Surviving Sepsis

Campaign
International
Guidelines for
Management of
Severe Sepsis and
Septic Shock: 2016
 Why we are spending time on
sepsis?
Mortality

Sepsis:
30% - 50%

Septic
Shock:
50% - 60%
 Why we are spending time on
sepsis?
Incidence 2500 Mortality
30 00
0

25 2000
0 00

20

Deaths/Year
1500
0 00
Cases/100,000

15
0 1000
00
10
0 500
00
5
0
0
0 AID Brea A SEPS
AID Brea 1st seps S st MI IS
S st MI is Canc
er
Canc
er
 Why the burden of sepsis
increasing?
 Increased geriatric population
 Increasing number of immunocompromised host
 Increasing drug resistant organism
 Increasing metabolic disorder
The third International Consensus 2016
Definition for Sepsis ( Sepsis 3)

SEPSIS IS A
 LIFE THREATENING
 ORGAN DYSFUNCTION
 CAUSEDBY A
DYSREGULATED HOST
RESPONSE
 TO INFECTION
Dysregulated host response leads to..
How to suspect sepsis?
Suspect sepsis…
 Change in international guideline

Sepsis 2
 Sepsis = SIRS + Infection
 Infection sepsis
severe sepsis septic
shock MODS
Sepsis 3
 Sepsis= infection + >2 SOFA score
from baseline
 NO Severe sepsis
SIRS to SOFA
SOFA SCORE VARIABLES
 Sequential Organ Failure Assessment
(SOFA)
► Previously known as Sepsis-related Organ Failure Assessment
because it was initially developed in 1994 to describe the degree
of organ dysfunction associated with sepsis in a mixed, medical-
surgical ICU patients.

► Nowadays, it has since been validated to describe the degree

of organ dysfunction in
various ICU patient groups with organ dysfunctions not due to
sepsis.

► The SOFA score involves six organ systems (respiratory,

cardiovascular, renal, hepatic, central nervous, coagulation), and
the function of each is scored from 0 (normal function) to 4 (most
abnormal), giving a possible score of 0 to 24.
 Sequential Organ Failure Assessment
(SOFA)
► Mortality rate increases as number of organs with dysfunction
increases.

► Unlike other scores, the worst value on each day is recorded.

► A key difference is in the cardiovascular component; instead of

the composite variable, the SOFA score uses a treatment-
related variable (dose of vasopressor agents).
Sequential Organ Failure Assessment (SOFA)

► Maximal (highest total) SOFA score: is the sum of highest

scores per individual during the entire ICU stay. A score of
>15 predicted mortality of 90%.

► Mean SOFA score (ΔSOFA): is the average of all total SOFA

scores in the entire ICU stay. ΔSOFA for 1st 10 days is significantly
higher in non-survivors.

► Delta SOFA score: maximum SOFA - admisiion s SOFA

Sequential Organ Failure
Assessment
qSOFA for Non ICU patients with
Infection –
early recognition of
severity
 SEPTIC SHOCK

 Septicshock is a subset of sepsis in

which profound circulatory, cellular
and metabolic abnormalities are
associated with a greater risk of
mortality than sepsis alonesepsis
alone
 CLINICAL CRITERIA FOR SEPTIC
SHOCK 2016

DESPITE ADEQUATE FLUID RESUSCITATION

VASOPRESSOR NEEDED TO MAINTAIN MAP > 65 mmHg
LACTATE >2 MMOL/LIT
 How is lactate produced?

If pyruvate production > oxidation in CAC then lactate

formation increases
 Management of Severe Sepsis

Initial Antibiotic
Resuscitation Diagnosis Therapy

Source
Fluid Therapy Vasopressors
Control

Corticosteroids Glucose
Blood Product
Control

Bicarbonate
Therapy
Initial
Resuscitation
 Initial Resuscitation
Sepsis and septic shock are medical
emergencies, and we recommend that
treatment and resuscitation begin immediately
(best practice statements, BPS).
In the resuscitation from sepsis-induced
hypoperfusion, at least 30 mL/kg of IV
crystalloid fluid be given within the first 3 h
(strong recommendation, low quality of
evidence).
 Initial Resuscitation
Following initial fluid resuscitation, additional
fluids be guided by frequent reassessment of
hemodynamic status (BPS).
Remarks Reassessment should include a thorough
clinical examination and evaluation of available
physiologic variables (heart rate, blood pressure,
arterial oxygen saturation, respiratory rate,
temperature, urine output, and others, as available)
as well as other noninvasive or invasive monitoring,
as available.
 Initial Resuscitation
An initial target MAP of 65 mmHg in
patients with septic shock requiring
vasopressors (strong recommendation,
moderate quality of evidence).
Guiding resuscitation to normalize lactate
in patients with elevated lactate levels as a
marker of tissue hypoperfusion (weak
recommendation, low quality of evidence).
 Application of Fluid Resuscitation in Adult Septic Shock
Sepsis-induced hypotension or lactate > 4 mmol/L
(Based on SSC bundle and CMS threshold)

