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Management of Sepsis & Septic Shock International Guidelines
Dr. Samaresh Das
@Samaresh
Key Concepts of Sepsis
o Sepsis is the primary cause of death from infection, especially if not
recognized and treated promptly. Its recognition mandates urgent
attention.
o Sepsis is a syndrome shaped by pathogen factors and host factors
(eg, sex, race and other genetic determinants, age, comorbidities,
environment) with characteristics that evolve over time.
o What differentiates sepsis from infection is an aberrant or
dysregulated host response and the presence of organ dysfunction.
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Key Concepts of Sepsis
o Sepsis-induced organ dysfunction may be occult; therefore, its
presence should be considered in any patient presenting with
infection. Conversely, unrecognized infection may be the cause
of new-onset organ dysfunction.
o Any unexplained organ dysfunction should thus raise the
possibility of underlying infection.
The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)
JAMA. 2016;315(8):801-810. doi:10.1001/jama.2016.0287.
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Why sepsis again ?
Why new definition?
Why new scoring system ?
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Why Sepsis is revisited again !!!o Sepsis & its associated complications - major public
health and economic burden in the industrialized world.o Outcomes may have serious short- or long-term
consequences such as amputation, damage to organs, or
cognitive dysfunction.o In the US, treatment of a patient with sepsis may cost up
to $50,000, translating to an annual nationwide economic
burden of $17 billion
Tsertsvadze, Alexander, Royle, Pamela, Seedat, Farah, Cooper, Jennifer, Crosby, Rebecca and McCarthy,
N. D.. (2016) Community-onset sepsis and its public health burden : a systematic review. Systematic
Reviews, 5 . 81.
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o In European studies, the treatment of severe sepsis in 2002
was estimated to cost approximately 25,000 . Assuming an
incidence of 100,000 new cases per year, the UK’s National
Health Service (NHS) expenditure for treating these cases
would amount to £2.5 billion annually
o
Daniels R. The incidence, mortality and economic burden of sepsis. In: NHS Evid Emerg & Urgent Care. 2009.
Sepsis is the leading cause of death in non-coronary care , with a mortality rate between 30-50%
Why Sepsis is revisited again !!!
@Samaresh
Why Sepsis is revisited again !!!
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Why new definition?
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Why new definitions ?
o Definitions of sepsis and septic shock were last
revised in 2001.
o Considerable advances have since been made into
the pathobiology (changes in organ function,
morphology, cell biology, biochemistry, immunology,
and circulation), management, and epidemiology of
sepsis, suggesting the need for reexamination.
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To know what distinguishes sepsis from uncomplicated infection as simple infection (which could simply controlled by rest and cup of hot tea!! )
“We need to differentiate a straightforward infection from one that can cause organ dysfunction or death”
Why new definitions ?
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The old definitions
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o Nonspecific SIRS criteria such as pyrexia or neutrophilia will
continue to aid in the general diagnosis of infection.
oThese findings complement features of specific infections (eg, rash,
lung consolidation, dysuria, peritonitis) that focus attention toward
the likely anatomical source and infecting organism.
o However, SIRS may simply reflect an appropriate host response
that is frequently adaptive.
o Sepsis involves organ dysfunction, indicating a pathobiology more
complex than infection plus an accompanying inflammatory
response alone.
Why new scoring system ?
@Samaresh
o The Sepsis-3 authors deemed SOFA superior to SIRS in
predicting hospital mortality, with a SOFA score ≥2 identifying a 2-
to 25-fold increased mortality
o Unfortunately, SOFA is a relatively complex tool, as it scores 6
different organ system markers on a 1-4 scale for each system.
o An increase in 2 points from baseline signifies a higher risk for
in-hospital mortalityo qSOFA can be rapidly scored at the bedside without blood tests, and it is hoped that it will facilitate prompt identification of an infection that poses a greater threat to life.
Why new scoring system ?
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Why new scoring system ?
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"WE NOW HAVE A SCIENTIFICALLY BASED CLASSIFICATION THAT
WILL GIVE THE CLINICIAN AT THE BEDSIDE NEW AND MORE
EFFECTIVE WAYS TO RECOGNIZE THE SEPTIC PATIENT AND THE
SEVERELY SEPTIC PATIENT SO AS TO AFFORD THE EARLIEST
POSSIBLE INTERVENTION,"
Timothy Buchman, MD, from Emory University in Atlanta
The care in sepsis is focused on prompt recognition and early treatment “Shift of focus from inflammation to Organ Dysfunction ”
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Sepsis
Sepsis is defined as life-threatening organ dysfunction
caused by a dysregulated host response to infection
o This new definition emphasizes the primacy of the
nonhomeostatic host response to infection, the
potential lethality that is considerably in excess of a
straightforward infection, and the need for urgent
recognition
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Here’s what has changed and how it will affect clinical practice
1. SIRS is no longer criterion for sepsis.
2. SIRS has been replaced with quick Sequential Organ
Failure Assessment (qSOFA) score
3. SOFA score is now used to clinically characterize
septic patients.
