A constant rate infusion (CRI) is prepared to give a patient a continuous dose of drug in intravenous (IV) fluids. This method is advantageous for administering continuous pain management or for drugs with a short half life, as the drug is maintained at effective plasma concentrations for the duration of the CRI (Creedon et al, 2012). CRIs can also be used to deliver liquid nutrition via feeding tubes for those patients unable to tolerate bolus feedings. CRIs can be utilized for many different patient needs such as pain management, blood pressure management, electrolyte supplementation, sedation, anaesthesia, and insulin administration. The drug can be administered without dilution, calculated to be mixed with concurrent IV fluids already being delivered at a pre-set rate, or prepared separate from IV fluids and titrated to different rates depending on patient needs (Silverstein and Hopper, 2009).

The role of the veterinarian is to choose the appropriate drug and dose for the patient. The role of the veterinary nurse includes calculating the appropriate amount of drug to be added to the fluids, monitoring the patient for the desired drug effect, and consulting with the veterinarian on rate changes depending on the patient status. Critical patients may require multiple types of IV fluids and CRIs, many which may be incompatible with each other (Figure 1). It is up to the veterinary nurse to understand which medications can be combined through the same IV line, which need protection from light (such as morphine, lidocaine, and metoclopramide if they are to be in a CRI for longer than 24 hours), and which drugs bind to the plastic used in IV bags and tubing (such as insulin) and therefore need special care. This information is contained in drug formularies which should be consulted before mixing any medications in the same IV fluid line (Trissel and Trissel, 2009) (Figure 2).

An example of a drug needing special care in CRI form is insulin. An insulin CRI can be created for diabetic ketoacidotic patients. Insulin will bind to the plastic in the IV tubing and if special care is not taken, the patient will not receive the appropriate dose even if the CRI is calculated correctly. After adding the insulin to the bag of fluids, 50 ml of the insulin CRI must be bled through the IV line and discarded. This allows for the insulin to bind to the plastic, and subsequent insulin will then be delivered to the patient in appropriate doses. Insulin CRIs expire after 24 hours and should be replaced to ensure efficacy (Creedon et al, 2012).

CRIs must be labelled with the drug name, the drug dose per millilitre, the time and date the CRI was mixed, and the initials of the person who created the CRI. The fluid bag must be labelled as well as noting the dose and calculation in the medical record (Figure 3). It is vital that CRIs are calculated correctly, as incorrect doses administered over multiple hours can be detrimental and even deadly to patients. A form can be created with the dose and calculations for nurses and veterinarians to check off and double check each other. Nurses also need to understand how to calculate how much of a drug the patient will receive if the fluid rate changes. Once a CRI is utilized, the fluid rate should be checked at least every 4 hours and matched to the medical record ordered dose.

## Calculations for fluids running at a pre-set rate

If the drug is to be added to fluids running at a set rate, it is important to know:

For example: a 12 kg dog has fluids running at 45 ml/hour. You are asked to make a metoclopramide (5 mg/ml) CRI at a dose of 1 mg/kg/day (Plunkett, 2000). How many ml do you add to a litre of fluids that will run at 45 ml/hour?

1 mg/kg/day means the dog needs 12 mg/day (24 hours) of metoclopramide (12 kg × 1 mg/kg/day)

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12/24 = 0.5 mg metoclopramide/hour (12 mg per day/24 hours in a day)

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1000/45 = 22.2 means one litre of fluids will last 22.2 hours (1000ml in a litre/hourly fluid rate)

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22.2 hours × 0.5 mg = 11.1 mg needed per 1 litre of fluids (hours of fluids in 1 litre × drug dose per hour)

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11.1/5 = 2.2 ml metoclopramide needed (drug dose / drug concentration)

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If you add 11.1 mg of metoclopramide (5 mg/ml) to 1 litre of fluids running at 45 ml/hour, a 12 kg dog will receive 1 mg/kg/day of metoclopramide

This calculation should be taken one step further to determine how many milligrams of metoclopramide are in each ml of fluid, so if the fluid rate changes the dose is known. If the dog's fluid rate is changed to 55 ml/hour, how much metoclopramide is the dog receiving?

