1. Sepsis 2016 Critical Updates in Management
Jennifer Williams, PhD, RN, ACNS-BC
Clinical Nurse Specialist
Emergency Services
Barnes-Jewish Hospital

2. incidence- 10th Leading Cause of Death
ADULTS
571,000/year in the US
Mortality
Severe Sepsis: 15-30%
Septic Shock: 20-60%
PEDIATRICS
40,000/year in the US
Severe Sepsis: 4-7%
Septic Shock: 13-34%
Wang et. Al 2007, Critical Care Medicine, Noah, 2014 Clinical Pediatric Emergency Medicine

3. pathophysiology

4. Systemic Inflammatory Response Syndrome (SIRS)
Two or more of the following:
Temperature > o or < 96.8 o
Heart Rate > 90 beats/min
Respiratory Rate > 20 or PaCo2 < 32
WBC > 12,000 or < 4,000

5. Sepsis and Severe Sepsis
Known or suspected infection
2 or more SIRS criteria
SEVERE SEPSIS
Sepsis plus one or more organ dysfunction

6. Septic Shock
Severe sepsis with hypotension unresponsive to fluid resuscitation
Shapiro et al, 2014 Rosen’s Emergency Medicine

7. Multi Organ Dysfunction Syndrome (MODS)
Homeostasis can not be maintained
Altered organ function
Cardiovascular
Respiratory
Urinary
Hepatic
CNS
Hematological

8. UNDERSTANDING OF SEPSIS PATHOPHYSIOLOGY
 Coagulation  Fibrinolysis
Endothelial Injury
 Inflammation
Organ Dysfunction
Death

9. IDENTIFYING ACUTE ORGAN DYSFUNCTION AS A MARKER OF SEVERE SEPSIS
Altered Consciousness
Confusion
Psychosis
Tachycardia
Hypotension
  CVP
Tachypnea
PaO2< 70 mm Hg
SaO2 < 90%
Oliguria
Anuria
 Creatinine
Pathophysiology
Shock begins when cardiovascular system fails
Alteration occurs in at least one component
Blood volume
Myocardial contractility
Blood flow
Vascular resistance
Stages of Shock— Stage I: Initiation
Hypoperfusion: inadequate delivery or extraction of oxygen
No obvious clinical signs
May be noticed if invasive hemodynamic monitoring in place
Early, reversible
Stages of Shock— Stage II: Compensatory
Sustained reduction in tissue perfusion
Initiation of compensatory mechanisms
Neural: baroreceptors and chmeoreceptors
Endocrine: ACTH and ADH
Chemical
Low oxygen tension
Hyperventilation and respiratory alkalosis
Neural Compensation
Baroreceptors
Sensitive to pressure changes
Chemoreceptors
Sensitive to chemical changes
Stimulation of the sympathetic nervous system
Increased heart rate
Increased contractility
Vasodilation of coronary arteries
Systemic vasoconstrictions
Shunting
Increased respiratory rate and depth
Endocrine Compensation
Response to low blood pressure
Stimulates anterior and posterior pituitary gland
Anterior pituitary
Aldosterone
Glycogenolysis/gluconeogensis
Stimulation of renin-angiotensin response
Posterior pituitary
Antidiuretic hormone
Provides body with glucose
Increases intravascular blood volume
Chemical Compensation
Ventilation-perfusion imbalances
Chemoreceptors in aorta and carotids
React to low oxygen tension
Respiratory rate and depth increase
Patient hyperventilates
Respiratory alkalosis occurs
Cause vasoconstriction of cerebral blood vessels
Attempt to increase oxygen supply
Negative effects on cerebral perfusion
Stages of Shock— Stage III: Progressive
Failure of compensatory mechanisms
Profound CV effects
Increased hypoperfusion
Vasoconstriction
Extremity ischemia
Cellular hypoxia
Lactic acid production
Failure Na/K pump
Increased capillary hydrostatic pressure
Intravascular fluid shifts
Interstitial edema
Decreased circulating intravascular volume
Decreased coronary perfusion
MDF released
Decreased myocardial contractility
Stages of Shock— Stage IV: Refractory
Prolonged inadequate tissue perfusion
Unresponsive to therapy
Contributes to multiple organ dysfunction and death
Jaundice
 Enzymes
 Albumin
 PT
 Platelets
 PT/APTT
 Protein C
 D-dimer

10. Physiologic Response to Sepsis
Poor tissue oxygenation is the core problem in sepsis.
“TIME IS TISSUE”
Rapid Treatment: Start BEFORE arrival!

