Surviving sepsis guidelines 2018 update

International
Guidelines for Management of Sepsis and Septic
Shock: 2016
Presenter : Dr. Sajith
Senior Resident
Moderator : Dr. Sri Hari
Asst. Professor

1. First edition in 2004
2. Previous Revisions in 2008 and 2012
3. Current revision started in 2014
4. Jointly sponsored by ESICM and SCCM

1. SIRS : Systemic inflammatory response syndrome
more than two of the following
1. Temp - <36dc or >38dc
2. TLC - <4000 or >12000 (or > 10% band forms in PS)
3. RR - >20/min or Pco2 <32 mmhg
4. PR - >90/min (without inotropes influence)

2. Sepsis : SIRS + known foci of infection
3. Severe Sepsis : sepsis leading to hypotension but
responds to fluids
4. Septic Shock : hypotension not even responding
fluids
5. MODS : failure of more than 2 organ systems

Changes in Sepsis 3
SIRS is Out……..SOFA is in
“Severe sepsis” removed

Sepsis: Life-threatening organ dysfunction caused by dysregulated host
response to infection
Septic Shock: Subset of sepsis with circulatory and cellular/metabolic
dysfunction associated with higher risk of mortality ( need for vasopressors
Lactate >2mmol/L)

The SOFA scoring system is useful in predicting the clinical outcomes
of critically ill patients. According to an observational study at an ICU in
Belgium, the mortality rate is
 At least 50% when the score is increased, regardless of initial score, in the
first 96 hours of admission
 27% to 35% if the score remains unchanged, and
 < 27% if the score is reduced.

1. The Quick SOFA Score was introduced by the Sepsis-3 group in Feb 2016
as a simplified version of the SOFA Score as an initial way to identify
patients at high risk for poor outcome (defined as in-hospital mortality, or
ICU length of stay ≥3 days) with an infection
2. The qSOFA simplifies the SOFA score drastically by only including its 3
clinical criteria and by including "any altered mentation" instead of
requiring a GCS <15.
3. Can easily and quickly be repeated serially on patients.
4. Score ranges from 0 to 3 . Score of 2 or more near the onset of infection
was associated with a greater risk of death or prolonged ICU stay.
5. Sepsis – 3 recommends qSOFA as a simple prompt to identify infected
patients outside the ICU who are likely to be septic.

These scores were designed as research
tools at a population level to predict which
patients with sepsis were likely to die…….they do
not define sepsis

qSOFA - poorly sensitive (60.8%)
moderately specific (72%)
SIRS - more sensitive but
less much specific
qSOFA - better sensitivity in ICU population
better specificity in non-ICU population

Most important change in the revision of SSC
bundles – 3hr and 6hr bundles combined into a single 1
Hour bundle with the explicit intention of beginning
resuscitation and management immediately

1. Sepsis and septic shock are medical emergencies, and we recommend that
treatment and resuscitation begin immediately (BPS).
2. We recommend that, in the resuscitation from sepsis induced
hypoperfusion, at least 30 mL/kg of IV crystalloid fluid be given within the
first 3 hours (strong recommendation, low quality of evidence).
3. We recommend that, following initial fluid resuscitation, additional fluids
be guided by frequent reassessment of hemodynamic status (BPS).
4. We recommend further hemodynamic assessment (such as assessing
cardiac function) to determine the type of shock if the clinical examination
does not lead to a clear diagnosis (BPS).

5. We suggest that dynamic over static variables be used to predict fluid
responsiveness, where available (weak recommendation, low quality of
evidence).
6. We recommend an initial target MAP of 65 mm Hg in patients with septic
shock requiring vasopressors (strong recommendation, moderate quality of
evidence).
7. We suggest guiding resuscitation to normalize lactate in patients with
elevated lactate levels as a marker of tissue hypoperfusion (weak
recommendation, low quality of evidence).

