Cocaine-related fatalities in New South Wales, Australia 1993–2002

Drug and Alcohol Dependence 77 (2005) 107–114

Cocaine-related fatalities in New South Wales, Australia 1993–2002 Shane Darkea,∗ , Sharlene Kayea , Johan Dufloub b

a National Drug and Alcohol Research Centre, University of New South Wales, NSW 2052, Australia Department of Forensic Medicine, Central Sydney Area Health Service, School of Medicine University of New South Wales, Department of Pathology, University of Sydney, NSW, Australia

Received 10 February 2004; received in revised form 21 July 2004; accepted 21 July 2004

Abstract Aim: To ascertain the demographic characteristics, circumstances of death, toxicological results, and major autopsy findings of cocaine-related fatalities. Design: Inspection of the coronial records of all cocaine-related deaths that occurred in New South Wales, Australia between 1 January 1993 and 31 December 2002. Setting: New South Wales, Australia. Findings: 146 cases were identified. Cocaine was implicated in the direct cause of death in 86% of cases, an antecedent cause in 8% and a significant condition contributing to death in 7%. The mean age of decedents was 34.1years, and 84% were male. Half were employed, and 26% were in professional employment. The predominant route of administration was injection (86%), however nasal (8%), oral (3%), smoking (1%), and anal (1%) administration were all recorded. The most common location of death was a private home (53%). No intervention occurred prior to death in 82% of cases. The median blood benzoylecgonine concentration was 0.40 mg/L (range 0.00–20.00 mg/L). Cases had a mean of 3.5 drugs, with morphine (79%) the most common co-occurring drug. In 5% of cases cocaine was the sole drug detected. Cardiac pathology was noted in 57% of cases, most commonly coronary artery atherosclerosis (39%) and cardiac hypertrophy (14%). In 15% of cases moderate to severe arterial occlusion was noted. Cerebrovascular pathology was noted in 22% of cases, most commonly cerebrovascular atherosclerosis (10%). Conclusions: Cocaine-related deaths are a significant clinical problem in New South Wales. © 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Cocaine; Mortality; Toxicology; Autopsy

1. Introduction Over the preceding two decades cocaine has emerged as a major cause of morbidity and mortality, particularly in the United States (Tardiff et al., 1996; Coffin et al., 2003; Kissin and Ball, 2003), where one third of drug-related emergency department presentations (Kissin and Ball, 2003) are cocainerelated. Cocaine-related deaths have also increased substantially in the United Kingdom and Europe (Sanchez et al., 1995; Office for National Statistics, 2002). Until the late 1990s the prevalence and frequency of cocaine use among Australian drug users was low, and the associated problems considered mild (Hall et al., 1991; Hando ∗

Corresponding author. Tel.: +61 2 9398 9338; fax: +61 2 9399 7143. E-mail address: [email protected] (S. Darke).

0376-8716/$ – see front matter © 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.drugalcdep.2004.07.004

et al., 1997). Since 1998, however, cocaine use has arisen as a significant drug problem in Australia, and in Sydney in particular. Sharp increases in use were recorded in 1998 and 2001 among injecting drug users (IDU), and among heroininjectors in particular (Darke et al., 2002). This trend has been particularly pronounced since the decline in the availability of heroin in Australia in 2001, with many heroin users switching to cocaine (Topp et al., 2003). Cocaine use in Australia is overwhelming of cocaine hydrochloride powder, and crack use is rare (Darke et al., 2002). Cocaine use is not, however, restricted to IDU. Previous research has indicated a separate group of higher socio-economic non-injecting cocaine users (Hando et al., 1997). This group is characterised as an employed, “functional” group of cocaine users. Multiple drugs are typically detected among cocainerelated fatalities, most commonly heroin and alcohol (Wetli

