Advanced Emergency Nursing Journal

Vol. 40, No. 2, pp. 94–103

Copyright 
C 2018 Wolters Kluwer Health, Inc. All rights reserved.

A P P L I E D

Pharmacology
Column Editor: Kyle A. Weant, PharmD, BCPS, FCCP
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Time Spent in the Emergency

Department and Outcomes in Patients
With Severe Sepsis and Septic Shock
RaeAnn Hirschy, PharmD, BCPS
Ethan Sterk, DO, FACEP
Rachel Dobersztyn, PharmD, BCPS
Megan A. Rech, PharmD, MSc, BCPS, BCCCP

Abstract
A majority of patients with severe sepsis and septic shock are first evaluated in the emergency de-
partment (ED). Methods such as screening tools have proven advantageous in earlier identification,
allowing for timely initiation of treatment. Delay in symptom presentation and ED overcrowding
contribute to deferment of sepsis bundle components and admission. To examine the impact of
time from ED arrival to inpatient admission on mortality and length of stay (LOS) in patients with
severe sepsis or septic shock. A retrospective analysis of adult patients with severe sepsis or septic
shock was completed for those presenting between January 2013 and December 2014. Patients
were dichotomized on the basis of the length of time from completed triage in the ED to intensive
care unit (ICU) admission (at less than 6 hr and at 6 hr or more). Of the 294 patients screened, 172
patients (58.5%) met inclusion criteria (n = 70 cases at less than 6 hr; n = 102 at 6 hr or more). Mean
wait time from ED arrival to ICU admission was 470.7 ± 333.9 min (range = 84–2,390 min). Groups
were similar in baseline, disease severity, and bundle characteristics. There were no differences in
the less than 6-hr group compared with the 6-hr-or-more group in rates of 30-day mortality (37.1%
vs. 32.4%; p = 0.52), as well as in-hospital (27.1% vs. 23.5%; p = 0.59) or 90-day mortality (42.9%
vs. 34.3%; p = 0.26). There were also no differences in hospital or ICU LOS. Timing of transfer from
the ED to the ICU was not found to impact mortality or LOS. These results suggest that the ED can
provide similar sepsis care to that in the ICU when transfer is delayed in patients with sepsis. Key
words: emergency department, overcrowding, sepsis, septic shock

Author Affiliations: Loyola University Medical Cen-
ter, Maywood, Illinois (Dr Hirschy); Loyola University
Medical Center, Maywood, Illinois (Drs Sterk, Dobersz-
tyn, and Rech); and College of Pharmacy, Midwestern
University, Downers Grove, Illinois (Dr Dobersztyn).
Disclosure: The authors report no conflicts of interest.
Corresponding Author: RaeAnn Hirschy, PharmD,
BCPS, Loyola University Medical Center, 2160 S 1st Ave,
Maywood, IL 60153 (raeann.hirschy@gmail.com).
S
EPSIS IS A LEADING CAUSE of mor-
tality, comprising 785,000 admissions
annually with a mortality rate of 28.6%
in the United States (Angus et al., 2001). A
review of epidemiological studies illustrated
DOI: 10.1097/TME.0000000000000188

