What is the first-line vasopressor (pressor) used in the management of septic shock?

First-Line Vasopressor in Septic Shock

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

Initial Management Protocol

• Administer a minimum of 30 mL/kg of crystalloids in the first 3 hours before or concurrent with vasopressor initiation 1, 2
• Start norepinephrine immediately if life-threatening hypotension exists—do not delay waiting to complete full fluid resuscitation 2
• Establish central venous access for safe norepinephrine administration 1, 2
• Place an arterial catheter as soon as practical for continuous blood pressure monitoring 1, 2

Why Norepinephrine Over Other Agents

Norepinephrine demonstrates superior survival compared to dopamine, with an 11% absolute risk reduction in mortality (number needed to treat = 9) and significantly fewer cardiac arrhythmias 3. The Surviving Sepsis Campaign gives norepinephrine a Grade 1B (strong) recommendation based on this mortality benefit 1.

Agents to Avoid as First-Line

• Dopamine: Use only in highly selected patients with low risk of tachyarrhythmias or absolute/relative bradycardia 1, 2. Dopamine is associated with higher mortality and more arrhythmias compared to norepinephrine 2, 3
• Phenylephrine: Not recommended except when norepinephrine causes serious arrhythmias, cardiac output is documented high with persistent hypotension, or as salvage therapy when all other agents fail 1, 2
• Low-dose dopamine for renal protection: Strongly contraindicated—provides no benefit 1, 2

Escalation Strategy for Refractory Hypotension

When norepinephrine alone fails to achieve MAP ≥65 mmHg despite adequate fluid resuscitation:

Second-Line Agent: Vasopressin

• Add vasopressin at 0.01 units/minute, titrating by 0.005 units/minute every 10-15 minutes to a maximum of 0.03 units/minute 2, 4
• Never use vasopressin as monotherapy—it must always be added to norepinephrine 1, 2, 4
• Doses above 0.03-0.04 units/minute should be reserved for salvage therapy only, as higher doses risk cardiac, digital, and splanchnic ischemia 1, 2
• Vasopressin provides a norepinephrine-sparing effect and may reduce complications from high-dose catecholamines 5

Third-Line Agent: Epinephrine

• Add epinephrine (0.05-2 mcg/kg/min) when norepinephrine plus vasopressin fail to achieve target MAP 1, 2
• Epinephrine increases myocardial oxygen consumption and causes transient lactic acidosis through β2-adrenergic stimulation, which can interfere with lactate clearance as a resuscitation endpoint 2, 6

Inotropic Support: Dobutamine

• Add dobutamine (2.5-20 mcg/kg/min) if persistent hypoperfusion exists despite adequate MAP and vasopressor therapy, particularly when myocardial dysfunction is evident 1, 2
• Dobutamine addresses cardiac output rather than vascular tone 2

Adjunctive Therapy for Refractory Shock

• Consider hydrocortisone 200 mg/day IV when hemodynamic stability cannot be achieved despite adequate fluid resuscitation and escalating vasopressor therapy 2, 7
• The decision is based on hemodynamic response, not a predetermined vasopressor dose cutoff 7
• Taper hydrocortisone when vasopressors are no longer required 7

Critical Monitoring Beyond Blood Pressure

• Assess tissue perfusion using lactate clearance, urine output, mental status, and capillary refill 2
• Monitor for signs of excessive vasoconstriction: digital ischemia, decreased urine output, rising lactate, or worsening organ dysfunction despite adequate MAP 2
• Titrate to adequate perfusion markers, not to supranormal blood pressure targets 2

Common Pitfalls to Avoid

• Do not delay norepinephrine for life-threatening hypotension while completing fluid resuscitation 2
• Do not use vasopressin as initial monotherapy—always add it to norepinephrine 1, 2
• Do not escalate vasopressin beyond 0.03-0.04 units/minute except as salvage therapy 1, 2
• Do not use dopamine as first-line—the evidence clearly favors norepinephrine for survival 1, 2, 3
• Do not rely solely on blood pressure numbers—monitor tissue perfusion markers 2