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and Wright, 1979; Tardiff et al., 1996; Coffin et al., 2003). It has been argued that the combination of cocaine and heroin is more dangerous than when either drug is used alone, as cocaine potentiates the tendency of opioids to depress respiration (Friedman et al., 1996; Platt, 1997). Consistent with this, non-fatal overdoses in the United States are more often associated with the concomitant use of these two drugs than with either drug alone (Ochoa et al., 2001). In addition, the concomitant ingestion of cocaine and alcohol produces cocaethylene, an active metabolite of cocaine that enhances and extends the effects of cocaine (Brookoff et al., 1996; Harris et al., 2003). The role of polydrug use in cocaine and other drug-related mortality is illustrated by a recent study of accidental drug overdoses in New York City over the period 1990–1998 (Coffin et al., 2003). Changes in the rates of both cocaine and heroin overdoses were related to changes in the rate of polydrug deaths, whilst the rate of single drug deaths remained stable. Many of the adverse effects of cocaine relate to route of administration. Cocaine injecting has been associated with more frequent injections, more frequent needle sharing, and higher HIV seroprevalence (Hartel et al., 1996; Platt, 1997). Regular intranasal use of cocaine is associated with nasal problems and cocaine smoking with pulmonary and respiratory complications (Platt, 1997; Karch, 2002). The regular use of cocaine by all routes of administration, however, has been associated with serious psychiatric sequelae, including paranoia, anxiety, depression, and excited delirium (American Psychiatric Association, 2000). Two of the most serious sequelae of cocaine use, cardiovascular and cerebrovascular complications, occur regardless of route of administration (Karch, 2002). In the United States chest pains and palpitations are among the most common complaints among cocaine users presenting to accident and emergency departments (Lange and Hillis, 2001; Kontos et al., 2003). Cocaine can cause myocardial ischaemia and infarction via several mechanisms: an increase in myocardial oxygen demand, vasoconstriction of the coronary arteries and coronary thrombosis (Moliterno et al., 1994; Rump et al., 1995; Friedman et al., 1996; Hollander et al., 1997; Wilson, 1998; Lange and Hillis, 2001; Kontos et al., 2003). Cocaineinduced cerebrovascular accidents are also well recognised; a recent US study reported a 14-fold increase in the risk of ischaemic or haemorrhagic stroke among cocaine users compared to matched controls (Pettiti et al., 1998). Although cocaine can induce cardiovascular complications in users with normal coronary arteries (Mittleman et al., 1999; Lange and Hillis, 2001; Vasica and Tennant, 2002), underlying atherosclerosis (particularly of the left coronary arteries) has been consistently demonstrated (Rump et al., 1995; Hollander et al., 1997; Wilson, 1998; Mittleman et al., 1999; Pavon-Jimanez et al., 1999; Karch, 2002; Vasica and Tennant, 2002; Kontos et al., 2003). The premature and accelerated development of coronary artery atherosclerosis, which increases the risk of cocaine-induced myocardial infarction, has been associated with the chronic use of cocaine (Friedman

et al., 1996; Hollander et al., 1997; Wilson, 1998; Mittleman et al., 1999; Lange and Hillis, 2001; Benzaquen et al., 2001; Kontos et al., 2003). Chronic cocaine use had also been associated with ventricular hypertrophy, a condition that can predispose to cocaine-induced myocardial ischaemia and/or arrhythmia (Om et al., 1993; Friedman et al., 1996; Benzaquen et al., 2001; Karch, 2002). While dose and frequency of use may influence the likelihood of coronary and cerebrovascular complications, the threshold over which potentially fatal reactions occur can vary widely between individuals. Toxic reactions can occur irrespective of dose, frequency of use, or route of administration, and have been reported with small amounts of cocaine and on the first occasion of use (Platt, 1997; Lange and Hillis, 2001; Karch, 2002). The absence of a strong dose-related response among cocaine fatalities has been argued to be due to the cardiotoxic effects of cocaine (Karch et al., 1991; Lange and Hillis, 2001; Karch, 2002). To date, few coronial studies have examined cocainerelated fatalities, and none have been conducted in Australia. In order to determine the extent and nature of cocaine-related fatalities, the current study examined cocaine-related deaths in New South Wales, the Australian state in which almost all cocaine use occurs (Darke et al., 2002). Specifically, the study aimed: 1. to determine the number and demographic characteristics of cocaine-related fatalities that occurred between 1 January 1993 and 31 December 2002; 2. to describe the circumstances of cocaine-related fatalities; 3. to determine the toxicological results from cocaine-related fatalities; and 4. to describe the major autopsy findings from cocainerelated fatalities.

