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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 Campaign recommendations (delivery of IV fluids, IV antibiotics,
recognition and treatment of severe sepsis and septic shock. Few and vasoactive infusions within 1 hr of shock recognition). The
reports have evaluated the impact of these recommendations in primary outcome was development of new or progressive mul-
pediatrics. We sought to determine if outcomes in patients who tiple organ dysfunction syndrome. Secondary outcomes included
received initial care compliant with the Surviving Sepsis Cam- mortality, need for mechanical ventilation or vasoactive medica-
paign time goals differed from those treated more slowly. tions, and hospital and PICU length of stay. Of the 321 children
Design: Single center retrospective cohort study. studied, 117 received Surviving Sepsis Campaign compliant care
Setting: Emergency department and PICU at an academic chil- in the emergency department and 204 did not. New or progres-
dren’s hospital. sive multiple organ dysfunction syndrome developed in nine of the
Patients: Three hundred twenty-one patients treated for septic patients (7.7%) who received Surviving Sepsis Campaign compli-
shock in the emergency department and admitted directly to the ant care and 25 (12.3%) who did not (p = 0.26). There were 17
PICU. deaths; overall mortality rate was 5%. There were no significant
Interventions: None. differences between groups in any of the secondary outcomes.
Measurements and Main Results: The exposure was receipt of Although only 36% of patients met the Surviving Sepsis Cam-
emergency department care compliant with the Surviving Sepsis paign guideline recommendation of bundled care within 1 hour of
shock recognition, 75% of patients received the recommended
interventions in less than 3 hours.
*See also p. 1011.
Conclusions: Treatment for pediatric septic shock in compliance
1
Division of Critical Care, Department of Pediatrics, University of Utah,
Salt Lake City, UT. with the Surviving Sepsis Campaign recommendations was not
2
Department of Mathematics, University of Utah, Salt Lake City, UT. associated with better outcomes compared with children whose
3
Pediatric Clinical Program, Intermountain Healthcare, Salt Lake City, UT. initial therapies in the emergency department were administered
4
Department of System Improvement, Primary Children's Hospital, Salt more slowly. However, all patients were treated rapidly and we
Lake City, UT. report low morbidity and mortality. This underscores the impor-
Current address for Dr. Ames: Department of Critical Care Medicine and tance of rapid recognition and treatment of septic shock. (Pediatr
Pediatrics, University of Pittsburgh, Pittsburgh, PA. Crit Care Med 2016; 17:e451–e458)
This study was performed at Primary Children’s Hospital.
Key Words: multiple organ dysfunction syndrome; pediatric critical
Supplemental digital content is available for this article. Direct URL cita-
care; septic shock; severe sepsis; Surviving Sepsis Campaign
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

P
Children’s Foundation Clinical Excellence Grants Program, which pro- ediatric septic shock is a major cause of morbidity and
vided support for data collection and management.
mortality in children, leading to over 20,000 U.S. inpa-
Dr. Workman received a grant from the Primary Children’s Foundation Clini-
cal Excellence Grants Program in support of this work. The remaining authors tient admissions and over 800 deaths annually (1). As first
have disclosed that they do not have any potential conflicts of interest. described by Rivers et al (2) in 2001, the early recognition of
For information regarding this article: E-mail: Jennifer.workman@hsc.utah.edu severe sepsis and septic shock combined with early goal-directed
Copyright © 2016 by the Society of Critical Care Medicine and the World therapy (including fluid resuscitation, administration of broad
Federation of Pediatric Intensive and Critical Care Societies spectrum empiric antibiotics, and the use of inotropic or vaso-
DOI: 10.1097/PCC.0000000000000906 pressor agents for persistent hemodynamic derangement)