11. Definition Changes in 2016
A task force of 19 leaders in the field of sepsis was convened by SCCM and the European Society of Intensive Care Medicine (ESICM)
Changes categories to sepsis and septic shock
The new diagnostic tool for sepsis : quickSOFA qSOFA, 2 of 3 indicators below
An alteration in mental status
A decrease in systolic blood pressure of less than 100 mm Hg
A respiration rate greater than 22 breaths/min
Septic Shock Definitions
Persisting hypotension requiring vasopressors to maintain MAP ≥65 mm Hg
Blood lactate >2 mmol/L despite adequate volume resuscitation
Singer M, Deutschman CS, Seymour C, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8): doi: /jama

12. Definition Changes in 2016 Concerns with Definition Changes
Later diagnosis
Based decisions on retrospective review of data
Consensus was of 2 organizations
Using the new definitions the denominator of hospital cases with expected mortality decreases (sepsis terminology would be used instead of severe sepsis or septic shock).
This gives the potential appearance that the organization is treating pateints poorly as the observed mortality is high in comparison.

13. Treatment protocol evidence evolution

14. Early goal Directed therapy
Single Center (Henry Ford)
263 Patients
Severe Sepsis/Septic Shock
Reduction in mortality of 12.6%
NNT of 8
Concerns
Difficult to parse out the individual impact of each intervention
Use of invasive central venous monitoring difficult to demonstrate benefit
Rivers E, Nguyen B, Havstad S, et al; Early Goal-Directed Therapy
Collaborative Group. Early goal-directed therapy in the treatment of severe
sepsis and septic shock. N Engl J Med Nov 8;345(19):
Objectives: To determine “whether early goal-directed therapy before admission to
the intensive care unit effectively reduces the incidence of multiorgan dysfunction,
mortality, and the use of health care resources among patients with severe sepsis or
septic shock.” (p. 1369)
Methods: this prospective randomized study was conducted at Henry Ford Hospital,
a large urban academic center, between March 1997 and March Adult patients
presenting to the emergency department with two criteria for the systemic
inflammatory response syndrome and either a systolic blood pressure of 90 mmHg or
less after a fluid challenge, or blood lactate of 4 mmol per liter or more were eligible
for inclusion. Patients were randomized to either early goal directed therapy
(EGDT) or standard therapy.
All patients in both groups underwent arterial in central venous catheterization.
Patients in the standard therapy group treated at the discretion of the treating
physicians according to a protocol that aimed at maintaining central venous pressure
(CVP) between 8 and 12 mmHg, mean arterial pressure (MAP) ≥ 65 mmHg, and
urine output ≥ 0.5 mL/kg/hr. These patients were admitted for inpatient care as soon
as possible.
Patients in the EGDT group were treated according to protocol for at least six hours
in the emergency department prior to admission. This protocol consisted of a 500 mL
bolus of fluid every 30 minutes to achieve a CVP of 8 to 12 mmHg. Vasopressors
were given to maintain a MAP of at least 65 mmHg, when necessary. Vasodilators
were given to maintain a MAP of less than 90 mmHg, when necessary. All patients
underwent continuous central venous oxygen saturation (ScvO2) monitoring. If the
ScvO2 was less than 70%, packed red blood cells were transfused to maintain a
hematocrit of at least 30%; if the ScvO2 was still less than 70% dobutamine was
infused at 2.5 µg per kilogram of body weight and titrated until the oxygen saturation
was 70% or higher.
The primary outcome was in-hospital mortality. Secondary outcomes included organ
dysfunction scores (APACHE II, SAPS II, and MODS), treatments administered, and
the consumption of healthcare resources (duration of vasopressor therapy and
mechanical ventilation and hospital length of stay). A total of 263 patients were
randomized, open 236 completed the initial six-hour study period. There were 133
subjects in the standard therapy group and 130 subjects in the EGDT group.
Limitations:
1. The intervention being assessed was a bundle, including many separate
interventions (ScvO2 monitoring, CVP monitoring, aggressive blood transfusion,
and the use of inotropic infusions). It is unclear which component(s) led to the
observed reduction in mortality.
2. The study was not blinded, and there is a very real risk of performance bias as a
result.
3. Patients in the EGDT received significant more IV fluids in the 6-hour treatment
window, which potentially could have resulted in the observed reduction in
mortality.
4. The protocol required central venous access and arterial cannulation in all
patients in both study arms. This is contrary to standard practice in many
institutions, where central venous and arterial access is reserved for patients
requiring vasopressors.
5. The study evaluated a treatment protocol with multiple components. It is difficult
to ascertain the actual benefit of each individual component.
Bottom Line:
This large, randomized trial conducted at a large academic institution in the US
demonstrated a significant reduction in mortality with the use of early-goal directed
therapy in severe sepsis and septic shock. The use of a treatment protocol as the
intervention makes it difficult to ascertain which individual components contributed
to the efficacy of the protocol. Patients in the EGDT group received nearly 1.5 more
liters of fluid in the first six hours than the usual care group, which may have had a
significant impact on the reduction in mortality. More recent studies have shown no
benefit to EGDT in these patients, likely due to the more aggressive management
utilized in sepsis currently.
Rivers E, Nguyen B, Havstad S, et al; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med Nov 8;345(19):

