Résumés du Congrès TIAFT - ICADTS \(28-30 août 2007, Seattle

169 Pages·2008·1.74 MB·English

Annales de Toxicologie Analytique, vol. XIX, n° 4, 2007
ORAL PRESENTATIONS RESULTS: There were 7,673 external cause deaths in
Victoria between July 2000 and June 2005. Of these,
COMMUNICATIONS ORALES
there were 2,086 (27%) external cause deaths contained
a toxicology report where alcohol was identified as
Postmortem toxicology positive (greater than 0). A toxicology report was not
attached in 1,420 (18.5%) cases and the remaining
Toxicologie postmortem
4,152 external cause cases contained a negative result
for alcohol. Of cases with a toxicology report 455
(5.4%) had a blood alcohol concentration (BAC) of less
Understanding forensic toxicology in
than 0.06 g/100 mL. There were 564 (7.4%) detected
relation to external-cause deaths
with alcohol (0.06 g/100mL to <0.16 g/100mL) and 659
J. KILLIAN(1), O. DRUMMER(2), J. OzANNE- (8.6%) had a toxic level of alcohol (>0.16 g/100 mL).
SMITH(1) Of all causes with alcohol detected, 2726 (37%) were
due to intentional self-harm, followed by 2005 (27%)
(1) Monash University Accident Research Centre,
being transport related, 932 (12%) due to poisoning and
Victoria, Australia
553 (7%) being fall related. The trends and themes of
(2) Monash University Department of Forensic other drugs will also be reported especially in relation
Medicine and Victorian Institute of Forensic Medicine, to traffic injuries.
Victoria, Australia CONCLUSIONS: The study results provide, for the
AIMS: Injuries are not only recognised as an important first time in Australia, a systematic examination of the
epidemiology of licit and illicit drugs in injury deaths
public health problem, but are also one of the major
due to all mechanisms.
causes of death. Injuries accounted for 9% of the world’s
deaths in 2000 and 12% of the world’s burden of disease
(Peden, M, McGee, K, et al (2002). The Injury Chart Buprenorphine-related deaths: low levels
Book: a graphical overview of the global burden of may be significant
injuries). It is known that drug-drug and/or drug-alcohol H. DRUID(1), M. ROMAN(2), R. KRONSTRAND(2)
interactions cause an increased risk of mortality. The use (1) Department of Forensic Medicine, Karolinska
of such mind-altering drugs in places of employment Institute, Stockholm, Sweden
or by drivers of motor vehicles, for example, places (2) Department of Forensic Genetics and Forensic
the individual and other members of the community Toxicology, National Board of Forensic Medicine,
at risk. However, the full extent of the involvement of Linköping, Sweden
drugs across the whole range of injury deaths is mostly AIMS: Buprenorphine is a partial mu-opioid receptor
unknown. Illegal drugs are more likely to be the cause agonist, and is used for the treatment of moderate to
of unintentional death than intentional. In contrast, in severe chronic pain, but has also been introduced as an
Australia, pharmaceuticals are more likely in self-harm, alternative to methadone in opiate substitution therapy.
Some years after its introduction on the Swedish market,
where analgesics and psychoactive drugs appear to
illegal use of buprenorphine started, and several deaths
be most commonly responsible for poisoning and/or
involving buprenorphine have been documented in
suicide (Drummer OH & Odell M (2001). The Forensic
Sweden. The aim of this study was to explore the femoral
Pharmacology of drugs of abuse. Chapter1.1: pp2-3).
blood and urine levels in buprenorphine-positive cases,
The study aimed to examine the presence and contribution
and to compare these concentrations with those observed
of alcohol and drugs in all external cause deaths for the in driving under the influence cases (DUI).
period 2000 to 2005 in Victoria, Australia (population
METHODS: A slightly modified previously
20.7 million). A secondary aim was to use the research published LC-MS/MS method (Kronstrand et al, JAT
results to assist with improving the National Coroners 2003;27:464-70) was used to determine buprenorphine
Information System (NCIS) as a tool for alcohol and on both postmortem cases and DUI cases where subjects
drug injury surveillance. either were prescribed buprenorphine, or when abuse
was suspected.
METHODS: The extent to which drugs and alcohol
RESULTS: The mean ± SD buprenorphine
contribute to unnatural deaths can now be described at
concentrations in postmortem femoral blood (all cases,
a population level for the first time in Australia using
n = 32) and in blood from DUI cases (n = 94) were 3.1
the NCIS (a national database of coronial information).
± 4.7 and 1.6 ± 1.8 ng/g, respectively. The overlap was
Associated toxicology reports were examined to
substantial both for buprenorphine and norbuprenorphine
determine the proportion of cases that contained alcohol levels. Additionally, in four postmortem cases, where
and drugs and the type and range (therapeutic, supra- intoxication was ruled out (causes of death: hanging =
therapeutic and toxic) of drugs. 2, pulmonary embolism = 1 and severe liver cirrhosis =
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Article available at http://www.ata-journal.org or http://dx.doi.org/10.1051/ata:2007030
Annales de Toxicologie Analytique, vol. XIX, n° 4, 2007
1), the mean (median) concentration was 7.8 (4.3) ng/g. detected using gas chromatography with nitrogen-
Hence it seems impossible to define a fatal level. It may phosphorus detector and confirmed using gas
be argued that buprenorphine was actually not involved at chromatography-mass spectrometry full scan mode
all in any of these deaths, explaining these toxicological after solid-phase extraction using Chem-Elut columns.
