What is the recommended intravenous amiodarone preparation, dosing, and maximum concentration for bolus and infusion, and what alternatives should be used if a central venous catheter is not available?

Intravenous Amiodarone: Preparation, Dosing, and Maximum Concentration Guidelines

For IV amiodarone administration, use a concentration ≤2 mg/mL for peripheral access and dilute exclusively in 5% dextrose in water (D5W); if concentrations >2 mg/mL are required, a central venous catheter is mandatory. 1, 2

Standard Dosing Protocol for Life-Threatening Arrhythmias

Rapid Loading (Cardiac Arrest/Unstable VT/VF)

• Initial bolus: 150 mg diluted in 100 mL D5W administered over 10 minutes 3, 1, 2
• Repeat bolus: An additional 150 mg may be given after 10-30 minutes if breakthrough arrhythmias persist 1, 2
• Early maintenance: 1 mg/min infusion for 6 hours (approximately 360 mg total) 3, 1, 2
• Late maintenance: 0.5 mg/min for the subsequent 18 hours (approximately 540 mg total) 3, 1, 2
• Total 24-hour dose: Approximately 1000 mg, with a maximum of 2.2 g per 24 hours 1, 2

Standard Loading (Hemodynamically Stable Arrhythmias)

• Initial loading: 150 mg (or 5 mg/kg, approximately 300 mg) over 1 hour 1
• Follow with the same maintenance infusion schedule as above 1

Critical Preparation and Administration Requirements

Diluent and Concentration

• Mandatory diluent: Use only 5% dextrose in water (D5W); normal saline causes drug precipitation 1, 2
• Peripheral access: Maximum concentration of 2 mg/mL to minimize phlebitis risk 1, 2, 4
• Central access: Concentrations >2 mg/mL up to 6 mg/mL are permissible only through a central venous catheter 1, 2
• Phlebitis prevention: Concentrations >2 mg/mL are associated with peripheral vein phlebitis rates up to 85% 4

Equipment and Delivery

• Infusion pump: Use a volumetric infusion pump; drop-counter devices can underdose by up to 30% 2
• In-line filter: Mandatory during all administrations 1, 2, 4
• Container type: For infusions >2 hours, use glass or polyolefin bottles only; do not use evacuated glass containers 2
• Maximum infusion rate: Do not exceed 30 mg/min for initial loading 2

Alternatives When Central Access Is Unavailable

Peripheral Administration Strategy

• Dilute to ≤2 mg/mL: This is the absolute maximum concentration for peripheral veins 1, 2
• Use in-line filter: Reduces phlebitis incidence significantly 4
• Implement nursing surveillance protocols: Decreases both phlebitis rates and severity 4
• Monitor infusion site: Increasing concentration from 1.2 mg/mL to 1.8 mg/mL significantly increases phlebitis risk 4

Alternative Antiarrhythmic Agents

If central access is unavailable and peripheral administration is problematic:

• Lidocaine: 1-1.5 mg/kg IV bolus for ventricular arrhythmias (ineffective for supraventricular arrhythmias) 1
• Procainamide: 20-50 mg/min infusion for stable monomorphic VT until arrhythmia suppression, hypotension, ≥50% QRS prolongation, or cumulative dose of 17 mg/kg 3, 1
• Electrical cardioversion: Prioritize if patient becomes hemodynamically unstable during pharmacologic therapy 1

Monitoring Requirements During Administration

Continuous Monitoring

• ECG surveillance: Mandatory for heart rate, AV conduction abnormalities, PR interval, QRS duration, and QT prolongation 1, 5
• Hemodynamic monitoring: Hypotension occurs in 16-26% of patients; bradycardia in 4.9% 1, 5, 6
• Heart block surveillance: Monitor for second- or third-degree AV block, which requires immediate discontinuation without pacemaker support 1

Dose Adjustment Triggers

• Bradycardia: If heart rate decreases by ≥10 beats per minute, reduce infusion rate 1
• Hypotension: Reduce rate or discontinue if systolic BP falls below 100 mmHg 1
• QTc prolongation: Mean QTc increases from 443 ms to 458 ms during therapy; monitor for excessive prolongation 6

Common Pitfalls and Caveats

Absolute Contraindications

• Bradycardia or heart block: Do not use in patients with baseline heart rate <60 bpm or second/third-degree heart block without a pacemaker unless immediately life-threatening 1, 5
• Wrong diluent: Never use normal saline or lactated Ringer's solution 1, 2

Drug Interactions Requiring Immediate Adjustment

• Digoxin: Reduce dose by 50% when starting amiodarone; levels predictably double 1, 5
• Warfarin: Reduce dose by one-third to one-half and monitor INR at least weekly for 6 weeks 1, 5
• Concomitant AV-nodal blockers: Beta-blockers, calcium channel blockers, or digoxin create additive bradycardia risk 1

Pharmacokinetic Considerations

• Onset of action: Antiarrhythmic effect typically appears 20-30 minutes after administration 1
• Peak effect: Most conversions to sinus rhythm occur after 6-8 hours and require ≥1 g cumulative dose 1
• Plasma levels: Decline rapidly to subtherapeutic levels within 60 minutes after initial bolus, necessitating continuous infusion 7

Electrolyte Management

• Maintain potassium >4 mmol/L: Hypokalemia increases pro-arrhythmic risk during amiodarone infusion 1
• Magnesium supplementation: Consider 8 mmol for refractory VF if hypomagnesemia is suspected 3