Sepsis

Terminology and criteria for systemic inflammation

In modern practice, the severity of the process is graded based on organ dysfunction. The following are distinguished:

• Severe sepsis is a condition accompanied by cardiovascular failure, acute respiratory distress syndrome (ARDS), or multiple organ dysfunction syndrome (MODS).
• Septic shock is the most severe degree, accompanied by marked manifestations of cardiovascular failure.

The foundation of the diagnosis is systemic inflammatory response syndrome (SIRS). To confirm it in children, at least 2 out of 4 criteria must be met (with mandatory adjustment for age norms):

1. Thermoregulation disorder: fever >38.5 °C or hypothermia <36 °C.
2. Tachycardia at rest (in infants under one year of life, bradycardia may also be significant).
3. Tachypnea at rest.
4. Complete blood count abnormalities: leukocytosis, leukopenia, or a left shift in the differential (more than 10% band neutrophils and immature forms).

Etiology and age-related features

The vast majority of cases are bacterial in nature. Viruses, fungi, and parasites are significantly less common causative agents. The spectrum of microorganisms directly depends on age:

• Children under 3 months: flora characteristic of neonatal infections dominates — Streptococcus agalactiae (Group B Streptococcus), Escherichia coli, Listeria monocytogenes.
• Children over 3 months: typical pyogenic flora and encapsulated bacteria come to the forefront — Neisseria meningitidis, Haemophilus influenzae (type b), Streptococcus pneumoniae, Staphylococcus aureus, and Gram-negative Enterobacteriaceae (Klebsiella spp., Salmonella spp.).

Pathogenesis: from toxin to multiple organ dysfunction syndrome

The development of sepsis is a cascading reaction in which the body's protective response gets out of control:

1. Trigger factor: penetration of bacterial toxins into the bloodstream.
2. Cytokine storm: toxins hyperactivate macrophages and neutrophils. A colossal release of mediators occurs. Macrophages secrete tumor necrosis factor-alpha (TNFα), interferon-gamma (IFNγ), interleukins (IL-1, IL-6), platelet-activating factor (PAF), and nitric oxide (NO). Neutrophils release prostaglandin E2.
3. Organ effects: an excess of TNFα and IL-1 acts on the hypothalamus, provoking fever, tachycardia, and tachypnea. PAF, NO, and prostaglandin E2 damage the endothelium, causing capillary leak syndrome and hypovolemia, and trigger disseminated intravascular coagulation (DIC). High doses of IL-6 directly suppress myocardial function.
4. Terminal stage: against the background of hypovolemia, cardiac damage, and impaired microcirculation, tissue hypoxemia develops. Cells switch to anaerobic glycolysis, and lactic acid accumulates. Progressive lactic acidosis and MODS are the main causes of death.

Clinical presentation and diagnostics

Symptoms consist of systemic manifestations and signs of the primary focus. In the early (compensatory) stages, there is fever, centralization of circulation (cold extremities with general hyperthermia), extremity pain, and oliguria. Later, hypothermia, abnormal breathing patterns, anuria, and altered consciousness join in. Specific signs depend on the pathogen: for example, Neisseria meningitidis infection is characterized by a stellate hemorrhagic rash with necrosis, and in infants with meningitis, bulging of the anterior fontanelle.

Key diagnostic methods:

• Complete blood count (CBC): leukocytosis with a left shift (less commonly leukopenia).
• Biomarkers: a sharp rise in C-reactive protein (CRP) and procalcitonin (the latter directly correlates with severity).
• Microbiology: blood and urine cultures are performed strictly before administering antibiotics.
• Blood gas analysis: confirmation of hypoxemia, hypercapnia, and metabolic acidosis.

Principles of therapy

The treatment of sepsis requires differentiation from oncological, autoimmune diseases, and acute endocrine disorders (e.g., acute adrenal insufficiency).

Main areas of therapy:

• Antibiotic therapy: initiated in the first hour ("golden hour"). Newborns are prescribed ampicillin + third-generation cephalosporins (cefotaxime); older children receive third-generation cephalosporins (ceftriaxone) with the possible addition of vancomycin. In immunodeficiency, fourth-generation cephalosporins (cefepime) are used.
• Infusion therapy: correction of hypovolemia with saline solutions and colloids under strict hemodynamic monitoring.
• Respiratory support: from oxygen delivery via nasal cannula to mechanical ventilation and extracorporeal membrane oxygenation (ECMO).
• Targeted support: if infusion therapy is ineffective, vasopressors (dopamine, epinephrine) are administered. Hydrocortisone is indicated for adrenal insufficiency, and intravenous immunoglobulins (IVIG) for refractory courses.

Class and exam questions

What else to study on this topic

• Pathophysiology of DIC development against the background of systemic inflammation
• Features of infusion therapy and fluid volume calculation in children
• Mechanisms of formation and compensation of lactic acidosis in tissue hypoxia
• Differential diagnosis of infectious and non-infectious SIRS
• Specifics of using extracorporeal membrane oxygenation (ECMO) in pediatrics

Other topics from the section «Chapter 12. Infectious and parasitic diseases»

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.