Treatment of Pediatric Septic Shock With
the Surviving Sepsis Campaign Guidelines
and PICU Patient Outcomes*
Jennifer K. Workman, MD1; Stefanie G. Ames, MD1; Ron W. Reeder, MS, PhD1,2;
E. Kent Korgenski, MS, MT (ASCP)3; Susan M. Masotti, BA4; Susan L. Bratton, MD, MPH1;
Gitte Y. Larsen, MD, MPH1
Objectives: The Surviving Sepsis Campaign recommends rapid
recognition and treatment of severe sepsis and septic shock. Few
reports have evaluated the impact of these recommendations in
pediatrics. We sought to determine if outcomes in patients who
received initial care compliant with the Surviving Sepsis Cam-
paign time goals differed from those treated more slowly.
Design: Single center retrospective cohort study.
Setting: Emergency department and PICU at an academic chil-
dren’s hospital.
Patients: Three hundred twenty-one patients treated for septic
shock in the emergency department and admitted directly to the
PICU.
Interventions: None.
Measurements and Main Results: The exposure was receipt of
emergency department care compliant with the Surviving Sepsis
*See also p. 1011.
1
Division of Critical Care, Department of Pediatrics, University of Utah,
Salt Lake City, UT.
2
Department of Mathematics, University of Utah, Salt Lake City, UT.
3
Pediatric Clinical Program, Intermountain Healthcare, Salt Lake City, UT.
4
Department of System Improvement, Primary Children's Hospital, Salt
Lake City, UT.
Current address for Dr. Ames: Department of Critical Care Medicine and
Pediatrics, University of Pittsburgh, Pittsburgh, PA.
This study was performed at Primary Children’s Hospital.
Supplemental digital content is available for this article. Direct URL cita-
tions appear in the printed text and are provided in the HTML and PDF
versions of this article on the journal’s website (http://journals.lww.com/
pccmjournal).
Supported, in part, by an award to Jennifer Workman from the Primary
Children’s Foundation Clinical Excellence Grants Program, which pro-
vided support for data collection and management.
Dr. Workman received a grant from the Primary Children’s Foundation Clini-
cal Excellence Grants Program in support of this work. The remaining authors
have disclosed that they do not have any potential conflicts of interest.
For information regarding this article: E-mail: Jennifer.workman@hsc.utah.edu
Copyright © 2016 by the Society of Critical Care Medicine and the World
Federation of Pediatric Intensive and Critical Care Societies
DOI: 10.1097/PCC.0000000000000906
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Unauthorized reproduction of this article is prohibited
Campaign recommendations (delivery of IV fluids, IV antibiotics,
and vasoactive infusions within 1 hr of shock recognition). The
primary outcome was development of new or progressive mul-
tiple organ dysfunction syndrome. Secondary outcomes included
mortality, need for mechanical ventilation or vasoactive medica-
tions, and hospital and PICU length of stay. Of the 321 children
studied, 117 received Surviving Sepsis Campaign compliant care
in the emergency department and 204 did not. New or progres-
sive multiple organ dysfunction syndrome developed in nine of the
patients (7.7%) who received Surviving Sepsis Campaign compli-
ant care and 25 (12.3%) who did not (p = 0.26). There were 17
deaths; overall mortality rate was 5%. There were no significant
differences between groups in any of the secondary outcomes.
Although only 36% of patients met the Surviving Sepsis Cam-
paign guideline recommendation of bundled care within 1 hour of
shock recognition, 75% of patients received the recommended
interventions in less than 3 hours.
Conclusions: Treatment for pediatric septic shock in compliance
with the Surviving Sepsis Campaign recommendations was not
associated with better outcomes compared with children whose
initial therapies in the emergency department were administered
more slowly. However, all patients were treated rapidly and we
report low morbidity and mortality. This underscores the impor-
tance of rapid recognition and treatment of septic shock. (Pediatr
Crit Care Med 2016; 17:e451–e458)
Key Words: multiple organ dysfunction syndrome; pediatric critical
care; septic shock; severe sepsis; Surviving Sepsis Campaign
P
ediatric septic shock is a major cause of morbidity and
mortality in children, leading to over 20,000 U.S. inpa-
tient admissions and over 800 deaths annually (1). As first
described by Rivers et al (2) in 2001, the early recognition of
severe sepsis and septic shock combined with early goal-directed
therapy (including fluid resuscitation, administration of broad
spectrum empiric antibiotics, and the use of inotropic or vaso-
pressor agents for persistent hemodynamic derangement)
 Workman et al
significantly improves survival in adults. This has also been
shown in children with septic shock who have been treated with
similar, pediatric specific guidelines (3–6). The growing body of
evidence in support of this approach to treatment is now out-
lined in the Surviving Sepsis Campaign (SSC) guidelines, a joint
effort of the Society of Critical Care Medicine and the European
Society of Intensive Care Medicine focused on reducing mor-
tality from sepsis worldwide. The most recent iteration of these
guidelines was distributed internationally in 2012, and provides
recommendations for the care of both adults and children with
severe sepsis and septic shock (7).
The pediatric SSC guidelines recommend administration of
IV fluid resuscitation, IV antibiotics, and infusion of vasoac-