94

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 April–June 2018 r Vol. 40, No. 2
a vast range in incidence and mortality in the
United States due to varying definitions and
identification methods (Kempker & Martin,
2016). Three recent controlled trials en-
rolling patients from more than 100 countries
revealed mortality rates ranging from 18.2%
to 29.5% (Mouncey et al., 2015; Peake et al.,
2014; Yealy et al., 2014). Increased recogni-
tion of sepsis and improved standards of care
have ultimately led to decreased mortality
rates across centers and protocols. However,
mortality rates remain high despite imple-
mentation of evidence-based practice such as
decreased time to assessment, fluids, and an-
tibiotics, as well as the creation of bundles and
screening tools (Dellinger et al., 2013; Kalich
et al., 2016; Kumar et al., 2006; Leisman et al.,
2016). In addition, sepsis is a huge economic
burden to society and a drain on limited
emergency department (ED) resources. Hos-
pitalization costs continue to rise and are re-
ported at more than $20 million in the United
States annually (Torio & Andrews, 2006).
Prior literature has found lower rates of sep-
sis bundle compliance and decreased time-
liness due to ED overcrowding in patients
with sepsis (Shin et al., 2013). Emergency de-
partment overcrowding has been attributed
to several factors, including seasonal illness,
uninsured patients, fewer resources on week-
ends and evenings, failure to adapt for pre-
dicted volume, boarding and delayed through-
put, and lack of a primary care physician
(Viccellio et al., 2008). Limited bed availabil-
ity and delayed discharges can significantly
increase ED wait times. Several strategies, in-
cluding a hospitalist team to help with care
and bed management, an attending physician
float shift, standard ED care, and rounding
inpatient teams, may help limit overcrowd-
ing; however, it still continues to impact pa-
tient outcomes (Baker & Esbenshade, 2015;
Chadaga et al., 2012; Nasim, Mistry, Harwood,
Kulstad, & Tommaso, 2013).
All of these factors may result in delayed
throughput for critically ill patients. To date,
there are conflicting data on whether faster
transfer times equate to better care and, con-
sequently, better outcomes. A retrospective
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Time Spent in the ED and Outcomes in Sepsis 95
cohort of 78 patients requiring intensive care
unit (ICU) admission due to mechanical venti-
lation demonstrated a positive trend between
time from ED presentation to ICU transfer,
ICU length of stay (LOS), and days of me-
chanical ventilation. However, only 15% of
the patients were admitted within 2 hr and
the mean transfer time was 250 ± 147.4 min
(Cline, Schertz, & Feucht, 2009). Other stud-
ies have shown time spent in the ED to signif-
icantly impact mortality after 6–8 hr (Chalfin
et al., 2007; Duke, Green, & Briedis, 2004).
One prospective cohort evaluating 401 ICU
admissions estimated that each hour of wait-
ing led to a 1.5% increased risk of death in the
ICU (Cardoso et al., 2011).
Available literature illustrates a significant
survival difference with faster time to ICU ad-
mission; however, patients with sepsis were
not the focus of these studies. Screening tools
and bundles are frequently set into place to
enable swift recognition and management of
patients with sepsis in the ED, but after ini-
tial resuscitative measures are completed, pa-
tients may remain in the ED for several hours.
Given the time-sensitive nature in the early
care of patients with sepsis, the purpose of
this study is to examine the relationship be-
tween time from ED arrival to inpatient ICU
admission on mortality in patients with severe
sepsis and septic shock.
METHODS
This was a retrospective cohort study
conducted at an academic medical center.
Institutional review board approval was
obtained prior to initiation. Patients were
identified on the basis of International Sta-
tistical Classification of Diseases and Related
Health Problems-9 (ICD-9) codes for severe
sepsis and septic shock. Although these
patients were discovered via ICD-9 codes,
they were then screened to ensure they met
criteria for inclusion, including severe sepsis
or septic shock. All patients 18 years or
older presenting to the ED between January
2013 and December 2014 and found to have
severe sepsis or septic shock were included.
 96
The following exclusion criteria applied:
transfer from an outside hospital; admission
to a non-medical ICU area; burn or trauma
injury; surgery; comfort care; and a primary
diagnosis of acute cerebral vascular event,
acute coronary syndrome, major cardiac
arrhythmia, seizure, overdose, or active gas-
trointestinal bleed. Clinical and demographic
data were obtained from the electronic med-
ical record. If a patient had more than one
encounter during the designated time period,
only the initial encounter was included. Time
from triage completed (“time zero”) to time
of ICU room admission was collected as a con-
tinuous variable, with patients dichotomized
into less than 6 hr and 6 hr or more for data
analysis, based on the 6-hr sepsis bundle
and previous studies (Chalfin et al., 2007;
Churpek et al., 2016; Dellinger et al., 2013).
The primary outcome was 30-day mortality
in patients admitted at less than 6 hr versus
those admitted at 6 hr or more. Secondary
outcomes included in-hospital mortality,
90-day mortality, hospital LOS, ICU LOS, and
ventilator-free days of 28 days.
Severe sepsis was defined on the basis of
consensus guidelines at the time the study
was conducted. Septic shock was defined
as severe sepsis with hypotension refractory
