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Management of Drug Shortages with 0.9% Sodium Chloride, Sterile Water for Injection, and EPINEPHrine

Problem: Ongoing drug shortages in healthcare have become commonplace, with only the severity and urgency of the issue changing with the specific drugs in short supply. According to numerous inquiries to ISMP and frequent communications with Erin Fox, PharmD, BCPS, FASHP, a recognized expert in drug shortages at the University of Utah Health, current shortages of 0.9% sodium chloride for injection vials, prefilled saline flushes, sterile water for injection vials, and EPINEPHrine injection emergency syringes and autoinjectors, are all creating serious safety concerns and requiring even more effort from healthcare facilities to circumnavigate. (The University of Utah provides information for the American Society of Health-System Pharmacists [ASHP] Drug Shortages Resource Center.)

0.9% Sodium Chloride Shortage

The most impactful shortage involves 0.9% sodium chloride in 10 mL, 20 mL, and 50 mL preservative-free, single-dose vials, prefilled flush syringes, and certain small volume (25 mL, 50 mL, 100 mL) bags. Shortages of the 0.9% sodium chloride vials have increased the demands for prefilled flush syringes, small volume bags, and vials of 23.4% sodium chloride, which have resulted in the current shortages of these products. Sodium chloride 0.9% is often needed to dilute or reconstitute certain medications. Also, nurses regularly use prefilled saline flush syringes, which are essential for vascular access device (VAD) maintenance and to reduce the risk of bloodstream infections.

Due to the shortage of 0.9% sodium chloride vials, we worry that the few remaining saline flushes are being used inappropriately and unsafely to dilute and reconstitute medications in patient care units, further depleting the supply and resulting in a serious safety issue. First, the mislabeling that occurs when medications are added to a prefilled saline flush syringe without applying a secondary label increases the risk for significant errors. In many cases, the manufacturer’s label is permanently affixed to the syringe barrel and contains product codes and a barcode specific to the prefilled saline syringe. When a medication is added to this syringe, the syringe frequently remains labeled only as 0.9% sodium chloride, and also lacks an appropriate barcode to scan because it now contains the diluted or reconstituted medication. Furthermore, most commercially available prefilled syringes of saline (and heparin) flushes are regulated by the US Food and Drug Administration (FDA) as devices, not as medications, since these products keep lines open as a result of a physical effect and have no therapeutic effect when used as directed. While these devices have received approval for the flushing of VADs, they have not been tested and approved for the reconstitution, dilution, or subsequent administration of medications.

Sterile Water for Injection Shortage

Most sterile water for injection vials (i.e., 5 mL, 10 mL, 20 mL, 50 mL, 100 mL) are in short supply. These vials are primarily used to reconstitute medications available as lyophilized powders. While the prescribing information for some medications suggests that an alternative sterile liquid can be used for reconstitution, many specify that sterile water for injection must be used. The consequences of using a different sterile liquid to reconstitute medications may be unknown but could include poor dissolution of the powder, precipitation, or deactivation of the active pharmaceutical ingredient before administration.

A pharmacist recently reported a dangerous workaround caused by the sterile water for injection shortage. Understanding the infection control risk, a nurse called a pharmacist’s attention to a sterile water for irrigation bottle (500 mL) that had been spiked with a port and was being used as a common-source bottle to prepare syringes of sterile water to reconstitute intravenous (IV) push antibiotics. However, the pharmacy had been preparing unit doses of sterile water for injection from larger bags in batches using a primary engineering control, and stocking the pharmacy-prepared unit doses of sterile water for injection in an automated dispensing cabinet (ADC) refrigerator for nurses to use when reconstituting lyophilized antibiotics. Not all staff knew the pharmacy had provided a supply of sterile water for injection in unit doses in the ADC.

It is an unsafe practice to prepare syringes used for flushing, dilution, or reconstitution for more than one patient from a common-source bottle or bag outside the pharmacy. In the pharmacy, the practice might be safe if primary engineering controls are used and strict sterile compounding regulations are followed. But outside of the pharmacy, there is a risk of contamination and disease transmission to a large group of patients, even if the solution is discarded after 24 hours. In addition, sterile water for irrigation is not labeled for use as an injection in patients. Sterile water for injection must pass a USP particulate-matter test that sterile water for irrigation does not have to pass, so they are not considered equivalent.

