Fatal drug poisonings: medico-legal reports and mortality statistics

Forensic Science International 136 (2003) 35–46

Fatal drug poisonings: medico-legal reports and mortality statistics R.A. Lahti*, E. Vuori Department of Forensic Medicine, University of Helsinki, P.O. Box 40, Helsinki 00014, Finland Received 11 December 2002; accepted 27 May 2003

Abstract The entire fatal drug poisoning panorama in Finland is considered in terms of three categories: accidental, self-inflicted and undetermined (whether accidental or with intent to harm) deaths. The study material consisted of all 500 deaths in 1997 that medical examiners, after examination(s) at the Forensic Toxicology Division (FTD) of the Department of Forensic Medicine, University of Helsinki, officially certified as resulting from drug poisoning. These deaths were matched with data on the same deaths registered at Statistics Finland (SF), the national mortality statistics office. The SF register included 72 additional instances of deaths resulting from drug poisoning. In all but two of these cases, the cause-of-death determination was based on a medico-legal inquest with autopsy and forensic toxicological examination(s) and was certified, in most of the cases, as due to the alcohol component in multiple-toxicant combinations. Reclassifying these deaths at SF to the category of drug component is in accordance with current International Classification of Diseases (ICD-10) regulation of coding ‘‘to the medicinal agent when combined with alcohol’’; the principle and practice, which is recommended to be amended to equalize the status of alcohol and drug when explicitly stated by a forensic examiner as the principal toxicant in combined poisonings. With regard to manner-of-death, the agreement rates between medico-legally proven deaths from drug poisoning and those registered at SF were 79.8% for accidents, 98.5% for suicides and 0% (nil) for undetermined deaths, at the level of threecharacter external cause codes (E-code). All deaths originally certified as undetermined were re-assigned, most frequently to the category of accidental death. Since within an advanced and sophisticated medico-legal system, a medical examiner’s evidencebased statement, even when the conclusion reached is undetermined (as to intent), should be taken as a compelling argument, the practice of reclassification cannot be considered advisable because assembled information is lost. Concerning the assigned drug-specific groups, the agreement according to the manner-of-death between certifications and registrations was fairly good. From among the accidents, however, opioid poisonings were re-assigned in 11 (29.7%) cases, mostly to the drug abuse/dependence categories, i.e. they were considered as natural deaths by the statistics office. The drugspecific observations were possible only by using the codes from the Anatomical Therapeutic Chemical (ATC) classification of drugs. This is why the incorporation of ATC codes into the ICD system, whenever reasonable, is recommended. # 2003 Elsevier Ireland Ltd. All rights reserved. Keywords: Fatal drug poisonings; Forensic toxicology; Medico-legal cause-of-death determination; Cause-of-death coding; Mortality statistics

1. Introduction In Finland, all deaths suspected to be due to poisoning are submitted to medico-legal cause-of-death determination [1].

* Corresponding author. Tel.: þ358-9-191-27467; fax: þ358-9-191-27518. E-mail address: [email protected] (R.A. Lahti).

This practice systematically includes forensic toxicological examination. These post-mortem examinations are centralized [2] to an authorized toxicological laboratory at the Forensic Toxicology Division (FTD) of the Department of Forensic Medicine, University of Helsinki, which guarantees virtually complete national coverage of fatal poisonings and as such the quality and homogeneity of results for subsequent use in epidemiological and other kinds of drug-specific studies.

0379-0738/$ – see front matter # 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/S0379-0738(03)00223-8

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R.A. Lahti, E. Vuori / Forensic Science International 136 (2003) 35–46

Medical examiners provide the FTD with a copy of their final report, i.e. the death certificate, of each death for which a toxicological examination is performed. In addition to their own laboratory results, the FTD register contains a medicolegal statement on the cause(s)- and manner-of-death, i.e. whether the death was considered to be an accident, suicide, homicide, undetermined or natural by the medical examiner. Finnish official mortality statistics, based on the same death certificates, are collected at Statistics Finland (SF), after possible consultation of an expert panel [3] and/or querying the certifier for additional information [4], in accordance with World Health Organization (WHO) principles and notes [5,6], and internal guidelines. WHO defines the causes of death to be entered on the death certificate as ‘‘all those diseases, morbid conditions or injuries which either resulted in or contributed to death and the circumstances of the accident or violence which produced any such injuries’’. The cause for primary tabulation, designated the underlying cause-of-death, is defined as ‘‘(a) the disease or injury which initiated the train of events leading directly to death, or (b) the circumstances of the accident or violence which produced the final injury’’ [5]. At SF, the 10th revision of the Statistical International Classification of Diseases (ICD-10) and Related Health Problems [6] is used to code the certified causes of death and to select the underlying cause-of-death. ICD-10 is divided into 21 sections, designated with Roman numerals. Sections I–XVII cover diseases and other morbid conditions, and section XVIII symptoms and signs. Section XIX categorizes injuries, poisonings and other consequences of external causes. Section XX, external causes of mortality (and morbidity), is primarily used to classify causes of injury and poisoning. The sections are subdivided into blocks, and each block into categories, with code numbers of their own. To describe a fatal injury, poisoning or other consequence of external cause for mortality statistics, two codes are applicable: a code from section XIX describing the nature of the injury, and a code from section XX describing the external cause, e.g. a suicide by overdose of insulin is coded at three-character level with X64 (for suicide) and T38 (for insulin poisoning). In mortality tabulation of underlying cause-of-death, the manner-of-death, i.e. code X64 in the example above, is the primary code. When death certification is correct, it is likely that the selected underlying cause-of-death agrees, before possible modification according to WHO regulations, with the originating antecedent cause-of-death as stated by the medical examiner. From a medico-legal as well as a statistical point of view, the correct determination of the cause and manner of a suspected fatal drug poisoning is essential. In general, the presence and quantity of poisonous common drugs in deceased persons can routinely be verified by modern toxicological methods. But, even when a suspicion of drug overdose arises from laboratory findings, drug poisoning as the cause-of-death cannot only be a ‘‘laboratory diagnosis’’; anamnestic information, circumstances surrounding the

