How to start an adrenaline infusion in a critically ill adult with hypotension unresponsive to noradrenaline and vasopressin?

Starting Adrenaline Infusion in Refractory Hypotension

When hypotension persists despite noradrenaline and vasopressin, commence an adrenaline (epinephrine) infusion at 0.05-0.1 mcg/kg/min peripherally while preparing for central access, and escalate by doubling the dose every 10 minutes if inadequate response. 1

Pre-Infusion Requirements

Before initiating adrenaline, ensure the following baseline management is optimized:

• Confirm adequate fluid resuscitation with at least 30 mL/kg crystalloid bolus, as inadequate volume loading will worsen organ hypoperfusion despite vasopressor support 2, 3
• Verify noradrenaline dosing has reached 0.25 mcg/kg/min (approximately 15-20 mcg/min in a 70 kg adult) before adding adrenaline 2
• Confirm vasopressin is running at 0.03-0.04 units/min, as this is the maximum recommended dose before adding additional agents 1, 2
• Establish arterial line monitoring for continuous blood pressure assessment, as frequent titration will be required 2, 3

Adrenaline Infusion Protocol

Initial Preparation and Dosing

• Standard concentration: Add 4 mg adrenaline to 250 mL D5W to create 16 mcg/mL solution 3
• Starting dose: 0.05-0.1 mcg/kg/min (3.5-7 mcg/min in a 70 kg adult) via continuous IV infusion 1, 2
• Administration route: Peripheral IV access is acceptable initially while preparing central access, as delays in vasopressor administration worsen outcomes 1

Titration Strategy

• Monitor blood pressure every 5-15 minutes during initial titration 3
• Target MAP ≥65 mmHg while assessing tissue perfusion markers (lactate clearance, urine output, mental status, capillary refill) 2, 3
• Escalate by doubling the bolus dose every 10 minutes if inadequate sustained response 1
• Maximum practical dose: 0.5-2 mcg/kg/min, though higher doses may be required in refractory shock 2, 3

Critical Monitoring Requirements

Hemodynamic Parameters

• Continuous arterial pressure monitoring is mandatory once adrenaline is initiated 2, 3
• Assess tissue perfusion beyond MAP: lactate trends, urine output >0.5 mL/kg/h, mental status, skin perfusion 2
• Monitor for excessive vasoconstriction: cold extremities, rising lactate despite adequate MAP, decreasing urine output 2

Cardiac Monitoring

• Watch for tachyarrhythmias, as adrenaline significantly increases this risk (RR 0.35 for ventricular arrhythmias when used early) 2
• Monitor for myocardial ischemia, particularly in patients with coronary disease, as adrenaline increases myocardial oxygen consumption more than noradrenaline 2
• Expect transient lactic acidosis from β2-adrenergic stimulation of skeletal muscle, which interferes with lactate clearance as a resuscitation endpoint 2

Adjunctive Therapies to Consider

When Myocardial Dysfunction is Present

• Add dobutamine 2.5-20 mcg/kg/min if persistent hypoperfusion exists despite adequate MAP and vasopressor therapy, particularly when echocardiography demonstrates reduced contractility 1, 2
• Start low (2.5 mcg/kg/min) and double every 15 minutes according to response, with dose usually limited by tachycardia or arrhythmias 2

For Refractory Shock

• Consider hydrocortisone 200 mg/day IV for shock reversal if hypotension remains refractory, as corticosteroids have decreased 28-day mortality in some large trials 2
• Evaluate for extracorporeal life support if available and patient is a candidate 1

Common Pitfalls and How to Avoid Them

Dosing Errors

• Never escalate vasopressin above 0.03-0.04 units/min before adding adrenaline, as higher vasopressin doses cause cardiac, digital, and splanchnic ischemia without mortality benefit 1, 2
• Do not use dopamine as an alternative, as it is associated with higher mortality and more arrhythmias compared to noradrenaline 2, 4
• Avoid phenylephrine in this scenario, as pure alpha-agonism may raise blood pressure numbers while actually worsening tissue perfusion 2

Volume Status Mistakes

• Never start adrenaline in hypovolemic patients, as vasoconstriction without adequate preload causes severe organ hypoperfusion despite "normal" blood pressure 2, 3
• Reassess volume status if adrenaline requirements rapidly escalate, as ongoing fluid losses may be present 2

Monitoring Gaps

• Do not rely solely on MAP targets—patients may have adequate blood pressure but poor tissue perfusion 2
• Trend lactate every 2-4 hours initially, recognizing that adrenaline causes transient elevation through β2-stimulation 2
• Watch for digital ischemia with high-dose catecholamines, particularly when combined with vasopressin 1, 2

Special Considerations

In Anaphylaxis Context

• Use higher initial bolus doses (50-200 mcg IV) rather than starting an infusion if anaphylaxis is the underlying cause 1
• Commence infusion at 0.05-0.1 mcg/kg/min only after more than three adrenaline boluses have been administered 1

In Septic Shock

• Adrenaline is the recommended second-line agent when noradrenaline plus vasopressin fail to achieve target MAP 2, 4
• Early administration may improve cardiac output through increased preload and contractility, even in patients with poor baseline cardiac function 5

Transition to Central Access

• Plan for central line placement as soon as practical, though peripheral administration is acceptable initially 1, 3
• If extravasation occurs, infiltrate phentolamine 5-10 mg diluted in 10-15 mL saline at the site immediately 3