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Two Unsafe Practices: Administration of a Product with a Precipitate and Reuse of a Saline Flush Syringe

Problem: Two events recently brought to our attention have again thrust unsafe injection and infusion practices into the limelight. One involves the dispensing and intravenous (IV) administration of a pharmacy-prepared product despite a visible precipitate, and the other involves the reuse of prefilled saline flush syringes for multiple patients, leading to the transmission of bloodborne diseases. We have not previously published the scattered reports we have received related to these unsafe practices, initially believing they were isolated cases. However, these recent events brought to our attention that this may be a more widespread problem, which healthcare providers may need to address with clinical training programs and stepped-up monitoring to ensure adherence with safe practices.

Dispensing and administration of a product with a visible precipitate

To ensure the safe intravascular delivery of medications and solutions, practitioners must be observant for potentially dangerous precipitates often caused by drug or diluent incompatibilities (e.g., acid-base reactions, mixing oppositely charged organic drug ions).1 In an analysis of more than 300 drug incompatibilities reported to the Pennsylvania Patient Safety Authority between 2009 and 2016, almost one in five mentioned the formation of a precipitate.2 Precipitation reactions are usually rapid and can be observed as crystals, haziness, or turbidity. If a precipitate is observed, the drug or solution should not be administered. The precipitate can lead to therapeutic failures due to drug inactivation, catheter occlusions, and varying levels of harm due to particulate embolization, ranging from thrombophlebitis to multi-organ failure or even death.3 The consequences can be particularly severe in pediatric patients.4

Since 1998, a total of 23 cases of precipitation have been reported to the ISMP National Medication Errors Reporting Program (ISMP MERP). In 17 cases, a pharmacist or nurse (or patient/caregiver in the home setting) noticed the precipitate and immediately remedied the problem or stopped the injection or infusion. Some of these cases involved compounding or flushing errors in which the wrong diluent, flush or base solution, or concentration/dose was used, which contributed to the formation of a precipitate. However, in 4 cases, the medication or solution was administered despite observing the precipitate.

In one of these cases, a patient with no previous cardiac or pulmonary disease died. A bag of calcium gluconate and potassium phosphate mixed in saline in the pharmacy appeared cloudy prior to administration, but the nurse still started the infusion. About an hour later, the patient was found in respiratory distress which quickly progressed to a fatal cardiac arrest. A different nurse had previously abandoned an attempt to administer the same solution due to its cloudy appearance, although she had not yet contacted the pharmacy. The nurse who then administered the solution decided to hang it after referencing a flawed hospital protocol that stated products with precipitates could be infused under “close observation” due to the risk of “sudden death.” An autopsy showed scattered pulmonary emboli, and the death was determined to be accidental and related to the infusion of the precipitated electrolyte infusion.

In the ISMP MERP database, there were two additional events in which nurses attempted to administer solutions despite observed precipitates. But fortunately, rapid IV line occlusions led to their discontinuation, although in one case, the solution was reinfused into another vein until that line also became occluded.

In 2015, ISMP learned of another event in which an 11-month-old baby received daily etoposide infusions over a 5-day period despite the presence of visible precipitates within the solution. The baby had a rare form of cancer, and four oncologists had worked together to create a custom chemotherapy treatment plan. Unfortunately, the dose of etoposide was mistranscribed as 33 mg per kg per day, instead of the correct dose of 3.3 mg per kg per day, for 5 days. The high concentration of the etoposide, which was diluted in 100 mL of normal saline, caused the drug to precipitate. Despite frequent occlusions and the need to constantly flush and reaccess the IV access port, none of the nurses reported the precipitate to a pharmacist or oncologist or stopped the infusion. Had they done so, perhaps the 10-fold dosing error could have been detected before the 5 days of therapy had been administered. When we learned of the error, the baby was being closely monitored for possible liver, renal, bone marrow, neurologic, and respiratory damage secondary to etoposide toxicity and particulate administration.

ISMP recently received another report about a compounding error with PROVAYBLUE (methylene blue) that led to precipitation of the drug and IV administration despite potentially visible particulates in the solution or IV tubing. 

Reuse of prefilled saline flush syringes

According to the Centers for Disease Control and Prevention (CDC), unsafe injection practices have affected more than 150,000 patients since 2001, including more than 50 documented outbreaks of viral hepatitis or bacterial infections.5 While many practitioners follow the CDC safe injection practices guideline,6 a survey of more than 5,000 practitioners about the use of needles, syringes, and vials suggests that some may be placing patients at risk for transmission of bloodborne diseases.7 For example, 1% of the survey respondents admitted to sometimes or always reusing a syringe for more than one patient.

We first learned about the unsafe practice of reusing a prefilled saline flush syringe from a 2013 press release issued by a New York hospital that was investigating possible disease transmission in 236 patients hospitalized during a 3-month period.8 In that case, a single nurse had been reusing prefilled saline syringes to flush the IV lines of multiple patients, mistakenly believing that the practice was safe. Luckily, no cases of disease transmission had been identified at the time of the press release.

