How do you add and titrate epinephrine (adrenaline) in a patient already on levophed (norepinephrine) at 20 micrograms (mcg)/min?

Adding Epinephrine to High-Dose Norepinephrine

When a patient is already on norepinephrine 20 mcg/min (approximately 0.3 mcg/kg/min in a 70 kg adult) and requires additional vasopressor support, add epinephrine at 2-10 mcg/min (0.03-0.15 mcg/kg/min) as a continuous IV infusion, preferably through central venous access. 1, 2

Initial Epinephrine Dosing Strategy

Starting Dose

• Begin epinephrine at 2-5 mcg/min (0.03-0.07 mcg/kg/min) as a continuous IV infusion 1, 2
• Prepare a standard concentration by adding 1 mg epinephrine to 250 mL D5W, yielding 4 mcg/mL 2
• Administer through central venous access whenever possible to minimize extravasation risk 2, 3

Titration Protocol

• Increase epinephrine by 2-5 mcg/min increments every 5-10 minutes based on blood pressure response and tissue perfusion markers 1, 2
• Target mean arterial pressure (MAP) ≥65 mmHg 2, 3
• Maximum recommended dose is 10 mcg/min for standard vasopressor support 1
• For refractory shock, doses up to 0.5 mcg/kg/min may be necessary 1

Monitoring Requirements During Dual Vasopressor Therapy

Hemodynamic Parameters

• Monitor blood pressure every 5-15 minutes during initial titration 2
• Place an arterial catheter for continuous blood pressure monitoring if not already present 2, 3
• Assess heart rate continuously, as epinephrine causes more tachycardia than norepinephrine alone 3

Tissue Perfusion Markers

• Evaluate lactate clearance, urine output (target >50 mL/h), mental status, and capillary refill 2, 3
• Monitor for signs of excessive vasoconstriction: cold extremities, decreased urine output, rising lactate 2
• Assess for myocardial ischemia, particularly in patients with coronary artery disease, as epinephrine increases myocardial oxygen consumption 1, 3

Critical Considerations When Combining Vasopressors

Volume Status

• Ensure adequate fluid resuscitation (minimum 30 mL/kg crystalloid) before escalating vasopressors, as vasoconstriction in hypovolemic patients causes severe organ hypoperfusion despite "normal" blood pressure 2, 3
• Continue crystalloid boluses (500-1000 mL) if signs of ongoing hypovolemia persist 1

Alternative Escalation Strategy

• Consider adding vasopressin 0.03-0.04 units/min instead of epinephrine when norepinephrine reaches 0.25 mcg/kg/min 2, 3
• Vasopressin may be preferred over epinephrine as it does not increase heart rate or myocardial oxygen demand 2
• If vasopressin is already on board, then epinephrine becomes the appropriate third agent 2

Inotropic Support Consideration

• If persistent hypoperfusion exists despite adequate MAP (suggesting myocardial dysfunction), add dobutamine 2.5-20 mcg/kg/min rather than escalating epinephrine 2
• Dobutamine provides inotropic support without the excessive vasoconstriction of high-dose catecholamines 2

Practical Administration Details

Preparation for Refractory Cases

• For anaphylaxis or refractory shock requiring higher doses, prepare a more concentrated solution: 1 mg epinephrine in 100 mL saline (10 mcg/mL) 2, 4
• This allows administration at 30-100 mL/h (5-15 mcg/min) for easier titration 2

Extravasation Management

• If extravasation occurs, immediately infiltrate phentolamine 5-10 mg diluted in 10-15 mL saline into the affected site to prevent tissue necrosis 2, 3
• Epinephrine causes severe tissue necrosis similar to norepinephrine 2

Common Pitfalls to Avoid

Inadequate Volume Resuscitation

• Never escalate to dual vasopressors without ensuring adequate intravascular volume, as this creates a "high pressure, low flow" state that worsens organ perfusion 2, 3
• The most common error is adding epinephrine when the patient actually needs more fluid 2

Excessive Tachycardia

• Epinephrine has stronger beta-1 effects than norepinephrine, causing significant tachycardia that increases myocardial oxygen demand 3, 5
• If heart rate exceeds 120-130 bpm, consider switching to vasopressin or phenylephrine instead 2, 3

Ignoring Tissue Perfusion

• Do not titrate solely to MAP targets—assess lactate clearance, urine output, mental status, and capillary refill 2, 3
• High doses of catecholamines can maintain blood pressure while worsening microcirculatory flow, particularly in the gastrointestinal tract 6

Drug Incompatibility

• Never mix epinephrine or norepinephrine with sodium bicarbonate or other alkaline solutions, as catecholamines are inactivated in alkaline environments 2

Special Clinical Scenarios

Perioperative Anaphylaxis

• In Grade III anaphylaxis (life-threatening hypotension/bronchospasm) unresponsive to other vasopressors, start epinephrine at 100 mcg IV bolus, then transition to infusion at 0.05-0.1 mcg/kg/min 1
• For persistent hypotension after 10 minutes, add norepinephrine infusion (0.05-0.5 mcg/kg/min) rather than escalating epinephrine alone 1

Beta-Blocker Toxicity

• Norepinephrine is more effective than dopamine for hypotension in beta-blocker toxicity 2
• Add glucagon 1-2 mg IV with infusion of 3-5 mg/h if hypotension persists despite catecholamines 1