Sepsis

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Sepsis

• Dr. Ibrahim Hadi
• Dr. Dalal AL-Matrouk

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Definitions

• Sepsis proven or suspected infection, with a
  systemic response (fever, tachycardia, tachypnea,
  leukocytosis)
• Severe Sepsis sepsis, with organ dysfunction
• Septic shock severe sepsis, with hypotension
  despite adequate fluid resuscitation

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Sepsis Defining a Disease Continuum
Infection/Trauma
Sepsis
Severe Sepsis
SIRS

• A clinical response arising from a nonspecific
  insult, including ? 2 of the following
• Temperature ?38oC or ?36oC
• HR ?90 beats/min
• Respirations ?20/min
• WBC count ?12,000/mm3 or ?4,000/mm3 or gt10
  immature neutrophils

SIRS with a presumed or confirmed infectious
process
SIRS Systemic Inflammatory Response Syndrome
Adapted from Bone RC, et al. Chest
19921011644 Opal SM, et al. Crit Care Med
200028S81
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Sepsis Defining a Disease Continuum
Infection/Trauma
Sepsis
SIRS
Severe Sepsis
Sepsis with ?1 sign of organ failure Cardiovascul
ar (refractory hypotension) Renal Respiratory Hepa
tic Hematologic CNS Metabolic acidosis
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Relationship Of Infection, SIRS, Sepsis Severe
Sepsis and Septic Shock
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Mortality Increases in Septic Shock Patients
Mortality
Incidence
Approximately 200,000 patients including 70,000
Medicare patients have septic shock annually
Balk, R.A. Crit Care Clin 200033752
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Clinical Signs of Septic Shock

• Hemodynamic Alterations
• Hyperdynamic State (Warm Shock)
• Tachycardia.
• Elevated or normal cardiac output.
• Decreased systemic vascular resistance.
• Hypodynamic State (Cold Shock)
• Low cardiac output

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Clinical Signs of Septic Shock

• Myocardial Depression.
• Altered Vasculature.
• Altered Organ Perfusion.
• Imbalance of O2 delivery and Consumption.
• Metabolic (Lactic) Acidosis.

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Infection
Endothelial Dysfunction
Inflammatory Mediators
Vasodilation
Hypotension
Vasoconstriction
Edema
Microvascular Plugging
Maldistribution of Microvascular Blood Flow
Ischemia
Cell Death
Organ Dysfunction
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• Therapy For Sepsis

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Evidence-Based Sepsis Guidelines

• Components
• Early Recognition, early appropriate use of
  antibiotics
• Early Goal-Directed Therapy
• Monitoring
• Resuscitation
• Pressor / Inotropic Support
• Steroid Replacement
• Source Control
• Glycaemic Control
• Nutritional Support
• Adjuncts Stress Ulcer Prophylaxis, DVT
  Prophylaxis, Transfusion, Sedation, Analgesia,
  Organ Replacement

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Early Antibiotic Therapy
Consensus, CCM04

• Start abx. therapy as early as possible, after
  getting cultures
• Broad spectrum, including one or two abx. likely
  effective against the suspected ICU pathogen
• Re-assess coverage within 48 72 hrs, guided by
  cultures

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Strategy For Therapy

• Optimize organ perfusion
• Control infection source
• Support dysfunctional organ system

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Therapeutic Strategies in Sepsis

• Optimize Organ Perfusion
• Expand effective blood volume.
• Hemodynamic monitoring.
• Early goal-directed therapy.

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Therapeutic Strategies in Sepsis

• Optimize Organ Perfusion
• Pressors may be necessary.
• Norepinephrine
• Vasopressin
• Epinephrine
• Dobutamine Norepinephrine

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Therapeutic Strategies in Sepsis

• Control Infection Source
• Drainage
• Surgical
• Radiologically-guided
• Culture-directed antimicrobial therapy
• Support of reticuloendothelial system
• Enteral / parenteral nutritional support
• Minimize immunosuppressive therapies

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Therapeutic Strategies in Sepsis

• Support Dysfunctional Organ Systems
• Renal replacement therapies (CVVHD, HD).
• Cardiovascular support (pressors, inotropes).
• Mechanical ventilation.
• Transfusion for hematologic dysfunction.
• Minimize exposure to hepatotoxic and nephrotoxic
  therapies.

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Surviving Sepsis Campaign InternationalGuideline
s for Management of Severe Sepsisand Septic
Shock 2012
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SURVIVING SEPSIS CAMPAIGN BUNDLES

• 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 30 mL/kg crystalloid for
  hypotension or lactate 4mmol/L

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SURVIVING SEPSIS CAMPAIGN BUNDLES

• TO BE COMPLETED WITHIN 6 HOURS
• 5) Apply vasopressors (for hypotension that does
  not respond to initial fluid resuscitation) to
  maintain MAP 65 mm Hg
• 6) In the event of persistent arterial
  hypotension despite volume resuscitation or
  initial lactate 4 mmol/L
• - Measure central venous pressure (CVP)
• - Measure central venous oxygen saturation
  (ScvO2)
• 7) Remeasure lactate if initial lactate was
  elevated
• Targets for quantitative resuscitation included
  in the guidelines are CVP of 8 mm Hg,
• ScvO2 of 70, and normalization of lactate.