results. However, in at least eleven of the intoxication An additional high-performance liquid chromatography
cases, buprenorphine was apparently the most suspected coupled to diode-array detection screening also
drug based on circumstances, and the yet the mean ± obtained the same results. Quantitative analysis of the
SD were only 2.0 ± 2.0. Further, these subjects typically two local anaesthetics, lidocaine and mepivacaine, was
presented with massive pulmonary edema with lung undertaken by GC-NPD by comparison of each peak-
weights averaging 1394 ± 312 g as compared to 1142 area ratio with that of the IS against blood calibration
± 297 g in postmortem controls (hangings, n = 1,979), curves (1, 5, and 10 mg/L). Limits of detection were
and often with froth in the airways, suggesting that an 0.05 mg/L, the upper limit of linearity was 10 mg/L,
overstimulation of the mu-opioid receptors in the brain accuracy was > 95%, and precision (n=3) demonstrated
stem resulting in respiratory depression as the basic CV’s < 7% at 5 mg/L for both compounds.
mechanism for their demise. No other opioid drugs RESULTS: Autopsy results showed general congestion
were present in their blood. The ratio norbuprenorphine with no specific signs of anaphylactic shock.
to buprenorphine in postmortem cases (mean 1.15) was Toxicological analysis revealed the presence of lidocaine
similar to that in DUI cases (mean 1.55), but in 20 of the and mepivacaine in heart blood, at concentrations of
postmortem cases the buprenorphine concentration was 4.9 and 16.2 mg/L, respectively. There are no defined
higher than that of norbuprenorphine suggesting recent anatomic or microscopic markers for toxicity caused by
intake. In addition, urine analysis indicated a period of local anesthesia and toxicology remains the diagnostic
abstinence before the last dose. mainstay.
CONCLUSIONS: In eleven postmortem cases effects CONCLUSIONS: Based on the autopsy findings, case
of buprenorphine was considered the main cause of history, and toxicology results, the forensic pathologists
death even though the blood concentrations were ruled that the cause of death was due to an overdose
comparable to those of DUI cases and postmortem of local anesthetic agents. The low complication rates
controls. This corroborates the notion that interpretation achieved in lipoplasty are due to adequately trained
of postmortem levels of opioid drugs warrants caution surgeons and anesthesia providers, and the diligent
and comprehensive review of each case. intraoperative and postoperative monitoring, which were
mostly neglected by the operating surgeon involved in
our case. Therefore the manner of death was considered
A fatality occurring during tumescent
accidental although due to gross medical negligence.
liposuction
M.A. MARTíNEz(1), S. BALLESTEROS(1), L.J. SEGU-
Dyadic death – an unusual family
RA(2), M. GARCíA(2)
tragedy
(1) Instituto Nacional de Toxicología y Ciencias
Forenses, Ministerio de Justicia, C/ Luis Cabrera 9, D. GEROSTAMOULOS(1), O.H. DRUMMER(1),
28002 Madrid, Spain M. BURKE(1), M.J. LyNCH(1), P. ByRNE(2)
(2) Instituto Anatómico Forense de Madrid, Ciudad (1) Victorian Institute of Forensic Medicine and
Universitaria s/n, 28040 Madrid, Spain Department of Forensic Medicine, Monash University
CASE REPORT: Over the past decade, liposuction (2) State Coroners Office, 57-83 Kavanagh St.,
has become the most frequently performed procedure Southbank, Victoria 3006, Australia
in aesthetic plastic surgery in many countries although CASE REPORT: This report involves the death
it should not be considered without complications. of two women (mother and daughter) in unusual
Tumescent local anesthesia is subcutaneous infiltration circumstances. A 15 year old girl (Ms A) had stayed
of very dilute lidocaine and epinephrine to produce overnight at the residence of a 26 year old man thought
subcutaneous swelling. Mepivacaine has never been to be her boyfriend. The boyfriend claimed he located
mentioned to be used in this kind of surgery. We report the young girl deceased in his room when he awoke at
a case of overdose with mepivacaine and lidocaine in about 10:00 a.m. the next morning. The boyfriend was
a 38-year-old patient who died during a procedure of also an acquaintance of the mother (41y) of the young
tumescent liposuction of abdomen and both thighs in an girl. The young girl’s brother was also at the boyfriend’s
outhospital clinic. According to one witness, the victim residence but had returned to his mother’s residence
suffered an episode of tonic-clonic convulsion. When late in the evening as he had to work the next day. The
the emergency medical services arrived the patient brother mentioned that when he left for work early that
was under cardiac arrest and the cardiopulmonary morning he heard his mother snoring lightly, but did not
resuscitation measures were of no use. disturb her. He stated when he returned home from work
METHODS: All drugs involved in the case were his mother was still in bed where he had seen her in the
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Annales de Toxicologie Analytique, vol. XIX, n° 4, 2007
morning. Upon checking her he found her deceased. The mother also had very similar drugs in her blood. The
mother suffered from depression and was prescribed a concentration of morphine (free) 10 mg/L detected in
number of drugs including fluoxetine, mirtazapine and the mother’s blood is extremely high – despite concerns
citalopram. regarding postmortem redistribution, postmortem
metabolism, degradation of glucuronides, tolerance and
METHODS: Both cases were subject to a full autopsy
pharmacogenetic differences between individuals, it is
and toxicological examination. This involved an
difficult to ignore the concentration of morphine and its
immunoassay urine/blood screen for amphetamines,
contribution to death.
benzodiazepines, cannabinoids, cocaine metabolites
CONCLUSIONS: In our opinion the use of this drug is
and opioids. Blood extracts were also analysed on a
consistent with excessive, intentional consumption and
capillary gas chromatographic screen using a nitrogen-
combination with the other drugs detected and is likely
phosphorus detector for basic and neutral drugs as well
to have caused this woman’s death. It is remarkable that
as an additional screen conducted by gradient elution
the drugs found in the mother are in keeping with those
high performance liquid chromatography. Drugs of
found in her daughter. Over the 4 months to the deaths
significance were quantified using either HPLC/DAD
the boyfriend had been prescribed morphine from a
or GC/MS. Further tests for alcohol and other volatiles
variety of doctors at different practices. During the
were separately conducted.
inquest the prescribing doctor spoke about the perennial
RESULTS: Pathological findings following the problem of doctors being unable to obtain access to a real
autopsy of the young girl showed no significant natural time data base of an individual’s prescription history due
disease, there was some pulmonary oedema, but no to privacy issues. The coroner deemed that both mother
other findings of note. There was no significant natural and daughter were not the victims of “foul play”, and
disease or injury detected in the mother following the overdose (in each case) was accidental. The coroner
autopsy. The concentrations of drugs detected in the also gave consideration to tightening the current “doctor
young girl are consistent with death from mixed drug shopping” guidelines to provide an earlier alert system.
toxicity (see table below) including recent heroin A mechanism for introducing a cross referenced system
use. Citalopram, fluoxetine and diazepam detected for pharmacies to notify the doctor shopping service of
in the young girl were prescribed for the mother. The over prescribed patients.