2. Methods 2.1. Case identification Permission was received from the NSW State Coroner to access the coronial records of all cocaine-related deaths that occurred in new south Wales between 1 January 1993 and 31 December 2002. A list was compiled by the NSW Coroner’s Office of all cases in which cocaine was determined to have been the cause of death, or a significant associated condition contributing to death. Cause of death is determined by the forensic pathologist on the basis of circumstances of death, a comprehensive autopsy, and toxicological analyses. Causes of death are categorised as: 1. Direct cause: disease or condition directly leading to death; 2. Antecedent cause: morbid conditions giving rise to the direct cause; and 3. Significant associated conditions contributing to death.

S. Darke et al. / Drug and Alcohol Dependence 77 (2005) 107–114

In New South Wales a case must be reported to the Coroner where: a person dies a violent or unnatural death; a person dies suddenly and the cause is unknown; a medical practitioner has not issued a death certificate stating the cause of death; the deceased was not attended by a medical practitioner in the three months prior to death; the person died within 24 h of having been administered an anaesthetic; the person died within a year and a day of an accident to which the cause of death may be attributable; the person died in a psychiatric hospital, or a variety of other institutions administering care or treatment (e.g. child care centres); the death occurs whilst the person was in police custody. 2.2. Data collection form Information on cause of death, demographic characteristics, drug use history, recent drug treatment history, circumstances of death, toxicological findings, and major autopsy findings were retrieved from the coronial files. Documents of particular relevance were: police reports, ambulance officer statements, witness statements, toxicological analyses, autopsy reports, and transcripts of coronial inquests (where conducted). The data collection form used in previous coronial studies conducted by the authors was employed (Darke et al., 2000). Occupational status was classified using the Australian Standard Classification of Occupations (Australian Bureau of Statistics, 1997). 2.3. Toxicological results Information on analytical toxicological results was obtained from reports of laboratory analyses performed by the Division of Analytical Laboratories (NSW Health Department), on blood and other specimens taken at autopsy. All cases referred to the Coroner had full quantitative toxicological analyses performed, and these reports are contained within the coronial files. Recent cocaine administration is determined by the presence of cocaine itself and/or the presence of benzoylecgonine, the major metabolite of cocaine. Morphine (the major metabolite of heroin) and blood alcohol concentrations were also recorded. Analyses to detect cocaethylene are not routinely conducted in NSW, so data were unavailable on this metabolite. To determine if posthumous processes affected blood concentrations of benzoylecgonine, morphine and alcohol, the period between estimated time of death and autopsy was recorded. 2.4. Autopsy findings Information was recorded on all major pathology noted in autopsy reports. Information of particular relevance was: findings on cardiac pathology, cerebrovascular pathology, pulmonary pathology and hepatic pathology. Coronary atherosclerosis was classified as mild, moderate or severe on the basis of comment by the forensic pathologist in the postmortem report, or by arterial occlusion ranges of 10–50% (mild), 51–75% (moderate) and >75% (severe).

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Table 1 Direct cause of death of cocaine-related fatalities Direct cause of death Cocaine toxicity

Males (n = 123) (%) 5

Combined drug toxicity 81 Drugs in combination with cocaine Opioids 79 Alcohol 16 Benzodiazepines 12 Amphetamines 7 Other drugs 9 Cardiac Pulmonary Cerebral Hanging Multiple organ failure Injury Gunshot Carbon monoxide poisoning

4 3 3 2 0 1 1 1

Females (n = 23) (%)

All (n = 146) (%)

4

5

74

81

70 9 22 0 22

77 15 14 6 11

0 4 4 4 4 4 0 0

3 3 3 2 1 1 1 1

2.5. Statistical analyses t-Tests were used for continuous data. Where distributions were highly skewed, medians were reported, and analysed using the Mann–Whitney U statistic. For dichotomous categorical variables, odds ratios (OR) and 95% confidence intervals (95% CI) were reported. The Chi-square statistic was reported for other categorical data. Spearman rank order correlations were used to correlate skewed distributions. All analyses were conducted using SPSS for Windows (release 11.0) (SPSS Inc., 2001).