death, autopsy findings and toxicological results together are necessary for a forensic examiner to form a justified, evidence-based opinion about the manner and cause(s) of death. The problems, if any, usually arise with multiple-drug poisonings. The medical examiner must identify the principal component from among a combination of toxicants when certifying the death, and the statistics office must correctly, according to the ICD regulations, select and code the underlying cause-of-death. As far as we know, a comparison of fatal drug poisonings by drug-specific toxicological diagnoses on death certificates with registered cause-of-death poisonings has not been published earlier. At the rougher main category level of ICD-10, in the Finnish cause-of-death data from 1995, the disagreement rate between certified and registered causes of death overall was 29.4%, and the false-positive and falsenegative rates for all fatal poisonings were 13.8 and 35.9%, respectively [3]. In multiple-toxicant poisonings, the effect on the number of fatal drug poisonings of the ICD-10 regulation of coding ‘‘to the medicinal agent when combined with alcohol’’ has not yet been clarified.

2. Materials and methods The study material consists of all deaths from drug poisoning in 1997, as reported by the medical examiner after toxicological analyses at the FTD, for a total of 504 deaths. Of these, 18 deaths were excluded because the death had occurred in 1996 and 14 deaths from the 1998 register were added since they were pronounced in 1997. The final number of deaths in the FTD material is 500. Each of these 500 medico-legally proven fatal poisonings were matched with the corresponding cause-of-death information at SF, and in every case, the counterpart was found. The study file was created with Excel-6 using the following variables on each death: case identification number, age and gender of the deceased, type of post-mortem, results of forensic chemical analyses performed, drug definition by the Anatomical Therapeutic Chemical (ATC) code [7], and ICD-10 code(s) (Table 1) for the underlying and other causes of death and for the manner-of-death (accidental, suicidal, undetermined or natural); all ICD codes are as stated by the forensic examiner and, correspondingly, as registered in the national mortality statistics. The study data were considered, firstly, by the medicolegally proven groups of accidents, suicides and undetermined deaths, and secondly, by the drug-specific grouping of drugs into antidiabetics, cardiovascular drugs, opioids, other analgesics, antiepileptics, neuroleptics, anxiolytics, hypnotics, antidepressants, amphetamines and other drugs. By comparing case reference information in the SF and FTD registers, deaths from drug poisonings not reported as such by the medical examiner were identified. These cases, ‘‘false-negative’’ drug poisonings from the SF point of view, numbered 72 and are dealt with here separately.

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Table 1 ICD-10 categories for drug poisonings as well as their drug-specific and external cause codes Category

Code

External causea (‘‘E-code’’)

Poisoning by Systemic antibiotics Other systemic anti-infectives and antiparasitics Hormones and their synthetic substitutes and antagonists, not elsewhere classified Non-opioid analgetics, antipyretics and antirheumatics Narcotics and psychodysleptics (hallucinogens) Anesthetics and therapeutic gases Antiepileptics, sedative-hypnotic and anti-Parkinsonism drugs

T36 T37 T38 T39 T40 T41 T42

X44;X64;Y14 X44;X64;Y14 X44;X64;Y14 X40;X60;Y10 X42;X62;Y12 X44;X64;Y14 X41;X61;Y11

Psychotropic drugs, not elsewhere classified Antidepressants Neuroleptics Psychostimulants with abuse potential Other or unspecified psychotropic drugs

T43 T430–T432 T433–T435 T436 T438–T439

X41;X61;Y11

Drugs primarily affecting the autonomic nervous system Primarily systemic and hematological agents, not elsewhere classified Agents primarily affecting the cardiovascular system Agents primarily affecting the gastrointestinal system Agents primarily acting on smooth and skeletal muscles and the respiratory system Topical agents primarily affecting skin and mucous membrane, and ophthalmological, Otorhinolaryngological and dental drugs Diuretics and other or unspecified drugs, medicaments and biological substances

T44 T45 T46 T47 T48 T49

X43;X63;Y13 X44;X64;Y14 X44;X64;Y14 X44;X64;Y14 X44;X64;Y14 X44;X64;Y14

T50

X44;X64;Y14

a

In medico-legal terms, external cause stands for the manner-of-death; codes X40–X44 for accidents, X60–X64 for suicides and Y10–Y14 for undetermined (whether accidental or self-inflicted) deaths.

(range 18–65) years and for females 57.1 (range 29–92) years. At the manner-of-death level, the SF agreed with 79 (79.8%) of these 99 deaths, coding them as accidents (Table 2). Three deaths (3.0%) were re-assigned to corresponding suicide categories, but 17 deaths (17.2%) were regarded as being of natural origin, mostly due to drug

3. Results 3.1. Accidents Accidental deaths numbered 99, comprising 19.8% of all fatal drug poisonings; 62 (62.6%) were male and 37 (37.4%) female deaths. The mean age was 46 years, for males 39.4

Table 2 Deaths medico-legally proven and certified as accidental drug poisonings and their registration, by ICD-10 E-categoriesa Certified as

Registered as

Total certifications

Accidents X40 X40 X41 X42 X43 X44

X41

Total accidents X42

X43

X44

X60 1 40 26 7 5

1 39 2 6 1

1 1

23 1 1

Suicides

3

X61

Total Natural suicides deaths X62

1 1 1

1 1 1

1 5 9 2

3 46 36 7 7

17

99

67b (67.7%) Total registrations 1 a

48

24

1

5

79c (79.8%) 1

1

1

Code series X40–X44 is for accidents, X60–X64 for suicides, see Table 1 for drug specification. b Agreements (agreement rate in parentheses) within accident categories. c Overall agreement (agreement rate in parentheses) between certified and registered accidents.