15. Current literature ProMISE (April 2015) ARISE (October 2014) ProCESS
(May 2014)
Large multi center studies

16. PROCESS trial 31 Academic Centers United States
ProCESS Investigators, Yealy DM, Kellum JA, Huang DT, et al. A randomized trial
of protocol-based care for early septic shock. N Engl J Med May
1;370(18):
Objectives: To determine “whether protocol- based resuscitation was superior to
usual care and whether a protocol with central hemodynamic monitoring to guide the
use of fluids, vasopressors, blood transfusions, and dobutamine was superior to a
simpler protocol that did not include these elements.” (p. 1684)
Methods: This multicenter open label randomized controlled trial was conducted
between March 2008 and May 2013 at 31 academic hospitals in the United States.
Adult patients, aged 18 years or older, in whom sepsis was suspected in the
emergency department, were recruited. Eligibility required two or more criteria for
systemic inflammatory response syndrome, and refractory hypotension or a serum
lactate level of 4 mmol per liter or higher. Refractory hypotension was defined as a
systolic blood pressure less than 90 mmHg or the need for a vasopressor to maintain
a systolic blood pressure greater than 90 mmHg after a fluid challenge.
Patients were randomly assigned in a 1:1:1 ratio, to either early goal directed therapy
(EGDT), standard therapy, or usual care.
 Patients in the EGDT group underwent central venous placement with central
venous pressure and ScvO2 measurement, and were treated according to a
protocol similar to that used by Rivers et al.
 Patients in the standard therapy group were treated with the use of a six-hour
resuscitation instruction set that did not require central venous access, but
involving administration of fluids and vasoactive agents to reach goals for systolic
blood pressure and shop index, as assessed clinically every hour. Patients in this
group received blood transfusion only if the hemoglobin was less than 7.5 g/dL.
 Patients in the usual care group were treated at the discretion of the bedside
providers with no prompting provided.
The primary outcome was in-hospital death from any cause at 60 days. Secondary
outcomes included death from any cause at 90 days, cumulative mortality at 90 days
and one year, the duration of vasopressor requirement, the duration of mechanical
ventilation requirement, and the duration of dialysis during the acute hospitalization.
Additional outcomes included length of hospital stay, length of intensive care unit
(ICU) stay, and hospital discharge disposition.
A total of 1351 patients were enrolled, care of whom withdrew from the study leading
a final cohort of 1341 patients in the final analysis. Of these 439 were randomized to
EGDT, 446 to standard care, and 456 to usual care. At 6 hours, incomplete protocol
adherence was noted in 11.9% of patients in the EGDT group and 4.4% of patients in
the standard therapy group. Thirty patients (6.8%) in the EGDT group did not
undergo central venous catheter placement. A central venous catheter was placed in
56.5% of patients in the standard therapy group and 57.9% of patients in the usual
care. Only 4% of patients in the standard therapy group and 3.5% in the usual care
group underwent serial monitoring of ScvO2, compared to 93.6% in the EGDT
group.
Limitations:
1. This was an open label trial and all clinicians aware of group allocation. It is
possible that significant performance bias on the part of the clinicians would affect
the outcomes.
2. A study coordinator provided time prompts to clinicians involved in the care of
patients in the EGDT and standard therapy groups. This does not reflect real
world care of septic patients in the emergency department and could bias the
results in favor of these two groups.
3. Patients were enrolled after being in the ED a median of over 3 hours, during
which time is likely that they received a significant amount of fluid as well as other
interventions. This could potentially wash out any benefit to EGDT. This likely
explains the significantly higher initial ScvO2 measurements in the EGDT group
compared to those seen in the study by Rivers et al.
Bottom Line:
This large, multicenter trial conducted at 31 academic hospitals in the US compared
early goal-directed therapy to a standard protocolized therapy and usual care for the
management of severe sepsis and septic shock. The results demonstrated no benefit
in either of the protocolized care groups, despite increased use of central venous lines
and increased ICU admission rates. These results suggest that monitoring of ScvO2
and blood transfusion to preset goals do not improve outcomes. It is likely that more
aggressive management of sepsis with larger volumes of fluids and earlier
administration of antibiotics explain the difference in outcomes in this study
compared to the original study by Rivers et al.

