What is the relationship between hypotension and sepsis (systemic inflammatory response syndrome)?

From the Guidelines

Hypotension in sepsis requires immediate intervention with intravenous fluids and vasopressors, with a target mean arterial pressure (MAP) of at least 65 mmHg, as recommended by the Surviving Sepsis Campaign guidelines 1.

Key Recommendations

• Start with crystalloid fluid resuscitation using 30 ml/kg of balanced crystalloids within the first 3 hours, as suggested by the 2016 Surviving Sepsis Campaign International Guidelines for Management of Sepsis and Septic Shock 1.
• If hypotension persists despite adequate fluid resuscitation, initiate norepinephrine as the first-line vasopressor at 0.05-3 mcg/kg/min to maintain a MAP of at least 65 mmHg, as recommended by the World Journal of Emergency Surgery 1.
• Vasopressin (0.03 units/min) can be added as a second agent if needed, as suggested by the Kidney International journal 1.
• Simultaneously, address the underlying infection with broad-spectrum antibiotics within 1 hour of recognition, obtaining blood cultures before antibiotic administration, as recommended by the Surviving Sepsis Campaign guidelines 1.
• Measure lactate levels to assess tissue perfusion, with elevated levels (>2 mmol/L) indicating more severe disease, as suggested by the Intensive Care Medicine journal 1.

Pathophysiology and Clinical Considerations

• Septic shock, defined as hypotension requiring vasopressors to maintain MAP ≥65 mmHg and serum lactate >2 mmol/L despite adequate fluid resuscitation, carries high mortality and demands aggressive management, as stated in the World Journal of Emergency Surgery 1.
• The pathophysiology involves systemic vasodilation, capillary leak, and myocardial depression due to inflammatory mediators, resulting in decreased vascular resistance and relative hypovolemia, as explained in the Intensive Care Medicine journal 1.
• Early recognition and treatment are crucial for improving outcomes in sepsis-induced hypotension, as emphasized by the Surviving Sepsis Campaign guidelines 1.

From the FDA Drug Label

1. INDICATIONS & USAGE 1.1 Hypotension associated with Septic Shock Epinephrine Injection USP, 1 mg/10 mL (0.1 mg/mL) is indicated to increase mean arterial blood pressure in adult patients with hypotension associated with septic shock.
2. CLINICAL STUDIES 14.1 Hypotension associated with Septic Shock Fourteen clinical studies from the literature documented that epinephrine increases the mean arterial pressure (MAP) in patients with hypotension associated with septic shock.

• Epinephrine is indicated to increase mean arterial blood pressure in adult patients with hypotension associated with septic shock 2.
• Clinical studies have shown that epinephrine increases the mean arterial pressure (MAP) in patients with hypotension associated with septic shock 2. Epinephrine can be used to treat hypotension in patients with sepsis, specifically those with septic shock.

From the Research

Hypotension and Sepsis

• Hypotension is a common condition associated with septic shock, and it is a major determinant of mortality in patients with septic shock 3.
• The extent and duration of hypotension are important factors in determining patient outcomes, with prolonged hypotension leading to increased morbidity and mortality 3.
• The current recommendation for managing septic shock includes the administration of intravenous fluids and vasopressors, with the goal of increasing mean arterial pressure and improving organ perfusion 3, 4.

Fluid Resuscitation

• The Surviving Sepsis Campaign guidelines recommend administering 30 ml/kg of crystalloid fluids for hypotension or lactate ≥4 mmol/L in patients with septic shock, but there is limited evidence to support this recommendation 4.
• Studies have shown that initial fluid resuscitation doses of 20-30 ml/kg may be associated with reduced 28-day mortality in patients with septic shock, but further research is needed to confirm this finding 4, 5.
• Fluid over-resuscitation can lead to complications such as delayed organ recovery, prolonged ICU and hospital length of stay, and increased mortality, highlighting the need for careful fluid management in patients with septic shock 3, 6.

Vasopressor Therapy

• Vasopressor therapy is a fundamental treatment for septic shock-induced hypotension, aiming to correct vascular tone depression and improve organ perfusion pressure 7.
• Norepinephrine is currently recommended as the first-line vasopressor in septic shock, with vasopressin and its analogues as second-line options 7.
• Early administration of vasopressors, preferably within the first hour of diagnosis, may have a multimodal action and potential advantages, leading to lower morbidity and mortality in patients with septic shock 3, 7.