3

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Table 3 Manner-of-death agreements and re-assignments of medico-legally proven accidental fatal drug poisonings, by the verified druga Drug

Agreementsb

Certified cases (n) Male

Female

Total

n

Re-assignments to Rate

c

Suicides

Natural causes

1

10 6 1 1 2

Antidiabetics

–

2

2

2

100

Cardiovascular drugs Digoxin Other

1 1 –

2 – 2

3 1 2

3 1 2

100 100 100

30 16 2 12 –

7 – 1 3 3

37 16 3 15 3

26 10 2 13 1

70.3 62.5 66.7 86.7 33.3

Antiepileptics

1

–

1

0

0

1

Neuroleptics Levomepromazine Promazine Thioridazine Chlorprothixene Others

9 4 3 1 – 1

7 2 – 2 – 3

16 6 3 3 – 4

14 6 3 2 – 3

87.5 100 100 66.7 – 75.0

2

Anxiolytics Benzodiazepines

1 1

– –

1 1

1 1

100 100

Hypnotics Zopiclone Temazepam Clomethiazole

3 2 1 –

3 – 2 1

6 2 3 1

5 2 2 1

83.3 100 66.7 100

Antidepressants Tricyclic SSRI Other

13 12 1 –

14 8 4 2

27 20 5 2

25 18 5 2

92.6 90.0 100 100

Amphetamines

1

1

2

1

50.0

Opioids Morphine/heroin Codeine/ethylmorphine Propoxyphene Other (tramadol)

Other drugs Total

3

1

4

2

50.0

62

37

99

79

79.8

1

1 1

1 1 1 1

1 1

1 2 2

18

a

Principal drug, in combinations. Agreement with the certified manner-of-death. c Number of agreements divided by the number of cases  100. b

abuse/dependence syndrome (11 cases) and to the various categories of cardiovascular diseases (4 cases). However, at the applied three-character code level of the external causes of death (‘‘E-code’’), only 67 (67.7%) cases completely agreed, the greatest increase (8 cases) and decrease (6 cases) observed in categories X41 and X43 (for codes used, see Table 1), respectively. In Table 3, the agreements and re-assignments of the medico-legally proven fatal drug overdose accidents with SF data are shown by the verified drug (i.e. the principal drug in drug combinations). The match is fairly good, except in the category of opioids, which has an agreement rate of only 70.3. Of the reported 16 morphine/heroin overdose deaths, six were re-classified to natural deaths: three to opioid dependence (ICD-10 code, F11.2) and three to multiple-drug

dependence syndrome (F19.2). Of the three tramadol overdose cases, two were re-assigned to the category of malignant diseases. Two deaths were transferred from the accidental death category to the suicide category. In neuroleptic accidents, the agreement rate was 87.5, 2 (out of 16) deaths being re-classified as natural deaths. The distribution of fatal drug accidents, by single-drug or multiple-toxicant poisonings as stated by the forensic examiner on the death certificate, is presented in Table 4. The majority (77.8%) of cases were multiple-toxicant poisonings, categories of two and more drugs with or without alcohol being the most numerous. Drug-alcohol cases dominated in males, with a relative proportion of 53.2%, and poisonings with two or more drugs and drug-alcohol cases were most common in females, each occurring in 37.8% of accidents.

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Table 4 Certified fatal drug poisonings by number of toxicants Certified mannerof-death, overall and by gender

One drug

n

%

Two or more drugs

One drug and alcohol

Two or more drugs and alcohol

Total

n

n

n

n

%

%

%

%

Accidents Males Females

22 (22.2) 13 (21.0) 9 (24.3)

13.4 12.6 14.8

30 (30.3) 16 (25.8) 14 (37.8)

17.6 16.5 19.2

23 (23.2) 15 (24.2) 8 (21.6)

25.8 28.3 22.2

24 (24.2) 18 (29.0) 6 (16.2)

31.2 38.3 20.0

99 (100) 62 (100) 37 (100)

19.8 20.7 18.5

Suicides Males Females

111 (34.2) 68 (36.4) 43 (31.2)

67.7 66.0 70.5

128 (39.4) 71 (38.0) 57 (41.3)

75.3 73.2 78.1

46 (14.2) 27 (14.4) 19 (13.8)

51.7 50.9 52.8

40 (12.3) 21 (11.2) 19 (13.8)

51.9 44.7 63.3

325 (100) 187 (100) 138 (100)

65.0 62.3 69.0

31 (40.8) 22 (43.1) 9 (30.6)

18.9 21.4 14.8

12 (15.8) 10 (19.6) 2 (8.0)

7.1 10.3 2.7

20 (26.3) 11 (21.6) 9 (36.0)

22.5 20.8 25.0

13 (17.1) 8 (15.7) 5 (20.0)

16.9 17.0 16.7

76 (100) 51 (100) 25 (100)

15.2 17.0 12.5

500 (100) 300 (100) 200 (100)

100 60.0 40.0

Undetermined Males Females Total Males Females

164 (32.8) 100 103 (34.3) 100 61 (30.5) 100

170 (34.0) 100 97 (32.3) 100 73 (36.5) 100

89 (17.8) 53 (17.7) 36 (18.0)

100 100 100

77 (15.4) 47 (15.7) 30 (15.0)

100 100 100

X44. One death was regarded as due to suicidal drowning rather than concomitant overdose of an unspecific betablocking agent. Not a single one of the reported suicides was re-classified as a natural death. In Table 6, the agreements and re-assignments at SF are shown by the verified principal drug. The overall agreement is nearly complete, 319 (98.5%) out of 324 cases; only sporadic cases in the categories of antidiabetics, opioids (codeine), hypnotics (zopiclone) and antidepressants (doxepine), one in each, were re-assigned to the category of accidental drug poisonings. One suicide, as stated earlier, was considered to be due to drowning instead of a concomitant overdose by an unspecific beta-blocking agent (propranolol). The principal drug in multiple-drug suicides

