International guidelines for management of severs sepsis & Septic Shock 2012

 Infection, documented or suspected, and
some of the following:
 General variables
 Fever (> 38.3°C)
 Hypothermia (core temperature < 36°C)
 Heart rate > 90/min–1 or more than two sd
above the normal value for age
 Tachypnea
 Altered mental status
 Significant edema or positive fluid balance
(> 20mL/kg over 24 hr)
 Hyperglycemia (plasma glucose > 140
mg/dL or 7.7 mmol/L) in the absence of
diabetes

 Inflammatory variables
 Leukocytosis (WBC count > 12,000 μL–1)
 Leukopenia (WBC count < 4000 μL–1)
 Normal WBC count with greater than
10% immature forms
 Plasma C-reactive protein more than
two sd above the normal value
 Plasma procalcitonin more than two sd
above the normal value

 Hemodynamic variables
 Arterial hypotension (SBP < 90mm Hg,
MAP 70mm Hg, or
 SBP decrease > 40mm Hg in adults or less
than two sd below normal for age

 Organ dysfunction variables
 Arterial hypoxemia (Pao2/Fio2< 300)
 Acute oliguria (urine output < 0.5mL/kg/hr
for at least 2 hrs despite adequate fluid
resuscitation)
 Creatinine increase > 0.5 mg/dL or 44.2
μmol/L
 Coagulation abnormalities (INR > 1.5 or aPTT
> 60s)
 Ileus (absent bowel sounds)
 Thrombocytopenia (platelet count <
100,000μL1)
 Hyperbilirubinemia (plasma total bilirubin >
4mg/dL or 70 μmol/L)

 Tissue perfusion variables
 Hyperlactatemia (> 1 mmol/L)
 Decreased capillary refill or mottling

 Severe sepsis definition =
 sepsis-induced tissue hypoperfusion or
organ dysfunction (any of the following
thought to be due to the infection)

 Sepsis-induced hypotension
 Lactate above upper limits laboratory normal
 Urine output < 0.5mL/kg/hr for more than 2 hrs
despite adequate fluid resuscitation
 Acute lung injury with PaO2/FIO2< 250 in the
absence of pneumonia as infection source
 Acute lung injury with PaO2/FIO2< 200 in the
presence of pneumonia as infection source
 Creatinine > 2.0mg/dL (176.8 μmol/L)
 Bilirubin > 2mg/dL (34.2 μmol/L)
 Platelet count < 100,000 μL
 Coagulopathy (international normalized ratio >
1.5

 Initial Resuscitation and Infection Issues
 Initial Resuscitation
 1. Protocolized, quantitative resuscitation of patients
with sepsis- induced tissue hypoperfusion (defined in
this document as hypotension persisting after initial
fluid challenge or blood lactate concentration ≥4
mmol/L).
 Goals during the first 6 hrs of resuscitation:
 a) Central venous pressure 8–12mm Hg
 b) Mean arterial pressure (MAP) ≥65mm Hg
 c) Urine output ≥0.5 mL/kg/hr
 d) Central venous (superior vena cava) or mixed
venous oxygen saturation 70% or 65%, respectively
(grade 1C).
 2. In patients with elevated lactate levels targeting
resuscitation to normalize lactate (grade 2C)

 B. Screening for Sepsis and Performance
Improvement
 1. Routine screening of potentially
infected seriously ill patients for severe
sepsis to allow earlier implementation of
therapy (grade 1C).
 2. Hospital–based performance
improvement efforts in severe sepsis (UG)

 C. Diagnosis
 1. Cultures as clinically appropriate before
antimicrobial therapy if no significant delay (>
45 mins) in the start of antimicrobial(s) (grade
1C).
 At least 2 sets of blood cultures (both aerobic
and anaerobic bottles) be obtained before
antimicrobial therapy with at least 1 drawn
percutaneously and 1 drawn through each
vascular access device, unless the device was
recently (<48hrs) inserted (grade 1C).
 2. Use of the 1,3 beta-D-glucan assay (grade
2B), mannan and anti-mannan antibody
assays (2C), if available and invasive
candidiasis is in differential diagnosis of cause
of infection.
 3. Imaging studies performed promptly to
confirm a potential source of infection (UG).