tive agents within the first hour of recognition and care of the
patient with septic shock (7). In 2007, in consideration of the
guidelines available at the time (8), our institution implemented
an emergency department (ED) septic shock guideline to facili-
tate early recognition and rapid treatment of pediatric septic
shock. Initially, the goals of this quality improvement initiative
focused on improved recognition, and over time were modi-
fied to the provision of care consistent with SSC goals. Within
the first 2 years of implementation, there was improved disease
recognition at presentation to the ED, augmented rates of early
treatment, and significantly decreased overall hospital length
of stay (LOS), but mortality remained stable (from 7% to 6%)
(9). Our hospital ED septic shock guideline has now been in
place for over 8 years, and has aided identification of over 1,000
patients who met shock criteria during their ED admission.
While many investigations report lower mortality and
resource utilization following implementation of septic
shock protocols (9–12), few have specifically linked pedi-
atric patient outcomes with receipt of bundled care within
1 hour of shock recognition that is recommended in the
SSC guidelines. Additionally, two recently published large
adult randomized controlled trials (RCTs) reported similar
mortality from protocolized septic shock treatment com-
pared with usual care (13, 14). Therefore, the objective of
the current study was to evaluate the association between
timely delivery of therapy for pediatric septic shock in the
ED in accordance with the SSC guidelines, and outcomes in
children admitted to the PICU. Our hypothesis is that chil-
dren treated according to SSC recommendations will have
decreased new or progressive multiple organ dysfunction
syndrome (NP-MODS).
MATERIALS AND METHODS
Study Design and Setting
We evaluated the relationship between pediatric ED care for
septic shock and outcomes of children requiring admission to
the PICU. We retrospectively selected patients presenting to
the ED with septic shock between 2008 and 2012, and reviewed
the hospital course and clinical outcomes. The study was con-
ducted at Primary Children’s Hospital (PCH), a tertiary care
pediatric hospital with 40,000 ED visits per year and 2,000
PICU admissions per year. The University of Utah Institutional
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Review Board approved the study and waived requirement for
informed consent.
Participant Selection Criteria
Initial patient selection was from the PCH Pediatric Septic
Shock Project Database, which was established with initiation
of the PCH ED septic shock guidelines in 2007. Patient records
were flagged for initial review and possible inclusion in this
database if they met any of the following broad criteria: 1) tri-
age in the ED to “emergent” status; 2) lactate drawn during ED
course; 3) PICU admission within 12 hours of presentation to
ED; 4) repeat visits to the ED within 48 hours of initial visit;
and 5) having a “rapid response” called on a patient within 12
hours of admission from the ED to an inpatient ward for man-
agement of sepsis. Following initial screening based on these
criteria, patients were retained in this database if their condi-
tion met the American College of Critical Care Medicine/Pedi-
atric Advanced Life Support (PALS) definition of septic shock:
known or suspected infection accompanied by temperature
abnormalities, vital sign abnormalities based on PALS vital sign
parameters for age, and physical examination consistent with
deficit in end-organ perfusion (5). The ACCM/PALS definition
of septic shock was utilized instead of the 2005 Consensus Defi-
nition (15) because of its usefulness in bedside diagnosis and
treatment in real time (16), as was necessary in the setting of
our hospital’s septic shock initiative.
We included subjects for the present study if they were
18 years old or younger on ED admission, and were admitted
directly from the ED to the PICU between January 2008 and
December 2012. Any patient admitted initially to the inpatient
floor and subsequently transferred to the PICU was excluded,
as care provided during the inpatient stay may have altered the
relationship between resuscitative ED care and patient out-
comes. We included patients in the present study beginning in
2008 instead of 2007 when the ED Guideline was initiated so
that the data reflected care of patients by adequately trained
staff familiar with the recommended interventions.
Exposures and Outcomes
The exposure was receipt of care in the ED in compliance with
the recommendations of the SSC, defined by administration
of antibiotics within 1 hour of arrival, administration of at
least 60 mL/kg IV resuscitation fluids within 1 hour of arrival
(or less if the patient’s perfusion deficit was reversed prior to
receiving 60 mL/kg as determined by improvement in vital
signs and documentation of improved perfusion on clinical
examination), and administration of an inotropic or vasoac-
tive agent for fluid-refractory patients within 1 hour of arrival.
The primary outcome measure was the development of
NP-MODS. Given the relatively low mortality rate in many
pediatric illnesses, a surrogate measure of disease sever-
ity is often used. Sepsis is associated with MODS (17), and
NP-MODS (the development of two or more organ dysfunc-
tions during hospitalization) has been used as a surrogate
measure in this way (18, 19). MODS assessment was based on
cardiovascular, pulmonary, renal, neurologic, hematologic, and