4. Severe sepsis is no more
5. Lactate is now part of septic shock criteria, along with
resistant hypotension.
Positive qSOFA= suspected infection plus ≥2 of the following:
1. Altered mental status (Glasgow Coma Scale score <15)
2. Systolic blood pressure ≤100 mm Hg3. Respiratory rate ≥22/min
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septic shock
Clinical construct of sepsis with persisting hypotension , requiring
vasopressors to maintain MAP ≥65 mm Hg and having a serum
lactate level >2 mmol/L (18 mg/dL)
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Clinical Criteria identifying patients with sepsis & septic shock
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Recommendations & Best Practice Statements
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Initial Resuscitaion with Sepsis & Septic Shock
1. Sepsis and septic shock are medical emergencies, treatment and resuscitation
should begin immediately (BPS).
2. Resuscitation for sepsis-induced hypoperfusion, at least 30 mL/kg of IV crystalloid
to be given within first 3 hours (strong recommendation, low quality of evidence).
3. 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 ( HR,BP, Spo2, RR, Temp, urine output, and other noninvasive or invasive
monitoring, as available.
4. 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).
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Fluid resuscitation in Sepsis
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5. Suggest dynamic over static variables be used to predict fluid
responsiveness, where available (weak recommendation, low quality of
evidence).
6. Initial target MAP of 65 mmHg in patients with septic shock requiring
vasopressors (strong recommendation, moderate quality of evidence).
7. Suggest guiding resuscitation to normalize lactate in patients with
elevated lactate levels as a marker of tissue hypoperfusion (weak
recommendation, low quality of evidence).
Initial Resuscitaion with Sepsis & Septic Shock
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Screening for Sepsis & Sepsis performance Improvement
Hospitals and hospital systems should have a performance
improvement program for sepsis, including sepsis screening for
acutely ill, high risk patients (BPS).
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Diagnosis
o Appropriate routine microbiologic cultures (including blood) to be
obtained before starting antimicrobial therapy
Remarks: Appropriate routine microbiologic cultures always include at least two sets of
blood cultures (aerobic & anaerobic).
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Antimicrobial therapy
1. IV antimicrobials should be initiated ASAP after recognition and
within 1 hr for both sepsis and septic shock (strong
recommendation, moderate quality of evidence).
2. 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. Systemic antimicrobial prophylaxis in patients with severe
inflammatory states of noninfectious origin (e.g., severe pancreatitis,
burn injury) (BPS).
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6. 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. Suggest combination therapy not to be routinely used for ongoing
treatment of most other serious infections, including bacteremia and
sepsis without shock (weak recommendation, low quality of
evidence).
8. Recommendation against combination therapy for the routine
treatment of neutropenic sepsis/bacteremia (strong
recommendation, moderate quality of evidence).
Antimicrobial therapy
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9. If combination therapy used for septic shock, de-escalate with
discontinuation of combination therapy within first few days in
response to clinical improvement and/or evidence of infection
resolution. (BPS).
10. Suggest duration 7 to 10 days is adequate for most serious
infections associated with sepsis and septic shock (weak
recommendation, low quality of evidence).
11. Suggest longer courses are appropriate in patients who have a slow
clinical response, undrainable foci of infection,bacteremia with Staph.
aureus, some fungal and viral infections, or immunologic deficiencies,
including neutropenia (weak recommendation, low quality of
evidence).
Antimicrobial therapy
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12. Suggest Shorter courses for those with rapid clinical resolution
following effective source control of intra-abdominal or urinary
sepsis (weak recommendation, low quality of evidence).
13. Daily assessment for de-escalation of therapy (BPS).
14. Suggest procalcitonin levels to support shortening the duration
of antimicrobial therapy (weak recommendation, low quality of
evidence).
15. Suggest procalcitonin levels to support the discontinuation of
empiric antibiotics , who initially appeared to have sepsis, but
subsequently have limited clinical evidence of infection (weak
recommendation, low quality of evidence).
Antimicrobial therapy
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Source Control
1. Specific anatomic diagnosis of infection requiring emergent source
control should be identified ASAP & required source control
intervention should be implemented ASAP after the diagnosis is
made (BPS).