to fluid resuscitation (Dellinger et al., 2013).
Data collection included the following base-
line characteristics: gender; ethnicity; age;
comorbidities (hypertension, diabetes melli-
tus, chronic obstructive pulmonary disease,
asthma, history of cancer or current cancer,
chronic kidney diseases, end-stage renal dis-
ease, myocardial infarction, coronary artery
disease, heart failure, dementia, liver disease,
human immunodeficiency virus infection,
and transplant); do not resuscitate status;
severe sepsis versus septic shock diagnosis;
and baseline lactate. Sequential Organ Failure
Assessment (SOFA) scores on Day 1 and Day 3
and their difference were collected, as well
as primary source of infection. Any missing
components for the SOFA score were given a
score of “0.” Other collected variables include
whether patient arrived by emergency med-
ical services (EMS), weekend presentation
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Advanced Emergency Nursing Journal
(defined as an ED arrival between 7 p.m.
Friday and 7 a.m. Monday), treatment with
corticosteroids, transfusion of blood prod-
ucts, time to ED room, time to ICU room
request, time to intravenous antibiotics, time
to intravenous fluids, use of vasopressors,
number of vasopressors received, and lo-
cation discharged to. All times (time to ED
room, time to ICU room request, time to
ICU room request, time to antibiotics, and
time to fluids) were equivalent to the time
of the stated event minus the time triage was
completed (time zero).
At our institution, the ED physician initiates
an inpatient room request; the inpatient unit
team monitors the patient until an inpatient
bed becomes available. During this time, the
ED nurses and staff provide care, with contact
with the inpatient team until transfer. The in-
patient team may round and make recommen-
dations, while the patient is still the responsi-
bility of the ED physician. The nurse to patient
ratio is up to 5:1 in the ED compared with 2:1
in the ICU. Throughout this study period, a
sepsis screening tool was used in the ED to
enhance recognition of patients with sepsis.
The ED physicians utilize a sepsis order set,
though sepsis therapy is initiated according
to physician preference.
Baseline demographics were characterized
using descriptive statistics, including median
with interquartile ranges and proportions.
The Shapiro–Wilk test was utilized for normal-
ity, and the Mann–Whitney U test was applied
for continuous data. Chi-squared and Fisher’s
exact tests were used, as appropriate, for cat-
egorical data. A logistic regression was per-
formed to identify predictors of 30-day mor-
tality. Factors with a p value of 0.2 or less
in the univariate analysis were considered for
inclusion in the multivariate analysis.
RESULTS
Overall, 294 patients were screened and 172
(58.5%) were included. Of those, 70 (40.7%)
were admitted within 6 hr and 102 (59.3%)
were admitted at 6 hr or more (see Figure 1).
The most common reasons for exclusion were
 April–June 2018 r Vol. 40, No. 2
Figure 1. Study flowchart for patient inclusion.
admission to a non-medical ICU area and
multiple encounters within the study period.
Baseline demographics were well matched
between groups (see Table 1). The median
age was 66 years, more than half of the pa-
tients were male, the most common ethnicity
was Caucasian, and septic shock was more
common than severe sepsis in both groups.
The most common sources of infection were
genitourinary (33.1%) and pulmonary (32%),
with no differences between groups in pri-
mary infection source. The average time to
ICU room admission was 470.7 ± 333.9 min
(range = 84–2,390 min). Figure 2 displays at
which time points all patients were admitted
and at what frequency.
There was a significant difference between
groups in time to room request, arrival via
EMS, and time to intravenous fluids and an-
tibiotics (see Table 2). Of note, the time to
ED room was negative on average in the less
than 6-hr group, due to a higher portion of
EMS transferring directly to an ED room prior
to completion of triage (triage was time zero,
so these patients were roomed in the ED prior
to triage completion). Significantly more pa-
tients admitted within 6 hr arrived via EMS
(75.7% at less than 6 hr vs. 54.9% at 6 hr or
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Time Spent in the ED and Outcomes in Sepsis 97
more; p < 0.01). No differences were found
between groups based on weekend admis-
sion, time to ED room, location discharged to,
administration of corticosteroids, blood prod-
uct transfusion, number or use of vasopres-
sors, or ventilator-free days. Those presenting
to the ED over the weekend had an average
time to admission of 380 min, whereas those
presenting during the week had an average
time to admission of 508 min.
The primary endpoint of 30-day mortality
was not different between groups (37.1% at
less than 6 hr vs. 32.4% at 6 hr or more; p =
0.52). There was also no difference in in-
hospital or 90-day mortality, as well as hospi-
tal or ICU LOS (see Table 3). Figure 3 demon-
strates mortality rates based on 4-hr admission
time blocks, with the highest proportion of
mortality occurring at 4–8 hr between arrival
to the ED and transfer to the ICU.
Logistic regression was conducted to exam-
ine the impact of the within 6-hr transfer time
to ICU on 30-day mortality. In addition to time
within 6 hr, arrival by EMS, septic shock, liver
disease, baseline lactate, SOFA scores, time
to antibiotics and fluids, and number of va-
sopressors were included in the model. The
factor influencing 30-day mortality included a
 98 Advanced Emergency Nursing Journal