EPINEPHrine Shortage

Currently, there are shortages of EPINEPHrine injection 1 mg/10 mL syringes (0.1 mg/mL) as well as certain EPINEPHrine autoinjectors (0.3 mg/0.3 mL, 0.15 mg/0.15 mL, 0.15 mg/ 0.3 mL). Autoinjectors are used for the emergency treatment of anaphylaxis. Emergency syringes are commonly found in code carts and used for the treatment of ventricular fibrillation or pulseless ventricular tachycardia unresponsive to initial defibrillation, pulseless electrical activity, and asystole. If prefilled syringes cannot be provided, ISMP has previously recommended providing an emergency kit containing vials of EPINEPHrine (1 mg/mL) and 0.9% sodium chloride (10 mL) for dilution, along with directions for preparing a 0.1 mg/mL concentration for IV push administration. Primarily, 0.9% sodium chloride is needed to facilitate the dilution of EPINEPHrine in vials and the administration of this critical emergency drug; however, 0.9% sodium chloride is also in short supply.

Safe Practice Recommendations: Sometimes drug shortages can lure practitioners and organizations to employ unsafe practices in order to provide immediate care. However, when drug shortages do occur, organize the response to seek safe alternatives and to comply as much as possible with medication safety best practices that embrace conservation and inventory management of the drug in short supply, as well as clinical management and error-mitigation strategies. The tiered strategies listed below should be based on your current inventory and will allow you to relax some of the conservation and inventory management strategies as your supply improves, while reserving some clinical management strategies ONLY after all resources have been exhausted.


  • Contact your wholesaler or the manufacturer’s representative to keep abreast of their inventory of products in short supply (purchase depends on hospital contracts and existing customer relationships).

  • Examine your current usage, inventory, distribution, and waste of a product in short supply and alternatives to develop conservation strategies for managing the inventory and prioritizing its use.

  • Work with your materials management department to transfer and centralize solutions in short supply and alternatives (e.g., small volume bags) to the pharmacy.

  • Use multiple pathways to communicate conservation strategies, practice changes, safe use of alternatives, and error-mitigation strategies to impacted practitioners.

  • Do NOT use IV solutions in containers (e.g., infusion bags, bottles, minibags) as common-source containers to prepare IV flush syringes or to dilute or reconstitute medications outside the pharmacy, even if labeled and only used for 24 hours.

  • Do NOT reuse a syringe or reuse any remaining solution or medication in the syringe (single use only).

  • Do NOT use multiple-dose vials for multiple patients in clinical areas; dedicate multiple-dose vials to a single patient.

0.9% Sodium Chloride Shortage

  • Once all inventory of saline flush syringes is in the pharmacy, employ the following pharmacy conservation strategies:

    • Reduce floor stock quantities to reserve inventory

    • Procure and dispense 10 mL (diameter) flush syringes that hold smaller volumes of saline (e.g., 3 mL or 5 mL fill volume) for use with central lines

    • Maximize the use of bag and vial systems for drug reconstitution or dilution and premixed medications (as available)

    • Consider alternative methods for reconstitution or dilution, such as pharmacy-prepared infusions

    • Reserve small volume bags of 0.9% sodium chloride for medication preparation

  • Employ the following nursing conservation strategies for saline flushes:

    • Eliminate unnecessary medication dilution

    • Reserve 10 mL (diameter) saline flushes for central lines as much as possible

    • Use large volume 0.9% sodium chloride bags for starting IV lines and administering blood products

  • Reserve 10 mL vials of 0.9% sodium chloride for use in emergency code cart kits dispensed (with EPINEPHrine) from the pharmacy.

  • Do NOT dilute or reconstitute medications by drawing up the contents into a commercially available, prefilled flush syringe of 0.9% sodium chloride and then administering the resultant product.

  • Do NOT reuse the same saline syringe to flush VADs before and after medication administration.

  • Do NOT use sterile water for injection for flushing VADs.

  • Remove IVs, central lines, and saline locks if not used for 24 hours or more.

  • Use central VADs with the least number of lumens needed.

  • Purchase saline flush syringes from a pharmacy outsourcer. 