3. Results 3.1. Number of cases and cause of death A total of 146 cases were identified. Cocaine was implicated in the direct cause of death in 86% (n = 125) of cases, was an antecedent cause in 8% (n = 11) and a significant contributing condition in a further 7% (n = 10). Cases peaked in 1998 (28 cases) and in 2001 (26). Drug toxicity was the direct cause of death in 86% of cases (Table 1). Death was attributed solely to cocaine toxicity in 5% of cases, and to combined drug toxicity in 81%. The most common drugs associated with cocaine as a cause of death were opioids (77% of cases), alcohol (15%) and benzodiazepines (14%). In 16 cases (11%) death was attributed to myocardial ischaemia/infarction, pneumonia, cerebrovascular accidents or multiple organ failure, due to or exacerbated by cocaine use. There were three cases of hanging in which cocaine was a significant associated condition: two cases were suicides, and one was an autoerotic asphyxial act. In two other cases of suicide (carbon monoxide poisoning, gunshot to head) cocaine

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Table 2 Demographic characteristics of decedents

Table 3 Circumstances of death

Males (n = 123)

Females (n = 23)

All (n = 146)

Age (years)

34.9

29.4

34.1

Employment (%) Unemployed Full-time (Professional occupation) Part-time Student Sex worker

46 51 (27) 2 1 0

22 39 (21) 0 13 26

42 49 (26) 1 3 4

Marriage status (% single) Australian born (%)

75 75

65 69

74 74

Treatment status (%) Not in treatment Methadone Naltrexone Drug free rehabilitation

92 7 1 1

83 9 4 4

90 7 1 1

intoxication was considered a significant contributing condition. In a further two cases death was due to multiple injuries sustained from falls whilst intoxicated with cocaine. 3.2. Demographic characteristics The mean age of decedents was 34.1years (S.D. 9.0, range 17–63 years), and 84% were male (Table 2). Males were, on average, five years older than females (34.9 versus 29.4 years, t144 = 2.8, p < .01). Most cases (74%) were aged in either their 20s or 30s. Only 2% (3 cases) were younger than 20 years. It is noteworthy that 4% of cases were aged 50 or older, and that two decedents were aged in their 60s. Three quarters of decedents were married or in defacto relationships, and three quarters were Australian born. Over half of the sample was employed, with females significantly more likely to be so (OR 3.10, 95%CI 1.08–8.89). Twenty six percent of decedents were employed in professional occupations: managers/administrators (3%, e.g. company director), professionals (10%, e.g. solicitor, accountant), associate professionals (13%, e.g. real estate agent, small business owner). Ten percent were enrolled in a drug treatment programme at the time of death: methadone maintenance (10 cases), naltrexone maintenance (2 cases), drug free residential communities (2 cases). 3.3. Circumstances of death The predominant form of cocaine administration was injection (86%) (Table 3). Non-parenteral routes were employed in 16% of cases: nasal (8%), oral (3%), smoking (1%) and anal (1%). In three cases, there was evidence that more than one route of administration had been employed shortly prior to death: injection + nasal, injection + smoking and oral + smoking. In 3% of cases, route could not be definitively established beyond the exclusion of injection.

