Sepsis Syndrome

Mid-term
Monday, 15.04.2024.
 Definition
• Sepsis is severe infection leading to organ dysfunction.
• It is a life-threatening medical emergency.
• Sepsis syndrome is defined as a continuum of manifestations.
• Sepsis has various etiologies and clinical presentations.
• It accounts for substantial morbidity and mortality.
 Prevalence
• The incidence is estimated to be 240-300 cases per 100.000 individuals.
• Mortality is 18-50% - one of the leading causes of preventable deaths.
• 70-80% cases occur in patients who are hospitalized for other conditions.
Systemic Inflammatory Response Syndrome
• Bacteremia – spreading of an infection from its primary site into the
bloodstream.
• Does not necessary result in sepsis.
• SIRS is characterized by:
 An elevated heart rate (>90 beats/min) and respiratory rate (>20 breaths/min)
 Fever (temp>38°C) or hypothermia (temp<36°C) Two or more of the following
must be present
 Increased peripheral WBC>12.000 or leukopenia (WBC<4000)
 Increased immature neutrophils (>10% bands).
 Sepsis steps
• Sepsis is defined as Systemic Inflammatory
Response Syndrome due to bacteremia – positive
blood cultures for bacteria.
• Severe sepsis – with organ dysfunction and
represents the progression of bacteria-induced
SIRS.
• Septic shock is sepsis with hypotension (systolic
BP <90mmHg).
Infection Severe stages of the same disease
Pathogenesis
• Lipopolisacharide (LPS) called endotoxin is
transported to macrophage and monocyte
receptors.
• Gram-positive bacteria produce peptidoglycans
and lipoteichoic acid that stimulate TLR2.
• Both TLR4 and TLR2 activate nuclear factor
kappa B (NF-κB) causing release of TNFα, IL-1β,
IL-6 and HMBG (high-mobility group protein).
• Gram-positive bacteria also secrete endotoxins:
• S. aureus – toxic shock syndrome toxin 1 (TSS-1)
• S. pyogenes – streptococcal pyogenic endotoxin A
(SPEA).
• Superantigens – directly stimulate T-cells.
Disseminated Intravascular Coagulopathy and Sepsis

• Proinflammatory cytokines activate the vascular

endothelium and monocytes to release tissue factor
(TF).
• TF activates the extrinsic coagulation cascade:
thrombin stimulates fibrinogen conversion to fibrin.
• Fibrin deposition and platelet activation lead to
microvascular thrombosis.
• It activates fibrinolysis resulting in increased level
of fibrin degradation products.
• The release of TF lead to coagulopathy and
microvascular thrombosis called disseminated
intravascular coagulopathy (DIC).
Acute DIC is a haemorrhagic disorder
characterised by multiple bruises
(ecchymoses), bleeding from mucosal sites
(such as lips and genitals)
 Pathogenesis of Septic Shock
• Severe sepsis can lead to septic shock, a medical
emergency.
• In the early stages of septic shock, patients
experience volume loss secondary to reduced oral
intake, altered volume distribution and capillary
leakage.
• A hallmark is a decrease in intravascular resistance
and increase of cardiac output – ‘warm shock’.
• Later stages are accompanied by decreased cardiac
output – ‘cold shock’:
• Frequent complication of acute respiratory
distress syndrome – ARDS .
 Physical findings
• Many hospitals use modified early warning system • Immediately treatment if patient have one more of the findings:
(MEWS) for identification of hospitalized patients
 Fever with a temperature >38°C or hypothermia <36°C
who are:
 Heart rate >90 BPM
• becoming critically ill
 Respiratory rate >20 BPM or CO2 blood gas level <32 mmHG
• at risk of progressing to cardiac or respiratory arrest beats per minute
 Peripheral WBC >12.000 cells per liter or <4000 cells per liter
• Periodically obtained by bedside nurse.

Sepsis should be considered in any patient with a MEOWS score > 4

• Auscultatory findings: respiratory sounds -
rales (crackles, precipitations), rhonchi
(wheeze)
• Abdomen: hypoactive or hyperactive bowel
sounds, abdominal distension, areas of
tenderness
• Skin: erythema, petechiae
• The temperature of the extremities: warm
skin, later cool and clammy extremities
(suggest hypoperfusion)
• Bleeding at puncture sites, in the gums and at
old wounds.
• History and examination should focus on
identifying the primary focus of infection.
• Pulmonary infection: cough, sputum
production and color of sputum, shortness of
breath, pleuristic chest pain, confusion
• Intra-abdominal infection: abdominal pain,
constipation, diarrhea, nausea, vomiting
• Meningitis: headaches, stiff neck and confusion
• Soft tissue infections: cuts, areas of skin
erythema, pain
 Acute management
Must be taken into account:
• Every minute counts! • Primary anatomic site of the infection
• Every hour of delay increases mortality of sepsis by • Local hospital antibiotic sensitivities
7,6% • Sensitivities of bacteria previously grown from the
possible site of bacteremia
• Activate the Sepsis 6 bundle and complete within 1 • Readjustment based on the blood culture results
hour. Avoid transfer until complete:
1. Deliver high flow oxygen
2. Draw blood cultures
3. Begin empiric antibiotic (delay of 36 h = 100%
mortality)
4. Draw serum lactate level
5. Begin rapid IV fluid administration
6. Begin closely monitoring urine output

The Sepsis Six is the name given to a bundle of medical therapies

designed to reduce mortality in patients with sepsis
Continued management (After first hour)
• Major concerns: hypotension and • If continued hypotension and hypoperfusion
hypoperfusion after Sepsis 6 bundle, monitor CVP (central
venous pressure)
• Monitoring of blood pressure, serum
lactate, skin color and temperature of • IV infusion to maintain CVP of 8-12 mmHg
the extremities • Use crystalloid solution, Ringer lactate or
Hartman solution to avoid hyperchloremia
• Maintain BP >65 mmHg
• Vasoconstrictor of choice is norepinephrine
• Serum lactate >4 m/M/L = mortality of
• Dopamine increases the risk of arrhythmias
40%
• Monitory extreme temperature
 Complications associated with sepsis
• Disseminated Intravascular
Coagulopathy
 Evidence of thrombosis and
bleeding
 Elevated prothrombin time, low
fibrinogen, high D-dimers
 Thrombocytopenia
 Uncontrolled bleeding
• Acute Respiratory Distress syndrome
1. Sepsis the most common cause
2. High cytokine levels and activated
neutrophils damage vascular
endothelial junctions causing fluid to
leak into the alveoli
3. Diffuse opacification – hallmark
4. Treatment – mechanical ventilation
 Adjunctive Therapies
• No efficacy
• Anti-inflammatory agents
• Monoclonal antibodies
• Anti-tumor necrosis factor-alpha antibodies
• Interleukin 1 antagonist
• Platelet-activating factor antagonist
• Activated protein C