We recommend that hospitals and hospital systems have a
performance improvement program for sepsis, including sepsis screening
for acutely ill, high-risk patients (BPS).

We recommend that appropriate routine microbiologic cultures
(including blood) be obtained before starting antimicrobial therapy in
patients with suspected sepsis or septic shock and 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).

1. We recommend that administration of IV antimicrobials be initiated
ASAP after recognition and within 1 hour for both sepsis and septic shock
(strong recommendation, moderate quality of evidence; grade applies to both
conditions).
2. We recommend 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).
3. We recommend that empiric antimicrobial therapy be narrowed
once pathogen identification and sensitivities are established and/or
adequate clinical improvement is noted (BPS).
4. We recommend against sustained systemic antimicrobial
prophylaxis in patients with severe inflammatory states of
noninfectious origin (e.g., severe pancreatitis, burn injury) (BPS).

6. We suggest empiric combination therapy (using at least
two antibiotics of different antimicrobial classes) aimed at
the most likely bacterial pathogen(s) for the initial
management of septic shock (weak recommendation, low
quality of evidence).
7. We suggest that combination therapy not be routinely
used for ongoing treatment of most other serious
infections, including bacteremia and sepsis without shock
(weak recommendation, low quality of evidence).
8. We recommend against combination therapy for the
routine treatment of neutropenic sepsis/bacteremia (strong
recommendation, moderate quality of evidence).

9. If combination therapy is initially used for septic shock, we recommend
de-escalation with discontinuation of combination therapy within the first
few days in response to clinical improvement and/or evidence of infection
resolution.
10. We suggest that an antimicrobial treatment duration of 7 to 10 days is
adequate for most serious infections associated with sepsis and septic shock
(weak recommendation, low quality of evidence)
11. We suggest that longer courses are appropriate in patients who have a
slow clinical response, undrainable foci of infection, bacteremia with S
aureus, some fungal and viral infections, or immunologic deficiencies,
including neutropenia. (weak recommendation, low quality of evidence).
12. We suggest that shorter courses are appropriate in some patients,
particularly those with rapid clinical resolution following effective source
control of intra-abdominal or urinary sepsis and those with anatomically
uncomplicated pyelonephritis (weak recommendation, low quality of
evidence).

13. We recommend daily assessment for de-escalation of antimicrobial
therapy in patients with sepsis and septic shock (BPS).
14. We suggest that measurement of procalcitonin levels can be used to
support shortening the duration of antimicrobial therapy in sepsis patients
15. We suggest that 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

1. We recommend that 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).
2. We recommend prompt removal of IV access devices that are a possible
source of sepsis or septic shock after other vascular access has been
established (BPS).

1. We recommend that a fluid challenge technique be applied where
fluid administration is continued as long as hemodynamic factors
continue to improve (BPS).
2. We recommend 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).
3. We suggest using either balanced crystalloids or saline for fluid
resuscitation of patients with sepsis or septic shock (weak
4. We suggest 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

5. We recommend against using hydroxyethyl starches (HESs) for
intravascular volume replacement in patients with sepsis or septic shock
(strong recommendation, high quality of evidence).
6. We suggest using crystalloids over gelatins when resuscitating patients
with sepsis or septic shock (weak recommendation, low quality of evidence).

1. We recommend NA as the first-choice vasopressor (strong
2. We suggest 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.
3. We suggest 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
4. We recommend against using low-dose dopamine for renal protection
(strong recommendation, high quality of evidence).

5. We suggest 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).
Remarks: If initiated, vasopressor dosing should be titrated to an end point
reflecting perfusion, and the agent reduced or discontinued in the face of
worsening hypotension or arrhythmias.
6. We suggest that all patients requiring vasopressors have an arterial
catheter placed as soon as practical if resources are available (weak
recommendation, very low quality of evidence).

