Current Management of Severe Sepsis and Septic Shock

1
Current Management of Severe Sepsis and Septic
Shock
Isabel C. Mira-Avendano, M.D. PGY-3
Resident Department of Medicine
2
Current Management of Severe Sepsis and Septic
Shock

• OBJECTIVES
• Review the Septic Shock Management Guidelines
• Know the main trials which are the base for that
  Guidelines
• Discuss the level of evidence for each
  recommendation

3
Introduction

• Severe Sepsis and Septic Shock are major
  healthcare problems
• High mortality
• Increasing in incidence
• APPROPRIATED AND RAPID MANAGEMENT INFLUENCE THE
  OUTCOME

4
Introduction

• SYSTEMIC INFLAMMATORY RESPONSE SYNDROME (SRIS)
• 2 o more of
• Fever oral temperature gt38C or hypothermia
  (lt36C)
• Tachypnea gt24 breaths/min
• Tachycardia heart reat gt90 beats/min

5
Introduction

• SYSTEMIC INFLAMMATORY RESPONSE SYNDROME (SRIS)
• 2 o more of
• Leukocytosis WBC gt12.000/ul, leukopenia
  lt4000/ul, or gt10 bands

6
Introduction

• SEPSIS
• SIRS in response to documented infection

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Introduction

• SEVERE SEPSIS
• Sepsis with evidence of acute organ dysfunction
• CV SBP lt90 mmHg or MAP lt70 mmHg
• RENAL urine output lt0.5 ml/kg/hr
• RESPIRATORY PaO2/FIO2 lt250
• HEMATOLOGIC platelet count lt80.000/ul
• METABOLIC ACIDOSIS pH lt7.30 or plasma lactate
  gt2mmol/L

8
Introduction

• SEPTIC SHOCK
• Severe Sepsis with refractory hypotension MAP
  lt60 mmHg after fluid resucitation (30-50cc/Kg
  crystalloids)

9
Introduction

• Guidelines have been created to improve outomes
  in severe sepsis and septic shock
• These Guidelines are evidence-based medicine
  methodology system

10
Introduction

• HOW THESE GUIDELINES WERE CREATED?

11
Introduction
12
Introduction
13
Introduction
14
Evidence-Based-Guidelines
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Updated International Guidelines
Crit Care Med 2008 36296-327
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International Guidelines Sepsis
Initial Resuscitation
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Initial Resuscitation
Central Venous O2 Saturation SVO2 ?
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Early-Goal Directed Therapy in Sepsis
NEJM 2001 3451368-77
19
NEJM 2001 3451368-77
20
NEJM 2001 3451368-77
21
Early-Goal Directed Therapy in Sepsis
22
Initial Resuscitation

• IF TIME IS MUSCLE IN CASE OF CARDIAC
• ISCHEMIC DISEASE.
• TIME IS L I F E IN CASE OF SEPSIS

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Initial Resuscitation

• During the first 6 hours, goals are
• CV pressure 8-12 mmHg. In mechanical ventilated
  patients or patients with known preexisting
  decreased ventricular compliance, target will be
  12 15 mmHg
• MAP gt 65 mmHg
• 
  Grade 1-B

24
Initial Resuscitation

• During the first 6 hours, goals are
• Urine output gt 0.5 ml/kg/h
• Central venous saturation (SVO2) gt 70
  Intermitent or continuous measurements of O2 are
  the same
• 
  Grade 1-B

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Initial Resuscitation

• During the first 6 hours, goals are
• If SVO2 is not achieved with fluid resuscitation,
  through the CVC target, then transfusion of red
  blood cells to achieve Ht of 30
• After that, if no goal SVO2 is achieved, start
  Dobutamine
• 
  Grade 1-B

26
International Guidelines Sepsis

• Diagnosis

27
Diagnosis

• Obtain appropriate cultures before antimicrobial
  therapy is initiated, if such cultures do not
  cause delay in antibiotic administration.
  Grade 1-C
• Imaging studies should be performed promptly in
  attempts to confirm a potential source of
  infection