Ms A* (daughter) Mother*
Drug Concentration Drug Concentration
Methamphetamine 0.05 mg/L
Methamphet. (urine) Detected
Morphine, free 0.1 mg/L Morphine, free 10 mg/L
Morphine, total (urine) Detected >15 mg/L
6-AM (urine) 0.03 mg/L
Citalopram 1.0 mg/L Citalopram 4.4 mg/L
Fluoxetine 0.8 mg/L Fluoxetine 0.2 mg/L
Diazepam 0.1 mg/L Diazepam 0.1 mg/L
Nordiazepam 0.1 mg/L Nordiazepam 0.1 mg/L
Δ9-THC 4 ng/mL Δ9-THC 4 ng/mL
Mirtazapine 0.6 mg/L
Valproic Acid 16 mg/L
*Femoral blood results unless otherwise specified; alcohol was not detected (<0.01 g/100 mL) in either deceased.
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The role of methamphetamine in cause methamphetamine predisposes them to greater risk of
injury and assault, and the socioeconomic consequences
and manner of death – an update
of drug use, together with the depression associated with
B.K. LOGAN(1), C. BANTA-GREEN(2), S. MILLER(2), drug withdrawal may contribute to suicidal ideation.
A.M. GORDON(1)

(1) Washington State Toxicology Laboratory, 2203
Death and brain injury from an apparent
Airport Way S., Seattle WA 98134, USA
(2) University of Washington, Alcohol and Drug Abuse intentional methomyl poisoning
Institute, 1107 NE 45th Street, Suite 120, Seattle, A. LOUIS(1), A. FUSARO(2), A.M. GORDON(1),
WA 98105-4631, USA B.K. LOGAN(1)
AIMS: The aim of this study is to examine the role (1) Washington State Patrol, Forensic Laboratory
of methamphetamine in deaths for four counties in Services Bureau, 2203 Airport Way S., Suite 360,
Washington State between 2000 and 2005. Seattle, WA 98134, USA
METHODS: Counties were selected for the accessibility (2) King County Medical Examiner’s Office, Seattle,
of their death investigation records in electronic format 325 9th Ave., Seattle, WA 98104, USA
and the fact that they are among the most populous,
AIMS: Pesticide poisoning is a common cause of
comprising 60% of the State’s population.
morbidity and mortality worldwide but is rarely
RESULTS: In 489 cases where the presence of encountered in the death investigation toxicology
methamphetamine was confirmed toxicologically, we laboratory in the United States. Methomyl (Acinate,
retrieved and reviewed medical examiner determinations Agrinate, DuPont 1179, NuBait,) is a highly toxic,
of the cause and manner of death. Of these cases, 337 class 1 carbamate insecticide which has been in use
(69%) of the cases were determined to be non-drug- with restrictions since 1970. Like all carbamates,
caused, where the presence of methamphetamine methomyl inhibits cholinesterase activity and results in
might be either a contributory or incidental finding. For symptoms of diarrhea, nausea and vomiting, abdominal
example, in the methamphetamine-present-non-drug- pain, excessive sweating and salivation, blurred
caused cases, the most common manner of death was vision, difficulty breathing, headache and muscular
suicide (25%), followed by homicide (23%), accident- fasciculation, leading to respiratory arrest and death.
traffic (18%), accident non-traffic (17%), and natural We present here a case of an apparent double methomyl
(12%). poisoning resulting in one fatality, and one non-fatal
152 (31%) of the deaths were determined to be drug case of anoxic brain injury.
caused. Of these drug-caused deaths, 97% were CASE HISTORY: A male subject and his female
reported as being accidental, and < 1% suicidal. The companion were drinking together when he suddenly
median methamphetamine concentration in drug-caused vomited, collapsed, and subsequently died. His
cases was 0.35 mg/L (range 0.01 - 34.64 mg/L, mean companion developed blindness and confusion and
1.53 mg/L), and was the same as in the non-drug caused was discovered approximately 22 hours later in her
deaths. These similarities emphasize the fact that blood apartment. She was seemingly unaware that the male
methamphetamine concentrations in and of themselves victim was deceased on the floor in front of her couch.
are insufficient to make a cause of death determination. Autopsy results in the male victim indicated early
The highest median value of methamphetamine decomposition and mild to moderate coronary artery
was among deaths ruled as accident-traffic-non- disease, but no obvious anatomic cause of death. The
drug-caused. In this group the median value was female victim was diagnosed with stroke as a result of
0.65 mg/L (range 0.02 - 3.72 mg/L, mean 0.83 mg/L). oxygen deprivation. Investigators initially suspected
This median value is higher than that from a prior study methanol or ethylene glycol poisoning based upon the
of methamphetamine fatalities (Logan et al., 1998), female victim’s symptoms.
