Systemic Inflammatory Response Syndrome (SIRS) PRANE

1
Systemic Inflammatory
Response Syndrome (SIRS)

• PRANEE
  SITAPOSA, MD.

2
SEPSIS and Its Disease spectrum

• Various stages of disease
• Bacteremia
• SIRS
• Sepsis syndrome
• Sepsis shock early and refractory

3
Definition

• Infection
• Presence of microorganisms in a normally sterile
  site.
• Bacteremia
• Cultivatable bacteria in the blood stream.
• Sepsis
• The systemic response to infection.
  If associated with proven or clinically
  suspected infection, SIRS is called sepsis.

American College of Chest Physicians/Society of
Critical Care Medicine Consensus Conference
Committee. Crit Care Med. 199220864-874.
4
SIRS
(Systemic Inflammatory Response Syndrome)

• The systemic response to a wide range of
  stresses.
• Temperature gt38C (100.4) or lt36C (96.8F).
• Heart rate gt90 beats/min.
• Respiratory rate gt20 breaths/min or
  PaCO2 lt32 mmHg.
• White blood cells gt 12,000 cells/ml or lt 4,000
  cells/ml or gt10 immature (band) forms.
• Note
• Two or more of the following must be present.
• These changes should be represent acute
  alterations from baseline in the absence of other
  known cause for the abnormalities.

American College of Chest Physicians/Society of
Critical Care Medicine Consensus Conference
Committee. Crit Care Med. 199220864-874.
5
Severe Sepsis

• Sepsis with organ hypoperfusion
  one of the followings
• SBP lt 90 mmHg
• Acute mental status change
• PaO2 lt 60 mmHg on RA (PaO2 /FiO2 lt 250)
• Increased lactic acid/acidosis
• Oliguria
• DIC or Platelet lt 80,000 /mm3
• Liver enzymes gt 2 x normal

American College of Chest Physicians/Society of
Critical Care Medicine Consensus Conference
Committee. Crit Care Med. 199220864-874.
6
MODS(Multiple Organ Dysfunction Syndrome)

• Sepsis with multiorgan hypoperfusion
• Two or more of the followings
• SBP lt 90 mmHg
• Acute mental status change
• PaO2 lt 60 mmHg on RA (PaO2 /FiO2 lt 250)
• Increased lactic acid/acidosis
• Oliguria
• DIC or Platelet lt 80,000 /mm3
• Liver enzymes gt 2 x normal
• 
  
  
  
  
  
  
  
  

American College of Chest Physicians/Society of
Critical Care Medicine Consensus Conference
Committee. Crit Care Med. 199220864-874.
7
Relationship between SIRS and Sepsis
Bone RC et al, Chest1992101164-55.
8
The Sepsis Continuum

• A clinical response arising from a nonspecific
  insult, with ?2 of the following
• T gt38oC or lt36oC
• HR gt90 beats/min
• RR gt20/min
• WBC gt12,000/mm3 or lt4,000/mm3 or gt10 bands

• SIRS with a
• presumed
• or confirmed
• infectious
• process

Sepsis with organ failure
Refractory hypotension
SIRS systemic inflammatory response
syndrome
Chest 19921011644.
9
Mortality rate in SIRS
Rangel-Frausto, et al. JAMA 273117-123, 1995.
10
The Response to Pathogens Cross-Talk
NEJM 2003348138-150.
11
Inflammatory Response to Sepsis
NEJM 20063551699-1713.
12
Procoagulant Response in Sepsis
NEJM 20063551699-1713.
13
Pathogenesis of sepsis and septic shock
Angus DC, et al. Crit Care Med 2001,
291303-1310.
14
Pathogenesis of Severe Sepsis
Infection
Microbial Products (exotoxin/endotoxin)
Cellular Responses
Platelet Activation
Cytokines TNF, IL-1, IL-6
CoagulationActivation
Kinins Complement
Oxidases
Coagulopathy/DIC Vascular/Organ System Injury
Endothelial damage
Endothelial damage
Multi-Organ Failure
Death
15
Normal Systemic Response to Infection and Injury
(1)

• Leukocytosis Mobilizes neutrophils into the
  circulation
• Tachycardia Increases cardiac output, blood
  flow to injuried tissue
• Fever Raises core temperature peripheral
  vasoconstriction shunts blood flow to
  injuried tissue. Occurs much more often
  when infection is the trigger for systemic
  responses

Mandell et al. Principals and Practice of
Infectious Diseases6th ed906906-926.
16
Normal Systemic Response to Infection and Injury
(2)

• Acute-Phase Responses
• Anti-infective
• Increases synthesis of complement factors,
  microbe pattern-recognition molecules(mannose-bind
  ing lectin, LBP, CRP, CD14, Others)
• Sequesters iron (lactoferrin) and zinc
  (metallothionein)

Mandell et al. Principals and Practice of
Infectious Diseases6th ed906906-926.
17
Normal Systemic Response to Infection and Injury
(3)

