Allard, P., Lamontagne, C., Bernard, P., & Tremblay, C. (1999). How effective are supplementary doses of opioids for dyspnea in terminally ill cancer patients? A randomized continuous sequential clinical trial. Journal of Pain and Symptom Management, 17(4), 256–265.

The objective of this study was to compare the efficacy of supplemental, oral, and parenteral opioid doses consisting of either 25% or 50% of the equivalent 4-hour opioid dose (i.e., total 24-hour opioid dose divided into 4-hour portions) in patients already receiving opioids on a regular basis.

The study reported on a sample of 33 terminally ill patients with cancer and dyspnea at rest who already were receiving opioids.

The study was conducted in three separate palliative care centers in Quebec, Canada.

The study was a randomized, double-blind, continuous sequential controlled trial.

Dyspnea intensity on the visual analog scale and respiratory rate were measured at baseline, 30, 60, 120, 180, and 240 minutes after dose.

The overall treatment effect, as measured by dyspnea intensity and respiratory frequency, was not significantly different for 25% or 50% of the equivalent four-hour opioid dose. A significant (p < 0.0001) decrease was found in pre- and post-dyspnea intensity. Dyspnea decrease was inverse to baseline dyspnea intensity (i.e., low dyspnea at baseline had greater decrease in dyspnea intensity whereas high dyspnea at baseline had less decrease).

• Authors reported that the sample required one more pair to offer definitive preference in favor of 25% of the four-hour dose.
• The finding was restricted to those already receiving regular opioids.
• The study was properly designed and conducted at multiple sites; however, the sample was limited.

Because 25% and 50% doses had the same effect, a supplementary dose of 25% of the equivalent four-hour opioid dose is recommended to reduce dyspnea for as long as four hours.