Presented at the 2012 AAPM Annual Meeting « Back

Comparison of Morning and Evening Dosing of Extended-Release Hydromorphone on Sleep-Disordered Breathing in Patients with Low Back Pain

Lynn Webster, MD lwebstermd@gmail¹, Matt Iverson, MPH¹, Mike Smith¹, Jane Steffens², (1) Lifetree Clinical Research, Salt Lake City, UT, (2) Covidien, St. Louis, MO

Introduction: Chronic opioid exposure has been associated with sleep-disordered breathing.1,2 We studied the effect of dosing time (AM or PM) of 24-hour ER hydromorphone on sleep physiology in low back pain patients. Materials and Methods: An Institutional Review Board approved the protocol. Following an open-label immediate-release hydromorphone titration phase, the subjects were randomized in a placebo-controlled, double-blind phase of AM or PM dosing of ER hydromorphone. Fifteen patients were stabilized on ER hydromorphone 8 mg (n=10), 12 mg (n=2), or 16 mg (n=3) administered once-daily either AM or PM for at least 14 days and then crossed over to the alternate dosing regimen. Overnight sleep studies were performed at baseline, following IR hydromorphone titration, and following each ER hydromorphone dosing period. Results: AM dosing appeared to produce fewer night-time respiratory events than PM dosing as demonstrated by lower mean Apnea-Hypopnea Index (AHI) scores (12.9 v 17.1, p=0.1248). Apnea episodes were also less frequent with AM dosing than PM dosing (52.9 v 62.3 events, p=0.0829). The number of oxygen desaturation events with AM dosing was less than half than with PM dosing (33.8 v 71.6 events, p=0.0870) as was the amount of time oxygen saturation was below 88% (17.7 v 40.8 minutes, p=0.2707). Pain control and most other sleep measures were comparable between the groups. Conclusions: Morning dosing of ER hydromorphone appeared to be associated with fewer respiratory events than evening dosing. References: 1)Farney RJ, Walker JM, Cloward TV, Rhondeau S. Sleep-disordered breathing associated with long-term opioid therapy. Chest 2003;123:632-9. 2)Webster LR, Choi Y, Desai H, Webster L, Grant JB. Sleep-disordered breathing and chronic opioid therapy. Pain Med 2008;9:425-32.

Funding: None