11.1 mg/1000ml = 0.0111 mg/ml (the number of mg divided by the number of ml of fluid to determine how many mg of drug are in 1ml)

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0.0111 × 55 = 0.61 mg/hour (0.0111 mg in 1 ml × fluid rate to determine how many mg/hour are being delivered to the dog)

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0.61 mg × 24 hours = 14.64 mg/day (dose per hour × hours in a day)

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14.64/12 = 1.22 mg/kg/day (mg per day / patient weight in kg)

This new dose of 1.22 mg/kg/day can be compared with the therapeutic dose for metoclopramide and appropriate steps taken as needed to ensure patient safety (Figure 5).

## Calculations for partially empty litre

Veterinary nurses are often asked to perform this calculation on a partially empty bag of fluids. In these cases, the calculation should be performed to determine how much drug is needed for a full litre (for labelling purposes) and then further calculated for the partially empty bag.

For example: a 6 kg cat has fluids running at 12 ml/hour. There are 600 ml remaining in the bag. You are asked to make a metoclopramide (5 mg/ml) CRI at a dose of 1 mg/kg/day (Plunkett, 2000). How many ml do you add to the 600 ml that is running at 12 ml/hour?

1 mg/kg/day means the cat needs 6 mg/day (24 hours) of metoclopramide (6 kg × 1 mg/kg/day)

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6/24 = 0.25 mg metoclopramide/hour (6 mg per day/24 hours in a day to determine how many mg/hour are needed)

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1000/12 = means there are 83.3 hours of fluid in the bag (1000 ml in a litre/hourly rate)

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83.3 hours × 0.25 mg = 20.8 mg needed per 1 litre of fluids (hours of fluids in 1 litre × hourly dose of drug)

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600/1000 = 0.6 (this is the factor of remaining fluids, amount remaining in the bag/1000 ml in a full litre)

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20.8 × 0.6 = 12.48 mg needed for 600 ml remaining in bag of fluids (mg needed for full litre × factor of remaining fluids)

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12.48/5 = 2.5 ml metoclopramide needed (drug dose/drug concentration)

## Calculations for titratable CRIs

Some CRIs are created to be titratable, meaning that the dose of drug is changed by adjusting the fluid rate until the appropriate response from the patient is reached. There will be a dose range as opposed to a set dose per hour. These CRIs will be created separately from the regular IV fluids and the rate may need to be changed frequently. This is especially common with analgesia CRIs, like fentanyl. In these situations, the CRI is calculated so that 1 ml/hour = 1 μg/kg/hour. This way, the maths is done prior to the fluid rate change. Because 1 ml/hour = 1 μg/kg/hour, a fluid rate of 5 ml/hour will deliver 5 μg/kg/hour. A fluid rate of 8 ml/hour = 8 μg/kg/hour. Doses can quickly be changed without needing to perform more maths equations (Plunkett, 2000).

For example: an 18 kg dog has sustained trauma and needs pain management administered as a CRI. You are asked to calculate a fentanyl (50 μg/ml) CRI and place the patient at 5 μg/kg/hour of fentanyl (Creedon et al, 2012), with the ability to titrate the dose as needed. You plan on making this CRI in a 60 ml syringe and delivering it on a syringe pump.

1 ml/hour = 18 μg/kg/hour (the patient weighs 18 kg, so you want 1 ml/hour to deliver 18 μg/hour)

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60 ml syringe = 60 hours of CRI (assuming 1 ml/hour, since 1 ml/hour = 1 μg/kg/hour)

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18 μg × 60 hours = 1080 μg (dose per hour × hours of CRI)

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1080/50 = 21.6 ml of fentanyl needed (drug dose/drug concentration)

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Run the CRI at 5 ml/hour to deliver 5 μg/kg/min to the 18 kg dog

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Because the equation used 60 ml as the total amount of fluids needed (including the drug you are adding), the total amount of fluid and drug in the CRI must be 60 ml. Prior to adding the drug, you must remove an equal amount of NaCl from the syringe or bag of fluids. In this case 21.6 ml of fentanyl is added to 38.4 ml of NaCl equaling a total volume of 60 ml. The label should read: fentanyl 21.6 ml qs 60 ml NaCl. The ‘qs’ means quantity sufficient, and means that the entire volume of the fentanyl and NaCl is 60 ml.

