Sepsis 2016: The

Protocol Watch
B. McLean
Clinical Specialist Critical Care
Grady Hospital, ATL, GA
www.barbaramclean.com
bamclean@mindspring.com
“Except on few occasions, the patient
appears to die from the body’s response
to infection rather than from it”

Sir William Osler – 1904

The Evolution of Modern Medicine
 Types of Shock
• Hypovolemic
• Distributive
• Cardiogenic
• Septic
 Types of Shock
Type Pathophysiology Signs & Symptoms

Hypovolemic ↓ PRELOAD: ↓CO, ↑SVR, ↑HR, ↓pulses, delayed cap

intravascular volume loss refill, dry skin, sunken
eyes, oliguria
Distributive ↓AFTERLOD (SVR)

Anaphylactic ↑CO, ↓SVR Angioedema, low BP,

wheezing,resp. distress
Spinal Normal CO, ↓SVR Low BP without
tachycardia; paralysis, h/o
trauma
Cardiogenic ↓CO, variable SVR Normal to ↑ HR, ↓ pulses,
delayed CR, JV
Septic Variable More to come
 Stage of Shock
• Compensated
― Maintains end organ perfusion
― BP is maintained usually by ↑HR

• Uncompensated
― Decrease micro-vascular perfusion
― Sign/symptoms of end organ dysfunction
― Hypotensive

• Irreversible
― Progressive end-organ dysfunction
― Cellular acidosis results in cell death
 Systemic Inflammatory Response
Syndrome (SIRS)
• Widespread inflammation due to infection,
trauma, burns, etc.
• Criteria – requires of the followings
― Core temp >38,5 ⁰C or <36 ⁰C
― Tachycardia (or bradycardia in infants)
― Tachypnea
― Elevated or depressed WBC or > 10% bands
 Severe Sepsis
Recommendation

Adult and Pediatric

Evidence-based studies

1. Early Detection
2. Early Treatment
• Sepsis
Resuscitation
Bundle
3. Monitor reliability and
outcomes

Literature is available upon request!

 Sepsis and Mortality
• Mortality 30-50%
• 1,400 people per day worldwide die from sepsis
• The 28-day mortality rate from sepsis is
similar to 1960’s rate for acute myocardial
infarction
 Sepsis is…..
• Frequent
― 751,000 US cases annually
• Deadly
― 500 death in US DAILY (one every 3 minutes)
• Costly
― Cost per case - $22,000- $57,700
• Increasing
― Estimated increase 1.5% annually
 Epidemiology: What’s up with that…?

Incidence [1993-2001]...a
75% increase in...
of Sepsis
severe sepsis...

Mortality [1993 - 2001]...a

17% reduction in
of Sepsis mortality.

Harrison, D. A., Welch, C. A., & Eddleston, J.

Martin, G. S., Mannino, D. M., Eaton, S., & Moss,
M. (2003). The epidemiology of sepsis in the United
States from 1979 through 2000. New England
Journal of Medicine, 348(16), 1546–1554.
Brun-Buisson, C., Meshaka, P., Pinton, P., Vallet,
B., EPISEPSIS Study Group. (2004). EPISEPSIS:
a reappraisal of the epidemiology and outcome of
severe sepsis in French intensive care units.
Intensive Care Medicine, 30(4), 580–588.
M. (2006). The epidemiology of severe sepsis
in England, Wales and Northern Ireland, 1996
to 2004: secondary analysis of a high quality
clinical database, the ICNARC Case Mix
Programme Database. Critical Care, 10(2),
R42.
 Immune Response
• Initial Response (Innate)
― Neutrophils
― Monocytes
― Survival depends on success of neutrophils
• Secondary Response (Adaptive)
― Antibody production
― Takes 4-7 days for initial exposure
• 1-2 days for subsequent exposures
Pathophysiology: Silent and
Deadly
 Types of Shock
• Hypovolemic Shock
- Loss of blood colume (plasma +
RBCs)
• External-surgery or trauma
• Internal-GI bleeding
• Cardiogenic Shock
- Hearts inability to pump
appropriate amount of blood
- Decreased Cardiac Output
• Obstructive Shock
- Subtype of Hypovolemic Shock
- Increase pressure of the jugular
vein → distended jugular vein
Septic Shock is
Combo Shock
• Neurogenic Shock
- Injury of the spine
- Loss of cardiac nerve fibers from
the sympathetic nerve fibers at
T1-T4 resulting in profound
bradycardia
- Diphoretic Skin
• Anaphylactic Shock
- Angioderma like recation
- Large Eruption or bumpy skin
- Edema, Massive Swelling
- Constricted Airways; Swollen
throat; Breathlessness and cough
- Weak or rapid pulse
 Pathophysiology of Sepsis
• The immune system
• Inflammation
• Vasodilatation
• ↑ vascular permeability
• ↑ O2 demand
• Anaerobic respiration and lactate
• Abnomal clotting and DIC
Cunnean J, Cartwright M. (2004) The Puzzle of Sepsis. AACN Clinical Issues Volume 15, Number 1, pp. 18-44

