System inflammatory response syndrome and

sepsis for surgery patients

Surgery department №2 DSMA

System inflammatory response syndrome (SIRS) -

Sepsis — SIRS + septic site

SIRS

• 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.

SIRS

• Systemic Inflammatory Response Syndrome Criteria (ACCP/SCCM Consensus)

– Temperature >38°C or <36°

– Heart rate >90 bpm

– Respiratory Rate>20 or PaCO2<32mmHg

– WBC>12,000/μl or <4,000/μl

Sepsis

• Sepsis: 2 or more-– Tachycardia >90bpm– Rectal temp>38°C or <36°C– Tachypnea(>20bpm)

• With 1 or more– Alteration in mental status– Hypoxemia (PaO2<72mmHG at FiO20.21)– Elevated plasma lactate– Oligouria

Sepsisclassification by ethiology

• Gram (+)• Gram (-)• Aerobic• Anaerobic• Mycobacterial• Staphylococcus• Streptococcus• Mixt-sepsis

Sepsisclassification by primary focus

• Post-traumatic:– burn– wound

• Lung• Angiogenic• Cardiogenic• Abdominal:

– Biliary– Pancreatic– Intestinal– Peritoneal– Appendicular

• Soft-tissue inglammation• Urological etc

Sepsisclassification by development with a time (stages)

• Toxemia

• Septicemia

• Septicopyemia

Sepsisclassification by clinical course

• Fulminant or the acutest

• Acute

• Chronic

Sepsis classification by clinical severity

Sepsis

Severe sepsis – sepsis + organ dysfunction

Septic shock – sepsis + hypotension

(Multiple organ dysfunction)

Sepsis

• Severe Sepsis– Tachycardia >90bpm– Rectal temp>38°C or <36°C

– Tachypnea(>20bpm) or PaCO2<32mmHg

– Hypotension despite fluid resuscitation– Presence of perfusion abnormalities: lactic

acidosis, oligouria, alteration in mental status

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-α- potentiates the activation of neutrophils and macrophages

• IL-8 – regulates neutrophil function, mediates lung injury in sepsis

Sepsis

• Mediators of Sepsis– Complement– Nitric Oxide– Lipid Mediators: Chemotaxis, Cell activation,

Vascular Permeability

Phospholipase A2

PAF

Eicosanoids

Sepsis

• Mediators of Sepsis– Adhesion Molecules

• Selectins

• Leukocyte Antigens

Sepsis

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

Sepsis

• Circulatory Manifestations– Downregulation of catecholamine receptors– Increased local vasodilating substances

• Nitric oxide

• Prostacyclin

• Decreased Oxygen

• Low pH

• Increased anaerobic metabolism

• Shunting

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

Sepsis

• Other Organ Dysfunction– GI

• Ileus

• Malabsorption

• Overgrowth of bacteria, Translocation

– Liver– Renal– CNS

Sepsis

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

Sepsis

• Risk Factors– Extremes of Age (<10 and >70 years)– Pre-existing Organ Dysfunction– Immunosuppression– Major Surgery, Trauma, Burns– Indwelling Devices– Prolonged Hospitalization– Malnutrition– Prior Antibiotic Treatment

Sepsis

• Principles for Management of Sepsis– Early Recognition– Early and Adequate Antibiotic Therapy– Source Control– Early Hemodynamic Resuscitation and continued

support– Drotrecogin Alpha (Apache II>25)– Tight Glycemic Control– Ventilatory Support

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%)

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 (<9mcg/dL)

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

ARDS

• Frequent Complication in Sepsis(40%)

• Adult Respiratory Distress Syndrome– Oxygenation abnormality: PaO2/FiO2 ratio less

than 200– Bilateral opacities on CXR– PAOP <18mm Hg or no evidence of L atrial

hypertension

ARDS

• Frequent Complication in Sepsis(40%)• Adult Respiratory Distress Syndrome

– Oxygenation abnormality: PaO2/FiO2 ratio less than 200

– Bilateral opacities on CXR– PAOP <18mm Hg or no evidence of L atrial

hypertension– Frequency of ARDS in sepsis 18-38%– 16% patients die w/irreversible respiratory failure

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

ARDS

• Management– Lung-Protective Strategy-Reduction of

Barotrauma– TV 5ml/kg– Longer inspiratory time

– Peak Inspiratory Pressure<35-40cmH2O

– Permissive Hypercapnea– PEEP

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)

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

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)

Sepsis

• Principles for Management of Sepsis– Early Recognition– Early and Adequate Antibiotic Therapy– Source Control– Early Hemodynamic Resuscitation and continued

support– Drotrecogin Alpha (Apache II>25)– Tight Glycemic Control– Ventilatory Support