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P T. 2017;42(8): 490-492,508
Medication Errors

Some IV Medications Are Diluted Unnecessarily in Patient-Care Areas, Creating Undue Risk

Matthew Grissinger RPh, FASCP

In the April 2014 issue of Nurse Advise–ERR, the Institute for Safe Medication Practices (ISMP) newsletter for nurses, readers were invited to complete a short survey about administering intravenous (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 the 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 ampules 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 syringes [sterile cartridge units, Pfizer]). 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 one-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 one in three respondents “often” or “always” dilute antiemetics, and almost one in five 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 “benzo-diazepines” 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., cortico steroids, 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. Reversal agents, such as 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. This decision 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.

In addition, 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 often-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. 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 that a smaller-diameter syringe can be used to administer a medication.1 In addition, a few respondents reported diluting medications for which the manufacturer specifically warns against dilution (e.g., darbepoetin alfa [Aranesp, Amgen]). 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 two minutes); or had a standard volume of diluent to use if administration was via a peripheral vein versus 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.

Safe Practice 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 the 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 P&T committee. For drugs that carry a high risk of extravasation and injury during IV administration, have the P&T 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 two 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 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.1 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.


Frequency of Further Dilution of Adult Medications Prior to IV Push Administration

Container Type or Medication Never
> 95%
Overall Rank*
Container Type
Single-dose vial or ampule of liquid medication 9 14 35 28 14 3.9
Multidose vial of liquid medication 36 15 23 15 11 3.0
Manufacturer’s prefilled syringe (e.g., Carpuject) 42 15 18 15 10 2.8
Syringe with patient-specific dose dispensed by pharmacy 63 17 8 7 5 2.1
Opioids/narcotics 20 13 19 21 27 3.2
Antianxiety/antipsychotic medications 22 14 18 23 24 3.1
Antiemetics 29 16 19 18 18 2.8
Anticonvulsants 58 11 10 9 11 2.1
Cardiovascular drugs (e.g., digoxin, metoprolol) 58 13 12 8 10 2.0
Naloxone 74 6 4 4 13 1.8
Flumazenil 81 6 4 3 6 1.5
Insulin (bolus) 85 6 2 2 5 1.4
Heparin (bolus) 91 6 1 1 1 1.2

IV = intravenous

*Ranking based on a scale from 1 to 5 with 1 representing “never” and 5 representing “always.”

Factors That Influence a Decision to Dilute Adult Medication Prior to IV Push Administration

Factor Never Sometimes No Influence Often Always Overall Rank*
Patient discomfort at injection site during injection 4 14 3 40 39 4.0
Type of Medication
Vesicants and/or irritants 6 13 7 31 43 3.9
Nonvesicants 25 30 30 9 6 2.4
Risk of Extravasation
Drugs with high risk of extravasation 8 13 11 29 38 3.8
Patients with high risk of extravasation 9 16 11 32 32 2.0
Devices with high risk of extravasation 13 13 19 26 29 3.5
Duration of Administration
Slow IV push 12 27 16 30 16 3.1
Rapid IV push 51 20 21 4 3 1.3
Volume of Medication
Low volume of medication 14 27 19 27 12 3.0
Site of Venous Access
Peripheral venous access 11 27 22 30 9 3.0
Central venous access 24 26 32 9 8 2.5
Type of IV Access
Saline lock/intermittent access site 17 23 25 25 10 2.9
Access port with continuous infusion 32 25 30 7 6 2.3

IV = intravenous

*Ranking based on a scale from 1 to 5 with 1 representing “never” and 5 representing “always.”

Author bio: 
Mr. Grissinger, an editorial board member of P&T, is Director of Error Reporting Programs at the Institute for Safe Medication Practices (ISMP) in Horsham, Pennsylvania (
  • Infusion Nurses Society. Infusion nursing standards of practice, standard 45: flushing and locking, practice criteria H. J Infus Nurs 2011;34;(1S):S59–S63.