Jurisdictional trends in opioid overdose deaths, 1988-96

This report analysed data on opioid overdose mortality between 1988 and 1996 to: examine differences between jurisdictions in the rate of fatal opioid overdose and the rate of increase in overdose; and estimate the proportion of all deaths which were attributed to opioid overdose. Australian Bureau of Statistics (ABS) data were obtained on the number of deaths attributed to opioid dependence (ICD 9 codes 304.0, 304.7) and accidental opioid poisoning (ICD 9 codes E850.0, E850.1). The highest rate of fatal overdose occurred in NSW, followed by Victoria. The standardised mortality rate among other jurisdictions fluctuated quite markedly. While the rate of opioid overdose has increased throughout Australia, the rate of increase has been greater in some of the less-populous states and territories than it has in NSW or Victoria. In 1996, approximately 6.5% of all deaths among people aged 15-24 years and approximately 10% of all deaths among those aged 25-34 were due to opioid overdose. During the interval from 1988 to 1996, the proportion of deaths attributed to opioid overdose increased. From 1988 to 1996, the proportion of deaths attributed to opioid overdose among individuals aged 25-34 years was approximately one-third that attributed to suicide, but this proportion had increased to approximately one-half by 1996. The rate of increase in the proportion of deaths attributed to opioid overdose was higher than the rate of increase in the proportion of deaths attributed to suicide.

Fluctuations in heroin purity and the incidence of fatal heroin overdose

In order to determine the role played by heroin purity in fatal heroin overdoses, time series analyses were conducted on the purity of street heroin seizures in south western Sydney and overdose fatalities in that region. A total of 322 heroin samples were analysed in fortnightly periods between February 1993 to January 1995. A total of 61 overdose deaths occurred in the region in the study period. Cross correlation plots revealed a significant correlation of 0.57 at time lag zero between mean purity of heroin samples per fortnight and number of overdose fatalities. Similarly, there was a significant correlation of 0.50 at time lag zero between the highest heroin purity per fortnight and number of overdose fatalities. The correlation between range of heroin purity and number of deaths per fortnight was 0.40. A simultaneous multiple regression on scores adjusted for first order correlation indicated both the mean level of heroin purity and the range of heroin purity were independent predictors of the number of deaths per fortnight. The results indicate that the occurrence of overdose fatalities was moderately associated with both the average heroin purity and the range of heroin purity over the study period. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.

Opioid overdose mortality in Australia, 1964-1997: birth-cohort trends

Objective: To examine trends in rates of opioid overdose deaths from 1964 to 1997 in different birth cohorts. Design: Age-period-cohort analysis of national data from the Australian Bureau of Statistics. Main outcome measures: Annual population rates of death attributed to opioid dependence or accidental opioid poisoning in people aged 15-44 years, by sex and birth cohort tin five-year intervals, 1940-1944 to 1975-1979). Results: The rate of opioid overdose deaths increased 55-fold between 1964 and 1997, from 1.3 to 71.5 per million population aged 15-44 years. The rate of opioid overdose deaths also increased substantially over the eight birth cohorts, with an incidence rate ratio of 20.70 (95% confidence interval, 13.60-31.46) in the 1975-1979 cohort compared with the 1940-1944 cohort. The age at which the cumulative rate of opioid overdose deaths reached 300 per million fell in successive cohorts (for men, from 28 years among those born 1955-1959 to 22 years among those born 1965-1974; for women, from 33 years among those born 1955-1959 to 27 years among those born 1965-1969). Conclusions: Heroin use in Australia largely began in the early 1970s and rates of heroin use have markedly increased in birth cohorts born since 1950.

Reducing the toll of opioid overdose deaths in Australia

Opioid overdose mortality among young adults in Australia has increased consistently over the past several decades. Among Australian adults aged 15-44 years, the number of these deaths has increased from six in 1964 to 600 in 1997. The rate (per million adults in this age group) increased 55-fold, from 1.3 in 1964 to 71.5 in 1997, The proportion of all deaths in adults in this age group caused by opioid overdose increased from 0.1% in 1964 to 7.3% in 1997, The magnitude of the increase makes it unlikely to be an artefact of changes in diagnosis, especially as similar increases have also been observed in other countries. These trends are also consistent,vith historical information which indicates that illicit heroin use first came to police attention in Sydney and Melbourne in the late 1960s, There is an urgent need to implement and evaluate a variety of measures to reduce the unacceptable toll of opioid overdose deaths among young Australians. These include: peer education about the risks of polydrug use and overdose after resuming opioid use after periods of abstinence, and attracting more dependent users into opioid maintenance treatment. Measures are also needed to improve responses to overdose by encouraging witnesses to call ambulances, training drug users in CPR, and trialling distribution of the opiate antagonist naloxone to users at high risk of overdose.

