How to make and use continuous rate infusions in private practice (Proceedings)

A continuous rate infusion (CRI) is a dosing regimen used to deliver a constant amount of drug per unit time. The most common CRIs are administered intravenously; however, other methods such as transdermal deliver mimic the characteristics of CRIs.

Intravenous CRIs are usually implemented when short-acting drugs are desired for long periods (e.g., propofol) or when consistent plasma concentrations of drugs are desirable (e.g., fentanyl). While very commonly used for anesthesia and analgesia, CRIs also are useful for administration of some antibiotics, antiemetics, and anticonvulsants. While the drugs used can vary, the underlying principals are similar.

Drug Selection

Most CRIs are of drugs with short duration of action. This technique facilitates rapid and accurate titration of dose to meet individual patient requirements. Drugs with longer duration of action such as morphine are also given by CRI, but the ability to rapidly change plasma drug concentration is blunted. Drugs with very long half lives are usually not given by CRI because intermittent dosing is technically easier. An exception would be when a long acting drug is slowly titrated up in effect to limit toxicity (e.g. phenobarbital).

Delivery Methods

Intravenous infusions are usually most accurately delivered with syringe pumps. Separating the drug from the intravenous fluid also allows independent dosage adjustment when needed. However, adding drug to intravenous fluids is also a useful method, especially when a relatively consistent dose is anticipated over a prolonged period. Specialized delivery devices are also available for infusion of drugs over a period of time and can be utilized when desired.

Transdermal delivery systems are similar to intravenous CRIs in that a relatively consistent delivery of drug is achieved. However, transdermal delivery has additional variables that require the practitioner to focus attention on the response of the patient. For example, with transdermal fentanyl patches there is considerable individual variation in the patch contact and delivery. Patients should be assessed for adequate therapeutic effect. Additionally, careful attention should be paid to compounded transdermal medications that reportedly have sustained release. Transdermal delivery is a rather complex process and not all medications available are well absorbed by this route.

Basic Calculation

The first step for calculation of a CRI is determining the amount of drug needed per unit time. This requires three things:

      1. Patient weight

      2. Desired dose

      3. Duration of the infusion

An example is delivery of fentanyl to a canine patient during anesthesia. The dog weighs 10 kg, the desired dose is 5 mcg/kg/h and the infusion is anticipated to last 3 h. The amount of drug needed in the 3 hour period is:

10 kg × 5 mcg/kg/h × 3 h = 150 mcg

The next step would be to determine the volume of drug you need in the time period. This requires that you know the concentration of the drug. In the case of fentanyl, it is commonly available as 50 mcg/mL. Therefore:

150 mcg / 50 mcg/mL = 3 mL of fentanyl

It is worth noting that at this point some drugs may be loaded onto a syringe pump and delivered without dilution. Fentanyl is a good example of this. However, some drugs are too concentrated to be accurately delivered without diluting them (e.g. dopamine). The final volume is empirical and should be small enough for easy administration, yet large enough to allow accurate delivery. With the example of fentanyl, I would typically dilute the 3 mL of 50 mcg/mL fentanyl into 15 or 30 ml of lactate Ringers solution and deliever at 5 or 10 ml/h. This is easily achieved on a syringe pump. If a pump is not available, you might add the fentanyl to a small bag of fluid and administer with an intravenous drip set. If a 250 ml bag is available you could add the 3 mL of fentanyl then deliver at appx 83 ml/h (250 mL / 3 h = 93.3 mL/h). One word of caution, double check that the volume or rate of fluid administration does not exceed the patient's capacity (e.g. 10 mL/kg/h during anesthesia or 60 mL/kg/day at 1x maintenance).

Drugs with a relatively large therapeutic dose range (e.g. fentanyl) require less accuracy with administration than drugs with narrow therapeutic ranges (e.g. dopamine). Syringe pumps are often preferred when accurate dosing is required.

A quick check of the math is to make sure the volume of drug seems reasonable. For example if the amount of drug required is on the order of liters, you probably have a math error. Additionally, you can estimate the amount needed by taking the amount given by intermittent injection divided by the dosing interval. For example if you usually would give the patient 0.5 ml of morphine every 6 hours you would anticipate using a similar amount in a 6 hour infusion.

Another common example would be adding morphine to intravenous fluids for overnight pain management following significant orthopedic surgery. Again using the 10 kg dog:

      1. Patient weight = 10 kg

      2. Desired dose = 0.1 mg/kg/h

      3. Duration of infusion = HERE IS THE TRICKY PART

To calculate the duration of infusion you would want to know how long a bag of fluid would last at the desired rate. If we chose 1x maintenance the hourly fluid rate would be:

(10 kg × 60 mL/kg/day) / (24 h/day) = 600 mL/day / 24 h/day = 25 mL/h

Therefore a 1L bag would last:

1000 mL / 25 mL/h = 40 h

In this example the duration of infusion would be calculated at 40 hours (although usually you would do a shorter infusion). If a shorter infusion is needed you can do one of several things:

      1. waste a fair amount of extra morphine and fluid

      2. use a small bag of fluids

      3. use a syringe pump or a second fluid pump instead of adding the morphine to the maintenance fluids.

To finish the calculation:

10 kg × 0.1 mg/kg/h × 40 h =40 mg of morphine/bag

The concentration of morphine is usually 15 mg/mL therefore

40 mg / 15 mg/mL = 2.6 mL morphine / bag

The SHORTCUT to performing this calculation for each patient usually is done by making a spreadsheet that will do it for you. This can be done easily on Excel or many PDAs and internet sites can do it for you. If using someone else's calculator make sure that you have the same assumptions for patient fluid dose, drug dose, and drug concentration. I prefer to do the calculation for each patient and it usually can be done in less than 60 seconds.

Fluid for Dilution

Most drugs which are used commonly for CRIs in human medicine have package inserts which instruct the preparer as to which fluid to use (e.g., 5% dextrose, 0.9% NaCl, etc.). Most package inserts will also provide instructions about protecting the solution from light and any chemical incompatibilities that may commonly occur. When making CRIs from drugs which are not sold specifically for dilution and continuous infusion, some general guidelines may be useful:

      1. Most package inserts recommend 5% dextrose as the diluent. However, many of the drugs given during anesthesia are compatible (at least in the short term) with most of the fluids used for intraoperative administration (e.g., Normosol R, lactate Ringers, 0.9% NaCl). If the solution becomes cloudy or the drug precipitates upon addition choose a different diluent.

      2. Most drugs which come in brown or colored vials are eventually degraded by light. The rate at which this occurs varies considerably, but if exposure to light is anticipated for a relatively long time protection would be wise (e.g. nitroprusside). When administering drugs over a relatively short period of time (e.g. 2 hours of anesthesia) protection from light does not usually make a noticeable difference in effectiveness or adverse events.

      3. Be aware that some drugs cause tissue necrosis when given perivascularly. Extra care should be paid to placement and maintenance of the iv catheter. Additionally, the incidence of severe tissue necrosis is usually (but not always) less when the drug is very dilute. Dopamine is one such drug that is commonly used during anesthesia.