17. Arise trial 51 Hospitals Varied Settings 5 Countries
ARISE Investigators; ANZICS Clinical Trials Group, Peake SL, Delaney A,
Bailey M, et al. Goal-directed resuscitation for patients with early septic shock.
N Engl J Med Oct 16;371(16):
Objectives: "to test the hypothesis that EGDT, as compared with usual care, would
decrease 90-day all-cause mortality among patients presenting to the emergency
department with early septic shock in diverse health care settings." (p. 1497)
Methods: This prospective, randomized, open-label trial was conducted between
October 5, 2008 and April 23, 2014 in 51 hospitals in a variety of settings in 5
countries (Australia, New Zealand, Finland, Hong Kong, and Ireland). Adult
patients aged 18 years or older were eligible if they had a suspected or confirmed
infection, two or more criteria of the systemic inflammatory response syndrome, and
either refractory hypotention (systolic blood pressure < 90 mmHg or mean arterial
pressure < 65 mmHg after fluid challenge) or a blood lactate level of 4.0 mmol/L or
more.
Patients were randomized to receive either early goal-directed therapy (EGDT) or
usual care for 6 hours. Patients in the usual care group were treated according to the
discretion of the clinical team, with the caveat that ScvO2 measurement was not
permitted. Patients in the EGDT group were treated by a separate study team, and
all these patients underwent arterial and central venous catheter placement with
continuous ScvO2 monitoring. The EGDT algorithm was followed for the first 6
hours of care.
The primary outcome was death from any cause within 90 days. Secondary outcomes
included survival time up to 90 days, ICU mortality, 28-day mortality, 60-day in-
hospital mortality, emergency department length of stay, ICU length of stay, hospital
length of stay, duration of mechanical ventilation, duration of vasopressor therapy,
duration of renal-replacement therapy, and destination at the time of discharge.
A total of 1600 patients were enrolled, 796 in the EGDT group and 804 in the usual
care group. Nine subjects dropped, leaving 793 patients and 798 patients in the two
groups, respectively. Refractory hypotension was present in 70% of patients in the
EGDT group and 69.8% in the usual care group, while an elevated lactate was found
in 46.0% of patients in the EGDT group and 46.5% in the usual care group.
Limitations:
1. This was an open label trial and all clinicians aware of group allocation. It is
possible that significant performance bias on the part of the clinicians would affect
the outcomes.
2. A separate study team not involved in the clinical care of other patients treated
patients in the EGDT group. This does not reflect real world care of septic
patients in the emergency department and could bias the results in favor of this
group.
3. Patients were enrolled after being in the ED a median just under 3 hours, during
which time they received a median of ~2.5 L of fluid as well as other interventions.
This could potentially wash out any benefit to EGDT. This likely explains the
significantly higher initial ScvO2 measurements in the EGDT group compared to
those seen in the study by Rivers et al.
4. The study was performed in a variety of clinical settings in several different
countries, potentially making it difficult to apply the results to a single large,
academic center (external validity). This does, however, make the results more
generalizable.
Bottom Line:
This large, multicenter, international trial compared early goal-directed therapy with
usual care for the management of severe sepsis and septic shock. The results
demonstrated no benefit to EGDT, despite increased use of central venous catheters,
vasopressors, and blood transfusions for this group. These results suggest that
monitoring of ScvO2 and blood transfusion to preset goals do not improve outcomes.
It is likely that more aggressive management of sepsis with larger volumes of fluids
and earlier administration of antibiotics explain the difference in outcomes in this
study compared to the original study by Rivers et al.

