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Published ahead of print on September 4, 2003, doi:10.1164/rccm.200211-1344OC

Am. J. Respir. Crit. Care Med., Volume 168, Number 10, November 2003, 1246-1251

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Submitted on November 22, 2002
Accepted on September 1, 2003

Reduction of Sleep Disordered Breathing after Physostigmine

Jan Hedner1*, Holger Kraiczi2, Yuksel Peker3, and Paul Murphy3

1 Sleep Laboratory and Pulmonary Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden; Clinical Pharmacology, Sahlgrenska University Hospital, Gothenburg, Sweden, 2 Clinical Pharmacology, Sahlgrenska University Hospital, Gothenburg, Sweden, 3 Sleep Laboratory and Pulmonary Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden

* To whom correspondence should be addressed. 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 (OSA). PHYS (0.12 µg/min/kg, 7-hour infusion) reduced mean apnea/hypopnea index (AHI) by 13.6 (95% CI 2.2-25.1) corresponding to 21.4% (95% CI -5.5-47.9) and increased minimum SaO2 by 8.7% (95% CI -0.3-17.7) 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 -43.6-77.7) 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 (TST) 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 (HR) was reduced by PHYS. Moreover, resting (early night placebo HR) was positively correlated with proportional reduction of REM AI (r = 0.69, p<0.02). BMI was negatively correlated with reduction of REM AHI (r = 0.77, p<0.02). This, predominantly REM related, reduction of OSA after PHYS may provide a new treatment option if the effects are maintained in long-term studies.
Key words: sleep, apnea, treatment, acetylcholine, physostigmine




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