 D. Antimicrobial Therapy
 1. Administration of effective intravenous
antimicrobials within the first hour of recognition of
septic shock (grade 1B) and severe sepsis without
septic shock (grade 1C) as the goal of therapy.
 2a. Initial empiric anti-infective therapy of one or
more drugs that have activity against all likely
pathogens (bacterial and/or fungal or viral) and that
penetrate in adequate concentrations into tissues
presumed to be the source of sepsis (grade 1B).
 2b. Antimicrobial regimen should be reassessed daily
for potential deescalation (grade 1B).
 3. Use of low procalcitonin levels or similar biomarkers
to assist the clinician in the discontinuation of empiric
antibiotics in patients who initially appeared septic,
but have no subsequent evidence of infection
(grade 2C).

 4a. Combination empirical therapy for
neutropenic patients with severe sepsis (grade
2B) and for patients with difficult-to-treat,
multidrug-resistant bacterial pathogens such as
Acinetobacter and Pseudomonasspp.(grade
2B).
 For patients with severe infections associated
with respiratory failure and septic shock,
combination therapy with an extended
spectrum beta-lactam and either an
aminoglycoside or fluoroquinolone is for P.
aeruginosa bacteremia (grade 2B).
 A combination of beta-lactam and macrolide
for patients with septic shock from bacteremic
Streptococcus pneumoniae infections (grade
2B).

 4b. Empiric combination therapy should not be
administered for more than 3–5 days. De-escalation
to the most appropriate single
therapy should be performed as soon as the
susceptibility profile is known (grade 2B).
 5. Duration of therapy typically 7–10 days;
longer courses may be 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 (grade 2C).
 6. Antiviral therapy initiated as early as possible
in patients with severe sepsis or septic shock of
viral origin (grade 2C).
 7. Antimicrobial agents should not be used in
patients with severe inflammatory states
determined to be of noninfectious cause

 E. Source Control
 1. A specific anatomical diagnosis of infection
requiring consideration for emergent source control
be sought and diagnosed or excluded as rapidly as
possible, and intervention be undertaken for source
control within the first 12 hr after the diagnosis is
made, if feasible (grade 1C).
 2. When infected peripancreatic necrosis is identified
as a potential source of infection, definitive
intervention is best delayed until adequate
demarcation of viable and nonviable tissues has
occurred (grade 2B).
 3. When source control in a severely septic patient is
required, the effective intervention associated with
the least physiologic insult should be used (eg,
percutaneous rather than surgical drainage of an
abscess) (UG).
 4. If intravascular access devices are a possible
source of severe sepsis or septic shock, they should
be removed promptly after other vascular access
has been established (UG).

 F. Infection Prevention
 1a. Selective oral decontamination and
selective digestive decontamination should
be introduced and investigated as a
method to reduce the incidence of
ventilator-associated pneumonia; This
infection control measure can then be
instituted in health care settings and regions
where this methodology is found to be
effective (grade 2B).
 1b. Oral chlorhexidine gluconate be used
as a form of oropharyngeal
decontamination to reduce the risk of
ventilator-associated pneumonia in ICU
patients with severe sepsis (grade 2B)

 TO BE COMPLETED WITHIN 3 HOURS:
 1) Measure lactate level
 2) Obtain blood cultures prior to administration of
antibiotics
 3) Administer broad spectrum antibiotics
 4) Administer 20 mL/kg crystalloid for hypotension or
lactate >4mmol/L
 TO BE COMPLETED WITHIN 6 HOURS:
 5) Apply vasopressors (for hypotension that does not
respond to initial fluid resuscitation)to maintain a mean
arterial pressure (MAP) ≥ 65 mm Hg
 6) In the event of persistent arterial hypotension despite
volume resuscitation (septicshock) or initial lactate >4
mmol/L (36 mg/dL):
- Measure central venous pressure (CVP)*
- Measure central venous oxygen saturation (ScvO2)*
 7) Remeasure lactate if initial lactate was elevated*

