Current recommendations for

the Management of Severe

Sepsis & Septic Shock

Dr. Amit Kocheta,

DNB Trainee
Anesthesiology & critical
care
BMHRC, Bhopal
 Introduction

• Severe sepsis & septic shock are major

healthcare problems
• Affects millions of individuals around the
world & killing one in four
• The speed and appropriateness of therapy
in initial hours, likely to influence outcome
 Definitions
• Sepsis: Infection with systemic manifestations
• Severe sepsis: Sepsis plus organ dysfunction or
tissue hypoperfusion
• Sepsis-induced hypotension: SBP < 90 or MAP
< 70 or a SBP decrease > 40 mm Hg or < 2 sd
• Septic shock: Sepsis-induced hypotension
persisting despite adequate fluid resuscitation
• Sepsis-induced tissue hypoperfusion: Either
septic shock, an elevated lactate, or oliguria
 Diagnostic criteria for sepsis
Infection, documented or suspected, and some of the following:
• General variables
• Fever (38.3°C)
• Hypothermia (core temperature 36°C)
• Heart rate 90 min1 or 2 SD above the normal value for age
• Tachypnea
• Altered mental status
• Significant edema or positive fluid balance (20 mL/kg over 24 hrs)
• Hyperglycemia (plasma glucose 140 mg/dL or 7.7 mmol/L) in the absence of diabetes

• Inflammatory variables
• Leukocytosis (WBC count 12,000 L1)
• Leukopenia (WBC count 4000 L1)
• Normal WBC count with 10% immature forms
• Plasma C-reactive protein 2 SD above the normal value
• Plasma procalcitonin 2 SD above the normal value

• Hemodynamic variables
• Arterial hypotension (SBP 90 mm Hg; MAP 70 mm Hg; or an SBP decrease 40 mm
Hg in adults or 2 SD below normal for age)
 Diagnostic criteria for sepsis cont.
• Organ dysfunction variables
• Arterial hypoxemia (PaO2/FIO2 300)
• Acute oliguria (urine output 0.5 mL/Kg hr or 45 mmol/L for at least 2 hrs, despite
adequate
• fluid resuscitation)
• Creatinine increase 0.5 mg/dL or 44.2 mol/L
• Coagulation abnormalities (INR 1.5 or a PTT 60 secs)
• Ileus (absent bowel sounds)
• Thrombocytopenia (platelet count, 100,000 L1)
• Hyperbilirubinemia (plasma total bilirubin 4 mg/dL or 70 mol/L)

• Tissue perfusion variables

• Hyperlactatemia ( upper limit of lab normal)
• Decreased capillary refill or mottling

