What is the next step in management for a patient with persistent hypotension despite receiving an intravenous (IV) fluid bolus and antibiotics?

Management of Persistent Hypotension After Initial Fluid Resuscitation in Septic Shock

The answer is B. Norepinephrine. After receiving an adequate initial fluid bolus (30 mL/kg) with persistent hypotension (BP 80/40 mmHg), the next step is immediate initiation of norepinephrine as the first-choice vasopressor, not additional fluid boluses. 1, 2

Rationale for Vasopressor Over Additional Fluids

Vasopressor initiation should not be delayed waiting for additional fluid boluses in fluid-refractory shock. 2 The patient has already received the recommended 30 mL/kg IV fluid bolus per Surviving Sepsis Campaign guidelines, which defines the threshold for adequate initial fluid resuscitation. 1 Persistent hypotension after this fluid challenge meets the operational definition of septic shock requiring vasopressor therapy. 3

• Patients with septic shock who remain hypotensive (systolic BP < 90 mmHg or MAP < 65 mmHg) after adequate initial fluid resuscitation require vasopressor support rather than additional fluid boluses. 2
• Additional fluid administration in fluid-refractory shock increases risk of fluid overload complications, which can delay organ recovery, prolong ICU length of stay, and increase mortality. 4
• The only justification for IV fluids in circulatory shock is to increase mean systemic filling pressure in volume-responsive patients to increase cardiac output—not applicable once adequate fluid resuscitation has been completed. 4

Norepinephrine as First-Line Vasopressor

Norepinephrine is recommended as the first-choice vasopressor with strong recommendation and moderate quality evidence. 1

• The Surviving Sepsis Campaign guidelines (2016) provide a Grade 1B recommendation (strong recommendation, moderate quality evidence) for norepinephrine as the initial vasopressor in septic shock. 1
• Norepinephrine should be initiated to target a mean arterial pressure (MAP) of ≥65 mmHg. 2, 5
• Vasopressor therapy should be administered simultaneously with fluid replacement to prevent and decrease duration of hypotension in vasodilatory shock. 6
• Very early administration of vasopressors, preferably during the first hour after diagnosis of septic shock, may lead to lower morbidity and mortality. 4

Practical Administration Details

• Initial dosing: Start norepinephrine at 0.02 mcg/kg/min, which can be initiated peripherally until central access is obtained. 2
• Standard dilution: Add 4 mg/4 mL of norepinephrine to 1,000 mL of 5% dextrose solution (yielding 4 mcg/mL concentration). 5
• Initial infusion rate: Begin with 2-3 mL/minute (8-12 mcg/minute of base), then titrate to achieve MAP ≥65 mmHg. 5
• Maintenance dosing: Average maintenance ranges from 0.5-1 mL/minute (2-4 mcg/minute of base), though individual variation is substantial. 5
• Central access: Administer through a large vein, preferably with central access as soon as practical, to minimize risk of tissue necrosis from extravasation. 2, 5
• Monitoring: Place an arterial catheter as soon as practical if resources are available for all patients requiring vasopressors. 1

Why Not Additional Fluid Boluses

• The current recommendation to administer 30 mL/kg fluid cannot be universally applied to all patients, and complications of fluid over-resuscitation are well-documented. 4
• Once the initial 30 mL/kg fluid challenge has been administered and hypotension persists, this defines fluid-refractory shock requiring vasopressor therapy rather than additional volume. 2, 3
• Continuing fluid administration in non-volume-responsive patients leads to tissue edema, impaired oxygen delivery, prolonged mechanical ventilation, and increased mortality. 4

Additional Vasopressor Options if Norepinephrine Insufficient

• Vasopressin: If MAP remains inadequate despite low-moderate dose norepinephrine (0.1-0.2 mcg/kg/min), add vasopressin 0.03-0.04 units/minute. 2
• Epinephrine: Can be added to or potentially substituted for norepinephrine when an additional agent is needed to maintain adequate blood pressure (Grade 2B recommendation). 1
• Hydrocortisone: If shock remains refractory after 4 hours of adequate vasopressor therapy, consider hydrocortisone 200 mg/day (50 mg IV every 6 hours or continuous infusion). 2

Common Pitfalls to Avoid

• Do not use dopamine as first-line agent except in highly selected patients with bradycardia and low arrhythmia risk (Grade 2C recommendation). 1, 2
• Do not delay vasopressor initiation waiting for additional fluid boluses once adequate initial resuscitation (30 mL/kg) has been completed. 2
• Do not use low-dose dopamine for renal protection (Grade 1A recommendation against). 1
• Avoid phenylephrine except in specific circumstances: serious arrhythmias with norepinephrine, known high cardiac output with persistently low BP, or salvage therapy. 1