System inflammatory response syndrome and sepsis for surgery patients

1. System inflammatory response syndrome and sepsis for surgery patients Surgery department №2 DSMA

2. System inflammatory response syndrome (SIRS) - Sepsis — SIRS + septic site

3. 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.

4. 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

5. 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

6. Sepsisclassification by ethiology • Gram (+) • Gram (-) • Aerobic • Anaerobic • Mycobacterial • Staphylococcus • Streptococcus • Mixt-sepsis

7. Sepsisclassification by primary focus • Post-traumatic: • burn • wound • Lung • Angiogenic • Cardiogenic • Abdominal: • Biliary • Pancreatic • Intestinal • Peritoneal • Appendicular • Soft-tissue inglammation • Urological etc

8. Sepsisclassification by development with a time (stages) • Toxemia • Septicemia • Septicopyemia

9. Sepsisclassification by clinical course • Fulminantor the acutest • Acute • Chronic

10. Sepsis classification by clinical severity • Sepsis • Severe sepsis – sepsis + organ dysfunction • Septic shock – sepsis + hypotension • (Multiple organ dysfunction)

11. 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

12. 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

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

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

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

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

17. 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

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

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

20. 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

21. 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

22. 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%)

23. 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)

24. 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

25. 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

26. 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

27. 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

28. ARDS • Management • Lung-Protective Strategy-Reduction of Barotrauma • TV 5ml/kg • Longer inspiratory time • Peak Inspiratory Pressure<35-40cmH2O • Permissive Hypercapnea • PEEP

29. 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)

30. 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

31. 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)

32. 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