Sepsis Management in the Emergency Department

Leslie Mullen

Department of Nursing, Youngstown State University

NURS 6901: Theoretical Foundations

Dr. Amy Weaver

November 10, 2021

 2
In patients admitted to the Emergency Department who present with symptoms of sepsis, how does
immediate activation of a sepsis protocol compared to delayed treatment affect length of hospital
stay and mortality rate?

Abstract

Researching and critiquing articles can provide a greater insight into how to appropriately identify

quantitative studies that prove to be meaningful to support your PICOT question. In this research paper,

I have identified six articles that support my PICOT question by stating their relevance and help support

the question of whether immediate implementation of sepsis protocols help reduce mortality in

patients. This research paper provides several studies that show positive outcomes of immediate sepsis

protocol implementation.

Keywords: sepsis, sepsis protocol, sepsis management, PICOT, emergency department,

mortality, length of stay.

 3
In patients admitted to the Emergency Department who present with symptoms of sepsis, how does
immediate activation of a sepsis protocol compared to delayed treatment affect length of hospital
stay and mortality rate?

Introduction

Researching articles on sepsis is a broad term and proved to be a difficult one. Several research

strategies were implemented that stemmed through EBSCOhost for the completion of this research

paper. Through EBSCOhost, many research databases were available for further searches. The databases

that were used were Medline Complete, CINAHL Plus, PubMed and Wiley Cochrane Library. By using

these databases, many appropriate quantitative research article studies on sepsis management were

displayed. The search words that were used were sepsis bundles, sepsis protocols, sepsis bundles in the

emergency department, sepsis and mortality rates and sepsis management in the emergency

department. Thousands of articles populated in these searches and a narrower search was performed by

a more specific search of sepsis interventions in the emergency department. To provide more specific

articles, the dates were adjusted to only include articles from 2010 on, to include only full text articles

and only those that are meta-analysis or systemic review publications.

Article #1

Sterling, S. A., Miller, W. R., Pryor, J., Puskarich, M. A., & Jones, A. E. (2015). The Impact of Timing of

Antibiotics on Outcomes in Severe Sepsis and Septic Shock: A Systematic Review and Meta-

Analysis. Critical care medicine, 43(9), 1907–1915.

https://doi.org/10.1097/CCM.0000000000001142

Abstract #1

Objectives: We sought to systematically review and meta-analyze the available data on the association

between timing of antibiotic administration and mortality in severe sepsis and septic shock.

Data sources: A comprehensive search criteria was performed using a predefined protocol.
 4
In patients admitted to the Emergency Department who present with symptoms of sepsis, how does
immediate activation of a sepsis protocol compared to delayed treatment affect length of hospital
stay and mortality rate?

Inclusion criteria: adult patients with severe sepsis or septic shock, reported time to antibiotic

administration in relation to emergency department triage and/or shock recognition, and mortality.

Exclusion criteria: immunosuppressed populations, review article, editorial, or nonhuman studies.

Data extraction: Two reviewers screened abstracts with a third reviewer arbitrating. The effect of time

to antibiotic administration on mortality was based on current guideline recommendations: 1)

administration within 3 hours of emergency department triage and 2) administration within 1 hour of

severe sepsis/septic shock recognition. Odds ratios were calculated using a random effect model. The

primary outcome was mortality.

Data synthesis: A total of 1,123 publications were identified and 11 were included in the analysis.

Among the 11 included studies, 16,178 patients were evaluable for antibiotic administration from

emergency department triage. Patients who received antibiotics more than 3 hours after emergency

department triage (< 3 hr. reference) had a pooled odds ratio for mortality of 1.16 (0.92-1.46; p = 0.21).

A total of 11,017 patients were evaluable for antibiotic administration from severe sepsis/septic shock

recognition. Patients who received antibiotics more than 1 hour after severe sepsis/shock recognition (<

1 hr. reference) had a pooled odds ratio for mortality of 1.46 (0.89-2.40; p = 0.13). There was no

increased mortality in the pooled odds ratios for each hourly delay from less than 1 to more than 5

hours in antibiotic administration from severe sepsis/shock recognition.

