What is sepsis and how is it treated?

What is Sepsis?

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, characterized by profound circulatory, cellular, and metabolic abnormalities that can lead to multiple organ failure and death. 1

Definition and Pathophysiology

• Sepsis represents a spectrum of severity with differential responses at local, regional, and systemic levels, involving a dysregulated inflammatory response that can lead to multi-organ failure 1
• The current definition framework (Sepsis-3) has moved away from previous concepts of SIRS (Systemic Inflammatory Response Syndrome) and "severe sepsis" to focus on organ dysfunction as the key characteristic 1
• Organ dysfunction can be clinically identified by an increase in the Sequential Organ Failure Assessment (SOFA) score of ≥2 points, which is associated with in-hospital mortality >10% 1
• Sepsis involves profound physiologic and biological abnormalities resulting from the body's extreme response to an infection 2

Identification of Sepsis

• Quick SOFA (qSOFA) consists of three clinical variables for rapid identification of patients at risk of sepsis outside the ICU setting 1:
  • Respiratory rate ≥22 breaths/min
  • Altered mental status (Glasgow Coma Scale score ≤13)
  • Systolic blood pressure ≤100 mmHg
• Presence of at least 2 qSOFA criteria suggests higher risk of poor outcomes typical of sepsis 1
• The SOFA score evaluates organ dysfunction across multiple systems including respiratory, cardiovascular, hepatic, coagulation, renal, and neurological 3
• Early recognition of sepsis is crucial for improving outcomes and reducing mortality 1, 4

Progression to Septic Shock

• Septic shock is defined as a subset of sepsis with particularly profound circulatory, cellular, and metabolic abnormalities associated with a greater risk of mortality 5
• Septic shock can be clinically identified by 5, 6:
  • Requirement for vasopressors to maintain mean arterial pressure ≥65 mmHg
  • Serum lactate level >2 mmol/L (>18 mg/dL) despite adequate fluid resuscitation
• Septic shock involves profound circulatory dysfunction characterized by vasodilation, increased vascular permeability, and microcirculatory dysfunction leading to tissue hypoperfusion 5

Treatment of Sepsis and Septic Shock

Initial Management

• Early recognition and prompt administration of intravenous fluids and vasopressors are mandatory for patients with sepsis 3
• Antimicrobials should be administered as soon as possible, ideally within the first hour of diagnosis, as delays are associated with increased mortality 4, 7
• Resuscitation targets include mean arterial pressure ≥65 mmHg, mental status, capillary refill time, lactate, and urine output 4

Fluid Resuscitation

• Intravenous fluid resuscitation plays an integral role in patients who are fluid responsive 4
• Crystalloid solutions should be the first choice as they are well tolerated and cost-effective 3
• Both balanced crystalloids and normal saline are reasonable options for resuscitation 4
• Fluid challenges should be administered rapidly to induce a quick response but not so fast that an artificial stress response develops 3

Vasopressor Therapy

• Early vasopressors should be initiated in those who are not fluid-responsive 4
• Norepinephrine is the recommended first-line vasopressor for septic shock 5, 4
• If hypotension persists, vasopressin should be considered, followed by epinephrine 4
• Administration of vasopressors through a peripheral 20-gauge or larger intravenous line is safe and effective when central access is not immediately available 4

Additional Therapies

• Steroids such as hydrocortisone and fludrocortisone should be considered in patients with refractory septic shock 4
• Source control is essential in managing intra-abdominal sepsis and other infection sources 3
• Optimizing antibiotic use is essential to ensure successful outcomes and to reduce adverse effects and drug resistance 7

Special Considerations

• Elderly patients may present with attenuated inflammatory responses and fewer clinical signs despite severe infection 1, 5
• Immunocompromised patients have increased susceptibility to sepsis due to pre-existing immune system dysfunction 1, 5
• Patient factors including age and comorbidities significantly affect the course of sepsis 1
• De-escalation and shortened courses of antimicrobials must be considered for most patients to prevent antimicrobial resistance 7

Common Pitfalls in Sepsis Management

• Failing to recognize perfusion abnormalities despite normal blood pressure in patients receiving vasopressors 6
• Delaying vasopressor initiation while continuing excessive fluid administration 6
• Not measuring lactate levels, which are essential for diagnosis according to current definitions 6
• Confusing septic shock with other forms of distributive shock, leading to inappropriate management 6