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Some IV medications are diluted unnecessarily in patient care areas, creating undue risk
June 19, 2014
In our April 2014 newsletter for nurses, Nurse Advise-ERR, we invited readers to complete a short survey about administering IV push medications to adult patients. The purpose of the survey was to learn about dilution practices before IV push administration. The survey was completed by 1,773 respondents, mostly registered nurses (97%), between April and June 2014. Most respondents were staff-level nurses (82%). Of the remaining respondents, some held supervisory or administrative positions (9%) and a few respondents (9%) were nurse educators, clinical nurse specialists, nurse practitioners, nursing students, and nursing faculty. The survey results suggest that nurses frequently dilute medications—a practice that might be necessary depending on the drug, but also one that may unnecessarily result in repackaging of prefilled syringes or other containers provided by the pharmacy. This practice often leads to unlabeled or mislabeled syringes, potential contamination of sterile IV medications, dosing errors, and other types of drug administration errors.

Scope of Medications Diluted

Overall, 83% of nurses responding to our survey reported that they further dilute certain IV push medications for adult patients prior to administration. Pertaining to the containers in which IV medications are provided, medications available in single-dose vials or ampuls were most often diluted (Table 1). Yet, at least half of the respondents often or always diluted medications provided in multiple-dose vials or manufacturer’s prefilled syringes (e.g., Carpuject syringe, others). Even when the pharmacy dispenses a prefilled syringe containing a patient-specific dose, as many as 20% or more respondents further dilute these medications; 12% often or always dilute these medications, and another 8% sometimes dilute the medications. Thus, further dilution of adult IV push medications is common in patient care units.

When asked about the dilution of specific drugs, opioids and antianxiety/antipsychotic medications were most frequently diluted (Table 1). For opioids alone, more than a quarter of respondents reported “always” diluting the drug before administration, and another 21% diluted the drug “often.” Almost half of all respondents reported they often or always dilute antianxiety/antipsychotic medications prior to IV push administration. More than 1 in 3 respondents often or always dilute antiemetics, and almost 1 in 5 respondents often or always dilute anticonvulsants or cardiovascular medications prior to IV push administration. The frequency of diluting opioids, antianxiety medications, anticonvulsants, and antiemetics was likely higher than reported, as survey respondents also included these agents under the category of “other” medications diluted, particularly HYDROmorphone and other “narcotics” in the opioid category, LORazepam and other “benzodiazepines” in the antianxiety category, promethazine in the antiemetic category, and various barbiturates found in the anticonvulsant category.

Many respondents reported diluting medications not specifically included in the survey, including drugs that may cause pain, irritation, or injury at the site during injection (e.g., corticosteroids, diphenhydrAMINE); medications that must be administered very slowly (e.g., ketorolac); medications for which manufacturers recommend dilution and immediate or timely use after dilution (e.g., famotidine, levothyroxine); and antibiotics. The reversal agents, naloxone (which can be diluted) and flumazenil, along with bolus doses of insulin and heparin, were least often diluted.

Factors That Influence Dilution

According to respondents, the factors that most frequently influenced their decision to further dilute a medication (Table 2) included: 

  • The anticipated discomfort at the injection site during injection
  • The vesicant or irritant nature of the medication
  • The high risk of extravasation with the medication or drug delivery device (e.g., butterfly)
  • The need to administer a medication very slowly via IV push (as rapid administration causes adverse effects)
  • The viscosity of the medication (e.g., LORazepam)
  • The difficulty in measuring a very small dose of medication

Respondents also told us they are more likely to dilute a medication that will be administered through a peripheral venous access site rather than a central venous access device. They were also more likely to dilute a medication administered via a saline lock or intermittent access site rather than an access port with a continuous infusion. A decision to dilute a specific medication was also influenced by a prescriber’s order or by a recommendation from a drug or device manufacturer, the pharmacy, an IV drug reference, or a hospital policy.

Additionally, numerous respondents provided reasons for diluting medications that may not be clinically necessary. Several respondents suggested it was safer to dilute all medications before IV push administration so that the drugs are always administered slowly, thus enabling more careful patient monitoring. Others felt there was no way to know how the patient would respond to a medication or if it would cause discomfort, so it was best to dilute all medications. Multiple respondents also reported the oft-unnecessary practice of withdrawing a medication from a vial or prefilled syringe then further diluting the medication in a larger syringe size or diameter if patients have an implanted port or a peripherally inserted central catheter (PICC). Some vascular access devices require lower injection pressures during flushing to avoid the risk of catheter damage if the line is clotted. A 10 mL syringe or a smaller syringe with the same 10 mL diameter delivers its contents under lower pressure than a 3 mL or smaller syringe. Thus, catheter manufacturers may recommend the use of a 10 mL syringe during a saline flush to confirm patency. What is not understood, however, is that once patency has been confirmed, experts agree (Infusion Nursing Standards of Practice, Standard 45. Flushing and Locking, Practice Criteria H.) that a smaller diameter syringe can be used to administer a medication. In addition, a few respondents reported diluting medications for which the manufacturer specifically warns against dilution (e.g., darbepoetin alfa). Several respondents also reported the practice of simply hanging a piggyback of normal saline to administer concurrently with an IV push medication to circumvent the need to dilute a medication—a practice that may not be appropriate without a prescriber’s order. 

