Chapter 22
Constant Rate Infusions
Just drip it in!
Carolyn Kerr
Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Canada
- Q. What is a constant rate infusion?
- A. A constant, or continuous, rate infusion (CRI) refers to the continuous administration of a dose of drug per unit of time. In veterinary medicine, CRIs are mostly commonly administered via the intravenous route with infusion doses and rates expressed as (mcg or mg)/kg/min or (mcg or mg)/kg/h. The goal of administering a drug as a CRI is to achieve and maintain a constant target concentration of drug in the blood for a desired period of time. As drugs have different patterns of distribution, metabolism, and excretion from the body (pharmacokinetic properties), they are administered at either a fixed rate or a variable rate to achieve constant plasma concentrations.
- Q. Why administer drugs as a CRI?
- A. Although the drugs we administer as a CRI in the peri-anesthetic period do not exert their effect in the vascular space, but rather at an effect (or receptor) site, the plasma concentrations generally correlate with clinical effects. Above a certain plasma level, the effect is excessive and below a certain level, the effects are inadequate. The traditional method of administering intermittent boluses of a drug intravenously results in peaks and valleys in that drug’s plasma concentrations, with corresponding waxing and waning of clinical effect. By administering a drug as a CRI, a near-constant plasma concentration of drug within the therapeutic range can be achieved, thereby producing a more consistent clinical effect and minimizing the risk of drug under- or overdosing. Moreover, it may be easier to titrate the administration of a drug to achieve the desired clinical effect compared with an intermittent bolus technique. When a drug is given as a CRI versus intermittent boluses, less quantity of drug is administered overall and the time from discontinuation of drug administration to termination of drug effect is generally more rapid and predictable.
- Q. What are common reasons to administer anesthetic/analgesic drugs by CRI?
- A. In veterinary medicine, some of the more common reasons for administering injectable drugs as infusions in the peri-anesthetic period include:
- A. providing and/or improving analgesia;
- reducing inhalant anesthetic requirements;
- producing a more stable anesthetic plane;
- providing hemodynamic support.
- Q. What is a loading dose and how do I know if I need to administer one if I plan on performing a CRI?
- A. When a clinician starts a CRI, the goal is generally to achieve target drug levels in a short period of time. The half-life of a drug is the sole factor that influences the rise in plasma concentrations to achieve the desired plasma concentrations at steady state when a drug is administered as an infusion [1]. When a drug is administered as a CRI, after five half-lives 97% of the desired plateau concentration will have been achieved. Clearly, the shorter a drug’s half-life, the faster the desired steady-state plasma concentration is reached. For many drugs it would take a considerable amount of time to achieve the desired blood concentrations if the initial method of administration was only a CRI without a loading dose. For example, the half-life of morphine is approximately 60 min in the dog; therefore, it would take 5 h to achieve the desired plateau concentration if the mode of administration was via a CRI alone. Recommended hourly rates of CRI drug administration generally assume the infusion is being administered following a loading dose of the drug that is being administered as an infusion. There are exceptions; for example, dopamine, dobutamine, and norepinephrine are drugs that do not need a loading dose to rapidly achieve desired concentrations due to their extremely short half-lives (see Chapter 17).
Loading doses can be administered as either a bolus or short-duration infusion to minimize the acute side effects associated with rapid increases in plasma concentrations of a drug. The loading dose is calculated as the desired plasma drug concentration multiplied by the volume of distribution at peak effect [2]. In veterinary medicine, the desired plasma concentrations or the volume of distribution at peak effect for individual drugs are rarely known, but clinical experience and extrapolation from research data has resulted in recommended doses that can be used as the loading dose.
- Q. How is an infusion rate determined?
- A. The recommended infusion rate for a drug is calculated by multiplying the desired plasma drug concentration by the clearance [1]. Pharmacokinetic data may have resulted in published recommended infusion rates for some drugs that are administered in veterinary patients. When published infusion rates are not available, an alternative approach for the clinician is to divide the effective dose by the typical duration of effect. For example, hydromorphone can be administered as a CRI. The typical dose recommended in the canine is 0.1–0.2 mg/kg and its duration of effect is approximately 4 h. The hourly infusion rate would therefore be 0.1–0.2 mg/kg divided by 4 h resulting in an infusion rate of 0.025–0.05 mg/kg/h [3].
While pharmacokinetic data or clinical experience can be used to determine an approximate infusion rate, they should be used only as a guide and each patient receiving a CRI should be assessed individually for their response to treatment, both desirable and undesirable. One of the major advantages of using a CRI is the ability to “fine tune” the dose of drug administration without inducing major changes in the degree of the desired effects, as might occur with a bolus administration.
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- Q. What are common reasons to administer anesthetic/analgesic drugs by CRI?
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