Conclusion: Using the available pooled data, we found no significant mortality benefit of administering

antibiotics within 3 hours of emergency department triage or within 1 hour of shock recognition in
 5
In patients admitted to the Emergency Department who present with symptoms of sepsis, how does
immediate activation of a sepsis protocol compared to delayed treatment affect length of hospital
stay and mortality rate?

severe sepsis and septic shock. These results suggest that currently recommended timing metrics as

measures of quality of care are not supported by the available evidence.

Why This Study is Appropriate for PICOT Question

The Surviving Sepsis Campaign has several guidelines in place for treating sepsis. One is the

administration of antibiotics within one hour of recognition of signs and symptoms of sepsis and within

3 hours of emergency department triage. This article states that the findings of their study do not

support the SSC guidelines of timing of antibiotic administration and further raise concern about the use

of time to antibiotic administration as a specific metric for treatment. The article did recognize that

failure to administer antibiotics at some point will be detrimental to the patient but the specific time at

which the shift begins to occur remains unknown. “It is plausible that in some patients the initiation of

resuscitation prior to the administration of antibiotics proves the most ideal circumstance for the host to

have a sustained and robust hemodynamic response to the propagation of the inflammatory cascade”

(Sterling, et al., 2015). This article is important to the PICOT question because it recognizes that

antibiotic therapy, which is a usual component of a sepsis bundle, is showing that the early

administration of these medications is not of substantial importance. The intervention of immediate

administration of within three hours of emergency triage is not proving to be beneficial with regards to

mortality rate. It is relevant because it examines the timeframe of activation of the sepsis bundle and

looks at the relationship between timing of one of the interventions and mortality rate.

Article #2
 6
In patients admitted to the Emergency Department who present with symptoms of sepsis, how does
immediate activation of a sepsis protocol compared to delayed treatment affect length of hospital
stay and mortality rate?

Kramer, R. D., Cooke, C. R., Liu, V., Miller, R. R., 3rd, & Iwashyna, T. J. (2015). Variation in the Contents of

Sepsis Bundles and Quality Measures. A Systematic Review. Annals of the American Thoracic

Society, 12(11), 1676–1684. https://doi.org/10.1513/AnnalsATS.201503-163BC

Abstract #2

Rationale: Sepsis contributes to one in every two to three inpatient hospital deaths. Early recognition

and treatment are instrumental in reducing mortality, yet there are substantial quality gaps. Sepsis

bundles containing quality metrics are often used in efforts to improve outcomes. Several prominent

organizations have published their own bundles, but there are few head-to-head comparisons of

content.

Objectives: We sought to determine the degree of agreement on component elements of sepsis bundles

and the associated timing goals for completion of each element. We additionally sought to evaluate the

amount of variation between metrics associated with bundles.

Methods: We reviewed the components of and level of agreement among several sepsis resuscitation

and management bundles. We compared the individual bundle elements, together with their associated

goals and metrics. We performed a systematic review (PubMed 2008-2015) and searched publicly

available online content, supplemented by interviews with key informants, to identify eight distinct

bundles. Bundles are presented as current as of April 2015.

Measurements and main results: Broadly, elements of care covered early resuscitation and short-term

management. Bundles varied from 6 to 10 elements, and there were 12 distinct elements listed across

all bundles. Only lactate collection and broad-spectrum antibiotics were common to all eight bundles,
 7
In patients admitted to the Emergency Department who present with symptoms of sepsis, how does
immediate activation of a sepsis protocol compared to delayed treatment affect length of hospital
stay and mortality rate?

although there were seven elements included in at least 75% of the bundles. Timing goals for the

collection of lactate and antibiotic administration varied among bundles from within 1 to 6 hours of

diagnosis or admission. Notably, no bundle included metrics evaluating timeliness or completeness of

sepsis recognition.