Baron RM, Baron MJ, Perrella MA. Pathology of sepsis: are we still asking the same questions? Am J Respir Cell Mol Biol. 2006; 34:
129-134

Robertson CM, Coopersmith CM. The systemic inflammatory response syndrome. Microbes infact 2006; 8: 1382-1389

Aird WC. The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome. Blood. 2003 May 15;101 (10):
3765-77
 Sepsis is an extremly complex response
syndrome evoked by microbial agents:
• Endothelium damage, microvascular dysfunction,
impaired tissue oxygen uptake with consecutive
organ damage
• Immunosuppression, anergy
• The sepsis is an auto-destructive process that
precipitates the dysfunction of multiple organ:
MODS (multiple organ dysfunction syndrome)
Cunnean J, Cartwright M. (2004) The Puzzle of Sepsis. AACN Clinical Issues Volume 15, Number 1, pp. 18-44

Baron RM, Baron MJ, Perrella MA. Pathology of sepsis: are we still asking the same questions? Am J Respir Cell Mol Biol. 2006; 34:
129-134

Robertson CM, Coopersmith CM. The systemic inflammatory response syndrome. Microbes infact 2006; 8: 1382-1389

Aird WC. The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome. Blood. 2003 May 15;101 (10):
3765-77
 Microvascular Plugging in Sepsis

• Decreased red cell deformability in inflammatory states

• Microvascular sequestration of activated leukocytes and
platelets
• Sepsis is a Procoagulant, Pro inflammation State
- The extrinsic pathway may be activated in sepsis by
upregulation of Tissue Factor on monocytes or endothelial
cells
- Fibrinolysis appears to be inhibited in sepsis by
upregulation of Plasminogen Activator Inhibitor
Pathophysiology of Severe Sepsis and
Indirect ARDS
Pathophysiology of Severe Sepsis
 Clinical Findings
• What is the first physiological factor in the
development of shock?
• Cells are hypermetabolic VO2
• Delivery inadequate to needsDa02
• So, what are the first symptoms you would expect to
find?
- ↑ respiratory rate: compensating for metabolic acidosis
- ↑ heart rate compensating for inadequate cardiac output
 Clinical Findings
• As shock progresses, what physiological effects are
seen?
• End-organ perfusion diminishes
• What symptoms would you expact to see?
- Altered mental status
- Decreased urine output
- Decreased blood pressure
- Mesenteric ischemia
- Inflammatory ARDS
“Our arsenals for fighting off bacteria are so
powerful, and involve so many different
defense mechanisms, that we are more in
danger from them than from the invaders”.

“ We live in the midst of explosive devices; we are

mined!”