• Diagnostic criteria for sepsis in the pediatric population

• signs and symptoms of inflammation plus infection with hyper- or hypothermia (rectal
temperature 38.5°C or 35°C),
• tachycardia (may be absent in hypothermic patients), and
• at least one of the following indications of altered organ function: altered mental
status, hypoxemia, increased serum lactate level, or bounding pulses.
 Recommendations
Management Supportive therapy
A. Initial Resuscitation A. Mechanical ventilation
B. Diagnosis B. Sedation/Analgesia & NMB
C. Antibiotic Therapy C. Glucose Control
D. Source Control D. Renal Replacement
E. Fluid Therapy E. Bicarbonate Therapy
F. Vasopressors F. DVT Prophylaxis
G. Inotropic Therapy G. Stress Ulcer Prophylaxis
H. Corticosteroids H. SDD
I. rhAPC I. Limitation of Support
J. Blood Products
Surviving sepsis campign: International guidelines for management
of severe sepsis & septic shock. Crit Care Med.  2008;36(1):296-327.
 Initial Resuscitation
1. Protocolized resuscitation: As hypoperfusion is
recognized or blood lactate conc ≥ 4 mmol/L
Goals in first 6 hrs:
• CVP 8-12 mm Hg
• MAP ≥ 65 mm Hg
• Urine output ≥ 0.5 mL/kg/hr
• ScvO2 or SmvO2 ≥ 70% or ≥ 65%, respectively
2. If goal not achieved: PRBCs to achieve a Hct of
≥ 30% &/or Dobutamine be used, to increase
CaO2 / COP & O2 delivery
 Diagnosis
1. Obtain appropriate cultures, before antimicrobial
therapy
• At least two blood cultures, percutaneously and
each vascular access device
• Cultures of other sites (preferably quantitative)
such as urine, CSF, wounds, resp secretions, or
other body fluids
2. Prompt imaging studies to confirm source of
infection, along with sampling if indicated.
Bedside USG is very useful in difficulty
www.usgain.com
 Role of biomarkers
• Currently the potential role of biomarkers for
diagnosis remains undefined
• The procalcitonin level, although often useful, is
problematic in patients with an ac inflammatory
pattern from other causes (postoperative, shock)
• In near future, rapid diagnostic methods (PCR,
micro-arrays) might prove extremely helpful for a
quicker identification of pathogens and major
antimicrobial resistance determinants
 Antibiotic Therapy
1. I/V antibiotic therapy be started ASAP, within
the first hour
2. Initial empirical anti-infective therapy include
one or more drugs that have activity against all
likely pathogens, penetrate in adeq
concentration into presumed source of sepsis
3. Antimicrobial regimen be reassessed daily to
optimize activity, prevent resistance, reduce
toxicity & costs

