SEPSIS

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SEPSIS

• Preeta John

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• SEPSIS AT ITS INCEPTION IS DIFFICULT TO
  RECOGNIZE BUT EASY TO TREAT LEFT UNATTENDED IT
  BECOMES EASY TO RECOGNIZE BUT DIFFICULT TO TREAT
  
• Machiavelli

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(No Transcript)
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SepsisDefinitions

• Based on ACCP/SCCM consensus panel
• Infection
• Inflammatory response to pathogen
• Classically Gram (-)
• Bacteremia
• Viable bacteria in blood

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SepsisDefinitions

• SIRS
• Widespread inflammatory response in absence of
  documented infection
• Need 2 or more
• Temp gt 380C (100.40F) or lt 360C (96.80F)
• Heart rate gt 90 bpm
• Respiratory rate gt 20 /min or PaCO2 lt 32 mmHg
• WBC gt 12000 cells/mm3 lt 4000 cells/mm3 or gt
  10 immature (band) form

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SepsisDefinitions

• Sepsis
• Systemic response to infection
• SIRS infection
• Severe sepsis
• Sepsis hypotension hypoperfusion or organ
  dysfunction

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SepsisDefinitions

• Sepsis shock
• Sepsis hypotension despite fluids clinical
  signs of hypoperfusion
• 40 of sepsis
• Hypotension
• SBP lt 90 mmHg or reduction of BP gt/ 40 mmHg
  from baseline

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SepsisDefinitions

• MODS
• Primary MODS early organ dysfunction
• Secondary MODS later organ dysfunction
• Most common manifestations of severe MODS
• ARDS acute renal failure DIC

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SepsisMortality Rates

• Overall 30 - 50
• By syndrome definition
• SIRS 7
• Sepsis 16
• Severe sepsis 20
• Septic shock 46

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Markers of sepsis

• Procalcitonin propeptide of calcitonin
  c cells of thyroid extrathyroid in sepsis
  normal level lt0.05ng/ml lt0.5-rules
  out infection 0.5-2- suspected
  sepsis gt2- 100 sepsis severity rises
  after 6hrs t1/2 24 hrs

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• CRP acute phase reactant liver
• asses severity of sepsis
• diff b/w bacterial viral infection
• poor specificity MIRHD tumors
• poor predictive value of sepsis
• normal lt6mg/l

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Surviving Sepsis CampaignGuidelines for
Management of Severe Sepsis and Septic Shock
Dellinger RP Carlet JM Masur H et al. for the
Surviving Sepsis Campaign Management Guidelines
Committee. Crit Care Med 2004 32858-873.
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Early goal directed therapy

• Goals of therapy within first 6 hours are

• C V P 8-12 mm Hg (12-15 on ventilated patients)
• Mean arterial pressure gt 65 mm Hg
• Urine output gt 0.5 mL/kg/hr
• ScvO2 or SvO2 70 if not achieved
• Transfuse PRBC to hematocrit gt 30
• Administer dobutamine (max 20 mcg/kg/min) to goal

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Rivers E. N Engl J Med 20013451368-77.
Dellinger et. al. Crit Care Med 2004 32
858-873.
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Lung protective ventilation

• Low tidal volumes 6 ml/kg coupled with plateau
  pressures lt30 cm H2O
• This decreases mortality from 40 to 31
• Lessens organ dysfunction
• A minimum amount of positive end expiratory
  pressure should be set to prevent lung collapse
  at end-expiration

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Antibiotic Therapy

• Start antibiotic therapy in the first hour of
  recognition of severe sepsis after obtaining
  appropriate cultures
• Empirical choice -one or more drugs with activity
  against likely pathogens
• 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

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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Fluid Therapy Choice of Fluid

• Fluid resuscitation - natural or artificial
  colloids or crystalloid
• 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 results 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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Steroids

• 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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Recombinant human Activated Protein C

• Drotrecogin alfa (activated) is recommended in
  patients at a high risk of death
• APACHE II score 25 or
• Sepsis-induced multiple organ failure or
• Septic shock or
• Sepsis induced acute respiratory distress
  syndrome
• Treatment should begin as soon as possible once
  patient identified as high risk of death
• Patients should have no absolute or relative
  contraindication related to bleeding risk

Bernard GR. N Eng J Med 2001344699-709.
Dellinger et. al. Crit Care Med 2004 32
858-873.
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Contraindications to use of rhAPC

• rhAPC (drotrecogin alfa activated) increases
  the risk of bleeding. rhAPC is contraindicated in
  Active internal bleeding
• Recent (within 3 months) hemorrhagic stroke
• Recent (within 2 months) intracranial or
  intraspinal surgery or severe head trauma
• Trauma with increased risk of life-threatening
  bleeding
• Presence of an epidural catheter
• Intracranial neoplasm or mass lesion or evidence
  of cerebral herniation
• platelet count be maintained at 30000 during
  infusion of rhAPC

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Vasopressors

• vasopressor therapy if fluid challenge fails to
  restore adequate blood pressure and organ
  perfusion
• Either norepinephrine or dopamine are first line
  agents to correct hypotension in septic shock
• Norepinephrine more potent than dopamine
• more effective at reversing hypotension in
  septic shock patients
• Dopamine in patients with compromised systolic
  function but causes tachycardia and is
  arrhythmogenic
• Vasopressin in refractory shock

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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Blood Product Administration

• Red blood transfusion when hemoglobin lt 7 g/dL
  
• in 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

Corwin HL. JAMA 20022882827-2835.
Dellinger et. al. Crit Care Med 2004 32
858-873.
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Blood Product Administration

• Platelet administration
• Transfuse for lt 5000/mm3
• Transfuse for 5000/mm3 30000/mm3 with
  significant bleeding risk
• Transfuse lt 50000/mm3 for invasive procedures
  or bleeding

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Glucose Control

• Best results obtained when blood glucose was
  maintained between 80 and 110 mg/dL in surgical
  sicu
• Glycemic control strategy should include a
  nutrition protocol with the preferential use of
  the enteral route

van den Berghe G. N Engl J Med
20013451359-1367.
Dellinger et. al. Crit Care Med 2004 32
858-873.
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Bicarbonate Therapy
Bicarbonate is not recommended for the purpose
of improving hemodynamics or reducing vasopressor
requirements for the treatment of hypoperfusion
induced lactic acidemia with pH 7.15

Cooper DJ. Ann Intern Med 1990112492-498. Mathie
u D. Crit Care Med 1991191352-1356.
Dellinger et. al. Crit Care Med 2004 32
858-873.
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Therapeutic Endpoints

• Capillary refill lt 2 sec
• Warm extremities
• Urine output gt 1 ml/kg/hr
• Normal mental status
• Decreased lactate
• Central venous O2 saturation gt 70

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NEJM OCT 2006
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Treatment strategies proven to change outcome in
severe sepsis

• Early goal directed therapy
• Lung protective ventilation
• Appropriate antibiotic coverage
• Activated protein C
• Tight control of sugars 80-100mg/dl
• Steroids

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A clinician armed with the sepsis bundles
attacks the three heads of severe sepsis
hypotension hypoperfusion and organ dysfunction.
Crit Care Med 2004 320(Suppl)S595-S597