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Additional Strategies to Improve Complete Delivery of Small-Volume Intermittent Infusions

In the December 3, 2020 newsletter, ISMP published an article to remind practitioners that up to half of the medication in a 50 mL small-volume intermittent infusion (medication diluted in a small bag) could remain in the tubing after intravenous (IV) administration when using a longer macrobore primary administration set connected to a patient’s vascular access device.1 Without adequate flushing of the tubing, the residual volume of the medication remaining in the tubing may not be administered to the patient, leading to a significant underdose. Furthermore, if the tubing is used later for medication or fluid administration, the residual volume left in the tubing from the previous infusion could result in an inadvertent bolus of the medication.

Oftentimes, the administration of a small-volume intermittent infusion through a primary administration set is due to the absence of a primary infusion or carrier fluid, which nurses cannot hang without an order. A primary administration set may also be used to address delayed doses caused by failing to open the roller clamp on a secondary infusion. Lack of practitioner awareness regarding the potentially significant loss of medication in the tubing coupled with scarce details in organizational policies and procedures about how to administer small-volume intermittent infusions and/or flush the tubing afterwards also contribute to the problem.

Results of a recent study suggest that the best practice to minimize medication loss in the tubing is to administer small-volume intermittent infusions as secondary infusions using a shorter secondary administration set with a compatible primary infusion.2 To promote this practice, one of several key recommendations we published in our previous article was to embed an order for an appropriate carrier fluid in order sets used to prescribe common small-volume intermittent infusions. This would enable nurses to administer the small bag as a secondary infusion as well as flush the residual volume through the tubing with the carrier fluid to deliver the full dose.

Since we published the article in December 2020, several US smart infusion pump vendors, including Ivenix, B. Braun, Baxter, BD, and ICU Medical, have communicated with ISMP to confirm the prevalence of this problem and to suggest other ways that the residual medication lost or retained in the tubing can be managed so that patients receive the full prescribed dose and/or do not receive an unintended bolus dose from any residual medication left in the tubing. In fact, one smart pump vendor sent ISMP a link to a recent news report about a series of events in the United Kingdom (UK) in which more than a dozen patients stopped breathing, and 40 additional patients experienced serious adverse effects, after a residual amount of a neuromuscular blocking agent used during anesthesia remained in the patients’ IV lines and was then inadvertently administered by unsuspecting practitioners who used the same IV lines postoperatively.3 One patient described ongoing nightmares associated with the horrifying error that left him fully conscious but unable to breathe. Within a 3-year period, 58 similar events were uncovered in the UK during a follow-up investigation.   

Based on the feedback we received from US smart infusion pump vendors, the following additional strategies should be considered to reduce the risk of underdoses and inadvertent bolus doses due to the residual volume of medication that may remain in the tubing after administration of small-volume intermittent infusions. Some of these recommendations can help you maximize options that might be available with your smart infusion pumps. Talk to your vendor’s clinical staff if you are uncertain regarding your pump’s functionality or for help with best practices specific to the vendor’s technology.

Administer as a Secondary Infusion

As previously recommended, most small-volume intermittent infusions should be administered as secondary infusions, not primary infusions. Some pumps will allow organizations to specify that all small-volume intermittent infusions must be delivered as a secondary infusion ONLY, including in a smart pump interoperability environment and regardless of whether the electronic health record allows such specifications. Some smart pumps will even allow each concentration of a medication delivered in a small bag to be configured as either a primary or secondary infusion. If the small-volume intermittent infusion is specified to be infused strictly as a secondary infusion, the clinician will either be alerted if they attempt to program it as a primary infusion, or they will only be provided with a secondary programming screen upon selection of the drug—they will not be able to program it as a primary infusion.

As an alternative, some smart pumps allow the use of short primary administration sets, which can be used to administer small-volume intermittent infusions. Using a short primary administration set avoids concerns with unopened roller clamps, head-height differentials, and limitations in concurrent flow rates, while significantly limiting the potential for significant residual volume remaining in the tubing.

Use Microbore Tubing

Consider using microbore (small bore) administration sets for the primary infusion or carrier fluid to minimize the residual volume left in the tubing. Microbore tubing has a lower priming volume compared to macrobore (regular bore) tubing. Thus, there will be less residual volume left in the tubing when using microbore tubing. For the small-volume intermittent infusion, use a secondary administration set with the smallest priming volume that can be used with the pump.

Provide an Accurate VTBI

When you combine the overfill volume that manufacturers add to each small bag with the volume of all the additives (e.g., antibiotic) injected into each pharmacy-prepared small-volume intermittent infusion, the bag contains more volume than the manufacturers’ labeled amount (e.g., 50 mL, 100 mL). If the clinician administering the small-volume intermittent infusion programs the pump to deliver only the manufacturer’s labeled volume, which is less than the actual volume in the small bag, it may cause the pump to stop the infusion at the programmed volume to be infused (VTBI), potentially leaving a clinically significant volume of the infusion in the small bag (and tubing). The patient may not receive the residual medication left in the small-volume intermittent infusion unless the clinician decides to estimate the remaining volume in the small bag and then reprogram the pump to deliver the full prescribed dose. Still, underestimating the residual volume left in the bag will result in underdosing or repeated, time-consuming attempts to administer the full dose. Overestimating the residual volume will result in an alarm and, in some pumps, may require air removal from the tubing. It may also cancel any “automatic secondary flushing” functionality available with the pump (see Flush the Line). Also, if there is a primary infusion or carrier fluid available, the pump might prematurely switch to this infusion at the predefined primary infusion or carrier fluid infusion rate (see Flush the Line for problems associated with this action).