Heroin overdose: causes and consequences

Over the past decade fatal opioid overdose has emerged as a major public health issue internationally. This paper examines the risk factors for overdose from a biomedical perspective. while significant risk factors for opioid overdose fatality are well recognized, the mechanism of fatal overdose remains unclear. Losses of tolerance and concomitant use of alcohol and other CNS depressants clearly play a major role in fatality; howeve, such risk factors do not account for the strong age and gender patterns observed consistently among victims of overdose. There is evidence that systemic disease may be more prevalent in users at greatest risk of overdose. We hypothesize that pulmonary and hepatic dysfunction resulting from such disease may increase susceptibility to both fatal and non-fatal overdose. Sequelae of non-fatal overdose are recognized in the clinical literature but few epidemiological data exist describing the burden of morbidity arising from such sequelae. The potential for overdose to cause persisting morbidity is reviewed.

Hair morphine concentrations of fatal heroin overdose cases and living heroin users

Aims To compare heroin and other opiate use of heroin overdose fatalities, current street heroin users and drug-free therapeutic community clients. Design Hair morphine concentrations that assess heroin use and other opiate use in the 2 months preceding interview or death were compared between heroin overdose fatalities diagnosed by forensic pathologists (fOD) (n = 42), current street heroin users (CU) (n = 100) and presumably abstinent heroin users in a drug-free therapeutic community (TC) (n = 50). Setting Sydney, Australia. Findings The mean age and gender breakdown of the three samples were 32.3 years, 83% male (FOD), 28.7 years, 58% male (CU) and 28.6 years, 60% male (TC). The median blood morphine concentration among the FOD cases was 0.35 mg/l, and 82% also had other drugs detected. There were large differences between the three groups in hair morphine concentrations, with the CU group (2.10 ng/mg) having concentration approximately four times that of the FOD group (0.53 ng/mg), which in turn had a concentration approximately six times that of the TC group (0.09 ng/mg). There were no significant differences between males and females in hair concentrations within any of the groups. Hair morphine concentrations were correlated significantly with blood morphine concentrations among FOD cases (r = 0.54), and self-reported heroin use among living participants (r = 0.57). Conclusions The results indicate that fatal cases had a lower degree of chronic opiate intake than the active street users, but they were not abstinent during this period.

Heroin overdose: Research and evidence-based intervention

Drug overdose is a major cause of Premature death and morbidity among heroin users. This article examines recent research into heroin overdose to inform interventions that will reduce the rate of overdose death. The demographic characteristics of overdose cases are discussed, including factors associated with overdose: polydrug use, drug purity, drug tolerance, routes of administration, and suicide. Responses by heroin users at overdoses are also examined. Potential interventions to reduce the rate of overdose and overdose-related morbidity are examined in light of the emerging data in this field.

Severe rhabdomyolysis following venlafaxine overdose.

Venlafaxine is a recently developed serotoninergic antidepressant whose reported toxicity at overdose levels includes central nervous system depression, seizures, and cardiovascular toxicity. The authors now present a case of venlafaxine overdose in a young woman complicated by a rise in plasma creatine kinase activity up to 52,600 U/L. Immediate therapy with intravenous fluids, bicarbonate, and furosemide was administered, and there were no further complications, notably no renal failure. This case supports the notion that venlafaxine can induce direct skeletal muscle toxicity leading to severe rhabdomyolysis. Therefore, clinicians should monitor muscle enzymes in patients with venlafaxine overdose to detect the development of rhabdomyolysis at an early stage and to initiate appropriate therapy rapidly.

Seizures after single-agent overdose with pharmaceutical drugs: Analysis of cases reported to a poison center.

