Sepsis– Updates

Dr. Catharine Leo

MRCEM RESIDENT
SIRS/sepsis/severe sepsis/septic shock
As per latest guidelines
Sequential Organ Failure Assessment (SOFA) Score

The following are the abnormal physiologic SOFA parameters, each of

which receives a score of 2 or higher:
• PaO2:FiO2, < 300 mmHg
• Platelets < 100 × 100/mm3
• Bilirubin ≥ 2 mg/dL
• Hypotension requiring vasopressor support
• Glasgow Coma Scale score ≤ 12
• Creatinine ≥ 2 mg/dL, or urine output < 500 mL/day.
 SIRS versus SOFA and qSOFA in
Sepsis

• Raith EP, Udy AA, Bailey M, McGloughlin S, MacIsaac C, Bellomo R, Pilcher DV. Prognostic accuracy of the SOFA score, SIRS
criteria, and qSOFA score for in-hospital mortality among adults with suspected infection admitted to the intensive care
unit. Jama. 2017 Jan 17;317(3):290-300.
SOFA Score
Sepsis vs Septic Shock
"Time zero” or “time of presentation” is defined as the time of
triage in the emergency department or, if referred from
another care location, from the earliest chart annotation
consistent with all elements of sepsis (formerly severe sepsis)
or septic shock ascertained through chart review."
 Surviving Sepsis Campaign Bundle: 2018 Update
HOUR-1 BUNDLE
• The most important change in the revision of the SSC bundles is that the 3-h and 6-h bundles have been combined into a single

“hour-1 bundle.
HOUR-1 BUNDLE
•Measure lactate level*
•Obtain blood cultures before administering antibiotics.
•Administer broad-spectrum antibiotics.
•Begin rapid administration of 30mL/kg crystalloid for
hypotension or lactate level ≥ 4 ​mmol/L.
•Apply vasopressors if hypotensive during or after fluid
resuscitation to maintain MAP ≥ 65 mm Hg.
•* Remeasure lactate if initial lactate is elevated (> 2 mmol/L).
 Measure Lactate Level
• Increase may represent tissue hypoxia, accelerated aerobic glycolysis
driven by excess beta-adrenergic stimulation, or other causes associated
with worse outcomes.
• A significant reduction in mortality with lactate guided resuscitation
(24−28).
• If initial lactate is elevated (> 2mmol/L), it should be remeasured within
2−4 h to guide resuscitation to normalize lactate in patients with elevated
lactate levels as a marker of tissue hypoperfusion.
 Blood Cultures

• Sterilization of cultures can occur within

minutes of the first dose of an appropriate
antimicrobial, so cultures must be obtained
before antibiotic administration to optimize the
identification of pathogens and improve
outcomes.
• Appropriate blood cultures include at least two
sets (aerobic and anaerobic).
Hemodynamic Support and
Adjunctive Therapy
 Antimicrobial Therapy
• Administration of effective IV antimicrobials within the 1st
hour of recognition.
a) Initial empiric anti-infective therapy of one or more drugs that
have activity against all likely pathogens & that penetrate in
adequate concentrations into tissues.
b) Empiric combination therapy should not be administered for
more than 3–5 days
c) Antimicrobial regimen should be reassessed daily for potential
de-escalation.
 Fluid Therapy
• Crystalloids as the initial fluid of choice in the
resuscitation of severe sepsis and septic shock.
• Albumin - when patients require substantial amounts
of crystalloids.
• Initial fluid challenge in patients with sepsis-induced
tissue hypoperfusion with suspicion of hypovolemia
to achieve a minimum of 30 mL/kg of crystalloids (a
portion of this may be albumin equivalent).
• Continued as long as there is hemodynamic
improvement either based on dynamic (eg, change in
pulse pressure, stroke volume variation) or static (eg,
arterial pressure, heart rate) variables.
Fluid resuscitation in Sepsis
 Procalcitonin
• Rises with bacterial infections (not viral!!!)
• Precursor to calcitonin (responsible for calcium homeostasis)
• Normal level is < 10 pg/ml (< 0.5 ng/ml)
• 0.5 – 2 ng/ml “grey zone” (repeat level in 6 – 24 hrs)
• > 10 ng/ml associated with severe sepsis/shock
• Half life of 25 – 30 hours