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Initial Resuscitation and Infection Issues

• Goals during the first 6 hrs of resuscitation
• a) Central venous pressure 812 mm Hg
• b) Mean arterial pressure (MAP) 65 mm Hg
• c) Urine output 0.5 mL/kg/hr
• d) Central venous or mixed venous oxygen
  saturation 70 or 65, respectively (grade 1C).
• In patients with elevated lactate levels
  targeting resuscitation to normalize lactate

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Initial Resuscitation and Infection Issues

• Antimicrobial Therapy
• 1. Administration of effective intravenous
  antimicrobials within the first hour of
  recognition of septic shock (grade 1B) and severe
  sepsis (grade 1C) as the goal of therapy.
• 2. Reasses AB therapy daily for deescalation
• 3. PCT level or other biomarkers for
  discontinuation for pts who have no subsequent
  evidence of infection
• Source control
• Infection prevention

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Hemodynamic Support and Adjunctive Therapy

• A. Fluid Therapy of Severe Sepsis
• Crystalloids as the initial fluid of choice in
  the resuscitation (grade 1B).
• Against the use of hydroxyethyl starches for
  fluid resuscitation (grade 1B).
• Albumin in the fluid resuscitation of severe
  sepsis and septic shock when patients require
  substantial amounts of crystalloids (grade 2C).
• Initial fluid challenge in patients with tissue
  hypoperfusion suspicion of hypovolemia to
  achieve a minimum of 30 mL/kg of crystalloids .

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Hemodynamic Support and Adjunctive Therapy

• B. Vasopressors
• Norepinephrine as the first choice vasopressor
  (grade 1B).
• Epinephrine (added to and substituted for
  norepinephrine) when an additional agent is
  needed to maintain adequate blood pressure (grade
  2B).
• Vasopressin 0.03 units/minute can be added to
  norepinephrine with intent of either raising MAP
  or decreasing NE dosage
• Low dose vasopressin is not recommended as the
  single initial vasopressor

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B. Vasopressors

• 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).
• Low-dose dopamine should not be used for renal
  protection

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B. Vasopressors

• 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
• (c) as salvage therapy when combined
  inotrope/vasopressors have failed to achieve MAP
  target (grade 1C).

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Hemodynamic Support and Adjunctive Therapy

• C. Inotropic Therapy
• A trial of dobutamine infusion up to 20
  mcg/kg/min be administered or added to
  vasopressor in the presence of
• myocardial dysfunction
• ongoing signs of hypoperfusion, despite achieving
  adequate intravascular volume and adequate MAP
  (grade 1C)

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Hemodynamic Support and Adjunctive Therapy

• D. Corticosteroids
• Not using hydrocortisone to treat adult septic
  shock patients if adequate fluid resuscitation
  and vasopressor therapy are able to restore
  hemodynamic stability. In case this is not
  achievable, we suggest intravenous hydrocortisone
  at a dose of 200 mg per day (grade 2C).
• 2. Not using the ACTH stimulation test to
  identify adults with septic shock who should
  receive hydrocortisone (grade 2B).
• 3. 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).

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Other Supportive Therapy of Severe Sepsis

• Blood Product Administration
• Once tissue hypoperfusion has resolved and in the
  absence of extenuating circumstances, such as
  myocardial ischemia, severe hypoxemia, acute
  hemorrhage, or ischemic heart disease, we
  recommend that red blood cell transfusion occur
  only when hemoglobin concentration decreases to
  lt7.0 g/dL to target a hemoglobin concentration of
  7.0 9.0 g/dL in adults (grade 1B).
• Not using erythropoietin as a specific treatment
  of anemia associated with severe sepsis (grade
  1B).

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Blood products administrationcontd

• Fresh frozen plasma not be used to correct
  laboratory clotting abnormalities in the absence
  of bleeding or planned invasive procedures (grade
  2D).
• Administer platelets prophylactically when counts
  are lt10,000/mm3 in the absence of apparent
  bleeding. We suggest prophylactic platelet
  transfusion when counts are lt 20,000/mm3 if the
  patient has a significant risk of bleeding.
  Higher platelet counts (50,000/mm3 are advised
  for active bleeding, surgery,
• or invasive procedures (grade 2D).

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Other Supportive Therapy of Severe Sepsis

• Immunoglobulins
• Not using intravenous immunoglobulins in adult
  patients with severe sepsis or septic shock
  (grade 2B).
• Selenium
• Not using intravenous selenium for the treatment
  of severe sepsis (grade 2C).

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Other Supportive Therapy of Severe Sepsis

• Glucose Control
• target an upper blood glucose 180 mg/dL rather
  than an upper target blood glucose 110 mg/dL
  (grade 1A).
• Renal Replacement Therapy
• 1. Continuous renal replacement therapies and
  intermittent hemodialysis are equivalent in
  patients with severe sepsis and acute renal
  failure (grade 2B).

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Other Supportive Therapy of Severe Sepsis

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

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Other Supportive Therapy of Severe Sepsis

• DVT Prophylaxis
• LMWH (grade 1B versus twice daily UFH, grade 2C).
  If creatinine clearance is lt30 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).
• Combination of pharmacologic therapy and
  intermittent pneumatic compression devices
  whenever possible (grade 2C).
• Septic patients who have a contraindication for
  heparin ? mechanical prophylactic treatment
  unless contraindicated.

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Other Supportive Therapy of Severe Sepsis

• Sedation, analgesia, MR
• Mechanichal ventilator setting in ARDS
• Nutrition
• Stress ulcer prophylaxis

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Thank you