What data supports the use of alteplase 1 mg versus 2 mg for catheter occlusions?
Background
Catheter-related thrombosis is a relatively common complication of central venous catheter insertion with reported rates of 14 to18% with approximately 5% of cases classified as symptomatic.1 Despite being relatively common, there are limited evidence-based guidelines for the management of catheter-related thrombosis. Patient-specific risk factors for catheter occlusions include hypercoagulable states such as malignancy, sepsis, critical illness, renal failure, previous venous thromboembolism (VTE), and use of certain drugs. Other risk factors include catheter type and insertion technique. Patients that are symptomatic may display features of site swelling and discomfort or venous distention; however, some patients may experience atypical symptoms such as jaw or shoulder pain. Complications of occluded catheters can include pulmonary embolism, loss of venous access, infection, post thrombotic syndrome, and delay in treatment.
Treatment of occluded catheters requires assessment of patient’s need for central access, functional status of the line, presence of an underlying prothrombotic state, and review of contraindications to anticoagulation.1 Assessment of these patient-specific factors will determine optimal treatment which may include removal of the occluded catheter, systemic coagulation, or thrombolytic agents. Alteplase, a thrombolytic agent, is indicated for the restoration of function to central venous access devices as assessed by the ability to withdraw blood.2 Alteplase is a tissue plasminogen activator (t-PA) which binds to fibrin in a thrombus and initiates local fibrinolysis by converting the entrapped plasminogen to plasmin. The package insert recommends instillations of 2 mg/2 mL of alteplase into catheters for patients weighing greater than or equal to 30 kg. For patients weighing less than 30 kg, it is recommended to instill 110% of the internal lumen volume of the catheter, not exceeding 2 mg/2 mL
Guideline Recommendations
For restoring patency and maintaining catheter function, the 2021 Infusion Nurses Society (INS) infusion therapy standards of practice recommends instilling alteplase in a catheter lumen in accordance with manufacturers’ directions for use with repeat doses up to one time should the first attempt be unsuccessful.3 The INS acknowledges that a lower dosage (1 mg/mL) of alteplase in lumens requiring ≤ 1 mL volume have demonstrated to be efficacious, however randomized controlled trials are needed to determine efficacy of alternative dosing.
The 2013 American Society of Clinical Oncology (ASCO) clinical practice guideline recommends the use of fibrinolytic therapy to restore patency to occluded, non-functioning catheters.4 The recommended dose of alteplase to restore patency and preserve catheter function is a 2 mg instillation.
Evidence Literature
The Table summarizes relevant recent and randomized controlled trials and nonrandomized studies. Doses used in randomized trials included 1 mg and 2 mg, both of which proved efficacious.5-6 There was no significant difference related to efficacy in dosing between alteplase 1 mg and 2 mg for catheter-related thrombosis. The trials included also did not show any significant adverse effects related to alteplase therapy. A non-randomized study showed no difference in efficacy for use of alteplase 1 mg versus 2 mg in peripherally inserted central catheter (PICC) lines.7 One prospective study showed statistical significance in favor of alteplase 2 mg over 1 mg for catheter-related thrombosis.8 Two other prospective studies showing efficacy of alteplase 1 mg for catheter-related thrombosis are also included in the table below.9-10
| Table. Overview of evidence examining alteplase for use in catheter occlusion.5-10 | ||||
|---|---|---|---|---|
| Study design and duration | Subjects | Interventions | Results | Conclusions |
| RCT |
||||
| El-Masri 20195 DB, SC, RCT | N = 48 adult patients 252 catheter occlusion events | Alteplase 1 mg versus alteplase 2 mg in restoring HDC function. | Primary: Alteplase treatments per a single HDC occlusion were statistically insignificant between the 2 mg and 1 mg group (85.7% vs 84.9%; p-value= 0.5) Secondary: Frequency of repeat doses did not differ significantly between the 2 mg and 1 mg group, (11.1% versus 15.1%; p-value=0.872) | Alteplase 1 mg is as effective as 2 mg in restoring HDC malfunction |
| Gittins 20076 Prospective, crossover, DB, RCT | N = 7 pediatric patients | Alteplase 1 mg/1mL versus heparin 5000 U/mL | Primary: Odds of forming a clot was 2.4 times greater in heparin group compared with alteplase (95% CI, 1.4 to 4.0; p = 0.001) Other: Mean weight of clots was 1.9 times heavier in heparin group versus alteplase (95% CI, 1.5 to 2.4; p<0.0005) | Alteplase is more effective than heparin in preventing blood clots developing in pediatric hemodialysis central lines |
| Cohort Studies |
||||
| Sapienza 20157 OL, SC nonrandomized quasi experimental trial | N = 168 adult patients 270 PICC line catheter occlusions recorded | Alteplase 2 mg/2 mL or alteplase 1 mg/1 mL doses. | Primary: Restored line patency after a maximum of 2 doses of alteplase was insignificant between the 1 mg/1 ml (93.3%) and 2 mg/2 ml (94.4%) groups (p=.72) | No statistical difference in the efficacy of maximum of 2 doses of alteplase 1 mg versus 2 mg in pediatric PICC lines |
