Position Statement on Heparin Safety Concerns

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. Highly publicized incidents with this medication at 3 major institutions in the United States skyrocketed safety concerns regarding heparin use to national attention.12 Safe use and monitoring of anticoagulants in particular are also highlighted by National Patient Safety Goal (NPSG) 03.05.01 of The Joint Commission (Oak Brook, IL) to “reduce the likelihood of patient harm associated with the use of anticoagulant therapy.”3(p4)Beginning in the early 2000s, there were several reports of heparin overdoses resulting in patient harm and death. The most notable of these cases were 3 children receiving 1000 times the recommended heparin flush dose and a fatal case concerning a toddler receiving the wrong concentration of heparin. These tragic events brought to light risks associated with different heparin concentrations and how special care and restrictions must be in place for anticoagulation agents to minimize the chance of medication errors.4In response to safety concerns, the US Food and Drug Administration (FDA, Silver Spring, MD) released a safety announcement in late 2012 regarding heparin, notifying health care professionals, caregivers, and patients about a container label-change mandate. Manufacturers were, and currently are, required to state the strength of heparin in the entire container, followed by the strength of the heparin in 1 mL of the product, by May 2013 at latest. This change brought heparin into compliance with US Pharmacopeia National Formulary section on injections (USP 35-NF 30, chapter 1).56Although the FDA-mandated label changes have helped to minimize mistakes, the diversity of heparin concentrations available on the market contributes to the risk of heparin dosing errors. The importance of heparin standardization for all indications used in individual hospital systems remains crucial to patient safety. The number of various heparin concentrations and volumes at each institution should be limited, and those different products should be physically separated in the pharmacy.56 For instance, storing therapeutic and prophylactic concentrations of heparin (1000 units/mL or higher) separate from the more-dilute formulations for heparin locks (100 units/mL or less) can reduce the chance of selecting the wrong product. In addition, continuous infusion preparations should be stored separately and be identified as high-alert medications. Hospital policies should address the storage of heparin, including whether storage in an automated dispensing cabinet is allowed, how boluses will be administered, and whether boluses may be given from a continuous infusion bag. Educating staff and physically separating these products can create safety barriers to better serve patients. In addition, stocking different forms of diverse concentrations, such as the 10 unit/mL flush available in a syringe, instead of a vial, can help create a visual check for the correct concentration. Visual checks should be performed by qualified individuals to ensure accuracy and safety. However, these visual checks should not rely on different colored packaging or numbering because those factors are subject to change and could actually increase error risk.7These safety concerns and availability issues have prompted many institutions to reevaluate the appropriateness of heparin use and the variety of concentrations available for their patients. As in the adult population, concentrated, premixed solutions are often used in pediatric patients for dialysis or for continuous infusion in the treatment of thromboembolic events. Maintenance of central venous line (CVL) patency for pediatric patients is unique because the heparin is often used in dilute concentrations and as flush solutions of 2 units/mL or less. Heparin is also used for CVL management in neonates, with flush solution concentrations ranging from 1 to 10 units/mL.89 In addition, heparin can be added to neonatal total parenteral nutrition or intravenous (IV) fluids in 0.5- to 1-unit/mL concentrations. Heparin flushes also continue to be used with pediatric patients and surgically placed central catheters (e.g., Broviac [C. R. Bard, Murray Hill, NJ] or Port-a-Cath [Smiths Medical, Ashford, England]) at 10 unit/mL or 100 unit/mL concentrations, with up to 1000 units/mL being used in dialysis catheters.2 In pediatric intensive care unit settings, heparin continuous infusions of 1 unit/mL have been shown to decrease phlebitis in peripheral arterial catheters.58–10In addition to the broad array of heparin storage devices marketed, concentrations available, and volumes used, some heparin products contain preservatives. This can add another layer of complexity to the formulary decision-making process. The presence of benzyl alcohol in some formulations is of concern for neonates and infants because this ingredient is known to cause toxicity and serious adverse events, including deaths, in this age group. Products that contain benzyl alcohol should not be stocked in areas providing care to patients younger than 1 year old.19Currently, The Joint Commission has requirements regarding high-risk, high-alert medications and anticoagulants. Some of those requirements, among others, include developing a medication process that integrates storing, dispensing, and monitoring; reduces the likelihood of harm with anticoagulants; and accurately reconciles medications across the continuum of care. There are several methods of fulfilling those requirements, and institutions may choose to implement multiple techniques to improve safety. Independent double checks are a common safety measure taken with high-risk medications and should be implemented when using heparin, particularly at therapeutic concentrations.17It is recommended that hospitals minimize heparin concentrations, for both CVL maintenance and systemic indications, and purchase commercially available products when available. If not commercially available, health care providers should consider purchasing from a 503b company. Either of these options ensures higher quality and safety standards than found in products individually compounded by hospitals. If compounding with heparin is necessary, technology should be used to improve safety. Fail-safes, constraints, and forcing functions are among the highest-quality error-prevention strategies because human error is almost entirely eliminated if the system is set up properly. These measures can be implemented through technologic processes, such as bar-coding.11 Dose-checking software can assist in preventing 10-fold or greater dosing errors, which are known to have occurred in pediatric patients. Dose-checking technology in the IV room has also been shown to reduce errors in IV admixtures and should be used when compounding high-risk medications, such as heparin.12 The use of smart-pump technology can also assist by providing another layer of dose checking before administration to a patient. Dosing protocols embedded in the order sets of electronic health records and staff education on heparin safety are also excellent tools to enhance safe practices.137 Failure modes and effects analysis of the use cycle of heparin medication may help institutions better understand current risks and the opportunities to optimize patient safety.In accordance with NPSG 03.05.01, evaluation of appropriate heparin use and available formulations is highly recommended for all institutions. Safety measures are especially important in institutions serving pediatric and neonatal populations, with emphasis placed on limiting the variety of formulations and concentrations available, based on appropriate use in specific patient-care areas. In the interest of patient safety, all institutions should evaluate the methods they currently use to handle anticoagulant agents, such as heparin, and take steps to minimize the risk of patient harm through education and technological risk-reduction strategies.