Eszopiclone increases the respiratory arousal threshold and lowers the apnoea/hypopnoea index in obstructive sleep apnoea patients with a low arousal threshold.
Recent insights into sleep apnoea pathogenesis reveal that a low respiratory arousal threshold (awaken easily) is important for many patients. As most patients experience stable breathing periods mediated by upper-airway dilator muscle activation via accumulation of respiratory stimuli, premature awakening may prevent respiratory stimuli build up as well as the resulting stabilization of sleep and breathing. The aim of the present physiological study was to determine the effects of a non-benzodiazepine sedative, eszopiclone, on the arousal threshold and the AHI (apnoea/hypopnoea index) in obstructive sleep apnoea patients. We hypothesized that eszopiclone would increase the arousal threshold and lower the AHI in patients with a low arousal threshold (0 to -15 cm H(2)O). Following a baseline overnight polysomnogram with an epiglottic pressure catheter to quantify the arousal threshold, 17 obstructive sleep apnoea patients, without major hypoxaemia [nadir SaO(2) (arterial blood oxygen saturation) >70%], returned on two additional nights and received 3 mg of eszopiclone or placebo immediately prior to each study. Compared with placebo, eszopiclone significantly increased the arousal threshold [-14.0 (-19.9 to -10.9) compared with -18.0 (-22.2 to -15.1) cm H(2)O; P<0.01], and sleep duration, improved sleep quality and lowered the AHI without respiratory event prolongation or worsening hypoxaemia. Among the eight patients identified as having a low arousal threshold, reductions in the AHI occurred invariably and were most pronounced (25±6 compared with 14±4 events/h of sleep; P<0.01). In conclusion, eszopiclone increases the arousal threshold and lowers the AHI in obstructive sleep apnoea patients that do not have marked overnight hypoxaemia. The greatest reductions in the AHI occurred in those with a low arousal threshold. The results of this single night physiological study suggest that certain sedatives may be of therapeutic benefit for a definable subgroup of patients. However, additional treatment strategies are probably required to achieve elimination of apnoea.
Sleep Disorders Program, Division of Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. deckert@rics.bwh.harvard.edu
Danny J
DJ
Eckert
Robert L
RL
Owens
Geoffrey B
GB
Kehlmann
Andrew
A
Wellman
Shilpa
S
Rahangdale
Susie
S
Yim-Yeh
David P
DP
White
Atul
A
Malhotra
D000328:Adult; D001143:Arousal / Q000187:drug effects*; D053961:Azabicyclo Compounds / Q000627:therapeutic use*; D004311:Double-Blind Method; D000069582:Eszopiclone; D006801:Humans; D006993:Hypnotics and Sedatives / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use*; D012119:Respiration / Q000187:drug effects*; D020181:Sleep Apnea, Obstructive / Q000188:drug therapy* / Q000503:physiopathology
D053961:Azabicyclo Compounds; D006993:Hypnotics and Sedatives; D010879:Piperazines; D000069582:Eszopiclone
Am Rev Respir Dis. 1985 Aug;132(2):216-9
3927805
Sleep Med. 2007 Aug;8(5):464-70
17512799
Chest. 2009 Apr;135(4):957-964
19118266
Sleep. 2007 Apr;30(4):478-88
17520792
Am Rev Respir Dis. 1993 Apr;147(4):887-95
8466125
Eur Respir J. 2010 Sep;36(3):569-76
20032012
Am J Respir Crit Care Med. 2003 Sep 15;168(6):645-58
12773321
Am Rev Respir Dis. 1983 Dec;128(6):980-3
6418046
Sleep Med Rev. 2003 Feb;7(1):81-99
12586532
Thorax. 2010 Feb;65(2):95-6
20147587
J Clin Sleep Med. 2005 Oct 15;1(4):367-71
17564403
Drugs. 2009;69 Suppl 2:77-91
20047352
Sleep. 2009 Mar;32(3):361-8
19294956
Eur Respir J. 1994 Nov;7(11):2011-5
7875274
J Clin Invest. 1992 May;89(5):1571-9
1569196
Am Rev Respir Dis. 1992 Nov;146(5 Pt 1):1256-60
1443881
N Engl J Med. 1993 Apr 29;328(17):1230-5
8464434
Respir Physiol Neurobiol. 2008 Jul 31;162(2):144-51
18577470
Am Rev Respir Dis. 1985 Jan;131(1):41-5
3966713
J Clin Sleep Med. 2009 Apr 15;5(2):122-9
19968044
Am J Respir Crit Care Med. 1995 Feb;151(2 Pt 1):450-4
7842205
Am J Respir Crit Care Med. 2005 Dec 1;172(11):1363-70
16100008
J Appl Physiol (1985). 2007 Dec;103(6):1929-41
17823298
Thorax. 2010 Feb;65(2):107-12
19850964
Sleep Med Rev. 2008 Feb;12(1):33-47
18201662
Eur Respir J. 1997 Jan;10(1):226-37
9032519
J Physiol. 1999 Nov 1;520 Pt 3:897-908
10545152
Am J Respir Crit Care Med. 2002 Sep 15;166(6):855-9
12231497
Am Rev Respir Dis. 1992 Feb;145(2 Pt 1):445-52
1736755
N Engl J Med. 1999 Mar 18;340(11):847-51
10080847
Proc Am Thorac Soc. 2008 Feb 15;5(2):144-53
18250206
Am J Respir Crit Care Med. 2014 Feb 1;189(3):373-4
24484350
N Engl J Med. 2005 Nov 10;353(19):2034-41
16282178
Eur Respir J. 1997 Nov;10(11):2573-7
9426097
Thorax. 2007 Oct;62(10):861-7
17412778
Sleep. 1992 Apr;15(2):173-84
11032543
Expert Opin Ther Targets. 2009 Jul;13(7):795-809
19530985
Chest. 1985 Apr;87(4):432-6
3979129
Sleep. 1999 Feb 1;22(1):69-75
9989367
J Physiol. 2007 Jun 15;581(Pt 3):1193-205
17395627
Am J Respir Crit Care Med. 2004 Mar 1;169(5):623-33
14684560
Am Rev Respir Dis. 1984 Feb;129(2):247-50
6421210
Sleep. 2010 Jun;33(6):739-44
20550013
J Clin Sleep Med. 2009 Dec 15;5(6):519-24
20465017
Eur Respir J. 2008 Jun;31(6):1308-12
18256066
Am Rev Respir Dis. 1990 Aug;142(2):295-300
2382892
Circ Res. 1988 Mar;62(3):620-31
3342479