Fatal Opioid Poisoning Research Articles

Receipt of opioid use disorder treatments prior to fatal overdoses and comparison to no treatment in Connecticut, 2016–17

ObjectiveTo determine the relative risk of death following exposure to treatments for OUD compared to no treatment. MethodsIn this retrospective cohort study we compiled and merged state agency data on accidental and undetermined opioid overdose deaths in 2017 and exposures to OUD treatment in the prior six months to determine incidence rates following exposure to different treatment modalities. These rates were compared to the estimated incidence among those exposed to no treatment to determine relative risk of death for each treatment exposure. ResultsIncidence rates for opioid poisoning deaths for those exposed to treatment ranged from 6.06±1.40 per 1000 persons exposed to methadone to 17.36±3.22 per 1000 persons exposed to any non-medication treatment. The estimated incidence rate for those not exposed to treatment was 9.80±0.72 per 1000 persons. With no exposure to treatment as referent, exposure to methadone or buprenorphine reduced the relative risk by 38% or 34%, respectively; the relative risk of non-medication treatments was equal to or worse than no exposure to treatment (RR = 1.27–1.77). Principal conclusionsExposure to non-MOUD treatments provided no protection against fatal opioid poisoning whereas the relative risk was reduced following exposures to MOUD treatment, even if treatment was not continued. Population level efforts to reduce opioid overdose deaths need to focus on expanding access to agonist-based MOUD treatments and are unlikely to succeed if access to non-MOUD treatments is made more available.

Combined effects of quetiapine and opioids: A study of autopsy cases, drug users and sedation in rats.

Fatal opioid poisonings often involve methadone or morphine. This study aimed to elucidate if quetiapine, a widely used sedative antipsychotic medication, may increase the risk of fatal opioid poisoning by additive inhibitory effects on the central nervous system. We used data from 323 cases of fatal methadone or/and morphine poisonings autopsied from 2013 to 2020, a survey of 34 drug users, and performed blinded placebo‐controlled studies in 75 Flinders Resistant Line rats receiving three cumulative intraperitoneal doses of vehicle, methadone (2.5, 10 and 15 mg/kg), morphine (3.75, 15 and 22.5 mg/kg), quetiapine (3, 10 and 30 mg/kg) or quetiapine combined with methadone or morphine. Quetiapine was detected in 20.4% of fatal opioid poisonings with a significantly increased frequency over time, primarily in low or therapeutic concentrations, and was not associated with methadone or morphine concentrations. Use of quetiapine, most commonly in low‐to‐moderate doses to obtain a sleep‐inducing or tranquillizing effect, was reported by 67.6% of survey respondents. In the animal studies, a significant impairment of sedation score, performance on the rotarod and open field mobility was observed in all treatment groups compared with vehicle. However, the effect of quetiapine plus the opioid was not significantly different from that of the opioid alone. Thus, no additive sedative effects were observed in rats. Our results suggest that quetiapine is more often an innocent bystander than a contributor to fatal opioid poisoning. However, the combined effects on other parameters, including blood pressure, cardiac rhythm and respiratory rate, need investigation.

Methadone-related death in detention

Oral methadone may be prescribed to detainees with the aim of minimising the risk of fatal opioid poisoning on release. To study the circumstances under which methadone-related deaths can occur in detention, we audited reports of 17 [14 male, 3 female; median (range) age 34 (22–52) years] such deaths, July 2010–December 2011. The median (range) methadone dose was 40 (10–110) mg/d (N = 16). The median (range) post-mortem blood methadone concentration was 0.42 (0.16–1.40) mg/L. Those who died within 7 days of the commencement of methadone treatment were significantly younger (Mann-Whitney U 102.5, p < 0.05), were prescribed a significantly lower dose (U = 80.0, p < 0.05) and had significantly lower blood methadone concentrations at death (U = 106.5, p < 0.02) than in those given methadone long-term. In 8 reports the prisoner had been recorded as either ‘sleepy’ (N = 7), or ‘unwell’ in the hours before death. In 13 deaths, the prisoner was either found dead first thing in the morning, or in one instance could not be roused (‘snoring heavily’). Pneumonia, tracheobronchitis, end-stage cirrhosis, and ischaemic heart disease/coronary artery atherosclerosis were cited as associated factors in four patients, all of whom were on long term stable methadone treatment. Attention to warning signs of likely methadone toxicity (daytime or excessive drowsiness, snoring, nausea/vomiting) and associated risk factors (use of drugs such as benzodiazepines and gabapentinoids, the presence of respiratory infection, liver or renal disease) could help minimise the risk of unexpected death in patients given methadone.

