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Reduction of Sleep-disordered Breathing after Physostigmine

Sleep Laboratory, Departments of Pulmonary Medicine and Clinical Pharmacology; and Sahlgrenska University Hospital, Göteborg, Sweden

Correspondence and requests for reprints should be addressed to Jan Hedner, M.D., Ph.D., Department of Pulmonary Medicine and Allergology, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden. E-mail: jan.hedner{at}lungall.gu.se

The cholinesterase inhibitor physostigmine (PHYS) was investigated in a double-blind, placebo-controlled, randomized, crossover trial of 10 male patients with moderate to severe obstructive sleep apnea. PHYS (0.12 µg/minute/kg, 7-hour infusion) reduced mean apnea/hypopnea index (AHI) by 13.6 (95% confidence interval [CI], 2.2–25.1) corresponding to 21.4% (95% CI, –5.5 to 47.9) and increased minimum Sa_O2 by 8.7% (95% CI, –0.3 to 17.7) corresponding to 23.2% (95% CI, 4.8–41.3). During the last third of the night, coinciding with predicted plasma concentration steady state, non-REM sleep AHI decreased by 19.2 (95% CI, 0.1–38.3) or 14.9% (95% CI, -43.6 to 77.7) and REM AHI by 33.8 (95% CI, 13.7–54.0) or 67.5% (95% CI, 49.7–85.3). Mean total sleep time was reduced by 74 minutes (95% CI, 33.9–114.9), but patients with the least pronounced sleep shortening had the largest reduction of AHI (r = 0.73, p < 0.02). The nocturnal decline in heart rate was reduced by PHYS. Moreover, resting (early-night placebo heart rate) was positively correlated with proportional reduction of REM apnea index (r = 0.69, p < 0.02). Body mass index was negatively correlated with reduction of REM AHI (r = 0.77, p < 0.02). This, predominantly REM-related, reduction of obstructive sleep apnea after PHYS may provide a new treatment option if the effects are maintained in long-term studies.

Key Words: sleep-disordered breathing • apnea • treatment • acetylcholine • physostigmine

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