Conclusions: There is a lack of consensus on component elements and timing goals across highly

recognized sepsis bundles. These differences highlight an urgent need for comparative effectiveness

research to guide future implementation and for metrics to evaluate progress. None of the widely

instituted bundles include metrics to evaluate sepsis recognition or diagnostic accuracy.

Keywords: bundles; guidelines; quality improvement; quality metrics; sepsis.

Why This Study is Appropriate for PICOT Question

This study shows that widely available bundles for early sepsis are present but display the

disagreement between among critical aspects of the components and implementation. Timing of

interventions vary from institution to institution. “Bundles exist as a non-evidence-based way to

prioritize evidence-based recommendations for sepsis care” (Kramer, et al., 2015). The difference

amongst the multiple sources highlights a gap in agreement how to accurately treat sepsis and record

quality measures. This article is appropriate because it examines how different sepsis bundles are from

institutions and sources such as Surviving Sepsis Campaign. There seems to be a consensus across the

board on most components such as fluid resuscitation, antibiotics, lactate measurement and evaluation

for hypoperfusion. Timing goals seem to vary from bundle to bundle. The outcome of this study states

that there is an urgent need for comparative effectiveness research to guide future management of

sepsis.
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In patients admitted to the Emergency Department who present with symptoms of sepsis, how does
immediate activation of a sepsis protocol compared to delayed treatment affect length of hospital
stay and mortality rate?

Article #3

Threatt D. L. (2020). Improving Sepsis Bundle Implementation Times: A Nursing Process Improvement

Approach. Journal of nursing care quality, 35(2), 135–139.

https://doi.org/10.1097/NCQ.0000000000000430

Abstract #3

Background: Early recognition of sepsis in the emergency room (ER) has been shown to improve

treatment intervention times and decrease mortality.

Local problem: Failure to recognize early signs and symptoms of sepsis in the ER has led to poor sepsis

bundle completion times.

Methods: A comparison of preintervention and postintervention data was performed to determine

whether sepsis bundle implementation times, mortality, and length of stay (LOS) improved.

Interventions: An ER Nurse Sepsis Identification Tool, leadership buy-in from key stakeholders, and

systemic inflammatory response syndrome (SIRS) education were implemented.

Results: Postintervention, average bundle compliance time decreased 458 minutes (P < .001), average

antibiotic administration time decreased 101 minutes (P < .001), overall sepsis mortality decreased 5.9%

(P = .074), and there was no change to LOS.

Conclusions: The implementation of an ER early sepsis identification tool, leadership buy-in, and SIRS

education can lead to improved bundle implementation times in the ER.

 9
In patients admitted to the Emergency Department who present with symptoms of sepsis, how does
immediate activation of a sepsis protocol compared to delayed treatment affect length of hospital
stay and mortality rate?

Why This Study is Appropriate for PICOT Question

As the interventions in the abstract state, this article looks at the use of a sepsis identification

tool that will be used by ER nurses to help identify those who meet criteria and initiate prompt

treatment. This article is appropriate because it identifies and looks at the use of an evidence-based

emergency department nurse sepsis screening tool to assist nurses and help identify early signs and

symptoms of sepsis. Immediate implementation of a sepsis bundle can begin for those who meet the

criteria. Patients are triaged and if these criteria for severe sepsis/septic shock are identified, these

patients are seen by a provider immediately so that treatment can being without delay. This article did

show that average length of stay for sepsis patients remained flat possibly due to patients’ multiple

comorbidities and complications during the post intervention phase.

Article #4

Milano, P. K., Desai, S. A., Eiting, E. A., Hofmann, E. F., Lam, C. N., & Menchine, M. (2018). Sepsis Bundle

Adherence Is Associated with Improved Survival in Severe Sepsis or Septic Shock. Western

Journal of Emergency Medicine: Integrating Emergency Care with Population Health, 19(5), 774–

781. https://doi-org.eps.cc.ysu.edu/10.5811/westjem.2018.7.37651

Abstract #4

Introduction: There have been conflicting data regarding the relationship between sepsis-

bundle adherence and mortality. Moreover, little is known about how this relationship may be

moderated by the anatomic source of infection or the location of sepsis declaration.