Lewis Thomas – 1972

Germs, New England Journal of Medicine
Coagulation and Impaired Fibrinolysis in
Severe Sepsis

Reprinted with permission from the National Initiative in Sepsis Education (NIPS)
 Septic Shock
Septic
Shock
Sepsis
• Temp • Sepsis
instability • SIRS • Sepsis • Hypotension
• Tachycardia • Infection • Hypotension after 40 ml/kg
•Tachypnea (presumed or • End organ • Pressor
•WBC ↓ or ↑ known) dysfunction requirement
Severe • Further evidence
Sepsis of low perfusion
SIRS
(lactate, oliguria,
AMS)
Using our language correctly
 SIRS-It All Starts Out So Innocent
• Systemic inflammatory Response Syndrome
- Manifested by 2 or more of the following Clinical presentations:
• Temperature > 38⁰C (100 4F) OR < 36⁰C (96,8 F)
• Heart rate > 90 per minute (contextual)
• RR > 20/min
- And Validated by 1 or more of the following lab results
• WBC 12,000 or >10% bands
• Increased PCT Members of the American College of Chest Physicians/Society
• Positive cultures of Crit Care Med Consensus Conference Committee: American
College of the chest Physician/Society of crit care Med
• PaC02 < 32 mmHg Consensus Conference: Definition for sepsis and organ failure
and guide lines for the use of innovative therapies in sepsis. Crit
Care Med 1992; 20: 864-874

Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H,

Opal SM, et al. (2013). Surviving sepsis campaign:
International guidelines for management of severe sepsis and
septic shock; 2012. Crit Care Med. 20013; 41(2): 580-637
 Sepsis: 1991 ACCP / SCCM Definitions
(no change in 2015)
• Infection
- Inflammatory response to microorganisme
- Invasion of normally sterile tissues
• Systemic Inflammatory Response Syndrome (SIRS)
- Two or more of the following :
• Core temperature >38 ⁰C or < 36 ⁰C (>100.4 ⁰F or < 96.8 ⁰F)
• Elevated heart rate (90 beats/min)
• Respiratory rate > 20 breaths/min or PaCO2 < 32 mmHg or
mechanical ventilation for acute respiratory process
• WBC count > 12,000/mm3 or < 4,000/mm3 or > 10% immature
neutrophils
 New Sepsis Definition
qSOFA

• An alteration in mental status (not the GCS)

• A decreased in SBP of less than 100 mmHg
• A respiratory rate > 22 bpm
 Key Different In New Definition

• Sepsis as infection and 2 or more SIRS is now just an

infection
• Severe sepsis is now sepsis
• Septic shock is
- Blood lactate < 2 mmol/L despite volume resuscitation
- Hypotension that persists after fluid resuscitation and
reuires vasopressors
• Sepsis definition now will carry a higher risk of death and
increased ICU LOS
 Rationale for New Definition

• Based on review of 2 million patients in

sepsis studies
• SIRS based on expert opinion
• SIRS should still be used when evaluating
The New Surviving Sepsis Campaign
Bundles-April 2015
New Volume and Tissue Perfusion
Elements
 Definition-Sepsis
• Sepsis
- SIRS PLUS a documentaded or suspect
infection
 Severe Sepsis: Definded
• Severe Sepsis-Sepsis with evidence of organ
dysfunction
• What is organ dysfunction?
- Respiratory PaO2/Fi02 ratio < 300
- Hepatic-Bilirubin > 4
- Hematologic- INR > 1.5 or platelets <100 K
- Neurologic – GCS 10-12
- Renal- Creatinine > 2.0
- Lactic Acid-Greater than 4
Identifying Acute Organ Dysfunction as
a masker of severe sepsis
Definition – Septic Shock
The Sepsis Continuum; FIRST, identify
Sepsis can be subtle until it so obvious
you can’t miss it
We thought we were on the right
track…..

