What is the definition, pathophysiology, and management of Sepsis (Systemic Inflammatory Response Syndrome)?

From the Guidelines

Sepsis is a life-threatening condition that requires immediate recognition and treatment, ideally within the first hour, with management following the Sepsis-3 criteria and the "Sepsis Bundle" to improve outcomes. The definition of sepsis has evolved to characterize it as a dysregulated host response to infection leading to organ dysfunction, with the Sepsis-3 criteria identifying it as a suspected infection plus a SOFA score increase of 2 or more points, or qSOFA criteria (altered mental status, respiratory rate ≥22, systolic blood pressure ≤100 mmHg) 1. Initial treatment should include obtaining blood cultures before antibiotics, administering broad-spectrum antibiotics within 1 hour, giving 30 mL/kg crystalloid fluid for hypotension or lactate ≥4 mmol/L, and applying vasopressors if hypotension persists after fluid resuscitation 1.

Key Management Strategies

• Obtain blood cultures before antibiotics
• Administer broad-spectrum antibiotics within 1 hour
• Give 30 mL/kg crystalloid fluid for hypotension or lactate ≥4 mmol/L
• Apply vasopressors if hypotension persists after fluid resuscitation Norepinephrine is the first-line vasopressor, starting at 0.05-0.1 mcg/kg/min, titrated to maintain MAP ≥65 mmHg, with vasopressin (0.03 units/min) added if needed 1. Source control is essential, removing infected material through drainage, debridement, or device removal. Ongoing management includes frequent reassessment, de-escalation of antibiotics based on culture results, daily sedation interruption, ventilator weaning protocols if intubated, glucose control, DVT prophylaxis, stress ulcer prevention, and nutritional support 1.

Pathophysiology and Outcomes

The pathophysiology of sepsis involves an initial hyperinflammatory response with cytokine release, followed by immunosuppression, leading to microcirculatory dysfunction, endothelial damage, coagulopathy, and ultimately multiple organ failure if not properly treated 1. Early identification and appropriate management in the initial hours after sepsis develops improves outcomes, with the goal of reducing morbidity, mortality, and improving quality of life 1.

From the Research

Definition of Sepsis

• Sepsis is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs [@\1@, @\2@, @\3@, @\4@, @\5@].

Pathophysiology of Sepsis

• The pathophysiology of sepsis involves a complex interplay between the host's immune response and the infectious agent, leading to a systemic inflammatory response syndrome (SIRS) [@\1@, @\4@].
• This can result in organ dysfunction, hypotension, and ultimately, septic shock [@\1@, @\4@].

Management of Sepsis

• The management of sepsis typically involves fluid resuscitation, antibiotic therapy, and supportive care [@\1@, @\2@, @\3@, @\4@, @\5@].
• Fluid resuscitation is a critical component of sepsis management, with the goal of restoring circulating fluid volume and optimizing stroke volume [@\1@, @\3@, @\5@].
• However, the optimal fluid resuscitation strategy remains unclear, with some studies suggesting that a more conservative approach may be beneficial [@\1@, @\3@, @\5@].

Fluid Resuscitation in Sepsis

• The Surviving Sepsis Campaign recommends rapid administration of 30 mL/kg of crystalloid fluids for hypotension or lactate ≥4 mmol/L in patients with septic shock [@\1@].
• However, some studies have found that a medium initial fluid volume dose (20-30 mL/kg) may be associated with reduced 28-day mortality [@\1@].
• Other studies have found that fluid resuscitation ≥30 mL/kg was not associated with improved outcomes, and may even be harmful in some cases [@\5@].

Key Considerations in Sepsis Management

• Early recognition and treatment of sepsis are critical to improving outcomes [@\1@, @\2@, @\3@, @\4@, @\5@].
• A comprehensive approach to sepsis management, including fluid resuscitation, antibiotic therapy, and supportive care, is essential [@\1@, @\2@, @\3@, @\4@, @\5@].
• Further research is needed to determine the optimal fluid resuscitation strategy and to improve our understanding of the pathophysiology of sepsis [@\1@, @\2@, @\3@, @\4@, @\5@].