Table 1. Patient baseline characteristics

Time to ICU less than Time to ICU 6 hr or

6 hr (n = 70), n (%) more (n = 102), n (%)
Characteristic or median [IQR] or median [IQR] p

Male sex 40 (57.1) 54 (52.9) 0.58

Race
Caucasian 39 (55.7) 50 (49) 0.39
African American 20 (28.6) 33 (32.5) 0.60
Hispanic 8 (11.4) 14 (13.7) 0.66
Asian 1 (1.4) 1 (1) 0.79
Other 2 (2.9) 4 (3.9) 0.71
Age (year) 66 [58–79.3] 66.5 [56–76] 0.47
Comorbidities
Hypertension 43 (61.4) 62 (60.8) 0.93
Diabetes mellitus 24 (34.3) 34 (33.3) 0.90
COPD 6 (8.6) 15 (14.7) 0.23
Asthma 3 (4.3) 4 (3.9) >0.99
Cancer 19 (27.1) 34 (33.3) 0.39
CKD/ESRD 14 (20) 23 (22.5) 0.69
Myocardial infarction 3 (4.3) 4 (3.9) >0.99
Coronary artery disease 17 (24.3) 16 (15.7) 0.16
Heart failure 7 (10) 16 (15.7) 0.28
Dementia 7 (10) 3 (2.9) 0.09
Liver disease 14 (20) 17 (16.7) 0.58
HIV infection 1 (1.4) 0 (0) 0.41
Transplant 7 (10) 4 (3.9) 0.12
Do not resuscitate 8 (11.4) 18 (17.6) 0.26
Septic shock 52 (74.3) 67 (65.7) 0.23
Lactate (mmol/L) 2.7 [1.6–5] 3.3 [1.9–5.8] 0.63
SOFA score Day 1 7 [4–10] 6 [3–9] 0.52
SOFA score Day 3 6 [2–9] 4 [2–8.3] 0.24
Change in SOFA score 0 [−1.3 to 2] 0 [−3 to 1] 0.15
Primary source
Central nervous system 1 (1.4) 0 (0) 0.41
Pulmonary 24 (34.3) 31 (30.4) 0.59
Abdominal 9 (12.9) 13 (12.7) 0.98
Genitourinary 21 (30) 36 (35.3) 0.47
Skin/soft tissue 5 (7.1) 4 (3.9) 0.49
Bacteremia 6 (8.6) 10 (9.8) 0.79
Other/unknown 4 (5.7) 8 (7.8) 0.76
Time to ICU 268 [185.8–313] 515.5 [421–644] <0.01

Note. CKD/ESRD = chronic kidney disease/end-stage renal disease; COPD = chronic obstructive pulmonary disease;
HIV = human immunodeficiency virus; ICU = intensive care unit; IQR = interquartile range; SOFA = Sequential Organ
Failure Assessment.

history of liver disease (odds ratio = 9.24; 95% DISCUSSION

CI [2.77, 30.83]). Transfer to ICU within 6 hr
Although prior research has found time
of ED presentation was not associated with
spent in the ED to inversely correlate with
reduced mortality.
mortality, our study does not support this

