Sepsis and Septic Shock Mazen Alakhras, MD, FCCP Systemi

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Sepsis and Septic ShockMazen Alakhras, MD, FCCP
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Background Population adjusted incidence of sepsis
Martin. NEJM 20033481546
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Hospital mortality rate of patients with sepsis
Martin. NEJM 20033481546
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Systemic inflammatory response syndrome (SIRS)

• SIRS - two of
• Temperature gt 38ºC or lt 36ºC
• Heart rate gt 90 per minute
• Respiratory rate gt 20 per minute or PaCO2 lt 32 mm
  Hg
• WBC gt 12,000 or lt 4,000/mm3, or gt 10 bands
• Sepsis Infection SIRS
• Severe organ dysfunction, hypoperfusion,
  hypotension
• Shock Severe sepsis resistant to fluid

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Index

• Initial Resuscitation
• Diagnosis
• Antibiotic therapy
• Source Control
• Fluid therapy
• Vasopressors
• Inotropic Therapy
• Steroids
• Recombinant Human Activated Protein C (rhAPC)
  drotrecogin alfa (activated)

• Blood Product Administration
• Mechanical Ventilation
• Sedation, Analgesia, and Neuromuscular Blockade
  in Sepsis
• Glucose Control
• Renal Replacement
• Bicarbonate Therapy
• Deep Vein Thrombosis Prophylaxis
• Stress Ulcer Prophylaxis
• Limitation of Support

Dellinger, et. al. Crit Care Med 2004, 32
858-873.
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Initial Resuscitation

• Resuscitation should begin as soon as severe
  sepsis or sepsis induced tissue hypoperfusion is
  recognized
• Elevated Serum lactate identifies tissue
  hypoperfusion in patients at risk who are not
  hypotensive
• Goals of therapy within first 6 hours are
  Grade B

• Central Venous Pressure 8-12 mm Hg (12-15 in
  ventilator pts)
• Mean arterial pressure gt 65 mm Hg
• Urine output gt 0.5 mL/kg/hr
• ScvO2 or SvO2 70 if not achieved with fluid
  resuscitation during first 6 hours
  - Transfuse PRBC to hematocrit gt 30 and/or
  - Administer dobutamine (max 20 mcg/kg/min)
  to goal

-
Rivers E. N Engl J Med 20013451368-77.
Dellinger, et. al. Crit Care Med 2004, 32
858-873.
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Early Goal-Directed Therapy Results
28-day Mortality
60
49.2
P 0.01
50
40
33.3
30
20
10
0
Standard Therapy n133
EGDT n130
Key difference was in sudden CV collapse, not
MODS
Rivers E. N Engl J Med 20013451368-77.
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Index

• Initial Resuscitation
• Diagnosis
• Antibiotic therapy
• Source Control
• Fluid therapy
• Vasopressors
• Inotropic Therapy
• Steroids
• Recombinant Human Activated Protein C (rhAPC)
  drotrecogin alfa (activated)

• Blood Product Administration
• Mechanical Ventilation
• Sedation, Analgesia, and Neuromuscular Blockade
  in Sepsis
• Glucose Control
• Renal Replacement
• Bicarbonate Therapy
• Deep Vein Thrombosis Prophylaxis
• Stress Ulcer Prophylaxis
• Limitation of Support

Dellinger, et. al. Crit Care Med 2004, 32
858-873.
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Diagnosis
Grade D

• Before the initiation of antimicrobial therapy,
  at least two blood cultures should be obtained
• At least one drawn percutaneously
• At least one drawn through each vascular access
  device if inserted longer than 48 hours
• Other cultures such as urine, cerebrospinal
  fluid, wounds, respiratory secretions or other
  body fluids should be obtained as the clinical
  situation dictates
• Other diagnostic studies such as imaging and
  sampling should be performed promptly to
  determine the source and causative organism of
  the infection
• may be limited by patient stability

Grade D
Grade E
Weinstein MP. Rev Infect Dis 1983535-53Blot F.
J Clin Microbiol 1999 36 105-109.
Dellinger, et. al. Crit Care Med 2004, 32
858-873.
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Index

• Initial Resuscitation
• Diagnosis
• Antibiotic therapy
• Source Control
• Fluid therapy
• Vasopressors
• Inotropic Therapy
• Steroids
• Recombinant Human Activated Protein C (rhAPC)
  drotrecogin alfa (activated)

• Blood Product Administration
• Mechanical Ventilation
• Sedation, Analgesia, and Neuromuscular Blockade
  in Sepsis
• Glucose Control
• Renal Replacement
• Bicarbonate Therapy
• Deep Vein Thrombosis Prophylaxis
• Stress Ulcer Prophylaxis
• Limitation of Support