3.2. Suicides Suicidal deaths numbered 325, comprising 65.0% of all fatal drug poisonings; 187 (57.5%) were male and 138 (42.5%) female deaths. The mean age was 44.9 years, 44.4 (range 19–86) years for males and 45.6 (range 13–81) years for females. The SF agreed with 319 (98.2%) of these 325 druginduced suicides and registered them as suicides (Table 5). However, only 291 (89.5%) deaths matched at the applied three-character ‘‘E-code’’ level (for codes, see Table 1). X61 was by far the most often selected category, mainly at the expense of category X63. Five deaths were re-assigned to the accidental categories, three to X41, one to X42 and one to

Table 5 Deaths medico-legally proven and certified as suicidal drug poisonings and their registration, by ICD-10 E-categoriesa Certified as

Registered as

Total certifications

Suicides X60 X60 X61 X62 X63 X64

X61

Total suicides X62

X63

X41

1 1

5 200 1 24

X64

Accidents

40 13 33

6 202 41 37 33

3

319c (98.5%)

3

X42

Total accidents X44

Other unnatural deaths

3 1

1

1 1

1

1

5

6 205 42 38 34

291b (89.5%) Total 5 registrations a

255

41

13

35

1

Code series X60–X64 is for suicides, X40–X44 for accidents, see Table 1 for drug specification. Agreements (agreement rate in parentheses) within suicide categories. c Overall agreement (agreement rate in parentheses) between certified and registered suicides. b

1

325

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Table 6 Manner-of-death agreements and re-assignments of medico-legally proven suicidal fatal drug poisonings, by the verified druga Drug

Antidiabetics

Agreementsb

Certified cases (n) Male

Female

Total

6

5

11

10

90.9

d

n

Re-assignments to Rate

c

Accidents 1

1e

Cardiovascular drugs Digoxin Other

20 – 20d

9 1 8

29 1 28

28 1 27

96.6 100 96.4

Opioids Morphine/heroin Codeine/ethylmorphine Methadone Propoxyphene Other (tramadol)

22 – 7 – 15 –

22 – 4 1 15 2

44 – 11 1 30 2

43 – 10 1 30 2

97.7 – 90.9 100 100 100

3 4

– 4

3 8

3 8

100 100

66 20 22 4 11 9

38 6 8 5 6 13

104 26 30 9 17 22

104 26 30 9 17 22

100 100 100 100 100 100

1 – 1

4 3 1

5 3 2

5 3 2

100 100 100

Hypnotics Temazepam Zopiclone Clomethiazole Other

16 6 10 – –

17 6 9 1 1

33 12 19 1 1

32 12 18 1 1

97.0 100 94.7 100 100

1

Antidepressants Tricyclic SSRI Other

44 33 7 4

32 27 2 3

76 60 9 7

75 59 9 7

98.7 98.3 100 100

1 1

Amphetamines

1

–

1

1

100 100

Other analgesics Antiepileptics Neuroleptics Levomepromazine Promazine Thioridazine Chlorprothixene Others Anxiolytics Benzodiazepines Others

Other drugs Total

3 186d

7

10

10

138

324

319

98.5

Other causes

1e 1 1

1

4

1e

a

Principal drug, in combinations. Agreement with the reported manner-of-death. c Number of agreements divided by the number of cases  100. d One forensic toxicologically negative case omitted. e Suicide by drowning. b

was changed six times during the coding and registration procedure at the SF, usually however within the drug-specific category used in the study. Distribution of drug-induced suicides according to singledrug and multiple-toxicant poisonings as stated by the forensic examiner on the death certificate is presented in Table 4. When compared with fatal drug accidents, the proportion of single-drug poisonings is significantly larger (34.2 versus 22.2%), especially in males (36.4 versus

21.0%), while the proportion of drug-alcohol cases is smaller, overall and in both genders. 3.3. Undetermined deaths After the complete medico-legal examination into causes and circumstances of death, 76 (15.2%) drug poisoning deaths were stated to be undetermined, i.e. were considered neither accidents nor suicides. Of these, 51 (67.1%) were

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Table 7 Deaths medico-legally proven and certified as undetermined drug poisonings and their registration, by ICD-10 E-categoriesa Certified as

Registered as

Total certifications

Accidents X41 Y11 Y12 Y13 Y14

45

Total registrations

53

a

X42

X43

Suicides X61

Total suicides

1

1

10

46 7 10 10

12

73

1

2 6

2

Natural deaths

X44 1 1

6 8

Total accidents

1 1 1

47 7 11 11

2

Code series Y10–Y14 is for undetermined deaths, X40–X44 for accidents and X60–X64 for suicides, see Table 1 for drug specification.

males and 25 (32.9%) females; a significant male overrepresentation when compared with the accident and especially the suicide categories. The mean age was 47.3 years, 46.8 (range 19–77) years for males and 48.3 (range 21–76) years for females. At SF, all deaths reported by the medical examiner as undetermined were re-classified (Table 7), i.e. the agreement between certified and registered deaths was nil with regard to the manner-of-death. Altogether 73 (96.1%) deaths were assigned to the accident categories, the X41 and X44 categories (for codes, see Table 1) gaining the most, 53 and 12 cases, respectively. Two deaths were considered as natural and one death as a suicide. In Table 8, the re-assignments are presented by the verified specific drug. In all, 74 deaths were accepted as drug overdose deaths, 73 as accidents and 1 as a suicide (due to a tricyclic antidepressant). Two deaths were re-assigned to the drug dependence syndrome, i.e. were regarded as natural deaths. The distribution of fatal undetermined drug poisonings in a single-drug/multiple-toxicant context is presented in Table 4. The proportion of single-drug poisonings is at its highest when compared with accidents and suicides: 40.8% overall and 43.1% in males. Alcohol cases dominate in females and are significantly more frequent than in the suicide category. 3.4. Fatal drug poisonings by drug-specific groups Of the 500 reported drug poisonings, 300 (60.0%) were male and 200 (40.0%) female fatalities. The mean age was 45.5 years, for males 43.8 (range 18–86) years and for females 48.1 (range 13–92) years. The effects of the registration procedure at SF on the classification of the manner-of-death of reported drug poisonings, by the drug-specific grouping used, is shown in Table 9. Tables 3, 6 and 8 can also be referred to for the certification and the registration of accidents, suicides and undetermined deaths, respectively. Neuroleptics was the most numerous drug poisoning group with 145 deaths, 93 (64.1%) for males and 52

