What dose of epinephrine should be started and how should it be titrated in a patient already on 15mcg/min of Levophed (norepinephrine)?

Adding Epinephrine to High-Dose Norepinephrine

When a patient on 15 mcg/min of norepinephrine requires additional vasopressor support, start epinephrine at 0.1-0.5 mcg/kg/min (approximately 7-35 mcg/min in a 70 kg adult) and continue titrating the norepinephrine up to 0.25 mcg/kg/min before escalating the epinephrine dose. 1

Initial Epinephrine Dosing Strategy

• Start epinephrine at 0.1 mcg/kg/min (approximately 7 mcg/min in a 70 kg patient) as a continuous IV infusion, preferably through central venous access 1
• The typical dosing range for epinephrine in septic shock is 0.1-2 mcg/kg/min 1
• Epinephrine should be added when norepinephrine reaches approximately 0.25 mcg/kg/min (roughly 17.5 mcg/min in a 70 kg patient) and hypotension persists despite adequate fluid resuscitation 1

Titration Algorithm

Primary strategy: Continue escalating norepinephrine first, then add epinephrine

• If the patient is at 15 mcg/min of norepinephrine (approximately 0.21 mcg/kg/min in a 70 kg patient), you are approaching the threshold where adding a second agent is appropriate 1
• Once epinephrine is started at 0.1 mcg/kg/min, continue titrating norepinephrine up to 0.25 mcg/kg/min before increasing the epinephrine dose 1
• After norepinephrine reaches 0.25 mcg/kg/min, titrate epinephrine upward in increments of 0.05-0.1 mcg/kg/min every 5-15 minutes based on blood pressure response 1
• Monitor blood pressure and heart rate every 5-15 minutes during initial titration of either agent 1

Target Blood Pressure and Monitoring

• Target mean arterial pressure (MAP) of 65 mmHg for most patients with septic shock 1
• Assess tissue perfusion markers beyond just MAP: lactate clearance, urine output >50 mL/h, mental status, and capillary refill 1
• Place an arterial catheter as soon as practical for continuous blood pressure monitoring when using dual vasopressors 1

Alternative Escalation: Consider Vasopressin Before Epinephrine

An important alternative approach: When norepinephrine reaches 0.25 mcg/kg/min, consider adding vasopressin 0.03-0.04 units/min as second-line therapy rather than epinephrine 1. This strategy may be preferable because:

• Vasopressin does not increase heart rate or cause arrhythmias like epinephrine 2
• Vasopressin can allow reduction of norepinephrine dose while maintaining MAP 2
• Do not increase vasopressin above 0.03-0.04 units/min; reserve higher doses only for salvage therapy 1

Critical Precautions with Epinephrine

Epinephrine has significant adverse effects that make it less favorable than norepinephrine-dobutamine combinations:

• Epinephrine causes transient lactic acidosis even when improving hemodynamics, which can confuse clinical assessment 3
• Epinephrine increases heart rate significantly more than norepinephrine and causes new arrhythmias in a substantial proportion of patients 3
• Epinephrine impairs splanchnic perfusion (increased gastric PCO2 gap) compared to norepinephrine-dobutamine, which improves it 3
• These effects occur despite similar improvements in cardiac index and global hemodynamics 3

When to Add Inotropic Support Instead

If the patient has evidence of myocardial dysfunction with persistent hypoperfusion despite adequate vasopressors:

• Add dobutamine up to 20 mcg/kg/min rather than escalating epinephrine 1
• Start dobutamine at 2.5 mcg/kg/min, doubling the dose every 15 minutes according to response 4
• Dose titration is usually limited by excessive tachycardia, arrhythmias, or ischemia 4

Administration Route Requirements

• Central venous access is strongly preferred for both norepinephrine and epinephrine to minimize extravasation risk and tissue necrosis 1
• If extravasation occurs with either agent, infiltrate phentolamine 5-10 mg diluted in 10-15 mL of saline at the site immediately 1
• Do not mix epinephrine or norepinephrine with sodium bicarbonate or other alkaline solutions in the IV line, as they are inactivated in alkaline solutions 1

Fluid Resuscitation Requirements

Critical pitfall to avoid: Never escalate vasopressors without ensuring adequate volume resuscitation first 1

• Administer a minimum 30 mL/kg crystalloid bolus before or concurrent with vasopressor escalation 1
• Vasoconstriction in hypovolemic patients causes severe organ hypoperfusion despite "normal" blood pressure 1
• Use balanced crystalloids (lactated Ringer's or Plasma-Lyte) preferentially over normal saline 1