• Anti-inflammatory
• Releases anti-inflammatory neuroendocrine
  hormones (cortisol, ACTH, epinephrine, a-MSH)
• Increases synthesis of proteins that help prevent
  inflammation within the systemic compartment
• Cytokine antagonists (IL-1Ra, sTNF-Rs)
• Anti-inflammatory mediators (e.g.,IL-4, IL-6,
  IL-6R, IL-10, IL-13, TGF-ß)
• Protease inhibitors (e.g.,a1-antiprotease)
• Antioxidants (haptoglobin)
• Reprograms circulating leukocytes (epinephrine,
  cortisol, PGE2, ?other)

Mandell et al. Principals and Practice of
Infectious Diseases6th ed906906-926.
18
Normal Systemic Response to Infection and Injury
(4)

• Procoagulant
• Walls off infection, prevents systemic spread
• Increases synthesis or release of fibrinogen,
  PAI-1, C4b
• Decreases synthesis of protein C, anti-thrombin
  III
• Metabolic
• Preserves euglycemia, mobilizes fatty acids,
  amino acids
• Epinephrine, cortisol, glucagon, cytokines
• Thermoregulatory
• Inhibits microbial growth
• Fever

Mandell et al. Principals and Practice of
Infectious Diseases6th ed906906-926.
19
Risk factors of sepsis

• aggressive oncological chemotherapy and radiation
  therapy
• use of corticosteroid and immunosuppressive
  therapies for organ transplants and inflammatory
  diseases
• longer lives of patients predisposed to sepsis,
  the elderly, diabetics, cancer patients, patients
  with major organ failure, and with
  granulocyopenia.
• Neonates are more likely to develop sepsis (ex.
  group B Streptococcal infections).
• increased use of invasive devices such as
  surgical protheses, inhalation equipment, and
  intravenous and urinary catheters.
• indiscriminate use of antimicrobial drugs that
  create conditions of overgrowth, colonization,
  and subsequent infection by aggressive,
  antimicrobial-resistant organisms.

Angus DC, et al. Crit Care Med 2001,
291303-1310.
20
Patients at increased risks of developing sepsis

• Underlying diseases neutropenia, solid tumors,
  leukemia, dysproteinemias, cirrhosis of the
  liver, diabetes, AIDS, serious chronic
  conditions.
• Surgery or instrumentation catheters.
• Prior drug therapy Immuno-suppressive drugs,
  especially with broad-spectrum antibiotics.
• Age males, above 40 y females, 20-45 y.
• Miscellaneous conditions childbirth, septic
  abortion, trauma and widespread burns, intestinal
  ulceration.

Angus DC, et al. Crit Care Med 2001,
291303-1310.
21
Source
(usually an endogenous source of infection)

• intestinal tract
• oropharynx
• instrumentation sites
• contaminated inhalation therapy equipment
• IV fluids.
• Most frequent sites of infection Lungs, abdomen,
  and urinary tract.
• Other sources include the skin/soft tissue and
  the CNS.

Angus DC, et al. Crit Care Med 2001,
291303-1310.
22
Diagnosis

• History
• community or nosocomially acquired infection
• immunocompromised patient
• exposure to animals, travel, tick bites,
  occupational hazards, alcohol use, seizures, loss
  of consciousness, medications
• underlying diseases specific infectious agents
• Some clues to a septic event include
• Fever or unexplained signs with malignancy or
  instrumentation
• Hypotension
• Oliguria or anuria
• Tachypnea or hyperpnea
• Hypothermia without obvious cause
• Bleeding

Angus DC, et al. Crit Care Med 2001, 291303-1310.
23
Specific Infectious agents

• Splenectomy (traumatic or functional)
• S pneumoniae, H influenzae, N meningitidis
• Neutropenia (lt500 neutrophil/ml)
• Gram-negative, including P aeruginosa,
  gram-positives, including S aureus
• Fungi, especially Candida species
• Hypogammaglobulinemia (e.g.,CLL)
• S pneumoniae, E coli
• Burns
• MRSA, P aeruginosa, resistant gram-negatives

MacArthur RD, et al.
Mosby, 20013-10. Wheeler AP, et
al. NEJM 1999340207-214. Chaowagul W, et
al. J Infect Dis 1989159890-899.
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Specific Infectious agents

• Aids
• P aeuginosa (if neutropenic), S aureus, PCP
  pneumonia
• Intravascular devices
• S aureus, S epidermidis
• Nosocomial infections
• MRSA, Enterococcus species, resistant
  gram-negative, Candida species
• Septic patients in NE of Thailand
• Burkholderia pseudomallei

MacArthur RD, et al.
Mosby, 20013-10.
Wheeler AP, et
al. NEJM 1999340207-214.
Chaowagul W, et
al. J Infect Dis 1989159890-899.
25
Diagnosis

• Physical Examination
• essential
• In all neutropenic patients and in patients with
  as suspected pelvic infection the physical exam
  should include rectal, pelvic, and genital
  examinations
• perirectal, and/or perineal abscesses
• pelvic inflammatory disease and/or abscesses, or
  prostatitis

