Sepsis and septic shock

1. Sepsis and septic shock Sir Run Run Shaw Hospital, 3rd floor of critical care medicine Zhejiang university school of medicine Jian-cang Zhou M.D.

2. Sepsis and Septic Shock Definitions Epidemiology Pathogenesis Principles of management

3. Definition - SIRS • Systemic Inflammatory Response Syndrome • Manifested by 2 or more of the following: • Temperature > 38°C (100.4F) or < 36°C (96.8F) • HR > 90 BPM • RR > 20/min or PaCO PaCO2 < 32 mm Hg • WBC 12,000 or >10% bands Systemic

4. Definition - Sepsis • Sepsis • SIRS PLUS a documented infection • Positive CXR • Positive U/A • Cellulitis /Abscess • Positive Blood Culture

5. Definition –Severe Sepsis • Severe Sepsis • One Sepsis related organ dysfunction (non-chronic) and/or: • Signs of hypoperfusion (Lactate>2, oliguria , altered mental status, mottling, desaturation, elevated LFT’s) AND/or • Hypotension • SBP <90 • MAP<60

6. Definition –Septic Shock • Septic Shock • Severe sepsis with persistent hypotension (refractory to fluid bolus) or: • Acute circulatory failure in an infected patient not explained by another cause . • Significant vasodilation (low SVR) is primary cause of hypotension . • Heart rate, CO, and Stroke Volume are usually good .

7. Definition - MODS • MODS - Multiple Organ Dysfunction Syndrome • More than one major system failure. • Related to significant mortality. • > 50%

9. Infection Parasite Severe Sepsis Virus SIRS Sepsis Fungus shock Trauma Severe SIRS Bacteria BSI Burns Adapted from SCCM ACCP Consensus Guidelines

10. Severe Sepsis Septic Shock SIRS Sepsis The Sepsis Continuum • A clinical response arising from a nonspecific insult, with 2 of the following: • T >38oC or <36oC • HR >90 beats/min • RR >20/min • WBC >12,000/mm3or <4,000/mm3 or >10% bands SIRS with a presumed or confirmed infectious process Sepsis with organ failure Refractory hypotension SIRS = systemic inflammatory response syndrome Chest 1992;101:1644.

11. Epidemiology

12. Comparable Global Epidemiology • 95 cases per 100,000 • 2 week surveillance • 206 French ICUs • 95 cases per 100,000 • 3 month survey • 23 Australian/New Zealand ICUs • 51 cases per 100,000 • England, Wales and Northern Ireland.

13. Martin et al: N Engl J Med 2003:348:1546

14. Where’s the infection ? Bernard & Wheeler NEJM 336:912, 1997

15. Pathogenesis

17. Sepsis and septic shock Bacterial infection Excessive host response Host factors lead to cellular damage Organ damage Death

18. Why sepsis is important?

19. Severe sepsis incidence and mortality increase with age Mortality Incidence Angus Crit Care Med 29:1301, 2001

20. Severe Sepsis • Major cause of morbidity and mortality worldwide. • Leading cause of death in noncoronary ICU. • 11th leading cause of death overall. • More than 750,000 cases of severe sepsis in US annually. • In the US, more than 500 patients die of severe sepsis daily.

21. Severe Sepsis is Common

22. Severe Sepsis is deadly

23. Comparison With Other Major Diseases Incidence of Severe Sepsis Mortality of Severe Sepsis Cases/100,000 Severe Sepsis‡ AIDS* Breast Cancer§ AMI† Breast AIDS* Colon CHF† Severe Sepsis‡ Cancer§ †National Center for Health Statistics, 2001.§American Cancer Society, 2001. *American Heart Association. 2000.‡Angus DC et al. Crit Care Med. 2001;29(7):1303-1310.

24. Severe Sepsis is a Significant Healthcare Burden • Sepsis consumes significant healthcare resources. • In a study of Patients who contract nosocomial infections, develop sepsis and survive: • ICU stay prolonged an additional 8 days. • Additional costs incurred were $40,890/ patient. • Estimated annual healthcare costs due to severe sepsis in U.S. exceed $16 billion.

25. How likely is it that the diagnosis of sepsis is being missed? Is it... Total (n=497) Intensive Care Physicians (n=237) Extremely likely Very likely Somewhat likely Not very likely Not likely at all Not sure Ramsay, Crit Care 2004 8:R409.