 G. Fluid Therapy of Severe Sepsis
 1.Crystalloids as the initial fluid of choice in the resuscitation of
severe sepsis and septic shock (grade 1B).
 2.Against the use of hydroxyethyl starches for fluid resuscitation
of severe sepsis and septic shock (grade 1B).
 3.Albumin in the fluid resuscitation of severe sepsis and septic
shock when patients require substantial amounts of crystalloids
(grade 2C).
 4.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). More rapid administration and greater
amounts of fluid may be needed in some patients (grade 1C).
 5. Fluid challenge technique be applied wherein fluid
administration is 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 (UG)

 H. Vasopressors
 1.Vasopressor therapy initially to target a mean arterial pressure (MAP) of
65mm Hg (grade 1C).
 2.Norepinephrine as the first choice vasopressor (grade 1B).
 3.Epinephrine (added to and potentially substituted for norepinephrine)
when an additional agent is needed to maintain adequate blood
pressure (grade 2B).
 4.Vasopressin 0.03 units/minute can be added to norepinephrine (NE)
with intent of either raising MAP or decreasing NE dosage (UG).
 5.Low dose vasopressin is not recommended as the single initial
vasopressor for treatment of sepsis-induced hypotension and vasopressin
doses higher than 0.03-0.04 units/minute should be reserved for salvage
therapy (failure to achieve adequate MAP with other vasopressor
agents) (UG).
 6.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) (grade 2C).
 7.Phenylephrine is not recommended in the treatment of septic shock
except in circumstances where (a) norepinephrine is associated with
serious arrhythmias, (b) cardiac output is known to be high and blood
pressure persistently low or (c) as salvage therapy when combined
inotrope/vasopressor drugs and low dose vasopressin have failed to
achieve MAP target (grade 1C).
 8.Low-dose dopamine should not be used for renal protection (grade
1A).
 9.All patients requiring vasopressors have an arterial catheter placed as
soon as practical if resources are available (UG)

 I .Inotropic Therapy
 1.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 (grade 1C).
 2.Not using a strategy to increase cardiac
index to predetermined supranormal levels
(grade 1B)

 J. Corticosteroids
 1.Not using intravenous hydrocortisone to treat adult
septic shock patients if adequate fluid resuscitation
and vasopressor therapy are able to restore
hemodynamic stability (see goals for Initial
Resuscitation). In case this is not achievable, we
suggest intravenous hydrocortisone alone at a dose
of 200mg per day (grade 2C).
 2.Not using the ACTH stimulation test to identify adults
with septic shock who should receive hydrocortisone
(grade 2B).
 3.In treated patients hydrocortisone tapered when
vasopressors are no longer required (grade 2D).
 4.Corticosteroids not be administered for the
treatment of sepsis in the absence of shock (grade
1D).
 5.When hydrocortisone is given, use continuous flow
(grade 2D)

 K. blood Product Administration
1.Once tissue hypoperfusion has resolved and in the
absence of extenuating circumstances, such as
myocardial ischemia, severe hypoxemia, acute
hemorrhage, or ischemic heart disease,=red blood
cell transfusion occur only when hemoglobin
concentration decreases to <7.0g/dL to target a
hemoglobin concentration of 7.0 –9.0g/dL in adults
(grade 1B).
 2.Not using erythropoietin as a specific treatment of
anemia associated with severe sepsis (grade 1B).
 3.Fresh frozen plasma not be used to correct
laboratory clotting abnormalities in the absence of
bleeding or planned invasive procedures (grade 2D)

 4.Not using antithrombin for the treatment
of severe sepsis and septic shock (grade
1B).
 5.In patients with severe sepsis, administer
platelets prophylactically when counts are
<10,000/mm3(10 x 109/L) in the absence of
apparent bleeding & prophylactic platelet
transfusion when counts are <
20,000/mm3(20 x 109/L) if the patient has a
significant risk of bleeding.
 Higher platelet counts (≥50,000/mm3[50 x
109/L]) are advised for active bleeding,
surgery, or invasive procedures (grade 2D)

 L. Immunoglobulins
 1.Not using intravenous immunoglobulins
in adult patients with severe sepsis or
septic shock (grade 2B).