18. Promise trial 56 Sites United Kingdom
Mouncey PR, Osborn TM, Power GS, et al; ProMISe Trial Investigators. Trial
of early, goal-directed resuscitation for septic shock. N Engl J Med Apr
2;372(14):
Objectives: To test "the hypothesis that the 6-hour EGDT resuscitation protocol is
superior, in terms of clinical and cost-effectiveness measures, to usual care in patients
presenting with early septic shock to National Health Service (NHS) emergency
departments in England." (p. 1302)
Methods: This prospective, randomized, open-label trial was conducted between
February 16, 2011 and July 24, 2014 at 56 sites in the United Kingdom. Adult
patients aged 18 years or older were eligible if they had a suspected or confirmed
infection, two or more criteria of the systemic inflammatory response syndrome, and
either refractory hypotention (systolic blood pressure < 90 mmHg or mean arterial
pressure < 65 mmHg after fluid challenge) or a blood lactate level of 4.0 mmol/L or
more.
Patients were randomized to receive either early goal-directed therapy (EGDT) or
usual care for 6 hours. Patients in the usual care group were treated according to the
discretion of the clinical team. Patients in the EGDT group underwent arterial and
central venous catheter placement with continuous ScvO2 monitoring. The EGDT
algorithm was followed for the first 6 hours of care.
The primary outcome was death from any cause within 90 days. Secondary outcomes
included all-cause mortality at 28 days, at time of discharge, and at one year;
Sequential Organ Failure Assessment (SOFA) score at 6 hours and 72 hours;
emergency department length of stay, ICU length of stay, and hospital length of stay;
duration of mechanical ventilation, duration of vasopressor therapy, duration of
renal-replacement therapy; quality of life as measured by the European Quality of
Life-5 Dimensions [EQ-5D] questionnaire at 90 days and one year; and cost at 90
days and one year.
A total of 1260 patients were enrolled. After the exclusion of 9 subjects there were
1251 in the initial analysis (625 in the EGDT group and 626 in the usual care group).
Eight subjects withdrew before 90 days, leaving 1243 subjects in the analysis of
outcomes (623 patients and 620 patients in the usual care group). respectively.
Refractory hypotension was present in 54.1% of patients in the EGDT group and
55.6% in the usual care group, while an elevated lactate was found in 65.4% of
patients in the EGDT group and 63.7% in the usual care group. The mean initial
ScvO2 value measured in the EGDT group was 70%.
Limitations:
1. This was an open label trial and all clinicians aware of group allocation. It is
possible that significant performance bias on the part of the clinicians would affect
the outcomes.
2. Patients were enrolled after being in the ED a median of over 2.5 hours, during
which time they received a median of ~2 L of fluid as well as other interventions.
This could potentially wash out any benefit to EGDT. This likely explains the
significantly higher initial ScvO2 measurements in the EGDT group compared to
those seen in the study by Rivers et al.
3. The study was performed in a variety of clinical settings in the UK, potentially
making it difficult to apply the results to a single large, academic center (external
validity). This does, however, make the results more generalizable.
Bottom Line:
This large, multicenter trial conducted at 56 hospitals in the UK compared early
goal-directed therapy with usual care for the management of severe sepsis and septic
shock. The results demonstrated no benefit to EGDT, despite a higher median length
of stay in the ICU for this group. These results suggest that monitoring of ScvO2 and
blood transfusion to preset goals do not improve outcomes. It is likely that more
aggressive management of sepsis with larger volumes of fluids and earlier
administration of antibiotics explain the difference in outcomes in this study
compared to the original study by Rivers et al.

19. Practice recommendations

20. Pathway of care Rapid Recognition Rapid Initiation of Treatment
3 Hour Bundle
6 Hour Bundle
Reassessment parameters
Critical Monitoring and Targeted Therapies

21. How do we recognize the patient?

22. ems interaction
Retrospective review of admissions between at a single center
13,249 /407,176 EMS encounters resulted in hospitalizations for severe sepsis
Pre-hospital care length of treatment: Average > 45 minutes for those hospitalized with severe sepsis
Received pre-hospital intravenous access (n = 4,842; 37%)
Greater than 40% of all severe sepsis hospitalizations arrived at the emergency department after EMS transport
Mortality: 2,596 (19.6%)
Incidence rate of severe sepsis was 3.3 per 100 EMS encounters
Overall incidence rate of hospitalization with severe sepsis among EMS encounters, as well as pre-hospital characteristics, admission diagnosis, and outcomes. Among 407,176 EMS encounters, we identified 13,249 hospitalizations for severe sepsis, of whom 2,596 died in the hospital (19.6%). The crude incidence rate of severe sepsis was 3.3 per 100 EMS encounters, greater than for acute myocardial infarction or stroke (2.3 per 100 and 2.2 per 100 EMS encounters, respectively). More than 40% of all severe sepsis hospitalizations arrived at the emergency department after EMS transport, and 80% of cases were diagnosed on admission. Pre-hospital care intervals, on average, exceeded 45 minutes for those hospitalized with severe sepsis. One-half or fewer of patients with severe sepsis were transported by paramedics (n = 7,114; 54%) or received pre-hospital intravenous access (n = 4,842; 37%).
EMS personnel care for a substantial and increasing number of patients with severe sepsis, and spend considerable time on scene and during transport. Given the emphasis on rapid diagnosis and intervention for sepsis, the pre-hospital interval may represent an important opportunity for recognition and care of sepsis.
Severe sepsis in pre-hospital emergency care: analysis of incidence, care, and outcome. Seymour CW, Rea TD, Kahn JM, Walkey AJ, Yealy DM, Angus DC, - Am. J. Respir. Crit. Care Med. - December 15, 2012; 186 (12);

