Heroin-induced respiratory depression and the influence of dose variation: within-subject between-session changes following dose reduction

TY - JOUR

T1 - Heroin-induced respiratory depression and the influence of dose variation: within-subject between-session changes following dose reduction

AU - Tas, Basak

AU - Jolley, Caroline

AU - Kalk, Nicola

AU - Bell, James

AU - Strang, John

AU - van der Waal, Robert

PY - 2020/10

Y1 - 2020/10

N2 - Background and aims: Globally, more than 100 000 people die annually from opioid overdose. Opportunities to study physiological events in at-risk individuals are limited. This study examined variation of opioid dose and impact on respiratory depression in a chronic injecting heroin user at separate time-points during his long-term diamorphine maintenance treatment. Design: A single-subject study over 5 years during which participant underwent experimental studies on diamorphine-induced respiratory depression, at changing maintenance doses. Setting: A clinical research facility. Participant. Male subject on long-term injectable diamorphine (pharmaceutical heroin) maintenance treatment for heroin addiction. Measurements: Physiological measures of oxygen saturation (SpO 2), end-tidal carbon dioxide (ETCO 2) and respiratory rate (RR) were used to indicate severity of respiratory depression. Findings: (1) After diamorphine injection, respiratory regulation became abnormal, with prolonged apnoea exceeding 20 sec (maximum 56 sec), elevated ETCO 2 (maximum 6.9%) and hypoxaemia (minimum SpO 2 80%). (2) Abnormalities were greater with highest diamorphine dose: average SpO 2 was 89.3% after 100 mg diamorphine versus 93.6% and 92.8% for the two 30-mg doses. (3) However, long apnoeic pauses and high levels of ETCO 2% were also present after lower doses. Conclusions: With marked inter-session variability, these findings corroborate observations of inconsistent relationships between opioid dose and overdose risk.

AB - Background and aims: Globally, more than 100 000 people die annually from opioid overdose. Opportunities to study physiological events in at-risk individuals are limited. This study examined variation of opioid dose and impact on respiratory depression in a chronic injecting heroin user at separate time-points during his long-term diamorphine maintenance treatment. Design: A single-subject study over 5 years during which participant underwent experimental studies on diamorphine-induced respiratory depression, at changing maintenance doses. Setting: A clinical research facility. Participant. Male subject on long-term injectable diamorphine (pharmaceutical heroin) maintenance treatment for heroin addiction. Measurements: Physiological measures of oxygen saturation (SpO 2), end-tidal carbon dioxide (ETCO 2) and respiratory rate (RR) were used to indicate severity of respiratory depression. Findings: (1) After diamorphine injection, respiratory regulation became abnormal, with prolonged apnoea exceeding 20 sec (maximum 56 sec), elevated ETCO 2 (maximum 6.9%) and hypoxaemia (minimum SpO 2 80%). (2) Abnormalities were greater with highest diamorphine dose: average SpO 2 was 89.3% after 100 mg diamorphine versus 93.6% and 92.8% for the two 30-mg doses. (3) However, long apnoeic pauses and high levels of ETCO 2% were also present after lower doses. Conclusions: With marked inter-session variability, these findings corroborate observations of inconsistent relationships between opioid dose and overdose risk.

KW - Depression

KW - HAT

KW - heroin

KW - opioid

KW - overdose

KW - respiratory

UR - http://www.scopus.com/inward/record.url?scp=85081403019&partnerID=8YFLogxK

U2 - 10.1111/add.15014

DO - 10.1111/add.15014

M3 - Article

SN - 0965-2140

VL - 115

SP - 1954

EP - 1959

JO - Addiction

JF - Addiction

IS - 10

ER -