Scheduling of Opioid Administration

The schedule of opioid administration should be individualized to optimize the balance between patient comfort and convenience. 'Around the clock' dosing and 'as needed's dosing both have a place in clinical practice.

'Around the Clock' Dosing

Patients with severe post-operative pain generally benefit from scheduled 'around the clock' dosing, which can provide the patient with continuous relief by preventing the pain from recurring. Clinical vigilance is required, however, when this approach is used in patients with no previous opioid exposure and when administering drugs that have long half-lives (metha-done or levorphanol) or produce metabolites with long half-lives (e.g. morphine-6-glucuronide and norpropoxyphene). In the latter situations, delayed toxicity may develop as plasma drug (or metabolite) concentrations rise toward steady state levels. Most patients who receive an 'around the clock' opioid regimen should also be provided a so-called 'rescue dose', which is a supplemental dose offered on an 'as needed' basis to treat pain that breaks through the regular schedule. The frequency with which the rescue dose can be offered depends on the route of administration and the time to peak effect for the particular drug. Oral rescue doses are usually offered up to every 1-2 hours and parenteral doses can be offered as frequently as every 15-30 minutes. The integration of 'around the clock' dosing with 'rescue doses' provides a method for safe and rational stepwise dose escalation, which is applicable to all routes of opioid administration. Patients who require more than 4-6 rescue doses per day should generally undergo escalation of the baseline dose. The quantity of the rescue medication consumed can be used to guide the dose increment. Controlled-release preparations of opioids can lessen the inconvenience associated with the use of 'around the clock' administration of drugs with a short duration of action. Currently, controlled-release formulations are available for administration by the oral, transdermal and rectal routes. The largest experience has been reported with oral controlled-release morphine preparations with 8-12 hours' duration of effect. Other controlled-release formulations include once-daily morphine preparations, controlled-release morphine suppositories and liquid suspension, transdermal fentanyl, and controlled-release tablets of oxycodone, hydromorphone, codeine and dihydrocodeine. Clinical experience suggests that controlled-release formulations should not be used to rapidly titrate the dose in patients with severe pain. The time required to approach steady-state plasma concentration after dosing is initiated or changed (at least 24 hours) may complicate efforts to rapidly identify the appropriate dose. Repeat-dose adjustments for patients with severe pain are performed more efficiently with short-acting preparations, which may be changed to a controlled-release preparation when the effective 'around the clock' dose is identified.

'As Needed' Dosing

In some situations, opioid administration on an 'as needed' basis, without an 'around the clock' dosing regimen, may be beneficial. In the opioid-naive patient, 'as needed' dosing may provide additional safety during the initiation of opioid therapy, particularly when rapid dose escalation is needed or therapy with a long half-life opioid such as methadone or levor-phanol is begun. 'As needed' dosing may also be appropriate for patients who have rapidly decreasing analgesic requirement or intermittent pain separated by pain-free intervals.

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