What are the indications and dosing guidelines for adrenaline (epinephrine) infusion?

Adrenaline Infusion: Indications and Dosing Guidelines

Adrenaline infusion is indicated when multiple bolus doses fail to control severe anaphylaxis or for hypotension associated with septic shock, with dosing starting at 1-4 mcg/min for adults (titrated up to 10 mcg/min) or 0.05-2 mcg/kg/min for weight-based protocols. 1, 2

Primary Indications for Adrenaline Infusion

Anaphylaxis Requiring Continuous Support

• Start an adrenaline infusion when several bolus doses (50 mcg IV) are required for severe hypotension or bronchospasm, as adrenaline has a short half-life. 1
• This typically occurs after 2-3 failed intramuscular or intravenous bolus attempts in refractory anaphylaxis 1
• The infusion provides sustained alpha-agonist activity (vasoconstriction), beta-agonist effects (inotropy and bronchodilation), and reduces further mediator release 1

Septic Shock with Persistent Hypotension

• Adrenaline infusion is indicated to increase mean arterial blood pressure in adult patients with hypotension associated with septic shock 2
• Consider adding adrenaline 0.1-0.5 mcg/kg/min when norepinephrine reaches 0.25 mcg/kg/min and hypotension persists 3

Preparation and Concentration

Standard Adult Preparation

• Add 1 mg (1 mL) of 1:1000 adrenaline to 250 mL of D5W to yield a concentration of 4.0 mcg/mL (1:250,000 solution). 1, 4
• This preparation allows for precise titration using standard infusion equipment 1

Alternative Concentration for Anaphylaxis

• An alternative 1:100,000 solution can be prepared by adding 1 mg adrenaline to 100 mL of saline 1, 4
• This is infused at 30-100 mL/h (5-15 mcg/min), titrated based on clinical response 1, 4

Pediatric Preparation ("Rule of 6")

• 0.6 × body weight (kg) = number of milligrams diluted to total 100 mL of saline; then 1 mL/h delivers 0.1 mcg/kg/min. 1, 4

Dosing Protocols

Adult Dosing for Anaphylaxis

• Initial infusion rate: 1-4 mcg/min (15-60 drops per minute with microdrop apparatus) 1, 4
• Titrate up to maximum of 10 mcg/min based on clinical response 1, 4
• Alternative protocol: Start at 5-15 mcg/min using the 1:100,000 solution, titrating up or down depending on response or toxicity 1
• Discontinue 30 minutes after resolution of all signs and symptoms 1

Adult Dosing for Septic Shock

• FDA-approved range: 0.05 mcg/kg/min to 2 mcg/kg/min, titrated to achieve desired mean arterial pressure 2
• Dilute in dextrose solution prior to infusion 2
• Infuse into a large vein 2
• Wean gradually when discontinuing 2

Pediatric Dosing

• 0.01 mg/kg (0.1 mL/kg of 1:10,000 solution up to 10 mg/min; maximum single dose 0.3 mg) 1
• Using the "Rule of 6" preparation, 1 mL/h delivers 0.1 mcg/kg/min 1, 4

Administration Requirements

Route and Access

• Infuse adrenaline into a large vein; central venous access is strongly preferred to minimize extravasation risk. 2, 3
• If central access unavailable, peripheral IV can be used temporarily with strict monitoring for extravasation 4

Critical Monitoring Parameters

• Monitor blood pressure and heart rate every 5-15 minutes during initial titration 4, 3
• Assess for signs of excessive vasoconstriction: cold extremities, decreased urine output 3
• Watch for cardiac adverse effects: arrhythmias, hypertension, myocardial ischemia 2
• Monitor for pulmonary edema, which may be fatal 2

Concurrent Fluid Resuscitation

• Administer saline 0.9% or lactated Ringer's solution at high rate via large-bore IV cannula (large volumes may be required). 1
• For septic shock, ensure adequate volume resuscitation before and during adrenaline administration 3
• In anaphylaxis with hypotension, rapid infusion of 1-2 liters normal saline at 5-10 mL/kg in first 5 minutes is recommended 1

Adjunctive Medications

Secondary Management in Anaphylaxis

• Chlorphenamine 10 mg IV (adult dose) 1
• Hydrocortisone 200 mg IV (adult dose) 1
• Combined H1 and H2 antagonists superior to either alone: diphenhydramine 25-50 mg IV plus ranitidine 50 mg IV 1
• Treat persistent bronchospasm with salbutamol infusion, consider aminophylline or magnesium sulfate 1

Alternative Vasopressors for Refractory Hypotension

• If blood pressure does not recover despite adrenaline infusion, consider metaraminol 1
• Vasopressin and norepinephrine may be used in anaphylaxis unresponsive to epinephrine 1
• Dopamine 2-20 mcg/kg/min may be required if epinephrine and fluid resuscitation fail 1

Critical Safety Considerations

Warnings and Precautions

• Monitor for acute severe hypertension 2
• Potential for serious cardiac arrhythmias and myocardial ischemia, particularly in patients with underlying heart disease 2
• Avoid extravasation into tissues, which causes local necrosis 2
• If extravasation occurs, infiltrate phentolamine 5-10 mg diluted in 10-15 mL saline at the site immediately 3
• Potential for oliguria or renal impairment 2

Drug Interactions

• Alpha blockers, vasodilators (nitrates), diuretics, antihypertensives, and ergot alkaloids counter the pressor effects 2
• Beta blockers, tricyclic antidepressants, MAO inhibitors, and COMT inhibitors potentiate adrenaline effects 2
• Beta blockers, halogenated anesthetics, quinidine, and cardiac glycosides increase arrhythmogenic potential 2
• For patients on beta-blockers with refractory cardiovascular effects, glucagon 1-5 mg IV over 5 minutes followed by infusion (5-15 mg/min) may be useful 1

Common Pitfalls to Avoid

Dosing and Route Confusion

• Never confuse anaphylaxis dosing (intramuscular boluses of 0.3-0.5 mg from 1:1000 solution) with cardiac arrest dosing (IV push of 1 mg from 1:10,000 solution). 5, 6
• Iatrogenic overdose from administering cardiac arrest doses for anaphylaxis causes potentially lethal cardiac complications including severe systolic dysfunction 5
• The 1:1000 concentration is for intramuscular use; 1:10,000 is for intravenous bolus use 5, 6

Premature Discontinuation

• Do not stop infusion prematurely—continue until 30 minutes after complete resolution of symptoms 1
• Protracted or biphasic reactions can occur; observe patients for at least 6 hours after acute event 7
• After severe reaction, close observation for 24 hours is recommended 1

Inadequate Fluid Resuscitation

• Failure to provide aggressive fluid resuscitation (crystalloid boluses of 20 mL/kg) alongside adrenaline infusion leads to inadequate response. 1
• In septic shock, minimum 30 mL/kg crystalloid bolus should be administered before or concurrent with adrenaline 3

Mixing with Incompatible Solutions

• Never mix adrenaline with sodium bicarbonate or other alkaline solutions in the IV line—adrenergic agents are inactivated in alkaline solutions. 3, 8

Post-Infusion Management

Observation and Monitoring

• Vital signs should be monitored continuously during infusion and for extended period after discontinuation 1
• After anaphylaxis, arrange transfer to appropriate Critical Care area 1
• Take Mast Cell Tryptase samples: initial sample during resuscitation, second at 1-2 hours, third at 24 hours or in convalescence 1

Weaning Protocol

• Wean adrenaline infusion gradually rather than abrupt discontinuation 2
• Reduce infusion rate incrementally while monitoring blood pressure and clinical response 2