which found a median of 0.35 mg/L for accident-
METHODS: Blood from both victims was analyzed
traffic-non-drug-caused deaths, with a range of 0.05 -
for volatiles by headspace gas chromatography and
2.60 mg/L. Among the 152 drug-caused deaths, the
headspace GC-MS. Drug screening was performed for
median concentration of methamphetamine was
cocaine, opiates, methadone, benzodiazepines, PCP,
significantly higher (p < 0.05) among methamphetamine-
amphetamines, barbiturates, tricyclic antidepressants,
only cases (median 0.52 mg/L, s.d. 3.67, n = 27) compared
cannabinoids and propoxyphene by EMIT, and for basic
to decedents for whom another CNS active drug was
and acid-neutral drugs by GC-MS. No drugs other than
detected in addition to methamphetamine (median 0.3
caffeine were detected in either victim. There was a
mg/L, s.d. 4.52). This suggests that mortality risk from
small amount of ethanol (0.02 gm/100 mL) in the male
lower levels of methamphetamine is increased when it victim’s blood. A sample of gastric contents from the
is combined with other drug use. decedent was extracted which indicated the presence of
CONCLUSIONS: Our data supports other literature methomyl in the basic fraction. It has a molecular weight
that suggests that the behavior of individuals using of 105 amu, and the molecular ion is the most abundant
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Annales de Toxicologie Analytique, vol. XIX, n° 4, 2007
ion, with two major fragments of 88 m/z and 58 m/z. aimed at tackling an increasing trend in drink driving
There was no indication of methomyl in either of the over recent years.
victims’ blood or in a swab of the decedent’s vomitus. On the drug driving scene, despite legislation in 2003
Analysis of other evidence from the scene confirmed allowing for drug screening devices to be used at the
the presence of methomyl in two drinking glasses, and roadside, no such devices have yet received government
in the liquid from the Jaegermeister bottle. approval. This is particularly disappointing as there is
RESULTS AND CONCLUSIONS: Methomyl increasing evidence that drug driving is a significant
detection is challenging as it is unstable at standard GC problem in the UK, and many other countries seem to
injection port temperatures. In this case, we were able to be having increased success in addressing this issue.
detect it only due to the high concentrations in the drinks These trends and initiatives in drink and drug driving
and the gastric content of the decedent. In this case the will be discussed together with options for progressing
gastric contents were the only biological sample which UK policy in near future.
tested positive for methomyl, highlighting the benefit of
comprehensive postmortem sampling.
Alcohol, drugs, and traffic safety in
Australia: initiatives and indicators
Worldwide trends in impaired
I.J. FAULKS(1), J.D. IRWIN(2)
driving
(1) Safety and Policy Analysis International, PO Box
Conducteurs alcoolisés : 140, Wahroonga NSW 2076, Australia
les grandes tendances (2) Department of Psychology, Macquarie University
NSW 2109, Australia
This paper reviews the status of alcohol, drugs and traffic
Alcohol and drug impaired driving in the
safety in Australia. Australian jurisdictions have made
UK: recent trends and future prospects
impressive improvements in road safety since the early
R. TUNBRIDGE 1970s. Road fatalities have more than halved, while
indicators of road use (population, vehicle registration,
Recent trends in drink driving in the UK have shown an
driver licensure, vehicle distance driven) have more than
increase in the level of driver fatalities over the 0.08%
doubled. Enforcement and public education campaigns
limit. This is almost certainly related to a decreasing
that specifically target drink driving, speeding, and non-
level of traffic enforcement and an associated reduced
use of seat belts have been successful. There has been an
level of roadside breath testing.
extensive shift in attitudes to drink driving in Australia,
The latter trend has also seen a substantially increased
and success in this area is serving as a valuable guide to
level of those drivers testing positive for alcohol
changing other undesirable road behaviours. Strategies
at the roadside over the past 5 years. It needs to be
to tackle drivers impaired by alcohol or other drugs are
established whether this trend is due to a ‘real’ increase
based on general deterrence and targeted operations.
in the incidence of drink driving or better targeting of
offenders. These actions reflect the national road safety strategy
Legislation was enacted in 2005 to allow for roadside and its analogues across the Australian jurisdictions.
evidential breath testing, but thus far no devices have A recent major initiative introduced in a number of
received government approval for police use. It is Australian jurisdictions is random roadside drug testing,
expected that such approval will be authorised during which supports and extends the previous random breath
2008. The UK government is committed to providing test (RBT) powers for impaired driving. Police now have
central funding for such devices, rather than requiring powers to: (a) stop drivers at random to test for alcohol
individual police forces to find funds from limited and arrest drivers who test over the legal prescribed limit;
resources. (b) stop drivers at random to test for specified drugs and
In a parallel initiative, the development of roadside issue a traffic notice or court attendance notice if certain
screening devices which record breath alcohol prescribed drugs are detected; (c) require a driver
concentration as well, as personal and demographic to undergo a sobriety test in certain circumstances,
data, is also being encouraged for UK use. Such devices and arrest drivers they believe are impaired by drugs
would allow a much clearer picture of the extent of for the purpose of blood and urine testing. Random
drink driving, including those driving with positive roadside drug testing supports an offence of drive
alcohol levels below the current UK drink drive level. with the presence of any of the following drugs: active
This data will be important in providing data for a new THC (cannabis); methylamphetamine (‘speed/ice’);
UK consultation on reducing the limit to 0.05%, due or methylenedioxymethamphetamine (MDMA or
later in 2007. ‘ecstasy’), as determined by testing in oral fluid, blood
The UK government is committed to providing central or urine. As well, the presence of morphine (unless
funding for such devices, rather than requiring individual proven for medicinal use) and cocaine in the blood or
police forces to fund this initiative. Both actions are urine of drivers can also constitute an offence. The
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usual penalties for drug driving include a substantial controls were tested for alcohol, and a number of licit
fine and loss of driver’s license. and illicit drugs. The relative risk of these psychoactive
Other major initiatives to combat impaired driving in substances was determined by calculating odds ratios.