We suggest that measurement of procalcitonin levels can be used to

support shortening the duration of antimicrobial therapy
 Vasopressors
• Vasopressor therapy initially to target a mean arterial
pressure (MAP) of 65 mm Hg.
• Norepinephrine as the first choice vasopressor.
• Epinephrine (added to and potentially substituted for
norepinephrine) when an additional agent is needed to
maintain adequate blood pressure.
• Vasopressin 0.03 units/minute can be added to
norepinephrine (NE) with intent of either raising MAP or
decreasing NE dosage.
• Dopamine as an alternative vasopressor agent to
norepinephrine only in highly selected patients (eg,
patients with low risk of tachyarrhythmias and absolute
or relative bradycardia)
 Inotropic Therapy
• A trial of dobutamine infusion up to 20
micrograms/kg/min be administered or added
to vasopressor (if in use) in the presence of
(a)myocardial dysfunction as suggested by
elevated cardiac filling pressures and low
cardiac output, or
(b)ongoing signs of hypoperfusion, despite
achieving adequate intravascular volume and
adequate MAP.
Vasopressor use for Septic Shock
Initial Resuscitation Goals
within first 6 hours
• CVP  8-12 mm Hg
• MAP  ≥ 65 mm Hg
• Urine Output  ≥ 0.5 ml/kg/hr
• Central Venous (SVC) or Mixed Venous Oxygen Saturation 70% or 65%
respectively

In patients with elevated lactate, target to decrease lactate

Supportive Therapy of Severe
Sepsis
Mechanical Ventilation of Sepsis- Induced ARDS

• Target a tidal volume of 6 mL/kg predicted

body weight in patients with sepsis-induced
ARDS.
• Initial upper limit goal for plateau pressures in
a passively inflated lung be ≤30 cm H2O.
• PEEP be applied to avoid alveolar collapse at
end expiration.
 Blood Product Administration

• Hemoglobin concentration decreases to <7.0

g/dL to target a hemoglobin concentration of
7.0 –9.0 g/dL in adults.
• Prophylactic platelet transfusion when
counts are < 20,000/mm3 (20 x 109/L) if the
patient has a significant risk of bleeding.
 Sedation, Analgesia, and
Neuromuscular Blockade
• Continuous or intermittent sedation be
minimized in mechanically ventilated sepsis
patients, targeting specific titration endpoints.
• A short course of NMBA of not greater than 48
hours for patients with early sepsis-induced
ARDS and a Pao2/Fio2 < 150 mm Hg
• Glucose Control: Target an upper blood
glucose ≤180 mg/dL rather than an upper
target blood glucose ≤ 110 mg/dL.
• Renal Replacement Therapy (RRT):
Continuous RRT and intermittent hemodialysis
are equivalent in patients with severe sepsis
and acute renal failure.
• Bicarbonate Therapy: in hypoperfusion-
induced lactic acidemia with pH ≥7.15
• Deep Vein Thrombosis Prophylaxis: daily
subcutaneous (LMWH) against venous
thromboembolism (VTE).
• Stress Ulcer Prophylaxis: using H2 blocker or proton
pump inhibitor.
• Prone position for sepsis-induced ARDS with
PaO2/FiO2 ratio <150.
• Elevate head of bed 30–45 degrees in mechanically
ventilated patients, spontaneous breathing trials, and
a weaning protocol.
• Early enteral nutrition, against parenteral nutrition in
the first 7 d
SSC recommends AGAINST
• Low dose Dopamine for renal protection
• Steroids (Only if on vasopressors – hydrocortisone
200mg/day)
• Erythropoietin for sepsis related anemia
• IV Immunoglobulins for sepsis or septic shock
• High frequency oscillatory ventilation (HFOV) for
sepsis induced ARDS
• ß2 agonists for sepsis-induced ARDS without
bronchospasm
• PA Catheter for patients with sepsis-induced ARDS
• Sodium bicarb therapy to improve hemodynamics or to reduce
vasopressor requirements
• Stress ulcer prophylaxis in patients without risk factors for GI
bleeding!
• Parenteral nutrition alone or in combination with enteral feedings
• Monitoring gastric residual volumes (only in feeding intolerance or
high risk aspiration)
• IV selenium, glutamine or arginine