Quetiapine and other antipsychotics combined with opioids in legal autopsy cases: A random finding or cause of fatal outcome?

Opioid poisoning is a frequent cause of death in drug addicts and occurs with opioid treatment. Quetiapine is often found in forensic autopsies and may increase the risk of fatal opioid poisoning by enhancing sedation, respiratory depression, hypotension and QT prolongation. We systematically searched for studies of acute toxicity of quetiapine or other antipsychotics combined with morphine or methadone. Case reports describing toxicity of quetiapine combined with morphine or methadone were also included. We retrieved one human study that observed pharmacokinetic interaction between quetiapine and methadone, and 16 other human studies. Fourteen investigated the combination of droperidol and morphine in treatment doses, and some indicated an additive sedative effect. Five animal studies with acepromazine in combination with morphine or methadone were located and indicated an additive effect on sedation and hypotension. Six forensic case reports in which death could have been caused solely by quetiapine, the opioid, or other drugs were found. Thus, acute toxicity of quetiapine combined with morphine or methadone has not been studied. Because of quetiapine's effects on alpha-adrenoceptors, muscarinic and histamine receptors, human ether-a-go-go-channels and methadone kinetics, we suggest further research to clarify if the indicated additive effects of opioids and droperidol or acepromazine are also true for quetiapine.

PP19 Opioid poisoning deaths: a national picture

BackgroundThe factors associated with opioid poisoning death are poorly understood. We performed a retrospective autopsy study of decedents of opioid poisoning in Wales in 2015. Using anonymised linked data, we describe demographic characteristics, patterns of emergency service utilisation, and clinical presentation prior to death.MethodsDecedents of opioid poisoning in Wales in 2015 were identified from Office of National Statistics (ONS) mortality data. Records were linked with the Emergency Department Dataset (EDDS) by the National Welsh Informatics Service (NWIS); and held in the Secure Anonymised Information Linkage (SAIL) databank. Data were accessed and analysed in the SAIL gateway.ResultsAge at death ranged from eighteen to seventy-eight years, with a mean of forty-two years. Average male age was forty-one years and average female age was forty-four and a half years. Seventy-six percent of decedents were men (n=98/112).Eight-seven percent of decedents (n=112/129) attended the emergency department in the three years prior to death; eighty-nine in the previous year, ninety-nine in the previous two years and 112 in the previous three years. Eighty-four percent of male and ninety-three percent of female decedents attended the ED in the three years prior to death.In total 665 attendances were made, half of which involved conveyance by ambulance. Attendances per individual ranged from one to sixty, with over half of decedents attending more than three times.Diagnostic codes were mostly missing or non-specific, with only six and a half percent of attendances representing twenty seven decedents, coded as drug related.ConclusionsMatching previously published data, we found that fatal opioid poisoning is preceded by a period of high emergency health service utilisation. On average decedents were in their fifth decade and more likely to be male than female. Attendances varied widely, with men less likely to attend than women.