We suggest 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

1. We recommend that RBC transfusion occur only when Hb is < 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).
2. We recommend against the use of erythropoietin for treatment of anemia
associated with sepsis (strong recommendation, moderate quality of
evidence).
3. We suggest against the use of FFP to correct clotting abnormalities in the
absence of bleeding or planned invasive procedures (weak recommendation,
very low quality of evidence).
4. We suggest prophylactic platelet transfusion when counts are
a. < 10,000/mm3 in the absence of apparent bleeding and
b. < 20,000/mm3 if the patient has a significant risk of bleeding.
c. ≥ 50,000/mm3 [50 × 109/L]) are advised for active bleeding, surgery, or
invasive procedures (weak recommendation, very low quality of evidence).

We suggest against the use of IV immunoglobulins in patients
with sepsis or septic shock (weak recommendation, low quality of evidence).

We make no recommendation regarding the use of blood purification
techniques.

1. We recommend against the use of antithrombin for the treatment of sepsis
and septic shock (strong recommendation, moderate quality of evidence).
2. We make no recommendation regarding the use of thrombomodulin or
heparin for the treatment of sepsis or septic shock

1. We recommend using a target tidal volume of 6 mL/kg predicted body
weight (PBW) compared with 12 mL/kg in adult patients with sepsis-induced
ARDS (strong recommendation, high quality of evidence).
2. We recommend using an upper limit goal for plateau pressures of 30 cm
H2O over higher plateau pressures in adult patients with sepsis-induced
severe ARDS (strong recommendation, moderate quality of evidence).
3. We suggest using higher PEEP over lower PEEP in adult patients with
sepsis-induced moderate to severe ARDS (weak recommendation, moderate
4. We suggest using recruitment maneuvers in adult patients with sepsis-
induced, severe ARDS (weak recommendation, moderate quality of
evidence).
5. We recommend using prone over supine position in adult patients with
sepsis-induced ARDS and a Pao2/Fio2 ratio < 150 (strong recommendation,

6. We recommend against using HFOV in adult patients with sepsis-induced
ARDS (strong recommendation, moderate quality of evidence).
7. We make no recommendation regarding the use of NIV for patients with
sepsis-induced ARDS.
8. We suggest using NMBAs for ≤ 48 hours in adult patients with sepsis
induced ARDS and a Pao2/Fio2 ratio < 150 mm Hg (weak recommendation,
moderate quality of evidence)
9. We recommend a conservative fluid strategy for patients with established
sepsis-induced ARDS who do not have evidence of tissue hypoperfusion
(strong recommendation, moderate quality of evidence).
10. We recommend against the use of β-2 agonists for the treatment of
patients with sepsis-induced ARDS without bronchospasm (strong

11. We recommend against the routine use of the PA catheter for patients
with sepsis-induced ARDS (strong recommendation, high quality of
evidence).
12. We suggest using lower tidal volumes over higher tidal volumes in adult
patients with sepsis-induced respiratory failure without ARDS (weak
13. We recommend that mechanically ventilated sepsis patients be
maintained with the head of the bed elevated between 30 and 45 degrees to
limit aspiration risk and to prevent the development of VAP (strong
14. We recommend using SBTs in mechanically ventilated patients with
sepsis who are ready for weaning (strong recommendation, high quality of
evidence).
15. We recommend using a weaning protocol in mechanically ventilated
patients with sepsis-induced respiratory failure who can tolerate weaning

We recommend that continuous or intermittent sedation be
minimized in mechanically ventilated sepsis patients, targeting specific
titration end points (BPS).

