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Effects of opioid, hypnotic and sedating medications on sleep-disordered breathing in adults with obstructive sleep apnoea

Overview of attention for article published in Cochrane database of systematic reviews, July 2015
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (85th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (52nd percentile)

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17 tweeters
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Effects of opioid, hypnotic and sedating medications on sleep-disordered breathing in adults with obstructive sleep apnoea
Published in
Cochrane database of systematic reviews, July 2015
DOI 10.1002/14651858.cd011090.pub2
Pubmed ID

Martina Mason, Christopher J Cates, Ian Smith


Obstructive sleep apnoea (OSA) is a common sleep disorder characterised by partial or complete upper airway occlusion during sleep, leading to intermittent cessation (apnoea) or reduction (hypopnoea) of airflow and dips in arterial oxygen saturation during sleep. Many patients with recognised and unrecognised OSA receive hypnotics, sedatives and opiates/opioids to treat conditions including pain, anxiety and difficulty sleeping. Concerns have been expressed that administration of these drugs to people with co-existing OSA may worsen OSA. To investigate whether administration of sedative and hypnotic drugs exacerbates the severity of OSA (as measured by the apnoea-hypopnoea index (AHI) or the 4% oxygen desaturation index (ODI)) in people with known OSA. We searched the Cochrane Airways Group Specialised Register (CAGR) of trials. The search was current as of March 2015. Randomised, placebo-controlled trials including adult participants with confirmed OSA, where participants were randomly assigned to use opiates or opioids, sedatives, hypnotics or placebo. We included participants already using continuous positive airway pressure (CPAP) or a mandibular advancement device. We used standard methodological procedures as recommended by The Cochrane Collaboration. Fourteen studies examining the effects of 10 drugs and including a total of 293 participants contributed to this review. Trials were small, with only two trials, which used sodium oxybate, recruiting more than 40 participants, and all but three trials were of only one to three nights in duration. Most participants had mild to moderate OSA with a mean AHI of 11 to 25 events/h, and only two trials recruited patients with severe OSA. Two trials investigating the effects of ramelteon, a treatment option for insomnia, recruited adults over 60 years of age with OSA and concomitant insomnia.The drugs studied in this review included remifentanil (infusion) 0.75 mcg/kg/h, eszopiclone 3 mg, zolpidem 10 and 20 mg, brotizolam 0.25 mg, flurazepam 30 mg, nitrazepam 10 mg to 15 mg, temazepam 10 mg, triazolam 0.25 mg, ramelteon 8 mg and 16 mg and sodium oxybate 4.5 g and 9 g. We were unable to pool most of the data, with the exception of data for eszopiclone and ramelteon.None of the drugs in this review produced a significant increase in AHI or ODI. Two trials have shown a beneficial effect on OSA. One study showed that a single administration of eszopiclone 3 mg significantly decreased AHI compared with placebo (24 ± 4 vs 31 ± 5; P value < 0.05), and a second study of sodium oxybate 4.5 g showed a significant decrease in AHI compared with placebo (mean difference (MD) -7.41, 95% confidence interval (CI) -14.17 to -0.65; N = 48).Only four trials reported outcome data on ODI. No significant increase, in comparison with placebo, was shown with eszopiclone (21 (22 to 37) vs 28.0 (15 to 36); P value = NS), zolpidem (0.81 ± 0.29 vs 1.46 ± 0.53; P value = NS), flurazepam (18.6 ± 19 vs 19.6 ± 15.9; P value = NS) and temazepam (6.53 ± 9.4 vs 6.56 ± 8.3; P value = 0.98).A significant decrease in minimum nocturnal peripheral capillary oxygen saturation (SpO2) was observed with zolpidem 20 mg (76.8 vs 85.2; P value = 0.002), flurazepam 30 mg (81.7 vs 85.2; P value = 0.002), remifentanil infusion (MD -7.00, 95% CI -11.95 to -2.05) and triazolam 0.25 mg in both rapid eye movement (REM) and non-REM (NREM) sleep (MD -14.00, 95% CI -21.84 to -6.16; MD -10.20, 95% CI -16.08 to -4.32, respectively.One study investigated the effect of an opiate (remifentanil) on patients with moderate OSA. Remifentanil infusion did not significantly change AHI (MD 10.00, 95% CI -9.83 to 29.83); however it did significantly decrease the number of obstructive apnoeas (MD -9.00, 95% CI -17.40 to -0.60) and significantly increased the number of central apnoeas (MD 16.00, 95% CI -2.21 to 34.21). Similarly, although without significant effect on obstructive apnoeas, central apnoeas were increased in the sodium oxybate 9 g treatment group (MD 7.3 (18); P value = 0.005) in a cross-over trial.Drugs studied in this review were generally well tolerated, apart from adverse events reported in 19 study participants prescribed remifentanil (n = 1), eszopiclone (n = 6), sodium oxybate (n = 9) or ramelteon (n = 3). The findings of this review show that currently no evidence suggests that the pharmacological compounds assessed have a deleterious effect on the severity of OSA as measured by change in AHI or ODI. Significant clinical and statistical decreases in minimum overnight SpO2 were observed with remifentanil, zolpidem 20 mg and triazolam 0.25 mg. Eszopiclone 3 mg and sodium oxybate 4.5 g showed a beneficial effect on the severity of OSA with a reduction in AHI and may merit further assessment as a potential therapeutic option for a subgroup of patients with OSA. Only one trial assessed the effect of an opioid (remifentanil); some studies included CPAP treatment, whilst in a significant number of participants, previous treatment with CPAP was not stated and thus a residual treatment effect of CPAP could not be excluded. Most studies were small and of short duration, with indiscernible methodological quality.Caution is therefore required when such agents are prescribed for patients with OSA, especially outside the severity of the OSA cohorts and the corresponding dose of compounds given in the particular studies. Larger, longer trials involving patients across a broader spectrum of OSA severity are needed to clarify these results.

Twitter Demographics

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Mendeley readers

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Geographical breakdown

Country Count As %
Brazil 2 <1%
United States 1 <1%
Spain 1 <1%
Unknown 211 98%

Demographic breakdown

Readers by professional status Count As %
Student > Master 38 18%
Student > Bachelor 28 13%
Researcher 27 13%
Student > Ph. D. Student 18 8%
Student > Postgraduate 15 7%
Other 39 18%
Unknown 50 23%
Readers by discipline Count As %
Medicine and Dentistry 88 41%
Nursing and Health Professions 25 12%
Pharmacology, Toxicology and Pharmaceutical Science 10 5%
Psychology 9 4%
Social Sciences 8 4%
Other 15 7%
Unknown 60 28%

Attention Score in Context

This research output has an Altmetric Attention Score of 11. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 04 February 2017.
All research outputs
of 15,641,217 outputs
Outputs from Cochrane database of systematic reviews
of 11,229 outputs
Outputs of similar age
of 232,973 outputs
Outputs of similar age from Cochrane database of systematic reviews
of 260 outputs
Altmetric has tracked 15,641,217 research outputs across all sources so far. Compared to these this one has done well and is in the 88th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 11,229 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 23.3. This one has gotten more attention than average, scoring higher than 59% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 232,973 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 85% of its contemporaries.
We're also able to compare this research output to 260 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 52% of its contemporaries.