What is acute organ dysfunction in sepsis?

Acute Organ Dysfunction in Sepsis

Acute organ dysfunction in sepsis refers to the life-threatening failure of one or more organ systems caused by a dysregulated host response to infection, which is associated with hospital mortality greater than 10%. 1

Definition and Identification

Acute organ dysfunction is the hallmark feature that distinguishes sepsis from a simple infection. According to the Third International Consensus Definitions for Sepsis and Shock (Sepsis-3), organ dysfunction in sepsis is identified by:

• An increase in the Sequential Organ Failure Assessment (SOFA) score of 2 points or more from baseline
• The SOFA score evaluates six organ systems:
  • Respiratory (PaO2/FiO2 ratio)
  • Cardiovascular (blood pressure and vasopressor requirements)
  • Hepatic (bilirubin levels)
  • Coagulation (platelet count)
  • Renal (creatinine levels and urine output)
  • Neurological (Glasgow Coma Scale) 1

Pathophysiology of Organ Dysfunction

The development of organ dysfunction in sepsis results from:

1. Dysregulated inflammatory response: An uncontrolled immune reaction to infection damages the body's own tissues and organs 2

2. Circulatory abnormalities: Including:

   • Vasodilation
   • Endothelial dysfunction
   • Microvascular thrombosis
   • Impaired tissue perfusion 3

3. Metabolic derangements:

   • Hyperglycemia initially, followed by hypoglycemia in later stages
   • Dysfunctional lipid metabolism with toxic accumulation of free fatty acids
   • Mitochondrial dysfunction leading to cellular energy failure 4

4. Organ crosstalk: Dysfunction in one organ system can trigger compensatory mechanisms in other systems, creating a cascade of damage across multiple organs 3

Common Manifestations of Organ Dysfunction

Acute organ dysfunction in sepsis commonly affects:

1. Respiratory system:

   • Acute lung injury (ALI)
   • Acute respiratory distress syndrome (ARDS)
   • Occurs in 25-42% of sepsis patients, increasing with persistent hypotension 4

2. Cardiovascular system:

   • Myocardial depression
   • Vasoplegic shock requiring vasopressors 1

3. Renal system:

   • Acute kidney injury
   • Decreased urine output
   • Elevated creatinine 1

4. Neurological system:

   • Altered mental status
   • Delirium
   • Encephalopathy 1

5. Hepatic system:

   • Elevated liver enzymes
   • Hyperbilirubinemia
   • Impaired synthetic function 5

6. Coagulation system:

   • Thrombocytopenia
   • Disseminated intravascular coagulation 1

Clinical Significance

The development of acute organ dysfunction in sepsis has profound clinical implications:

• It marks the progression from infection to sepsis
• Each additional failing organ system increases mortality risk
• Septic shock (a subset of sepsis with circulatory and metabolic abnormalities) is associated with hospital mortality rates exceeding 40% 1
• Early recognition of organ dysfunction is crucial for timely intervention

Monitoring and Assessment

Organ dysfunction in sepsis can be monitored using:

• SOFA score: Comprehensive assessment of six organ systems
• qSOFA score: Rapid bedside assessment including:
  • Altered mental status
  • Systolic blood pressure ≤100 mmHg
  • Respiratory rate ≥22/min 1
• Laboratory markers: Including lactate levels, which reflect tissue hypoperfusion and cellular metabolic dysfunction

Clinical Implications

Recognition of acute organ dysfunction in sepsis should trigger:

• Immediate administration of broad-spectrum antibiotics (within 1 hour for high-risk patients)
• Appropriate fluid resuscitation (30 ml/kg crystalloid for hypotension)
• Close monitoring (every 30 minutes for high-risk patients)
• Consideration of vasopressor support for persistent hypotension 1

Pitfalls and Caveats

• Organ dysfunction may develop at different rates and with varying severity across different organ systems
• Pre-existing organ dysfunction can complicate assessment of sepsis-related changes
• Excessive fluid resuscitation may worsen certain types of organ dysfunction, particularly pulmonary edema
• The development of immunoparalysis in later stages of sepsis can lead to recurrent or persistent infections 5

Understanding acute organ dysfunction is essential for early recognition and appropriate management of sepsis, which remains critical for improving patient outcomes.