Changing times
Changing practice
Guidelines for Sepsis
 The 2013 update for the Surviving Sepsis
Campaign
• Key Points
- Dobutamine infusion trial up to 20 μg/kg/minute administered or added to
vasopressor ijn the case of myocardial dysfunction or ongoing signs of
hypoperfusion (grade 1C)
• Corticosteroids
- No corticosteroids in the absence of refractory shock (grade 1D)
• Blood Products
- After tissue hypoperfusion is corrected, red blood cell transfusion only when
hemoglobin concentrartion decreases to < 7.0 g/dL, to a terget hemoglobin
concentration of 7.0-9.0 g/dL in adults (grade 1B)
- see more at :
http://www.jwatch.org/em201302220000001/2013/02/22/new-surviving-sepsis-
campaign-guidelines#sthash.8IEaVd6e.dpuf

Dellinger RP et al. Surviving sepsis campaign; International guidelines for management of severe sepsis and septic
shock, 2012. Crit Care Med 2013 Feb; 41:580. – See more at:
http://www.jwatch.org/em201302220000001/2013/02/22/new-surviving-sepsis-campaign-
guidelines#sthash.8IEaVd6e.dpuf
 The 2013 update for the Surviving Sepsis Campaign
• Key Points
• Resuscitation Goals In First 6 hours
- Central venous pressure 8 to 12mmHg (grade 1C)
- Mean arterial pressure (MAP) ≥ 65 mmHg (grade 1 C)
- Urine output ≥ 0.5 mL/kg/hour (grade 1 C)
• Antimicrobials
- Intravenous administration within 1 hour of recognition of septic shock (grade 1B) and severe sepsis without septic
shock (grade 1C)
• Fluids
- Crystalloids as first choice for initial fluid resuscitation (grade 1B)
- Initial minimum crystalloid challenge of 30 mL/kg (grade 1C)
• Vasopressors and Inotropes
- Norepinephrine as first choice (grade 1B) with epinephrine added or potentially substituted when adequate blood
pressure cannot be maintained (grade 2B)
- Phenylephrine not recommended except if norepinephrine is associated with serious arrythmias, if cardiac output is
high and blood pressure persistently low, or as salvage therapy when MAP target is not achieved (grade 1C)

Dellinger RP et al. Surviving sepsis campaign; International guidelines for management of severe sepsis and septic
shock, 2012. Crit Care Med 2013 Feb; 41:580. – See more at:
http://www.jwatch.org/em201302220000001/2013/02/22/new-surviving-sepsis-campaign-
guidelines#sthash.8IEaVd6e.dpuf
 The Guidelines
• 48 pages with NO magic bullets
• Very few spesific therapies directed at the early
stages of sepsis pathophysiology
• Numoreous important recommendations (and
numerous controversial ones)
• Requires repetitive, complex assessments
• Many interventions are time-sensitive
Sepsis Without Walls; Ensuring All Patients Receive Optimal, Time-Sensitive Care
September 25, 2015
The Johns Hopkins University School of Medicine
Baltimore, Maryland, USA

However, while we wait for the policymakers to stand up and take notice, there is
another way to address this fast-killing disease. Already there are many hospitals
globally committed to setting up schemes that introduce briefings on Sepsis for
hospital workers and introductions into learning who to target and screen for sepsis
in the emergency department. These schemes can then feedback on how to better
improve the rates of mortality amongst Sepsis victims by identifying and how to
best treat the first stages of the disease in the Golden Hour.

Treating Sepsis in the “Golden Hour” is a real opportunity to reduce the drastic
levels of eeople who are still dying or are seriously affected by Sepsis. However,
the key to treatment within this crucial time period comes through awareness. Only
a global approach to tackling Sepsis and reinforcing recognition at every level will
drive an initiative to reduce the amount of deaths in every country.
 Always was and always will
• Identify
• Anibiotics and nidus control
• Volume resuscitation
• Inotropic
 The Bundles
• SURVIVING SEPSIS CAMPAIGN BUNDLES

TO BE COMPLETED WITHIN 3 HOURS:

1) Measure lactate level
2) Obtain blood cultures prior to administration of antibiotics
3) Administer broad spectrum antibiotics
4) Administer 30 ml/kg crystalloid for hypotension or lactate
≥ 4 mmol/L
 The Bundles
• SURVIVING SEPSIS CAMPAIGN BUNDLES