26. Management

27. Management of Sepsis Recognition Supportive care Source control Antibiotics Specific (adjunctive) therapy

28. Key Components(1) • Fluid resuscitation • Appropriate cultures prior to antibiotic administration • Early targeted antibiotics and source control • Use of vasopressors/inotropes when fluid resuscitation optimized

29. Key Components(2) • Evaluation for adrenal insufficiency • Stress dose corticosteroid administration • Recombinant human activated protein C (xigris) for severe sepsis • Low tidal volume mechanical ventilation for ARDS • Tight glucose control

30. Key Components(3):Prevent Complications of Critical Illness ----General • Prophylaxis for DVT • Stress ulcer prophylaxis • Prevention of nosocomial pneumonia by elevation of head to 45 degrees • Facilitate extubation by daily interruption of sedation and early SBT • Narrowing of antibiotic spectrum when appropriate

31. Treatment of Septic Shock • Initiate broad-spectrum\Site specific antibiotics • Goal is administration within three hours of arrival in ED. • Several studies support the concept of “earlier the better” • Early\Appropriate antibiotics appear to affect outcomes. • Cochrane paper underway on subject

32. Treatment of Septic Shock • Antibiotic Choices • Base on suspected pathogen information. • Remember previous cultures on your patient! • Adapt to local pathogens\antibiotogram. • Consider MRSA coverage • Many institutions routinely include. • Many paths to same destination.

33. Severe Sepsis Septic Shock SIRS Sepsis Therapy Across the Sepsis Continuum • Drainage • Debridement • Device removal • Definitive control • resection • amputation 62% 28% Antibiotics and Source Control Chest 2000;118(1):146 Chest 1992;101:1644.

34. Severe Sepsis Septic Shock SIRS Sepsis Therapy Across the Sepsis Continuum * Early Goal Directed Therapy Antibiotics and Source Control Early Goal-Directed Therapy (EGDT): involves adjustments of cardiac preload, afterload, and contractility to balance O2 delivery with O2 demand Chest 1992;101:1644.

35. 6 Hour Resuscitation Bundle • Early Identification • Early Antibiotics and Cultures • Early Goal Directed Therapy

36. Resuscitation Bundles Management Bundles

37. 6 - hour Severe Sepsis/Septic Shock Bundle • Early Detection: • Obtain serum lactate level. • Early Blood Cx/Antibiotics: • within 3 hours of presentation. • Early EGDT: • Hypotension (SBP < 90, MAP < 65) or lactate > 4 mmol/L: • initial fluid bolus 20-40 ml of crystalloid (or colloid equivalent) per kg of body weight. • Vasopressors: • Hypotension not responding to fluid • Titrate to MAP > 65 mmHg. • Septic shock or lactate > 4 mmol/L: • CVP and ScvO2 measured. • CVP maintained >8 mmHg. • MAP maintain > 65 mmHg. • ScvO2<70%with CVP > 8 mmHg, MAP > 65 mmHg: • PRBCs if hematocrit < 30%. • Inotropes.

39. 24 - hour Severe Sepsis and Septic Shock Bundle • Glucose control: • maintained on average <150 mg/dL (8.3 mmol/L) • Drotrecogin alfa (activated): • administered in accordance with hospital guidelines • Steroids: • for septic shock requiring continued use of vasopressors for equal to or greater than 6 hours. • Lung protective strategy: • Maintain plateau pressures < 30 cm H2O for mechanically ventilated patients

40. What Pressors for Septic Shock ? • Several non-randomized studies and one small prospective randomized study of dopamine vs norepinephrine for septic shock suggest that survival may be improved with the use of norepinephrine

43. Severe Sepsis Septic Shock SIRS Sepsis Therapy Across the Sepsis Continuum Early Goal Directed Therapy Antibiotics and Source Control Insulin and tight glucose control * Chest 1992;101:1644.

44. Glucose Control: Mechanisms • Stress hyperglycemia is common in sepsis • Glucose has pro-inflammatory effects • Insulin resistance is common in sepsis • Insulin has an anti-inflammatory effect, possibly via NOS. • Benefit is likely related to both insulin itself and lowering of blood glucose