Sepsis Overview

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Sepsis Overview

• December 5, 2006

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Sepsis

• Continuum of clinical pathophysiology and
  severity
• Process rather than an event
• Mild dysfunction to frank organ failure
• Changes in the function of every organ system
  mediated by the host immune system.

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Sepsis

• Systemic Inflammatory Response Syndrome-ACCP/SCCM
  Consensus
• Temperature gt38C or lt36
• Heart rate gt90 bpm
• Respiratory Rategt20 or PaCO2lt32mmHg
• WBCgt12,000/µl or lt4,000/µl

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Sepsis

• Sepsis 2 or more-
• Tachycardia gt90bpm
• Rectal tempgt38C or lt36C
• Tachypnea(gt20bpm)
• With 1 or more
• Alteration in mental status
• Hypoxemia (PaO2lt72mmHG at FiO20.21)
• Elevated plasma lactate
• Oligouria

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Sepsis

• Severe Sepsis
• Tachycardia gt90bpm
• Rectal tempgt38C or lt36C
• Tachypnea(gt20bpm) or PaCO2lt32mmHg
• Hypotension despite fluid resuscitation
• Presence of perfusion abnormalities lactic
  acidosis, oligouria, alteration in mental status

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Sepsis

• Mediators of Sepsis
• Lipospolysaccharide (gram-negative bacteria)
• Lipoteichoic acid (gram-positive bacteria
• Peptidoglycan
• Cytokines
• IL-1 mediates systemic effects of infection
• IL-6 effects liver function
• TNF-a- potentiates the activation of neutrophils
  and macrophages
• IL-8 regulates neutrophil function, mediates
  lung injury in sepsis

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Sepsis

• Mediators of Sepsis
• Complement
• Nitric Oxide
• Lipid Mediators Chemotaxis, Cell activation,
  Vascular Permeability
• Phospholipase A2
• PAF
• Eicosanoids

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Sepsis

• Mediators of Sepsis
• Adhesion Molecules
• Selectins
• Leukocyte Antigens

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Sepsis

• Circulatory Manifestations
• Vasodilation
• Tachycardia
• Increased Cardiac Output
• Depressed Myocardial Function
• Increased Delivery
• Decreased Extraction

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Sepsis

• Circulatory Manifestations
• Downregulation of catecholamine receptors
• Increased local vasodilating substances
• Nitric oxide
• Prostacyclin
• Decreased Oxygen
• Low pH
• Increased anaerobic metabolism
• Shunting

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Sepsis

• Pulmonary Dysfunction
• Endothelial Injury
• Interstitial Edema
• Alveolar Edema
• Neutrophil entrapment
• Injury Type I pneumocyte
• Hyperplasia Type II pneumocyte
• Continued Neutrophil, monocyte, leukocyte and
  platelet aggregation

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Sepsis

• Other Organ Dysfunction
• GI
• Ileus
• Malabsorption
• Overgrowth of bacteria, Translocation
• Liver
• Renal
• CNS

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Sepsis

• Organisms
• Lower Respiratory Tract Infections (25)
• Urinary Tract Infections (25)
• Gastrointestinal Infections (25)
• Soft Tissue Infections (15)
• Reproductive Organs (5)

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Sepsis

• Risk Factors
• Extremes of Age (lt10 and gt70 years)
• Pre-existing Organ Dysfunction
• Immunosuppression
• Major Surgery, Trauma, Burns
• Indwelling Devices
• Prolonged Hospitalization
• Malnutrition
• Prior Antibiotic Treatment

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Sepsis

• Principles for Management of Sepsis
• Early Recognition
• Early and Adequate Antibiotic Therapy
• Source Control
• Early Hemodynamic Resuscitation and continued
  support
• Drotrecogin Alpha (Apache IIgt25)
• Tight Glycemic Control
• Ventilatory Support

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Sepsis

• Drotrecogin-alpha/Recombinant Human Activated
  Protein C
• Reduced levels of anti-inflammatory mediators
• Activated Protein C
• Inhibits thrombosis
• Decreases inflammation
• Promotes fibrinolysis
• Side Effect Bleeding
• PROWESS study group
• Lower mortality rate (24.7 vs. 30.8)

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Sepsis

• Steroids???
• Older trials used high doses
• Recent trials suggest low dose, with taper and
  tight glycemic control may improve outcome
• Vasopressor-dependent shock
• Cosyntropin Stim Test-Relative Adrenal
  Insufficiency (lt9mcg/dL)

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Sepsis

• Experimental Therapies
• Dopexamine- beta 2 adrenergic and dopaminergic
  effects, NO alpha adrenergic activity
• Vasopressin- reduces inducible NO synthase,
  upregulates endogenous catecholamine receptors
• Phosphodiesterase Inhibitors-ionotropic agents
  with vasodilating actions
• Nitric Oxide Inhibitors- N-monomethyl-l-arginine

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ARDS

• Frequent Complication in Sepsis(40)
• Adult Respiratory Distress Syndrome
• Oxygenation abnormality PaO2/FiO2 ratio less
  than 200
• Bilateral opacities on CXR
• PAOP lt18mm Hg or no evidence of L atrial
  hypertension

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ARDS

• Frequent Complication in Sepsis(40)
• Adult Respiratory Distress Syndrome
• Oxygenation abnormality PaO2/FiO2 ratio less
  than 200
• Bilateral opacities on CXR
• PAOP lt18mm Hg or no evidence of L atrial
  hypertension
• Frequency of ARDS in sepsis 18-38
• 16 patients die w/irreversible respiratory
  failure

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ARDS

• Pathophysiology
• Injury to Alveolocapillary unit
• Exudative Phase
• Endothelial injury, immune cell infiltration,
  pneumocyte and endothelial injury and necrosis
• Proliferative Phase
• Organization of exudate, myofibroblast
  proliferation
• Conversion of exudate to fibrous tissue
• Fibrotic Phase
• Remodeling of fibrosis, microcystic honeycomb
  formation and traction bronchiectasis

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ARDS

• Management
• Lung-Protective Strategy-Reduction of Barotrauma
• TV 5ml/kg
• Longer inspiratory time
• Peak Inspiratory Pressurelt35-40cmH2O
• Permissive Hypercapnea
• PEEP

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Acute Renal Failure

• Increases Mortality in ICU 30
• Physiology
• Glomerular Filtration dependent on perfusion
  pressure (MAP 60-80mmHg)
• Less than 60mmHG
• Decreased flow
• Arterial dilation in pre-glomerular arterioles
  (prostaglandins)
• Constriction of post-glomerular arterioles
  (angiotensin II)

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Acute Renal Failure

• As Renal Perfusion Falls
• Increased reabsorption in proximal tubules
• 90 water is reabsorbed (normal is 60)
• Decreased fluid to the distal tubules
• Loss of potassium elimination
• Tubular cells dependent on aerobic respiration
• Ascending loop is most sensitive to ischemia

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Acute Renal Failure

• Dose all drugs appropriately
• Correction of Metabolic Acidosis
• Isotonic Bicarbonate
• Cannot Correct Ongoing Hypoperfusion
• Renal Replacement Therapy
• Absolute indication
• Acidosis
• Hyperkalemia
• Uremia (relative)

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Sepsis

• Principles for Management of Sepsis
• Early Recognition
• Early and Adequate Antibiotic Therapy
• Source Control
• Early Hemodynamic Resuscitation and continued
  support
• Drotrecogin Alpha (Apache IIgt25)
• Tight Glycemic Control
• Ventilatory Support