Undetected Respiratory Depression in People with Opioid Use Disorder

B. Tas; N. J. Kalk; M. Lozano- García; G. F. Rafferty; P. S.P. Cho; M. Kelleher; J. Moxham; J. Strang; C. J. Jolley

doi:10.1016/j.drugalcdep.2022.109401

Undetected Respiratory Depression in People with Opioid Use Disorder

B. Tas^*, N. J. Kalk, M. Lozano- García, G. F. Rafferty, P. S.P. Cho, M. Kelleher, J. Moxham, J. Strang, C. J. Jolley

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

Background: Opioid-related deaths are increasing globally. Respiratory complications of opioid use and underlying respiratory disease in people with Opioid Use Disorder (OUD) are potential contributory factors. Individual variation in susceptibility to overdose is, however, incompletely understood. This study investigated the prevalence of respiratory depression (RD) in OUD treatment and compared this to patients with chronic obstructive pulmonary disease (COPD) of equivalent severity. We also explored the contribution of opioid agonist treatment (OAT) dosage, and type, to the prevalence of RD. Methods: There were four groups of participants: 1) OUD plus COPD (‘OUD-COPD’, n = 13); 2) OUD without COPD (‘OUD’, n = 7); 3) opioid-naïve COPD patients (‘COPD'n = 13); 4) healthy controls (‘HC'n = 7). Physiological indices, including pulse oximetry (SpO₂%), end-tidal CO₂ (ETCO₂), transcutaneous CO₂ (TcCO₂), respiratory airflow and second intercostal space parasternal muscle electromyography (EMG_para), were recorded continuously over 40 min whilst awake at rest. Significant RD was defined as: SpO₂%< 90% for > 10 s, ETCO₂ per breath > 6.6 kPa, TcCO₂ overall mean > 6 kPa, respiratory pauses > 10 s Results: At least one indicator was observed in every participant with OUD (n = 20). This compared to RD episode occurrence in only 2/7 HC and 2/13 COPD participants (p < 0.05,Fisher's exact test). The occurrence of RD was similar in OUD participants prescribed methadone (n = 6) compared to those prescribed buprenorphine (n = 12). Conclusions: Undetected RD is common in OUD cohorts receiving OAT and is significantly more severe than in opioid-naïve controls. RD can be assessed using simple objective measures. Further studies are required to determine the association between RD and overdose risk.

Original language	English
Article number	109401
Journal	Drug and alcohol dependence
Volume	234
Early online date	10 Mar 2022
DOIs	https://doi.org/10.1016/j.drugalcdep.2022.109401
Publication status	Published - 1 May 2022

Keywords

Comorbidity
Lung disease
Opioid substitution treatment
Opioids
Overdose
Respiratory depression

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.drugalcdep.2022.109401

Undetected Respiratory Depression in_TAS_Publishedonline1May2022_GREEN AAMAccepted author manuscript, 323 KBLicence: CC BY-NC-ND

Cite this

@article{333dc9abe6014ea78515c4227c050fbf,

title = "Undetected Respiratory Depression in People with Opioid Use Disorder",

abstract = "Background: Opioid-related deaths are increasing globally. Respiratory complications of opioid use and underlying respiratory disease in people with Opioid Use Disorder (OUD) are potential contributory factors. Individual variation in susceptibility to overdose is, however, incompletely understood. This study investigated the prevalence of respiratory depression (RD) in OUD treatment and compared this to patients with chronic obstructive pulmonary disease (COPD) of equivalent severity. We also explored the contribution of opioid agonist treatment (OAT) dosage, and type, to the prevalence of RD. Methods: There were four groups of participants: 1) OUD plus COPD ({\textquoteleft}OUD-COPD{\textquoteright}, n = 13); 2) OUD without COPD ({\textquoteleft}OUD{\textquoteright}, n = 7); 3) opioid-na{\"i}ve COPD patients ({\textquoteleft}COPD'n = 13); 4) healthy controls ({\textquoteleft}HC'n = 7). Physiological indices, including pulse oximetry (SpO2%), end-tidal CO2 (ETCO2), transcutaneous CO2 (TcCO2), respiratory airflow and second intercostal space parasternal muscle electromyography (EMGpara), were recorded continuously over 40 min whilst awake at rest. Significant RD was defined as: SpO2%< 90% for > 10 s, ETCO2 per breath > 6.6 kPa, TcCO2 overall mean > 6 kPa, respiratory pauses > 10 s Results: At least one indicator was observed in every participant with OUD (n = 20). This compared to RD episode occurrence in only 2/7 HC and 2/13 COPD participants (p < 0.05,Fisher's exact test). The occurrence of RD was similar in OUD participants prescribed methadone (n = 6) compared to those prescribed buprenorphine (n = 12). Conclusions: Undetected RD is common in OUD cohorts receiving OAT and is significantly more severe than in opioid-na{\"i}ve controls. RD can be assessed using simple objective measures. Further studies are required to determine the association between RD and overdose risk.",