Abstract Context. Seizures during intoxications with pharmaceuticals are a well-known complication. However, only a few studies report on drugs commonly involved and calculate the seizure potential of these drugs. Objectives. To identify the pharmaceutical drugs most commonly associated with seizures after single-agent overdose, the seizure potential of these pharmaceuticals, the age-distribution of the cases with seizures and the ingested doses. Methods. A retrospective review of acute single-agent exposures to pharmaceuticals reported to the Swiss Toxicological Information Centre (STIC) between January 1997 and December 2010 was conducted. Exposures which resulted in at least one seizure were identified. The seizure potential of a pharmaceutical was calculated by dividing the number of cases with seizures by the number of all cases recorded with that pharmaceutical. Data were analyzed using descriptive statistics. Results. We identified 15,441 single-agent exposures. Seizures occurred in 313 cases. The most prevalent pharmaceuticals were mefenamic acid (51 of the 313 cases), citalopram (34), trimipramine (27), venlafaxine (23), tramadol (15), diphenhydramine (14), amitriptyline (12), carbamazepine (11), maprotiline (10), and quetiapine (10). Antidepressants were involved in 136 cases. Drugs with a high seizure potential were bupropion (31.6%, seizures in 6 of 19 cases, 95% CI: 15.4-50.0%), maprotiline (17.5%, 10/57, 95% CI: 9.8-29.4%), venlafaxine (13.7%, 23/168, 95% CI: 9.3-19.7%), citalopram (13.1%, 34/259, 95% CI: 9.5-17.8%), and mefenamic acid (10.9%, 51/470, 95% CI: 8.4-14.0%). In adolescents (15-19y/o) 23.9% (95% CI: 17.6-31.7%) of the cases involving mefenamic acid resulted in seizures, but only 5.7% (95% CI: 3.3-9.7%) in adults (≥ 20y/o; p < 0.001). For citalopram these numbers were 22.0% (95% CI: 12.8-35.2%) and 10.9% (95% CI: 7.1-16.4%), respectively (p = 0.058). The probability of seizures with mefenamic acid, citalopram, trimipramine, and venlafaxine increased as the ingested dose increased. Conclusions. Antidepressants were frequently associated with seizures in overdose, but other pharmaceuticals, as mefenamic acid, were also associated with seizures in a considerable number of cases. Bupropion was the pharmaceutical with the highest seizure potential even if overdose with bupropion was uncommon in our sample. Adolescents might be more susceptible to seizures after mefenamic acid overdose than adults. "Part of this work is already published as a conference abstract for the XXXIV International Congress of the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) 27-30 May 2014, Brussels, Belgium." Abstract 8, Clin Toxicol 2014;52(4):298.

The functional outcome and recovery of patients admitted to an intensive care unit following drug overdose: a follow-up study.

Patients who have overdosed on drugs commonly present to emergency departments, with only the most severe cases requiring intensive care unit (ICU) admission. Such patients typically survive hospitalisation. We studied their longer term functional outcomes and recovery patterns which have not been well described. All patients admitted to the 18-bed ICU of a university-affiliated teaching hospital following drug overdoses between 1 January 2004 and 31 December 2006 were identified. With ethical approval, we evaluated the functional outcome and recovery patterns of the surviving patients 31 months after presentation, by telephone or personal interview. These were recorded as Glasgow outcome score, Karnofsky performance index and present work status. During the three years studied, 43 patients were identified as being admitted to our ICU because of an overdose. The average age was 34 years, 72% were male and the mean APACHE II score was 16.7. Of these, 32 were discharged from hospital alive. Follow-up data was attained on all of them. At a median of 31 months follow-up, a further eight had died. Of the 24 surviving there were 13 unemployed, seven employed and four in custody. The median Glasgow outcome score of survivors was 4.5, their Karnofsky score 80. Admission to ICU for treatment of overdose is associated with a very high risk of death in both the short- and long-term. While excellent functional recovery is achievable, 16% of survivors were held in custody and 54% unemployed.This resource was contributed by The National Documentation Centre on Drug Use.

A fatal overdose of cocaine associated with coingestion of marijuana, buprenorphine, and fluoxetine. Body fluid and tissue distribution of cocaine and its metabolites determined by hydrophilic interaction chromatography-mass spectrometry(HILIC-MS).

