5.15 Sepsis

Sepsis
A.Mickienė, MD, PhD

2017/2018
What is Sepsis?
Definitions (ACCP/SCCM)
• Sepsis:
• Known or suspected infection, plus
• >2 SIRS Criteria.
• Severe Sepsis:
• Sepsis plus >1 organ dysfunction.
Septic Shock
MODS
.
SIRS (Systemic Inflammatory Response
Syndrome):
if ≥ 2
■ Temperature >38°C or <36°C
■ HR > 90 beats/min
■ RR >20/min or PaCO2 <32mmHg
■ WBC >12 x 109/l or <4 x 109/l or >10%
immature bands
Relationship Between Sepsis and
SIRS
Other
Bacteremia
Fungemia Trauma
Infection SEPSIS SIRS
Viremia
Parasitemia Burn
Other
Pancreatitis
Definitions (ACCP/SCCM):
• Septic Shock: Sepsis induced with
hypotension despite adequate
resuscitation along with the presence of
perfusion abnormalities which may
include, but are not limited to lactic
acidosis, oliguria, or an acute alteration
in mental status.
Definitions
• Multiple Organ Dysfunction Syndrome
(MODS): The presence of altered organ
function in an acutely ill patient such that
homeostasis cannot be maintained
without intervention.
Predisposition
■ Pre-existing disease
◆ Cardiac, Pulmonary, Renal
◆ HIV
■ Age (extremes of age)

■ Gender (males)
■ Genetics
◆ TNF polymorphisms
Clinical Signs of Sepsis
• Fever.
• Leukocytosis.
• Tachypnea.
• Tachycardia.
• Reduced Vascular Tone.
• Organ Dysfunction.
Clinical Signs of Septic Shock
• Hemodynamic Alterations
• Hyperdynamic State (“Warm Shock”)
• Tachycardia.
• Elevated or normal cardiac output.
• Decreased systemic vascular resistance.
• Hypodynamic State (“Cold Shock”)

• Low cardiac output.
Organ Dysfunction
■ Lungs Ø Adult Respiratory Distress Syndrome
■ Kidneys Ø Acute Tubular Necrosis
■ CVS Ø Shock
■ CNS Ø Metabolic encephalopathy
■ PNS Ø Critical Illness Polyneuropathy
■ Coagulation Ø Disseminated Intravascular Coagulopathy
■ GI Ø Gastroparesis and ileus
■ Liver Ø Cholestasis
■ Endocrine Ø Adrenal insufficiency
■ Skeletal Muscle Ø Rhabdomyolysis
üSpecific therapy exists

Epidemiology:
Sources of Sepsis
The International Cohort Study
Severe Septic
Sepsis Shock
Respiratory 66 53
Abdomen 9 20
Bacteremia 14 16
Urinary 11 11
Multiple - -
Microbiology of Sepsis
The International Cohort Study
Severe Septic
Sepsis Shock
Gram-positive 44 40
Gram-negative 47 47
Fungal 9 13
Polymicrobial - -
Mediators of Septic Response
Pro-inflammatory Mediators
• Bacterial Endotoxin
• TNF-α
• Interleukin-1
• Interleukin-6
• Interleukin-8
• Platelet Activating Factor (PAF)
• Interferon-Gamma
• Prostaglandins
• Leukotrienes
• Nitric Oxide
Anti-inflammatory Mediators
• Interleukin-10
• PGE2
• Protein C
• Interleukin-6
• Interleukin-4
• Interleukin-12
• Lipoxins
• GM-CSF
• TGF
• IL-1RA
Why is Sepsis Important?
Epidemiology: Mortality rate
Question: Why do Septic
Patients Die?
• Answer: Organ Failure

Organ Failure and Mortality
•Knaus, et al. (1986):
•Direct correlation between number of organ
systems failed and mortality.
•Mortality Data:
#OSF D1 D2 D3 D4 D5 D6 D7
1 22% 31% 34% 35% 40% 42% 41%
2 52% 67% 66% 62% 56% 64% 68%
3 80% 95% 93% 96% 100 100 100
% % %
Organ failure in sepsis
P/F
Platelets
Bili
BP
GCS
Cr/UOP
Vincent, J.-L., Sakr, Y., Sprung, C. L., Ranieri, V. M., Reinhart, K., Gerlach, H., Moreno, R., et al. (2006). Sepsis in European intensive care units: results of the SOAP study.
Critical Care Medicine, 34(2), 344–353.
Infection
Inflammatory Endothelial
Vasodilation
Mediators Dysfunction
Hypotension Microvascular Plugging Vasoconstriction Edema
Maldistribution of Microvascular Blood Flow
Ischemia
Cell Death
Organ Dysfunction
Sepsis is diagnosed if there are signs/symptoms
of infection and Sequential (Sepsis-Related)
Organ Failure Assessment Score changes in ≥ 2
scores
New terms and definitions
Sepsis is defined as life-threatening organ dysfunction caused by

a dysregulated host response to infection.
Organ dysfunction can be identified as an acute change in total