Australia in recent years include responsible service of Furthermore, data on publicity campaigns, rehabilitation
alcohol programs, and the commencement of alcohol programmes, medical examinations, and crash data was
ignition interlock programs and interventions targeting collected and analyzed.
repeat drink driving offenders for assessment of Between 1970 and 1999 the proportion of drivers with a
alcohol-dependence. Promotion of the use of personal BAC above 0.5 g/L in weekend nights dropped from 15%
alcohol breathalyzer devices is also occurring. Support to 4.3%. Reductions in this downward trend occurred
for interventions targeting first-time drink driving and mainly after police enforcement was intensified. After
drug driving offenders is lagging, however, despite a a period with a more or less stable proportion of illegal
stated need for more effective partnerships to be built BACs, a new decline could be observed since 2003.
between the road safety and health sectors to better However, this decline was solely visible at relatively
address issues involving alcohol and other drug use. low BACs (≤ 1.3 g/L). Despite efforts of police and
Some technologies, notably dataloggers and vehicle government, the proportion of the highest BAC offenders
tracking through GPS, offer promise for a better dealing (> 1.3g/L) did not decrease over the past six years.
with impaired drivers, but there has been little policy Results from the case-control study in Tilburg and
development to date. surroundings indicate that this category is responsible
Across the Australian jurisdictions there are now for about three quarters of all alcohol related severe
an agreed suite of drink driving and drug driving injury crashes.
performance indicators, including: incidence of alcohol The declining trend of drink-driving offenders is not
and drug use by drivers and riders killed in crashes; crash reflected in the trend of registered alcohol related
incidence during ‘high alcohol’ periods; incidence of fatalities. Estimations of the proportion of alcohol-
drink driving reported from RBT operations; incidence related road toll which are based on both the results of
of illegal alcohol and drug levels per 1,000 tests; the annual road side surveys and the results of the case-
community perspectives of the level of RBT enforcement control study in Tilburg, indicate a more or less stable
and likelihood of being tested; and number of offenders proportion of alcohol related fatalities over the period
and non-offenders using alcohol interlocks. from 1999 to 2005.
A governmental policy is needed to lower the alcohol-
Drink-driving trend in the Netherlands; related road toll significantly. Police enforcement should
be targeting high BAC drivers and effective measures
need for a new government policy
should be introduced such as alcolock programmes
S. HOUWING, R. MATHIJSSEN
including alcoholism treatments for alcohol-dependent
SWOV Institute for Road Safety Research, drivers.
Leidschendam, the Netherlands
This paper presents the drink-driving trend during
Trends in the alcohol-fatal crash problem
autumn/fall weekend nights in the Netherlands as well
in Canada
as the trend of the alcohol-related road toll. Since 1970,
annual roadside surveys have been conducted. The D.R. MAyHEW
objective of these surveys is to obtain an insight into the Traffic Injury Research Foundation, 171 Nepean Street,
patterns of drink-driving and into the effect of measures. Suite 200, Ottawa, ON, Canada K2P 0B4
Road side survey sessions are distributed over Friday and
OBJECTIVE: This paper examines recent trends in
Saturday nights, and random breath testing is performed
the alcohol-fatal crash problem in Canada to determine
between 10 pm and 4 am, collecting data from about
if the magnitude of the problem has been increasing or
30,000 motorists, annually. Breath testing is performed
decreasing.
by police officers. Since random breath testing by the
METHOD: Information on the presence and amount of
police is legally permitted in the Netherlands, non-
alcohol in fatally injured drivers is used in this paper as
response is virtually non-existent.
an index of the alcohol fatal-crash problem in Canada.
Between 2000 and 2004 a large case-control study was
conducted in the Netherlands to assess relative injury Trends in the problem are examined using a variety of
risk of driving under the influence of psychoactive indicators derived from the “STRID” fatality database
substances. The case sample consisted of seriously (Strategy to Reduce Impaired Driving) – e.g. the percent
injured car drivers who were admitted to the Accident of fatally injured drivers positive for alcohol.
Emergency department of the St. Elisabeth Hospital in RESULTS: Canada experienced a steady decline in
the city of Tilburg. Controls consisted of motorists who the percentage of fatally injured drivers who had been
were taken at random from moving traffic in the Tilburg drinking from 1987 to 1990. This was followed by
police district which is located in the hospital catchment an increase in 1991 and basically no change in 1992.
area. Body fluids (blood and urine) of both cases and Between 1992 and 1999 the percent of fatally injured
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drivers with positive BACs gradually declined – i.e., the level of alcohol involvement. States vary widely in
48% in 1992, compared to 33% in 1999. Since 1999, the involvement of alcohol in fatal crashes with state-
the percent of fatally injured drivers with positive to-state percentages of fatal crashes involving alcohol
BACs has increased to 38% in 2001, declined to 35% ranging from 12% to 50% in 2005.
in 2002, increased to 38% in 2003, and returned to 35% The lack of progress may in part result from the fact that,
in 2004. while many effective strategies are well known, they are
CONCLUSIONS: The magnitude of the alcohol-fatal not implemented as widely or as vigorously as possible.
crash problem in Canada has fluctuated in recent years For example, well-publicized sobriety checkpoints
and the problem remains significant. Further efforts are have been shown to have a significant impact on
needed to address it effectively. impaired driving, but they tend to be implemented only
sporadically and only in limited areas of the country.
Some aspects of the impaired driving problem have
Alcohol related road accidents in
been particularly difficult to change. For example,
Germany – status till 2005
a higher percentage of motorcycle operators in fatal
H. SCHULzE, S. SCHOENEBECK crashes have alcohol in their systems as compared to
Federal Highway Research Institute (Bundesanstalt für drivers of passenger cars. In other areas, some progress
Strassenwesen), P.O. Box 10 01 50, D-51427 Bergisch is apparent. The number of licensed drivers younger
Gladbach, Germany than 21 declined by 14 percent between 1982 and 2004
while the number of underage drinking drivers in fatal
In 2005, 22,004 alcohol-related injury accidents and 603
crashes declined by 62 percent during that period. Thus,
killed were registered in the official German accident
it appears that the MLDA 21 law and the national zero
database. These figures represent 6.5% of all injury
tolerance law had a substantial effect on underage
accidents and 11.2% of all road accident fatalities.
drinking and driving.
