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Recombinant tissue plasminogen activator to restore catheter patency: efficacy and safety analysis from a multihospital NICU system

Abstract

Objective:

In 2001, the US Food and Drug Administration approved recombinant tissue plasminogen activator (alteplase, Cathflo Activase) to reestablish patency of central catheters occluded, presumably, by a fibrin clot. We conducted a multicenter quality improvement study to determine the value of this procedure in our Neonatal Intensive Care Unit (NICUs), including analyses of efficacy, safety and costs.

Study Design:

We conducted a retrospective quality analysis of neonates in level III NICUs, who received alteplase for the purpose of reestablishing patency of occluded central catheters.

Results:

Alteplase was administered to 169 neonates, each given one to four doses, totaling 205 episodes of administration. The most common type of catheter where alteplase was used was percutaneously inserted central catheter (PICC) lines (78% of uses), 8% were umbilical venous catheters (UVCs), 6% arterial lines, 5% chest tubes and 3% other catheters. Postnatal age at first dose ranged from 0 to 132 days (median, 12); dosed patients were 22 to 41 weeks gestation at birth (median, 31). Fifty-eight percentage of administrations restored catheter function. Success was more likely at younger postnatal age (10±2 days old in successful vs 14±1 days in unsuccessful treatments; P=0.023). Seventy-two percentage of the re-canalized catheters remained functional until they were no longer needed (2 to 30 days later). Nine percentage of episodes were treated with a second dose 1 to 17 days later for re-occlusion and 50% of those were successful. Bleeding consequences were identified in only one case, where three separate lines were treated (chest tube, PICC and UVC) within a 6-h period. Costs to the health system of doses, minus savings to the system by not needing to replace lines, averaged a net of $34 per dose.

Conclusions:

The apparent safety and favorable value analysis prompted us to develop a consistent approach to alteplase usage in the Intermountain Healthcare NICUs, using the data in this report to standardize the guidelines across our health system.

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References

  1. Hébert M, Lesept F, Vivien D, Macrez R . The story of an exceptional serine protease, tissue-type plasminogen activator (tPA). Rev Neurol (Paris) 2016; 172 (3): 186–197.

    Article  Google Scholar 

  2. Ansah DA, Patel KN, Montegna L, Nicholson GT, Ehrlich AC, Petit CJ . Tissue plasminogen activator use in children: bleeding complications and thrombus resolution. J Pediatr 2016; 171: 67–72.e2.

    Article  CAS  Google Scholar 

  3. Smith LH . Alteplase for the management of occluded central venous access devices: safety considerations. Clin J Oncol Nurs 2008; 12 (1): 155–157.

    Article  Google Scholar 

  4. Zivin JA . Acute stroke therapy with tissue plasminogen activator (tPA) since it was approved by the U.S. Food and Drug Administration (FDA). Ann Neurol 2009; 66 (1): 6–10.

    Article  Google Scholar 

  5. Raad II, Hanna HA . Intravascular catheter-related infections: new horizons and recent advances. Arch Intern Med 2002; 162 (8): 871–878.

    Article  CAS  Google Scholar 

  6. Blaney M, Shen V, Kerner JA, Jacobs BR, Gray S, Armfield J et al. Alteplase for the treatment of central venous catheter occlusion in children: results of a prospective, open-label, single-arm study (The Cathflo Activase Pediatric Study). J Vasc Interv Radiol 2006; 17: 1745–1751.

    Article  Google Scholar 

  7. Dunn AL, Abshire TC . Recombinant tissue plasminogen activator may reduce frequency of central venous access device infection in hemophilia patients undergoing immune tolerance therapy. Pediatr Blood Cancer 2008; 50 (3): 627–629.

    Article  Google Scholar 

  8. Anderson D, Pesaturo K, Casavant J, Ramsey E . Alteplase for the treatment of catheter occlusion in pediatric patients. Ann Pharm 2013; 47: 405–410.

    Google Scholar 

  9. Haas N, Haas S . Central venous catheter techniques in infants and children. Curr Opin Anaesthesiol 2003; 16: 291–303.

    Article  Google Scholar 

  10. Jacobs B, Haygood M, Hingl J . Recombinant tissue plasminogen activator in the treatment of central venous catheter occlusion in children. J Pediatr 2001; 139: 593–596.

    Article  CAS  Google Scholar 

  11. Lee E . Alteplase use for prevention of central line occlusion in a preterm infant. Ann Pharm 2002; 36: 272–274.

    Google Scholar 

  12. Soylu H, Brandao L, Lee K . Efficacy of local instillation of recombinant tissue plasminogen activator for restorting occluded central venous catheters in neonates. J Pediatr 2009; 156 (2): 197–201.

    Article  Google Scholar 

  13. Sharma RP, Ree CJ, Ree A . Efficacy and safety of a single 2 mg dose or 4 mg double dose of alteplase for 50 occluded chest ports using a unique instillation technique. Int J Angiol 2008; 17 (3): 125–128.

    Article  Google Scholar 

  14. Gilarde JA, Chung AM, Vidal R, Falkos S . Efficacy and economic evaluation of a volume-based cathflo activase protocol versus a fixed-dose alteplase protocol for catheter occlusions in pediatric patients. J Pediatr Pharmacol Ther 2006; 11 (4): 237–244.

    PubMed  PubMed Central  Google Scholar 

  15. Ernst FR, Chen E, Lipkin C, Tayama D, Amin AN . Comparison of hospital length of stay, costs, and readmissions of alteplase versus catheter replacement among patients with occluded central venous catheters. J Hosp Med 2014; 9 (8): 490–496.

    Article  Google Scholar 

  16. Thakarar K, Collins M, Kwong L, Sulis C, Korn C, Bhadelia N . The role of tissue plasminogen activator use and systemic hypercoagulability in central line-associated bloodstream infections. Am J Infect Control 2014; 42: 417–420.

    Article  CAS  Google Scholar 

  17. CathfloTM Activase® (Alteplase) [packasge insert]. Genentech, Inc.: South San Francisco, CA, USA, 2001.

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Correspondence to R D Christensen.

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Scott, D., Ling, C., MacQueen, B. et al. Recombinant tissue plasminogen activator to restore catheter patency: efficacy and safety analysis from a multihospital NICU system. J Perinatol 37, 291–295 (2017). https://doi.org/10.1038/jp.2016.203

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