 10
In patients admitted to the Emergency Department who present with symptoms of sepsis, how does
immediate activation of a sepsis protocol compared to delayed treatment affect length of hospital
stay and mortality rate?

Methods: This was a multi-center, retrospective, observational study of adult patients with a hospital

discharge diagnosis of severe sepsis or septic shock. The study included patients who presented to one

of three Los Angeles County Department of Health Services (DHS) full-service hospitals January 2012 to

December 2014. The primary outcome of interest was the association between sepsis bundle adherence

and in-hospital mortality. Secondary outcome measures included in-hospital mortality by source of

infection, and the location of sepsis declaration.

Results: Among the 4,582 patients identified with sepsis, overall mortality was lower among those who

received bundle-adherent care compared to those who did not (17.9% vs. 20.4%; p=0.035). Seventy five

percent (n=3,459) of patients first met sepsis criteria in the ED, 9.6% (n=444) in the intensive care unit

(ICU) and 14.8% (n=678) on the ward. Bundle adherence was associated with lower mortality for those

declaring in the ICU (23.0% adherent [95% confidence interval{CI} {16.8-30.5}] vs. 31.4% nonadherent

[95% CI {26.4-37.0}]; p=0.063), but not for those declaring in the ED (17.2% adherent [95% CI {15.8-

18.7}] vs. 15.1% non-adherent [95% CI {13.0-17.5}]; p=0.133) or on the ward (24.8% adherent [95% CI

{18.6-32.4}] vs. 24.4% non-adherent [95% CI {20.9-28.3}]; p=0.908). Pneumonia was the most common

source of sepsis (32.6%), and patients with pneumonia had the highest mortality of all other subsets

receiving bundle non-adherent care (28.9%; 95% CI [25.3-32.9]). Although overall mortality was lower

among those who received bundle-adherent care compared to those who did not, when divided into

subgroups by suspected source of infection, a statistically significant mortality benefit to bundle-

adherent sepsis care was only seen in patients with pneumonia.

Conclusion: In a large public healthcare system, adherence with severe sepsis/septic shock

management bundles was found to be associated with improved survival. Bundle adherence seems to

be most beneficial for patients with pneumonia. The overall improved survival in patients who
 11
In patients admitted to the Emergency Department who present with symptoms of sepsis, how does
immediate activation of a sepsis protocol compared to delayed treatment affect length of hospital
stay and mortality rate?

received bundle-adherent care was driven by patients declaring in the ICU. Adherence was not

associated with lower mortality in the large subset of patients who declared in the ED, nor in the smaller

subset of patients who declared in the ward.

Why This Study is Appropriate for PICOT Question

Components of sepsis care have evolved into core measures put forth by the Centers for

Medicare and Medicaid Services. Since compensation is partially driven by meeting these measures, a

push for compliance and accurate reporting has been taking place. This article is appropriate because it

validates the intervention of an immediate activation of a sepsis protocol and shows an improvement in

mortality rate. In this study, one set of criteria is presented so there are clear and concise guidelines.

The results show that delay in implementation can lead to an increase in mortality rate. This study is

relevant because adherence with sepsis bundles show a position correlation with overall improvement

in survival. While the lower mortality rate with adherence to bundles is showing positive, this is mostly

driven by ICU patients and not ED patients.

