The sepsis syndrome

1. The sepsis syndrome Divya Ahuja, M.D. November , 2009

2. Severe Sepsis is a Significant Healthcare Burden • Sepsis consumes significant healthcare resources. • In a study of patients who 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. • In the US, more than 500 patients die of severe sepsis daily.

4. Severe Sepsis is deadly

5. Revised definitions • Systemic inflammatory response syndrome (SIRS) • Sepsis • Severe sepsis • Septic shock

6. Systemic Inflammatory Response Syndrome (SIRS) • Two or more of the following • temperature > 38 degrees C (100.4 F) • respirations > 20/minute • Heart rate > 90 beats per minute • leukocyte count > 12,000/cmm or < 4000/cmm or with > 10% band forms

7. Definitions (ACCP/SCCM) • Sepsis: • Known or suspected infection, plus • >2 SIRS Criteria. • Severe Sepsis: • Sepsis plus >1 organ dysfunction. • Multi Organ Dysfunction Syndrome. • Septic Shock.

8. Relationship Between Sepsis and SIRS BACTEREMIA SEPSIS TRAUMA BURNS INFECTION SEPSIS SIRS PANCREATITIS

9. Some etiologies of sepsis • Pneumonia • Bacteremia/endocarditis • Skin and soft tissue infection • Meningitis • Urosepsis • Intrabdominal infection secondary to viscus rupture • Pelvic inflammatory disease • Etc., etc., etc.

10. Septic shock • Definition: Sepsis-induced hypotension despite fluid resuscitation and/or inotropic support, plus hypoperfusion abnormalities • The hallmark of septic shock is low systemic vascular resistance, which distinguishes it from hemorrhagic shock and cardiogenic shock.

11. Clinical Signs of Septic Shock • Myocardial Depression. • Altered Vasculature. • Altered Organ Perfusion. • Imbalance of O2 delivery and Consumption. • Metabolic (Lactic) Acidosis.

12. Definitions (ACCP/SCCM): • Multiple Organ Dysfunction Syndrome (MODS): The presence of altered organ function in an acutely ill patient such that homeostasis cannot be maintained without intervention.

13. Multiple Organ Failure • Some physiologic descriptors • Serum creatinine • Platelet count • pO2/FiO2 ratio • Serum bilirubin • Glasgow coma score

15. Infection Endothelial Dysfunction Vasodilation Inflammatory Mediators Hypotension Microvascular Plugging Vasoconstriction Edema Maldistribution of Microvascular Blood Flow Ischemia Cell Death Organ Dysfunction

16. Case #1 • 20-year-old college student • General malaise, low-grade fever, and rapid development of purplish discoloration on his face. (from when he left his house to the time he arrived at the emergency room). • Blood cultures were drawn and he was admitted to the intensive care unit

18. Presentation • Febrile, tachycardic, systolic BP-70 • Creatinine- 3.6, poor urine output • Platelets-46000 • INR- 2.6 • Obtunded mental status • Needing maximum ventilatory support

19. Patient’s Blood Cultures

20. Case # 1 continued • Meningococcemia with Waterhouse-Friderichsen Syndrome and DIC • Treat with penicillin, ceftriaxone or chloramphenicol. • Family members and hospital employees in contact with respiratory secretions should receive prophylaxis.

21. Continuum of severity • Incidence of positive blood cultures increases along the continuum • Increased mortality rate • Severe organ dysfunction manifested as • Acute respiratory distress syndrome • Acute renal failure • Disseminated intravascular coagulation

22. Disseminated intravascular coagulopathy

23. Acute Respiratory Distress Syndrome

24. Evaluation of blood cultures • True-positive versus false-positive (contamination; pseudobacteremia) • Transient versus intermittent versus continuous • Polymicrobial versus unimicrobial • Primary versus secondary

25. Clues to contamination • Microorganisms that are usually not pathogenic, unless isolated from multiple cultures (e.g., coagulase-negative staphylococci; Bacillus species, corynebacterium) • < 2 positive cultures and/or delayed growth and/or < 1 cfu/ml • Doesn’t “fit” the clinical picture • Repeat blood cultures are helpful in differentiating between contamination and true bacteremia

26. Patterns of bacteremia • Transient: caused by manipulation of a flora-containing body surface • Intermittent: typical of most infections giving rise to positive blood cultures • Sustained (or continuous): characteristic of intravascular infections--endocarditis, endarteritis, suppurative thrombophlebitis, infected AV fistula

27. Bacteremia and sepsis • Persistent bacteremia is a poor prognostic marker • Staphylococcus aureus bacteremia is a common ID consult and has a 10-30% incidence of endocarditis associated with it • Severe sepsis: Blood cultures are positive in 20% to 40% of cases • Septic shock: Blood cultures are positive in 40% to 70% of cases

28. Risk factors for nosocomial sepsis • Gram-negative bacilli: diabetes mellitus; tumors; cirrhosis; burns; invasive procedures; neutropenia • Gram-positive cocci: vascular access lines, devices • Fungi: immunosuppression; broad-spectrum antibiotic therapy