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 April–June 2018 r Vol. 40, No. 2 Time Spent in the ED and Outcomes in Sepsis 99

of prompt care of patients with sepsis, as well

Figure 2. Time to ICU room. ICU = intensive care
unit.
finding. We did not find a difference in
mortality between those admitted at less than
6 hr versus 6 hr or more. Critically ill patients
are managed in the ED via the inpatient team
until an ICU bed is available, for which wait
times can vary significantly depending on
numerous factors (Viccellio et al., 2008). Pre-
vious reports have illustrated the importance
as the detriment of delayed ICU room admis-
sion (Cardoso et al., 2011; Chalfin et al., 2007;
Cline et al., 2009; Duke et al., 2004; Kumar
et al., 2006; Mouncey et al., 2015; Peake et al.,
2014; Rivers et al., 2001; Yealy et al., 2014).
This study adds to the growing literature ex-
ploring the impact of time to ICU admission
from the ED in the critically ill population.
Our study was unique, as it focused on
the septic population whereas prior studies
showing an increase in mortality evaluated all
ICU admissions (Cardoso et al., 2011; Chalfin
et al., 2007; Churpek et al., 2016; Duke et al.,
2004). A recent multicenter study identified
an association between a delayed transfer
(more than 6 hr), which was 46% of total
patients, and mortality (33.2% vs. 24.5%; p <
0.001). This translated to a 3% increase in odds
of mortality per hour of delay (Churpek et al.,
2016). A retrospective observational study in-
vestigated septic ED patients with early (less
than 6 hr) and late (6 hr or more) admission

Table 2. Patient treatment course

Time to ICU less Time to ICU 6 hr or

than 6 hr (n = 70), more (n = 102),
n (%) or median n (%) or median
Characteristic [IQR] [IQR] p

Arrival by EMS 53 (75.7) 56 (54.9) <0.01

Weekend presentation 26 (37.1) 24 (23.5) 0.05
Corticosteroids 33 (47.1) 43 (42.2) 0.52
Transfusion of blood products 16 (22.9) 29 (28.4) 0.41
Time to ED room (min) −6.5 [−11 to 0] 0 [−6.3 to 5.3] <0.01
Time to ICU room request (min) 122.5 [86.3–165] 202 [141–289] <0.01
Time to intravenous antibiotics (min) 100.5 [63–171.5] 128.5 [86–210] 0.01
Time to intravenous fluids (min) 22 [3.5–57.5] 46 [22.8–117] <0.01
Use of vasopressors 51 (72.9) 64 (62.7) 0.17
Number of vasopressors 1 [0–2] 1 [0–2] 0.08
Discharged status
Home 19 (27.1) 40 (39.2) 0.10
Nursing facility 28 (40) 30 (29.4) 0.15
Hospice 4 (5.7) 7 (6.9) >0.99
Deceased 19 (27.1) 24 (23.5) 0.59
Transfer 0 (0) 1 (1) >0.99

Note. ED = emergency department; EMS = emergency medical services; ICU = intensive care unit; IQR = interquartile
range.

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 100 Advanced Emergency Nursing Journal

Table 3. Patient outcomes

Time to ICU less than Time to ICU 6 hr or

6 hr (n = 70), n (%) more (n = 102), n (%)
Characteristic or median [IQR] or median [IQR] p

In-hospital mortality 19 (27.1) 24 (23.5) 0.59

30-day mortality 26 (37.1) 33 (32.4) 0.52
90-day mortality 30 (42.9) 35 (34.3) 0.26
Hospital LOS (days) 10 [7–16] 10 [7–15] 0.65
ICU LOS (days) 5 [2–12] 4 [2–7.3] 0.23
VFD of 28 days (days) 28 [19–28] 28 [26–28] 0.10
Mechanical ventilation 38 (54.3) 47 (46.1) 0.29

Note. ICU = intensive care unit; LOS = length of stay; VFD = ventilator-free days.