1. We recommend a protocolized approach to blood glucose
management in ICU patients with sepsis, commencing insulin dosing
when two consecutive blood glucose levels are > 180 mg/dL. This
approach should target an upper blood glucose level ≤ 180 mg/dL
rather than an upper target blood glucose level ≤ 110 mg/dL (strong
recommendation, high quality of evidence).
2. We recommend that blood glucose values be monitored every 1 to 2
hours until glucose values and insulin infusion rates are stable, then
every 4 hours thereafter in patients receiving insulin infusions (BPS).
3. We recommend that glucose levels obtained with point of- care
testing of capillary blood be interpreted with caution because such
measurements may not accurately estimate arterial blood or plasma
glucose values (BPS).
4. We suggest the use of arterial blood rather than capillary blood for
point-of-care testing using glucose meters if patients have arterial
catheters (weak recommendation, low quality of evidence).

1. We suggest that either CRRT or intermittent RRT be used in patients with
sepsis and acute kidney injury (weak recommendation, moderate quality of
evidence).
2. We suggest using CRRT to facilitate management of fluid balance in
hemodynamically unstable septic patients (weak recommendation, very low
3. We suggest against the use of RRT in patients with sepsis and acute
kidney injury for increase in creatinine or oliguria without other definitive
indications for dialysis (weak recommendation, low quality of evidence).

We suggest 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

1. We recommend pharmacologic prophylaxis UFH or LMWH against venous
thromboembolism (VTE) in the absence of contraindications to the use of
these agents (strong recommendation, moderate quality of evidence).
2. We recommend LMWH rather than UFH for VTE prophylaxis in the
absence of contraindications to the use of LMWH (strong recommendation,
3. We suggest combination pharmacologic VTE prophylaxis and mechanical
prophylaxis, whenever possible (weak recommendation, low quality of
evidence).
4. We suggest mechanical VTE prophylaxis when pharmacologic VTE is
contraindicated (weak recommendation, low quality of evidence).

1. We recommend that stress ulcer prophylaxis be given to patients with
sepsis or septic shock who have risk factors for GI bleeding (strong
recommendation, low quality of evidence)
2. We suggest using either PPIs or H2RAs when stress ulcer prophylaxis is
indicated (weak recommendation, low quality of evidence).
3. We recommend against stress ulcer prophylaxis in patients without risk
factors for GI bleeding (BPS).

1.We recommend against the administration of early parenteral nutrition
alone or parenteral nutrition in combination with enteral feedings (but rather
initiate early enteral nutrition) in critically ill patients with sepsis or septic
shock who can be fed enterally (strong recommendation, moderate quality of
evidence).
2. We recommend against the administration of parenteral nutrition alone or
in combination with enteral feeds (but rather to initiate IV glucose and
advance enteral feeds as tolerated) over the first 7 days in critically ill
patients with sepsis or septic shock for whom early enteral feeding is not
feasible (strong recommendation, moderate quality of evidence).
3. We suggest the early initiation of enteral feeding rather than a complete
fast or only IV glucose in critically ill patients with sepsis or septic shock
who can be fed enterally (weak recommendation, low quality of evidence).
4. We suggest either early trophic/hypocaloric or early full enteral feeding in
critically ill patients with sepsis or septic shock; if trophic/hypocaloric
feeding is the initial strategy, then feeds should be advanced according to
patient tolerance (weak recommendation, moderate quality of evidence).

5. We recommend against the use of omega-3 fatty acids as an immune
supplement in critically ill patients with sepsis or septic shock (strong
6. We suggest against routinely monitoring gastric residual volumes
(GRVs) in critically ill patients with sepsis or septic shock (weak
recommendation, low quality of evidence). However, we suggest
measurement of gastric residuals in patients with feeding intolerance
or who are considered to be at high risk of aspiration (weak
recommendation, very low quality of evidence).
Remarks: This recommendation refers to nonsurgical critically ill
patients with sepsis or septic shock.
7. We suggest the use of prokinetic agents in critically ill patients
with sepsis or septic shock and feeding intolerance (weak