(35.9%) for females (Table 9). Levomepromazine (41 cases; 28.3%), promazine (38; 26.2%) and chlorprotixene (19; 13.1%) were the three most common drugs. Medical examiners deemed 16 (11.0%) deaths from neuroleptic overdose to be accidents (Table 3), 104 (71.7%) suicides (Table 6) and 25 (17.2%) undetermined deaths (Table 8). At SF, no reported neuroleptic overdose suicide was contested, i.e. the agreement rate was 100% (Table 6). Of the 16 accidents, 2 were re-classified as natural deaths (Table 3), 1 due to chronic alcoholic pancreatitis and the other to pulmonic embolus with acute cor pulmonale. All but one (considered to be due to drug dependence syndrome) of the medicolegally undetermined deaths were coded as accidents (Table 8). Antidepressants caused 127 fatal poisonings, 73 (57.5%) in males and 54 (42.5%) in females (Table 9). Amitriptyline (47 cases), doxepine (40 cases) and citalopram (12 cases) were the three most frequent causative agents. Of these fatal antidepressant cases, 27 (21.3%) were reported as accidents (Table 3), 76 (59.8%) as suicides (Table 6) and 24 (18.9%) as undetermined deaths (Table 8) by medical examiners. At SF, one reported accident was re-coded as a suicide and one as being due to drug dependence, i.e. to a natural cause (Table 3). One suicide was re-classified as an accident (Table 6). Of the medico-legally undetermined deaths, 1 was coded as a suicide and all other 23 cases as accidental poisonings (Table 8). Psychostimulants were represented by three fatal amphetamine poisonings: one reported and registered as a suicide, and two poisonings reported as accidental deaths, one of which was re-coded at SF as a natural death from chronic drug abuse/dependence. Medico-legal fatal opioid poisonings numbered 88. Of these, 58 (65.9%) were males and 30 (34.1%) females (Table 9). Forty-nine (55.7%) deaths were due to dextropropoxyphene, 18 (20.5%) to morphine/heroin (in practice, at least 12 due to heroin) and 14 (15.9%) to codeine, highlighting the three most numerous drugs in this category. According to the medical examiners’ reports, 37 (42.0%) opioid poisonings were accidents (Table 3); however, SF coded 10 of these as natural deaths (drug abuse/dependence  8, cardiovascular disease  1 and metastasized breast

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Table 8 Manner-of-death agreements and re-assignments of medico-legally proven undetermined fatal drug poisonings, by the verified druga Drug

Agreementsb

Certified cases (n) Male

Female

Total

n

Re-assignments to c

Rate

Accidents

Antidiabetics

3

1

4

0

0

4

Cardiovascular drugs Digoxin Other

2 1 1

5 1 4

7 2 5

0

0

7 2 5

Opioids Morphine/heroin Codeine/ethylmorphine Propoxyphene Other

6 1 1 4 –

1 1 – – –

7 2 1 4 –

0

0

7 2 1 4

Antiepileptics

2

–

2

0

0

2

18 5 5 3 2 3

7 4 – 1 – 2

25 9 5 4 2 5

0

0

24 8 5 4 2 5

Anxiolytics Benzodiazepines

1 1

– –

1 1

0

0

Hypnotics Temazepam

– –

2 2

2 2

0

0

2 2

Antidepressants Tricyclic SSRI Other

16 12 3 1

8 7 1 –

24 19 4 1

0 18

0

23

3

1

4

0

0

3

51

25

76

0

0

73

Neuroleptics Levomepromazine Promazine Thioridazine Chlorprothixene Others

Other drugs Total

Suicides

Natural causes

1 1

1

1 1

4 1 1 1

2

a

Principal drug, in combinations. Agreement with the reported manner-of-death. c Number of agreements divided by the number of cases  100. b

cancer  1) and one of these as a suicide. Forty-four (50.0%) opioid deaths were reported as self-intentional (Table 6), mostly from dextropropoxyphene, SF agreeing with all but one codeine poisoning, which was coded as an accident. All medico-legally undetermined seven (8.0%) deaths (Table 8) were classified as accidents at the SF. Hypnotics caused 41 deaths, 19 male and 22 female fatalities (Table 9). Most frequently, zopiclone (21 cases) and temazepame (17) were detected. On the whole, 33 were reported as suicides, 6 as accidents and 2 as undetermined deaths. At SF, of the reported accidents (Table 3), one was recoded as a cardiac disease and of the reported suicides (Table 6) one as an accident, while both two undetermined deaths (Table 8) were regarded as accidents. Of the fatal poisonings from cardiovascular drugs, totaling 38 cases (Table 9), digoxin was responsible for two male and two female deaths. Consistent with certification, one death was considered as suicidal and one as accidental at SF,

whereas two undetermined deaths (Table 8) were re-classified as accidents. The group ‘‘other’’ (34 cases) consists exclusively of antihypertensive drugs and beta-blocking agents, 21 for males and 13 females. Cardiovascular drug poisonings reported as suicides (Table 6) numbered 29. Three deaths were reported and registered as accidents (Table 3). All but one of these deaths were similarly classified by SF; one suicide was considered to be committed by drowning rather than simultaneous drug overdose. The manner-ofdeath remained undetermined (Table 8) after the complete medico-legal examination in five deaths due to antihypertensive drugs; all of these were registered as accidents by SF. Fatal insulin poisonings numbered 16 (Table 9), including 9 (56.3%) male and 7 (43.7%) female cases. In addition, one fatal female poisoning from an oral antidiabetic agent (metformin) was present. Of these 17 fatal antidiabetic poisonings, 11 (64.7%) deaths were reported as suicides (Table 6), SF agreeing with all but one which was considered