Males (n = 123) %

Females (n = 23) %

All (n = 146) %

Route of administration Injection 87 Nasal 7 Oral 3 Smoked 2 Anal 2 Unspecified non-parenteral 3

78 13 4 0 0 4

86 8 3 1 1 3

Suicide Prison releasea Weekend death

5 6 58

22 4 50

8 6 57

Location of death Home Hotel Hospital Public location Shooting gallery

49 20 9 19 4

73 0 13 9 4

53 16 10 17 4

Presence of others Alone Others present Segregated from others

43 42 15

30 39 30

41 41 18

Interventions None Ambulance Hospital Bystander CPR Other intervention

81 16 9 3 0

83 9 13 4 0

82 15 10 3 0

a

Within month prior to death.

Eight percent of cases were suicides. Females were significantly more likely than males to have died by suicide (22% versus 5%, OR 5.42, 95% CI 1.50–19.61). Seven of these cases were injectors and four non-injectors. In six cases, suicide was by deliberate drug overdose. In five cases, suicide was by other means: hanging (2), gunshot (1), jumping from a height (1), carbon monoxide poisoning (1). Six percent of cases were released from prison in the month prior to death. Of these eight cases, two died on the day of release and a further five within a week. Time of death within a period of 6 h was determined in 114 cases. These deaths were distributed throughout the day, with no significant difference between time periods. Day of death was determined in 135 cases. Deaths were not uniformly dis2 tributed throughout the week (χ6d.f. = 19.4, p < 0.005), with a disproportionate number of deaths occurring on weekends (OR 1.76, 95% CI 1.09–2.85) (Table 3). There was no significant difference in the number of deaths that occurred across months, with no summer peak. By far the most common location for death to occur was private home (53%). A significantly greater proportion of females died in home environment (OR 2.98, 95% CI 1.10–8.05) (Table 3). Forty four percent of cases died in their own home, the single most common location of death. No intervention occurred prior to death in 82% of cases. Potential interventions included formal medical intervention,

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Table 4 Toxicology results Druga

Males (n = 123)

Cocaine concentrationsb Blood cocaine (mg/L) Blood benzoylecognine (mg/L) Presence of other drugs (%) Morphine Codeine Alcohol Cannabis Benzodiazepines Amphetamines Methadone Antidepressants Antipsychotics MDMA (“ecstasy”) Miscellaneous other drugs No. drug classes a b

0.12 0.30 97 80 55 37 36 25 21 10 6 3 3 15 3.5

Females (n = 23) 0.06 0.50 87 77 61 30 13 26 0 13 13 0 0 9 3.1

All (n = 146) 0.10 0.40 95 79 56 36 32 25 18 10 7 3 3 14 3.5

Detected in blood, urine or liver. n = 140.

bystander CPR, or other direct interventions by non-medical personnel. Equal proportions of cases died alone, or with others present. Eighteen percent died segregated from others (e.g. in a different room). No intervention prior to death occurred in 34 of the 60 cases where others were present. 3.4. Toxicology Blood toxicology results were available for cocaine and benzoylecgonine in 140 cases. Blood cocaine was detected in 64% of cases. Among these cases, the median blood cocaine concentration was 0.10 mg/L (range 0.01–8.00 mg/L) (Table 4). Males and females did not differ significantly in the proportion in which cocaine was detected (64 versus 68%), or in median blood cocaine concentrations (0.12 versus 0.06 mg/L). The median blood benzoylecgonine concentration was 0.40 mg/L (range 0.00–20.00 mg/L), with no significant difference between males and females (Table 4). The range of blood benzoylecgonine concentrations are presented in Fig. 1. Time between death and autopsy was not correlated with blood benzoylecgonine concentration (rho = −0.12, p > 0.20). Toxicological results indicating the presence of drugs in the body (e.g. blood, liver, urine) were available for all cases. In 5% of cases cocaine and/or benzoylecgonine was the sole drug detected (females 13%, males 3%). Cases had a mean of 3.5 (S.D. 1.3, range 1–7) drugs present at time of death, with no difference between males and females (3.5 versus 3.1). The most common co-occurring drug was morphine (79%) (Table 4). The median blood morphine concentration of cases was 0.52mg/L (range 0.01–12.0 mg/L). Time between death and autopsy was not significantly correlated with blood morphine concentration (rho = −0.01, p > 0.90). There was a significant positive correlation between blood morphine and

