Sepsis and the Systemic Inflammatory Response Syndrome

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Sepsis and the Systemic Inflammatory Response
Syndrome
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Outline

1. Definitions and Diagnostic Criteria
2. Pathophysiology
3. Prognosis
4. Treatment
5. Example Cases

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What is SIRS?

• The systemic inflammatory response syndrome is
  systemic level of acute inflammation, that may or
  may not be due to infection, and is generally
  manifested as a combination of vital sign
  abnormalities including fever or hypothermia,
  tachycardia, and tachypnea.

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Definitions

• Severe SIRS SIRS in which at least 1 major
  organ system has failed.
• Sepsis SIRS which is secondary to infection.
• Severe Sepsis Severe SIRS which is secondary to
  infection.
• Septic Shock Severe sepsis resulting in
  hypotensive cardiovascular failure.

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Criteria for SIRS

• Requires 2 of the following 4 features to be
  present
• Temp gt38.3 or lt36.0 C
• Tachypnea (RRgt20 or MVgt10L)
• Tachycardia (HRgt90, in the absence of intrinsic
  heart disease)
• WBC gt 10,000/mm3 or lt4,000/mm3 or
• gt10 band forms on differential

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Criteria for Severe SIRS

• Must meet criteria for SIRS, plus 1 of the
  following
• Altered mental status
• SBPlt90mmHg or fall of gt40mmHg from baseline
• Impaired gas exchange (PaO2/FiO2 ratiolt200-250)
• Metabolic acidosis (pHlt7.30 lactate gt 1.5 x
  upper limit of normal)
• Oliguria (lt0.5mL/kg/hr) or renal failure
• Hyperbilirubinemia
• Coagulopathy (platelets lt 80,000-100,000/mm3,
  INR gt2.0, PTT gt1.5 x control, or elevated fibrin
  degredation products)

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Relationship Between SIRS and Sepsis
Adapted from Marini JJ, et al. Critical Care
Medicine, 2nd ed. 1997.
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Risk Factors for SIRS/Sepsis

• Extremes of age
• Indwelling lines/catheters
• Immunocompromised states
• Malnutrition
• Alcoholism
• Malignancy
• Diabetes
• Cirrhosis
• Male sex
• Genetic predisposition?

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Pathophysiology
Although inflammation is essential to host
response against infection, SIRS results from a
dysregulation of the normal response, with
massive, uncontrolled release of pro-inflammatory
mediators.
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Pathophysiology

• Vasodilation
• Activation of ATP-sensitive K channels in the
  vascular smooth muscle
• Increased synthesis of NO as a result of
  increased levels of the enzyme, inducible NO
  synthase
• Deficiency of vasopressin
• Intravascular Volume Depletion
• Increased capillary permeability leading to
  third-spacing of fluid
• Concurrent volume loss from vomiting or diarrhea

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Prognosis

• Overall mortality from SIRS/sepsis in the U.S. is
  approximately 20. Mortality is roughly linearly
  related to the number of organ failures, with
  each additional organ failure raising the
  mortality rate by 15.
• Hypothermia is one of the worst prognostic signs.
  Patients presenting with SIRS and hypothermia
  have an overall mortality of 80.

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Treatment

• Fluid Resuscitation
• Vasopressors
• Antibiotics
• Eradication of infection
• Ventilatory support, activated protein C,
  steroids, glycemic control, nutrition

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Treatment(Fluid Resuscitation)

• Rapid, large volume infusions are generally
  indicated in all patients with septic shock.
• Some patients require up to 10L of crystalloid in
  the first 24 hours, with an average requirement
  of 4-6L.
• Although resuscitation with colloid will
  necessitate less overall volume of fluid, there
  is no difference between patients treated with
  colloid versus crystalloid in the development of
  pulmonary edema, length of stay, or survival.

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Treatment(Vasopressors)

• These are second line agents in the treatment of
  septic shock (after volume resuscitation).
• A goal MAP should be 60-65mmHg, although urine
  output, mental status, and skin perfusion are
  better variables to use in monitoring adequate
  perfusion.

