Drug-related fatalities in Cologne 1989-2000 with special reference to methadone.

All drug-associated deaths from 1989 to 2000* were analysed at the Institute for Legal Medicine in Cologne. Information about sex, gender, drug consumption, time, place and circumstances of death could be analysed. 605 cases were recorded, in 518 cases a toxicological analysis and in 171 cases an autopsy was possible. If all information allowed a declaration of the cause of death, mostly acute drug intoxication was found. Heroin poisoning heads the list, often combined with benzodiazepines and alcohol. In comparison with other studies the percentage of methadone positive specimens is low, even if the proportion of specimens being positive for methadone increased from 1989 to 2000. Our results are discussed with regard to other studies and information about the regional structures of maintenance treatment.

Introduction

The issues "drug consumption" and "drug-related deaths" have always been and will always be of interest to the general public and the scientific community. In Germany a total of 2023 drug-related deaths were registered last year (2000), making it the largest number since 1992. Methadone is increasingly being discussed in context with deaths associated with maintenance treatment A recent change to the legislation on which such treatment is based in Germany stipulates that the treating physician have an additional qualification and (re)introduces a centralised registry for all patients undergoing maintenance treatment. As for the political reasoning behind this decision, it is probably mainly based on surveys of the drug scene with a high percentage of methadone-associated deaths. Thus, in 2000 methadone was found in body fluids of 22.7% of those dying after a drug overdose in the Federal Republic of Germany (31). A survey in Hamburg revealed that the figure was over 60% (24). Other national and international studies have stressed the link between methadone and drug-related deaths (1, 2, 4, 6, 7, 9, 10, 12-16, 18, 19, 21-25, 28, 31, 35, 38, 40). Our Institute also investigates deaths in the drug scene to differentiate the causes of death, based on toxicological screening attention is focussed on methadone. We first present our own results and then discuss the relevance of such, usually regional, investigations.

Methods

Cases in which drug consumption was registered in context with the cause of death for the years 1989 to 2000 were selected from amongst the total deaths registered at our Institute (an average of 1000 per year). Extensive investigations were possible, in particular for the last two years (Köln Fortune Project Nos. 172/1998 & 75/1999). The anamnesis data were in the main based on statements made by the investigating authority. Along with personal data, it was particularly habits of consumption, circumstances leading to death and cause of death that were taken into consideration during the analysis. A total of 605 drug-related deaths were registered; in 518 cases material was available for a chemical-toxicological test; an autopsy was carried out in 171 cases. On the subject of maintenance treatment, separate research was carried out on the deaths made known to us by approaching special methadone units and doctors' practices. The following criteria were taken into account when attempting to establish the cause of death as "drug-related": signs of acute, intravenous drug consumption (e.g., finding an empty syringe or other utensils used by drug addicts), locating what seemed to be fresh puncture marks during the post-mortem examination (which could not be attributed to emergency treatment), eyewitness accounts regarding acute consumption with subsequent worsening of the person's condition, toxicological analysis of the blood (immunochemical and chromatographic testing for drugs, medicaments and alcohol), the results of an autopsy (if possible).