Although alcohol-related accidents still contribute to
It may be that we are approaching the limits of policy and
a considerable amount to the overall number of injury
deterrence to suppress impaired driving. This possibility,
accidents they have been declining steadily during the
along with the dramatic advances in technology, has led
last decade – by more than 40% - whereas the overall
some advocates and policy makers to promote the wider
number of injury accidents has declined by 13% during
application of technological approaches to preventing
the same time. Moreover, the number of casualties
impaired driving. Currently, many states are considering
shows a respectable downward trend. Especially the
more vigorous use of alcohol ignition interlocks for
reduction in fatalities by 65% between 1995 and 2005 is
impaired driving offenders and two states have passed
far above average.
legislation mandating interlocks for first offenders. A
As a result the proportion of accident-involved road
Blue Ribbon panel has also been organized to examine
users influenced by alcohol decreased from 4.9% to
how technology could be used to prevent driving over
3.4% between 1995 and 2005 whereas the share of
the legal limit in the general population through the
alcohol related casualties was reduced from 9.8% to
installation of alcohol detection technologies in all
6.5% during the same period of time.
vehicles. Such strategies would mark a new direction
The presentation will give an overview of the
for the impaired driving field and could bring about the
development of alcohol-related injury accidents between
progress that has been lacking for so long.
1995 and 2005 as well as an insight into their structure –
with special emphasis on the topics of driver’s age and
Worldwide trends in alcohol and drug
BAC-levels.
impaired driving
Trends in impaired driving in the United B.M. SWEEDLER
States: time for a new paradigm? Safety and Policy Analysis International, L.L.C., 3798
Mosswood Drive, Lafayette, CA 94549, USA
K. STEWART(1), J. FELL(2)
This paper will summarize the latest trends in a number
(1) Safety and Policy Analysis International, 3798
of industrialized countries around the world and discuss
Mosswood Drive, Lafayette, CA 94549, USA
the reasons for the changes that occurred, and review
(2) Pacific Institute for Research and Evaluation,
current programs designed to produce further reductions
Calverton, MD 20705, USA
in impaired driving. In the decade of the 1980s, there
This paper is presented as part of the session on were impressive declines in drinking and driving in
worldwide trends in impaired driving. It provides much of the industrialized world. The declines included
analysis of the current situation in the United States. about 50% in the Great Britain, 28% in Canada and
After 15 years of decline, in the last decade, the percentage The Netherlands, 32% in Australia, 37% in Germany
of fatal crashes that involve alcohol has stalled at about and 26% in the U.S. These declines did not continue
40%. It is apparent that policies, enforcement levels, in the early part of the 1990s. In some countries, there
geographic, and other factors play a role in determining were actually increases. Toward the middle and latter
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Annales de Toxicologie Analytique, vol. XIX, n° 4, 2007
part of the decade the increases stabilized and we again Intoxications : case reports
began to see some decreases. However, these decreases
Intoxications : études de cas
have been at a slower rate than the dramatic decreases
in the 1980s. Toward the end of the 1990s and in the
new century, the record has been mixed. Clear trends Postmortem cesium concentrations in a
have emerged. Some countries (France and Germany) cancer patient: a case report
continued to reduce drinking and driving while in other
N. NUWAyHID(1), D. WICKHAM(2), A.M. GORDON(1),
countries (Australia, Canada, United Kingdom and the
B.K. LOGAN(1)
United States), there was stagnation and in some cases
small increases or even large increase as was the case (1) Washington State Toxicology Laboratory, Forensic
in Sweden. Trends on drug impaired driving are also Laboratory Services Bureau, Washington State Patrol,
beginning to emerge in some countries. These trends 2203 Airport Way South, Seattle, WA 98134, USA
will also be discussed. (2) Clark County Medical Examiner, 900 West 13th
Street, Vancouver, WA 98666, USA
Drugs in driving – the South Australian CASE REPORT: Cesium (Cs) is an alkali metal found
experience in the earth’s crust. Low incidence of cancer has been
observed in geographical areas where soil or water is
P. FELGATE, P. HARPAS
rich in cesium. Tumor burden has also been reported to
Forensic Science South Australia, Forensic Science decrease in patients treated with cesium chloride (CsCl).
Centre, 21 Divett Place, Adelaide, South Australia The efficacy and safety of CsCl therapy is scientifically
On the 1st of July 2006 new Road Traffic legislation came not well established and therefore, not used in traditional
into effect in South Australia, which allowed for the random medicine. Instead, it is used as a complementary and
drug testing of oral fluid from drivers. It also allowed for alternative therapy for cancer. Herein, we present a case
the testing of blood samples from drivers injured in motor of a cancer patient self-medicating with CsCl and the
vehicle accidents for drugs as well as alcohol. postmortem concentrations of Cs in tissues.
The random testing of drivers for alcohol and the A 55-year-old female presented with metastatic carci–
testing of blood from all people involved in a motor noma of the gastro-esophageal junction. She was treated
vehicle accident who attend a prescribed hospital has with chemotherapy and radiotherapy prior to laparotomy
been in force in South Australia since the early 1960’s. and jejunostomy at which time the diagnosis was
New legislation has now allowed the random testing confirmed to be advanced metastatic adenocarcinoma of
of drivers and the testing of injured drivers for three probable ovarian origin. She was treated with oxycodone
prescribed drugs (D9-THC), methylamphetamine and and IV hydromorphone to control her pain. Oxycodone
3,4-methylenedioxymethamphetamine (MDMA). was then substituted with hydrocodone and fentanyl.
All positive oral fluid samples from the roadside Fentanyl dose was gradually increased from 100 to
testing are submitted to the Forensic Science Centre for 300 ug/hr over a three and the half month period. She
confirmation. This presentation will examine the number also received magnesium and potassium supplements
of confirmed positive samples and the proportion of since her serum electrolytes were low. She then resorted
each of the prescribed drugs present. This data will be to CsCl as a complementary and alternative therapy. The
compared to the proportions of these prescribed drugs alleged dose she took was 6-9 g/day.
found in the blood samples taken from injured drivers. METHODS: Cesium was measured by ICP/MS at
It is estimated that the South Australian Police will National Medical Services Inc. Fentanyl, hydrocodone
conduct 9,000 oral fluid tests in the 12-month period to and diphenhydramine were quantified by GC-MS
the end of June 2007 with an expected positive rate of post liquid/liquid extraction. Hydromorphone and
approximately 3.4%. It is estimated that approximately hydrocodone were quantified by LC-MS following
1,000 blood samples from injured drivers will be solid phase extraction.
analysed in this same period.