hepatic function, and evaluated based on the patient’s worst
function for a given time period based on the criteria outlined
by Proulx et al (18, 19) (Supplementary Table 1, Supplemental
Digital Content 1, http://links.lww.com/PCC/A279).
In the present study, NP-MODS was assessed on days 1, 2,
5, 8, 12, 16, and 18 (or until hospital discharge, whichever was
sooner). Data were abstracted both from the Intermountain
Enterprise Data Warehouse (EDW) and by manual chart
review. Additional outcome measures including mortality,
PICU, and hospital LOS, and hospital resource utilization were
investigated using the EDW. All data were stored within the
University of Utah Division of Pediatric Critical Care Data
Coordinating Center secure server.
Statistical Analysis
Standard descriptive statistics were used to summarize patient
characteristics. Groups were compared by exposure, using
Fisher exact test for categoric variables and Wilcoxon signed
rank test for continuous variables. Relative risk ratios were cal-
culated using Epi Info (Centers for Disease Control and Pre-
vention, Atlanta, GA) to determine risk factors associated with
development of NP-MODS and death. Multiple logistic regres-
sion was used to estimate the relationship between receipt of
SSC compliant care and adjusted odds of NP-MODS (primary
outcome). Variables were selected for inclusion in the multivari-
able models based on a priori clinical rationale, and included
age, sex, presence of a complex chronic condition (CCC) (20),
type of infection identified (bacterial vs viral), and Pediatric
Index of Mortality (PIM) 2 scores. All analyses were performed
using SAS version 9.4 (SAS Institute Inc., Cary, NC).
RESULTS
There were 913 children who presented to the ED with sep-
tic shock during the study period. Of these, 321 children met
inclusion criteria, and among these, there were 117 children
(36%) who received timely care compliant with SSC guide-
lines and 204 who did not. There were no differences between
groups with respect to sex, race, presence of a CCC, median
PIM2 scores, or type or site of infection (Table 1). The most
common site of infection in both groups was the lungs, and
just over 60% of children had an infectious organism identi-
fied by either bacterial or viral testing. Younger children were
more likely to receive SSC compliant care (median age, 3 vs
7 yr; p < 0.05). Children treated in the first 3 years of the study
(2008–2010) were significantly less likely to have received SSC
compliant care (rate ratio [RR], 0.6; 95% CI, 0.4–0.8).
An analysis of the interventions received during ED care
between the two groups is shown in Table 2. Receipt of SSC
compliant care was not associated with day (weekday vs week-
end) or time (day shift vs night shift) of presentation (p = 0.49
and p = 0.85, respectively). Children who received SSC com-
pliant care statistically differed from those who did not with
respect to time to first fluid bolus (difference in median time,
16 min; p < 0.01). However, there was no difference in the total
volume of IV fluids administered during the ED stay, and time
to receipt of total IV fluids was similar (Fig. 1). Among the
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Online Clinical Investigations
