What is the cause of hypotension in sepsis?

Causes of Hypotension in Sepsis

Hypotension in sepsis is primarily caused by vasodilation induced by the systemic inflammatory response syndrome to infection, combined with hypovolemia from capillary leak syndrome and myocardial dysfunction. 1

Pathophysiological Mechanisms

1. Vasodilation

• Systemic inflammatory response: The dysregulated host response to infection triggers widespread vasodilation 1, 2
• Nitric oxide overproduction: Activation of inducible nitric oxide synthase (iNOS) leads to excessive vasodilation 3
• ATP-sensitive potassium channels: Over-activation of KATP channels contributes to vascular dysfunction and decreased vascular tone 3
• Inflammatory mediators: Release of vasodilatory inflammatory mediators impairs vascular reactivity 4

2. Hypovolemia

• Capillary leak syndrome: Increased vascular permeability leads to fluid shifting from intravascular to interstitial spaces 1
• True fluid loss: Can occur from various sources including fever, vomiting, diarrhea, or decreased oral intake 1
• Interstitial edema formation: Despite fluid accumulation in tissues, intravascular volume remains depleted 1

3. Cardiac Dysfunction

• Myocardial depression: Sepsis-induced cardiac dysfunction contributes to decreased cardiac output 1
• Altered vasomotor tone: Changes in vascular resistance affect cardiac performance 1
• Adrenal insufficiency: In some instances, relative adrenal insufficiency may contribute to hemodynamic instability 1

Clinical Manifestations of Sepsis-Induced Hypotension

• Arterial hypotension: Systolic blood pressure ≤90 mmHg or a decrease ≥40 mmHg from baseline 1, 2
• Mean arterial pressure: Often falls below 70 mmHg 2
• Signs of tissue hypoperfusion:
  • Cold peripheries and prolonged capillary refill time
  • Oliguria
  • Altered mental status
  • Lactic acidosis (lactate >2 mmol/L) 1, 2

Vasoplegia in Septic Shock

Vasoplegia (severe vasodilation with vascular hyporeactivity to vasoconstrictors) is a key factor in septic shock mortality due to persistent and irreversible hypotension 4, 3. Contributing mechanisms include:

• Endothelial injury
• Arginine-vasopressin system dysfunction
• Increased concentrations of vasodilator peptides (adrenomedullin, calcitonin gene-related peptide)
• Muscle hyperpolarization
• Oxidative stress causing endothelial dysfunction
• Inactivation of catecholamines by oxidation 4, 3

Management Implications

Understanding these mechanisms guides treatment approaches:

• Fluid resuscitation: Addresses hypovolemia, with at least 20 mL/kg of intravenous crystalloid solution recommended as initial bolus 1, 2
• Vasopressor therapy: Required when hypotension persists despite adequate fluid resuscitation 2, 5
• Monitoring: Continuous evaluation of clinical signs, peripheral perfusion, and vital organ function is essential 2

Important Considerations

• Young patients may maintain alertness despite severe cardiovascular collapse, potentially leading to underestimation of shock severity 1
• Cryptic shock can occur without arterial hypotension but is indicated by elevated blood lactate levels (>4 mmol/L) 1
• Fluid type matters: Recent evidence suggests lactated Ringer's solution may be associated with improved survival compared to normal saline in sepsis-induced hypotension 6
• In patients with advanced chronic kidney disease, an early restrictive fluid strategy prioritizing vasopressors may be associated with better outcomes 7

Understanding the complex, multifactorial mechanisms of hypotension in sepsis is crucial for effective management and improved patient outcomes.