23. Is recognition and documentation critical?
Retrospective review of sepsis patients (EMS and Walk-In)
Common Characteristics
Older (71.5 vs 55.7 years old)
Higher Admission Rate (97.2 vs 85.4%)
Higher Frequency of Severe Sepsis (47.4 vs 25.8%)
Higher Frequency of Septic Shock (12.4 vs 4.0%)
Higher Mortality within 28 days (17.9 vs 7.2%)
Not Identified as Septic by EMS
Higher overall mortality (25.7 vs 12.9%)
Temperature is critical to identification as being septic (OR 11.2)
Objective Sepsis is a serious disease leading to high
mortality. Early recognition is important because treatment
is most effective when started quickly. The primary aim of
this retrospective cohort study was to assess how many
sepsis patients are documented as septic by ambulance
staff. The secondary aims were to investigate how many
sepsis patients are transported by ambulance, to compare
them with patients transported otherwise, to investigate
which factors influence documentation of sepsis and to
assess whether documentation influences mortality.
Methods We retrieved all data from ambulance and
emergency department charts of patients who visited the
internist in the emergency department from March 2011
to July 2012.
Results In total, 47.4% (n=363) sepsis patients were
transported by ambulance. These patients were older (71.5
vs years, P<0.0001), admitted more frequently (97.2 vs.
85.4%, P<0.001), significantly more frequently had severe
sepsis (47.4 vs. 25.8%, P<0.0001) or septic shock (12.4 vs.
4.0%, P<0.0001), and died more frequently within 28 days
(17.9 vs. 7.2%, P<0.0001) than those who were transported
otherwise. In 41.9% of ambulance patients, sepsis was not
documented by ambulance staff. Measurement of
temperature was important for documentation of sepsis
(odds ratio 11.2, 95% confidence interval 5.2–24.4). In 32.1%
of ambulance patients, sepsis could have been identified by
assessing vital signs. Mortality in these nondocumented
patients was higher than that in documented patients (25.7
vs. 12.9%, P=0.003).
Conclusion Ambulance patients are seriously ill, but
sepsis is often not documented by ambulance staff.
Nondocumentation is associated with high mortality and
could be resolved by assessing vital signs, particularly the
temperature. European Journal of Emergency Medicine
00:000–000 Copyright © 2015 Wolters Kluwer Health, Inc.
All rights reserved.
European Journal of Emergency Medicine 2015, 00:000–000
Keywords: emergency medical services, prehospital emergency care,
recognition, sepsis
aDepartment of Internal Medicine, Section of Acute Medicine, bDepartment of
Internal Medicine, Section of Geriatric Medicine, cDepartment of Anaesthesiology,
dSchool of CAPHRI, Maastricht University Medical Centre + , Maastricht
University and eRegionale Ambulance Voorziening Zuid-Limburg, Maastricht, The
Netherlands

24. Recognition applied: screening tools

25. Treatment initiation
3 hour bundle

26. Treatment initiation 3 hour bundle Serum lactate measured
Blood culture obtained prior to antibiotics
Broad-spectrum antibiotics within 3 hour of presentation to the ED, or within 1 hour in currently hospitalized patients
Deliver an initial minimum of 30 ml/kg of crystalloid if hypotensive or elevated lactate > 4 mmol/L

27. Does field treatment improve survival in sepsis?
1350 Patients with Severe Sepsis
23% IVF from EMS
7% IV Catha Only from EMS
Median IVF administered: 500mL
Administration of any IVF was associated with reduced hospital mortality (OR 0.46)
Placement of an IV associated with reduced hospital mortality (OR 0.3)
Abstract
Introduction: Prompt treatment of severe sepsis in the Emergency Department reduces deaths, but the role of
prehospital fluid resuscitation is unknown. We sought to determine the risk-adjusted association between prehospital
fluid administration and hospital mortality among emergency medical services (EMS) patients admitted with severe
sepsis.
Methods: We performed a prospective, observational study of patients hospitalized with severe sepsis on admission
among 45,394 adult EMS encounters taken to 15 hospitals from 11/2009 to 12/2010 by a two-tier EMS system in King
County, Washington. The region mandated recording of prehospital intravenous catheter and fluid administration in
prehospital records, along with detailed demographic, incident, physiologic, and hospital adjustment variables. We
determined the effect of prehospital intravenous catheter or fluid versus no catheter or fluid on all-cause mortality
using multivariable logistic regression.
Results: Of all encounters, 1,350 met criteria for severe sepsis on admission, of whom 205 (15%) died by hospital
discharge, 312 (23%) received prehospital intravenous fluid, 90 (7%) received a prehospital catheter alone and 948
(70%) did not receive catheter or fluid. EMS administered a median prehospital fluid volume of 500 mL (interquartile
range (IQR): 200, 1000 mL). In adjusted models, the administration of any prehospital fluid was associated with
reduced hospital mortality (Odds ratio =0.46; 95% Confidence interval: 0.23, 0.88; P =0.02) compared to no prehospital
fluid. The odds of hospital mortality were also lower among severe sepsis patients treated with prehospital intravenous
catheter alone (Odds ratio =0.3; 95% Confidence interval: 0.17 to 0.57; P <0.01).
Conclusions: In a population-based study, the administration of prehospital fluid and placement of intravenous
access were associated with decreased odds of hospital mortality compared with no prehospital catheter or fluid.