entire cohort, median time to first fluid bolus was 23.0 minutes
(interquartile range, 10.0–39.5), and 62% of the cohort received
adequate fluid resuscitation within the first hour of care (as
determined by resolution of perfusion defect, improvement in
vital signs). Those who received SSC complaint care had a sig-
nificantly shorter median time to antibiotic administration (44
vs 94 min; p < 0.01) and time to administration of vasoactive
infusion (47.5 vs 130 min; p < 0.01). There were 145 patients
(45%) who did not receive antibiotics within 1 hour of ED
arrival, and 18 patients (55%) who did not receive vasoactive
medications within 1 hour of becoming hypotensive. Overall,
75% of patients received empiric antibiotics within 1.8 hours
and vasoactive medications within 2.8 hours.
There were 119 children (37%) who had MODS on day 1
of their hospital stay, 133 (41%) with MODS at any point dur-
ing hospitalization, and 34 (11%) who developed NP-MODS.
There were 17 deaths (5%). Risk of death was significantly
associated with presence of a CCC (RR, 5.0; 95% CI, 1.8–13.8),
but risk of NP-MODS was not. Among those who died, only
two were previously healthy. Fifteen of the deaths resulted from
eventual withdrawal of support despite maximal and escalat-
ing therapies, including the two previously healthy children.
Duration of hospitalization prior to death ranged from several
hours to 1 month. There were no differences between groups
with respect to development of NP-MODS, the maximum
number of dysfunctional organ systems, individual organ dys-
functions (with the exception of hematologic), or mortality in
either the adjusted or unadjusted analyses (Table 3).
Children with a documented bacterial infection were sig-
nificantly more likely to develop NP-MODS compared to
those with viral infections or no source of infection identified
(p < 0.01, data not shown). Among patients with a CCC,
receipt of SSC compliant care suggested a trend toward
decreased risk of NP-MODS (RR, 0.17; 95% CI, 0.02–1.3)
and mortality (RR, 0.14; 95% CI, 0.02–1.04); however, these
differences did not achieve statistical significance. Among
the entire cohort, 32% required mechanical ventilation dur-
ing the hospitalization and 31% required blood pressure
support with continuous infusion of vasoactive medications.
Neither of these two measures, nor median hospital or PICU
LOS, differed significantly between groups (Table 3).
DISCUSSION
This single center retrospective cohort study of ED septic
shock care and PICU patient outcomes revealed no sig-
nificant association between receipt of bundled care within
1 hour of ED arrival and development of NP-MODS, mor-
tality, or hospital resource utilization. Interestingly, we also
found that risk of death was associated with presence of a
CCC but risk of NP-MODS was not. It is likely that those
with NP-MODS who had a CCC were more likely to progress
to death, while those who were previously healthy were more
likely to recover. We had hypothesized that receiving care
within 1 hour, in accordance with the current recommenda-
tions for pediatric septic shock (7), would be associated with
improved outcomes.
 Workman et al