More recently, the March 10, 2017, issue of Morbidity and Mortality Weekly Report (MMWR) described a very similar event, this time in a Texas hospital. A nurse who worked in a telemetry unit had been reusing prefilled saline syringes to flush the lines of multiple patients, which led to a case of hepatitis C transmission.9 The unsafe practice was discovered after noticing that the nurse would often leave a partially filled saline flush syringe near a computer work station. When a nurse manager investigated this practice, the nurse voluntarily reported reusing syringes during the previous 6 months, believing it was cost-effective and safe if no fluids had been withdrawn into the syringe prior to injecting the saline. The nurse had been working on the unit for 18 months but had not been taught that this was an unsafe practice by other staff members.

Because all telemetry unit patients were required to have IV access, all 392 living patients potentially exposed to this unsafe practice were notified about the possible exposure to bloodborne diseases and the need for laboratory testing. One of two patients who tested positive for hepatitis C had been admitted to the unit during the same time as a patient with known preexisting chronic hepatitis C infection. Genotyping and molecular sequencing identified that both were infected with an identical strain, which accounts for only about 1% of all hepatitis C infections in the US. The CDC concluded that at least one of the hepatitis C infections was likely transmitted as a result of inappropriate reuse and sharing of the saline flushes between multiple patients.9

Safe Practice Recommendations:

ISMP is concerned that the reports of IV drug administration despite observed particulates, and the reuse of prefilled saline flush syringes, are signals of more widespread unsafe practices that illustrate the need for ongoing education and stepped-up monitoring. Given the potential for harm associated with these unsafe practices, several opportunities exist to reduce the risk of errors.


Provide initial orientation and annual education on injection and infusion safety, and include new and temporary nurses, pharmacists, and pharmacy technicians. Assess and reinforce practitioner competence associated with even the most basic concepts of infection control and aseptic technique, including recognition that any form of syringe and/or needle reuse is dangerous and should be prohibited. All nurses, pharmacists, and pharmacy technicians should also be taught to observe medications and solutions for precipitates, and to avoid dispensing or administering an injection or infusion if precipitates are visible or a solution that should be clear is cloudy. Provide actual examples or pictures of drugs that have precipitated10 so practitioners who have never seen this reaction know exactly what to look for.

Also, be sure practitioners understand how to identify and avoid drug incompatibilities when preparing and administering medications or solutions or flushing IV lines (e.g., thoroughly flushing the line before administering an incompatible drug, administering certain medications through a separate injection port or site). The use of an in-line filter for solutions that are prone to precipitation can also help prevent particulates from entering the body; however, precipitates can still form in the tubing below the filter, and filters may become blocked, signaling a need to investigate.2

Policies and procedures

Review organizational policies and procedures related to safe injection and infusion practices to ensure that the principles of infection control, aseptic technique, the CDC safe injection practices guideline,6 and the ISMP Safe Practice Guidelines for Adult IV Push Medications11 have been incorporated. Policies and protocols should also be very clear regarding the need to avoid or immediately discontinue any injection or infusion if particulates are observed in medications or solutions. 


It is essential to monitor adherence with proper injection and infusion techniques in all settings where medications are prepared and administered. Consider developing a checklist12 based on the CDC safe injection practices guideline6 that can be used to conduct the surveillance process and collect the data. Syringe reuse, if identified, should be immediately corrected, and patients should always be notified of any potential exposures and the need for testing.9 


  1. Newton DW. Drug incompatibility chemistry. Am J Health Syst Pharm. 2009;66(4):348-57.
  2. Grissinger M. Analysis of reported drug interactions: a recipe for harm to patients. Pa Pat Saf Advis. 2016;13(4):137-48.
  3. US Food and Drug Administration. Information for healthcare professionals: ceftriaxone (marketed as Rocephin and generics). April 21, 2009.  
  4. Höpner JH, Schulte A, Thiessen J, Knuf M, Huth RG. Preparation of a compatibility chart for intravenous drug therapy in neonatal and pediatric intensive care units. Klin Padiatr. 2007;219(1):37-43.
  5. Centers for Disease Control and Prevention. The One & Only Campaign. 2017.
  6. Siegel JD, Rhinehart E, Jackson M, Chiarello L, Healthcare Infection Control Practices Advisory Committee. Safe injection practices to prevent transmission of infections to patients. In: 2007 guideline for isolation precautions: preventing transmission of infectious agents in healthcare settings. Atlanta: US Department of Health and Human Services; 2007.
  7. Pugliese G, Gosnell C, Bartley JM, Robinson S. Injection practices among clinicians in United States health care settings. Am J Infect Control. 2010;38(10):789-98.
  8. Guthrie Health. Guthrie Corning Hospital alerts patients to possible saline flush syringe reuse. February 7, 2013.
  9. Arnold S, Melville SK, Morehead B, Vaughan G, Moorman A, Crist MB. Notes from the field: hepatitis C transmission from inappropriate reuse of saline flush syringes for multiple patients in an acute care general hospital—Texas, 2015. MMWR. 2017;66(9):258-60.
  10. B. Braun. Drug incompatibility. Risk prevention in infusion therapy.
  11. ISMP. ISMP safe practice guidelines for adult IV push medications. 2015.
  12. ASC Quality Collaboration. Safe injection practices toolkit. 2017.