How to dilute urokinase in acute myocardial infarction (MI)?

Urokinase Dilution Protocol for Acute Myocardial Infarction

For acute myocardial infarction, urokinase should be diluted in 0.9% sodium chloride (normal saline) solution rather than 5% dextrose to minimize drug adsorption and maintain optimal activity. 1

Dilution Procedure

Recommended Diluent

• Use 0.9% sodium chloride (normal saline) as the diluent of choice
• Avoid 5% dextrose solution, particularly at lower concentrations (1500 IU/mL), as it can cause 15-20% loss of urokinase activity in PVC containers 1

Container Selection

• Glass containers are preferred for preparation
• If using plastic containers, higher concentrations (5000 IU/mL or greater) minimize adsorption losses 1

Administration System

• Polypropylene or glass syringes can safely maintain urokinase potency for up to 24 hours 1
• When using PVC administration sets with dextrose solutions, be aware that additional drug losses may occur

Dosing Considerations

Pharmacokinetics

• Urokinase has a short elimination half-life of approximately 12.6 ± 6.2 minutes 2
• The drug is rapidly cleared by the liver with a distribution volume of 11.5 L 2
• Patients with hepatic impairment may require dosage adjustments due to reduced clearance 2

Timing of Administration

• Thrombolytic therapy should be initiated within the first 6 hours of symptom onset for optimal clinical outcomes 3
• Administration after 6 hours from symptom onset shows limited benefit in limiting necrotic focus or reducing mortality 3

Monitoring During Administration

Coagulation Parameters

• Monitor fibrinogen levels, as they may decrease and remain low for 12-24 hours after discontinuation 2
• Watch for increased circulating fibrin and fibrinogen degradation products 2
• Be aware that changes in coagulation and fibrinolytic assay results do not necessarily correlate with embolus resolution 2

Clinical Response

• Assess for reperfusion signs (resolution of chest pain, ST-segment resolution, reperfusion arrhythmias)
• Improvement on pulmonary angiography, lung perfusion scanning, and hemodynamic measurements should be evident within 24 hours 2

Important Precautions

Contraindications

• Avoid use in patients with previous hemorrhagic stroke, other strokes or cerebrovascular events within 1 year, known intracranial neoplasm, active internal bleeding, or suspected aortic dissection 4

Relative Contraindications

• Use with caution in patients with severe uncontrolled hypertension, history of prior cerebrovascular accident, current use of anticoagulants, recent trauma or major surgery, noncompressible vascular punctures, recent internal bleeding, pregnancy, or active peptic ulcer 4

Practical Tips

• Prepare the solution immediately before use
• If storage is necessary, polypropylene or glass syringes can maintain potency for up to 24 hours 1
• Higher concentrations of urokinase (5000 IU/mL or greater) are less susceptible to adsorption losses when diluted in dextrose solutions 1

By following this dilution protocol, you can ensure optimal urokinase activity for treating acute myocardial infarction while minimizing drug loss through adsorption to administration systems.