RT Journal Article
SR Electronic
T1 The effect of acute morphine on obstructive sleep apnoea: a randomised double-blind placebo-controlled crossover trial
JF Thorax
JO Thorax
FD BMJ Publishing Group Ltd and British Thoracic Society
SP 177
OP 184
DO 10.1136/thoraxjnl-2018-211675
VO 74
IS 2
A1 Luke Rowsell
A1 Keith K H Wong
A1 Brendon J Yee
A1 Danny J Eckert
A1 Andrew A Somogyi
A1 James Duffin
A1 Ronald R Grunstein
A1 David Wang
YR 2019
UL http://thorax.bmj.com/content/74/2/177.abstract
AB Objective Anaesthesiology guidelines suggest that opioids worsen obstructive sleep apnoea (OSA) despite no randomised controlled trial evidence. We therefore conducted a randomised controlled trial to evaluate the effects of a common clinical dose of morphine on OSA, and to identify clinical phenotype and genotype vulnerability to opioid-respiratory depression.Methods Under a double-blind, randomised, crossover design, 60 male patients with OSA attended two visits to the hospital sleep laboratory, at least 1 week apart. Either 40 mg controlled-release oral morphine or placebo was administered. Awake ventilatory chemoreflex tests were performed post dose and prior to overnight polysomnography monitoring. Blood was sampled before sleep and the next morning for toxicology and genotype analyses. Sleep time with oxygen saturation (SpO2) <90% (T90) was the primary outcome.Results Despite a large inter-individual variability, 40 mg morphine did not worsen T90 and apnoea–hypopnoea index, and only decreased the SpO2 nadir by 1.3%. In patients with severe OSA, a lower baseline CO2ventilatory response threshold correlated with the worsening of T90, apnoea–hypopnoea index and oxygen desaturation index with morphine use. Patients with OSA and the A118G OPRM1 polymorphism of A/A and A/G had a significantly different morphine effect on awake ventilatory chemosensitivity and T90 during sleep.Conclusions 40 mg oral controlled-release morphine did not worsen OSA in men, challenging traditional thinking that OSA will be worsened by opioids. Individual opioid response in patients with OSA may relate to baseline CO2 response threshold and OPRM1 genotype. Our study findings may pave the way for a precision medicine approach to avoid opioid-related risks.Trial registration number The Australian and New Zealand Clinical Trial Registry, ACTRN12613000858796.