An observational study of the severity of respiratory depression in chronic opioid dependence

First published: 10 May 2019 | Last updated: 20 May 2019


Opioid-related deaths are at an all-time high in the UK (ONS,2016), with a 64% increase since 2014.  Opioid agonists (e.g. heroin, morphine and methadone) have an inhibitory action at respiratory centres in the brain. Respiratory depression occurs when this action leads to a depreciative and disruptive effect on regular breathing rhythm and neural respiratory drive, and impairs the adequately balanced levels of blood oxygen and carbon dioxide. Death by opioid overdose is usually from respiratory failure (Goodman & Gilman, 2011). Our previous findings suggest that the degree of acute opioid-induced respiratory depression is greatest in opioid-dependent patients (ODP) with chronically-suppressed neural respiratory drive (signals coming from the brain to the breathing muscles; NRD) as a consequence of problematic drug use (Jolley et al 2015).

An observational physiological study was conducted in order to investigate whether ODP exhibit more severe respiratory depression than matched non-drug-dependent controls.


A convenience sample of seven opioid-maintained patients with normal lung function attending a local community Drug & Alcohol Treatment Centre were matched with seven healthy controls with no history of drug/alcohol addiction. Matched variables included age, body mass index (BMI), gender and lung function (as measured by a pulmonary function test).

Continuous measurements of respiratory outcome measures were taken over 40mins at rest in a clinical respiratory laboratory setting: SpO2%, end-tidal CO2 (ETCO2), transcutaneous CO2 (TcCO2), respiratory airflow and NRD, as quantified using second intercostal space parasternal muscle electromyography (EMGpara).

Significant respiratory depression was defined as: SpO2%<90% for >10s, ETCO2 per breath >6.5kPa, TcCO2 overall mean >6.5kPa, respiratory pauses >10s.


Physiological criteria that demonstrated significant respiratory depression: ETCO2 and TcCO2 in 5/7 and 3/7 ODP, respectively (compared to 2/7 and 0/7 healthy controls, respectively), and SpO2% in 2/7 ODP and 0/7 healthy controls. Respiratory pauses were seen in 5/7 ODP and 0/7 healthy controls. Overall, there was a greater frequency of significant respiratory depression in ODP (p=0.021 Fisher’s exact test) than in healthy controls. There was also a trend towards an inverse relationship between 1) EMGpara and ETCO2 (r=-0.36, p=0.2) and 2) EMGpara and TcCO2 (r=-0.45, p=0.1).


ODP exhibit significant respiratory depression in everyday life. In some patients apnoeas and peak ETCO2 reached levels approaching thresholds that would be considered near-life-threatening under usual clinical circumstances. Further studies are required to determine the association between respiratory depression and overdose risk.


Dr PSP Cho: Division of Asthma, Allergy & Lung Biology, King ‘s College London, UK. Dr M Lozano-Garcia: Biomedical Signal Processing and Interpretation group, Institute for Bioengineering of Catalonia (IBEC) & Biomedical Research Networking Centre in Bio

Basak Tas