Table 1. Demographic Features and Clinical Characteristics of the Cohort

Surviving Sepsis Campaign Compliant
Overall
Demographic No (n = 204) Yes (n = 117) (n = 321)

Year group, n (%)

 2008–2010 109 (53.4) 39 (33.3) 148 (46.1)
 2011–2012 95 (46.6) 78 (66.7) 173 (53.9)
Age (yr), median (IQR) 6.7 (1.4–13.3) 3.4 (1.0–12.5) 5.4 (1.2–12.9)
Male, n (%) 106 (52.0) 59 (50.4) 165 (51.4)
Race, n (%)
 Unknown 6 (2.9) 2 (1.7) 8 (2.5)
  Native Hawaiian or other Pacific Islander 8 (3.9) 12 (10.3) 20 (6.2)
 White 139 (68.1) 84 (71.8) 223 (69.5)
 Hispanic 32 (15.7) 7 (6.0) 39 (12.1)
 Black 4 (2.0) 1 (0.9) 5 (1.6)
 Other 12 (5.9) 6 (5.1) 18 (5.6)
 Asian 3 (1.5) 3 (2.6) 6 (1.9)
  American Indian or Alaska Native 0 (0.0) 2 (1.7) 2 (0.6)
Presence of complex chronic condition, n (%) 63 (30.9) 41 (35.0) 104 (32.4)
Pediatric Index of Mortality 2 score, median (IQR) 1.4 (1.1–3.1) 1.9 (1.3–4.8) 1.6 (1.1–4.0)
Immune compromised, n (%) 6 (2.9) 5 (4.3) 11 (3.4)
Trach dependent, n (%) 19 (9.3) 9 (7.7) 28 (8.7)
Presumed site of initial infection, n (%)
 CNS 10 (4.9) 10 (8.5) 20 (6.2)
 Blood 46 (22.5) 28 (23.9) 74 (23.1)
 Genitourinary 17 (8.3) 12 (10.3) 29 (9.0)
  Skin, soft tissue, bone, joint, throat or sinuses 20 (9.8) 8 (6.8) 28 (8.7)
 Abdomen 18 (8.8) 12 (10.3) 30 (9.3)
 Lungs 76 (37.3) 35 (29.9) 111 (34.6)
  No site identified 17 (8.3) 12 (10.3) 29 (9.0)
Type of infection, n (%)
  Culture negative 43 (21.1) 30 (25.6) 73 (22.7)
  Positive bacterial culture 96 (47.1) 57 (48.7) 153 (47.7)
  Positive viral testing 30 (14.7) 18 (15.4) 48 (15.0)
  Presumed nonpulmonary bacterial infection 11 (5.4) 4 (3.4) 15 (4.7)
  Presumed bacterial pneumonia 24 (11.8) 8 (6.8) 32 (10.0)
IQR = interquartile range.

Our findings are in contrast with several previously pub-
lished investigations that showed a significant relationship
between the timeliness of septic shock treatment and patient
outcomes in both adults (2, 21–24) and children (3, 4, 9, 25), and
which form the basis for the SSC Guidelines (7). Several recent
studies that evaluated compliance with various components of
the pediatric SSC Guidelines, in particular antibiotic admin-
istration within 1 hour and fluid bolus administration within
1 hour, have similarly reported decreased mortality, organ
­dysfunction, and hospital resource utilization (9, 26, 27).
When comparing these investigations to the present study,
although the infectious profiles (site of infection, causative

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 Online Clinical Investigations

Table 2. Comparison of Interventions Received During Emergency Department Care

Surviving Sepsis Campaign Compliant
Overall
ED Intervention No (n = 204) Yes (n = 117) (n = 321) pa

Minutes from ED arrival to first fluid bolus < 0.01

  n 201 115 316
  Median (IQR) 30.0 (15.0–45.0) 14.0 (5.0–25.0) 23.0 (10.0–39.5)
Total IV fluids (mL/kg) 0.40
  n 204 117 321
  Median (IQR) 55.6 (40.0–63.4) 59.5 (40.0–66.7) 57.1 (40.0–65.4)
Minutes from ED arrival to antibiotic administration < 0.01
  n 203 117 320
  Median (IQR) 94.0 (66.0–147.0) 44.0 (30.0–60.0) 66.5 (45.0–109.0)
Minutes from ED arrival to vasoactive medication < 0.01
administration
  n 47 30 77
  Median (IQR) 130.0 (90.0–205.0) 47.5 (32.0–76.0) 98.0 (54.0–170.0)
ED = emergency department, IQR = interquartile range.
p values are based on Wilcoxon signed rank tests.
a