keywords = "Comorbidity, Lung disease, Opioid substitution treatment, Opioids, Overdose, Respiratory depression",

author = "B. Tas and Kalk, {N. J.} and {Lozano- Garc{\'i}a}, M. and Rafferty, {G. F.} and Cho, {P. S.P.} and M. Kelleher and J. Moxham and J. Strang and Jolley, {C. J.}",

note = "Funding Information: This research was conducted as part of a PhD studentship, funded departmentally at King{\textquoteright}s College London and the article was prepared with support from the Society for the Study of Addiction as well as the NIHR Biomedical Research Centre at Maudsley. Funding Information: BT is supported by the National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and King's College London. Funding Information: Thank you to staff at the Chest Unit, King's College Hospital and at Lorraine Hewitt House, South London and the Maudsley NHS Trust. CJJ, GFR, JM, ML-G declare no conflict of interest. BT is supported by the National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and King's College London. NJK's research is supported by the National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and King's College London. PSPC reports an investigator-initiated grant with Merck on a project outside of the submitted work. MK has carried out research funded by Indivior, Camerus and Mundipharma and received honoraria from Gilead. JS: JS is a researcher and clinician who has worked with a range of governmental and non-governmental organisations, and with pharmaceutical companies to seek to identify new or improved treatments from whom he and his employer (King's College London) have received honoraria, travel costs and/or consultancy payments: this includes, last 3 years, MundiPharma, Camurus, Accord/Molteni Farma and trial medication supply from Camurus. For a fuller account, see athttp://www.kcl.ac.uk/ioppn/depts/addictions/people/hod.aspx. JS's research is supported by the National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and King's College London. JS is an NIHR Senior Investigator. Funding Information: NJK's research is supported by the National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and King's College London. Funding Information: MK has carried out research funded by Indivior, Camerus and Mundipharma and received honoraria from Gilead. Publisher Copyright: {\textcopyright} 2022 Elsevier B.V.",

year = "2022",

month = may,

day = "1",

doi = "10.1016/j.drugalcdep.2022.109401",

language = "English",

volume = "234",

journal = "Drug and alcohol dependence",

issn = "0376-8716",

publisher = "Elsevier",

}

TY - JOUR

T1 - Undetected Respiratory Depression in People with Opioid Use Disorder

AU - Tas, B.

AU - Kalk, N. J.

AU - Lozano- García, M.

AU - Rafferty, G. F.

AU - Cho, P. S.P.

AU - Kelleher, M.

AU - Moxham, J.

AU - Strang, J.

AU - Jolley, C. J.

N1 - Funding Information: This research was conducted as part of a PhD studentship, funded departmentally at King’s College London and the article was prepared with support from the Society for the Study of Addiction as well as the NIHR Biomedical Research Centre at Maudsley. Funding Information: BT is supported by the National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and King's College London. Funding Information: Thank you to staff at the Chest Unit, King's College Hospital and at Lorraine Hewitt House, South London and the Maudsley NHS Trust. CJJ, GFR, JM, ML-G declare no conflict of interest. BT is supported by the National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and King's College London. NJK's research is supported by the National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and King's College London. PSPC reports an investigator-initiated grant with Merck on a project outside of the submitted work. MK has carried out research funded by Indivior, Camerus and Mundipharma and received honoraria from Gilead. JS: JS is a researcher and clinician who has worked with a range of governmental and non-governmental organisations, and with pharmaceutical companies to seek to identify new or improved treatments from whom he and his employer (King's College London) have received honoraria, travel costs and/or consultancy payments: this includes, last 3 years, MundiPharma, Camurus, Accord/Molteni Farma and trial medication supply from Camurus. For a fuller account, see athttp://www.kcl.ac.uk/ioppn/depts/addictions/people/hod.aspx. JS's research is supported by the National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and King's College London. JS is an NIHR Senior Investigator. Funding Information: NJK's research is supported by the National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and King's College London. Funding Information: MK has carried out research funded by Indivior, Camerus and Mundipharma and received honoraria from Gilead. Publisher Copyright: © 2022 Elsevier B.V.