Continued……………
 Antibiotic Therapy
4. Combination therapy for known or suspected
Pseudomonas infections
5. Combination empirical therapy for neutropenic
patients with severe sepsis
6. Empirical combination therapy NR for > 3-5 d.
Single therapy as soon as susceptibility known
7. Duration of therapy typically be 7-10 d; longer
courses may be appropriate in selected pts
8. In noninfectious conditions, antimicrobials be
stopped promptly
 Source Control
1. Specific anatomical diagnosis of infection be
sought within first 6 hrs, amenable to source
control measures
2. In infected peripancreatic necrosis, definitive
intervention is best delayed until adequate
demarcation
3. Effective intervention with least physiologic
insult be employed
4. When intravascular devices are a possible
source, remove them promptly
 Fluid Therapy
1. Fluid resuscitation with either natural/artificial,
colloids or crystalloids. There is no evidence-
based support for one type of fluid over another
2. SAFE study indicated that albumin was safe and
equally effective as crystalloid
3. As volume of distribution is much larger for
crystalloids than for colloids, Crystalloids requires
more fluid to achieve the same end points and
results in more edema, but less expensive
4. Initially target a CVP of ≥ 8 mm Hg (12 mm Hg in
ventilated patients). Further fluid is often required
Continued……………
 Fluid Therapy
5. Fluid challenge technique be applied wherein
fluid administration is continued as long as
hemodynamic improvement continues :
• In hypovolemia ≥ 1000 mL of crystalloids or
300-500 mL of colloids over 30 min
• More rapid & greater amounts in sepsis-
induced tissue hypoperfusion
• Amount reduced when cardiac filling pressures
increase without hemodynamic improvement
 Vasopressors
1. They sustain life & maintain perfusion in life-
threatining hypotension, even in hypovolemia.
Maintain MAP ≥ 65 mm Hg
2. Either norepinephrine or dopamine be first choice
to correct hypotension in septic shock
3. Following drugs NR as initial vasopressor
• Epinephrine: tachycardia, reduced splanchnic
circulation & hyperlactemia
• Phenylephrine: decrease in stroke volume
• Vasopressin: lower levels in septic shock. Low
doses may be effective in refractory pts.
Terlipressin has similar effects but is long lasting
Continued……………
 Vasopressors
4. Epinephrine first alternative in septic shock,
poorly responsive to nor-epineph or dopamine
5. Low-dose dopamine NR for renal protection
6. All patients requiring vasopressors have IBP
monitoring.
• In shock states, NIBP is commonly inaccurate;
IBP provide a more appropriate, continuous
and reproducible measurement.
 Inotropic Therapy
1. Dobutamine infusion be administered in
presence of myocardial dysfunction as
suggested by elevated cardiac filling pressures
and low cardiac output
2. Guidelines recommend against the use of a
strategy to increase cardiac index to
predetermined supranormal levels
 Corticosteroids
1. I/V hydrocortisone be given only when BP is
poorly responsive to fluid & vasopressors
2. ACTH stimulation test should’t be used to identify
who should receive hydrocortisone
3. Dexamethasone NR, if hydrocort is available, can
lead to suppression of HPA axis
4. Fludrocortisone is optional if hydrocort is used
5. Wean from steroid when vasopressors no longer
required
6. Hydrocortisone > 300 mg/d should’t be used
7. Corticosteroids NR for the treatment of sepsis in
the absence of shock
Recombinant Human Activated Protein C
1. Recommended for adult patients with high risk
of death, APACHE II ≥ 25 or MODS, if there
are no contraindications
2. Not recommended for adult patients with
severe sepsis and low risk of death, APACHE
II < 20 or one organ failure
• Increased risk of bleeding with rhAPC, in
surgical pts & invasive procedures. Decision
depends on assessing mortality reduction vs
increases in bleeding & cost
 Blood Product Administration
1. PRBC indicated when Hb < 7.0 g/dL, to a target
of 7.0-9.0 g/dL in adults
2. Erythropoietin should’t be used for anemia assoc
with severe sepsis (except RF induced)
3. FFP NR to correct lab clotting abnormalities in
absence of bleeding or planned invasive
procedures
4. Antithrombin NR for treatment of septic shock,
increased risk of bleeding when used with
heparin
Continued……………
 Blood Product Administration
5. Platelets transfusion:
• Indicated when counts < 5000/mm3 regardless
of apparent bleeding
• May be considered when counts 5000-
30,000/mm3 when significant risk of bleeding
• Counts ≥ 50,000/mm3 are typically required for
surgery or invasive procedures
 Mechanical Ventilation of Sepsis-
Induced ALI/ ARDS
1. Target a TV of 6 mL/kg PBW
2. Maintain PP ≤ 30 cm H2O, Considering chest
wall compliance
3. No single mode of ventilation advantageous
over others that respects same principles of
lung protection
4. Permissive hypercapnia may be allowed to
minimize PP & TV. Limitations in pts with met
acidosis & C/I in raised ICP. NaHCO3 or THAM
may be used in selected pts to facilitate it
Continued……………
 Mechanical Ventilation
5. Use PEEP (> 5 cm H20 ) to avoid extensive
lung collapse at end-expiration. It keeps lung