Dellinger, et. al. Crit Care Med 2004, 32
858-873.
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Antibiotic Therapy

• Start intravenous antibiotic therapy within the
  first hour of recognition of severe sepsis after
  obtaining appropriate cultures
• Empirical choice of antimicrobials should include
  one or more drugs with activity against likely
  pathogens, both bacterial or fungal
• Penetrate presumed source of infection
• Guided by susceptibility patterns in the
  community and hospital
• Continue broad spectrum therapy until the
  causative organism and its susceptibilities are
  defined

Grade E Grade D
Kreger BE. Am J Med 198068344-355. Ibrahim
EH. Chest 2000118146-155. Hatala R. Ann
Intern Med 1996124-717-725.
Dellinger, et. al. Crit Care Med 2004, 32
858-873.
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Antibiotic Therapy
Grade E

• Reassess after 48-72 hours to narrow the spectrum
  of antibiotic therapy
• Duration of therapy should typically be 7-10 days
  and guided by clinical response
• Some experts prefer combination therapy for
  Pseudomonas infections or neutropenic patients
• Stop antimicrobials promptly if clinical syndrome
  is determined to be noninfectious

Grade E
Grade E
Grade E
Dellinger, et. al. Crit Care Med 2004, 32
858-873.
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Index

• Initial Resuscitation
• Diagnosis
• Antibiotic therapy
• Source Control
• Fluid therapy
• Vasopressors
• Inotropic Therapy
• Steroids
• Recombinant Human Activated Protein C (rhAPC)
  drotrecogin alfa (activated)

• Blood Product Administration
• Mechanical Ventilation
• Sedation, Analgesia, and Neuromuscular Blockade
  in Sepsis
• Glucose Control
• Renal Replacement
• Bicarbonate Therapy
• Deep Vein Thrombosis Prophylaxis
• Stress Ulcer Prophylaxis
• Limitation of Support

Dellinger, et. al. Crit Care Med 2004, 32
858-873.
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Source Control
Grade E

• Evaluate patients for focus of infection amenable
  to source control measures
• Drainage of an abscess or local focus of
  infection
• Debridement of infected necrotic tissue
• Removal of a potentially infected device
• Definitive control of a source of ongoing
  microbial contamination
• Source control methods must weigh benefits and
  risks of the specific intervention
  

Grade E
Jimenez MF. Intensive Care Med 200127S49-S62. Bu
falari A. Acta Chir Belg 199696197-200.
Dellinger, et. al. Crit Care Med 2004, 32
858-873.
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Source Control Examples of Potential Sites

• Drainage
• Intra-abdominal abscess - Septic
  arthritis
• Thoracic empyema -
  Pyelonephritis, cholangitis
• Debridement
• Necrotizing fasciitis -
  Mediastinitis
• Infected pancreatic necrosis -
  Intestinal infarction
• Device Removal
• Infected vascular catheter
• Urinary catheter
• Colonized endotracheal tube
• Definitive Control
• Sigmoid resection for diverticulitis
• Amputation for clostridial myonecrosis
• Cholecystectomy for gangrenous cholecystitis

Dellinger, et. al. Crit Care Med 2004, 32
858-873.
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Index

• Initial Resuscitation
• Diagnosis
• Antibiotic therapy
• Source Control
• Fluid therapy
• Vasopressors
• Inotropic Therapy
• Steroids
• Recombinant Human Activated Protein C (rhAPC)
  drotrecogin alfa (activated)

• Blood Product Administration
• Mechanical Ventilation
• Sedation, Analgesia, and Neuromuscular Blockade
  in Sepsis
• Glucose Control
• Renal Replacement
• Bicarbonate Therapy
• Deep Vein Thrombosis Prophylaxis
• Stress Ulcer Prophylaxis
• Limitation of Support

Dellinger, et. al. Crit Care Med 2004, 32
858-873.
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Case

• An 80 year-old female is transferred from the
  regular hospital floor to the ICU for severe
  sepsis. Resuscitation in the first 6 hours should
  try to achieve all of the following EXCEPT
• Central venous pressure of 8 mm Hg
• Mean arterial pressure of 65 mm Hg
• Central venous oxygen saturation of 70
• Urine output of 0.5 mL/Kg.h
• Cardiac index of 4 L/min.mm2

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Rivers. NEJM 20013451368
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Septic shock - resuscitation

• Aim for higher CVP (12-15 mm Hg)
• Positive pressure ventilation
• Increased intrathoracic pressure
• Increased intra-abdominal pressure
• Chronic pulmonary disease and cardiomyopathy