| Yaseen 20138 Retrospective, SC cohort study | N = 237 adult patients | Alteplase 2 mg versus 1 mg in restoring HDC function. | Primary: Resolution of occluded HDC was significantly more in 2 mg versus 1 mg group (89.8% vs. 80.6%; p=.036) Secondary: Time to catheter removal was longer in the 2 mg group compared to the 1 mg group (p=0.019) Mean survival times were 782 days for the 1 mg group and 955 days for the 2 mg group | Treatment of dysfunctional HDC with 2 mg alteplase is superior to 1 mg in terms of resolution of occlusion, catheter removal, and catheter survival time |
| Haymond 20059 Prospective, OL study | N = 50 adult patients | Alteplase 1 mg/lumen versus alteplase 1 mg/lumen with an additional 1mg dose | Primary: Successful restoration of catheter patency following alteplase administration was 72% after the first dose and 83% after the second dose Secondary: 62% of patients required a subsequent alteplase course. Median time to next course was 14 days (range, 2 to 58 days) | Low dose alteplase 1 mg/lumen is effective for temporary treatment of occluded permanent CVC lines with repeat doses as needed. |
| O’Mara 200310 Prospective trial | N = 25 adult patients 30 catheters 62 total catheter occlusions | Alteplase 1 mg/lumen evaluated at 30 min and 60 min, and redosed if still occluded | Primary Complete restoration of hemodialysis CVC occlusions occurred in 23 cases (of 62 cases; 37.1%). In general, 15 catheters received only 1 dose of alteplase, while the remaining 15 catheters were treated for 2 or more discrete episodes of low catheter blood flow. Catheters that received more than 1 dose of alteplase had a mean of 12.5 days between doses Other: Partial restoration of hemodialysis CVC occurred in 20 cases (of 62 cases; 32.3%). 19 cases were designated as treatment failures; 12 cases had to undergo radiologic evaluation. | Alteplase at a dose of 1 mg/mL is effective for restoring patency in hemodialysis CVC catheters. |
| Abbreviations: DB: double blind; CI: confidence interval; CVC: central venous catheter; HDC: hemodialysis catheter; OL: open-label; PICC, peripherally inserted central catheter; RCT: randomized controlled trial; SC: single center |
||||
Conclusion
Overall, most studies evaluated in this FAQ suggest that dosing of alteplase from 1 mg to 2 mg for catheter occlusions are both efficacious and safe with minimal adverse effects. However, the optimal dosing of alteplase is not yet clearly defined by guidelines, and further studies are needed to clarify the optimal dose of alteplase in catheter occlusions for both adult and pediatric patients. Evaluation of the patient is essential for optimal care of patients experiencing catheter occlusions, and treatment should be patient specific.
References
- Wall C, Moore J, Thachil J. Catheter-related thrombosis: A practical approach. J Intensive Care Soc. 2016;17(2):160-167. doi:10.1177/1751143715618683
- Cathflo Activase. [Package Insert]. South San Fransisco, CA. Genentech, Inc. 2020.
- Gorski LA, Hadaway L, Hagle ME, et al. Infusion Therapy Standards of Practice, 8th Edition. J Infus Nurs. 2021;44(1S Suppl 1):S1-S224. doi:10.1097/NAN.0000000000000396
- Schiffer CA, Mangu PB, Wade JC, et al. Central venous catheter care for the patient with cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2013;31(10):1357-1370. doi:10.1200/JCO.2012.45.5733
- El-Masri MM, El Nekidy WS, Soong D, Kadri A. Efficacy of alteplase 1 versus 2 mg dose in restoring haemodialysis catheter function (Alte-dose 2): A randomized double-blind controlled study. Nephrology (Carlton). 2020;25(6):491-496. doi:10.1111/nep.13631
- Gittins NS, Hunter-Blair YL, Matthews JN, Coulthard MG. Comparison of alteplase and heparin in maintaining the patency of paediatric central venous haemodialysis lines: a randomised controlled trial. Arch Dis Child. 2007;92(6):499-501. doi:10.1136/adc.2006.100065
- Sapienza SP, Ciaschini DR. Intraluminal Volume Dose Alteplase for the Clearance of Occluded Peripherally Inserted Central Catheter Lines at a Long-Term Acute Care Hospital: Efficacy and Economic Impact. Hosp Pharm. 2015;50(3):202-207. doi:10.1310/hpj5003-202
- Yaseen O, El-Masri MM, El Nekidy WS, et al. Comparison of alteplase (tissue plasminogen activator) high-dose vs. low-dose protocol in restoring hemodialysis catheter function: the ALTE-DOSE study. Hemodial Int. 2013;17(3):434-440. doi:10.1111/hdi.12004
- Haymond J, Shalansky K, Jastrzebski J. Efficacy of low-dose alteplase for treatment of hemodialysis catheter occlusions. J Vasc Access. 2005;6(2):76-82. doi:10.1177/112972980500600206
- O’Mara NB, Ali S, Bivens K, Sherman RA, Kapoian T. Efficacy of tissue plasminogen activator for thrombolysis in central venous dialysis catheters. Hemodial Int. 2003;7(2):130-134. doi:10.1046/j.1492-7535.2003.00024.x
Prepared by:
Jordan Spurling, PharmD
PGY1 Pharmacy Practice Resident
University of Illinois at Chicago College of Pharmacy
Reviewed and Edited by:
Faria Munir, PharmD, MS, BCPS
Clinical Assistant Professor, Drug Information Specialist
University of Illinois at Chicago College of Pharmacy
The information presented is current as January 13, 2023. This information is intended as an educational piece and should not be used as the sole source for clinical decision-making.