No high flow oxygen and Pneumonia or ALI with high ESRD on hemodialysis
No ESRD on dialysis or CHF flow oxygen requirements or CHF

Rapid infusion Not intubated/ Intubated/

of 30 ml/kg mechanically ventilated mechanically ventilated Total of 30 ml/kg crystalloid*
Crystalloid* with frequent reassessment
of oxygenation
Consider Rapid infusion
If
intubaon/mechanical of 30 ml/kg
Yes
venlaon to facilitate crystalloid *
30 ml/kg crystalloid *
If no
Total of 30 ml/kg with
frequent reassessment of
oxygenaon

Considerations post 30ml/kg crystalloid infusion

1. Continue to balance fluid resuscitaon and vasopressor dose with attention to maintain tissue perfusion and minimize interstitial edema
2. Implement some combinaon of the list below to aid in further resuscitaon choices that may include addional fluid or inotrope therapy
• blood pressure/heart rate response,
• urine output,
• cardiothoracic ultrasound,
• CVP, ScvO2,
• pulse pressure variaon
• lactate clearance/normalizaon or
• dynamic measurement such as response of flow to fluid bolus or passive leg raising
3. Consider albumin fluid resuscitaon, when large volumes of crystalloid are required to maintain intravascular volume.
Diagnosis
 Diagnosis
• Appropriate routine microbiologic cultures
(including blood) be obtained before
starting antimicrobial therapy in patients
with suspected sepsis or septic shock if
doing so results in no substantial delay in
the start of antimicrobials (BPS).
•Remarks Appropriate routine microbiologic
cultures always include at least two sets of blood
cultures (aerobic and anaerobic).
Antimicrobial
Therapy
 Antimicrobial Therapy
• Administration of IV anti-microbials be
initiated as soon as possible after recognition
and within 1 h for both sepsis and septic
shock (strong recommendation, moderate
quality of evidence; grade applies to both
conditions).
 Antimicrobial Therapy
• Empiric broad-spectrum therapy with one or
more antimicrobials for patients presenting with
sepsis or septic shock to cover all likely
pathogens (including bacterial and potentially
fungal or viral coverage) (strong
recommendation, moderate quality of
evidence).
• Empiric antimicrobial therapy be narrowed once
pathogen identification and sensitivities are
established and/or adequate clinical
improvement is noted (BPS).
 Antimicrobial Therapy
Antimicrobial treatment duration of 7–10
days is adequate for most serious
infections associated with sepsis and
septic shock (weak recommendation, low
quality of evidence).
 Antimicrobial Therapy
Measurement of procalcitonin levels can be
used to support shortening the duration of
antimicrobial therapy in sepsis patients (weak
recommendation, low quality of evidence).
Procalcitonin levels can be used to support
the discontinuation of empiric antibiotics in
patients who initially appeared to have sepsis,
but subsequently have limited clinical
evidence of infection (weak recommendation,
low quality of evidence).
Source
Control
 Source Control
A specific anatomic diagnosis of infection
requiring emergent source control be
identified or excluded as rapidly as
possible in patients with sepsis or septic
shock, and that any required source
control intervention be implemented as
soon as medically and logistically practical
after the diagnosis is made (BPS).
 Source Control
• Prompt removal of intravascular access
devices that are a possible source of sepsis or
septic shock after other vascular access has
been established (BPS).
 Fluid Therapy
• Crystalloids as the fluid of choice for initial
resuscitation and subsequent intravascular
volume replacement in patients with sepsis
and septic shock (strong recommendation,
moderate quality of evidence).
• Against using hydroxyethyl starches
(HESs) for intravascular volume replacement in
patients with sepsis or septic shock (strong
recommendation, high quality of evidence).
 Fluid Therapy
Using albumin in addition to crystalloids for
initial resuscitation and subsequent
intravascular volume replacement in
patients with sepsis and septic shock
when patients require substantial amounts
of crystalloids (weak recommendation, low
quality of evidence).
 Vasopressors
Norepinephrine as the first choice
vasopressor (strong recommendation,
moderate quality of evidence).
Adding either vasopressin (up to 0.03 U/min)
(weak recommendation, moderate quality of
evidence) or epinephrine (weak
recommendation, low quality of evidence) to
norepinephrine with the intent of raising MAP
to target, or adding vasopressin (up to 0.03
U/min) (weak recommendation, moderate
quality of evidence) to decrease
norepinephrine dosage.
 Vasopressors
Using dopamine as an alternative
vasopressor agent to norepinephrine only
in highly selected patients (e.g., patients
with low risk of tachyarrhythmias and
absolute or relative bradycardia) (weak
recommendation, low quality of evidence).
Against using low-dose dopamine for renal
protection (strong recommendation, high
quality of evidence).
 Vasopressors
Using dobutamine in patients who show
evidence of persistent hypoperfusion
despite adequate fluid loading and the use
of vasopressor agents (weak
recommendation, low quality of evidence).
 Vasopressors
• All patients requiring vasopressors have an
arterial catheter placed as soon as practical if
resources are available (weak
recommendation, very low quality of
evidence).
 Vasopressor Use for Adult Sepc Shock
(with guidance for steroid administraon)
Iniate norepinephrine (NE) and trate up to 35-90 μg/min
to achieve MAP target 65 mm Hg