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Workman et al

significantly improves survival in adults. This has also been Review Board approved the study and waived requirement for
shown in children with septic shock who have been treated with informed consent.
similar, pediatric specific guidelines (3–6). The growing body of
evidence in support of this approach to treatment is now out- Participant Selection Criteria
lined in the Surviving Sepsis Campaign (SSC) guidelines, a joint Initial patient selection was from the PCH Pediatric Septic
effort of the Society of Critical Care Medicine and the European Shock Project Database, which was established with initiation
Society of Intensive Care Medicine focused on reducing mor- of the PCH ED septic shock guidelines in 2007. Patient records
tality from sepsis worldwide. The most recent iteration of these were flagged for initial review and possible inclusion in this
guidelines was distributed internationally in 2012, and provides database if they met any of the following broad criteria: 1) tri-
recommendations for the care of both adults and children with age in the ED to “emergent” status; 2) lactate drawn during ED
severe sepsis and septic shock (7). course; 3) PICU admission within 12 hours of presentation to
The pediatric SSC guidelines recommend administration of ED; 4) repeat visits to the ED within 48 hours of initial visit;
IV fluid resuscitation, IV antibiotics, and infusion of vasoac- and 5) having a “rapid response” called on a patient within 12
tive agents within the first hour of recognition and care of the hours of admission from the ED to an inpatient ward for man-
patient with septic shock (7). In 2007, in consideration of the agement of sepsis. Following initial screening based on these
guidelines available at the time (8), our institution implemented criteria, patients were retained in this database if their condi-
an emergency department (ED) septic shock guideline to facili- tion met the American College of Critical Care Medicine/Pedi-
tate early recognition and rapid treatment of pediatric septic atric Advanced Life Support (PALS) definition of septic shock:
shock. Initially, the goals of this quality improvement initiative known or suspected infection accompanied by temperature
focused on improved recognition, and over time were modi- abnormalities, vital sign abnormalities based on PALS vital sign
fied to the provision of care consistent with SSC goals. Within parameters for age, and physical examination consistent with
the first 2 years of implementation, there was improved disease deficit in end-organ perfusion (5). The ACCM/PALS definition
recognition at presentation to the ED, augmented rates of early of septic shock was utilized instead of the 2005 Consensus Defi-
treatment, and significantly decreased overall hospital length nition (15) because of its usefulness in bedside diagnosis and
of stay (LOS), but mortality remained stable (from 7% to 6%) treatment in real time (16), as was necessary in the setting of
(9). Our hospital ED septic shock guideline has now been in our hospital’s septic shock initiative.
place for over 8 years, and has aided identification of over 1,000 We included subjects for the present study if they were
patients who met shock criteria during their ED admission. 18 years old or younger on ED admission, and were admitted
While many investigations report lower mortality and directly from the ED to the PICU between January 2008 and
resource utilization following implementation of septic December 2012. Any patient admitted initially to the inpatient
shock protocols (9–12), few have specifically linked pedi- floor and subsequently transferred to the PICU was excluded,
atric patient outcomes with receipt of bundled care within as care provided during the inpatient stay may have altered the
1 hour of shock recognition that is recommended in the relationship between resuscitative ED care and patient out-
SSC guidelines. Additionally, two recently published large comes. We included patients in the present study beginning in
adult randomized controlled trials (RCTs) reported similar 2008 instead of 2007 when the ED Guideline was initiated so
mortality from protocolized septic shock treatment com- that the data reflected care of patients by adequately trained
pared with usual care (13, 14). Therefore, the objective of staff familiar with the recommended interventions.
the current study was to evaluate the association between
timely delivery of therapy for pediatric septic shock in the Exposures and Outcomes
ED in accordance with the SSC guidelines, and outcomes in The exposure was receipt of care in the ED in compliance with
children admitted to the PICU. Our hypothesis is that chil- the recommendations of the SSC, defined by administration
dren treated according to SSC recommendations will have of antibiotics within 1 hour of arrival, administration of at
decreased new or progressive multiple organ dysfunction least 60 mL/kg IV resuscitation fluids within 1 hour of arrival
syndrome (NP-MODS). (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
MATERIALS AND METHODS
examination), and administration of an inotropic or vasoac-
Study Design and Setting tive agent for fluid-refractory patients within 1 hour of arrival.
We evaluated the relationship between pediatric ED care for The primary outcome measure was the development of
septic shock and outcomes of children requiring admission to NP-MODS. Given the relatively low mortality rate in many
the PICU. We retrospectively selected patients presenting to pediatric illnesses, a surrogate measure of disease sever-
the ED with septic shock between 2008 and 2012, and reviewed ity is often used. Sepsis is associated with MODS (17), and
the hospital course and clinical outcomes. The study was con- NP-MODS (the development of two or more organ dysfunc-
ducted at Primary Children’s Hospital (PCH), a tertiary care tions during hospitalization) has been used as a surrogate
pediatric hospital with 40,000 ED visits per year and 2,000 measure in this way (18, 19). MODS assessment was based on
PICU admissions per year. The University of Utah Institutional cardiovascular, pulmonary, renal, neurologic, hematologic, and