Results

An overview of all drug-related deaths from 1989 to 2000 with special reference to methadone described an increase of drug related deaths up to more than 80 cases in 1994. The following years showed a decrease until 1998. Since 1999 the number of cases increased again, in 2000 62 drug addicts died. Based on the results of the chemical-toxicological analysis, 14 of a total of 518 cases indicated methadone was present in the urine or blood. This corresponds to just under 3% of all investigated deaths. The chronological distribution of the cases shows, after initially only sporadically proven methadone use, a marked increase in the year 2000 (10% or 6 cases, in 1999 only 3 cases). The spectrum of all substances found in body fluids and/or organs shows a clear dominance of opiates, followed by benzodiazepines. Cocaine plays a minor role; "other drugs" includes substances such as LSD and amphetamines. It was not possible to establish the cause of death in all cases, particularly when the results of an autopsy were not available or the results of the toxicological screening could not be clearly evaluated (as was the case for 32% of the men and 22% of the women). Drug intoxication was - as was expected - top of the list with 65% (men) and 69% (women). The percentage of all identified substances (mostly combined consumption) is given in the following list: 77% heroin, 14% benzodiazepines, 9% cocaine, 6% other medicines, 3% methadone, 3% cannabinoide, 1% other drugs and 42% BAC levels ³ 0.5?. Obvious suicides, accidents (especially road accidents) and death following illness are the exception (<1% and 2%, respectively). In most cases details on apparent, acute, intravenous drug consumption prior to death were known, which is why even for those deaths without a post-mortem examination and toxicological results which cannot be clearly interpreted, a lethal intoxication seems to suggest itself. The table 1 provide an overview of the 14 cases of proven methadone consumption. The persons were split into two groups: one with and one without current (acute) history of methadone treatment. Our collection of cases, evaluating the results of the toxicological screening following Heinemann et al. (18) indicates two cases of methadone mono-intoxication (case 1 and 4). Case 1 was caused by a false estimation of the individual opiate tolerance by the physicians. The cases number 8, 9 and 10 showed high concentrations of methadone, although in combination with considerable quantities of alcohol or benzodiazepines in the sense of a methadone-dominated mixed intoxication. The cases number 5 and 13 probably followed acute heroin overdose; case number 6 was a doxepine-dominated intoxication. Two people died as a result of serious polytrauma (cases number 7 and 11). The remaining three cases (number 2, 3 and 14) can be classed as mixed intoxication without relevant methadone influence or other dominant substances. The methadone concentration was evalutaed according to the concentration classes of Barrett et al. (2).

Discussion

A concluding evaluation of the results - even when this is a cautious assessment - shows that in our survey intoxication with methadone as the only substance is the exception and, tragically, also iatrogenically induced. This observation supports statements by other authors on the problem of treatment errors during the course of maintenance treatment, especially at the beginning (13, 23, 25, 28). Evaluating drug-related deaths based on the results of toxicological screening is not unproblematical (14, 15, 20, 22, 26, 36, 37, 39). Therefore, drug-related deaths must be assessed with caution, taking the patient's history and the circumstances of death into account and, ideally, in context with the results of an autopsy. Of those cases investigated by our Institute, five of the 14, or rather 518, cases investigated can be classed as methadone-associated deaths in the stricter sense, corresponding to just 1% of all investigated cases. In our cases the main problem is also - analogous to the entire population of investigated drug-related deaths - consumption of additional drugs, especially in those patients in therapy (i.a. 2, 8, 10-12, 16-19, 27, 33). The main substances involved are alcohol and benzodiazepines. As well as investigating each individual case, "system-relevant" facts have to be taken into account. Maintenance treatment has become established in Germany since 1990, with an increasing number of patients being treated each year (5). At June 2000: 2633 doctors providing maintenance treatment on German State health insurance schemes were treating 32,972 patients. A comparison of these figures with those as at June 1999 showed an increase in patients on maintenance treatment of 29% - within the space of one year (34). In Cologne 25 therapy places were created in August 1989 as part of a test phase for methadone/ polamidone-assisted treatment of heroin addicts in Germany. The range of therapies needed was expanded; at present around 1000 patients are undergoing supervised maintenance treatment. The exact number of patients on maintenance treatment is unknown, as there is no duty to register them; at present details are based on the number of patients whose treatment is being paid for by state health insurance schemes. Up until the beginning of 2000, take-home doses were dealt with conservatively and no thorough statistics are as yet available (data for Germany see (43)). Research into methadone maintenance treatment in the case of those drug-related deaths registered by us in the years 1999 and 2000 showed that only a few people were undergoing such therapy right up until when they died (cf. Table 1). In six cases, the maintenance treatment ended more than 12 months previously; in 10 cases the time between the end of the therapy and death was 1 to 12 months. Based on around 1000 patients in Cologne and using the figures for deaths with current history of maintenance treatment to project a figure for the total number of patients undergoing maintenance treatment, in 1999 and 2000 0.3% and 0.6%, respectively, of those undergoing such therapy died. If all the registered drug-related deaths are related to the estimated total of around 7000 drug addicts living in Cologne, then, for example, in 1999 and 2000 0.6% and 0.9%, respectively, of drug addicts died. The death rate amongst patients on maintenance treatment at least appears to be slightly lower when based on these figures. In view of the declared aim of maintenance treatment, namely to reduce the number of deaths due to acute opiate intoxication, the goal has been achieved cf. also 7, 30, 32, 33, 42). In addition, a recent study in Hamburg (3) shows that it has a positive influence on drug-related crime; comparable data for Cologne are not available.

