What is the first line vasopressor for sepsis?

First-Line Vasopressor for Sepsis

Norepinephrine is the mandatory first-choice vasopressor for septic shock, initiated as soon as hypotension persists after fluid resuscitation, with a target mean arterial pressure (MAP) of 65 mmHg. 1, 2

Initial Resuscitation Protocol

Before or concurrent with norepinephrine initiation, you must administer a minimum of 30 mL/kg of crystalloids in the first 3 hours. 1, 2 This fluid resuscitation is not optional—starting vasopressors in a hypovolemic patient causes severe organ hypoperfusion despite "normal" blood pressure numbers. 2 However, in life-threatening hypotension (systolic <70 mmHg), start norepinephrine immediately as an emergency measure while fluid resuscitation continues, rather than waiting for complete volume repletion. 2

Why Norepinephrine is First-Line

The Surviving Sepsis Campaign provides a strong recommendation with moderate quality evidence for norepinephrine as first-choice vasopressor. 1 Norepinephrine reliably increases blood pressure through both alpha-adrenergic vasoconstriction and modest beta-1 adrenergic cardiac stimulation, maintaining cardiac output while raising systemic vascular resistance. 2 This dual mechanism makes it superior to pure vasoconstrictors like phenylephrine, which may raise blood pressure on the monitor while actually worsening tissue perfusion. 2

Administration Requirements

• Central venous access is strongly preferred to minimize extravasation risk and tissue necrosis. 1, 2 If central access is unavailable or delayed, peripheral IV administration can be used temporarily with strict monitoring. 2
• Place an arterial catheter as soon as practical for continuous blood pressure monitoring in all patients requiring vasopressors. 1, 2
• Starting dose: 0.1-0.5 mcg/kg/min (approximately 7-35 mcg/min in a 70 kg adult), titrated to achieve MAP ≥65 mmHg. 2, 3

Escalation Strategy for Refractory Hypotension

When norepinephrine reaches 0.25 mcg/kg/min and hypotension persists despite adequate fluid resuscitation, add vasopressin at 0.03 units/minute rather than continuing to escalate norepinephrine alone. 1, 2 This "decatecholaminization" strategy reduces complications from high-dose norepinephrine. 4 Never use vasopressin as monotherapy—it must always be added to norepinephrine, not used as the sole initial vasopressor. 1, 2

If additional support is needed:

• Add epinephrine (0.1-0.5 mcg/kg/min) as a third agent when vasopressin plus norepinephrine fail to achieve target MAP. 1, 2
• Add dobutamine (up to 20 mcg/kg/min) if persistent hypoperfusion exists despite adequate vasopressors, particularly when myocardial dysfunction is evident. 1, 2

Agents to Avoid

Dopamine should NOT be used as first-line therapy. 1, 2 It is associated with higher mortality and more cardiac arrhythmias compared to norepinephrine, with a grade 2C recommendation to use it only in highly selected patients with low risk of tachyarrhythmias or absolute/relative bradycardia. 1 The evidence clearly favors norepinephrine over dopamine. 5, 6

Low-dose dopamine for renal protection is strongly discouraged (grade 1A)—it has no benefit and should never be used for this indication. 1, 2

Phenylephrine is NOT recommended except in three specific circumstances: (1) norepinephrine causes serious arrhythmias, (2) cardiac output is documented to be high with persistently low blood pressure, or (3) as salvage therapy when all other agents have failed. 1, 2 Phenylephrine may raise blood pressure numbers while compromising microcirculatory flow and worsening tissue perfusion. 2

Monitoring Beyond Blood Pressure

Do not rely solely on MAP—monitor markers of tissue perfusion including lactate clearance, urine output (>50 mL/h), mental status, and capillary refill. 2, 3 Titrate vasopressors to achieve adequate perfusion markers, not to supranormal blood pressure targets. 2

Critical Pitfalls to Avoid

• Do not delay norepinephrine waiting to complete all fluid resuscitation if life-threatening hypotension exists. 2
• Do not escalate vasopressin above 0.03-0.04 units/minute—higher doses are associated with cardiac, digital, and splanchnic ischemia and should be reserved only for salvage therapy. 1, 2
• Do not use hydroxyethyl starch for fluid resuscitation—it is strongly contraindicated due to increased mortality (51% vs 43%, p=0.03) and renal injury. 1, 3
• Address hypovolemia first—vasoconstriction in hypovolemic patients causes severe organ hypoperfusion despite "normal" blood pressure. 2, 3