What is the main cause of hypotension in sepsis?

Main Causes of Hypotension in Sepsis

The primary cause of hypotension in sepsis is vasodilation induced by the systemic inflammatory response to infection, combined with hypovolemia from capillary leak syndrome and myocardial dysfunction. 1

Pathophysiological Mechanisms

Hypotension in sepsis results from multiple interrelated mechanisms:

1. Vasodilation:

   • Dysregulated host response to infection triggers widespread vasodilation 2
   • Endothelial dysfunction leads to release of pro-inflammatory and vasoactive mediators 3
   • Altered vasomotor tone affects systemic vascular resistance 2

2. Hypovolemia:

   • Capillary leak syndrome causes fluid shifting from intravascular to interstitial spaces 1
   • True fluid loss from fever, vomiting, diarrhea, or decreased oral intake 2
   • Interstitial edema formation reduces effective circulating volume 2

3. Cardiac Dysfunction:

   • Sepsis-induced myocardial depression reduces cardiac output 1
   • Only 10-20% of adults with sepsis develop cardiac failure characterized by persistently low cardiac index 2
   • Myocardial dysfunction contributes to decreased tissue perfusion 2

4. Additional Factors:

   • Relative adrenal insufficiency may contribute to hemodynamic instability in some cases 2
   • Decreased vasopressin levels in later stages of septic shock 4

Clinical Manifestations

The hemodynamic effects of sepsis present as:

• Cold peripheries and prolonged capillary refill time 2
• Oliguria due to reduced renal perfusion 2
• Altered mental status from decreased cerebral perfusion 2
• Elevated lactate levels (>2 mmol/L) indicating tissue hypoperfusion 2

Severity Spectrum

Hypotension in sepsis exists on a spectrum:

• Non-sustained hypotension (single or intermittent episodes) still confers a threefold increase in mortality risk 5
• Cryptic shock can occur without arterial hypotension but is indicated by elevated lactate levels 2
• Septic shock is defined as persistent hypotension despite adequate fluid resuscitation, with evidence of tissue hypoperfusion 2

Management Implications

Understanding the pathophysiology guides treatment:

• Initial fluid resuscitation addresses hypovolemia with at least 20 mL/kg of intravenous crystalloid solution 2
• Vasopressor therapy (with norepinephrine as first-line) is required when hypotension persists despite adequate fluid resuscitation 2
• Target MAP of 65-70 mmHg is recommended during hemodynamic support 2
• In patients with advanced chronic kidney disease, an early restrictive fluid strategy prioritizing vasopressors may be associated with better outcomes 6
• Lactated Ringer's solution may be preferred over normal saline for initial fluid resuscitation 7

Special Considerations

• Young patients may maintain alertness despite severe cardiovascular collapse, potentially leading to underestimation of shock severity 2
• Pediatric septic shock often presents with signs of cardiac failure and hypovolemia 2
• Fluid overload should be avoided, particularly in patients with generalized peritonitis, as it may aggravate gut edema and increase intra-abdominal pressure 2

Understanding that vasodilation, hypovolemia, and cardiac dysfunction are the primary mechanisms of hypotension in sepsis allows for targeted therapeutic interventions to improve tissue perfusion and reduce mortality.