28. Lactate sampling- best sample choice
Comparison of microsamples of arterial, venous and capillary blood
Correlations with lab tested arterial sample
Venous sample most effective at early detection of severe sepsis
Objective: We evaluate the capacity of arterial (ABL), peripheral venous (VBL), and capillary (CBL) blood lactate
concentration to early detect the presence of severe sepsis in patients admitted to the emergency department
for a septic syndrome.
Methods: Patients with signs of sepsis presenting to the emergency department were prospectively
enrolled. Blood lactate was measured using a handheld point-of-care analyzer on microsamples of arterial,
peripheral venous, and capillary blood. An arterial blood sample was dispatched to the central laboratory
as a reference measurement.
Results: A total of 103 patients were enrolled in the study, with 63 patients presenting with a severe sepsis.
There was a strong correlation between the point of care and the reference blood lactatemeasurement. The
CBL, VBL, and ABL were all significantly different (3.01±0.29, 2.51±0.21, and 2.03±0.18 mmol/L, respectively;
P b .001). The VBL value was the most efficient to detect early the presence of severe sepsis (areas
under the receiver operating characteristic curves were 0.85 ± 0.04, 0.76 ± 0.05, and 0.75 ± 0.05 for
VBL, ABL, and CBL, respectively; P b .01). Mortality at 28 days was related to the severity of sepsis (28.6%
vs 7.5%) and to the number or organ dysfunctions (P b .01). Arterial blood lactate, VBL, and CBL were all significantly
associated with the 28th-day mortality.
Conclusions: Initial VBL may be used efficiently to assess the severity of sepsis, and it could even be more
effective than ABL and CBL to early detect the presence of severe sepsis.

29. How much can we push? “Sepsis Kit” Blood Cultures 2 grams Ceftriaxone
IVF Administration
Therapy initiated if sepsis suspected by the physician in the ambulance/helicopter
Median time to IVF/ABX: 19 min (18-24)
Median transport time: 56 min (46-67)
Sepsis Diagnosis confirmed in 87.5%
46.4% Severe Sepsis/Septic Shock
Correct ABX: 69%
Median IVF Prior to ED: 2.5 L (1.5-3)
Introduction: Early antimicrobial administration is associated
with increased survival in patients with septic
shock (1). Actual data showed a relevant incidence rate of
severe sepsis with 3.3 per 100 emergency medical service
encounters (2). For this reason, three emergency medical
services (EMS) vehicles and one rescue helicopter were
equipped with a ‘‘Sepsis Kit’’ containing 2 g Ceftriaxone
and two blood culture sets. Objectives: Retrospective observational
study to evaluate the accuracy of diagnosing sepsis
and initiate immediate antimicrobial treatment in the prehospital
setting. Methods: Emergency physicians were asked
to initiate sepsis therapy with the ‘‘Sepsis Kit’’ directly on
site. If sepsis was suspected, the emergency physician obtained
blood cultures and started antimicrobials as well as
fluid therapy on site. The patient was then transferred to the
hospital. The sepsis diagnosis was confirmed by clinical and
laboratory findings in the Emergency Department (ED).
Also, time from first contact with EMS to the first dose of antibiotic
was recorded. Results: Fifty-six patients with suspected
sepsis were admitted to the ED between March 2012
and April Patients’ median age was 73 years (interquartile
range [IQR] 65–82 years), initial body temperature
39.4C (IQR 38.7–39.7C), peripheral oxygen saturation
91% (IQR 86–94%), heart rate 108 beats/min (IQR 91–
126), and mean arterial pressure 102 mm Hg (IQR 80–114).
Sixty-four percent had tachypnea. SAPS2 (Simplified Acute
Physiology Score) was 30 (IQR 26–35). Time until administration
of antimicrobials and intravenous fluids was median
19 min (IQR 18–24). No allergic reaction was observed. Patients
arrived at the hospital after 56 min (IQR 46–67).
Workup in the ED confirmed the sepsis diagnosis in 49 patients
(87.5%). Twenty-six patients (46.4%) had severe sepsis
or septic shock. Most common sources of sepsis were respiratory
(43%), urogenital (21%), skin and soft tissue (8.9%), and
abdominal (8.9%). Initial median values were procalcitonin
0.5 ng/mL (IQR 0.2–2.0), leukocytes 11 Gpt/L (IQR 9–15),
C-reactive protein 65 mg/L (IQR 35–139), and serum lactate
2.1 mmol/L (IQR 1.4–3.6). Sixty-one percent of patients had
a positive blood culture. Ceftriaxone was the appropriate antibiotic
therapy in 69% of patients. Patients received 2.5 L
(IQR 1.5–3.0) crystalloids until admitted to the ED. Only 5
patients (8.9%) were discharged from the hospital on the
same day. Three patients (5.4%) died. Conclusions: The majority
of preclinical sepsis diagnoses proved to be correct.
Furthermore, in about two-thirds of patients, blood cultures
were positive and the initial antibiotic proved to be appropriate.
It seems worthwhile to begin early sepsis treatment in the
prehospital setting. Preclinical initiation of broad antimicrobial
therapy seems to lower the overall mortality rate. Further
studies are necessary