Fig. 1. Blood benzoylecgonine concentrations.

blood benzoylecgonine concentrations (rho = 0.18, p < 0.05). Codeine was detected in 56% of cases. However, in most cases this was an artefact of heroin administration; the median blood codeine concentration was low (0.05 mg/L), and in almost all cases (78/81) morphine was also detected. Alcohol was detected in 36% of cases, with a median blood concentration of 0.07 g/100 ml (range 0.01–0.30 g/100 ml). Time between death and autopsy were not significantly correlated with blood alcohol concentrations (rho = −0.11, p > 0.20). There was a significant negative correlation between blood benzoylecgonine and blood alcohol concentrations (rho = −0.22, p < 0.01). Whilst cannabis was detected in 32% of cases, blood THC was detected in only six cases. 3.5. Major post-mortem findings Autopsy reports were available for 145 cases (122 males, 23 females). No autopsy was conducted in one case. Cardiac pathology was noted in 57% of cases (Table 5). Decedents with cardiac pathology were significantly older (36.5 versus 31.1 years, t143 = 3.7, p < 0.001) and more likely to be male (OR 11.68, 95% CI 1.72–12.73). The most common pathology was coronary artery atherosclerosis (39% of cases) (Table 5). There was a large difference between males and females in the presence of atherosclerosis (45% versus 9%, OR 8.62, 95%CI 1.94–38.38). In 15% of cases (all male), moderate or severe arterial occlusion was noted. The most common sites of atheroma were the aorta (26%) and the left coronary arteries (23%). Cardiac hypertrophy was noted in 14% of cases, all of whom were male. Cerebrovascular pathology was noted in 22% of cases (Table 5). There were no differences in gender or age between cases where cerebrovascular pathology was noted and other cases. The most commonly reported cerebrovascular pathology was atherosclerosis (10%), most commonly of the basal vessels of the brain (6%).

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Table 5 Cardiac and cerebrovascular pathology of decedents Males Females (n = 122) % (n = 23) %

All (n = 145) %

62 46 11 7 25 2

26 9 0 0 9 0

57 39 9 6 23 1

Sites of coronary atherosclerosis Left coronary arteries 26 Right coronary arteries 17 Aorta 30 Unspecified 9

4 4 4 0

23 15 26 8

Hypertrophy

16

0

14

Cerebrovascular pathology Atherosclerosis Basal vessels Carotid arteries Circle of Willis Hippocampus

23 12 7 5 2 1

17 0 0 0 0 0

22 10 6 4 1 1

Hypoxic damage

2

4

4

Old cortical damage

2

0

1

Haemorrhage

2

0

1

Other cerebrovascular pathology

4

5

4

Cardiac pathology Atherosclerosis Severe Moderate Mild Unspecified

Pulmonary pathology was noted in 27% of cases. Bronchopneumonia was noted in 14% of cases, and bronchitis in a further 3%. Histologically obvious hepatic pathology was noted in 39% of cases, most commonly hepatitis C (HCV) related hepatic changes (22%). Steatosis was noted in 15% of cases, and cirrhosis in 3%. Congestion of the spleen was noted in 12% of cases, and of the kidneys in 11%. Pathology other than those listed above was noted in 20% of cases. The most common organs in which other pathology was noted were the kidneys (6%) and the spleen (3%).

4. Discussion A substantial number of cocaine-related deaths occurred over the study period. The peak years of deaths (1998, 2001) correspond to the years in which cocaine use and availability was at its highest (Darke et al., 2002). The most common cause of death was drug toxicity, in most cases attributed to two or more drugs, a pattern consistent with that seen in the United States (Tardiff et al., 1996; Coffin et al., 2003). Consistent with the strong relationship between heroin and cocaine use (Darke et al., 2002; Coffin et al., 2003), opioids were the drugs most commonly reported in toxic combination with cocaine. Deaths were not restricted to direct toxicity, however, with approximately one tenth of cases directly due to complications of cocaine use, such as myocardial infarction or cerebrovascular accident.