29. Clinical findings in sepsis • Early: apprehension, hyperventilation, altered mental status • Complications: hypotension, bleeding, leukopenia, thrombocytopenia, organ failure • Lungs: cyanosis, acidosis, full-blown ARDS

30. Clinical findings in sepsis (2) • Kidneys: oliguria, anuria, tubular necrosis • Liver: jaundice and transaminitis • Heart: heart failure, stunned myocardium • Gastrointestinal: nausea, vomiting, diarrhea, stress ulceration • Systemic: lactic acidosis

31. Clinical findings in sepsis (3) • Petechiae early in course: suspect especially meningococcemia, RMSF • Ecthyma gangrenosum: Ps. aeruginosa • Generalized erythroderma: Toxic Shock Syndrome

32. Ecthyema gangrenosum Petechiae

33. Skin lesions in septicemias (1) • Neisseria meningitidis: erythematous macules or petechiae and purpura • Rocky Mountain spotted fever: petechiae, purpura • Staphylococcus aureus: “purulent purpura” • Pseudomonas aeruginosa: ecthyma gangrenosum

34. Skin lesions in septicemia (2) • Salmonella typhi: “Rose spots” • Hemophilus influenzae: cellulitis • Endocarditis: petechiae; Osler’s nodes (painful lesions of finger and toe pads); Janeway lesions (painless lesions of palms or soles) • Anthrax: papules-->vesicles-->eschar • Fungemias

36. A 50 yo man presents to emergency room with severe pain and swelling of LLE. On exam, temperature is 40.0 ºC, pulse rate is 135/min, respiration rate is 35/min, and blood pressure is 80/40

37. Which of the following is the most appropriate initial therapy? • LLE elevation • X-ray of LLE • Surgical consultation • Oral antibiotics

38. Necrotizing fasciitis • Necrotizing fasciitis usually results from an initial break in skin (trauma or surgery) • It is deep: may involve the fascial and/or muscle compartments • The initial presentation is that of cellulitis

39. Necrotizing fasciitis: Red flags • Severe pain (out of proportion of skin findings) • Bullae (due to occlusion of deep blood vessels) • Skin necrosis or ecchymosis • Gas in soft tissue (palpation or imaging) • Systemic toxicity • Rapid spread during antibiotic therapy

40. Necrotizing fasciitis • Monomicrobial: S. pyogenes, S. aureus, anaerobic streptococci,…. Most are community acquired and present in the limbs in patients with DM or vascular insufficiency • Polymicrobial: aerobic and anaerobic (bowel flora), Usually associated with abdominal surgical procedures, decubitus ulcer, perianal ulcer, bartholin abscess, IV drug injection

41. Staphylococcal bacteremia • Complications: endocarditis; metastatic infection; sepsis syndrome • Staphylococci adhere avidly to endothelial cells and bind through adhesin-receptor interactions • Fulminant onset; high fever, erythematous rash with subsequent desquamation, and multiorgan damage • DDx: Rocky Mountain spotted fever, streptococcal scarlet fever, leptospirosis

43. Streptococcal toxic shock syndrome • Early onset of shock and organ failure associated with isolation of group A streptococci • Necrotizing fasciitis present in about 50% of cases • Early symptoms: Myalgias, malaise, chills, fever, nausea, vomiting, diarrhea • Pain at minor trauma site may be first symptom

45. Sepsis in the asplenic patient • Frequently fulminant with massive bacteremia • Streptococcus pneumoniae accounts for 50% to 90% of infections and 60% of deaths • Other pathogens: Haemophilus influenzae, Neisseria meningitidis, Capnocytophagacanimorsus (after dog bites), Babesia microti (babesiosis)

46. 64 year old WM • Presents with fever, hypotension, cellulitis with bullous skin lesions • PMH: cirrhosis • SH: recently returned from New Orleans, likes oysters

47. Vibrio vulnificussepsis • Organism found in warm seawater and in shellfish (90% of deaths due to seafood in U.S.) • Cirrhosis a major risk factor to sepsis, with rapid onset • Chills, fever, characteristic skin lesions (bullae with hemorrhagic fluid; necrotizing fasciitis, other) • Also causes wound infection after exposure to salt water

48. 41 year old WM • Fever, “worst headache ever,” myalgias, rash • Returned from family camping trip in Smoky Mountain National Park 1 week PTA

49. Rocky Mountain spotted fever • Generalized infection of vascular endothelium • Headache typically severe. Fever may be low-grade and rash may be absent (“spotless fever”) when patient first seen • Suspect with flu-like illness and severe headache in endemic areas!

50. 65 year old woman • PMH diabetes • During influenza epidemic, presents with fever, chills, aching all over (myalgia) • PE: bibasilar rales; no murmur, febrile • Blood cultures (2/2) are positive for S. aureus