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Sepsis and Septic Shock Mazen Alakhras, MD, FCCP Systemi

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Title: Sepsis and Septic Shock Mazen Alakhras, MD, FCCP Systemi


1
Sepsis and Septic Shock Mazen Alakhras, MD, FCCP
2
Background Population adjusted incidence of sepsis
Martin. NEJM 20033481546
3
Hospital mortality rate of patients with sepsis
Martin. NEJM 20033481546
4
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

5
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.
6
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7
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.
8
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9
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.
10
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.
11
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 1983535-53 Blot F.
J Clin Microbiol 1999 36 105-109.
Dellinger, et. al. Crit Care Med 2004, 32
858-873.
12
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.
13
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.
14
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.
15
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.
16
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.
17
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.
18
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.
19
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20
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

21
Rivers. NEJM 20013451368
22
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

23
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.
24
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.
25
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

26
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.
27
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28
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.
29
Hypovolemic shock
  • Fluid!! Fluid!! Fluid!!
  • Vasopressors if MAP lt 60 mm Hg

30
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.
31
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.
32
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.
33
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.
34
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.
35
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.
36
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.
37
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.
38
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.
39
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