PP19 Opioid Poisoning Deaths: A National Picture

Introduction:The factors associated with opioid poisoning death are poorly understood. We performed a retrospective autopsy study of decedents (a term used for people who are deceased) of opioid poisoning in Wales in 2015. Using anonymized linked data, we describe demographic characteristics, patterns of emergency service utilization, and clinical presentation prior to death.Methods:Decedents of opioid poisoning in Wales in 2015 were identified from the Office of National Statistics (ONS) mortality dataset. Records were linked with the Emergency Department Dataset (EDDS) by the National Welsh Informatics Service (NWIS); and held in the Secure Anonymized Information Linkage (SAIL) databank. The data were accessed and analyzed in the SAIL gateway.Results:Age at death ranged from eighteen to seventy-eight years, with a mean age of forty-two years. Average male age was forty-one years and average female age was forty-four and a half years. Seventy-three percent of decedents were men (n = 228/312). Eight-seven percent of decedents (n = 281/312) attended the emergency department in the three years prior to death. In total 2081 attendances were made, forty-one percent of which involved conveyance by ambulance. Attendances per individual ranged from one to 114, with over half of decedents attending more than three times. Diagnostic codes were mostly missing or non-specific, with only seven and a half percent of attendances representing eighty-two decedents, coded as drug related. Treatment codes were also mostly missing or non-specific, with sixteen percent of attendances representing 148 attendees attributed a treatment code. Thirty-nine percent of attendances (n = 822) ended in treatment and discharge, whilst twenty-seven percent (n = 562) led to hospital admission.Conclusions:Matching previously published data, we found that fatal opioid poisoning is preceded by a period of high emergency health service utilization. On average decedents were in their fifth decade and more likely to be male than female. Attendances varied widely, with men less likely to attend than women.

Fatal opioid poisoning: a counterfactual model to estimate the preventive effect of treatment for opioid use disorder in England

A counterfactual model was used to estimate the number of fatal opioid-related poisonings prevented by public treatment services for opioid use disorder (OUD) in England between April 2008 and March 2011. Patient OUD treatment episode data recorded by the English National Drug Treatment Monitoring System were linked to data on opioid deaths recorded by the Office for National Statistics. The source population was the official estimate of non-medical opioid users (aged 15-64 years; approximately 260 000 each year). The target population was all individuals (aged 15-64 years) treated for OUD in the study period (n = 220 665). The outcome measure was fatal opioid-related poisoning (opioid death). The opioid death rate [per 100 person-years (PY)] and mortality rate ratios (MRR) were computed for study year, age group (15-24, 25-34, 35-64 years) and for three treatment-related states: time spent 'prior to treatment', 'during treatment' and 'after treatment'. Between April 2008 and March 2011, there were 3731 opioid deaths in the study: 741 during treatment (0.20 per 100 PY; referent category); 2722 prior to treatment [0.77 per 100 PY; MRR = 3.76, 95% confidence interval (CI) = 3.18-4.44]; and 268 after treatment (0.41 per 100 PY; MRR = 1.99, 95% CI = 1.64-2.41). By counterfactual estimation, national OUD treatment services prevented an average of 880 opioid deaths each year (95% CI = 702-1084). Between April 2008 and March 2011, a counterfactual model shows that the English public treatment system for opioid use disorder prevented an average of 880 deaths each year from opioid-related poisoning. Counterfactual models of mortality prevention can be used for outcome and performance monitoring of substance use disorder treatment systems.

Pharmacogenetics of Neonatal Opioid Toxicity Following Maternal Use of Codeine During Breastfeeding: A Case–Control Study

A large number of women receive codeine for obstetric pain while breastfeeding. Following a case of fatal opioid poisoning in a breastfed neonate whose codeine prescribed mother was a CYP2D6 ultrarapid metabolizer (UM), we examined characteristics of mothers and infants with or without signs of central nervous system (CNS) depression following codeine exposure while breastfeeding in a case-control study. Mothers of symptomatic infants (n = 17) consumed a mean 59% higher codeine dose than mothers of asymptomatic infants (n = 55) (1.62 (0.79) mg/kg/day vs. 1.02 (0.54) mg/kg/day; P = 0.004). There was 71% concordance between maternal and neonatal CNS depression. Two mothers whose infants exhibited severe neonatal toxicity were CYP2D6 UMs and of the UGT2B7*2/*2 genotype. There may be a dose-response relationship between maternal codeine use and neonatal toxicity, and strong concordance between maternal-infant CNS depressive symptoms. Breastfed infants of mothers who are CYP2D6 UMs combined with the UGT2B7*2/*2 are at increased risk of potentially life-threatening CNS depression.