Article #5

Seymour, C. W., Gesten, F., Prescott, H. C., Friedrich, M. E., Iwashyna, T. J., Phillips, G. S., Lemeshow, S.,

Osborn, T., Terry, K. M., & Levy, M. M. (2017). Time to Treatment and Mortality during

Mandated Emergency Care for Sepsis. The New England journal of medicine, 376(23), 2235–

2244. https://doi.org/10.1056/NEJMoa1703058

Abstract #5

Methods: We studied data from patients with sepsis and septic shock that were reported to the New

York State Department of Health from April 1, 2014, to June 30, 2016. Patients had a sepsis protocol

initiated within 6 hours after arrival in the emergency department and had all items in a 3-hour bundle
 12
In patients admitted to the Emergency Department who present with symptoms of sepsis, how does
immediate activation of a sepsis protocol compared to delayed treatment affect length of hospital
stay and mortality rate?

of care for patients with sepsis (i.e., blood cultures, broad-spectrum antibiotic agents, and lactate

measurement) completed within 12 hours. Multilevel models were used to assess the associations

between the time until completion of the 3-hour bundle and risk-adjusted mortality. We also examined

the times to the administration of antibiotics and to the completion of an initial bolus of intravenous

fluid.

Results: Among 49,331 patients at 149 hospitals, 40,696 (82.5%) had the 3-hour bundle completed

within 3 hours. The median time to completion of the 3-hour bundle was 1.30 hours (interquartile

range, 0.65 to 2.35), the median time to the administration of antibiotics was 0.95 hours (interquartile

range, 0.35 to 1.95), and the median time to completion of the fluid bolus was 2.56 hours (interquartile

range, 1.33 to 4.20). Among patients who had the 3-hour bundle completed within 12 hours, a longer

time to the completion of the bundle was associated with higher risk-adjusted in-hospital mortality

(odds ratio, 1.04 per hour; 95% confidence interval [CI], 1.02 to 1.05; P<0.001), as was a longer time to

the administration of antibiotics (odds ratio, 1.04 per hour; 95% CI, 1.03 to 1.06; P<0.001) but not a

longer time to the completion of a bolus of intravenous fluids (odds ratio, 1.01 per hour; 95% CI, 0.99 to

1.02; P=0.21).

Conclusion: More rapid completion of a 3-hour bundle of sepsis care and rapid administration of

antibiotics, but not rapid completion of an initial bolus of intravenous fluids, were associated with lower

risk-adjusted in-hospital mortality. (Funded by the National Institutes of Health and others.)

Why This Study is Appropriate for PICOT Question

This article reviewed patients with sepsis and septic shock that were reported to the state of

New York Department of Health over a two-year period. The study is appropriate for the PICOT question

because is concludes that more rapid completion of three-hour bundles of sepsis care and rapid
 13
In patients admitted to the Emergency Department who present with symptoms of sepsis, how does
immediate activation of a sepsis protocol compared to delayed treatment affect length of hospital
stay and mortality rate?

administration of antibiotics, but not rapid completion of an initial bolus of intravenous fluids were

associated with a lower risk adjusted hospital mortality rate. It shows correlation between a longer

completion time of three-hour bundles and an increase in risk adjusted hospital mortality.

Article #6

Whitfield, P. L., Ratliff, P. D., Lockhart, L. L., Andrews, D., Komyathy, K. L., Sloan, M. A., Leslie, J. C., &

Judd, W. R. (2020). Implementation of an adult code sepsis protocol and its impact on sep-1 core

measure perfect score attainment in the ed. The American Journal of Emergency Medicine, 38(5),

879–882. https://doi.org/10.1016/j.ajem.2019.07.002

Abstract #6

Introduction: Timely management of sepsis has become an urgent concern among most hospitals.

Institutions have been searching for unique ways to increase the quality of care and timely adherence to

proven therapies. The objective of this study was to determine the impact of an Adult Code Sepsis

Protocol on the rate of SEP-1 perfect score attainment (PSA) among patients who presented to the

emergency department (ED) with severe sepsis or septic shock, as defined by the Centers for Medicare

and Medicaid Services (CMS).

Methods: This was a retrospective, observational cohort study in a 35-bed tertiary care hospital ED from

December 2016 to February 2018. Adults (≥18 years of age) who met the CMS-case definition of severe

sepsis or septic shock presenting to the ED either prior to or after implementation of an Adult Code

Sepsis Protocol were included.

 14
In patients admitted to the Emergency Department who present with symptoms of sepsis, how does
immediate activation of a sepsis protocol compared to delayed treatment affect length of hospital
stay and mortality rate?

