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.

3
(No Transcript)
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 gt 38 degrees C (100.4 F)
• respirations gt 20/minute
• Heart rate gt 90 beats per minute
• leukocyte count gt 12,000/cmm or lt 4000/cmm or
  with gt 10 band forms

7
Definitions (ACCP/SCCM)

• Sepsis
• Known or suspected infection, plus
• gt2 SIRS Criteria.
• Severe Sepsis
• Sepsis plus gt1 organ dysfunction.
• Multi Organ Dysfunction Syndrome.
• Septic Shock.

8
Relationship Between Sepsis and SIRS

BACTEREMIA
TRAUMA
SEPSIS
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

14
(No Transcript)
15
Infection
Endothelial Dysfunction
Inflammatory Mediators
Vasodilation
Hypotension
Vasoconstriction
Edema
Microvascular Plugging
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

17
(No Transcript)
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
Patients 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)
• lt 2 positive cultures and/or delayed growth
  and/or lt 1 cfu/ml
• Doesnt 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 Oslers nodes (painful
  lesions of finger and toe pads) Janeway lesions
  (painless lesions of palms or soles)
• Anthrax papules--gtvesicles--gteschar
• Fungemias

35
(No Transcript)
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

42
(No Transcript)
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

44
(No Transcript)
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, Capnocytophaga canimorsus
  (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 vulnificus sepsis

• 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

51
Infective endocarditis definitions

• Septic vegetations of the endocardium usually
  involving the heart valves or other areas of
  turbulent flow
• Acute endocarditis occurs on normal heart valves,
  is caused by highly virulent bacteria and leads
  to death in lt 6 weeks
• Subacute endocarditis is caused by less virulent
  bacteria and has a more indolent course.

52
Diagnosis of endocarditis

• Revised Duke Criteria positive blood cultures
  plus echocardiography with or without minor
  criteria
• Heart murmurs (especially regurgitant)
• Splinter hemorrhages (nail beds)
• Osler nodes (finger pulps painful)
• Petechiae pustular purpura (Staph)
• Roth spots (fundi)

53
(No Transcript)
54
(No Transcript)
55
(No Transcript)
56
(No Transcript)
57
Etiologies of endocarditis

• Viridans streptococci most common (30-40)
  Staphylococci - 20-30
• Other streptococci include enterococci and
  Streptococcus bovis
• Less common aerobic gram-negative rods HACEK
  organisms fungi anaerobic bacteria Brucella
  Coxiella burnetti Chlamydia psittaci
• Culture-negative (lt5 to 24)

58
Therapeutic Strategies in Sepsis

• Optimize Organ Perfusion
• Expand effective blood volume.
• Hemodynamic monitoring.
• Early goal-directed therapy.
• Pressors may be necessary

59
Therapeutic Strategies in Sepsis

• Control Infection Source
• Drainage
• Surgical
• Radiologically-guided
• Culture-directed antimicrobial therapy
• Support of reticuloendothelial system
• Enteral / parenteral nutritional support
• Minimize immunosuppressive therapies

60
Therapeutic Strategies in Sepsis

• Support Dysfunctional Organ Systems
• Renal replacement therapies (CVVHD, HD).
• Cardiovascular support (pressors, inotropes).
• Mechanical ventilation.
• Transfusion for hematologic dysfunction.
• Minimize exposure to hepatotoxic and nephrotoxic
  therapies.

61
Evidence-Based Sepsis Guidelines
62
Sepsis-summary

• Look at the host (age, immunedeficiency,-HIV,
  cancer, steroids, cirrhosis, dialysis,
• Clinical assessment for MOD (vitals, perfusion,
  mental status, urine output)
• Lab parameters-platelets, creatinine, coags,
  leukocytosis vs. leukopenia
• Hemodyanamic, ventilatory support, antibiotics
• HIT HARD and HIT EARLY and then deescalate based
  on emerging microbiological data