8. We suggest placement of post-pyloric feeding tubes in critically ill
patients with sepsis or septic shock with feeding intolerance or who
are considered to be at high risk of aspiration (weak recommendation,
low quality of evidence)
9. We recommend against the use of IV selenium to treat sepsis and
septic shock (strong recommendation, moderate quality of evidence).
10. We suggest against the use of arginine to treat sepsis and septic
shock (weak recommendation, low quality of evidence)
11. We recommend against the use of glutamine to treat sepsis and
septic shock (strong recommendation, moderate quality of evidence).
12. We make no recommendation about the use of carnitine for sepsis
and septic shock

1. We recommend that goals of care and prognosis be discussed with patients
and families (BPS).
2. We recommend that goals of care be incorporated into treatment and end-
of-life care planning, utilizing palliative care principles where appropriate
3. We suggest that goals of care be addressed as early as feasible, but no later
than within 72 hours of ICU admission (weak recommendation, low quality
of evidence).

The Surviving Sepsis campaign launched in 2004, is aimed at improving
diagnosis, management and survival of patients with sepsis.
Care bundles are a group of best evidence based interventions which when
instituted together, gives maximum outcome benefit.

2004
The intial sepsis bundles
incorporated a two – phased
approach using the 6 – hour
resuscitation bundle and the 24 –
hour management bundle,
measuring 11 quality indicators
2012
Evidence cited in the 2012
SSC guidelines supported removal
of the 24hr bundle, which resulted in
the 3- and 6-hr bundles measuring
several quality indicators. Both the
original 6- and 24-hr bundles and the
revised 2012 sepsis bundles were
widely adopted in hospitals around
the world

1. Age : <1 year - >65 years
2. Immunocomprimised
3. Recent surgery
4. Chronic disease
5. Wounds
6. Previous sepsis
7. Invasive diseases

The concept entails the preventive use of a mixture of topical anti microbial
agents with activity against aerobic G negative bacteria, S.aureus and yeasts to
eradicate and prevent carriage with these pathogens, thereby preventing ICU-
acquired infections.
Selective oropharyngeal decontamination (SOD) consists of an
oropharyngeal paste, usually tobramycin, colistin and amphoteric B,
administered 4 times a day.
Selective digestive decontamination (SDD) contains the same paste,
supplemented with a suspension (with the same antimicrobial agents)
administered through the nasogastric tube and a 4-day course of
intravenously administered cephalosporins (usually cefotaxime).
The effects on patient outcome have been extensively investigated in ICUs
with low levels of antibiotic resistance and include a reduction in ICU
Mortality, hospital mortality, 28-day mortality and ICU-acquired bacteremia.

On the basis of the individual data of 16,528 patients from six randomized
studies in settings with low levels of antibiotic resistance, the effectiveness of
SDD and SOD was not modified by type of ICU admission.
SDD and SOD improved hospital and ICU survival compared to standard
care in both surgical and medical patients, with SDD being more
effective than SOD.

 Lactate is a parameter of global tissue hypoperfusion and is essential in
identifying patients with “cryptic” shock who require focused early goal-
directed therapy (EGDT)
 Most of the lactate produced in shock state is due to inadequate oxygen
delivery resulting in tissue hypoxia and causing anaerobic glycolysis.
 Moreover, a hypermetabolic state, with glycolysis enhanced by
catecholamines, contributes to the accumulation of lactate .
 Thus, hyperlactatemia and lactic acidosis are common in patients with septic
shock and are associated with significant morbidity and mortality
 As a result, the Third International Consensus Definitions for Sepsis and
Septic Shock (Sepsis-3) has included hyperlactatemia over 2 mmol/L in the
revised definition of septic shock
 A few recent studies showed that an early lactate clearance strategy and a
lactate-guided resuscitation reduced mortality in patients with sepsis and
septic shock

Glucose is converted to
pyruvate in the cytosol as part
of glycolysis.
In aerobic conditions, pyruvate
is transported into the
mitochondria through MCT,
while phosphate
dehydrogenase and thiamine
diphosphate are converted into
acetyl-CoA to produce ATP via
Krebs cycle, which is also called
TCA cycle.
In anaerobic conditions, Krebs
cycle activity is reduced, thus,
this allows the LDH to enhance
lactate formation in the cytosol.
Excess lactate is transported
into the mitochondria again
through MCTs and is oxidized
to pyruvate in the Krebs cycle
pathway.
MCT, mono-carboxylate transporter;
ATP, adenosine triphosphate; LDH,
lactate dehydrogenase; TCA,
tricarboxylic acid.

