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Zopiclone effects on breathing at sleep in stable chronic obstructive pulmonary disease

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Abstract

Purpose

More than half of patients with chronic obstructive pulmonary disease (COPD) experiences sleep-related problems and about one fourth uses hypnotics regularly. We explored what the effect zopiclone, a commonly used hypnotic, had on nocturnal gas exchange and the apnea/hypopnea frequency in stable COPD.

Methods

Randomized crossover study of 31 (ten males) inpatients at a pulmonary rehabilitation hospital, median age 64 years, of which 20 had a forced expiratory volume first second <50 % of predicted. Subjects investigated in randomized order of either baseline sleep or intervention with 5 mg zopiclone by polysomnography including transcutaneous measurement of carbon dioxide pressure increased (ΔPtcCO2).

Results

Zopiclone increased the mean ΔPtcCO2 from baseline both in rapid eye movement (REM) sleep, non-REM sleep, and even in stage N0 (awake after sleep onset) with a mean (SD) of 0.25 (0.40) kPa, 0.22 (0.32) kPa, and 0.14 (0.27) kPa, respectively. Subjects with sleep hypoventilation as defined by the American Academy of Sleep Medicine increased from 6 subjects (19 %) to 13 subjects (42 %) (P = 0.020). REM sleep minimum oxygen saturation (minSpO2) did not change significantly from baseline median (interquartile range [IQR]) minSpO2 81.8 (12.1) % to zopiclone sleep median (IQR) minSpO2 80.0 (12.0) % (P = 0.766). Interestingly, zopiclone reduced the number of apneas/hypopneas per hour (AHI) in subjects with overlap (AHI ≥ 15) with a median difference (IQR) of −8.5 (7.8) (N = 11, P = 0.016).

Conclusions

In stable COPD, zopiclone moderately increases the mean ΔPtcCO2 without changing minSpO2 at night and reduces AHI in overlap (COPD and obstructive sleep apnea) subjects.

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Notes

  1. According to the AASM, SH is scored when there is an increase in the PaCO2 (or surrogate) ≥10 mmHg ([1.3 kPa] in comparison to an awake supine value) to a value exceeding 50 mmHg (6.7 kPa) for ≥10 min or the PaCO2 (or surrogate) >55 mmHg (7.3 kPa) for ≥10 min [18]

  2. PICO50, Radiometer, Copenhagen, Denmark

  3. Radiometer, Copenhagen, Denmark

  4. Medcare Flaga, Reykjavik, Iceland

  5. Radiometer, Basel, Switzerland

  6. In a previous study of 100 COPD subjects [22], the mean increase (standard deviation) in PtcCO2 during spontaneous sleep was 0.49 (0.32) kPa.

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Acknowledgments

PSG hardware and software were provided by ResMed, Norway. The authors wish to thank the staff at Glittreklinikken for the enthusiastic support and participation in the data collection. Financial support was received from the Norwegian ExtraFoundation for Health and Rehabilitation, LHL’s Research fund, Glittreklinikken, and the Norwegian National Centre of Excellence in Home Mechanical Ventilation. Minor grants were received from the Norwegian Lung Medicine Society/Takeda Nycomed, Major Eckbo’s endowments, and the University of Bergen.

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Authors and Affiliations

  1. LHL-klinikkene Glittre, Glittreklinikken, postboks 104 Åneby, 1485, Hakadal, Norway

    Nils Henrik Holmedahl & Ivar Ellingsen

  2. ENT Department, Lovisenberg Diakonale Hospital, Oslo, Norway

    Britt Øverland

  3. Norwegian National Centre of Excellence in Home Mechanical Ventilation, Haukeland University Hospital, Bergen, Norway

    Ove Fondenes

  4. Department of Clinical Science, University of Bergen, Bergen, Norway

    Nils Henrik Holmedahl & Jon Andrew Hardie

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  1. Nils Henrik Holmedahl
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Correspondence to Nils Henrik Holmedahl.

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Holmedahl, N.H., Øverland, B., Fondenes, O. et al. Zopiclone effects on breathing at sleep in stable chronic obstructive pulmonary disease. Sleep Breath 19, 921–930 (2015). https://doi.org/10.1007/s11325-014-1084-8

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