What is the first-line vasopressor to give to a patient in shock, such as septic shock, cardiogenic shock, or hypovolemic shock, requiring vasopressor support?

First-Line Vasopressor in Shock

Norepinephrine is the mandatory first-line vasopressor for septic shock, cardiogenic shock, and most forms of distributive shock requiring vasopressor support. 1, 2, 3

Initial Vasopressor Protocol

• Start norepinephrine immediately when hypotension persists after fluid resuscitation (minimum 30 mL/kg crystalloid in first 3 hours), targeting a mean arterial pressure (MAP) of 65 mmHg. 1, 2, 3

• Administer norepinephrine through central venous access whenever possible to minimize extravasation risk, though peripheral administration is acceptable as an emergency measure in life-threatening hypotension. 1, 2

• Place an arterial catheter for continuous blood pressure monitoring as soon as practical—this is essential for all patients requiring vasopressors. 1, 2, 3

• Do not delay norepinephrine initiation while pursuing aggressive fluid resuscitation if severe hypotension threatens organ perfusion. 1

Why Norepinephrine Over Other Agents

The evidence strongly favoring norepinephrine is compelling and consistent across all major critical care guidelines:

• Norepinephrine reduces 28-day mortality by 11% absolute risk reduction compared to dopamine (number needed to treat = 9 patients), with a Grade 1B strong recommendation from the Surviving Sepsis Campaign. 1

• Norepinephrine carries 53% lower risk of supraventricular arrhythmias (RR 0.47; 95% CI 0.38-0.58) and 65% lower risk of ventricular arrhythmias (RR 0.35; 95% CI 0.19-0.66) compared to dopamine. 1

• Norepinephrine increases MAP through alpha-adrenergic vasoconstriction with modest beta-1 cardiac stimulation, maintaining cardiac output while raising systemic vascular resistance—unlike phenylephrine which may compromise tissue perfusion despite raising blood pressure numbers. 1

Escalation Strategy for Refractory Hypotension

When norepinephrine alone fails to achieve target MAP despite adequate fluid resuscitation, follow this algorithmic approach:

Second-Line Agent: Vasopressin

• Add vasopressin at 0.03 units/minute (starting range 0.01-0.03 units/minute) when norepinephrine requirements remain elevated or exceed 0.25-0.50 mcg/kg/min. 1, 2, 3

• Never use vasopressin as monotherapy—it must always be added to norepinephrine, not used as the sole initial vasopressor. 1, 2, 3

• Do not exceed 0.03-0.04 units/minute except as salvage therapy when all other vasopressors have failed, as higher doses are associated with cardiac, digital, and splanchnic ischemia. 1, 2

• Vasopressin provides a norepinephrine-sparing effect through a different signaling pathway (V1 receptor), which may reduce catecholamine-related complications. 4, 5

Third-Line Agent: Epinephrine

• Add epinephrine at 0.05-2 mcg/kg/min when norepinephrine plus vasopressin fail to achieve target MAP. 1, 3

• Epinephrine should be added as a third agent rather than escalating vasopressin beyond 0.03-0.04 units/minute. 1

• Be aware that epinephrine causes transient lactic acidosis through β2-adrenergic stimulation of skeletal muscle, which interferes with lactate clearance as a resuscitation endpoint. 1

Addressing Persistent Hypoperfusion: 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, 3

• Dobutamine addresses cardiac output rather than vascular tone—use it when the problem is pump failure, not just vascular collapse. 3, 6

Critical Agents to Avoid

Dopamine: Use Only in Highly Selected Patients

• Dopamine should only be used in highly selected patients with low risk of tachyarrhythmias or absolute/relative bradycardia—it is associated with higher mortality and significantly more arrhythmias compared to norepinephrine. 1, 2, 3

• The Society of Critical Care Medicine strongly discourages the use of low-dose dopamine for renal protection—this has no benefit and should never be done. 1, 2

Phenylephrine: Avoid Except in Specific Circumstances

• Do not use phenylephrine as first-line therapy—it may raise blood pressure on the monitor while actually worsening tissue perfusion through excessive vasoconstriction. 1, 2, 3

• Phenylephrine is only appropriate when: (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, 3

Special Considerations by Shock Type

Cardiogenic Shock

• Norepinephrine remains first-line for vasopressor support in cardiogenic shock with hypotension. 3, 6

• Consider inotropes (dobutamine, dopamine, or phosphodiesterase III inhibitors) as first-line agents when the primary problem is myocardial contractility rather than vascular tone. 3

• In afterload-dependent states (aortic stenosis, mitral stenosis), phenylephrine or vasopressin may be preferred to avoid increasing heart rate. 3

Obstructive Shock

• Address the underlying obstruction first—this is the definitive treatment. 3

• Use norepinephrine if persistent hypotension with tachycardia exists after addressing the obstruction. 3

Hypovolemic Shock

• Volume resuscitation is the primary treatment—vasopressors are temporizing measures only. 3

• Norepinephrine may be used as a bridge while achieving adequate volume resuscitation in life-threatening hypotension. 3

Monitoring Beyond Blood Pressure

• Do not rely solely on MAP—assess tissue perfusion using lactate clearance, urine output, mental status, and skin perfusion/capillary refill. 1, 3

• Consider cardiac output monitoring, especially when using pure vasopressors like vasopressin that do not provide inotropic support. 3

• Monitor for signs of excessive vasoconstriction: digital ischemia, decreased urine output, rising lactate, or worsening organ dysfunction despite adequate MAP. 1

Common Pitfalls to Avoid

• Do not delay norepinephrine while completing fluid resuscitation if hypotension is life-threatening—early vasopressor use is appropriate when diastolic blood pressure is critically low. 1

• Never use vasopressin as the sole initial vasopressor—it must always be added to norepinephrine. 1, 2, 3

• Do not escalate vasopressin beyond 0.03-0.04 units/minute—add epinephrine instead. 1

• Avoid using dopamine as first-line therapy—the mortality and arrhythmia data clearly favor norepinephrine. 1, 2, 3

• Do not use low-dose dopamine for renal protection—this is strongly discouraged and has no benefit. 1, 2