Chromatographic separation of highly polar basic drugs with ideal ionspray mass spectrometry volatile mobile phases is a difficult challenge. A new quantification procedure was developed using hydrophilic interaction chromatography-mass spectrometry with turbo-ionspray ionization in the positive mode. After addition of deuterated internal standards and simple clean-up liquid extraction, the dried extracts were reconstituted in 500 microL pure acetonitrile and 5 microL was directly injected onto a Waters Atlantis HILIC 150- x 2.1-mm, 3-microm column. Chromatographic separations of cocaine, seven metabolites, and anhydroecgonine were obtained by linear gradient-elution with decreasing high concentrations of acetonitrile (80-56% in 18 min). This high proportion of organic solvent makes it easier to be coupled with MS. The eluent was buffered with 2 mM ammonium acetate at pH 4.5. Except for m-hydroxy-benzoylecgonine, the within-day and between-day precisions at 20, 100, and 500 ng/mL were below 7 and 19.1%, respectively. Accuracy was also below +/- 13.5% at all tested concentrations. The limit of quantification was 5 ng/mL (%Diff < 16.1, %RSD < 4.3) and the limit of detection below 0.5 ng/mL. This method was successfully applied to a fatal overdose. In Switzerland, cocaine abuse has dramatically increased in the last few years. A 45-year-old man, a known HIV-positive drug user, was found dead at home. According to relatives, cocaine was self-injected about 10 times during the evening before death. A low amount of cocaine (0.45 mg) was detected in the bloody fluid taken from a syringe discovered near the corpse. Besides injection marks, no significant lesions were detected during the forensic autopsy. Toxicological investigations showed high cocaine concentrations in all body fluids and tissues. The peripheral blood concentrations of cocaine, benzoylecgonine, and methylecgonine were 5.0, 10.4, and 4.1 mg/L, respectively. The brain concentrations of cocaine, benzoylecgonine, and methylecgonine were 21.2, 3.8, and 3.3 mg/kg, respectively. The highest concentrations of norcocaine (about 1 mg/L) were measured in bile and urine. Very high levels of cocaine were determined in hair (160 ng/mg), indicating chronic cocaine use. A low concentration of anhydroecgonine methylester was also found in urine (0.65 mg/L) suggesting recent cocaine inhalation. Therapeutic blood concentrations of fluoxetine (0.15 mg/L) and buprenorphine (0.1 microg/L) were also discovered. A relatively high concentration of Delta(9)-THC was measured both in peripheral blood (8.2 microg/L) and brain cortex (13.5 microg/kg), suggesting that the victim was under the influence of cannabis at the time of death. In addition, fluoxetine might have enhanced the toxic effects of cocaine because of its weak pro-arrhythmogenic properties. Likewise, combination of cannabinoids and cocaine might have increase detrimental cardiovascular effects. Altogether, these results indicate a lethal cocaine overdose with a minor contribution of fluoxetine and cannabinoids.

Body fluid and tissue analysis using filter paper sampling support prior to LC-MS/MS: application to fatal overdose with colchicine

Because of the various matrices available for forensic investigations, the development of versatile analytical approaches allowing the simultaneous determination of drugs is challenging. The aim of this work was to assess a liquid chromatography-tandem mass spectrometry (LC-MS/MS) platform allowing the rapid quantification of colchicine in body fluids and tissues collected in the context of a fatal overdose. For this purpose, filter paper was used as a sampling support and was associated with an automated 96-well plate extraction performed by the LC autosampler itself. The developed method features a 7-min total run time including automated filter paper extraction (2 min) and chromatographic separation (5 min). The sample preparation was reduced to a minimum regardless of the matrix analyzed. This platform was fully validated for dried blood spots (DBS) in the toxic concentration range of colchicine. The DBS calibration curve was applied successfully to quantification in all other matrices (body fluids and tissues) except for bile, where an excessive matrix effect was found. The distribution of colchicine for a fatal overdose case was reported as follows: peripheral blood, 29 ng/ml; urine, 94 ng/ml; vitreous humour and cerebrospinal fluid, < 5 ng/ml; pericardial fluid, 14 ng/ml; brain, < 5 pg/mg; heart, 121 pg/mg; kidney, 245 pg/mg; and liver, 143 pg/mg. Although filter paper is usually employed for DBS, we report here the extension of this alternative sampling support to the analysis of other body fluids and tissues. The developed platform represents a rapid and versatile approach for drug determination in multiple forensic media.