organisms) were similar, our entire cohort had faster time to reported by Weiss et al (27). This group also reported a signifi-
antibiotic and fluid bolus administration, as well as substan- cant reduction in mortality, organ failure, vasoactive infusions,
tially lower hospital mortality rates. For example, 44% of our and ventilator days when antibiotics were given within 3 hours
cohort received antibiotics within 1 hour of ED arrival, and compared to later (27). It should be noted, however, that the
88% within 3 hours, compared to 18% and 51%, respectively, Weiss et al (27) used a slightly different definition of septic
shock, and therefore their
cohort may have been more
severely ill than that of the
present study. A similar recent
investigation of adult patients
with septic shock also reported
improvement in clinical out-
comes with antibiotic receipt
within 3 hours (28). If antibi-
otic administration within 3
hours is the time-point associ-
ated with significant improve-
ment in clinical outcomes, the
present study would likely not
be able to detect this difference
as the majority of our cohort
received antibiotics within this
timeframe.
Similar to use of antibiot-
ics, fluid resuscitation and
administration of vasoactive
infusions were more consis-
tent with the goals of the SSC
Figure 1. Comparison of median time from emergency department (ED) arrival to receipt of IV fluids in mL/kg in our cohort than what has
between those who received care in compliance with the time goals of the Surviving Sepsis Campaign (SSC)
guidelines, indicated by the dashed line, and those who did not, indicated by the solid line. Median times were been reported in previous
similar between groups. pediatric studies (4, 9, 27). A

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 Workman et al

Table 3. Organ Dysfunction, Mortality, and Hospital Resource Utilization Outcomes in Patients
Who Received Surviving Sepsis Campaign Compliant Care Versus Those Who Did Not
Surviving Sepsis Campaign
Compliant Adjusted
Unadjusted Adjusted OR/ Effect
Outcome Variable No (n = 204) Yes (n = 117) p Valuesa Rate Ratiob Difference

Organ dysfunction
  Maximum organ failuresc 1.0 (1.0–2.0) 1.0 (1.0–2.0) 0.14 1.07 (0.88–1.29)
  New or progressive multiple 25 (12.3%) 9 (7.7%) 0.26 0.61 (0.27–1.39)
organ dysfunction syndrome
  Cardiovascular dysfunction 153 (75.0%) 97 (82.9%) 0.12 1.59 (0.85–2.96)
  Respiratory dysfunction 65 (31.9%) 44 (37.6%) 0.33 0.97 (0.56–1.68)
  Hematologic dysfunction 42 (20.6%) 37 (31.6%) 0.03 1.76 (1.02–3.05)
  Renal dysfunction 19 (9.3%) 9 (7.7%) 0.69
  Hepatic dysfunction 12 (5.9%) 3 (2.6%) 0.27
  Neurologic dysfunction 7 (3.4%) 2 (1.7%) 0.50
Mortality 13 (6.4%) 4 (3.4%) 0.31
Resource utilization
  Hospital length of stay (d) 5.4 (3.0–10.2) 5.9 (2.9–12.0) 0.86 1.57 (–1.92 to 5.05)
  PICU length of stay (d) 1.7 (0.9–4.2) 1.8 (0.8–5.7) 0.88 –0.05 (–2.73 to 2.63)
  Mechanical ventilation 59 (28.9%) 43 (36.8%) 0.17 1.13 (0.64–1.98)
  Continuous infusion of 63 (30.9%) 38 (32.5%) 0.80 1.14 (0.67–1.95)
vasoactive agents
OR = odds ratio.
a
Unadjusted p values are based on Fisher exact test for binary outcomes and the rank-sum test for others.
b
No aggressive care is the reference for odds ratios (ORs), rate ratios, and effect differences. Adjusted analyses control for age, sex, presence of complex chronic
condition, type of infection, and Pediatric Index of Mortality 2 score. Logistic regression is used for binary outcomes with at least 30 cases. Poisson regression is
used for maximum organ failures. Standard linear regression is used for length of stay. OR, rate ratio, and effect difference estimates are accompanied by 95% CIs.
c
Data are expressed as n (%) or median (interquartile range) for each group.