R.A. Lahti, E. Vuori / Forensic Science International 136 (2003) 35–46

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Table 9 Manner-of-death agreements and re-assignments of medico-legally proven fatal drug poisonings, by the verified druga Drug

Antidiabetics

Certified cases (n)

Agreements

Re-assignments (n) to b

Male

Female

Total

9

8

17

12

70.6

5

c

d

n

Rate

Accidents

Suicides

Natural causes

Cardiovascular drugs Digoxin Other

23 2 21c

15 2 13d

38 4 34

31 2 29

81.6 50.0 85.3

7 2 5

Opioids Morphine/heroin Codeine/ethylmorphine Methadone Propoxyphene Tramadol

58 17 10 – 31 –

30 1 5 1 18 5

88 18 15 1 49 5

69 10 12 1 43 3

78.4 55.6 80.0 100 87.8 60.0

8 2 2

1

10 6 1

4

1

1 2

3 7

– 4

3 11

3 8

100 72.7

2

1

93 29 30 8 13 13

52 12 8 8 6 18

145 41 38 16 19 31

118 32 33 11 17 25

81.4 78.0 86.8 68.8 89.5 80.6

24 8 5 4 2 5

3 1

3 2 1

4 3 1

7 5 2

6 4 2

85.7 80.0 100

1 1

Hypnotics Temazepam Zopiclone Clomethiazole Other

19 7 12 – –

22 10 9 2 1

41 17 21 2 1

37 14 20 2 1

90.2 82.4 95.2 100 100

3 2 1

Antidepressants Tricyclic SSRI Other

73 57 11 5

54 42 7 5

127 99 18 10

100 77 14 9

78.5 77.8 77.8 90.0

24 19 4 1

Amphetamines

2

1

3

2

66.7

Other analgesics Antiepileptics Neuroleptics Levomepromazine Promazine Thioridazine Chlorprothixene Others Anxiolytics Benzodiazepines Others

Other drugs Total

9 299c

9 199d

1 1

1 1

2 2

1 1

1

18

12

66.7

3

498

398

79.9

77

3 3

20

a

Principal drug, in combinations. Number of agreements divided by the number of cases  100. c One forensic toxicologically negative case omitted. d One death from drowning omitted. b

to be an accident. Two (11.8%) of the deaths due to antidiabetics were regarded as accidents (Table 3), by both medical examiners and mortality statistics, whereas all four (23.5%) medico-legally undetermined deaths (Table 8) were coded as accidents at SF. From the data presented in Table 9, the overall stability of certified manner-of-death categories, whether accidents, suicides or undetermined deaths, by the specific drug groups used, can be determined as the difference between the total number of certifications (column Total) and the final statistical classification of the deaths (column Agreements);

statistical data treatment has not changed the sequence in frequency of the top five drug groups, i.e. in descending order, neuroleptics, antidepressants, opioids, hypnotics and cardiovascular drugs. 3.5. Multiple-toxicant poisonings Fatal poisonings from more than one drug, i.e. poisonings due to one drug and alcohol or to two or more drugs with or without alcohol, are referred to here as multiple-toxicant poisonings. These poisonings predominated in the study

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Table 10 Manner-of-death agreements and re-assignments of medico-legally proven fatal drug poisonings, by the number of toxicants Number of toxicants

Certified cases (n)

Agreements n

Re-assignments (n) to

Ratea

Accidents

Suicides

Mental disordersb

Other diseases

One drug Accident Suicide Undetermined

164 22 111 31

11 109 0

50.0 98.2 0.0

– 2 31

1 – None

6 None None

4 None None

Two or more drugs Accident Suicide Undetermined

170 30 128 12

22 126 0

73.3 98.4 0.0

– 2 12

1  None

6 None None

1 None None

One drug and alcohol Accident Suicide Undetermined

89 23 46 20

23 46 0

100 100 0.0

– None 19

None – None

None None 1

None None None

Two or more drugs and alcohol Accident Suicide Undetermined

77 24 40 13

23 38 0

95.8 95.0 0.0

– 2 11

1 – 1

None None 1

None None None

500 99 325 76

79 319 0

79.8 98.5 0.0

– 6 73

3 – 1

12 None 2

5 None None

Total Accident Suicide Undetermined death a b

Number of agreements divided by the number of cases  100. Due to psychoactive substance use (from F10 to F19, in ICD-10).

material, representing 67.2% of cases overall, with males accounting for 65.7% and females 69.5% (Table 4). At the statistics office, the classification of fatal drug poisoning presupposes the selection of the principal drug for coding to the internationally applicable drug poisoning categories of X40–X44 (for accidents), X60–X64 (for suicides) and Y10– Y14 (for undetermined deaths). In Table 10, the agreements and re-classifications, by the manner-of-death, of reported multiple-toxicant poisonings at SF are shown. The undetermined deaths are all re-classified. Agreement was complete (agreement rate 100%) in the group of ‘‘one drug and alcohol’’, whether accidents or suicides, and nearly complete (agreement rate 95.0–98.4%) in all other suicidal combinations of toxicants, accident being preferred in the statistics for the six re-assigned deaths. From among reported accidents involving two or more drugs, eight deaths were re-classified: six as drug abuse/dependence, one as other disease and one as suicide. The most marked reassignment rate was for single-drug accidents, with one-half (11) of cases being re-classified: six to the category of drug abuse/dependence (all of them opioids), four to the group of other diseases and one to the category of suicides. 3.6. ‘‘False-negative’’ drug poisonings From among the medico-legally reported 500 drug poisonings (accidents, suicides, undetermined deaths),

