What is the recommended dose of alteplase (tissue plasminogen activator) for a clogged Peripherally Inserted Central Catheter (PICC)?

Recommended Alteplase Dose for Clogged PICC Lines

The recommended dose of alteplase for a clogged PICC line is 2 mg in 2 mL, instilled into the catheter lumen with a dwell time of 30-120 minutes. 1

Dosing Protocol

Standard Adult Dosing

• Dose: 2 mg in 2 mL solution
• Administration: Instill directly into the catheter lumen
• Dwell time: 30-120 minutes
• Assessment: Check catheter function after 30 minutes; if still occluded, continue dwell for up to 120 minutes
• Second dose: If catheter remains occluded after the first dose, a second identical dose may be administered

Pediatric Dosing

• For patients ≥30 kg: 2 mg in 2 mL solution
• For patients <30 kg: 110% of the estimated internal lumen volume, not to exceed 2 mg in 2 mL 1

Efficacy and Evidence

Clinical trials have demonstrated high success rates with alteplase for clearing occluded central venous catheters:

• FDA-approved clinical trials showed restoration of function in 75% of catheters after one dose and 85.1% after two doses 1
• The COOL trials demonstrated that function was restored in 798 of 1,064 patients (75%) after one dose and 905 patients (85.1%) after two doses 2
• For PICC lines specifically, a study of 240 patients showed a cumulative efficacy rate of 92.9% after a maximum of two doses 3

Administration Method

Two administration methods have been studied:

1. Dwell method: Instill alteplase into the catheter and allow it to remain for 30-120 minutes
2. Push method: Administer alteplase over approximately 30 minutes

Research comparing these methods found no significant difference in efficacy (82% success with push vs. 65% with dwell, p=0.08) 4. However, the dwell method is more commonly used in clinical practice due to its simplicity.

Safety Profile

Alteplase has demonstrated an excellent safety profile for catheter clearance:

• In clinical trials, no intracranial hemorrhage events were reported 1, 2
• Serious adverse events were rare, with only 0.3% gastrointestinal bleeding, 0.3% thrombosis, and 0.4% sepsis reported within 30 days of treatment 2
• The Cathflo Activase Pediatric Study confirmed safety in children with no intracranial hemorrhage events (95% CI, 0%-1.2%) 5

Important Clinical Considerations

• Initial approach: Before using alteplase, attempt forceful irrigation with saline as a first-line intervention 4
• Non-thrombotic occlusions: Different solutions should be used based on the cause:
  • Lipid occlusion: 70% ethanol or sodium hydroxide
  • Mineral precipitates: 0.1 N hydrochloric acid
  • Drug precipitates: Treatment depends on pH 4
• Higher efficacy: Evidence suggests that the 2 mg dose is more effective than lower doses (1 mg), with significantly lower risk of catheter removal due to unresolved thrombosis (10% vs 19%) 4

Algorithm for Management of Occluded PICC Lines

1. Rule out mechanical occlusion (kinking, malposition)
2. First attempt: Forceful saline irrigation
3. If unsuccessful, determine likely cause of occlusion:
   • If thrombotic: Administer alteplase 2 mg/2 mL (adjust for pediatric patients <30 kg)
   • If non-thrombotic: Use appropriate solution based on suspected precipitate
4. Assess at 30 minutes after alteplase administration
5. If still occluded: Continue dwell for up to 120 minutes
6. If remains occluded: Administer second dose with same protocol
7. If still occluded after two doses: Consider mechanical interventions (guidewire, fibrin sheath stripping) or catheter replacement

Alteplase is the agent of choice for thrombotic catheter occlusions, with strong evidence supporting its efficacy and safety profile across different catheter types, including PICCs 4, 1.