28
International Guidelines Sepsis

• Antibiotic Therapy

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Antibiotic Therapy

• Critical Care Medicine 2006. 34, 6
• Retrospective Cohort study
• 2731 patients with Septic Shock
• 50 of them received effective antimicrobial
  administration within the first hour of
  documented hypotension
• Increased survival was seen among them

30
Antibiotic Therapy

• IV antibiotic therapy must be started as early as
  possible and within the first hour of recognition
  of severe sepsis or septic shock
• Broad spectrum therapy until the causative
  organisms and susceptibilities are known
• Evidence 1-C

31
International Guidelines Sepsis

• Source of Control

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Source of Control

• Specific anatomical diagnosis of infection
  requiring consideration of emergent source of
  control, should be sought and diagnosed as
  rapidly as possible and within the first 6 hours
  following presentation
• Grade 1-C

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Source of Control
34
Source of Control
35
International Guidelines Sepsis

• Fluid Therapy

36
Fluid Management in Sepsis
37
Fluid Management in Sepsis
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Fluid Therapy

• Fluid resuscitation could be done with either
  crystalloids or colloids.
• 
  Grade 1-B

39
International Guidelines Sepsis
Vasopressor Support in Septic Shock
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Vasopressor Support in Septic Shock

• Below a certain MAP, autoregulation is lost
  and perfusion becomes linearly depend on pressure

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Vasopressor Support in Septic Shock

• MAP should be maintained over 65 mmHg
• Vasopresor therapy is required to maintain
  perfusion in the face of life-threatening
  hypotension, even when hypovelemia has been not
  resolved
• 
  Evidence C-1

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Vasopressor Support in Septic Shock

• Use either Norepinephrine (NE) or Dopamin (Dopa)
  as the first choice vasopressor agent to correct
  hypotension
• Epinephrine (Epi), Phenylephrine or vasopressin
  should not be administered as the initial
  vasopressor in septic shock
• 
  Evidence C-1

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Vasopressor Support in Septic Shock
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Vasopressin in Sepsis
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Vasopressin in Sepsis

• In physiologic doses 0.01-0.04 U/min, is
  synergistic with exogenous cathecholamines,
  yielding a pressor response without evidence of
  organ hypoperfussion
• In pharmacologic doses gt0.04 U/min, the
  vasopressor effect is associated with
  vasoconstriction of renal, mesenteric, pulmonary
  and coronary vasculature

46
Vasopressor Support in Septic Shock

• Vasopressin 0.03 0.04 U/min may be added to NE,
  to raise BP in patients with refractory Septic
  Shock
• Evidence C-1

47
Vasopressor Support in Septic Shock

• Low dose Dopa not be used for renal protection
  
• 
  Evidence 1-A
• All patients requiring vasopressors must have an
  arterial catheter placed
• 
  Evidence 1-C

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Inotropic Support in Septic Shock
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Inotropic Support in Septic Shock

• Consider Dobutamine as first choice Inotrope for
  patient with measured or suspected low cardiac
  output, in the presence of adequate left
  ventricular filling pressure and adequate MAP
• 
  Evidence 1-C

50
International Guidelines Sepsis
Corticoid Therapy in Septic Shock
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Corticoid Therapy in Septic Shock
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Corticoid Therapy in Septic Shock
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Corticoid Therapy in Sepsis
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Corticoid Therapy in Sepsis

• Use Hydrocortisone only after confirm that BP is
  poorly responsive to fluid resuscitation and
  vasopressor therapy
• Evidence 2-C
• Use no more that 300 mg/day, which will be wean
  when vasopressors are no longer required
• Evidence 2-C
• Not use ACTH stimulation test
• Evidence 2-B