As in other studies (Sanchez et al., 1995; Tardiff et al., 1996; Coffin et al., 2003), males constituted the bulk of cases. To an extent this reflects the preponderance of males among cocaine users (Australian Institute of Health and Welfare, 2002). However, while males constitute approximately 60% of cocaine users, they comprised over 80% of cases in the current study. Unlike heroin-related deaths, where males are substantially more likely to have alcohol detected (Darke and Zador, 1996), there were no substantial gender differences in polydrug using patterns to explain this overrepresentation. Males were, however, five times more likely to have coronary disease, which may have contributed to their over-representation. The average age of decedents was in the mid-thirties, similar to overseas studies (Tardiff et al., 1996; Coffin et al., 2003). These were not young, inexperienced drug users. In fact, one in seven decedents were older than 45 years, and two were in their sixties. By contrast, only 4% of NSW heroinrelated fatalities were found to be older than 45 years (Darke et al., 2000). Few cases were in drug treatment at the time of death. In stark contrast to heroin-related fatalities (Darke and Zador, 1996; Darke et al., 2000), the majority of decedents were employed. In fact, a quarter of all decedents were in professional occupations. The employment status of decedents is consistent with research indicating two distinct populations of cocaine users in Australia: an employed, “functional” group of cocaine users, and a lower socio-economic, primarily unemployed, drug entrenched group of IDU (Hando et al., 1997). It should be noted, however, that the majority of cases with higher socio-economic status had also injected cocaine prior to death. The distinction is thus not simply between routes of administration, but between different social groups of users. In contrast to the population use of cocaine, where nasal use predominates (Australian Institute of Health and Welfare, 2002), injection was the most common route of administration among fatalities. Cases were not restricted to injectors, however, as has been reported elsewhere (e.g. Wetli and Wright, 1979). Sixteen percent of cases died after using non-injecting routes of administration, far higher than the 1% reported among NSW heroin-related deaths (Darke et al., 2000). This may reflect the larger proportion of cocaine users who use non-parenteral routes of administration compared to heroin users (Australian Institute of Health and Welfare, 2002). There was an over-representation of deaths on weekends. By contrast, studies of heroin-related deaths consistently report no weekend peak, reflecting the high proportions of unemployed, dependent users in this population (Darke and Zador, 1996). No intervention occurred prior to death in the vast majority of cases, partially reflecting cases who died without others present. However, it also reflects the fact that reactions by drug users present at overdoses are poor (Darke and Zador, 1996): in over half of cases where others were present, no intervention occurred.