Determination of Diluent Volume

For those who dilute medications, the survey asked respondents whether they used a standard volume of diluent every time for each specific medication. The response was nearly split with just a little less than half (49%) indicating that the volume of diluent was variable, even for a single drug. Respondents were also asked to describe how they determined the volume of diluent to use. The responses were highly variable. For example, respondents reported diluent volumes anywhere from 1 mL to 10 mL, equal parts drug and diluent (1:1 ratio), or drug—diluent ratios between 1:½ and 1:¾ of the drug volume. Those who diluted to a total of 10 mL using a 10 mL syringe reported difficulty withdrawing the medication from a prefilled syringe, sometimes fearing they had lost some of the actual drug. A small number of respondents reported that they: had a list of diluents and standard volumes available in a medication room; used a standard formula of diluting with 1 mL of diluent per minute of time needed to slowly administer the drug (e.g., 2 mL of diluent added to a drug to be administered over 2 minutes); or had a standard volume of diluent to use if administration was via a peripheral vein vs. a central vascular device. No respondents described a dilution process that would result in a specific concentration (e.g., add 4 mL of diluent to 1 mL of drug to equal xx mg/5 mL). As suggested by the variability of dilution methods and volumes, less than half of respondents (43%) reported organizational policies or guidelines on dilution. Most of the remaining respondents (44%) were unsure whether their organization had such policies or guidelines.

Mislabeled Syringes

The survey also asked nurses whether they have ever drawn the medication being diluted into a manufacturer’s prefilled syringe of diluent such as 0.9% sodium chloride. More than half (54%) of the staff nurses responding to the survey reported that they had done so, but only 37% of nurses in supervisory or administrative roles reported such a practice. This practice results in a syringe labeled as only containing the diluent but actually contains the diluent and drug. Unless the syringe is relabeled or the drug is immediately administered, it could be mistaken as a syringe containing the diluent.

Recommendations

In light of the survey findings, ISMP recommends serious consideration of the following actions to reduce the risk of medication errors or other adverse patient outcomes associated with dilution of medications prior to IV push administration. (While the survey focused on dilution of adult medications, similar issues, including administration of excess fluids, may exist with pediatric IV push medications. Thus, these recommendations may be applicable to the pediatric population.)

Poll the nursing staff. Conduct a nursing survey (similar to the ISMP survey) to learn the extent and variability of dilution of adult IV push medications. Use the survey results to inform the organization about potentially unsafe dilution practices, and to establish standard practice expectations and guidelines for drugs that require dilution based on the manufacturer’s instructions.

Consider risk-benefit ratio. For drugs that may improve patient comfort or the accuracy of measuring the dose if diluted, have pharmacy research the safety of dilution in the absence of manufacturers’ recommendations. If appropriate, seek approval for dilution from the pharmacy and therapeutics committee. For drugs that carry a high risk of extravasation and injury during IV administration, have the pharmacy and therapeutics committee determine if safer medication alternatives exist. This may not be possible for chemotherapy vesicants but should be a serious consideration if still using IV promethazine as an antiemetic (which ISMP highly discourages).      

Pharmacy dilution. When possible, require pharmacy to prepare any IV push medications that must be diluted according to the manufacturer’s guidelines or hospital policy. The syringe of diluted medication should be labeled for each patient with the patient’s name, drug name, strength, dose, directions for administration (e.g., slow IV push over 2 minutes), and expiration date/time.

Nursing dilution. If stability requires drug dilution immediately prior to IV push administration, provide exact directions for dilution to nurses via written or electronic guidelines or checklists that provide standard diluent volumes and resulting concentrations. Also provide dilution instructions on the medication administration record or other document readily accessible during drug administration. Be sure directions for measuring the patient’s dose are included, as well as proper labeling of the drug’s concentration after dilution. If a dose calculation is required after dilution, require an independent double check of the dose before administering the drug. Encourage nurses to always reference the hospital’s standard guidelines when diluting medications, and to call the pharmacy with questions (as commercial drug references may provide less specific recommendations than hospital guidelines). 

Educate nurses. If the nursing survey in your organization identifies episodes of dilution not supported by the official drug labeling or other reliable source, conduct educational programs to dispel myths and help nurses see the risks associated with these practices. For example, an update may be in order based on the Infusion Nurses Society (INS) guidelines that note it is safe to administer an IV push medication via a central line using a 3 mL syringe as long as patency has been verified using a 10 mL (or 10 mL diameter) syringe to flush the line. Discourage nurses from drawing medications directly into a prefilled syringe containing a diluent by heightening their perceptions of the risks associated with an unlabeled or mislabeled syringe. Be sure nurses understand the need for a prescriber’s order to hang and infuse a small-volume parenteral solution, even though it serves as a means to “dilute” an IV push medication and is administered in small quantities. Dispel any misunderstandings regarding the safety of diluting all adult IV push medications prior to administration.

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