Sepsis

Sepsis (from Ancient Greek σῆψις — putrefaction) is a life-threatening organ dysfunction caused by a dysregulated host response to infection. According to the Sepsis-3 definition (2016), the essence of sepsis lies not in the infection itself but in the body’s uncontrolled and damaging immune reaction to it.

This pathological response injures host tissues and organs and impairs their normal function. Without prompt diagnosis and treatment, sepsis can progress to multiple organ failure and death. It is therefore a medical emergency with high mortality that requires rapid recognition and intensive management.

Aetiology and pathophysiology

Sepsis may develop from an infectious focus at virtually any site in the body. It can be caused by bacteria (most commonly), fungi, viruses, or protozoa.

Most common sites of infection include:

• Lungs: pneumonia
• Abdominal cavity: peritonitis, abscesses, necrotizing pancreatitis
• Urinary tract: pyelonephritis
• Skin and soft tissues: cellulitis, infected wounds
• Device-related infections: catheter-associated infections

In response to infection, the immune system releases large amounts of inflammatory mediators (cytokines), triggering what is often described as a “cytokine storm”. This generalized inflammatory reaction leads to widespread vasodilation, increased vascular permeability, and activation of the coagulation system, sometimes resulting in disseminated intravascular coagulation (DIC). As these processes progress, microcirculatory flow deteriorates, arterial pressure falls, and tissues receive inadequate oxygen delivery (hypoperfusion). Cellular hypoxia disrupts metabolism and ultimately causes dysfunction of vital organs such as the kidneys, lungs, liver, heart, and brain.

Clinical Significance

The diagnosis of sepsis is based on the presence of organ dysfunction in a patient with suspected or confirmed infection. For rapid bedside assessment, clinicians often use the qSOFA (quick Sequential Organ Failure Assessment) score, which includes three criteria:

1. Altered mental status: change in Glasgow Coma Scale.
2. Tachypnea: respiratory rate ≥ 22 breaths per minute.
3. Low systolic blood pressure: ≤ 100 mmHg. p.

When two or more of these criteria are present in a patient with infection, the risk of sepsis and poor outcomes is high. If the condition progresses, patients may develop septic shock — a state of profound hypotension that does not respond to adequate fluid resuscitation and requires vasopressors to maintain organ perfusion.

Management of sepsis is time-sensitive and is usually provided in an intensive care setting. Key elements of initial management, reflecting current guidelines and the Hour-1 Sepsis Bundle, include:

• Immediate administration of broad-spectrum antimicrobials.
• Rapid intravenous fluid resuscitation to restore effective circulating volume.
• Source control of infection (e.g., surgical drainage or debridement of an abscess, removal of an infected intravascular device).
• Vasopressor therapy if hypotension persists despite adequate fluid resuscitation.
• Support of failing organs as needed, including mechanical ventilation for respiratory failure or renal replacement therapy for severe acute kidney injury.

Differential Diagnosis

The clinical picture of sepsis with multiorgan dysfunction can mimic several other life-threatening conditions. It should be distinguished from cardiogenic shock (for example, following an acute myocardial infarction), hypovolemic shock (such as from major blood loss), and anaphylactic shock. Similar systemic manifestations may also occur in severe noninfectious inflammatory disorders, including acute necrotizing pancreatitis or extensive polytrauma. Evidence suggesting an infectious cause includes a clearly identifiable focus of infection, positive microbial cultures, and elevated inflammatory biomarkers, particularly C-reactive protein (CRP) and procalcitonin.