What is the recommended adrenaline (epinephrine) infusion rate for an adult patient with septic shock?

Adrenaline Infusion Rate for Septic Shock

Epinephrine should be added to norepinephrine at a starting dose of 0.05 mcg/kg/min, titrated in increments of 0.03 mcg/kg/min up to a maximum of 0.3 mcg/kg/min (or approximately 2 mcg/kg/min based on FDA labeling), when norepinephrine alone or norepinephrine plus vasopressin fail to achieve target mean arterial pressure of 65 mmHg. 1, 2

Algorithmic Approach to Epinephrine Use

Step 1: Establish First-Line Therapy

• Initiate norepinephrine as the mandatory first-choice vasopressor, targeting MAP ≥65 mmHg after administering at least 30 mL/kg crystalloid resuscitation 1, 2
• Administer norepinephrine through central venous access with continuous arterial blood pressure monitoring 1, 2

Step 2: Escalation Protocol Before Epinephrine

• Add vasopressin at 0.03 units/minute when norepinephrine alone fails to maintain target MAP, rather than immediately escalating to epinephrine 1, 2
• Vasopressin should never be used as monotherapy and doses above 0.03-0.04 units/minute should be reserved only for salvage therapy 2, 3

Step 3: When to Add Epinephrine

• Add epinephrine as a second or third-line agent when norepinephrine plus vasopressin fail to achieve target MAP 2
• The Surviving Sepsis Campaign suggests epinephrine as an alternative to vasopressin when additional vasopressor support is needed 1

Step 4: Specific Dosing Protocol

• Start at 0.05 mcg/kg/min (approximately 3.5 mcg/min in a 70 kg patient) 4
• Titrate in increments of 0.03 mcg/kg/min every 10-15 minutes based on hemodynamic response 4
• Maximum dose: 0.3 mcg/kg/min (approximately 21 mcg/min in a 70 kg patient), though FDA labeling supports up to 2 mcg/kg/min 2, 4

Critical Considerations and Monitoring

Hemodynamic Effects

• Epinephrine provides both alpha-adrenergic vasoconstriction and beta-adrenergic cardiac stimulation, improving cardiovascular parameters more effectively than dobutamine when added to norepinephrine 4
• However, epinephrine causes transient lactic acidosis through β2-adrenergic stimulation of skeletal muscle, which interferes with lactate clearance as a resuscitation endpoint 2

Cardiac Safety Profile

• Epinephrine significantly increases the risk of cardiac arrhythmias, with a 65% risk reduction in ventricular arrhythmias when norepinephrine is used instead (RR 0.35; 95% CI 0.19-0.66) 2
• Epinephrine increases myocardial oxygen consumption more than norepinephrine, making it less safe in patients with potential cardiac ischemia 2
• Use with extreme caution in patients receiving cardiac glycosides, digitalis, or antiarrhythmics due to additive sympathomimetic effects 2

Alternative to Epinephrine: Dobutamine

• Consider dobutamine (2.5-20 mcg/kg/min) instead of epinephrine if persistent hypoperfusion exists despite adequate MAP and vasopressor therapy, particularly when myocardial dysfunction is evident 1, 2
• Dobutamine addresses cardiac output rather than vascular tone and should be titrated to perfusion endpoints 1, 2
• Reduce or discontinue dobutamine if worsening hypotension or arrhythmias develop 1

Common Pitfalls to Avoid

Do Not Use Epinephrine as First-Line Therapy

• Norepinephrine demonstrates superior survival compared to epinephrine monotherapy and should always be initiated first 2
• The mortality difference between norepinephrine and epinephrine monotherapy shows no significant benefit (RR 0.96; 95% CI 0.77-1.21), but norepinephrine has fewer adverse effects 2

Do Not Escalate Vasopressin Beyond 0.03-0.04 Units/Minute

• Add epinephrine as a third agent when norepinephrine exceeds moderate doses, rather than escalating vasopressin beyond 0.03-0.04 units/minute 2
• Higher vasopressin doses are associated with cardiac, digital, and splanchnic ischemia 2

Monitor for Lactic Acidosis

• Epinephrine causes lower arterial pH and higher serum lactate compared to dobutamine, which can confound assessment of tissue perfusion 4
• Despite this metabolic effect, 28-day mortality and major adverse effects are comparable between epinephrine and dobutamine strategies 4

Consider Adjunctive Corticosteroids

• Add hydrocortisone 200 mg/day IV for shock reversal if hypotension remains refractory to vasopressors, though this should not substitute for appropriate vasopressor escalation 2, 5
• Taper hydrocortisone when vasopressors are no longer required 1, 5

Practical Dosing Summary

For a 70 kg patient:

• Starting dose: 3.5 mcg/min (0.05 mcg/kg/min)
• Titration increments: 2.1 mcg/min (0.03 mcg/kg/min) every 10-15 minutes
• Maximum dose: 21 mcg/min (0.3 mcg/kg/min)

The key principle is that epinephrine should never be used as monotherapy but rather added to norepinephrine (with or without vasopressin) when first-line therapy fails to achieve hemodynamic targets, while carefully monitoring for arrhythmias and metabolic derangements. 1, 2, 4