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Fluid Therapy Choice of Fluid
Grade C

• Fluid resuscitation may consist of natural or
  artificial colloids or crystalloids
• No evidenced-based support for one type of fluid
  over another
• Crystalloids have a much larger volume of
  distribution compared to colloids
• Crystalloid resuscitation requires more fluid to
  achieve the same endpoints as colloid
• Crystalloids result in more edema

Choi PTL. Crit Care Med 199927200-210. Cook D.
Ann Intern Med 2001135205-208. Schierhout G.
BMJ 1998316961-964.
Dellinger, et. al. Crit Care Med 2004, 32
858-873.
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Fluid Therapy Fluid Challenge
Grade E

• Fluid challenge in patients with suspected
  hypovolemia may be given
• 500 - 1000 mL of crystalloids over 30 mins
  (20ml/kg)
• 300 - 500 mL of colloids over 30 mins
• Repeat based on response and tolerance
• Input is typically greater than output due to
  venodilation and capillary leak
• Most patients require continuing aggressive fluid
  resuscitation during the first 24 hours of
  management

Dellinger, et. al. Crit Care Med 2004, 32
858-873.
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The Volume Properties of 1-L Fluid Infusion

• Fluid Volume (mL)
• Intracellular Extra-cellular
• Interstitial Plasma
• D5W 660 255 85
• NS or LR -100 825 275
• 3 NaCl -2950 2690 990
• 5 Albumin 0 500 500
• Whole blood 0 0 1000

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Index

• Initial Resuscitation
• Diagnosis
• Antibiotic therapy
• Source Control
• Fluid therapy
• Vasopressors
• Inotropic Therapy
• Steroids
• Recombinant Human Activated Protein C (rhAPC)
  drotrecogin alfa (activated)

• Blood Product Administration
• Mechanical Ventilation
• Sedation, Analgesia, and Neuromuscular Blockade
  in Sepsis
• Glucose Control
• Renal Replacement
• Bicarbonate Therapy
• Deep Vein Thrombosis Prophylaxis
• Stress Ulcer Prophylaxis
• Limitation of Support

Dellinger, et. al. Crit Care Med 2004, 32
858-873.
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Vasopressors
Grade E

• Initiate vasopressor therapy if appropriate fluid
  challenge fails to restore adequate blood
  pressure and organ perfusion
• Vasopressor therapy should also be used
  transiently in the face of life-threatening
  hypotension, even when fluid challenge is in
  progress
• Either norepinephrine or dopamine are first line
  agents to correct hypotension in septic shock
• Norepinephrine is more potent than dopamine and
  may be more effective at reversing hypotension in
  septic shock patients
• Dopamine may be particularly useful in patients
  with compromised systolic function but causes
  more tachycardia and may be more
  arrhythmogenic

Grade D
LeDoux D. Crit Care Med 2000282729-2732. Regnie
r B. Intensive Care Med 1977347-53. Martin C.
Chest 19931031826-1831.
Martin C. Crit Care Med 2000282758-2765.
DeBacker D. Crit Care Med 2003311659-1667.
Hollenberg SM. Crit
Care Med 1999 27 639-660.
Dellinger, et. al. Crit Care Med 2004, 32
858-873.
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Hypovolemic shock

• Fluid!! Fluid!! Fluid!!
• Vasopressors if MAP lt 60 mm Hg

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Index

• Initial Resuscitation
• Diagnosis
• Antibiotic therapy
• Source Control
• Fluid therapy
• Vasopressors
• Inotropic Therapy
• Steroids
• Recombinant Human Activated Protein C (rhAPC)
  drotrecogin alfa (activated)

• Blood Product Administration
• Mechanical Ventilation
• Sedation, Analgesia, and Neuromuscular Blockade
  in Sepsis
• Glucose Control
• Renal Replacement
• Bicarbonate Therapy
• Deep Vein Thrombosis Prophylaxis
• Stress Ulcer Prophylaxis
• Limitation of Support

Dellinger, et. al. Crit Care Med 2004, 32
858-873.
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Inotropic Therapy
Grade E

• In patients with low cardiac output despite
  adequate fluid resuscitation, dobutamine may be
  used to increase cardiac output
  
• Should be combined with vasopressor therapy in
  the presence of hypotension
  
• It is not recommended to increase cardiac index
  to target an arbitrarily predefined elevated
  level
• Patients with severe sepsis failed to benefit
  from increasing oxygen delivery to supranormal
  levels by use of dobutamine