20 cases were considered to be ‘‘false-positives’’ at SF, leaving 480 deaths in the drug poisoning category. However, in 1997, the total number of deaths from drug poisonings was 552 according to Finnish mortality statistics [11], 220 being tabulated as accidents and 332 as suicides. What then are these 72 additional, from the SF point of view ‘‘false-negative’’, drug poisonings, comprising 13.0% of the national mortality figure for drug poisonings?. Sixty-three of these deaths were multiple-toxicant poisonings in which medical examiners gave preference to the alcohol (60 ethanol, 1 methanol, 2 isopropanol) component rather than drug component, i.e. reported the death as due to alcohol poisoning. Of these, two ethanol poisonings and the only methanol poisoning were reported as suicides; all of the others (60 cases) were stated as accidents. In seven cases, performing post-mortem forensic toxicological examination was not considered appropriate at the medico-legal autopsy because of the time interval elapsed after drug ingestion; the medical examiner’s drug poisoning diagnosis was based on clinical laboratory findings soon after hospital admission. In two poisoning deaths, occurring after several days of hospital care and examinations, a clinical post-mortem was performed, which is against the prevailing legal provisions in the inquest into causes of death.

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4. Discussion The pathway from findings to compiling mortality statistics is a long winding one, from medical cause-of-death determination via death certification, selection and coding of causes of death, to the cause-of-death register and mortality statistics. With regard to suspected poisoning deaths, like all other unnatural deaths, the medical portion of this chain of events in Finland is attended by medical examiners within a nationwide specialized, adequately occupied and facilitated provincial or university organization. In suspected fatal poisonings, forensic toxicology is systematically incorporated into the medico-legal investigations, guaranteeing the quality of data upon which conclusions on cause-of-death are based. In Finland, the cause-of-death determination and medical death certification is enacted by legislative and administrative statutes, and the practical completion of the certificate by guidelines on the form itself and in the national adaptation (Tautiluokitus ICD-10) of the ICD-10. On the death certificate form, there are separate spaces for two ICD-10 codes for each unnatural cause-of-death diagnosis for the certifier to complete: one for the external cause and one for the most important injury or the principal toxicant in poisonings. Medical examiners completing death certificate forms have adopted this practice rather well. However, personal and regional differences do occur, in the way in which particularly concomitant poisonous agents are specified, causing difficulties when the forms reach SF. The problem with multiple causative toxicants is solved at the statistics office by ICD-10 statement: ‘‘If one component is specified as the (main) cause-of-death, code to that component; if no component is specified as the causeof-death, code to the category provided for the combination, e.g. mixed antiepileptics (T42.5). Otherwise, if the components are classified to the same three-character category, code to the appropriate subcategory for ‘‘Other’’; if not, code to T50.9 (drugs not otherwise specified)’’. Since the use of combination categories for drugs, just as the promotion of the subcategories ‘‘Other’’ and ‘‘Unspecified’’, inevitably leads to a loss of drug-specific information, the use of these categories is not advisable. In addition, the broad ICD categories of drugs covered by single underlying cause codes make it difficult to gather information on particular poisons of interest [9]. A means to meet the need for further specificity in drug poisoning mortality statistics would be implementation of the ATC classification [7] of drugs. The ATC codes for specification of drugs have been used in the FTD statements and on death certificate forms in Finland since 1997. At SF, this practice has produced extra problems because of the current statistical application of ICD codes only (categories from T36 through T50 in ICD-10) for the tabulation of drugspecific causes; much time and human effort are therefore wasted in transforming the ATC codes into ICD codes. The incorporation of ATC codes into the ICD classification or making these two classifications otherwise compatible with

45

each other is necessary. ATC codes could then be applied in drug poisonings alongside ICD codes, whenever reasonable and practical. This, together with reliable medico-legal cause-of-death determination and comprehensive forensic toxicological examinations, would be worth striving for to promote a proper compilation of national as well as international drug poisoning statistics. In death certification, the goal should be as uniform a practice as possible. Nevertheless, problems may arise at the statistics office, where the principal drug from a combination of synergetic agents has to be selected and coded for the underlying cause-of-death tabulation and mortality statistics. The primary assumption is always that entries on the medical part of the death certificate are valid and correct. When consulted by a nosologist, the medical expert only interprets and specifies reported facts and assesses the consistency of medical causal relationship(s) between causes leading to death. When needed, the certifier is queried for further or more specific information. Toxicological results can also be checked from the FTD, which has been increasingly done in recent years. In 1997, the year of this study, and still in 1998, the FTD register was only used sporadically. Since then, toxicological results of 110–175 poisoning deaths have been checked yearly by the SF medical expert, in mutual understanding with the head of the FTD. Much of this effort could be avoided, however, if all pertinent laboratory findings were reported on death certificates by the medical examiner. From the standpoint of mortality statistics based on the underlying cause-of-death tabulation, the external cause of poisoning (section XX of ICD-10) is most important, both nationally and internationally. In Finnish practice, the certified external cause-of-death can be verified by the statistician in many ways: cross-checking the stated ‘‘E-code’’ and the ticked box from among the alternatives for accident, suicide, homicide and undetermined death and by inference from the circumstances of death reported on the certificate in the ‘‘Summary’’ section. If the notes are consistent with each other, the poisoning death-when accidental or self-inflicted– can be coded and registered for mortality statistics. But if the poisoning death remains undetermined after complete medico-legal examination(s), practices differ. The medical examiner reports such a death invariably as undetermined as to the manner-of-death. At SF, as we have discovered, the death is classified as an accident; categories for drug poisonings of undetermined intent (Y10–Y14) are not used at all. This differs from the practice employed when ICD-9 was in use (up to the end of 1995). In 1995, the entity of undetermined poisonings by solid or liquid substances existed in the mortality statistics, 88 deaths being tabulated [10]. In 1996, the year of implementation of ICD-10 in Finland, such deaths were only 20 in number [11]. And, in 1997, none. SF argues for the change by stating that matters are carried out ‘‘according to ICD-10’’ [12]. This is justified since the ICD-10 note on the event of undetermined death says: ‘‘This section covers events where available information is insufficient to enable a medical or legal authority to make a distinction between

