Sepsis and septic shock

Introduction

Sepsis is a leading cause of preventable death worldwide. Current estimates are that globally over 30 million people may suffer from sepsis each year and cause or contribute to more than 5 million deaths per year. Septic shock is a subset of sepsis in which circulatory dysfunction is profound enough to substantially increase mortality. Septic shock is associated with disparate mortality rates around the world. In the United States, septic shock mortality was reported at 39.3%, whereas in India it was 65.2%. In Australia and New Zealand, the reported mortality is substantially lower at 22.0% for septic patients admitted to an intensive care unit (ICU). Over the past decade, the incidence of sepsis has continually risen. Optimal time-critical care of the septic patient in the ED is crucial, as early intervention in several areas has been shown to reduce mortality.

Aetiology and pathophysiology

The majority of organisms responsible for causing sepsis are bacterial, although changes in their distribution have occurred over time. A study of 14,000 ICU patients in 75 countries demonstrated that 70% of infected patients had positive microbial isolates. Of these, 62% were gram-negative (20% Pseudomonas spp. and 16% Escherichia coli ), 47% were gram-positive (20% Staphylococcus aureus ) and 19% were fungi.

The most common site of infection was the lungs (64%), followed by the abdomen (20%), bloodstream (15%) and renal/genitourinary tract (14%).

The pathogenic mechanisms in sepsis are complex and involve proinflammatory and anti-inflammatory responses. The specific response in any patient, including duration and extent, depends on characteristics of both the pathogen and the host. Pathogen factors include virulence and microbial load, whereas host factors include age, comorbidities and genetics.

Pattern-recognition receptors are responsible for initiating the immune response following recognition of an invading pathogen. Receptors are found in the cell membrane (Toll-like receptors and C-type lectin receptors) and in the cytoplasm (nucleotide-binding oligomerization domain-like receptors and retinoic acid–inducible gene 1–like receptors).

Inflammatory mediators, such as tumour necrosis factor α (TNF-α) and the interleukins, are produced by the host, resulting in the activation of neutrophils, direct injury to the endothelium with increased vascular permeability and the release of nitric oxide (NO), the latter resulting in vasodilation. Modification of the coagulation cascade causes an increase in procoagulant factors and lower levels of the anticoagulant factors protein C, protein S and antithrombin III. These pro-inflammatory and procoagulant responses lead to reduced vascular resistance, relative hypovolaemia, loss of vasoregulatory control in microvascular beds, reduced myocardial contractility, acute lung injury and renal dysfunction.

Definitions

In 2016, a task force of the European Society of Intensive Care Medicine and the Society of Critical Care Medicine released the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3), which included the following:

• Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Organ dysfunction can be identified as an acute change in the total Sequential (Sepsis-related) Organ Failure Assessment (SOFA) score of ≥2 points consequent to the infection.

• Septic shock is a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality.

Use of the Systemic Inflammatory Response Syndrome (SIRS) criteria to define sepsis and the term severe sepsis are no longer included in the Sepsis-3 definitions.

History and examination

The diagnosis of sepsis can be challenging, as signs and symptoms can be vague and non-specific, leading to delays in early management. Temperature, heart rate, respiratory rate, blood pressure, level of consciousness and oxygen saturation should be assessed in all patients with suspected sepsis. Risk factors should be identified and patients asked about a history of productive cough, shortness of breath, dysuria, frequency of urination, offensive-smelling or discoloured urine, vomiting, diarrhoea, abdominal pain, breach of skin integrity (including insect bite, burns, wounds), headache, photophobia, non-blanching rash and joint swelling and pain. A comprehensive examination should include the head and neck, oropharynx and ears, skin, chest including lungs and heart, abdomen, pelvis, limbs, and joints.

Patients may initially present with mild tachycardia and fever. As severity progresses, they may then develop signs of shock, including altered mental status, cyanosis, hypotension and oliguria.