Pay close attention to the given dose of drug, as some drugs will be dosed as μg/kg/min. Dopamine is one such drug. The dose is titrated up depending on patient response and will be weaned down as improvement is seen. Having this CRI calculated so that 1 ml/hour = 1 μg/kg/min will make frequent dose changes a simple process and will allow the nursing staff to avoid performing complicated maths each time a change needs to be made.

For example: a 15 kg dog has been battling hypotension and you are asked to calculate a dopamine (40 mg/ml) CRI, and then start administering 5 μg/kg/min to the dog (Plunkett, 2000). For ease of titrating, you will make the CRI so that 1 ml/hour = 1 μg/kg/min. You will be making the CRI in a 100 ml bag of NaCl (Figure 6).

1 ml/hour needs to equal 15 μg/min (the patient weighs 15 kg, so you want 1 ml/hour to deliver 15 μg/min)

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15 × 60 = 900 μg/hour (because your fluid rate is in ml/hour, you must convert your dose into μg/hour, to do this you multiply the 15 μg/min by 60 min in a hour)

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900/1000 = 0.9 mg/hour (because your drug concentration is in mg/ml, you need to convert mcg into mg by dividing by 1000)

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100/1 = 100 hours (100 ml of fluid will last 100 hours running at a rate of 1 ml/hour)

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0.9 mg × 100 hours = 90 mg dopamine needed per 100 ml NaCl (multiply the dose of drug per hour by the number of hours of fluid in the bag)

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90/40 = 2.25 ml dopamine needed (the dose of drug that you want divided by the drug concentration)

Because the equation used 100 ml as the total amount of fluids needed including the drug that was added, the total amount of NaCl and dopamine must be 100 ml. From the 100 ml bag, remove 2.25 ml of NaCl, then add 2.25 ml of dopamine. 1 ml/hour means that 15 kg dog will be receiving 1 μg/kg/min, so to deliver 5 μg/kg/min you increase the rate to 5 ml/hour (Figure 7).

With small patients or those that cannot tolerate high rates of IV fluids, it may not be appropriate to run a CRI at 10 or 15 ml/hour. In those patients it may be appropriate to calculate their CRI so that 1 ml/hour = 10 μg/kg/min, or 1 ml/hour = 5 μg/kg/hour etc. The remainder of the maths remains the same.

Some CRIs will have multiple medications added at once. Each drug will need to be calculated separately and an equal amount of fluids removed from the bag before each drug is added (Silverstein and Hopper, 2009). For example, if you are making a methodone/ketamine/lidocaine CRI and you need to add 10 ml of methadone, 75 ml of lidocaine, and 6 ml of ketamine and the maths was performed assuming a total of 1 litre of fluids, you need to remove a total of 91 ml of fluid from that litre before adding all of the medications.

Remember to double check your calculations with the veterinarian or head nurse and clearly label all CRIs. Before combining a CRI with other fluids, fluid additives, or IV medications, be sure to check their compatibility. Practice makes perfect; use the following CRI orders to practice your newly found skills in CRI calculations.

## Conclusion

CRIs provide benefits to both veterinary patients and the staff charged with monitoring those patients. With the skills necessary to calculate and monitor various CRIs, nurses can advocate for better patient care and provide more specific therapies for critical disease.

## Test Your Knowledge

**ANSWERS: 1)** 11 mg/litre **2)** 41.6 mg/litre; 12.5 mg added to 300 ml. With rate increase, patient will receive 2.9 mg/kg/day **3)** 60 mg dopamine qs 250 ml NaCl **4)** 1700 µg fentanyl qs 100 ml NaCl