Table 1. Toxicological case report

case no.	methadone mg/L	morphine mg/l (free)	other drugs	BAC ?
1	0,66	ø	ø	0,00
2	0,21	ø	Cannabis, Diazepam, Doxepin	> 1,00
3	0,20	ø	Bromazepam	< 0,05
4	0,44	ø	ø	< 0,05
5	0,22	0,58	Diazepam, Antidepressant	> 0,50
6	0,21	ø	Doxepin, Carbamazepin	> 1,00
7	0,26	ø	Cannabis, Diazepam	> 0,50
8*	1,58	0,03	Diazepam	> 2,00
9* #	0,62	ø	Diazepam	> 0,05
10* #	0,43	ø	Diazepam	> 1,50
11* #	0,11	ø	ø	< 0,50
12*	< 0,05	0,10	Amphetamines	0,00
13* #	< 0,05	0,29	MDMA	< 0,05
14*	< 0,05	ø	Cannabis, Imipramin	< 0,05
* cases without current maintenance treatment (M.T.) # cases with M.T. in the past

In conclusion, one can state that there are no relevant problems due to methadone-associated deaths in the city of Cologne with about 1 million citizens. In comparison to other surveys in big cities with subsequent public discussion of methadone maintenance treatment, this result seems remarkable to us. Furthermore, the problem of unauthorised access to methadone, for example, by small children with subsequent intoxication (e.g. 16, 21) has only been documented once in Cologne to date. In principle the small number of cases reported here confirms that methadone related death among drug addicts is not associated with maintenance treatment, although it is at least jointly responsible for the death of some patients. Methadone-associated deaths usually - in comparison to other investigations (see 11, 19, 27) - affect people, who are not undergoing maintenance treatment, particularly when deaths at the beginning of maintenance treatment due to wrong dosage/wrong treatment by a doctor are not taken into account. In our opinion it is not possible at present to carry out extensive comparisons of the various evaluations of the topic "methadone-associated deaths in the drug scene", as neither complete nor transparent information is available on the respective basis for evaluating individual cases as well as the system-relevant data. Thus the question of whether the initially obvious connection between the structure of a maintenance treatment programme and the rate of deaths under the influence of methadone is actually a causal relationship (as the example of Hamburg seemed to suggest) or not must remain unanswered for the time being. As, however, these questions may possibly lead to factors which can be influenced, we believe it is very important in the interest of further discussions to collate the following information:

1. Case-related, individual parameters, in particular data relating to general anamnesis, habits of consumption, circumstances of death and statements regarding cause of death, taking into account toxicological and morphological screening;

2. System-related, structural parameters, in particular data relating to the number and composition of the group of drug addicts and the patients undergoing maintenance treatment, results regarding morbidity and mortality in the populations investigated, rules on access to and course of the maintenance treatment in the region concerned.

When discussing the pros and cons of maintenance treatment, the regional conditions and findings regarding the population of drug addicts and the patients undergoing maintenance treatment should be considered together (e.g. 18, 41, 42).

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