 M. Selenium
 1.Not using intravenous selenium for the
treatment of severe sepsis (grade 2C)

 N.History of Recommendations
Regarding Use of Recombinant
Activated Protein C (rhAPC)
 A history of the evolution of SSC
recommendations as to rhAPC (no
longer available) is provided

 O. Mechanical Ventilation of Sepsis-
Induced Acute Respiratory Distress
Syndrome (ARDS)
 1.Target a tidal volume of 6mL/kg predicted
body weight in patients with sepsis-induced
ARDS (grade 1A vs. 12 mL/kg).
 2.Plateau pressures be measured in patients
with ARDS and initial upper limit goal for
plateau pressures in a passively inflated
lung be ≤30cm H2O (grade 1B).
 3.Positive end-expiratory pressure (PEEP) be
applied to avoid alveolar collapse at end
expiration (atelectotrauma) (grade 1B).
 4.Strategies based on higher rather than
lower levels of PEEP be used for patients
with sepsis- induced moderate or severe
ARDS (grade 2C)

 5.Recruitment maneuvers be used in sepsis
patients with severe refractory hypoxemia
(grade 2C).
 6.Prone positioning be used in sepsis-induced
ARDS patients with a
Pao2/Fio2ratio ≤100mm Hg in facilities that
have experience with such practices
(grade 2B).
 7.That mechanically ventilated sepsis
patients be maintained with the head of
the bed elevated to 30-45 degrees to limit
aspiration risk and to prevent the
development of ventilator-associated
pneumonia (grade 1B).

 8.That noninvasive mask ventilation (NIV) be used in
that minority of sepsis-induced ARDS patients in
whom the benefits of NIV have been carefully
considered and are thought to outweigh the risks
(grade 2B).
 9.That a weaning protocol be in place and that
mechanically ventilated patients with severe sepsis
undergo spontaneous breathing trials regularly to
evaluate the ability to discontinue mechanical
ventilation when they satisfy the following criteria:
 a) arousable;
 b) hemodynamically stable (without vasopressor
agents);
 c) no new potentially serious conditions;
 d) low ventilatory and end-expiratory pressure
requirements; and e) low Fio2requirements which can
be met safely delivered with a face mask or nasal
cannula.
 If the spontaneous breathing trial is successful,
consideration should be given for extubation (grade
1A).

 10.Against the routine use of the
pulmonary artery catheter for patients
with sepsis-induced ARDS (grade 1A).
 11.A conservative rather than liberal fluid
strategy for patients with established
sepsis-induced ARDS who do not have
evidence of tissue hypoperfusion (grade
1C).
 12.In the absence of specific indications
such as bronchospasm, not using beta 2-
agonists for treatment of sepsis-induced
ARDS (grade 1B).

 P. Sedation, Analgesia, and Neuromuscular
blockade in Sepsis
 1.Continuous or intermittent sedation be
minimized in mechanically ventilated sepsis
patients, targeting specific titration
endpoints (grade 1B).
 2.Neuromuscular blocking agents (NMBAs)
be avoided if possible in the septic patient
without ARDSdue to the risk of prolonged
neuromuscular blockade following
discontinuation.
 If NMBAs must be maintained, either
intermittent bolus as required or continuous
infusion with train-of-four monitoring of the
depth of blockade should be used (grade
1C)

 3.A short course of NMBA of not greater
than 48 hours for patients withearly
sepsis-induced ARDS and a Pao2/Fio2<
150 mm Hg (grade 2C)