30. 6 Hour Bundle
Vasopressors for MAP less than 65 mmHg after fluid resuscitation
Reassess volume status and tissues perfusion if persistent hypotension (MAP < 65) after initial fluid resuscitation or lactate > 4 mmol/L
Remeasure lactate if initial level elevated

31. Fluid balance Initial aggressive fluid resuscitation is gold standard
Prospective study to determine if fluid balance had an impact on mortality rate in patients with severe sepsis or septic shock
Daily and accumulated fluid balance at 24, 48, 72 and 96 hours with 28-day mortality
Non-survivors demonstrated higher accumulated positive fluid balance at 48, 72 and 96 hours
Higher SOFA scores in the non-survivor group
Objective: The objective was to assess whether fluid balance had a determinant impact on mortality rate in a
cohort of critically ill patients with severe sepsis or septic shock.
Design: A prospective and observational study was carried out on an inception cohort.
Setting: The setting was an intensive care unit of a university hospital.
Patients: Patients admitted consecutively in the intensive care unit who were diagnosed with severe sepsis or
septic shock were included.
Interventions: Demographic, laboratory, and clinical data were registered, as well as time of septic shock onset,
illness severity (Simplified Acute Physiology Score II, Sepsis-related Organ Failure Assessment), and comorbidities.
Daily and accumulated fluid balance was registered at 24, 48, 72, and 96 hours. Survival curves representing
28-day mortality were built according to the Kaplan-Meier method.
Results: A total of 42 patients were included in the analysis: men, 64.3%;mean age, 61.8±15.9 years. Septic shock
was predominant in 69% of the cases. Positive blood cultures were obtained in 17 patients (40.5%). No age, sex,
Sepsis-related Organ Failure Assessment, creatinine, lactate, venous saturation of O2, and troponin differences
were observed upon admission between survivors and nonsurvivors. However, higher Simplified Acute Physiology
Score II was observed in nonsurvivors, P=.016. Nonsurvivors also showed higher accumulated positive fluid
balance at 48, 72, and 96 hours with statistically significant differences. Besides, significant differences (P = .02)
were observed in the survival curvewith the risk of mortality at 72 hours between patients with greater than 2.5
L and less than 2.5 L of accumulated fluid balance.
Conclusions: Fluid administration at the onset of severe sepsis or septic shock is the first line of hemodynamic
treatment. However, the accumulated positive fluid balance in the first 48, 72, and 96 hours is associated with
higher mortality in these critically ill patients.

32. Pediatric considerations: Initial resuscitation
Respiratory Distress/Hypoxemia
Face mask, HFNC, NP CPAP
IV Access
PIV, IO access for IVF and inotropes in absence of central lines
Intubate AFTER Cardiovascular Resuscitation
Resuscitation End Points
Capillary refill < 2 sec, Normal BP for age, Normal pulses with no difference between central and peripheral pulses, warm extremities, urine output > 1mL/kg/hr, normal mental status
Follow PALS guidelines
Evaluate for pneumothorax, Tamponade or endocrine emergencies and reverse as appropriate when shock is refractory to treatment

33. Pediatric considerations: Ongoing Therapy
Empiric antibiotic coverage with blood cultures (but do not delay abx)
Aggressive source control
Consider ECMO for refractory shock with respiratory failure
Corticosteroid administration if fluid refractory, catecholamine resistant or adrenal insufficiency
Monitor sedation drug toxicity (narrower therapeutic window)
Glucose infusions with insulin therapy in newborns (secondary to insulin resistance or failure to produce insulin)
Avoid DVT or Stress Ulcer Prophylaxis in pre-pubertal children

35. Summary
Rapid early recognition- at home, in the clinic, in the ED or on the inpatient unit
Early screening: lactate, SIRS
Rapid IV fluids (30mL/kg IVF bolus challenge)
Early source identification and management (IV abx, broad spectrum, source control)
Vasopressors/Intubation/Critical Care management for persistent shock
Family/Patient Education for at risk conditions