TO BE COMPLETED WITHIN 6 HOURS:

5) Apply vasopressors (for hypotension that does not respon to initial fluid
resuscitation) to maintain a mean arterial pressure (MAP) ≥ 65 mmHg
6) In the event of persistent arterial hypotension despite volume resuscitation
(septic shock) or initial lactate ≥ 4 mmol/L (36 mg/Dl):
- Measure central venous pressure (CVP)*
- Measue central venous oxygen saturation (ScvO2)*
7) Remeasure lactate if initial lactate was elevated*

*Target for quantitative resuscitation included in the guidelines are CVP of ≥ 8

mmHg; ScvOs ≥ 70%, and normalization of lactate.
 MOST Important “Time Zero”
• Time Zero = time of presentation
- ED, Medical Floors, ICU
• Both bundles time based
• Most important time based elements:
- Antibiotic timing
- Resuscitation timing (EGDT)
The resuscitation challenge
Protocolized Australasion The
Care for Early Resuscitation in Protocolized
Septic Shock Sepsis Evaluation Management in
(ProCess) (ARISE) Sepsis
 ProMise, ProCess and ARISE Trials
• Key points
- Fluid administration similar in both control and experimenttal
groups
- Vasopressor use similar in both groups
- Antibiotic administrated similarly in both gorups
- Lactate obtained in both groups
- Mortality rates (<20%) is not s common outside centers with
well designed sepsis recognition/management programs
• Problems-Antibiotics and fluids given in both control and
experimental groups within 3 hours.
 Take Away Points
• If patients are
- Identified early
- Receive antibiotics EARLY
- Receive IVF EARLY
• Then ScvO2 and CVP monitoring does not seem to
add a benefit
• BUT EGDT with Scvo2 not really tested since
resuscitation had already occurred
 Types of Fluids
• Is normal saline normal ?
• Lactated Ringers vs normal saline
comparable?
 Setting Goals
• Discuss goals of care and prognosis with patients and
families (grade 1B).
– Sepsis has a high mortality rate. Families should understand and
recognize that determining what the patient’s wishes are may
help dictate the aggressiveness of theraphy
• Incorporate goals of care treatment and end-of-life care
planning, utilizing palliative care principles where
appropriate (grade 1B).
• Address goals of care as early as feasible, but no later
than within 72 hours of ICU admission (grade 2C).
Implementing Sepsis Protocols
 Benefits and Barriers
• Improved
- Patient identification
• Coding and reimbursement
• SOI/ROM
- Reduced mortality
- Improved compliance with bundles
• Barriers
- Multidisciplinary cooperation
- Funding
- Education
 Goals in resuscitation
• Initial fluid resuscitation:
• CVP 8-12, MAP >65, UOP 0,5 ml/kg/hr, ScVO2 70% and
Lactate Clearance.
• Give enough volume to maximize stroke volume. Start with
20cc/kg in most patients. Goal?
• Give vasopressors to raise the MAP enough to maintain
adequate end-organ perfusion.
• Assessment of Cardiac Function
• UOP and Lactate Clearance are nice global indication of
success
 Resuscitation
• Crystalloids are favored as the initial fluid
• Hydroxyethyl straches are likely harmful
• Albumin may have a role, particularly if a lot
of fluid is given
• A lower Hb target (-7) is generally accepted
 Four process or outcome measures to
monitor on an ongoing basis

Select from the universe of measures; or – Create

your own measures

Two of the measure must be clinical

Other two measures can be clinical

Administrative, utilization, or satisfaction
 Examples
Repeat lactate within 6 hours if initial
Lactate > 2.0

