What is the recommended dose of Alprostadil (prostaglandin E1 analogue) in milligrams per kilogram for patients following replant surgeries and free flap surgeries?

Alprostadil Dosing for Replant and Free Flap Surgeries

For replant and free flap surgeries, initiate alprostadil at 0.05-0.1 mcg/kg/min via continuous intravenous infusion, with a recommended starting dose of 0.1 mcg/kg/min based on FDA labeling, then titrate down to the lowest effective dose (typically 0.01-0.025 mcg/kg/min) that maintains adequate blood flow. 1

Initial Dosing Protocol

• Start with 0.1 mcg/kg/min as the recommended initial infusion rate, though adequate clinical response has been documented starting at 0.05 mcg/kg/min 1
• Administer via continuous intravenous infusion into a large vein 1
• After achieving therapeutic response (improved blood flow velocity in the flap), reduce the infusion rate progressively 1

Dose Titration Strategy

• Stepwise reduction sequence: 0.1 → 0.05 → 0.025 → 0.01 mcg/kg/min 1
• The goal is to identify the lowest possible dosage that maintains adequate perfusion 1
• If response to 0.05 mcg/kg/min is inadequate, dosage can be increased up to 0.4 mcg/kg/min, though higher rates generally do not produce greater effects 1
• Evidence from free flap surgery demonstrates that alprostadil significantly increases maximal arterial blood flow velocity (from 22.5 cm/s to 26.3 cm/s at 30 minutes post-administration) without hemodynamic complications 2

Administration Details

• Dilute 1 mL of alprostadil (500 mcg) in appropriate volumes of Sodium Chloride Injection USP or Dextrose Injection USP 1
• Avoid direct contact of undiluted solution with volumetric infusion chamber walls, as this may cause haziness 1
• Prepare fresh infusion solutions every 24 hours and discard any solution older than 24 hours 1

Sample Dilution for 0.1 mcg/kg/min:

• Add 1 ampoule (500 mcg) to 100 mL saline/dextrose = 5 mcg/mL concentration
• Infusion rate: 0.02 mL/min per kg body weight 1
• Example: For a 70 kg patient: 0.02 mL/min/kg × 70 kg = 1.4 mL/min or 84 mL/hr 1

Clinical Evidence Supporting Use

• Lipo-prostaglandin E1 (lipid-encapsulated formulation) administered 10 minutes after vascular anastomosis significantly increases arterial maximal flow velocity in free flaps without causing hypotension, bradycardia, or other complications 2
• The vasodilatory effect occurs within 30 minutes of administration 2
• No prostaglandin-related complications (hypothermia, facial flushing, diarrhea, apnea, seizures) were observed in free flap reconstruction patients 2

Monitoring Parameters

• Assess flap perfusion using duplex ultrasonography to measure maximal blood flow velocity before and 30 minutes after alprostadil administration 2
• Monitor arterial blood pressure, heart rate, and cardiac output, though significant hemodynamic changes are not expected at therapeutic doses 2
• Watch for common side effects: fever, apnea, flushing, bradycardia, hypotension, and seizures, though these may be related to the patient's underlying surgical condition 3

Critical Caveats

• The FDA-approved dosing is derived from neonatal cardiac surgery experience, not specifically from replant/free flap surgery 1, 3
• The evidence for free flap surgery uses lipo-PGE1 formulation, which may have different pharmacokinetics than standard alprostadil 2
• Duration of infusion in replant/free flap surgery is typically limited to the immediate perioperative period (hours to days), unlike the prolonged infusions used in neonatal cardiac patients 1, 2
• Prepare fresh solutions every 24 hours to maintain drug stability 1