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Palliative Care Perspectives : Chapter 4: Pain Management : Principles of Basal and Breakthrough (Incident) Drug Dosing

Having determined the opioid to be used and the route of administration, the next questions that usually arise are, "What basal (around-the-clock) drug dose should I prescribe, and what breakthrough (short-acting) drug should I prescribe for breakthrough, or incident, pain?" Much of the art of good pain medication prescription lies in calculating the relative basal and breakthrough doses.

Most patients who have chronic pain require around-the-clock drug dosing. How does one determine the relative basal and breakthrough doses? The following principle is helpful: the more chronic the pain, the more one should rely on the basal dose; the more acute (or unstable) the pain, the more one should depend on the breakthrough, or short-acting, dose.46

Palliative Care Note
The more chronic the pain, the more one should rely on the basal dose. The more acute, or unstable, the pain, the more one should rely on the breakthrough, or short-acting, dose.

In treating chronic, relatively stable pain, a good rule of thumb is that the breakthrough dose should be at approximately that dose that will double the serum opioid level over the basal level when the peak effect has been obtained. This is because a 100% increase (doubling the dose) is usually quite safe. The total dosage of breakthrough medication taken in 24 hours should rarely exceed the 24 hour basal dose in chronic, stable pain. If it does exceed this (or whenever very frequent dosing is given), the basal dose usually needs to be increased. Breakthrough doses should be administered at intervals such that the peak effect of the drug given via a certain route occurs before the next possible breakthrough dose. It is unnecessary and undesirable to schedule breakthrough doses based on the duration of action of the drug. For short-acting oral opioids, such as morphine, the peak effect occurs in approximately one hour. The duration of action of oral morphine in most patients is four hours. Generally, oral morphine as a breakthrough drug should be dosed q1-2 hours, not q4 hours. SR oral opioids usually show a peak effect in three to six hours. IV peak effects correlate with lipid solubility. Peak effect is usually seen in 10 to 15 minutes for morphine. For SC/IM administration, peak effect may occur somewhat later than that for IV. Transmucosal fentanyl demonstrates peak plasma levels in approximately 20 minutes.

Palliative Care Note
Breakthrough doses should be ordered at time intervals slightly longer than the time to peak effect.

The importance of this principle can be appreciated by considering "standard medical practice" in many hospitals and nursing homes. Most clinicians still order oral short-acting opioids every four to six hours PRN pain. Consider this practice more closely. Most short-acting oral opioids do last approximately four hours, assuming normal pharmacokinetics. Dosing every six hours makes no sense, as the drug has worn off significantly by that time. If the patient required exactly the prescribed opioid dose every four hours to relieve pain and if nursing staff administered the opioid exactly at four hours, then adequate analgesia would be achieved. However, q4h dosing effectively prohibits drug titration against pain, given the drug lasts only four hours. Nurses (and other care providers) often cannot respond immediately at four hours to administer a new dose. Delays of 30 to 60 minutes are not uncommon. During this time the drug may wear off. The peak effect of the new dose will not occur for another hour. The chance of inadequately treated pain in this gap increases substantially. Of course, patients should not generally require opioids as frequently as every one to two hours. If this does occur, it means that either the drug dose is too low or adjustments must be made in basal drug dosing. I suspect the bad habit of prescribing short-acting oral opioids q4-6h arose both from a misunderstanding that stressed dosing based on duration of action, not peak effect, and from concerns about acetaminophen or aspirin toxicity if combination drugs were being used. The misunderstanding can be addressed through education.

Palliative Care Note
For stable, chronic pain a breakthrough dose should roughly double the serum opioid level when peak effect is achieved.

In very unstable, or acute, pain situations it is often appropriate to use no basal dose or to rely primarily on short-acting breakthrough doses. As pain stabilizes and comes under control (and if pain persists in a chronic form), the daily dosage of the short-acting agent used can be of help in calculating a new basal drug dose. The key to appropriate management is flexibility and frequent reevaluation.

When raising the basal dose, it is important to remember to increase by percentage, not milligram. At a minimum an increase should be 25% of the prior dosage. Commonly, the dose is increased by 25% to 100%. In higher dose ranges, physicians tend to underdose because they often increase dosages by milligrams. For example, many physicians are quite comfortable increasing morphine from 2 to 4 mg per hour (a 100% increase of 2 mgs) but will seriously underdose in increasing a patient from 20 mg to 22 mgs (a 10% increase of 2 mgs).

Palliative Care Note
Increase drug doses (by any route) by percentage, not milligram.

Many times I have made the mistake of dutifully increasing the basal drug dose while ignoring the breakthrough dose. For example, 10 mg of morphine may have been a reasonable breakthrough dose when the patient was on 30 mg of sustained-action morphine q12h, but it is clearly inadequate if the basal dose has risen to 90 mg q12h. It is important to remember to adjust breakthrough doses in parallel to basal doses.

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Palliative Care Perspectives

James L. Hallenbeck, M.D.

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Copyright 2003 by Oxford University Press, Inc.

The online version of this book is used with permission of the publisher and author on web sites affiliated with the Inter-Institutional Collaborating Network on End-of-life Care (IICN), sponsored by Growth House, Inc.