2. Prompt removal of intravascular access devices that are a possible
source of sepsis or septic shock after other vascular access has
been established (BPS).
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Fluid Therapy
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Fluid Therapy1. Fluid challenge technique be applied where fluid administration is
continued as long as hemodynamic factors continue to improve
(BPS).
2. Crystalloids as the fluid of choice for initial resuscitation and
subsequent intravascular volume replacement (strong
recommendation, moderate quality of evidence).
3. Suggest either balanced crystalloids or saline (weak
recommendation, low quality of evidence).
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4. Suggest using albumin in addition to crystalloids (weak
recommendation, low quality of evidence).
5. Against using hydroxyethyl starches for intravascular volume
replacement in patients with sepsis or septic shock (strong
recommendation, high quality of evidence).
6. Suggest using crystalloids over gelatins when resuscitating
patients with sepsis or septic shock (weak recommendation,
low quality of evidence)
Fluid Therapy
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Vasopressor use for Septic Shock
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Vasoactive medication 1. Norepinephrine as the first-choice vasopressor (strong recommendation,
moderate quality of evidence).
2. 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 mean arterial pressure to target, or adding vasopressin (up to 0.03
U/min) (weak recommendation, moderate quality of evidence) to decrease
norepinephrine dosage.
3. Suggest using dopamine as an alternative vasopressor agent to
norepinephrine in highly selected patients (e.g., patients with low risk of
tachyarrhythmias and absolute or relative bradycardia) (weak
recommendation, low quality of evidence).
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4. Against using low-dose dopamine for renal protection (strong
recommendation, high quality of evidence).
5. Suggest using dobutamine in patients with persistent
hypoperfusion despite adequate fluid loading and vasopressor
(weak recommendation, low quality of evidence)
6. Suggest arterial catheter placed as soon as practical if resources
are available on patients requiring vasopressors
(weak recommendation, very low quality of evidence).
Vasoactive medication
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Corticostroids
Suggest against using IV hydrocortisone if adequate fluid resuscitation
and vasopressor are able to restore hemodynamic stability
If not achievable, suggest IV hydrocortisone at a dose of 200 mg per day
(weak recommendation, low quality of evidence).
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Blood Products
1. RBC transfusion only when Hb < 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. Against the use of erythropoietin for treatment of anemia
associated with sepsis (strong recommendation, moderate quality
of evidence).
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3. Suggest against FFP in the absence of bleeding or planned
invasive procedures (weak recommendation, very low quality of
evidence).
4. Suggest platelet transfusion in < 10,000/mm3 (10 × 109/L) in
the absence of apparent bleeding & < 20,000/mm3 (20 ×
109/L) if significant risk of bleeding. Higher platelet counts
(≥50,000/mm3 [50 x 109/L]) are advised for active bleeding,
surgery, or invasive procedures (weak recommendation, very
lowquality of evidence).
Blood Products
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ImmunoglbulinsSuggest against use of IV immunoglobulins in patients with
sepsis or septic shock (weak recommendation, low quality of
evidence).
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Blood purification
No recommendation regarding the use of blood purification
techniques.
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Anticoagulants
1. Against the use of antithrombin for the treatment of sepsis and
septic shock (strong recommendation, moderate quality of
evidence).
2. No recommendation regarding the use of thrombomodulin or
heparin for the treatment of sepsis or septic shock.
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Mechanical ventilation 1. Target Vt of 6 mL/kg predicted body weight with sepsis-induced
ARDS (strong recommendation, high quality of evidence).
2. Upper limit for plateau pressures of 30 cmH2O (strong
recommendation, moderate quality of evidence).
3. Suggest higher PEEP in adult patients with sepsis-induced
moderate to severe ARDS (weak recommendation, moderate quality
of evidence).
4. Suggest recruitment maneuvers (weak recommendation, moderate
quality of evidence).
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5 . Prone over supine ventilation ( Pao2/Fio2 ratio < 150) (strong
recommendation, moderate quality of evidence).
6. Against using ( HFOV) (strong recommendation, moderate quality
of evidence).
7. No recommendation regarding the use of noninvasive ventilation
8. Suggest using neuromuscular blocking agents for ≤ 48 with P:F
< 150 mm Hg (weak recommendation, moderate quality of evidence).
9. Conservative fluid strategy for patients who do not have evidence
of tissue hypoperfusion (strong recommendation, moderate quality
of evidence).
Mechanical ventilation
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10. Against ß-2 agonists for the treatment of patients with sepsis-
induced ARDS without bronchospasm(strong recommendation,
moderate quality of evidence).
