Statement on Heparin Safety and Shortages

Heparin is an anticoagulant that has been used for a variety of indications, from thromboembolic prophylaxis and treatment to central venous access management. It is supplied in multiple concentrations for therapeutic and prophylactic use (1000 units/mL or higher) as well as in more dilute concentrations (100 units/mL or less) for heparin-lock flush solutions. Incidents with this medication at institutions across the country have brought safety concerns with heparin use to national attention. Safe use and monitoring of anticoagulants in particular is also highlighted by JCAHO’s National Patient Safety Goal (NPSG) 3E to “reduce the likelihood of patient harm associated with the use of anticoagulation therapy.”

DESCRIPTION OF ISSUE

Over the past 2 years, heparin overdoses have been widely publicized. In September 2006, three premature infants died after receiving an overdose of heparin at a hospital in Indiana. Due to an error in stocking the automated dispensing cabinet, 1 mL heparin 10,000 units/mL vials were dispensed instead of the 1 mL heparin 10 units/mL vials usually stocked in its place. In November 2007, a similar error occurred at a California hospital due to the same look-alike labeling issue. Though these incidents heightened awareness of heparin as a high-risk medication causing many institutions to reevaluate their dispensing practices, this did not prevent another occurrence in July 2008 at a Texas hospital. Unlike the previous 2 incidents, this was not a result of product labeling or packaging but rather of the mixing process in the pharmacy. In contrast, this hospital had implemented a process change to prevent the same error by having the pharmacy dispense the heparin flush solutions instead of nurse preparation. Though it prevented one cause for error, this incident showed it was still possible for a heparin error to occur.

RATIONALE 

These safety concerns have prompted many institutions to reevaluate the appropriateness of heparin use and variety of concentrations available at their institutions. In addition to therapeutic use for treatment and prophylaxis of thromboembolic events, pediatric and neonatal patients may require heparin for prophylaxis of central venous line- (CVL-) related thromboembolic events. These solutions are commercially available as premixed admixtures. Similarly to the adult population, these concentrated premixed solutions are often used in pediatrics for dialysis patients or for continuous infusion treatment of thromboembolic events. Unlike in the adult population, heparin can be used in dilute concentrations and as flush solutions to maintain CVL patency. There is conflicting data on the use of heparin in maintaining line patency in neonates as well as variability amongst neonatologists and pediatric practitioners on clinical use of heparin for thromboembolic prophylaxis. Due to this inconsistency, clinical guidelines and treatment standards on use of heparin in pediatric and neonatal patients are difficult to establish.

Heparin flushes continue to be used in pediatric patients, particularly with surgically placed central catheters (e.g. Broviac or Port-a-cath) at 10 unit/mL or 100 unit/mL concentrations. Continuous infusion of 1 unit/mL heparin has been shown to decrease phlebitis in peripheral arterial catheters. Heparin is also used for CVL management in neonates using flush solution concentrations ranging from 1 to 10 units per mL. It can also be added to neonatal parenteral nutrition or intravenous fluids in 0.5 to 1 unit per mL concentrations. Prefilled syringes of preservative –free heparin solutions are commercially available in 1 unit, 2 units, 10 units and 100 units per mL. Though these syringes are color-coded, they may start to look similar when ordered in the same syringe size. However various syringe sizes are available and may help to differentiate one concentration and volume from another in the right combinations.

CONCLUSION 

 In accordance with NPSG 3E, the evaluation of appropriate heparin use and available formulations is highly recommended for all institutions. Safety measures are especially important in institutions serving the pediatric and neonatal populations, for instance, limiting the variety of formulations and concentrations based on appropriate use in specific patient care areas. This may involve extensive communication with each patient care area and a grid may be helpful in documenting each area’s predominant uses of heparin. Once appropriate dosage formulations are established for each of these uses, stock for each patient care area, particularly those with automated dispensing devices, should be limited only to these formulations.   Pharmacy admixture processes for heparin should also be reviewed and evaluated for safe practices. It is advisable to minimize risk at your institution by 1) limiting stock specific to appropriate indications within each patient care area, 2) utilizing commercially available prefilled syringes prepared under Good Manufacturing Practices, 3) assuring appropriate verification processes in admixture of heparin dilutions, particularly where a double-check with two pharmacists may be warranted with this high-risk medication and 4) storing lower concentrations commonly used for pediatrics separate from higher adult concentrations within pharmacy stock areas to minimize look-alike issues.

The Pediatric Pharmacy Advocacy Group (PPAG) recognizes the place in therapy of heparin in neonates and children for central venous access management. Despite safety concerns, it has been shown to be effective both prophylactically for maintaining line patency as well as for treatment of thromboembolic disorders in the pediatric population. It is the position of PPAG that the benefit of heparin use exceeds the safety concerns in neonates and children when institutions serving these patients take the safety measures to minimize these risks.  

FUTURE DIRECTIONS

PPAG will continue to pursue collaboration with other healthcare-related associations in a multidisciplinary effort to seek a safer, standardized approach to heparin use in the pediatric population

REFERENCES

American Society of Health-System Pharmacists. ASHP therapeutic position statement on the institutional use of 0.9% sodium chloride injection to maintain patency of peripheral indwelling intermittent infusion devices. Am J Health-Syst Pharm. 2006; 63:1273–5

Central Venous Access Device Guideline Panel. Managing central venous access devices in cancer patients: a clinical practice guideline. Toronto (ON): Cancer Care Ontario (CCO); 2006 Sep 25. 39 p. (Evidence-based series; no. 16-1). [67 references]

Klenner AF et al. Benefit and risk of heparin for maintaining peripheral venous catheters in neonates: a placebo-controlled trial. J of Pediatr 2003;143(6):741-5.

Shah PS et al. A Randomized, Controlled Trial of Heparin Versus Placebo Infusion to Prolong the Usability of Peripherally Placed Percutaneous Central Venous Catheters (PCVCs) in Neonates: The HIP (Heparin Infusion for PCVC) Study. Pediatrics 2007;119(1):e284-91.

Shah PS, Shah VS. Continuous heparin infusion to prevent thrombosis and catheter inclusion in neonates with peripherally placed percutaneous central venous catheters. Cochrane Database of Systematic Reviews 2008, Issue 2. Art No.: CD002772. DOI: 10.1002/14651858.CD002772.pub3.

ISMP Medication Safety Alert – Acute Care Edition.