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Treatment(Antibiotics)

• Empiric antibiotic therapy should be instituted
  immediately after appropriate cultures have been
  drawn, taking into consideration the likely
  source of infection,
• In general, therapy should include two effective
  agents from different classes, for example, a
  beta-lactam and an aminoglycoside

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Treatment(Mechanical Ventilation)

• Nearly all patients with septic shock require
  supplemental oxygen, and approximately 80
  require mechanical ventilation.
• Use of mechanical ventilation not only may
  improve oxygenation, but the necessary sedation
  /- paralysis may improve organ perfusion by
  diverting blood flow away from the diaphragm.

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Treatment(Activated Protein C)

• The PROWESS trial showed that patients who
  received a 96hr infusion of APC within 24 hours
  of presentation had a statistically lower 28-day
  mortality rate (25 vs. 31).
• Treatment was of greater benefit in the most
  acutely ill patients (APACHE II score 25).
• APC has been found to not be cost effective in
  those patients with APACHE II scores lt25 or in
  those with relatively low life-expectancy even in
  the event of survival from sespis.

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Protocol for Early Goal Directed Therapy in
Septic Shock
(Adapted from NEJM 2001 3451368-77, in which
patients receiving this goal-directed therapy had
im-proved in-hospital mortality compared to those
with standard therapy, 31 to 47.)
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Case 1

• An 82 year old nursing home resident is brought
  to the ER by ambulance for an intermittent fever
  that has lasted about 36 hours. She is currently
  complaining of some chills and a sensation of
  thirst. Her past medical history is significant
  for diabetes, hypertension, and COPD. Her vitals
  on exam T38.6, HR95, BP128/65, RR16, O2
  sat94 on RA. She is mildly diaphoretic, but
  the remainder of her exam is otherwise normal.

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Case 2

• A 45 year old homeless IV drug user is brought to
  the ER by a friend because he looked really sick
  today and wasnt making any sense. He has had
  recent admissions to the hospital for alcohol
  withdrawal, and is known to have early cirrhosis
  without a history of encephalopathy. His vitals
  on presentation T39.5, HR137, BP114/40,
  RR18, O2 sat96 on RA. On exam, he appears
  both acutely and chronically ill, and is
  lethargic and only oriented to self. He has
  crackles at the right lung base, a 2/6 systolic
  murmur at the right upper sternal border. His
  abdomen is benign, however he has a severe
  cellulitis with underlying fluctuance beneath his
  right forearm.

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Case 3

• As the on-call intern, you are called to attend
  to a cross-cover patient on a non-monitored bed
  a 56 year old alcoholic admitted yesterday for
  alcoholic pancreatitis. Upon admission, he was
  placed on D5 ½NS at 125cc/hr, made NPO, and
  given morphine prn for pain control. During
  sign-out, you were told he had mild
  pancreatitis and that there is nothing to do.
  However, when the nursing assistant went in to
  take his vitals, she found him to be in mild to
  moderate respiratory distress and looking bad.
  His vitals at this time T36.5, HR140,
  BP125/50, RR34, O2 sat85 on 4L. Upon exam,
  he is tremulous, but alert and oriented. His
  lungs have diffuse crackles bilaterally. His
  abdomen is moderately tender in the epigastric
  region, but without peritoneal signs. The
  patient is currently complaining of shortness of
  breath and states that he feels terrible.

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Case 4

• A 67 year old man with metastatic colon cancer is
  brought to the ER by his wife because he
  developed a high fever and was just not
  looking very well for the past day. She became
  stuck in traffic on the way to the hospital, and
  during the 60 minute trip he has become confused
  and sweaty. His vitals upon arrival T40.5,
  HR135, BP76/30, RR34, O2 sat84 on RA. On
  exam, he appears cachectic and acutely ill. He
  is lethargic and is mumbling incoherently. His
  lung exam is significant for moderate bilateral
  crackles. Cardiac exam is significant only for a
  regular tachycardia. His abdomen appears mildly
  tender diffusely, but without peritoneal signs.
  The remainder of the exam is unremarkable.