RESULTS: Postmortem toxicological analyses of
The methodology used for the laboratory analysis
peripheral blood revealed the presence of: fentanyl (12
will be discussed. Solid phase extraction followed by
ng/mL), hydrocodone (13 ng/mL), hydromorphone
derivatisation with PFPA and GC-MS analysis is used
(< 1 ng/mL), and diphenhydramine (0.50 mg/L).
for the analysis of amphetamines in oral fluid and blood.
Cesium concentrations were: peripheral blood
Liquid-liquid extraction and derivatisation with PFPA
(1250 mg/L), central blood (670 mg/L), vitreous
and GC-MS analysis is used for the analysis of D9-THC
(112 mg/L), liver (160 mg/Kg), kidney (138 mg/
in oral fluid and blood.
Kg), and brain (155 mg/Kg). Baseline concentrations
are < 0.27 mg/L in blood (National Medical Services
Inc.) and 3-5 x 10-3 mg/Kg in control tissues (Centeno
et al). The reported Cs concentrations in tissues from 2
decedents are: blood (84, 28 mg/L), liver (337, 40 mg/
Kg), kidney (120, 44 mg/Kg), and brain (46, 17 mg/Kg)
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Annales de Toxicologie Analytique, vol. XIX, n° 4, 2007
(Centeno et al). While these results show that the highest 8 ng on column respectively. The Relative Standard
concentrations of cesium are in the liver and kidney, our Deviation for atracurium besylate determination at
results demonstrate that cesium is highly concentrated 50 μg/mL was 2.2%.
in peripheral blood. The blood Cs levels in our case is The selectivity of the method was verified against
5-15 times higher than the reported ones. endogenous compounds due to the matrices for which
CONCLUSIONS: Although the forensic implication blank blood and urine samples extracted separately in
of CsCl therapy in humans is currently not well the same way was injected and checked for the absence
understood, CsCl is potentially a life threatening agent. of interfering compounds.
Experimentally, CsCl is used to induce QT interval CASE REPORT AND CONCLUSIONS: The
prolongation and cardiac arrhythmias in animals. These method was validated and successfully applied in a
conditions in addition to hypokalemia and syncope have case of fatality, where a 31 year old Sri Lankan male
been recently reported in human patients who received anesthetist, attached to a Government hospital was found
CsCl as an alternative or preventative therapy against unconscious in his duty room at night. An IV canula with
cancer. The cause of death in the presented case was a syringe was found in situ in one hand and an empty
signed as cardiac dysrhythmia associated with probable atracurium besylate vial was found at the scene. Medical
cesium toxicity and manner of death was natural. investigations revealed that he was already dead and a
postmortem was carried out by the Judicial Medical
Officer. The samples from the body including blood,
Toxicological analysis of atracurium
bile, urine and tissues from the injection site together
besylate in biological materials by using
with the butterfly IV set with an empty injection syringe
HPLC and empty atracurium vial recovered from the scene
were sent to the Toxicology Section of the Government
S. TENNAKOON, K.A.P.B. PERERA, L.S. HATU-
Analyst’s Department for examination. On analyzing
RUSINGHE, U.S.S. UDUGAMPAL
the samples, 10.5 μg/mL, 28.8 μg/mL and 51.8 μg/mL
Government Analyst’s Department, Independence
atracurium besylate were identified in blood, bile and
Square, Colombo 07, Sri Lanka
urine samples respectively. Further, atracurium besylate
AIMS: Atracurium Besylate is a highly selective, was identified in the empty vial, empty injection syringe
competitive (non-depolarizing) neuromuscular blocking recovered from the scene and the tissues taken from the
agent used in anesthesiology. Following intravenous injection site. This was the first recorded fatal case of
administration atracurium is predominantly degraded, atracurium besylate poisoning in Sri Lanka and possibly
under physiological temperature and pH, by Hoffmann the first case of suicide in Sri Lanka involving atracurium
elimination to laudanosine. The aim of this study is besylate.
to present a method for the toxicological analysis of
atracurium in biological materials using HPLC.
Aniline lethality in humans: metabolic
METHODS: An isocratic reversed phase HPLC method
fate and pharmacokinetics in an animal
coupled with UV detection has been developed for the
model
determination of atracurium in human blood, urine,
bile and tissues from the injection sites. The extraction B. BRUNET(1,2), G. PéPIN(3), S. MARCHAND(1,4),
technique used was simple and rapid; where blood, M. PINSARD(5), P. MURA(1)
urine, bile and macerated injection site tissue samples (1) CHU Poitiers, Service de Toxicologie et
were acidified with 0.5 M sulphuric acid to pH 4.2 and Pharmacocinétique, Poitiers, France;
vortex mixed for 1 minute with acetonitrile. The samples
(2) INSERM E-0324, Université Poitiers, Faculté de
were centrifuged; acetonitrile layer was separated and
Médecine et de Pharmacie, Poitiers, France;
evaporated. A 20 μL aliquot of acetonitrile extract was
(3) Laboratoire TOXLAB, Paris, France;
injected onto the HPLC column. The extraction recovery
was 79.6% at 50 μg/mL atracurium in blood. (4) INSERM ERI-23, Université Poitiers, France;
The extracts were separated with a Lichospher Si-60 (5) CHU Poitiers, Service de Réanimation Médicale,
(150 mm x 4.6 mm I.D, 5 μm particle size) column. Poitiers, France
A mobile phase consisting of acetonitrile and AIMS: A 55-year-old man was brought to the emergency
0.1 M dipotassium hydrogen ortho phosphate room after vomiting, confusion and severe general
buffer (pH=5) in a ratio of 40:60 v/v was used at a cyanosis. Immediate toxicological analyses revealed
flow rate of 1mL/min and UV detection was done at this was the result of aniline ingestion. He died 40 hours
280 nm. later. An autopsy and toxicological investigations were
RESULTS: Linear detector responses were observed required and an animal model was used for a better
for the calibration curve standards in the range of knowledge of aniline metabolism.