11. Against the routine use of the PA catheter (strong recommendation,
high quality of evidence).
12. Suggest lower tidal volumes over higher tidal volumes in adult
patients with sepsis-induced respiratory failure without ARDS (weak
recommendation, low quality of evidence).
Mechanical ventilation
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Mechanical ventilation
13. Mechanically ventilated sepsis patients with head up between 30
& 45 degrees to limit aspiration risk & to prevent VAP(strong
recommendation, low quality of evidence).
14. SBT in ventilated patients with sepsis who are ready for weaning
(strong recommendation, high quality of evidence).
15. Using a weaning protocol in ventilated patients who can tolerate
weaning (strong recommendation, moderate quality of evidence).
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Sedation and Analgesia
Continuous or intermittent sedation to minimized in mechanically
ventilated sepsis patients, targeting specific titration end points
(BPS).
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Glucose Control1. Protocolized approach to control glucose , commencing insulin
dosing when two consecutive blood glucose levels are > 180 mg/dL.
Target an upper blood glucose level ≤180 mg/dL (strong
recommendation, high quality of evidence).
2. Blood glucose 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. Glucose levels obtained with point-of-care testing of capillary blood
be interpreted with caution because may not accurately estimate
arterial blood or plasma glucose values (BPS).
4. Suggest use of arterial blood rather than capillary blood for point-
of-care testing using glucose meters if patients havearterial
catheters (weak recommendation, low quality of evidence).
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Renal replacement Therapy
1. Suggest either continuous or intermittent renal replacement
therapy (RRT) be used in patients with sepsis and AKI(weak
recommendation, moderate quality of evidence).
2. Suggest using continuous therapies to facilitate management of
fluid balance in hemodynamically unstable septic patients
(weak recommendation, very low quality of evidence).
3. 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).
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Bicarbonate Therapy
suggest against the use of NaHCo3 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).
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Venous Thromboprophylaxis
1. Pharmacologic prophylaxis (UFH or LMWH) against VTE in the absence
of contraindications (strong recommendation, moderate evidence).
2. LMWH rather than UFH for VTE prophylaxis in the absence of
contraindications to the use of LMWH (strong recommendation,
moderate quality of evidence).
3. Suggest combination pharmacologic VTE prophylaxis and mechanical
prophylaxis, whenever possible (weak recommendation,low quality of
evidence).
4. Suggest mechanical prophylaxis when pharmacologic VTE is
contraindicated (weak recommendation, low quality of evidence).
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Stress Ulcer Prophylaxis
1. To be given to patients with sepsis or septic shock who have
risk factors for GI bleeding (strong recommendation, low
quality of evidence).
2. Suggest using either PPI or H-2 receptor antagonists when
stress ulcer prophylaxis is indicated (weak recommendation,
low quality of evidence).
3. Recommendation against stress ulcer prophylaxis in patients
without risk factors for GI bleeding (BPS).
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Nutrition
1. Against the 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. Against 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).
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3. Suggest early initiation of enteral feeding rather than a complete
fast or only IV glucose (weak recommendation, low quality of
evidence).
4. 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).
Nutrition
@Samaresh
5. Against the use of omega-3 fatty acids as an immune supplement
(strong recommendation, low quality of evidence).
6. Suggest against routinely monitoring gastric residual volumes (weak
recommendation, low quality of evidence). 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. Suggest prokinetic agents in critically ill patients with sepsis or
septic shock and feeding intolerance (weak recommendation, low
quality of evidence).
8. Suggest post-pyloric feeding tubes with feeding intolerance / at high
risk of aspiration (weak recommendation, low quality of evidence).
Nutrition
@Samaresh
9. Against the use of IV selenium (strong recommendation, moderate
quality of evidence).
10. Suggest Against the use of arginine to treat sepsis and septic
shock (weak recommendation, low quality of evidence).
11. Against the use of glutamine to treat sepsis and septic shock
(strong recommendation, moderate quality of evidence).
12. No recommendation about the use of carnitine for sepsis and
septic shock.
Nutrition
@Samaresh
Setting Goals of Care
1. Goals of care and prognosis be discussed with patients and
families (BPS).
2 . Goals of care be incorporated into treatment and end-of-life
care planning, utilizing palliative care principles
where appropriate (strong recommendation, moderate quality
of evidence).
3. 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
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Take Home points
o Early recognition screening
o Early resuscitation with Crystaloid 30ml/kg( albumin )
o Culture and Abx ASAP
o MAP & CO : Vasopressor ( NE) / lactate
o Frequent Volume assessment / Dynamic measures
o Once stable – De-escalate
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Thanks