55
International Guidelines Sepsis
Recombinant Activated Protein-C in Severe Sepsis
and Septic Shock
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Activated Protein C in Severe Sepsis
NEJM 2001 344699-709
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Activated Protein C in Severe Sepsis
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Activated Protein C in Severe Sepsis
NEJM 2001 344699-709
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Activated Protein C in Severe Sepsis
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Activated Protein C in Severe Sepsis
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Activated Protein C in Severe Sepsis
NEJM 2005 3531332-41
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Activated Protein C in Severe Sepsis
NEJM 2005 3531332-41
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Activated Protein C in Severe Sepsis
NEJM 2005 3531332-41
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Activated Protein C in Severe Sepsis

• Use its in patients with high risk of death,
  multiple organ failure, APACHE gt 25, if its, is
  not contraindicated
• 
  Evidence 2-B
• Patients with severe sepsis and low risk of
  death, most of who will have APACHE lt 25 or one
  organ failure, should not receive Activated
  Protein C
• 
  Evidence 1-A
• 
  

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International Guidelines Sepsis

• SUPPORTIVE THERAPY OF SEVERE SEPSIS
• Mechanical Ventilation of Sepsis-induced ALI/ARDS

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Mechanical Ventilation of Sepsis-induced ALI/ARDS
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Mechanical Ventilatory Support in ARDS
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Mechanical Ventilatory Support in ARDS
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Mechanical Ventilatory Support in ARDS
NEJM 2000 3421301-8
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Mechanical Ventilatory Support in ARDS

• Target a tidal volume of 6 ml/kg of PBW
• 
  Evidence 1-B
• Upper limit goal for Plateau Pressure less than
  30 cmH2O
• 
  Evidence 1-B
• Permissive hypercapnia be allowed in the patients
  if needed
• 
  Evidence 1-C
• Raising PEEP keeps lung units open

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International Guidelines Sepsis

• SUPPORTIVE THERAPY OF SEVERE SEPSIS
• Sedation, Analgesia, and Neuromuscular blockade
  in Sepsis

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Sedation, Analgesia, and Neuromuscular blockade
in Sepsis

• Use sedation protocols with sedation goal
• Daily interruption of continuous infusion
  sedation with awakening and retitration if
  necessary
• 
  
• 
  Evidence 1-B

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Sedation, Analgesia, and Neuromuscular blockade
in Sepsis

• Neuro Muscular blockage agents (NMBA) should be
  avoided if possible in the septic patient
• 
  Grade 1-B

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International Guidelines Sepsis

• SUPPORTIVE THERAPY OF SEVERE SEPSIS
• Glucose Control

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Tight Glucose Control in Sepsis
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Tight Glucose Control in Sepsis
NEJM 2001 3451359-67
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Tight Glucose Control in Sepsis
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Tight Glucose Control in Sepsis
NEJM 2006 354449-61
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Tight Glucose Control in Sepsis

• Maintain Glucose levels less than 150, using
  validated protocol for insulin dose adjustments
  (enteral preferred)
• 
  Evidence 2-C

80
International Guidelines Sepsis

• SUPPORTIVE THERAPY OF SEVERE SEPSIS
• Renal Replacement Therapy

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Renal Replacement Therapy

• Continuous Renal Replacement Therapies and
  Intermitent Hemodialysis are equivalent in
  patients with severe sepsis and ARF
• 
  Evidence 2-B

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Renal Replacement Therapy

• Use Continuous therapies to facilitate management
  of fluid balance in hemodynamically unstable
  septic patients
• 
  Evidence 2-B

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International Guidelines Sepsis

• SUPPORTIVE THERAPY OF SEVERE SEPSIS
• Bicarbonate Therapy

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Bicarbonate Therapy

• Recommendation is against the use of
  Sodium-Bicarbonate therapy for the purpose of
  improving hemodynamics or reducing vasopressor
  requirements in patients with hypotension-induced
  lactic acidemia with pH gt 7.15
• 
  Evidence 1-B

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Conclusion
Crit Care Med 2004 320Suppl S595-7
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Conclusion
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Thanks