0.2 - 100 μg/mL. The limit of detection (S/N ratio =3) METHODS: Antemortem and postmortem toxicological
and limit of quantitation (S/N ratio=10) for atracurium analyses were performed in blood and stomach contents
were 0.1μg/mL or 2 ng on column and 0.4 μg/mL or by GC-MS and HPLC-DAD. Hair specimens were
264
Annales de Toxicologie Analytique, vol. XIX, n° 4, 2007
analyzed by LC-MS/MS. Methemoglobin levels were Getting high by smoking hyoscine
determined in blood on a CO-oximeter. To determine butylbromide?!
the kinetic profile of aniline and its metabolites and the
M. FRASCHT, S. SCHNEIDER, P. LEMMER,
subsequent production of methemoglobin, a large white
M. SCHUMAN, R. WENNIG
pig was used. The animal received a single oral dose
of aniline (0.07 mL/Kg) and 10 blood samples were National Health Laboratory, CRP - Santé, Toxicology
collected during a 360 min period. Division, University of Luxembourg, 162a, avenue de
la Faïencerie, L-1511, Luxembourg
RESULTS: Human case. At admission, a methe-
moglobin level of 68% was determined in blood. Aniline AIMS: Hyoscine butylbromide (N-butyl-S-(-)-
was present in stomach contents (0.47 μg/mL) and in scopolammonium bromide), commercialised in Europe,
plasma (8 ng/mL). Acetaminophen and acetanilide were under the brand name “BUSCOPAN®”, is commonly
also present in plasma (5.5 and 22.5 μg/mL, respectively) used as antispasmodic agent. Recently our laboratory
and in stomach (20 and 12 μg/mL, respectively). After was requested to elucidate the case of a prison inmate
an immediate stomach pump treatment and methylene claiming to smoke crushed BUSCOPAN® tablets in
blue infusion (2 mL/Kg), methemoglobin decreased cigarettes and experiencing agitation, hallucinations
to 25.5% after 4 hours but then increased up to 69.0% and aggressive behaviour. The aim of this study
after 18 hours. Two successive exchange transfusions is to determine if thermal degradation of hyoscine
were then performed and methemoglobin subsequently butylbromide in smoked cigarettes generates hyoscine
decreased to a level of 4.6% but the patient died from (S-(-)-scopolamine)?
a systemic failure. Aniline and its metabolites were not METHODS: A series of 8 cigarettes with and without
identified in hair. Animal experiment. After oral aniline filters, fortified with 10 mg of hyoscine butylbromide,
administration to the pig, the plasma concentrations and were investigated by different smoking modes
the associated methemoglobinemia were as follows: (continuous, puff-by-puff). The smoke of the burning
cigarettes was collected with an ammonium buffer –
Time Aniline Acetanilide Acetaminophen Methemoglobin acetonitrile mixture, whereas the ashes and the filter
(min) (ng/mL) (μg/mL) (μg/mL) (%)
were extracted with methanol. After centrifugation and
0 0 0 0 0,5 addition of atropine (I.S.) the samples were analyzed
15 3,7 26,9 1,2 0,8 by LC-MS/MS in ESI mode. Validation experiments
30 4,5 24,4 2,7 2,2 included specificity, linearity, sensitivity, precision
and accuracy (Method published in: J. Anal. Toxicol.,
45 4,2 27,6 4,8 3,0
31 (2007), 220-223). In particular, the potential
60 4,2 28,6 4,9 5,2
breakdown of hyoscine butylbromide during analysis
90 4,5 30,3 4,5 5,7
was excluded as no scopolamine could be detected
120 4,1 30,5 7,6 9,1 when hyoscine butylbromide alone was injected into
180 3,5 28,2 9,5 11,8 LC-MS/MS.
240 2,5 27,1 8,0 11,7 RESULTS: Hyoscine was detected in the 3 matrices
360 1,7 30,8 10,8 11,4 (smoke, ashes, and filter) in all smoking modes.
Quantities of hyoscine in smoke were highest in
cigarettes without filters (range 131 – 238 µg/cigarette)
CONCLUSIONS: This human case indicates that
and lowest in cigarettes with filters but smoked in the
in an acute intoxication with aniline involving high
puff-by-puff mode (range 98 – 166 μg /cigarette).
levels of methemoglobin, exchange transfusion
The results indicate that a consumer smoking a
should be performed rapidly after methylene blue
cigarette fortified with a crushed BUSCOPAN® tablet
infusion. The results obtained in human as well as in
containing 10 mg of hyoscine butylbromide inhales
pig indicate that when administered orally, aniline is
100 to 150 μg of hyoscine. Although literature reports
rapidly metabolised to acetanilide and acetaminophen.
about hyoscine inhalation is lacking, pulmonary
Furthermore the very low concentration ratio of aniline
administered drugs are generally rapidly and nearly
to metabolites suggests a pre-systemic metabolism. The
completely absorbed. Thus even low doses of hyoscine
low concentration for aniline in plasma in contrast to
may cause the effects observed in the case of the prison
stomach contents also supports this hypothesis. The
inmate.
animal experiment indicated that both metabolites were
still present at increasing concentrations 6 hours after CONCLUSIONS: Reports of persons claiming
aniline administration. Aniline concentration decreased to smoke Buscopan® should be taken seriously
after 90 min whereas methemoglobin levels were still and prescription of Buscopan® tablets to prison
increasing at the end of the experiment. inmates should be reconsidered. Further studies will
be necessary to elucidate the thermolysis reaction
mechanism.
265