to the ICU. This study found no difference for
in-hospital mortality, with 22.63% in the early
group and 24.67% in the delayed admission
group (p = 0.68). The study by Agustin,
Price, Andoh-Duku, and LaCamera (2017) has
similar population, grouping, and time based
on triage time to ICU admission. The study
differs in its focus on in-hospital mortality
and bundle compliance (Agustin et al., 2017).
No difference was observed in 30-day mor-
tality between patients admitted at less than
6 hr and 6 hr or more. Significantly more pa-
tients within the less than 6-hr group arrived
via EMS; this group also had faster times to
sepsis interventions such as fluids and antibi-
otics, suggesting earlier recognition of sep-
sis. A retrospective review of 359 included
patients found that those with severe sep-
sis who arrived via EMS, rather than walk-
in, had more overt signs of severity of ill-
ness (Femling, Weiss, Fullerton, Erik, & Tarby,
2012). Although the patients had no differ-
ence in SOFA scores and severity, those ad-
mitted at a faster rate did arrive significantly
more often via EMS. This lack of significant dif-
ference in mortality advocates a similar level

Figure 3. Frequency of 30-day mortality according to time to intensive care unit transfer.

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 April–June 2018 r Vol. 40, No. 2
of care provided by the ED during this initial
presentation time frame. Because of the av-
erage admission time of approximately 8 hr,
a post hoc analysis grouped patients by an
8-hr time cutoff and observed no difference
between groups in 30-day mortality.
Although time to ICU transfer did not signif-
icantly impact mortality, liver disease was in-
dependently predictive of 30-day mortality in
a multivariate logistic regression. Historically,
patients with liver disease have been shown
to have a mortality rate exceeding 70%, which
is approximately double that of those without
liver disease, though their sepsis can be dif-
ficult to diagnose. Those with cirrhosis are
at an increased risk of infection, have an
enhanced inflammatory response, and may
have delayed diagnosis due to preexisting
organ dysfunction (Gustot, Durand, Lebrec,
Vincent, & Moreau, 2009).
On the basis of average admission times,
weekend patients were admitted more ex-
pediently than those admitted on a week-
day, which contradicts previous study find-
ings (Powell, Khare, Courtney, & Feinglass,
2013). Although not applicable to every site,
weekends reportedly have fewer elective ad-
missions, an increase in patients admitted
through the ED, delays in time to procedures,
and lower acuity with decreased likeliness for
admission or mortality (Ryan, Levit, & Davis,
2006; Schoenfeld & McKay, 2010). Those ad-
mitted over a weekend exhibited faster admis-
sion times than those during the week despite
prior literature and potential factors for over-
crowding (Powell et al., 2013; Viccellio et al.,
2008).
Limitations
Limitations include the retrospective study
design at a single medical center, which
limits external validity at other sites based on
site-specific practices, and dependence on
chart review where there can be errors due
to improper or incorrect charting, inappro-
priate ICD-9 coding, and reviewer bias. Sepsis
initiatives and health care are constantly
evolving. This study extrapolated patients on
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Time Spent in the ED and Outcomes in Sepsis 101
the basis of ICD-9 codes for septic shock and
severe sepsis. However, ICD-10 codes are
more current. Furthermore, new consensus
definitions were recently published for sepsis,
though these altered definitions have not yet
been widely accepted. Updates include the
removal of severe sepsis from the nomencla-
ture and a shift toward categorizing severity
of organ dysfunction utilizing either quick
SOFA (qSOFA) score at baseline or change in
SOFA score (Singer et al., 2016). Although we
collected data on SOFA score on Days 1 and
3, ICD-9 codes used to identify patients were
based on the previous definitions for severe
sepsis and septic shock (Dellinger et al.,
2013). Missing SOFA score components were
equated to “0,” which could falsely lower
SOFA scores and therefore severity of illness.
CONCLUSION
Sepsis is a severe, fatal, and costly condition
that burdens hospitals; however, we found
no difference in mortality or LOS between pa-
tients with sepsis admitted to the ICU from
the ED within 6 hr versus 6 hr or more, sug-
gesting that the ED can provide similar sepsis
care even when transfer is delayed in patients
with sepsis. Despite these findings, hospitals
should continue to focus on recognition and
care of patients with sepsis.
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