Do I titrate up on norepinephrine once epinephrine is added at a dose of 15 mcg/min?

Vasopressor Titration Strategy After Adding Epinephrine

Once epinephrine is added to norepinephrine at 15 mcg/min, you should NOT continue titrating norepinephrine upward—instead, titrate the epinephrine dose while maintaining or potentially reducing norepinephrine. 1

Rationale for This Approach

The key principle is that epinephrine becomes your primary titration agent once added, rather than continuing to escalate norepinephrine indefinitely. Here's why:

Escalation Sequence in Refractory Shock

• Norepinephrine remains first-line and should be titrated initially to achieve MAP ≥65 mmHg 1, 2
• Add vasopressin (0.03-0.04 units/min) when norepinephrine reaches 0.25 mcg/kg/min (approximately 15-20 mcg/min in a 70 kg patient) rather than continuing to escalate norepinephrine alone 1
• Epinephrine (0.1-0.5 mcg/kg/min) should be added when norepinephrine plus vasopressin fail to achieve adequate MAP and tissue perfusion 1

Why Not Continue Escalating Norepinephrine

• Higher norepinephrine doses (>10 mcg/min) are associated with increased mortality and should be avoided when possible 2
• Excessive norepinephrine causes severe vasoconstriction that may worsen end-organ perfusion despite "normal" blood pressure 1
• Combination therapy is superior to monotherapy escalation in refractory shock 1

Practical Titration Protocol

Once you've added epinephrine at your current state (norepinephrine 15 mcg/min, vasopressin presumably on board, epinephrine just started):

Immediate Actions

• Start epinephrine at 0.1 mcg/kg/min (approximately 5-10 mcg/min in adults) 3
• Maintain norepinephrine at current dose (15 mcg/min) initially 1
• Ensure vasopressin is at 0.03-0.04 units/min (do not exceed this dose) 1

Titration Strategy

• Titrate epinephrine upward by 0.05-0.1 mcg/kg/min increments every 10-15 minutes to achieve MAP ≥65 mmHg and adequate tissue perfusion markers 3
• Monitor tissue perfusion closely: lactate clearance, urine output >50 mL/h, mental status, capillary refill 1
• Once MAP stabilizes with epinephrine, consider reducing norepinephrine gradually by 25% decrements every 30 minutes as tolerated 2

Maximum Dosing Considerations

• Epinephrine can be titrated up to 0.5 mcg/kg/min (approximately 30-40 mcg/min in adults) 1, 3
• If MAP remains inadequate despite epinephrine 0.5 mcg/kg/min plus norepinephrine plus vasopressin, consider adding dobutamine (up to 20 mcg/kg/min) if myocardial dysfunction is present 1

Critical Monitoring During Epinephrine Infusion

Metabolic Concerns

• Epinephrine causes transient lactic acidosis and splanchnic hypoperfusion that typically resolves within 24 hours 4
• Monitor lactate levels closely—rising lactate with epinephrine may reflect metabolic effects rather than worsening shock 4
• Epinephrine increases cardiac double product (heart rate × systolic BP), raising myocardial oxygen demand 5

Hemodynamic Monitoring

• Place arterial catheter for continuous BP monitoring if not already present 1, 2
• Monitor heart rate closely—epinephrine causes significant tachycardia compared to norepinephrine 5
• Assess for arrhythmias, particularly at higher epinephrine doses 3

Common Pitfalls to Avoid

Don't Continue Escalating Norepinephrine Alone

• Continuing to push norepinephrine beyond 0.25-0.3 mcg/kg/min without adding other agents increases mortality and worsens organ perfusion 1, 2
• The goal is balanced vasopressor therapy, not maximal single-agent dosing 1

Don't Forget Adequate Volume Resuscitation

• Ensure at least 30 mL/kg crystalloid bolus has been given before or concurrent with vasopressor escalation 1
• Vasoconstrictors in hypovolemic patients cause severe organ hypoperfusion despite "normal" blood pressure 1

Don't Ignore Inotropic Support

• If cardiac output remains low despite adequate MAP, add dobutamine rather than continuing to escalate vasopressors 1
• Persistent hypoperfusion with adequate MAP suggests pump failure, not just vasodilation 1

Special Consideration for Cardiogenic Shock

• In cardiogenic shock specifically, epinephrine may worsen outcomes compared to norepinephrine, with higher rates of refractory shock (37% vs 7%, p=0.008) 5
• If your patient has cardiogenic shock rather than distributive shock, strongly consider norepinephrine plus dobutamine instead of adding epinephrine 4, 5