What are the guidelines for using vasoconstrictors (e.g. norepinephrine, vasopressin) in clinical practice?

Vasopressor Guidelines for Clinical Practice

First-Line Vasopressor Selection

Norepinephrine is the mandatory first-choice vasopressor for septic shock and most forms of vasodilatory shock, initiated immediately when hypotension persists after adequate fluid resuscitation (minimum 30 mL/kg crystalloid), with a target mean arterial pressure (MAP) of 65 mmHg. 1, 2, 3

• Norepinephrine provides reliable vasoconstriction through alpha-adrenergic receptor stimulation while maintaining cardiac output through modest beta-1 adrenergic effects 1, 4
• Dopamine should be avoided as first-line therapy—it is associated with significantly higher mortality and more arrhythmias compared to norepinephrine, and should only be considered in highly selected patients with low risk of tachyarrhythmias or absolute/relative bradycardia 1, 2, 5
• Administration requires central venous access whenever possible to minimize extravasation risk, with arterial catheter placement recommended as soon as practical for continuous blood pressure monitoring 2, 3, 5

Vasopressor Administration Protocol

Initial Setup and Monitoring

• Verify central venous access before initiating vasopressors 3
• Place arterial catheter for continuous blood pressure monitoring as soon as practical 2, 5
• Monitor blood pressure and heart rate every 5-15 minutes during initial titration 5
• Assess perfusion markers beyond MAP: capillary refill, urine output (≥0.5 mL/kg/h), lactate clearance, and mental status 1, 3, 5

Norepinephrine Dosing

• Start at 0.1-0.5 mcg/kg/min and titrate to achieve MAP ≥65 mmHg 3
• Doses above 0.25-0.50 mcg/kg/min (approximately 15 mcg/min in a 70 kg patient) indicate severe shock requiring addition of second-line agents rather than further norepinephrine escalation 2, 3, 6

Second-Line Vasopressor Strategy

When norepinephrine requirements remain elevated or target MAP cannot be achieved, add vasopressin at a fixed dose of 0.03 units/minute—do not use vasopressin as monotherapy. 1, 2, 3, 5

Vasopressin Addition Protocol

• Standard dose: 0.03 units/minute (range 0.01-0.03 units/minute) 2, 5
• Vasopressin acts on V1 receptors independent of catecholamine pathways, providing complementary vasoconstriction and norepinephrine-sparing effects 2, 3, 6
• Maximum dose should not exceed 0.03-0.04 units/minute except as salvage therapy, due to risk of cardiac, digital, and splanchnic ischemia 1, 3, 5
• After adding vasopressin, either raise MAP to target or decrease norepinephrine dosage while maintaining hemodynamic stability 2, 5

Evidence for Vasopressin Timing

• Early addition of vasopressin (within 3 hours of norepinephrine initiation) is associated with faster time to shock resolution (37.6 vs 60.7 hours) and decreased ICU length of stay compared to late addition 7
• The VANISH trial showed vasopressin reduced renal replacement therapy requirements (25.4% vs 35.3%) compared to norepinephrine alone, though kidney failure-free days were not significantly different 8

Third-Line and Refractory Shock Management

If hemodynamic targets remain unmet despite norepinephrine plus vasopressin, add epinephrine (0.05-2 mcg/kg/min) as a third agent rather than increasing vasopressin beyond 0.03-0.04 units/minute. 2, 3, 5

Alternative Escalation Options

• Epinephrine provides both alpha and beta-adrenergic stimulation, increasing both vasoconstriction and cardiac output 1, 3
• Dobutamine (up to 20 mcg/kg/min) should be added for persistent hypoperfusion despite adequate vasopressor support when myocardial dysfunction is evident, particularly when ScvO2 <70% 1, 3, 5
• Hydrocortisone 200 mg/day (50 mg IV every 6 hours) may be considered for refractory shock after 4 hours of norepinephrine or epinephrine at ≥0.25 mcg/kg/min 3

Agents to Avoid and Critical Pitfalls

Dopamine

• Strongly discouraged for renal protection—this practice has no benefit and should never be used for this indication 1, 2, 5
• Low-dose dopamine (<3 mcg/kg/min) for "renal effect" is contraindicated and offers no protection 1
• Associated with higher mortality and arrhythmias compared to norepinephrine 1, 2

Phenylephrine

• Not recommended except in specific circumstances: norepinephrine-induced serious arrhythmias, documented high cardiac output with persistent hypotension, or salvage therapy when all other agents have failed 1, 2, 3, 5
• Pure alpha-agonist activity may raise blood pressure numbers while compromising microcirculatory flow and tissue perfusion 2

Excessive Vasoconstriction Warning

• Monitor for signs of excessive vasoconstriction: cold extremities, digital ischemia, decreased urine output, rising lactate, or worsening organ dysfunction despite adequate MAP 2, 5
• Titrate to adequate perfusion markers, not to supranormal blood pressure targets 2

Special Populations

Pediatric Considerations

• Norepinephrine is recommended as first-line vasoactive drug in pediatric septic shock 1
• Age-specific insensitivity to dopamine exists in infants <6 months due to incomplete sympathetic innervation 1
• Phosphodiesterase III inhibitors may be considered in cases of low cardiac output with normal arterial pressure 1

Heart Failure Patients

• Norepinephrine can be used safely in septic shock patients with preexisting heart failure, though it may increase myocardial oxygen requirements 2
• Continue chronic beta-blockers unless acute hemodynamic decompensation or cardiogenic shock is present 2
• Add dobutamine for persistent hypoperfusion when myocardial dysfunction is evident 2

Cardiogenic Shock

• Inotropes (dobutamine) should be reserved for patients with severe reduction in cardiac output causing vital organ hypoperfusion 1
• Vasopressors with prominent vasoconstrictor action (norepinephrine) increase LV afterload and should be restricted to patients with persistent hypoperfusion despite adequate cardiac filling pressures 1
• Vasodilators (nitroprusside, nitroglycerin) are first-line for normal blood pressure with high SVR, followed by milrinone if toxicity develops 1

Drug Interactions and Monitoring

Critical Drug Interactions (Vasopressin)

• Catecholamines: additive hemodynamic effects requiring dose adjustment 9
• Indomethacin: may prolong vasopressin effects on cardiac index and SVR 9
• Ganglionic blocking agents: may increase pressor effect 9
• SSRIs, tricyclic antidepressants, haloperidol: may increase both pressor and antidiuretic effects 9

Extravasation Management

• Infiltrate 5-10 mg phentolamine diluted in 10-15 mL saline into extravasation site immediately to prevent tissue necrosis 2