Angus DC, et al. Crit Care Med 2001,
291303-1310.
26
Signs and Symptoms

• Nonspecific symptoms of sepsis not
  pathognomonic
• fever
• chills
• constitutional symptoms of fatigue, malaise
• anxiety or confusion
• absent symptoms in serious infections, especially
  in elderly individuals

Angus DC, et al. Crit Care Med 2001, 291303-1310.
27
Complications

• Adult respiratory distress syndrome (ARDS)
• Disseminated Intravascular Coagulation (DIC)
• Acute Renal failure (ARF)
• Intestinal bleeding
• Liver failure
• Central Nervous System dysfunction
• Heart failure
• Death

Angus DC, et al. Crit Care Med 2001, 291303-1310.
28
Surviving Sepsis Campaign
Guidelines for Management of Severe Sepsis and
Septic Shock
Dellinger RP, et al. Crit Care Med 2004
32858-873.
29
Diagnosis

• 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

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.
30
Sepsis resuscitation bundle

• Serum lactate measured
• Blood cultures obtained before antibiotics
  administered
• Improve time to broad-spectrum antibiotics
• In the event of hypotension or lactate gt 4 mmol/L
  (36 mg/dL)
• a. Deliver an initial minimum of 20 mL/kg of
  crystaloid (or colloid
  equivalent)
• b. apply vasopressors for ongoing hypotension
• In the event of persistent hypotension despite
  fluid resuscitation or lactate gt 4 mmol/L (36
  mg/dL)
• a. achieve central venous pressure of gt 8 mmHg
• b. achieve central venous oxygen saturation of gt
  70

Hurtado FJ. et al. Crit Care Clin2006
22521-9.
31
Sepsis management bundle

• Fluid resuscitation
• Appropriate cultures prior to antibiotic
  administration
• Early targeted antibiotics and source control
• Use of vasopressors/inotropes when fluid
• resuscitation optimized

Surviving Sepsis Campaign Management Guidelines
Committee. Crit Care Med 2004 32858-873.
32
Sepsis management bundle

• Evaluation for adrenal insufficiency
• Stress dose corticosteroid administration
• Recombinant human activated protein C (xigris)
  for severe sepsis
• Low tidal volume mechanical ventilation for ARDS
• Tight glucose control

Surviving Sepsis Campaign Management Guidelines
Committee. Crit Care Med 2004 32858-873.
33
Infection Control

• Appropriate cultures prior to antibiotic
• administration
• Early targeted antibiotics and source control

Surviving Sepsis Campaign Management Guidelines
Committee. Crit Care Med 2004 32858-873.
34
Early Goal-Directed Therapy
CVP central venous
pressure MAP mean arterial
pressure ScvO2 central
venous oxygen
saturation
NEJM 20013451368-77.
35
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



NEJM 20013451368-77.
36
Antibiotic use in Sepsis (1)

• The drugs used depends on the source of the
  sepsis
• Community acquired pneumonia
• third (ceftriaxone) or fourth (cefepime)
  generation cephalosporin is given with an
  aminoglycoside (usually gentamicin)
• Nosocomial pneumonia
• Cefipime or Imipenem-cilastatin and an
  aminoglycoside
• Abdominal infection
• Imipenem-cilastatin or Pipercillin-tazobactam and
  aminoglycoside

Angus DC, et al. Crit Care Med 2001,
291303-1310.
37
Antibiotic use in Sepsis (2)

• Nosocomial abdominal infection
• Imipenem-cilastatin and aminoglycoside or
  Pipercillin-tazobactam and Amphotericin B
• Skin/soft tissue
• Vancomycin and Imipenem-cilastatin or
  Piperacillin-tazobactam
• Nosocomial skin/soft tissue
• Vancomycin and Cefipime
• Urinary tract infection
• Ciprofloxacin and aminoglycoside

Angus DC, et al. Crit Care Med 2001,
291303-1310.
38
Antibiotic use in Sepsis (3)

• Nosocomial urinary tract infection
• Vancomycin and Cefipime
• CNS infection
• Vancomycin and third generation cephalosporin or
  Meropenem
• Nosocomial CNS infection
• Meropenem and Vancomycin
• Drugs will change depending on the most likely
  cause of the patient's sepsis
• Single drug regimens are usually only indicated
  when the organism causing sepsis has been
  identified and antibiotic sensitivity testing

Angus DC, et al. Crit Care Med 2001, 291303-1310.
39
New Drug in Treating Severe Sepsis

• It is the first agent approved by the FDA
  effective in the treatment of severe sepsis
  proven to reduce mortality. Activated Protein C
  (Xigris) mediates many actions of body
  homeostasis. It is a potent agent for the
• suppression of inflammation
• prevention of microvascular coagulation
• reversal of impaired fibrinolysis

Angus DC, et al. Crit Care Med 2001, 291303-1310.
40
NEJM3551699-1723.
41
Sepsis Cascade
42
Activated Protein C (Xigris)
NEJM3551640,
October 19, 2006.
43
Thank you