 Q. Glucose Control
 1.A protocolized approach to blood glucose
management in ICU patients with severe sepsis
commencing insulin dosing when 2
consecutive blood glucose levels are
>180mg/dL.
 This protocolized approach should target an
upper blood glucose ≤180mg/dL rather than
an upper target blood glucose ≤110mg/dL
(grade 1A).
 2.Blood glucose values be monitored every 1–2
hrs until glucose values and insulin infusion rates
are stable and then every 4 hrs thereafter
(grade 1C).
 3.Glucose levels obtained with point-of-care
testing of capillary blood be interpreted with
caution, as such measurements may not
accurately estimate arterial blood or plasma
glucose values (UG)

 R. Renal Replacement Therapy
 1.Continuous renal replacement
therapies and intermittent hemodialysis
are equivalent in patients with severe
sepsis and acute renal failure (grade 2B).
 2.Use continuous therapies to facilitate
management of fluid balance in
hemodynamically unstable septic
patients (grade 2D).

 S. bicarbonate Therapy
 1.Not using sodium bicarbonate therapy
for the purpose of improving
hemodynamics or reducing vasopressor
requirements in patients with
hypoperfusion-induced lactic acidemia
with pH ≥7.15 (grade 2B)

 T. Deep Vein Thrombosis Prophylaxis
 1.Patients with severe sepsis receive daily
pharmacoprophylaxis against venous
thromboembolism (VTE) (grade 1B). This should
be accomplished with daily subcutaneous low-molecular
weight heparin (LMWH) (grade 1B
versus twice daily UFH, grade 2C versus three
times daily UFH).
 If creatinine clearance is <30 mL/min, use
dalteparin (grade 1A) or another form of
LMWH that has a low degree of renal
metabolism (grade 2C) or UFH (grade 1A).
 2.Patients with severe sepsis be treated with a
combination of pharmacologic therapy and
intermittent pneumatic compression devices
whenever possible (grade 2C)

 3.Septic patients who have a
contraindication for heparin use –
 (eg, thrombocytopenia, severe
coagulopathy, active bleeding, recent
intracerebral hemorrhage) not receive
pharmacoprophylaxis (grade 1B), but
receive mechanical prophylactic
treatment, such as graduated
compression stockings or intermittent
compression devices (grade 2C), unless
contraindicated.
 When the risk decreases start
pharmacoprophylaxis (grade 2C)

 U. Stress Ulcer Prophylaxis
 1.Stress ulcer prophylaxis using H2 blocker
or proton pump inhibitor be given to
patients with severe sepsis/septic shock
who have bleeding risk factors (grade
1B).
 2.When stress ulcer prophylaxis is used,
proton pump inhibitors rather than H2RA
(grade 2D)
 3.Patients without risk factors do not
receive prophylaxis (grade 2B)

 V. Nutrition
 1.Administer oral or enteral (if necessary)
feedings, as tolerated, rather than either
complete fasting or provision of only
intravenous glucose within the first 48
hours after a diagnosis of severe
sepsis/septic shock (grade 2C).
 2.Avoid mandatory full caloric feeding in
the first week but rather suggest low
dose feeding (eg, up to 500 calories per
day), advancing only as tolerated
(grade 2B)

 3.Use intravenous glucose and enteral
nutrition rather than total parenteral
nutrition (TPN) alone or parenteral
nutrition in conjunction with enteral
feeding in the first 7 days after a
diagnosis of severe sepsis/septic shock
(grade 2B).
 4.Use nutrition with no specific
immunomodulating supplementation
rather than nutrition providing specific
immunomodulating supplementation in
patients with severe sepsis (grade 2C).

 W. Setting Goals of Care
 1.Discuss goals of care and prognosis
with patients and families(grade 1B).
 2.Incorporategoals of care into
treatment and end-of-life care planning,
utilizing palliative care principles where
appropriate (grade 1B).
 3.Address goals of care as early as
feasible, but no later than within 72 hours
of ICU admission (grade 2C).

International guidelines for management of severs sepsis & Septic Shock 2012

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International guidelines for management of severs sepsis & Septic Shock 2012