MAP target MAP target not achieved

achieved and judged
poorly responsive to NE

Add vasopressin up to
Connue norepinephrine alone or
0.03 units/min to achieve
add vasopressin 0.03 units/min
MAP target*
with ancipaon of decreasing
norepinephrine dose

MAP target MAP target

* Consider IV steroid administraon achieved not achieved
** Administer IV steroids
*** SSC guidelines are silent on phenylephrine
Notes: Add epinephrine up to
• Consider dopamine as niche vasopressor in the presence 20-50 μg/min to achieve MAP
of sinus bradycardia. target**
• Consider phenylephrine when serious tachyarrhythmias
occur with norepinephrine or epinephrine.
• Evidence based medicine does not allow the firm
establishment of upper dose ranges of norepinephrine, MAP target MAP target
epinephrine and phenylephrine and the dose ranges achieved not achieved
expressed in this figure are based on the authors
interpretaon of the literature that does exist and personal
preference/experience. Maximum doses in any individual Add phenylephrine up to
paent should be considered based on physiologic response 200-300 μg/min to
and side effects. achieve MAP target***
Corticosteroids
 Corticosteroids
• Against using IV hydrocortisone to treat septic
shock patients if adequate fluid resuscitation
and vasopressor therapy are able to restore
hemodynamic stability. If this is not
achievable, we suggest IV hydrocortisone
at a dose of 200 mg per day (weak
recommendation, low quality of evidence).
Blood Products
 Blood Product Administration
RBC transfusion occur only when
hemoglobin concentration decreases to
<7.0 g/dL in adults in the absence of
extenuating circumstances, such as
myocardial ischemia, severe hypoxemia,
or acute hemorrhage (strong
recommendation, high quality of evidence).
 Blood Product Administration
Prophylactic platelet transfusion
when counts are <10,000/mm3 in the
absence of apparent bleeding and
when counts are <20,000/mm3 if the
patient has a significant risk of bleeding.
Higher platelet counts (≥50,000/mm3) are
advised for active bleeding, surgery, or
invasive procedures (weak
recommendation, very low quality of
evidence).
Glucose Control
 Glucose Control
A protocolized approach to blood glucose
management in ICU patients with severe
sepsis commencing insulin dosing when 2
consecutive blood glucose levels are >180
mg/dL. This protocolized approach should
target an upper blood glucose ≤180
mg/dL rather than an upper target blood
glucose ≤ 110 mg/dL (strong
recommendation, high quality of evidence).
 Glucose Control
Blood glucose values be monitored every
1–2 hrs until glucose values and insulin
infusion rates are stable and then every
4 hrs thereafter in patients receiving
insulin infusions (BPS).
Bicarbonate
Therapy
 Bicarbonate Therapy
• Against the use of sodium bicarbonate
therapy to improve hemodynamics or to
reduce vasopressor requirements in patients
with hypoperfusion-induced lactic acidemia
with pH ≥ 7.15 (weak recommendation,
moderate quality of evidence).
• Intensive Care Medicine
• doi: 10.1007/s00134-017-4683-6SSC
G u i d e l i n e s 2016
• SSC GUIDELINE 2016
• Intensive Care Medicine
• doi: 10.1007/s00134-017-4683-6
• Surviving Sepsis Campaign:
• International Guidelines for Management
• of Sepsis and Septic Shock: 2016