Results: The primary outcome of SEP-1 PSA, which was abstracted in an all-or-none fashion, increased

from 30.7% to 71.3% (p b 0.001). Inpatient mortality was reduced from 4% to 0% (p = 0.011) after

protocol implementation. Protocol initiation also resulted in a significant reduction in both time to

initiation of appropriate, empiric and effective antimicrobial therapy, based on culture results by 48 and

111 min, respectively (p b 0.001). There were no significant differences in other secondary outcomes

including ICU length-of-stay, readmission, or economic outcome measures. Conclusions: The addition of

an Adult Code Sepsis Protocol in the ED significantly increased the rate of SEP-1 PSA, reduced inpatient

mortality, and improved the time to initiation of effective antimicrobial therapy.

Why This Study is Appropriate for PICOT Question

Centers for Medicare and Medicaid Services along with Surviving Sepsis Campaign adopted the

SEP-1 core measure to improve compliance rates in evidence-based treatment bundles. Implementation

of an adult code sepsis protocol resulted in significant improvement in the rate of SEP-1 perfect score

attainment among patients who presented to the emergency department with severe sepsis or septic

shock. This article is relevant to the PICOT question because there is a correlation between

implementation of a sepsis protocol and completion of bundles in a timely manner, it proves to reduce

mortality for patients who are septic.

 15
In patients admitted to the Emergency Department who present with symptoms of sepsis, how does
immediate activation of a sepsis protocol compared to delayed treatment affect length of hospital
stay and mortality rate?

References

Kramer, R. D., Cooke, C. R., Liu, V., Miller, R. R., 3rd, & Iwashyna, T. J. (2015). Variation in the Contents of

Sepsis Bundles and Quality Measures. A Systematic Review. Annals of the American Thoracic

Society, 12(11), 1676–1684. https://doi.org/10.1513/AnnalsATS.201503-163BC

Milano, P. K., Desai, S. A., Eiting, E. A., Hofmann, E. F., Lam, C. N., & Menchine, M. (2018). Sepsis Bundle

Adherence Is Associated with Improved Survival in Severe Sepsis or Septic Shock. Western

Journal of Emergency Medicine: Integrating Emergency Care with Population Health, 19(5), 774–

781. https://doi-org.eps.cc.ysu.edu/10.5811/westjem.2018.7.37651

Seymour, C. W., Gesten, F., Prescott, H. C., Friedrich, M. E., Iwashyna, T. J., Phillips, G. S., Lemeshow, S.,

Osborn, T., Terry, K. M., & Levy, M. M. (2017). Time to Treatment and Mortality during

Mandated Emergency Care for Sepsis. The New England journal of medicine, 376(23), 2235–

2244. https://doi.org/10.1056/NEJMoa1703058

Sterling, S. A., Miller, W. R., Pryor, J., Puskarich, M. A., & Jones, A. E. (2015). The Impact of Timing of

Antibiotics on Outcomes in Severe Sepsis and Septic Shock: A Systematic Review and Meta-

Analysis. Critical care medicine, 43(9), 1907–1915.

https://doi.org/10.1097/CCM.0000000000001142

Threatt D. L. (2020). Improving Sepsis Bundle Implementation Times: A Nursing Process Improvement

Approach. Journal of nursing care quality, 35(2), 135–139.

https://doi.org/10.1097/NCQ.0000000000000430
 16
In patients admitted to the Emergency Department who present with symptoms of sepsis, how does
immediate activation of a sepsis protocol compared to delayed treatment affect length of hospital
stay and mortality rate?

References

Whitfield, P. L., Ratliff, P. D., Lockhart, L. L., Andrews, D., Komyathy, K. L., Sloan, M. A., Leslie, J. C., &

Judd, W. R. (2020). Implementation of an adult code sepsis protocol and its impact on sep-1 core

measure perfect score attainment in the ed. The American Journal of Emergency Medicine, 38(5),

879–882. https://doi.org/10.1016/j.ajem.2019.07.002