of a protocolized approach can facilitate earlier
transfer from the ED to the MICU. This should alleviate
some of the pressures caused by limited personnel time in a
busy ED. However, the collaborative approach and the use
of a formal feedback mechanism did not overcome the
problem of poor compliance rates with the sepsis inter-
vention protocol. Interestingly, the use of ‘‘sepsis consul-
tative teams’’ had similar rates of failure [33]. Low
compliance rates appear to be common in clinical practice
[20, 33, 34]. Clearly, the adoption of evidence-based
guidelines needs to continue to be a focus of leaders in the
field of septic shock to create an organizational commit-
ment to quality improvement [42–44]. Through a program
of nurse and physician education and regular communica-
tion, we were able to introduce the protocol and decrease
the time to resuscitation for patients with severe sepsis or
septic shock. However, barriers to universal implementa-
tion clearly persisted throughout the 6 months and dem-
onstrated the challenges in translating evidence into
clinical practice [30–32]. Our approach incorporated many
of the core principles of quality control, namely, the sepsis
intervention program was adequately described, continu-
ously monitored, and improvements suggested based on
feedback. It promoted improved coordination and collab-
oration between different departments in the hospital, but
our success was limited due to a failure to create an
organizational culture of a uniform approach to manage-
ment of patients with sepsis.
In conclusion, the results of this study demonstrate that
it is possible to introduce a collaborative protocol of sepsis
care that may facilitate transfer of patients from the ED to
intensive care areas. We believe that these results should
encourage physicians to introduce collaborative protocols
for patients who present to the emergency department with
Lung (2011) 189:11–19 17
123
evidence of sepsis and hypoperfusion as evidenced by a
lactate of greater than 4 and/or hypotension.
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