Docstoc

Systemic Inflammatory Response Syndrome

Document Sample
Systemic Inflammatory Response Syndrome Powered By Docstoc
					Systemic Inflammatory
Response Syndrome
(SIRS)



         PRANEE SITAPOSA, MD.
SEPSIS and It’s Disease
spectrum
 Various stages of disease
     Bacteremia
     SIRS
     Sepsis syndrome
     Sepsis shock : early and refractory
             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. 1992;20:864-874.
            SIRS
            (Systemic Inflammatory Response Syndrome)

             The systemic response to a wide range of stresses.
                   Temperature >38°C (100.4°) or <36°C (96.8°F).
                   Heart rate >90 beats/min.
                   Respiratory rate >20 breaths/min or
                    PaCO2 <32 mmHg.
                   White blood cells > 12,000 cells/ml or < 4,000 cells/ml or
                    >10% 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. 1992;20:864-874.
             Severe Sepsis

  Sepsis with organ hypoperfusion
    one of the followings :
      SBP < 90 mmHg

      Acute mental status change

      PaO2 < 60 mmHg on RA (PaO2 /FiO2 < 250)

      Increased lactic acid/acidosis

      Oliguria

      DIC or Platelet < 80,000 /mm3
      Liver enzymes > 2 x normal


American College of Chest Physicians/Society of Critical Care Medicine Consensus
Conference Committee. Crit Care Med. 1992;20:864-874.
             MODS
             (Multiple Organ Dysfunction Syndrome)
 Sepsis with multiorgan hypoperfusion
  Two or more of the followings:
    SBP < 90 mmHg

    Acute mental status change

    PaO2 < 60 mmHg on RA (PaO2 /FiO2 < 250)

    Increased lactic acid/acidosis

    Oliguria

    DIC or Platelet < 80,000 /mm3
    Liver enzymes > 2 x normal



American College of Chest Physicians/Society of Critical Care Medicine Consensus
Conference Committee. Crit Care Med. 1992;20:864-874.
Relationship between SIRS
and Sepsis




           Bone RC et al, Chest1992;101:164-55.
            The Sepsis Continuum
                                           Severe           Septic
       SIRS            Sepsis              Sepsis           Shock


A clinical response
 arising from a             SIRS with a      Sepsis with    Refractory
 nonspecific insult, with   presumed        organ failure   hypotension
 2 of the following:       or confirmed
   T >38oC or <36oC        infectious
   HR >90 beats/min        process
   RR >20/min
   WBC >12,000/mm3 or        SIRS = systemic inflammatory
    <4,000/mm3 or >10%            response syndrome
    bands                                           Chest 1992;101:1644.
Mortality rate in SIRS




        Rangel-Frausto, et al. JAMA 273:117-123, 1995.
The Response to Pathogens
      “Cross-Talk”




               NEJM 2003;348:138-150.
Inflammatory Response to
Sepsis




                NEJM 2006;355:1699-1713.
Procoagulant Response in
Sepsis




                NEJM 2006;355:1699-1713.
Pathogenesis of sepsis and
septic shock




      Angus DC, et al. Crit Care Med 2001, 29:1303-1310.
 Pathogenesis of Severe Sepsis
                           Infection

                      Microbial Products
                     (exotoxin/endotoxin)

                      Cellular Responses
 Platelet    Coagulation                 Kinins      Cytokines
Activation    Activation   Oxidases    Complement   TNF, IL-1, IL-6

                      Coagulopathy/DIC
                 Vascular/Organ System Injury




                      Multi-Organ Failure


                            Death
            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 ed;906:906-926.
             Normal Systemic Response to
             Infection and Injury (2)
 Acute-Phase Responses
      Anti-infective
         Increases  synthesis of complement factors, microbe
          pattern-recognition molecules(mannose-binding lectin,
          LBP, CRP, CD14, Others)
         Sequesters iron (lactoferrin) and zinc (metallothionein)




  Mandell et al. Principals and Practice of Infectious Diseases6th ed;906:906-926.
            Normal Systemic Response to
            Infection and Injury (3)
 Anti-inflammatory
      Releases anti-inflammatory neuroendocrine hormones
       (cortisol, ACTH, epinephrine, α-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-β)
         Protease inhibitors (e.g.,α1-antiprotease)
         Antioxidants (haptoglobin)
      Reprograms circulating leukocytes (epinephrine,
       cortisol, PGE2, ?other)
 Mandell et al. Principals and Practice of Infectious Diseases6th ed;906:906-926.
             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 ed;906:906-926.
           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, 29:1303-1310.
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, 29:1303-1310.
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, 29:1303-1310.
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, 29:1303-1310.
        Specific Infectious agents
 Splenectomy (traumatic or functional)
    S pneumoniae, H influenzae, N meningitidis
 Neutropenia (<500 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, 2001:3-10.
                                 Wheeler AP, et al. NEJM 1999;340:207-214.
                            Chaowagul W, et al. J Infect Dis 1989;159:890-899.
         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, 2001:3-10.
                                Wheeler AP, et al. NEJM 1999;340:207-214.
                           Chaowagul W, et al. J Infect Dis 1989;159:890-899.
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

              inflammatory disease and/or
        pelvic
         abscesses, or prostatitis


           Angus DC, et al. Crit Care Med 2001, 29:1303-1310.
    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, 29:1303-1310.
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, 29:1303-1310.
  Surviving Sepsis Campaign


Guidelines for Management of
Severe Sepsis and Septic Shock




            Dellinger RP, et al. Crit Care Med 2004; 32:858-873.
          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 1983;5:35-53
                                                Blot F. J Clin Microbiol 1999; 36: 105-109.

                              Dellinger, et. al. Crit Care Med 2004, 32: 858-873.
          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 > 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 > 4 mmol/L (36 mg/dL)
    a. achieve central venous pressure of > 8 mmHg
    b. achieve central venous oxygen saturation of > 70%

                          Hurtado FJ. et al. Crit Care Clin;2006; 22:521-9.
                 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; 32:858-873.
                 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; 32:858-873.
                 Infection Control

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




Surviving Sepsis Campaign Management Guidelines Committee. Crit Care Med 2004; 32:858-873.
                    Early Goal-Directed
                          Therapy


CVP : central
      venous
      pressure

MAP : mean
      arterial
      pressure

ScvO2: central
       venous
       oxygen
       saturation




                    NEJM 2001;345:1368-77.
     Early Goal-Directed Therapy
     Results 28-day Mortality
60
              49.2%
50                         P = 0.01*

40
                                        33.3%
30

20

10

0
       Standard Therapy                 EGDT
               n=133                    n=130
 *Key difference was in sudden CV collapse, not MODS
                                   NEJM 2001;345:1368-77.
       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, 29:1303-1310.
       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, 29:1303-1310.
          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, 29:1303-1310.
           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, 29:1303-1310.
NEJM;355:1699-1723.
Sepsis Cascade
Activated Protein C (Xigris)




              NEJM;355:1640, October 19, 2006.

				
DOCUMENT INFO
Shared By:
Categories:
Tags:
Stats:
views:30
posted:8/6/2012
language:English
pages:43