The onset and severity of acute opioid toxicity in heroin overdose cases: a retrospective cohort study at a supervised injecting facility in Melbourne, Australia.

AIM: To differentiate the severity of acute opioid toxicity and describe both the clinical and physiological features associated with heroin overdose in a cohort of witnessed overdose cases. METHODS: Witnessed heroin overdose cases over a 12-month period (30 June 2018 - 30 June 2019) at the Medically Supervised Injecting Room (MSIR) in Melbourne, Australia were examined. The severity of acute opioid toxicity was classified according to the level of clinical intervention required to manage the overdose cases where an escalating level of care was provided. Heroin overdose cases were classified into one of three graded severity categories and a fourth complicated heroin overdose category. RESULTS: A total of 1218 heroin overdose cases were identified from 60,693 supervised injecting visits over the study period. On the spectrum of toxicity, 78% (n = 955) of overdose cases were classified as Grade 1 severity, 7% (n = 83) as Grade 2 severity, and 13% (n = 161) as Grade 3 acute opioid toxicity severity cases, as well as 2% (n = 19) classified as complicated heroin overdose cases. The median onset time for heroin overdose cases was 17 min (IQR 11-28 min) from the time the individual was ready to prepare and inject heroin until clinical intervention was initiated. CONCLUSION: We demonstrated that heroin overdose is a dynamic illness and cases differ in the severity of acute opioid toxicity. The risk of airway occlusion including positional asphyxia was an early and consistent feature across all levels of toxicity, while exaggerated respiratory depression together with exaggerated depression of consciousness was increasingly observed with greater levels of toxicity. We also demonstrated the importance of early intervention in overdose cases, where in a large cohort of heroin overdose cases there were no fatal outcomes, a very low hospitalisation rate and most cases were able to be managed to clinical resolution on-site.

Challenges with take-home naloxone in reducing heroin mortality: a review of fatal heroin overdose cases in Victoria, Australia.

AIM: Take-home naloxone (THN) programs have been implemented in order to reduce the number of heroin-overdose deaths. Because of recent legislative changes in Australia, there is a provision for a greater distribution of naloxone in the community, however, the potential impact of these changes for reduced heroin mortality remains unclear. The aim of this study was to examine the characteristics of the entire cohort of fatal heroin overdose cases and assess whether there was an opportunity for bystander intervention had naloxone been available at the location and time of each of the fatal overdose events to potentially avert the fatal outcome in these cases. METHODS: The circumstances related to the fatal overdose event for the cohort of heroin-overdose deaths in the state of Victoria, Australia between 1 January 2012 and 31 December 2013 were investigated. Coronial data were investigated for all cases and data linkage was performed to additionally investigate the Emergency Medical Services information about the circumstances of the fatal heroin overdose event for each of the decedents. RESULTS AND DISCUSSION: There were 235 fatal heroin overdose cases identified over the study period. Data revealed that the majority of fatal heroin overdose cases occurred at a private residence (n = 186, 79%) and where the decedent was also alone at the time of the fatal overdose event (n = 192, 83%). There were only 38 cases (17%) where the decedent was with someone else or there was a witness to the overdose event, and in half of these cases the witness was significantly impaired, incapacitated or asleep at the time of the fatal heroin overdose. There were 19 fatal heroin overdose cases (8%) identified where there was the potential for appropriate and timely intervention by a bystander or witness. CONCLUSION: This study demonstrated that THN introduction alone could have led to a very modest reduction in the number of fatal heroin overdose cases over the study period. A lack of supervision or a witness to provide meaningful and timely intervention was evident in most of the fatal heroin overdose cases.

An analysis of issues in the classification and reporting of heroin-related deaths.

AIMS: To investigate the extent of variability in the reporting of heroin-related deaths in Victoria, Australia. Additionally, to identify opportunities to improve the accuracy and consistency of heroin-related death reporting by examining variability in the attribution, death certification, classification and coding of heroin-related death cases. METHODS: Heroin-related deaths in Victoria, Australia during a 2-year period (2012-13) were identified using the National Coronial Information System (NCIS) and used as the 'gold standard' measure in this study. Heroin-related death data from the Australian Institute of Health and Welfare (AIHW) and Australian Bureau of Statistics (ABS) were then compared. Differences in the number of deaths reported as well as the classification and coding assigned to the identified heroin-related death cases were investigated by cross-referencing these data sets and examining the assigned ICD-10 codes. RESULTS: A total of 243 heroin-related deaths were identified through the NCIS compared with 165 heroin-related deaths reported by the AIHW and assigned the heroin-specific ICD-10 code of T40.1. Forty per cent of all the missed heroin-related death cases resulted from either the attribution of the death to morphine toxicity or with non-specific drug toxicity certification; 30% occurred where the cases had been attributed to heroin but there were irregularities in death certification. Additional missed heroin-related death cases occurred as a result of late initial registration of these deaths to the Registry of Births, Deaths and Marriages, and where these cases were then not assessed by the ABS for classification and coding purposes. CONCLUSIONS: In Victoria, Australia, in 2012 and 2013, the overall number of heroin-related deaths was under-reported by 32% compared with the number of deaths currently identified by the Australian Bureau of Statistics and reported by the Australian Institute of Health and Welfare.

Determining the effective dose of street-level heroin: A new way to consider fluctuations in heroin purity, mass and potential contribution to overdose.