If an accurate total VTBI was determined upfront, provided on the pharmacy label, and used to program the pump, most of these issues could be eliminated. Thus, ISMP has long recommended that the pharmacy label on the bag explicitly states how to deliver the entire dose, including all overfill and additive amounts. The pharmacy should include the actual total VTBI on the label, combining an estimate of the manufacturer’s overfill, the exact volume of all additives, and the stated volume in the bag (e.g., 50 mL). Vendors of small-volume intermittent infusions can provide hospitals with a targeted amount and range of overfill in each of their products. For infusions in which the dose remaining in the tubing must also be infused to deliver the entire dose, the label and the medication administration record (or a standard procedure for intermittent infusions) should specify that the tubing should be flushed with a particular diluent and volume. When the rate of administration is critical, as for some medications given intermittently by an infusion pump, ensure that information about the rate of administration and flush is built into relevant protocols and smart infusion pumps.

If the pharmacy admixture label cannot display the total VTBI (including overfill and additives) or if the small-volume intermittent infusion will be assembled by clinicians in patient care units right before administration (e.g., two-part, ready-to-mix delivery systems), organizations should consider prepopulating the total VTBI in the infusion pump’s drug library by estimating the manufacturer’s overfill and determining the volume of additives used for common small-volume intermittent infusions. Another viable option is to weigh a sampling of commonly used small-volume intermittent infusion bags after preparation (using gravimetrics) to determine the total volume, and to use this amount for subsequent VTBI labeling, programming, and/or prepopulation in the infusion pump’s drug library. A third option is to use commercially available premixed small-volume intermittent infusions. While each premixed bag contains a small amount of overfill, the additional volume in each bag also includes full-concentration drug solution, meaning that programming the pump to deliver the labeled volume (e.g., 50 mL, 100 mL) typically results in the patient receiving the full dose of medication, as long as the medication remaining in the tubing has been administered to the patient.  

Most organizations realize that an accurate VTBI is critical for chemotherapy infusions and might weigh each of these prepared infusion bags to get an accurate total volume; still, the primary way to ensure patients receive the full dose of medication at the required time and at the intended rate of infusion is to provide an accurate VTBI for all small-volume intermittent infusions. If your facility uses smart pumps which allow the clinician to automatically infuse the entire contents of the secondary container via an “infuse to empty” function, encourage clinicians to not alter this default setting which allows the entire dose to be administered to the patient.

Use Pump Alarms to Detect Unopened Clamps

Historically, closed roller clamps on small-volume intermittent infusions have happened more frequently than reported, leading to delays in administration and/or omissions. There is no easy remedy for this human failure mode; however, some infusion pumps can sense an upstream occlusion if the roller clamp leading to the intermittent infusion is closed, thereby alerting the clinician to check and release any clamps. Also, some pumps require the clinician to confirm that the roller clamp is open when starting the infusion, even calling the clinician back to the pump if this verification does not occur. Please be aware that this functionality might not exist when the pump is operating in “anesthesia mode.”

Flush the Line

Most pumps can be programmed to automatically switch to the primary infusion or carrier fluid when the small-volume intermittent infusion is complete. However, even though the bag might be empty, the medication from the intermittent infusion that remains in the tubing will often be delivered at the primary infusion or carrier fluid rate, which is often different (e.g., slower) than the intermittent infusion rate. So, it might take hours to deliver the volume remaining in the intermittent infusion tubing. But with one newer model smart pump, clinicians can program, at the intermittent infusion rate, an “automatic secondary flush” using an adequate volume from the primary infusion or carrier fluid to clear the tubing. After that specific volume has been infused to clear the tubing, the rate of infusion will return to the previously programmed primary infusion or carrier fluid rate.

Alternatively, clinicians can choose to be notified after the intermittent infusion completes so they can manually flush the tubing at the appropriate rate of administration or use a line flushing feature on the pump to clear the tubing and deliver the full dose, and then switch to the primary infusion or carrier fluid. In some cases, the pump will deliver a very low rate of infusion until the clinician acknowledges the “call back” to the pump at the end of the intermittent infusion. With both the automatic secondary flush and a clinician “call back” for a manual flush or pump line flushing functionality, clinicians will need to know the residual volume (also known as the “priming volume”) available in administration sets.

Clinicians, including anesthesia providers, will also need to know the residual volume available in administration sets to flush the tubing used to administer medications (e.g., neuromuscular blocking agents, oxytocin, opioids) to prevent an inadvertent bolus dose of any leftover medication in the tubing. Staff education about the risks of administering an inadvertent bolus dose of medication due to not flushing or changing the administration set after medical or surgical procedures or after medication administration may also be required.


We hope organizations will use these recommendations, as well as those we previously published in our December 2020 newsletter,1 to develop a standard procedure that describes exactly how clinicians should administer small-volume intermittent infusions in their organization, with a goal of flushing residual volumes remaining in administration sets to deliver the full dose and avoiding inadvertent bolus doses.


  1. ISMP. Hidden medication loss when using a primary administration set for small-volume intermittent infusions. ISMP Medication Safety Alert! 2020;25(24):1-4.
  2. Harding M, Stefka S, Bailey M, Morgan D, Anderson A. Best practice for delivering small-volume intermittent intravenous infusions. J Infus Nurs. 2020;43(1):47-52.
  3. Lintern S. Dozens of patients left conscious but unable to breathe after NHS drug errors. Independent UK News. March 4, 2021. Accessed March 30, 2021.