 In patients with sepsis and septic shock, hyperlactatemia is promoted by
glycolytic flux via anaerobic metabolism with tissue hypoxia, β-adrenergic
receptor stimulation by endo/exogenous catecholamine, and decreased
clearance due to hepatic and renal dysfunction.
 It reduces cardiac contractility and vascular hypo-responsiveness to
vasopressors; however, it is closely associated with poor prognosis.
 Therefore, during sepsis and septic shock management, lactate levels
should be re-measured and normalized.
 To normalize the lactate levels, we have to
1.Reduce glycolytic flux,
2.Enhance lactate removal, and
3.Induce pyruvate metabolism in the Krebs cycle.
 However, the most important treatment is to control the underlying
infection.

 The broth culture method is the gold standard for the diagnosis of
bacterial infection, but a definitive result can take 24 hours or more before
a conclusive diagnosis.
 A number of the inflammatory markers, such as TLC, CRP, and cytokines
(TNF-α, IL-1β, or IL-6), have been applied in the diagnosis of
inflammation and infection, but their lack of specificity has generated a
continued interest to develop more specific clinical laboratory tests.
 One promising marker has been PCT, whose concentration has been
found to be elevated in sepsis.
 Owing its specificity to bacterial infections, PCT has been proposed as a
pertinent marker in the rapid diagnosis of bacterial infection, especially for
use in hospital emergency departments and intensive care units

 Procalcitonin is a 116 amino acid peptide that has an approximate MW of
14.5 kDa and belongs to the calcitonin (CT) superfamily of peptides
 Procalcitonin (PCT) is a biomarker that exhibits greater specificity than
other proinflammatory markers (eg, cytokines) in identifying patients with
sepsis and can be used in the diagnosis of bacterial infections
 The short half-life (25–30 hours in plasma) of PCT, coupled with its virtual
absence in health and specificity for bacterial infections, gives it a clear
advantage over the other markers of bacterial infection
 Procalcitonin expression occurs in a tissue-specific manner.
 In the absence of infection, transcription of the CALC-1 gene for PCT in the
non-neuroendocrine tissue is suppressed, except in the C cells of the
thyroid gland where its expression produces PCT, the precursor of CT in
healthy and non-infected individuals.

 The synthesized PCT then undergoes post-translational processing to
produce small peptides and mature CT, which is generated as a result of
the removal of the C-terminal glycine from the immature CT by
peptidylglycine α-amidating monooxygenase (PAM).Mature CT is stored
in secretary granules and is secreted into the blood to regulate the calcium
concentration.
 In the presence of microbial infection, non-neuroendocrine tissues also
express the CALC-1 gene to produce PCT.
 A microbial infection induces a substantial increase of CALC-1 gene
expression in all parenchymal tissue and differentiated cell types in the
body producing PCT.8 Its levels increase significantly in severe systemic
infections, as compared to other parameters of microbial infections.
 The function of PCT synthesized in the non-neuroendocrine tissues under
microbial infection is presently unclear; however, its detection has helped
in the differential diagnosis of inflammatory processes

This new sepsis “hour-1 bundle,” based on
the 2016 guidelines, should be introduced to emergency
department, floor, and ICU staff as the next iteration of
ever-improving tools in the care of patients with sepsis
and septic shock as we all work to lessen the global
burden of sepsis.

Surviving sepsis guidelines 2018 update

Surviving sepsis guidelines 2018 update

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