BACKGROUND & AIMS: Heroin use is associated with a disproportionately high level of morbidity and mortality with most deaths attributable to drug overdose. Aggregate heroin purity data has been used to examine the relationship between overdose and variability in street-level heroin, however heroin purity data alone may not be the most appropriate nor a sensitive enough measurement tool for this assessment. The aim of this study was to measure the variability in effective dose of street-level heroin seizures, accounting for variation in both purity and mass, and determine the proportion of samples with higher than expected effective dose that would not be detected using a purity-only measure. METHODS: Data on Victorian heroin seizures ≤150mg in mass made between 01/01/2012 and 31/12/2013 were obtained from the Victoria Police Forensic Services Department. The effective dose of heroin in each sample was determined by multiplying the mass and purity variables. Effective dose outlier samples were considered as those containing either greater than 1.5-2 times or >2 times the median effective dose of heroin for the sample data. RESULTS: The 983 street-level heroin samples of ≤150mg had a median mass of 92mg (IQR of 43mg), a median purity of 13% (range 3.6%-80.9%) and a median effective dose of 12.0mg of heroin (IQR 6.6mg; range 0.4mg-111mg). Approximately one in 13 samples (8%) and one in 17 samples (6%) contained between 1.5-2 times and >2 times the median effective dose of heroin respectively. CONCLUSION: The effective dose of heroin is a more appropriate measure than purity to identify outlier samples that containing larger than expected doses of heroin compared to typical doses that may be expected by users. Together with other identified risk factors, fluctuation in the effective dose of heroin contained in street-level samples may contribute to the potential for overdose.

Catch and release: evaluating the safety of non-fatal heroin overdose management in the out-of-hospital environment.

Background: The aim of this study was to investigate the safety of the management of non-fatal heroin overdose in the out-of-hospital environment; irrespective of whether or not naloxone had been administered. Heroin toxicity-related deaths as well as heroin intoxication-related traumatic deaths following patient-initiated refusal of transport were investigated. Methods: Heroin-related deaths in the state of Victoria, Australia between 1 January 2012 and 31 December 2013 were investigated and data linkage to pre-hospital Emergency Medical Services performed, in order to identify whether the death was related to the last episode of care by paramedics. The number of non-fatal heroin overdose events over the study period were also examined. Results and discussion: There were a total of 3921 heroin-related attendances by paramedics during the study period, including 2455 cases that involved treatment but where the patient was not transported to hospital. There were also 243 heroin-related deaths identified over the study period and 93% (n = 225) of those cases were matched with Ambulance Victoria electronic patient care records. Data linkage revealed 31 heroin-related deaths where there had been a recent presentation with a non-fatal heroin overdose to paramedics; however, none of these deaths were related to that episode of care, including for 11 individuals that were treated on scene by paramedics but not transported to the hospital. Conclusions: This study demonstrated that the treatment of uncomplicated heroin overdose in the out-of-hospital environment was safe in terms of mortality, irrespective of whether or not naloxone had been administered. In all of the non-fatal heroin toxicity cases attended by paramedics, whether or not transported to hospital, death occurred as a result of a subsequent and unrelated heroin overdose.

The attribution of a death to heroin: A model to help improve the consistent and transparent classification and reporting of heroin-related deaths.

INTRODUCTION: Accurate attribution of heroin-related deaths, as well as the differentiation from other opioid analgesic-related deaths, is essential from a public health perspective. Heroin-related deaths involve a number of complexities where heroin-specific or non-specific metabolites and indicators (6-acetylmorphine [6-AM], morphine, and codeine) may or may not be detected. The aims of this study were therefore to develop a model for improved consistency in the attribution of heroin-related deaths and to determine areas of variation in the current decision-making processes. METHODS: A model was developed using different toxicological indicators of heroin use (6-AM, morphine to codeine ratio (M:C) or morphine alone) along with investigative evidence of heroin use (circumstances, scene and clinical findings) which were used to assign a weighted score. The combined scores for the toxicological and investigative evidence were used to determine the relative strength of association for the death being attributable to heroin according to three categories: suspected; likely; or strong. An expert panel was convened to validate the model and a series of test cases were provided to a cohort of forensic toxicologists and pathologists in order to identify sources of variation in decision-making within this group. The model was also evaluated for sensitivity and specificity by reviewing potential heroin-related cases and examining the evidence associated with the attribution of these cases to heroin or not. RESULTS AND DISCUSSION: Across all potential heroin-related death cases, the use of this model enabled a greater level of consistency in the attribution of death to heroin, especially in cases where 6-AM was not detected. The largest amount of variation in the attribution of a death to heroin was observed with potential intoxication-related deaths and in toxicity cases where a M:C ratio only was reported, even more than when no toxicological evidence was available. The reviewed cases highlighted the same variation in the attribution of a death to heroin, including a large number of cases that were attributed to morphine where 6-AM was not detected. CONCLUSION: This model provides a useful tool for improved accuracy and consistency in the differentiation, attribution and reporting of heroin-related deaths. Previously challenging cases where death occurred after a significant period of time and either no 6-AM was detected or no samples were taken, are able to be captured using this model.

Sex-specific behavioural effects of environmental enrichment in a transgenic mouse model of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterised by motor neuron degeneration, muscle wasting and paralysis. While twin studies support a role for both genetic and environmental factors in ALS, the nature of environmental modifiers is unknown. We therefore compared onset and progression of disease symptoms in female and male transgenic ALS mice (expressing the human SOD1(G93A) gene mutation) and their wild-type littermates, housed in environmentally enriched versus standard conditions. Environmental enrichment significantly improved motor performance, as measured using the accelerating rotarod, in particular for female mice. This enhanced motor coordination was observed for both SOD1(G93A) and wild-type mice, suggesting this effect is independent of genotype. Female SOD1(G93A) mice housed with environmental enrichment were found to reach overt end-stage disease sooner than their standard-housed littermates. However, male SOD1(G93A) mice did not show significantly accelerated disease progression. This evidence for environmental modulation of ALS pathogenesis in transgenic mice provides insights into activity-dependent aspects of the disease process, and may help identify molecular targets for pharmacological modulators as future therapeutics.