recent investigation in the adult septic shock population evalu-
ated the effect of elapsed time of both interventions on mor-
tality and found that patients who received larger volume fluid
resuscitation within the first hour followed by vasoactive infu-
sion over the next several hours had the lowest mortality rates
(29). This would support the low mortality rate in our cohort
as the majority of patients received adequate fluid resuscita-
tion in the first hour, with initiation of a vasoactive infusion
between hours 1 and 2.
Our study includes patients beginning in 2008, approximately
1 year after implementation of our ED septic shock guidelines
and in the setting of continuous process improvement efforts
focused on meeting the 1-hour time goals of the SSC. With this
ongoing effort, children who presented to the ED in septic shock
during the study period received resuscitative efforts that ben-
efited from this focused quality effort. While only 36% of the
study cohort received all bundle measures within 1 hour, many
more received these interventions within 2 or 3 hours, and very
few delayed beyond 3 hours. Thus, the two groups compared
may not have had clinically important differences in their ED
care despite statistically significant differences in the number of
minutes to each intervention. While all children did not receive
all interventions within the 1-hour goal of the SSC, the hospi-
tal initiative for improving ED septic shock care in accordance
with the SSC apparently raised the level of care for all patients.
By maintaining this as the goal, children received the care
they needed on the time scale sufficient to improve outcomes.
Compliance with the 1-hour goal has continued to improve at
our institution and with that, we have decreased hospital mor-
tality even further than is reported here (9).
Our findings are similar to those of the Randomized Trial
of Protocol-Based Care for Early Septic Shock trial, a multi-
center RCT that evaluated the effect of protocolized, goal-
directed septic shock treatment similar to that proposed by
Rivers et al (2), versus either protocol-based standard therapy,
or usual care on 60-day mortality in adults with septic shock.
In this investigation, while the three arms of the trial differed
significantly in the volume and timing of resuscitative fluids,
the use of vasopressors, endpoints used to manage resuscita-
tive efforts (Svo2, central venous pressure, clinician judgment),
mortality, organ failure, and hospital resource utilization did
not differ among the three arms (13). Interestingly, the major-
ity of patients received IV antibiotics as well as at least 2 L of
IV fluids on average prior to randomization. Similar findings

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were recently reported in the Australasian Resuscitation In
Sepsis Evaluation trial, another large RCT of adult septic shock
patients (14). Despite the null findings of these two large RCTs
as well as our study, the results of all three underscore the
importance of early recognition and rapid treatment of the
patient in septic shock (30, 31).
Our study has several limitations. Exposure assignment was
performed by individuals who were unaware of patient out-
comes, limiting systematic exposure misclassification; however,
this assignment was based solely on information available from
ED documentation, which was not always 100% complete, par-
ticularly with respect to care given prior to arrival at our facil-
ity. Furthermore, there is potential for confounding due to
severity of illness, as those patients who presented with more
severe disease may have been more likely to receive SSC com-
pliant care, but may also have had worse outcomes secondary
to their advanced disease process. To limit this, illness severity
was controlled for in the adjusted analysis using PIM2 scores,
though these did not differ significantly between the two groups.
Further limiting our statistical analysis, the sample size may have
been too small to detect a significant difference in NP-MODS,
as our power analysis was based on a 45% MODS rate in chil-
dren with septic shock and our cohort’s rate of MODS was only
41% and NP-MODS was only 11%. Additionally, patients in our
cohort had lower PIM2 scores and fewer comorbid conditions
than many other similar investigations, which makes it difficult
to directly compare NP-MODS and mortality between stud-
ies. Alternatively, our patients may have also benefitted from
the rapid treatment of their condition and reversal of the shock
state, resulting in lower rates of morbidity and mortality. Finally,
the retrospective design and relatively small single-center sample
limits the generalizability of our results.
CONCLUSIONS
In this retrospective cohort study evaluating the effect of timely
pediatric ED septic shock care on PICU patient outcomes, we
found no difference between those who received all interven-
tions within the first hour of care in compliance with SSC
guidelines versus those who did not. Because patients who did
not meet SSC guideline goals still received their resuscitative
interventions quickly and overall had a very low mortality, our
study reinforces the importance of early recognition and rapid
treatment of pediatric septic shock. Although the SSC goal of 1
hour for receipt of initial therapy may not be the clinically sig-
nificant cut point for improved outcomes, striving to achieve
this goal through system improvement efforts has been essen-
tial to improving morbidity and mortality in our hospital.
ACKNOWLEDGMENTS
We thank Roni Lane, MD, from the University of Utah, Depart-
ment of Pediatrics, for her outstanding leadership of the Pri-
mary Children’s Sepsis Work group and her careful review of
this article. We also thank Tanya Stout from Primary Children’s
Hospital, Department of Systems Improvement, for her contri-
butions to the septic shock database used in this study.
Pediatric Critical Care Medicine www.pccmjournal.org e457
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