Grade A
Gattinoni L. N Eng J Med 19953331025-1032. Hayes
MA. N Eng J Med 19943301717-1722.
Dellinger, et. al. Crit Care Med 2004, 32
858-873.
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Index

• Initial Resuscitation
• Diagnosis
• Antibiotic therapy
• Source Control
• Fluid therapy
• Vasopressors
• Inotropic Therapy
• Steroids
• Recombinant Human Activated Protein C (rhAPC)
  drotrecogin alfa (activated)

• Blood Product Administration
• Mechanical Ventilation
• Sedation, Analgesia, and Neuromuscular Blockade
  in Sepsis
• Glucose Control
• Renal Replacement
• Bicarbonate Therapy
• Deep Vein Thrombosis Prophylaxis
• Stress Ulcer Prophylaxis
• Limitation of Support

Dellinger, et. al. Crit Care Med 2004, 32
858-873.
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Steroids
Grade C

• Intravenous corticosteroids are recommended in
  patients with septic shock who require
  vasopressor therapy to maintain blood pressure
• Administer intravenous hydrocortisone 200-300
  mg/day for 7 days in three or four divided doses
  or by continuous infusion
• Shown to reduce mortality rate in patients with
  relative adrenal insufficiency

Annane, D. JAMA, 2002 288 (7) 868
Dellinger, et. al. Crit Care Med 2004, 32
858-873.
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Index

• Initial Resuscitation
• Diagnosis
• Antibiotic therapy
• Source Control
• Fluid therapy
• Vasopressors
• Inotropic Therapy
• Steroids
• Recombinant Human Activated Protein C (rhAPC)
  drotrecogin alfa (activated)

• Blood Product Administration
• Mechanical Ventilation
• Sedation, Analgesia, and Neuromuscular Blockade
  in Sepsis
• Glucose Control
• Renal Replacement
• Bicarbonate Therapy
• Deep Vein Thrombosis Prophylaxis
• Stress Ulcer Prophylaxis
• Limitation of Support

Dellinger, et. al. Crit Care Med 2004, 32
858-873.
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Recombinant human Activated Protein C
Grade B

• Recombinant human Activated Protein C
  Drotrecogin alfa (activated) is recommended in
  patients at a high risk of death
• Treatment with drotrecogin alfa (activated)
  should begin as soon as possible once a patient
  has been identified as being at high risk of
  death
• Patients should have no absolute or relative
  contraindication related to bleeding risk that
  outweighs the potential benefit of rhAPC

Bernard GR. N Eng J Med 2001344699-709.
Dellinger, et. al. Crit Care Med 2004, 32
858-873.
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Index

• Initial Resuscitation
• Diagnosis
• Antibiotic therapy
• Source Control
• Fluid therapy
• Vasopressors
• Inotropic Therapy
• Steroids
• Recombinant Human Activated Protein C (rhAPC)
  drotrecogin alfa (activated)

• Blood Product Administration
• Mechanical Ventilation
• Sedation, Analgesia, and Neuromuscular Blockade
  in Sepsis
• Glucose Control
• Renal Replacement
• Bicarbonate Therapy
• Deep Vein Thrombosis Prophylaxis
• Stress Ulcer Prophylaxis
• Limitation of Support

Dellinger, et. al. Crit Care Med 2004, 32
858-873.
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Blood Product Administration
Grade B

• Red blood transfusion should occur only when
  hemoglobin decreases to lt 7 g/dL
• Once tissue hypoperfusion has resolved and in the
  absence of extenuating circumstances such as
  significant coronary artery disease, acute
  hemorrhage or lactic acidosis
• Target hemoglobin of 7 9 g/dL
• Routine use of fresh frozen plasma to correct
  laboratory clotting abnormalities in the absence
  of bleeding or planned invasive procedures is not
  recommended

Grade E
Corwin HL. JAMA 20022882827-2835.
Dellinger, et. al. Crit Care Med 2004, 32
858-873.
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Index

• Initial Resuscitation
• Diagnosis
• Antibiotic therapy
• Source Control
• Fluid therapy
• Vasopressors
• Inotropic Therapy
• Steroids
• Recombinant Human Activated Protein C (rhAPC)
  drotrecogin alfa (activated)

• Blood Product Administration
• Mechanical Ventilation
• Sedation, Analgesia, and Neuromuscular Blockade
  in Sepsis
• Glucose Control
• Renal Replacement
• Bicarbonate Therapy
• Deep Vein Thrombosis Prophylaxis
• Stress Ulcer Prophylaxis
• Limitation of Support

Dellinger, et. al. Crit Care Med 2004, 32
858-873.
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Thank You