units open to participate in gas exchange &
increase PaO2
6. Prone positioning in pts requiring potentially
injurious levels of FiO2 or PP & who are not at
high risk for adverse consequences
7. Unless C/I, head end elevated 30-45° to limit
aspiration risk and prevent VAP. Pts should’t
be fed enterally with head of the bed at 0°
Continued……………
 Noninvasive mask ventilation
• Advantages: better communication, lower
incidence of infection, reduced sedation &
improved outcome
• Unfortunately, only suitable in few cases
1. Mild-mod hypoxemic Resp failure, responsive to
relatively low levels of PS and PEEP
2. Stable hemodynamics
3. Comfortable and easily arousable
4. Able to protect airway & spont clear secretions
5. Anticipated to recover rapidly
Continued……………
 Weaning protocol
1. Regular spontaneous breathing trials to evaluate
ability to discontinue MV
• Criteria : Arousable, hemodyn stable, no new
serious conditions, low ventilatory and PEEP req,
safely managed with a face mask or nasal cannula
• Options: low level of PS, CPAP, or a T-piece
• If successful, consider for extubation
2. Routine use of PA catheter NR
3. Conservative fluid strategy for pts with ALI, who
don’t have tissue hypoperfusion, decreases days
of ventilation and ICU stay
 Sedation & Analgesia
1. Follow sedation protocols with a sedation goal
2. Intermittent bolus or continuous infusion to
predetermined end points (sedation scales)
3. Daily interruption/lightening of cont infusion with
awakening & retitration if necessary
• Benefits include potentially shorter duration of
mechanical ventilation & ICU stay, better
assess of neurologic function & reduced costs
 Neuromuscular Blockade
1. Avoided if possible in septic pts, due to risk of
prolonged blockade following discontinuation
2. If required to facilitate MV, either int bolus or
cont infusion with TOF monitoring be used
3. When used appropriately:
• Improve chest wall compliance
• Prevent respiratory dyssynchrony
• Reduce Paw pressures
• Reduce O2 consumption by decreasing work of
breathing & resp muscle blood flow
 Glucose Control
1. Following stabilization, pts with severe sepsis
and hyperglycemia should receive I/V insulin
2. Use a validated protocol for insulin dose & target
glucose levels to < 150 mg/dL
3. Intensive insulin therapy causes a reduction in
ICU mortality/ morbidity
4. All patients on insulin receive a glucose calorie
source & values monitored every 1-2 hrs until
stable and then every 4 hrs
• A large RCT NICE-SUGAR (> 6,000 pts), planned to
compare target blood sugar 80-110 vs. 140-180 mg/dL
Normoglycemia in Intensive Care Evaluation & Survival
Using Glucose Algorithm Regulation
 Renal Replacement
1. Continuous RRT & intermittent hemodialysis are
equivalent in pts with severe sepsis & ARF
2. Use continuous therapies to facilitate manag of
fluid balance in hemodyn unstable septic pts
Bicarbonate Therapy
• NaHCO3 therapy NR for improving hemodyn or
reducing vasopressors in pts with hypoperfusion-
induced lactic acidemia with pH ≥ 7.15
• It is assoc with Na+ and fluid overload, increase
in lactate and PCO2 & decrease in serum Ca++
 DVT Prophylaxis
1. Low-dose UFH, 2-3 times/d; or LMWH daily,
unless C/I (thrombocytopenia, coagulopathy,
active bleeding, recent ICH)
2. Patients who have C/I for heparin receive
mechanical prophylaxis ie, GCS or IPC
3. In very high-risk pts, with severe sepsis and H/O
DVT, trauma, or ortho surgery, a combination
therapy be used
• In very high risk pts, LMWH is proven superior
than UFH
• UFH is preferred over LMWH in moderate to
severe renal dysfunction
 Stress Ulcer Prophylaxis
• H2 blocker or PPIs be given to pts with severe
sepsis to prevent upper GI bleed. The benefit
of prevention must be weighed against the
potential effect of an increased stomach pH on
develop of VAP

Consideration for Limitation of Support

• Advance care planning, communication of
likely outcomes & realistic goals of treatment,
should be discussed with patients and families.
• Decisions for less aggressive or withdrawal of
support may be in the patient's best interest
 Recommendations specific to pediatric
severe sepsis
• The overall mortality is much lower than adults.
• In addition to age-appropriate differences in vital
signs, definition of SIRS requires either temp or
leukocyte abnormalities. Severe sepsis requires
sepsis plus CVS dysfunction or ARDS or two or
more other organ dysfunctions
1. Greater use of physical exam therap end points
2. Dopamine as first drug of choice for hypotension
3. Steroids only in adrenal insufficiency
4. rhAPC not recommended
 Conclusions
• Strong agreement among a large cohort of
international experts regarding recommendations
for best current care of pts with severe sepsis
• EBR are the first step toward improved outcomes
for this important group of critically ill patients
• Significant program support & educational
materials at no cost to the user
www.survivingsepsis.org

Surviving Sepsis Campaign: International Guidelines for

Management of Severe Sepsis and Septic Shock.
Crit Care Med.  2008;36(1):296-327
Thanks

Homage & Hope

BMHRC, Bhopal