PY - 2022/5/1

Y1 - 2022/5/1

N2 - Background: Opioid-related deaths are increasing globally. Respiratory complications of opioid use and underlying respiratory disease in people with Opioid Use Disorder (OUD) are potential contributory factors. Individual variation in susceptibility to overdose is, however, incompletely understood. This study investigated the prevalence of respiratory depression (RD) in OUD treatment and compared this to patients with chronic obstructive pulmonary disease (COPD) of equivalent severity. We also explored the contribution of opioid agonist treatment (OAT) dosage, and type, to the prevalence of RD. Methods: There were four groups of participants: 1) OUD plus COPD (‘OUD-COPD’, n = 13); 2) OUD without COPD (‘OUD’, n = 7); 3) opioid-naïve COPD patients (‘COPD'n = 13); 4) healthy controls (‘HC'n = 7). Physiological indices, including pulse oximetry (SpO2%), end-tidal CO2 (ETCO2), transcutaneous CO2 (TcCO2), respiratory airflow and second intercostal space parasternal muscle electromyography (EMGpara), were recorded continuously over 40 min whilst awake at rest. Significant RD was defined as: SpO2%< 90% for > 10 s, ETCO2 per breath > 6.6 kPa, TcCO2 overall mean > 6 kPa, respiratory pauses > 10 s Results: At least one indicator was observed in every participant with OUD (n = 20). This compared to RD episode occurrence in only 2/7 HC and 2/13 COPD participants (p < 0.05,Fisher's exact test). The occurrence of RD was similar in OUD participants prescribed methadone (n = 6) compared to those prescribed buprenorphine (n = 12). Conclusions: Undetected RD is common in OUD cohorts receiving OAT and is significantly more severe than in opioid-naïve controls. RD can be assessed using simple objective measures. Further studies are required to determine the association between RD and overdose risk.

AB - Background: Opioid-related deaths are increasing globally. Respiratory complications of opioid use and underlying respiratory disease in people with Opioid Use Disorder (OUD) are potential contributory factors. Individual variation in susceptibility to overdose is, however, incompletely understood. This study investigated the prevalence of respiratory depression (RD) in OUD treatment and compared this to patients with chronic obstructive pulmonary disease (COPD) of equivalent severity. We also explored the contribution of opioid agonist treatment (OAT) dosage, and type, to the prevalence of RD. Methods: There were four groups of participants: 1) OUD plus COPD (‘OUD-COPD’, n = 13); 2) OUD without COPD (‘OUD’, n = 7); 3) opioid-naïve COPD patients (‘COPD'n = 13); 4) healthy controls (‘HC'n = 7). Physiological indices, including pulse oximetry (SpO2%), end-tidal CO2 (ETCO2), transcutaneous CO2 (TcCO2), respiratory airflow and second intercostal space parasternal muscle electromyography (EMGpara), were recorded continuously over 40 min whilst awake at rest. Significant RD was defined as: SpO2%< 90% for > 10 s, ETCO2 per breath > 6.6 kPa, TcCO2 overall mean > 6 kPa, respiratory pauses > 10 s Results: At least one indicator was observed in every participant with OUD (n = 20). This compared to RD episode occurrence in only 2/7 HC and 2/13 COPD participants (p < 0.05,Fisher's exact test). The occurrence of RD was similar in OUD participants prescribed methadone (n = 6) compared to those prescribed buprenorphine (n = 12). Conclusions: Undetected RD is common in OUD cohorts receiving OAT and is significantly more severe than in opioid-naïve controls. RD can be assessed using simple objective measures. Further studies are required to determine the association between RD and overdose risk.

KW - Comorbidity

KW - Lung disease

KW - Opioid substitution treatment

KW - Opioids

KW - Overdose

KW - Respiratory depression

UR - http://www.scopus.com/inward/record.url?scp=85126625998&partnerID=8YFLogxK

U2 - 10.1016/j.drugalcdep.2022.109401

DO - 10.1016/j.drugalcdep.2022.109401

M3 - Article

AN - SCOPUS:85126625998

SN - 0376-8716

VL - 234

JO - Drug and alcohol dependence

JF - Drug and alcohol dependence

M1 - 109401

ER -

Undetected Respiratory Depression in People with Opioid Use Disorder

Abstract

Keywords

UN SDGs

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