Vulnerability to opioid-related respiratory depression in obstructive sleep apnea

Summary

The proposed study is aiming to identify sleep apnea patients and normal individuals most vulnerable to opioid-induced respiratory depression, using novel respiratory techniques.

Supervisor(s)

Dr David Wang

Research Location

Woolcock Institute of Medical Research

Program Type

Masters/PHD

Synopsis

Prescription opioid poisoning deaths have increased substantially in recent years. Acute opioid use reduces vital ventilatory chemoreflexes as well as upper airway patency, therefore obstructive sleep apnea (OSA) is a major risk factor for postoperative morbidity and mortality. However, there is a large inter-individual variability among OSA patients and normal individuals in response to opioids. It is important to develop a clinically useful approach to identify those individuals most vulnerable to opioid-induced respiratory depression.In our pilot study, we found that subjects with higher central chemosensitivity had significantly worse respiratory depression during sleep with the use of a mild CNS depressant (temazepam). We hypothesise that the effect will be magnified using a stronger CNS depressant such as morphine. If this hypothesis can be verified, then a simple 10-minute ventilatory chemoreflex test may help to identify those OSA patients and normal subjects most vulnerable to opioid-induced respiratory depression.Using a double-blind, placebo-controlled and cross-over design, 80 men (20 respectively in 4 subgroups of mild, moderate, severe OSA, and normal subjects) will undergo two polysomnographic sleep studies using either 30mg of oral morphine (MS Contin) or placebo. Baseline ventilatory chemoreflexes will be tested twice. Blood samples will be taken before and after sleep. We are aiming to test whether individual vulnerability to opioid-induced respiratory depression is related to baseline ventilatory chemosensitivity (primary outcome), to opioid metabolism variability, and/or to genetic polymorphism (secondary outcomes). This is a potentially pivotal study in the quest to minimize the soaring number of opioid-related deaths.

Keywords

Sleep, opioid, control of breathing, Sleep apnea, Pain

Opportunity ID

The opportunity ID for this research opportunity is: 1187