Coming Up Short: Maintaining Safety in the Face of Drug Shortages

Commentary by Steven Plogsted, PharmD

The Case

A 1-month-old preterm infant in the neonatal intensive care unit (NICU) was receiving the standard 500 mL bag of 0.45% sodium chloride (NaCl) with heparin at low rates to maintain IV line patency. The patient developed hyponatremia, and the clinicians recognized the need to deliver a more concentrated sodium solution with less free water. Therefore, the order was given to change the IV fluid to a 500 mL bag of 0.9% NaCl with heparin. However, due to a natural disaster affecting the manufacture and supply chain for IV fluids, very few 0.9% NaCl 500 mL bags were available in the region. The hospital and clinical team were asked to conserve the supply and use alternatives wherever possible, so the order was modified to use 100 mL 0.9% NaCl bags, which were available.

Since the total volume was much smaller, a lower concentration formulation of heparin was required: 100 units/mL compared to the usual concentration of 1000 units/mL. However, the verifying pharmacist discovered that the wrong concentration (1000 units/mL) had been used to compound the fluids. Further investigation revealed that this error had occurred on five other occasions, each committed by different technicians. Fortunately, because a minimal amount of heparin and fluid were infused each day, the error did not adversely affect this patient (or the others). However, the error did lead to the performance of additional blood tests (mostly activated partial thromboplastin time measures).

The Commentary

Commentary by Steven Plogsted, PharmD

Drug shortages, simply defined as a situation in which the demand or projected demand for a drug exceeds the supply (1), are common and have the potential to cause serious medication errors and patient safety concerns. According to the Food and Drug Administration (FDA), new drug shortages peaked in 2011 and have fallen steadily.(2) This was primarily the result of the FDA Safety and Innovation Act, which gave the FDA more authority to deal with drug shortages. The act increased FDA resources and also allowed them to work more closely with drug manufacturers to notify the FDA when they planned a reduction or discontinuation of a critical drug, giving the end users time to find alternative resources or therapies. Although drug shortages can have direct consequences—such as when a critical medication is unavailable, this case illustrates how a seemingly safe substitution strategy can lead to medication errors. In the case, an infant received an incorrect concentration of a medication due to a compounding error, one set up by a change in normal practice necessitated by a shortage of IV fluids. This case raises two different patient safety concerns: (i) errors involving heparin and saline and (ii) errors caused or magnified by drug shortages.

Errors involving heparin occur all too often. For example, in 2007 at a Los Angeles hospital, a massive heparin overdose was administered to three infants.(3) This event was highly publicized because it involved twins of actor Dennis Quaid and his wife. The Institute for Safe Medication Practices (ISMP) reported in 2008 that at least 17 heparin errors occurred in the neonatal intensive care unit (NICU) at a Texas hospital, which resulted in the death of two infants.(4) One reason for these errors is that heparin is available in a number of concentrations, ranging from 10 units/mL to 20,000 units/mL. The labels on individual products often look alike or sound alike (LASA). A recent study reported that 33% of medication errors attributed to LASA medications were the result of confusion over packaging or labeling.(5) Errors like these often are detected only after a patient has experienced a significant adverse event such as a severe bleed or internal hemorrhage. With heparin, an overdose can lead to a stroke, or even death, especially in vulnerable populations such as neonates.

Just like errors involving heparin, errors involving saline injection can lead to devastating outcomes. In a highly publicized case in 2006, a young child in Ohio died due to an improperly compounded normal saline solution.(6) The incident occurred when the technician used the wrong concentration of sodium when filling up a saline bag, and the pharmacist failed to notice the error. Although some improvements have been made in labeling and packaging, extreme care should be taken whenever heparin or saline are handled, whether in the pharmacy during compounding or stocking a Pyxis-type cabinet on the units. Barcoding technology or mandated double checking when removing heparin from floor stock can help minimize the chance of inadvertently selecting the wrong concentration. To improve safety during compounding, all persons associated with the process should receive specialized training in preparing IV medications, there should be minimal distractions in the compound area, and all calculations should be double checked by at least two pharmacists. To improve the safety environment of the compounding area, the area should contain only the products needed to compound a specific product thereby minimizing the chance of retrieving the incorrect items. Areas used to compound IV solutions should be separate from areas used to compound parenteral nutrition solutions, and all compound IV solutions with dextrose concentrations greater than 10% should have a refractive index performed on the final product.

