|dc.contributor.author||Rowsell, Luke Joshua||-|
|dc.description.abstract||This thesis aims to evaluate the effect of 40mg oral slow release morphine on obstructive sleep apnea (OSA) and awake ventilatory chemoreflexes in 60 OSA men in a randomised, double-blind placebo controlled crossover study. The study attempts to phenotype and genotype the potentially large variability of OSA response to a common dose of morphine using cutting edge techniques.
We found that morphine caused mild respiratory depression but did not affect the percent of TST spent below 90% oxygen saturation (T90), nor apnea-hypopnea index (AHI). However, large inter-individual variability was observed. Morphine tended to improve T90 in A/G vs A/A OPRM1 genotype subjects. 2. Morphine reduced slow wave sleep and rapid eye movement (REM) sleep overall, however did not attenuate REM sleep in subjects with (CT + TT) vs CC HTR3B genotype. Total sleep time (TST) increased following morphine in C/C vs (C/T + T/T) ABCB1 genotype subjects only. 3. CO2 ventilatory recruitment threshold (VRT) was increased and hypercapnic/hypoxic ventilatory response (HCVR/HVR) was depressed overall. HCVR depression following morphine was greater in A/G vs A/A OPRM1 subjects, and C/C vs (C/T + T/T) ABCB1 subjects. 4. A mechanism by which morphine may improve OSA in some OSA patients through reducing chemosensitivity and widening CO2 reserve was proposed. 5. Negative linear relationships were found in severe OSA patients between baseline VRT and morphine effect on AHI, oxygen desaturation index, arousal index and T90. 6. Subjects with extreme improvement in T90 following morphine were older, had higher VRT and were often A/G OPRM1 genotype compared to those with greatest deterioration.
In conclusion, 40mg morphine on average only caused mild respiratory depression but with a large variability in men with OSA. The large inter-individual variability may be partly explained by baseline awake chemoreflexes. Certain genotypes associated with differential morphine effect on OSA were identified.||en_AU|
|dc.publisher||University of Sydney||en_AU|
|dc.publisher||Sydney Medical School||en_AU|
|dc.publisher||Central Clinical School||en_AU|
|dc.rights||The author retains copyright of this thesis. It may only be used for the purposes of research and study. It must not be used for any other purposes and may not be transmitted or shared with others without prior permission.||en_AU|
|dc.subject||obstructive sleep apnea||en_AU|
|dc.title||The Effect of Acute Oral Morphine on Obstructive Sleep Apnea||en_AU|
|dc.type.pubtype||Doctor of Philosophy Ph.D.||en_AU|
|dc.description.disclaimer||Access is restricted to staff and students of the University of Sydney . UniKey credentials are required. Non university access may be obtained by visiting the University of Sydney Library.||en_AU|
|Appears in Collections:||Sydney Digital Theses (University of Sydney Access only)|