PhD Student

PhD Student

Background: Globally, more than 100,000 people die annually from opioid overdose, and this number continues to increase. In the UK, opioid-related deaths are at an all-time high. Respiratory depressant effects of opioids (e.g. heroin) include impaired chemo-responsiveness to disturbed blood gas homeostasis (oxygen (O2) and carbon dioxide (CO2)) as well as reduced neural respiratory drive (signals coming from brain to breathing muscles). Although implicated in heroin overdose deaths, acute opioid-induced respiratory depression is poorly understood.

Aim: To investigate the acute physiological responses to incremental dose increases of injected pharmaceutical heroin (diamorphine) in a laboratory setting.

Methods: Participants: patients prescribed long-term diamorphine maintenance treatment. Dose schedule (% usual prescribed diamorphine dose): Visit 1  –  100%; Visit 2 – 110%; Visit 3 – 120%; Visit 4 – 100%. Measurements: Pulse oximetry (SpO2%), end-tidal CO2 , transcutaneous CO2 , respiratory airflow and neural respiratory drive (NRD), quantified using parasternal intercostal muscle electromyography (EMGpara). Recordings were made continuously from 3 minutes pre-dose to 60 minutes post-dose.

Results: Preliminary findings for three participants show significant respiratory depression post-dose in every dosing session with a distinctive intermittent breathing pattern, prolonged periods of apnoea, and resultant raised CO2 and hypoxaemia. There was significant inter-individual variability in the degree of additional respiratory depression observed following incremental doses of diamorphine.

Discussion: The magnitude of respiratory depressant effects of incremental dose increases in diamorphine is unpredictable and subject to inter-individual variability. This gives an experimental insight into the phenomenon of heroin overdose which we consider essential to inform better public response to the overdose crisis.

Co-Authors

Basak Tas: National Addiction Centre, Institute of Psychiatry, Psychology & Neuroscience, King ‘s College London Dr Caroline J Jolley: Centre for Human & Applied Physiological Sciences, King’s College London Dr James Bell: National Addiction Centre, Institute of Psychiatry, Psychology & Neuroscience, King ‘s College London Dr Nicola J Kalk: National Addiction Centre, Institute of Psychiatry, Psychology & Neuroscience, King ‘s College London Dr Alastair Boyd: South London and Maudsley NHS Foundation Trust Rob Vanderwaal: South London and Maudsley NHS Foundation Trust Dr Maria Leong: King ‘s College Hospital NHS Trust Dr Gerrard F Rafferty: Centre for Human & Applied Physiological Sciences, King’s College London Professor Sir John Strang: National Addiction Centre, Institute of Psychiatry, Psychology & Neuroscience, King ‘s College London

Conflicts of interest:

BT, CJJ, NJK, AB, RV, ML, GFR declare no conflict of interest.
JS is a researcher and clinician who has worked with a range of types of treatment and rehabilitation service-providers. He has also 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 work with, during past 3 years, Martindale, Reckitt-Benckiser/Indivior, MundiPharma, Braeburn/Camurus and trial medication supply from Camurus and iGen. His employer (King’s College London) has registered intellectual property on a novel buccal naloxone formulation and he has also been named in a patent registration by a Pharma company as inventor of a concentrated nasal naloxone spray. For a fuller account, see JS’s web-page athttp://www.kcl.ac.uk/ioppn/depts/addictions/people/hod.aspx
JB has received consultancy funding from Martindale Pharma, support to attend conferences from Indivior, and fees for acting on an Indivior Advisory Board.