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hepatic function, and evaluated based on the patient’s worst entire cohort, median time to first fluid bolus was 23.0 minutes
function for a given time period based on the criteria outlined (interquartile range, 10.0–39.5), and 62% of the cohort received
by Proulx et al (18, 19) (Supplementary Table 1, Supplemental adequate fluid resuscitation within the first hour of care (as
Digital Content 1, http://links.lww.com/PCC/A279). determined by resolution of perfusion defect, improvement in
In the present study, NP-MODS was assessed on days 1, 2, vital signs). Those who received SSC complaint care had a sig-
5, 8, 12, 16, and 18 (or until hospital discharge, whichever was nificantly shorter median time to antibiotic administration (44
sooner). Data were abstracted both from the Intermountain vs 94 min; p < 0.01) and time to administration of vasoactive
Enterprise Data Warehouse (EDW) and by manual chart infusion (47.5 vs 130 min; p < 0.01). There were 145 patients
review. Additional outcome measures including mortality, (45%) who did not receive antibiotics within 1 hour of ED
PICU, and hospital LOS, and hospital resource utilization were arrival, and 18 patients (55%) who did not receive vasoactive
investigated using the EDW. All data were stored within the medications within 1 hour of becoming hypotensive. Overall,
University of Utah Division of Pediatric Critical Care Data 75% of patients received empiric antibiotics within 1.8 hours
Coordinating Center secure server. and vasoactive medications within 2.8 hours.
There were 119 children (37%) who had MODS on day 1
Statistical Analysis of their hospital stay, 133 (41%) with MODS at any point dur-
Standard descriptive statistics were used to summarize patient ing hospitalization, and 34 (11%) who developed NP-MODS.
characteristics. Groups were compared by exposure, using There were 17 deaths (5%). Risk of death was significantly
Fisher exact test for categoric variables and Wilcoxon signed associated with presence of a CCC (RR, 5.0; 95% CI, 1.8–13.8),
rank test for continuous variables. Relative risk ratios were cal- but risk of NP-MODS was not. Among those who died, only
culated using Epi Info (Centers for Disease Control and Pre- two were previously healthy. Fifteen of the deaths resulted from
vention, Atlanta, GA) to determine risk factors associated with eventual withdrawal of support despite maximal and escalat-
development of NP-MODS and death. Multiple logistic regres- ing therapies, including the two previously healthy children.
sion was used to estimate the relationship between receipt of Duration of hospitalization prior to death ranged from several
SSC compliant care and adjusted odds of NP-MODS (primary hours to 1 month. There were no differences between groups
outcome). Variables were selected for inclusion in the multivari- with respect to development of NP-MODS, the maximum
able models based on a priori clinical rationale, and included number of dysfunctional organ systems, individual organ dys-
age, sex, presence of a complex chronic condition (CCC) (20), functions (with the exception of hematologic), or mortality in
type of infection identified (bacterial vs viral), and Pediatric either the adjusted or unadjusted analyses (Table 3).
Index of Mortality (PIM) 2 scores. All analyses were performed Children with a documented bacterial infection were sig-
using SAS version 9.4 (SAS Institute Inc., Cary, NC). nificantly more likely to develop NP-MODS compared to
those with viral infections or no source of infection identified
RESULTS (p < 0.01, data not shown). Among patients with a CCC,
There were 913 children who presented to the ED with sep- receipt of SSC compliant care suggested a trend toward
tic shock during the study period. Of these, 321 children met decreased risk of NP-MODS (RR, 0.17; 95% CI, 0.02–1.3)
inclusion criteria, and among these, there were 117 children and mortality (RR, 0.14; 95% CI, 0.02–1.04); however, these
(36%) who received timely care compliant with SSC guide- differences did not achieve statistical significance. Among
lines and 204 who did not. There were no differences between the entire cohort, 32% required mechanical ventilation dur-
groups with respect to sex, race, presence of a CCC, median ing the hospitalization and 31% required blood pressure
PIM2 scores, or type or site of infection (Table 1). The most support with continuous infusion of vasoactive medications.
common site of infection in both groups was the lungs, and Neither of these two measures, nor median hospital or PICU
just over 60% of children had an infectious organism identi- LOS, differed significantly between groups (Table 3).
fied by either bacterial or viral testing. Younger children were
more likely to receive SSC compliant care (median age, 3 vs DISCUSSION
7 yr; p < 0.05). Children treated in the first 3 years of the study This single center retrospective cohort study of ED septic
(2008–2010) were significantly less likely to have received SSC shock care and PICU patient outcomes revealed no sig-
compliant care (rate ratio [RR], 0.6; 95% CI, 0.4–0.8). nificant association between receipt of bundled care within
An analysis of the interventions received during ED care 1 hour of ED arrival and development of NP-MODS, mor-
between the two groups is shown in Table 2. Receipt of SSC tality, or hospital resource utilization. Interestingly, we also
compliant care was not associated with day (weekday vs week- found that risk of death was associated with presence of a
end) or time (day shift vs night shift) of presentation (p = 0.49 CCC but risk of NP-MODS was not. It is likely that those
and p = 0.85, respectively). Children who received SSC com- with NP-MODS who had a CCC were more likely to progress
pliant care statistically differed from those who did not with to death, while those who were previously healthy were more
respect to time to first fluid bolus (difference in median time, likely to recover. We had hypothesized that receiving care
16 min; p < 0.01). However, there was no difference in the total within 1 hour, in accordance with the current recommenda-
volume of IV fluids administered during the ED stay, and time tions for pediatric septic shock (7), would be associated with
to receipt of total IV fluids was similar (Fig. 1). Among the improved outcomes.

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

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

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Sepsis Investigators Network: Transfusion strategies for patients in
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ment of Pediatrics, for her outstanding leadership of the Pri- 20. Feudtner C, Christakis DA, Connell FA: Pediatric deaths attribut-
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