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R.A. Lahti, E. Vuori / Forensic Science International 136 (2003) 35–46

accident, self-inflicted injuries, but not poisoning, when not specified whether accidental or with intent to harm.’’ On the other hand, because the medical examiner’s statement always reflects an informed opinion about the conditions and their interrelationships, deaths specified as undetermined regarding manner-of-death must be taken as proven fact and ‘‘should not be disregarded lightly’’ [5]. Thus, undetermined (as to intent) poisonings as the tabulated cause-of-death in the underlyingcause-of-death coding should be accepted. Accordingly, the category of undetermined poisonings has again been opened and is used with careful consideration, including querying the certifier, consulting a medical expert (R.A.L.) or even confirming the toxicological laboratory data. The consequence of this practice is as follows: deaths of undetermined intent numbered 2 in 1998 [13], 13 in 1999 [14] and 13 in 2000 [15]. The results of this study support the continuance of this practice in striving for increased validity of national mortality statistics and international comparisons of mortality. The boundary between acute drug poisoning (accidental or undetermined) and drug dependence syndrome is governed by the ICD-10 note [6] on preference of dependence syndrome to poisoning when the selected code is within the range of F10 through F19, the block ‘‘Mental disorders due to psychoactive substance use’’, and a corresponding dependence syndrome is mentioned on the death certificate. This principle appears to be consistently applied by SF; in accidents, 18 fatal poisonings and in the undetermined poisoning category, 2 deaths were assigned to the reported corresponding dependence syndrome. This practice significantly affected medico-legally proven poisonings by opioids, both accidents and overall. Altogether 10 (27.0%) out of 37 accidents (Table 5) and 10 (11.4%) out of 88 poisonings overall (Table 10) have been missed from the mortality statistics based on the underlying cause-of-death coding, a fact every provider of Finnish mortality statistics should know. Does this practice reflect prevailing social reality reliably for preventive purposes? We contend that it does not and suggest that the whole, correct, crude picture instead be presented to the policy makers. According to the present study, the SF register, i.e. the national mortality statistics of Finland, included 72 ‘‘extra’’ drug poisonings when compared with those reported by medical examiners. The majority (63 cases) of these deaths were due to poisonings where alcohol was combined with drug(s), the drug component having been considered to be the main component at SF. In the ICD-10, the problem of multiple-toxicant poisonings is covered by the following paragraph: ‘‘If one component of the combination is specified as the cause-of-death, code to that component; if no component is specified as the cause-of-death, code to the (possible) category provided for the combination. Otherwise, if the components are classified to the same threecharacter category, code to the appropriate subcategory for ‘‘Other’’; if not, code to T50.9 (Other or unspecified drug poisoning). Combinations of medicinal agents with alcohol should be coded to the medicinal agent.’’ Today, when

alcohol and drug(s) are often taken together to reach a state of intoxication and when the intoxication then accidentally leads to death, the categorical guidance to code these cases according to the drug component appears inappropriate, both medico-legally and for the purposes of public health, distorting statistics of both alcohol [8] and drug poisonings. The problem can be solved simply by equating alcohol with a medicinal agent in the above-cited ICD-10 paragraph.

Acknowledgements Our gratitude is due to Riitta Harala, Director of Population Statistics, and Hilkka Ahonen, Senior Statistician, of Statistics Finland, for the cause-of-death data from 1997 (permit TK53-1783-99). Helena Liuha, Kaija Saarela and Tarja Ruotsalainen of the Department of Forensic Medicine, University of Helsinki, are thanked for their unselfish practical assistance. We also thank Carol Ann Pelli for linguistic revision. References [1] Act (459/73) and Statute (948/73) on the Inquest into the Cause-of-Death (in Finnish). [2] Statute (169/48) on the Department of Forensic Chemistry of Helsinki University (in Finnish). [3] R.A. Lahti, A. Penttila¨ , The validity of death certificates: routine validation of death certification and its effects on mortality statistics, Forensic Sci. Int. 115 (2001) 15–32. [4] R.A. Lahti, A. Penttila¨ , The cause-of-death query in validation of death certification by expert panel; effects on mortality statistics in Finland, 1995, Forensic Sci. Int. 131 (2003) 113–124. [5] International Statistical Classification of Diseases and Related Health Problems, 10th Revision, vol. 2, Instruction Manual, WHO, Geneva, 1993. [6] International Statistical Classification of Diseases and Related Health Problems, 10th Revision, vol. 1, Tabular List, WHO, Geneva, 1993. [7] La¨ a¨ kkeiden luokitus (ATC) ja ma¨ a¨ ritetyt vuorokausiannokset (DDD) 1999 (in Finnish), based on Anatomical Therapaeutic Chemical (ATC) Classification Index by WHO Collaborating Centre for Drug Statistics Methodology, Oslo, 1999. [8] R.A. Lahti, E. Vuori, Fatal alcohol poisoning: medicolegal practices and mortality statistics, Forensic Sci. Int. 126 (2002) 203–209. [9] R.J. Flanagan, C. Rooney, Recording acute poisoning deaths, Forensic Sci. Int. 128 (2002) 3–19. [10] Statistics Finland, Causes of Death 1995, Health, vol. 5, Helsinki, 1996. [11] Statistics Finland, Causes of Death 1996, Health, vol. 3, Helsinki, 1999. [12] Statistics Finland, Causes of Death 1997, Health, vol. 3, Helsinki, 2000. [13] Statistics Finland, Causes of Death 1998, Health, vol. 5, Helsinki, 2000. [14] Statistics Finland, Causes of Death 1999, Health, vol. 3, Helsinki, 2001. [15] Statistics Finland, Causes of Death 2000, Health, vol. 1, Helsinki, 2002.