Order lactates with every blood culture order

Blood cultures drawn prior to antibiotic

Administration

Fluids given within 3 hours of time zero

 CMS Core Measure
• Measure Description: This measure will focus on patients
aged 18 years and older who present with symptoms of severe
sepsis or septic shock. These patients will be eligible for the 3
hour (severe sepsis) and/or 6 hour (septic shock) early
management bundle.
• Numerator Statement: If :
- measure lactate level
- obtain blood cultures prior to antibiotics
- administer broad spectrume antibiotics
- administer 30 ml/kg crystalloid for hypotension or lactate >=4
mmol/L
 Screening
• Routine screening of potentially infected
seriously ill patients for severe sepsis to allow
earlier implementation of therapy (grade 1C)
• Hospital based performance improvement
efforts in severe sepsis
 Definiting the severity of sepsis
• Importance of looking for organ failure is self
evident
• Identification of “shock” dramatically alters
the treatment and mortality
– Blood Pressure, Response to Fluid, LACTATE
 Antibiotics
• Multiple large, observational studies have shown the
time to administration of antibiotics to be strongly
associated with improve survival.

• I’m not aware of a single physician that recommends

withholding or slowing down the time to antibiotics in
a patient with severe sepsis.

• Our “time to needle” or “door to ballon” metric.

Source Control
 Source Control
• Don’t be satisfied with a diagnosis of sepsis
and no source.

• If a source exists and is potentially

removeable, get the ball rolling
 Inotropes
• Improves Cardiacs Output
- Must be on board if failed therapy with fluids
- Increase risk of atrial, ventricular arrhytmias
• Increases demand of Myocardial O2 in pt.s
with CAD-Caution
- Dobutamine
- Milrinone, Nesiritide-Not used in Septic Shock
 Inotropes
• Dobutamine
– β-adrenergic inotropic agent
– β1 > β2 ≥ α 1
– Vasodilatation due to stimulation of the beta
receptor
– Can be an add on to nor-epinephrine in sepsis
– 2.5-5 mcg/kg/min
 Vasopressors
• Must be on board if failed therapy with fluids
• Considered when Systolic BP < 90 mmHg,
MAP <60-65 mmHg
• Titrate slowly to achieve MAP w/o impairing
SV
• Norepinephrine, Epinephrine, Phenylephrine
 Vasopressors
• Norepinephrine (Levophed)
– First line agent for septic shock
– Stimulates α 1,2 > β 1
– Increase MAP by vasoconstriction on peripheral
vascular beds
 Vasopressors
• Epinephrine (Adrenaline)
– Nonspesific α and β-adrenergic agonist
– Significant peripheral vasoconstriction- Last line therapy
for refractory shock
– 1-10 mcg/min
• Phenylephrine (Neosynephrine)
– Selective α 1-agonist
– Rapid onset, short duration, and primary vascular effects,
and it is least likely to produce tachycardia
– Limitted use-preferred in tachyarrhythmia
 How do We Identify Sepsis Now?
• In absence of biomarkers, must rely on crude
physical indicators
 Euipment to Evaluate Patient

• Don’t take vital signs, take a lactate

– Point of care
• Evaluation of ventilation
– Capnography
– Blood Gases
• Point of care
• Hemodynamic Assessment
– Stroke volume
What Type of Hemodynamic Monitoring?

• CVP and PAOP should never be used in isolation

– Inconsistent in revealing information about volume
and flow
– Marik et al. Based on the results of our systemic
review, we believe that CVP should no longer be
routinely measured in the ICU, operating room, or
emergency department.
 Temporal order of events
(each event can take minutes to hours)

1. Stroke volume falls

- Heart rate compensates to keep cardiac output normal
Many reasons for heart rate to increase
2. Cardiac output falls
- Heart rate compensation fails
- Vasoconstriction (increase in SVR), BP remains unchanged
3. Increased oxygen extraction of hemoglobin
- Peripheral initially (StO2)
- Central later (ScvO2)
4. Blood Pressure, urine output change
 Question?
• If we recognized Possible Sepsis Early, treated
IMMEDIATELY with fluids and antibiotics , could we
reduce mortality rate?
• Reduce Mortality by 20% system wide
– Sepsis most frequent diagnosis associated with mortality
system-wide
 What to do....?
• Single most important issue is failure to
identify!
• STAT….fluids, cultures, antibiotics and source
control

Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and
shock. Nengl J Med 2001; 345:1368-1377

Kolief MH, Sherman G, Ward S, et al. Inadequate antimicrobial treatment of infections: a risk factor
for hospital mortality among critically ill patients. Chest 1999;115:462-474
McLean Model Sepsis Identification
 Severe Sepsis Recommendations
Adult and Pediatric
Evidence-based studies

1. Early Detection
2. Early Treatment
3. Sepsis Resuscitation
Bundle
4. Monito reliability and
outcomes
 SSC/NQF Bundle : Sepsis 0500
TO BE COMPLETED WITHIN 3 HOURS OF TIME OF
PRESENTATION:
1. Measure lactate level
2. Obtain blood cultures prior to administration of antibiotics
3. Administer broad spectrum antibiotics
4. Administer 30 ml/kg crystalloid for hypotension or lactate
≥ 4 mmol/L
“time of presentation” is defined as the time of triage in the Emergency
Department or, if presenting from another care venue, from the earliest chart
annotation consistent with all elements severe sepsis or septic shock ascertained
through chart review.
 SSC/NQF Bundle : Sepsis 0500
TO BE COMPLETED WITHIN 6 HOURS:
5) Apply vasopressors (for hypotension that does not respon to initial fluid
resuscitation) to maintain a mean arterial pressure (MAP) ≥ 65 mmHg
6) In the event of persistent arterial hypotension despite volume resuscitation
(septic shock) or initial lactate ≥ 4 mmol/L (36 mg/Dl):
- Measure central venous pressure (CVP)*
- Measue central venous oxygen saturation (ScvO2)*
7) Remeasure lactate if initial lactate was elevated*

*Target for quantitative resuscitation included in the guidelines are CVP of ≥ 8

mmHg; ScvOs ≥ 70%, and normalization of lactate.
 2015 Guideline: Small Changes
• TIME zero!
• Early antibiotics
• Aggressive fluids
– Colloids and crystalloid, consider plasmalyte
• Levophad, Epinephrine and Vasopressin
• Inotropics
• Glucose control at BS 190 x 2
• Corticosteroids 200-300 continuously
• Use of dynamic measures for flluids resuscitation
• Dobutamine moves up the ladder
 Putting It All Together
• Protocol will change with literature
• Early goal directed therapy still valid/Likely to change
• Early aggressive antibiotics remain key/Resistance
emerging
• Glycemic control still has benefit
• Consider adrenal insufficiency in fluid and vasopressor
refractory shock
• Low tidal volume remains the best practice
• Exciting new therapies/monitoring on horizon
 Just Do It!
• Identify Sepsis as early as possible
• Broad Spectrum antibiotics ASAP and identify
source(s) of infection
• Identify severity: Vitals, mental status, UOP,
LACTATE, other labs
• Volume and physiologic resuscitation ASAP with
GOALS
• Tweak your system so these things happen FAST
 Acute Phase
• Identify Sepsis as early as possible
• Broad Spectrum antibiotics ASAP and identify
source(s) of infection
• Identify severity: Vitals, mental status, UOP,
LACTATE, other labs
• Volume and physiologic resuscitation ASAP with
GOALS
• Tweak your system so these things happen FAST
 Sepsis Identification

• Train all providers

• Vital sign/Laboratory alerting systems

• ?Biomarkers
 Surviving Sepsis Campaign

Within 3 Hours…
1. Check Lactic Acid
2. Send Blood Cultures
3. Give Antibiotics
4. 30 mL/kg IVF (if low BP/HIGH Lactate)
 Surviving Sepsis Campaign
CVP ScvO2 Cardiac US Passive Leg Raise

Within 6 Hours…
1. Vasopressors if MAP <65 mmHg

2. Re-assess Volume Status & Tissue Perfusion

3. Re-Check Lactic Acid (Unless Initially Normal)