SOFA score ≥ 2 points consequent to the infection.
• The baseline SOFA score can be assumed to be zero in patients

not known to have preexisting organ dysfunction.
• A SOFA score ≥ 2 reflects an overall mortality risk of

approximately 10% in a general hospital population with
suspected infection. Even patients presenting with modest
dysfunction can deteriorate further, emphasizing the seriousness
of this condition and the need for prompt and appropriate
intervention, if not already being instituted.
quickSOFA(qSOFA)
• Respiratory rate ≥ 22/min,
• Altered mentation
• Systolic BP ≤ 100 mmHg
Sepsis should be suspected when the patient has

signs/symptoms of infection and ≥ 2 qSOFA
criteria.
• Patients with suspected infection who are likely to have a
prolonged ICU stay or to die in the hospital can be promptly
identified at the bedside with qSOFA, ie, alteration in
mental status, systolic blood pressure ≤ 100mmHg, or
respiratory rate ≥ 22/min.
• Septic shock is a subset of sepsis in which underlying

circulatory and cellular/metabolic abnormalities are profound
enough to substantially increase mortality.
• Patients with septic shock can be identified with a clinical

construct of sepsis with persisting hypotension requiring
vasopressors to maintain MAP ≥ 65mmHg and having a
serum lactate level >2 mmol/L despite adequate volume
resuscitation. With these criteria, hospital mortality is in
excess of 40%.
Therapy For Sepsis
Therapeutic Strategies in Sepsis
• Optimize Organ Perfusion
• Expand effective blood volume.
• Hemodynamic monitoring.
• Early goal-directed therapy.
• 16% reduction in absolute risk of in-house
mortality.
• 39% reduction in relative risk of in-house
mortality.
• Decreased 28 day and 60 day mortality.
• Less fluid volume, less blood transfusion, less
vasopressor support, less hospital length of stay.
• Control Infection Source
• Drainage
• Surgical
• Radiologically-guided
• Culture-directed antimicrobial therapy
• Support of reticuloendothelial system

• Enteral / parenteral nutritional support
• Minimize immunosuppressive therapies

• 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.
Evidence-Based Sepsis Guidelines
Empirical therapy of sepsis
Source of infection Etiology Antibiotics
Respiratory system S. pneumoniae Cefuroxim or

H. influenzae Ampicillin + sulbactam ± Gentamycin
S. aureus
K. pneumoniae > 60 year old people or treated with antibiotics within
L. pneumophila 3 months:
Ceftriaxon or Cefotaxim ± Gentamycin
In suspicion of Legionella – add Azithromycin or

Flourochinolon
Urinary tract Enterobacteriaceae (E.coli, Ceftriaxon or Cefotaxim

Klebsiella, Proteus)
B group β hemolytic OR:
streptococcus
Enterococcus spp. Ciprofloxacin
Intestinal tract Polymicrobial infection: Ampicillin + sulbactam ± Gentamycin

Enterobacteriaceae
(E.coli, Klebsiella, OR:
Enterobacter)
+ Ceftriaxon or Cefotaxim + Metronidazol,
Bacteroides fragilis and
other anaerobs, Ciprofloxacin + Metronidazol,
+
Enterococcus spp. Piperacillin + tazobactam
Skin and soft tissue S.aureus, Cefazolin or Cefuroxim ± metronidazol,
S.pyogenes,
rerely – Ampicillin + sulbactam
Enterobacteriaceae,
Bacteroides fragilis and OR:
other anaerobs Clindamycin + Ciprofloxacin
CNS S. pneumoniae, Ceftriaxon or cefotaxim + ampicillin

N. meningitidis,
L. monocytogenes, OR:
rerely – H.influenzae, Meropenem
S.aureus,
β haemolytic streptococcus,
Enterobacteriaceae
Unknown etiology, E.coli, Klebsiella, Ceftriaxon or Cefotaksim ± Gentamycin
S.aureus, S.pneumoniae,
unknown source, β haemolytic OR:
streptococcus, Ampicillin + sulbactam ± Gentamycin
community acquired
N.meningitidis,
sepsis,
H.influenzae,
normal immunity rerely - Salmonella,
Listeria monocytogenes
Doses (i/v)
Antibiotic Dose Daily dose (g)
Ampicillin 2-3 g ×4 8-12
Ampicillinas + sulbactam 1,5-3 g ×4 6-12
Cefazolin 2g ×3 6
Cefuroxim 1,5 g ×3-4 4,5-6
Ceftriaxone 1-2 g ×2 2-4
Gentamycin 3-5 mg/kg ×1
Ciprofloxacin 0,4 g ×2 0,8
Metronidazol 0,5 g ×3 1,5
Corrected if impaired renal or liver function!!!

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Sepsis

A.Mickienė, MD, PhD

■ Age (extremes of age)

• Hypodynamic State (“Cold Shock”)

üSpecific therapy exists

• Answer: Organ Failure

Hypotension Microvascular Plugging Vasoconstriction Edema

Maldistribution of Microvascular Blood Flow

Sepsis is defined as life-threatening organ dysfunction caused by

Organ dysfunction can be identified as an acute change in total

• The baseline SOFA score can be assumed to be zero in patients

• A SOFA score ≥ 2 reflects an overall mortality risk of

Sepsis should be suspected when the patient has

• Septic shock is a subset of sepsis in which underlying

• Patients with septic shock can be identified with a clinical

• Culture-directed antimicrobial therapy

• Support of reticuloendothelial system

• Minimize immunosuppressive therapies

• Renal replacement therapies (CVVHD, HD).

• Cardiovascular support (pressors, inotropes).

• Transfusion for hematologic dysfunction.

• Minimize exposure to hepatotoxic and

Respiratory system S. pneumoniae Cefuroxim or

In suspicion of Legionella – add Azithromycin or

Urinary tract Enterobacteriaceae (E.coli, Ceftriaxon or Cefotaxim

Intestinal tract Polymicrobial infection: Ampicillin + sulbactam ± Gentamycin

CNS S. pneumoniae, Ceftriaxon or cefotaxim + ampicillin

Corrected if impaired renal or liver function!!!

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