  • In a complete outage: Have pharmacy prepare saline flushes (e.g., repackaged from bags and labeled appropriately) in compliance with sterile compounding regulations. Assign a beyond-use date based on USP <797>.

Sterile Water for Injection Shortage

  • Employ the following pharmacy conservation strategies:

    • Switch to premixed products, bag and vial systems, or dual-chamber flexible containers whenever possible

    • Reserve vials of sterile water for injection for the reconstitution of medications

    • Batch the preparation of medications that require reconstitution in compliance with USP <797> to minimize waste

    • Switch to a large-volume bag of sterile water for injection for reconstitution of medications using a closed system dispensing device 

  • Do NOT use bacteriostatic water for injection in place of sterile water for injection (unless directed in the prescribing information), especially for intrathecal or epidural injections or for neonates.

  • Do NOT use 0.9% sodium chloride in place of sterile water for injection (unless directed in the prescribing information) to reconstitute medications, which can result in hyperosmotic solutions at or near the saturation point and cause crystallization or infusion site reactions.

  • Do NOT use sterile water for irrigation in place of sterile water for injection.

  • In a complete outage: Have pharmacy repackage large bags (1,000 mL or less, not pharmacy bulk packages) of sterile water for injection into empty sterile vials in compliance with sterile compounding regulations. Assign a beyond-use date based on USP <797>. ONLY repackage the sterile water for injection into syringes as a last resort if empty sterile vials are not available, as sterile water for injection prepared in syringes risks mix-ups with saline flush syringes.

EPINEPHrine Shortage

  • Conserve EPINEPHrine emergency syringes for code carts and code situations.

  • Limit the number of emergency EPINEPHrine syringes stocked in code carts.

  • If using 1 mg/1 mL vials in lieu of emergency syringes, package the vial, diluent (10 mL of 0.9% sodium chloride), and syringe label in a kit prominently labeled with the drug name and strength, and include instructions for preparing a dilution equivalent to a prefilled 1 mg/10 mL emergency syringe (i.e., EPINEPHrine 1 mg/mL: Dilute 1 mg [1 mL] in 9 mL of 0.9% sodium chloride for a final concentration of 0.1 mg/mL).

  • Quarantine expired EPINEPHrine products and check with FDA about extended dating before discarding (FDA has extended the expiration date for certain lots of EPINEPHrine syringes).

  • Do NOT stock the 30 mL multiple-dose EPINEPHrine vials in code carts, emergency boxes, or floor stock.

  • Purchase syringes of EPINEPHrine (0.1 mg/mL, 1 mg/10 mL) from a pharmacy outsourcer.

  • In a complete outage of EPINEPHrine syringes and 0.9% sodium chloride vials: ONLY if all resources are exhausted and prefilled saline flush syringes are needed for dilution of EPINEPHrine during code situations, withdraw the EPINEPHrine into an empty syringe and use a Luer-lock-to-Luer-lock transfer device (e.g., Health Care Logistics; BBraun), which must be provided with EPINEPHrine kits on code carts, to withdraw the 0.9% sodium chloride from the prefilled saline flush syringe into the syringe with the pre-drawn EPINEPHrine. Avoid diluting or reconstituting medications by drawing up the contents into a commercially available, prefilled flush syringe of 0.9% sodium chloride and then administering the resultant product. If you must do this as a last resort during code situations, the saline flush syringe MUST be relabeled, covering the original contents and barcode and replacing it with a new label showing that EPINEPHrine is in the syringe (provide the new label in a kit). Another last-resort option is to provide a 250 mL bag of 0.9% sodium chloride labeled as a flush solution that can be used to dilute EPINEPHrine—but only during a single code. The bag should be immediately disposed of after the code. These last-resort options should NOT be utilized outside of emergency code situations.

Sources of recommendations

  1. Drug Shortages Resource Center

  2. ASHP Connect posting from Kevin Hansen

  3. ASHP and the University of Utah Drug Information Service Sterile Water for Injection Shortage Frequently Asked Questions

  4. FDA Drug Shortages

  5. Infusion Nurses Society and National Coalition for IV Push Safety Saline Flush and Vial Shortage

  6. ISMP Safe Practice Guidelines for Adult IV Push Medications