Adding to confusion about concentration in the case above was a drug shortage involving sterile saline. The FDA report on drug shortages for 2017 highlighted the effect of Hurricane Maria on the availability of sterile saline, which had already been intermittently in short supply.(1) Medication errors as a result of drug shortages can have a significant impact on patient safety. A 2013 survey was sent to 1516 directors of pharmacy, and they reported that out of 171 responses, 70.8% reported a delay in treatment, 48.5% reported patients received suboptimal therapies, 15.8% reported a treatment failure, and 1.2% reported a death related to various drug shortages.(7) In a more recent survey conducted by ISMP targeting directors of pharmacy or their designees, out of 300 respondents, 87% reported that the shortages impacted emergency care, 85% reported effects on anesthesia care, and 5% reported effects on IV therapies for patients.(8)

Drug shortages occur for a variety of reasons. Natural disasters (such as hurricanes), interruption in the supply of or unavailability of raw materials, manufacturing quality assurance issues, discontinuation of a product, a general increase in demand (such as when an established drug receives an additional indication, increasing its demand), lack of profitability for a particular product, or when production quotas have been met for the year.(9) When these drug shortages occur, especially if it is an acute event, institutions must try to find alternatives for those products. In this case, prescribers may not have been as familiar with the drug dosing or adverse effects of the drug alternatives, which puts patients at increased risk for an adverse event. Changes to the hospital's drug formulary due to product substitution can also cause confusion since adjustments to the drug library in the electronic health record (EHR) are required and may not be able to be implemented in a timely fashion.

Several strategies can help minimize the effects of drug shortages on patient safety. Development of a hospital-wide drug shortage subcommittee can be effective in anticipating and developing solutions to a drug shortage by managing the available resources. Pharmacists, nurses, physicians, laboratory personnel, and members of the information systems department should be included, as each has a unique perspective on the problem. Involving upper management is critical for implementing any plan as they can help fulfill the plan if staff resistance is encountered. Frequent communications with staff regarding shortages along with frequent in-service education activities (when alterations from standard treatment plans are related to a particular shortage) can keep everyone focused on safety issues.

In a case like this one, in which there will be widespread substitution of the volume of IV bags, the pharmacy should look at the prescribing and compounding history. Once they determine which compounds are frequently used, a set of recommendations for how to add heparin or other additives could have been made available, either through educational materials or perhaps embedded in computerized decision support.

Take-Home Points

Drug shortages are common and have the potential to cause serious medication errors. Although the number of shortages has declined in recent years, they most likely will continue to occur.
One of the best strategies for preventing or minimizing adverse events associated with drug shortages is to have plans in place to deal with the shortages.
All members of the health care team must maintain a higher level of vigilance in times of significant drug shortages—from prescribing alternative regimens to familiarizing themselves with the alternative products. However, such strategies should include not just the substitution for the unavailable drug or product, but also the impact on other collateral prescriptions such as other additives to compounded drugs or fluids.
Resource management can be key to preventing a significant shortage from affecting proper patient care.

Steven Plogsted, PharmD
Clinical Pharmacist Nutrition Support Service
Nationwide Children's Hospital
Columbus, OH

References

1. Report on Drug Shortages for Calendar Year 2017. U.S. Food and Drug Administration. Silver Spring, MD: Department of Health and Human Services; 2017. [Available at]

2. Drug Shortages. U.S. Food and Drug Administration. Silver Spring, MD: Department of Health and Human Services. [Available at]

3. Another Heparin Error: Learning From Mistakes So We Don't Repeat Them. Horsham, PA: Institute for Safe Medication Practices; 2007. [Available at]

4. Heparin Errors Continue Despite Prior, High-Profile Fatal Events. Horsham, PA: Institute for Safe Medication Practices; 2008. [Available at]

5. Shao SC, Lai EC, Owang KL, Chen HY, Chan YY. Look-alike medication packages and patient safety. J Patient Saf. 2018;14:e47-e48. [go to PubMed]

6. Vivian JE. Criminalization of medication errors. US Pharm. 2009;34:66-68. [Available at]

7. McLaughlin M, Kotis D, Thomson K, et al. Effects on patient care caused by drug shortages: a survey. J Manag Care Pharm. 2013;19:783-788. [go to PubMed]

8. Drug Shortages Continue to Compromise Patient Care. Horsham, PA: Institute for Safe Medication Practices; 2018. [Available at]

9. Holcombe B, Maddox TW, Plogsted S. Drug shortages: effect on parenteral nutrition therapy. Nutr Clin Pract. 2018;33:53-61. [go to PubMed]