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There were wide variations in cocaine and benzoylecgonine concentrations. A sizable proportion of cases had extremely high cocaine and/or benzoylecgonine concentrations, ranging up to more than 8 and 20 mg/L respectively. However, a large proportion of cases had low blood concentrations. One possible explanation for this finding may relate to the fact that alcohol was detected in one-third of cases. As noted above, the concomitant ingestion of cocaine and alcohol produces cocaethylene, an active metabolite of cocaine that enhances, and extends, the effects of cocaine (Brookoff et al., 1996; Harris et al., 2003). The production of cocaethylene has been demonstrated to reduce levels of urine cocaine and benzoylecgonine (Harris et al., 2003). The finding that there was a negative correlation between blood alcohol and cocaine concentrations is consistent with this hypothesis. Unfortunately, cocaethylene is not routinely tested for in Australia. The toxicological data are also consistent, however, with previous research, which suggests that death may occur even in the presence of low cocaine concentrations (Platt, 1997; Lange and Hillis, 2001; Karch, 2002). One reason suggested for this phenomenon relates to the effects of cocaine on the heart (Karch et al., 1991; Lange and Hillis, 2001; Karch, 2002). The cumulative cardiotoxic effects of cocaine may produce pathology in which even a small amount of cocaine may result in death. Low blood concentrations of cocaine have also been shown to produce acute vasospasm (Moliterno et al., 1994; Lange and Hillis, 2001; Karch, 2002). In addition, the consumption of cocaine with other drugs, particularly opioids and alcohol, may substantially increase the risk of cocaine overdose (Friedman et al., 1996; Platt, 1997). In almost all cases, drugs in addition to cocaine were detected, consistent with the toxicology of cases elsewhere (Wetli and Wright, 1979; Tardiff et al., 1996; Coffin et al., 2003). Morphine was the drug most commonly detected in combination with cocaine. The combination of cocaine and heroin has also been found to be the most common combination among studies of fatalities conducted in the United States (Wetli and Wright, 1979; Tardiff et al., 1996; Coffin et al., 2003). The prevalence of this drug combination, in part, reflects the strong association between cocaine and heroin use in Australia and elsewhere (Darke et al., 2002b). However, the effects of combining these two drugs must be considered. As noted above, it has been argued that the combination of these drugs is more dangerous than when either is used alone. It may also be speculated that respiratory depression may induce cardiac failure among cases where cardiac disease is present, as it was in a large proportion of cases in this study. Cardiac pathology was noted in over half of cases. Males were more likely to have cardiac pathology, and constituted all cases with severe pathology. This is consistent with higher death rates among males from cardiac disease across the broader population. Atherosclerosis of the coronary arteries was commonly reported, as has been noted amongst cocaine users elsewhere (Rump et al., 1995; Hollander et al., 1997; Wilson, 1998; Mittleman et al., 1999; Pavon-Jimanez

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et al., 1999; Karch, 2002; Vasica and Tennant, 2002; Kontos et al., 2003). Fifteen percent of cases had moderate to severe atheroma, all of whom were male. The extent of the gender difference is illustrated by the fact that approximately half of males had some degree of atheroma, compared to only one-tenth of females. The most common sites of cardiovascular atheroma were the aorta and the left coronary arteries. As noted above, previous research has reported a strong relationship between cocaine use and left coronary artery atheroma. Cardiac hypertrophy was reported in 14% of cases, all of whom again were males. Like coronary artery atheroma, cardiac hypertrophy has been associated with cocaine use (Om et al., 1993; Friedman et al., 1996; Benzaquen et al., 2001; Karch, 2002). The mechanism behind cocaine-induced cardiac hypertrophy is believed to relate to the increased cardiac demands for oxygen that result from cocaine consumption. Atherosclerosis of the cerebrovascular system was noted in a substantial minority of cases, most commonly among the basal vessels and carotid arteries. Given the central role of these vessels in supplying blood to the brain, findings of atherosclerosis among these cases may have serious implications for cocaine users. A range of other pathology was also noted. Overall, the post-mortem reports suggest that the general health of cases was poor at the time of death. The current study indicates that cocaine-related deaths are a significant clinical problem in NSW. The demographic characteristics indicate a large number of employed individuals, and a significant proportion who do not inject. Any interventions would thus have to move beyond IDU, and also address employed, non-injecting cocaine users. Information on the role of polydrug use would be vital, particularly in relation to heroin and alcohol, as would improving responses to cocainerelated events. In addition, education on the cardio-toxic effects of cocaine would be central. Increasing the number of cocaine users enrolled in drug treatment may also reduce the number of cocaine-related fatalities. The current study indicates that cocaine-related mortality and morbidity are an area deserving further clinical and research attention.

Acknowledgments This research was funded by the Australian Government Department of Health and Ageing. The authors wish to thank staff at Glebe and Westmead Coroners Courts. In particular, we wish to thank Diane Flecknoe, Michael Littlejohn, Noel Drew and Joanne Ross.

References American Psychiatric Association, 2000. Diagnostic and Statistical Manual of Mental Disorders (4th ed. Text Revision). American Psychiatric Association, Washington, DC. Australian Bureau of Statistics, 1997. Australian Standard Classification of Occupations (2nd Edition). Australian Bureau of Statistics, Canberra.

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