National Institute of Toxicology and Forensic Sciences. Sevilla. SPAINAthens May 16-17, 2018

Carmen Jurado

Number of cases ⇒ 4773

Drug seizures

165Living people

963

Post-mortem

3645

Non-Violent Deaths

1906

Violent Deaths

1725

1873

20

4

0 500 1000 1500 2000

Natural/Undetermined Death

Sudden Death Sports

Sudden Infant Death

Non-Violent Deaths

To examine whether a potentially toxic compound is:

� Directly considered as being the cause of death

� Indirectly involved ⇒ Chronic consumption

Role of Toxicology:

Experience of INT-CF

Data from the Literature

“Sudden cardiac death (SCD) is an unexpected death due to cardiac causes

that occurs within one hour of symptoms onset. SCD is also considered the

unexpected death of an apparently healthy person who was fine within 24

hours prior the death.

477347174784463247274725

5

38

28

20

16

14

0

1000

2000

3000

4000

5000

6000

2012 2013 2014 2015 2016 2017

0

5

10

15

20

25

30

35

40Total nº Cases SD-Sports

Evolution 2012 – 2017:

0

5

10

15

20

25

30

35

Sex� 110 Men

� 4 Women

Distribution by age

Nu

mb

er

of

case

s

<30 60-7030-40 40-50 50-60

Age (Years)

70-80

Distribution by exercise

Percentage (%)

0 5 10 15 20

Basketball

Diving

Swimming

Golf

Football

Footing

Paddel/Tenis

Gym

Cycling

Period: 2012 – 2017

Positives

16.7%

Negatives

83.3%

Cocaine

3.03%

Ethanol

4.54%

Other Compounds

12.12%

Ethanol

Concentrations (g/L)0 0,5 1 1,5

Other compounds

Intensive

Therapy

� Ibuprofen� Phenobarbital

� Mirtazapine� Torasemide

� Bromazepam� Sertraline

� Trazodone� Lormetazepam

� Venlafaxine� Hidoxycine

� Midazolam

� Lidocaíne

45 year old man. After playing paddle tennis he took a shower. Just going out from

the locker room he collapsed.

Autopsy findings:

� Intense pulmonary edema

� Coronary arteriosclerosis

� 90% stenosis in right coronary artery

Blood and Urine for toxicological analysis

Cocaine

N.D.

N.D.

BE

0.29 mg/L

0.32 mg/L

Blood

Urine

Recent consumption

Luke, J. L., Farb, A., Virmani, R., and Sample, R. H. B., Sudden Cardiac Death During Exercise in a Weight Lifter Using Anabolic Androgenic

Steroids: Pathological and Toxicological Findings, Journal of Forensic Sciences (1990) 35 (6): 1441 1447

� 21 year old man collapsed during

weight-lifting workout

� Family report:

� AAS parenterally (testosterone

and nandrolone) several months

� No significant illness in the past

medical history

Toxicological results

� Ethanol ………………….

� Drugs of abuse ………….

� Nandrolone metabolites:

� 19-nor-androsterone …

� 19-noretiocholanolone .

� 19-nor-epiandrosterone .

Negative

Negative

230 ng/mL

52 ng/mL

32 ng/mL

V. Fineschi, I. Riezzo, F. Centini, E. Silingardi, M. Licata, G. Beduschi, S. B. Karch, Sudden cardiac death during anabolic steroid abuse:

morphologic and toxicologic findings in two fatal cases of bodybuilders, Int J Legal Med (2007) 121: 48–53

� 29-year-old bodybuilder

� Weight lifting workout at the gym a

few hours before

� 30-year-old male bodybuilder

� Weight lifting workout at the gym a few

hours before

Toxicological resultsEthanol and Drugs of Abuse Negatives in both cases

� Stanozolol ………

� (T/E) ratio………

43 ng/mL

28.7

� Norandrosterone ……….

� (T/E) ratio ..…………….

43 ng/mL

42

Case 1 Case 2

M. Montisci, R. El Mazloum, G. Cecchetto, Cl. Terranova, S. D. Ferrara, G. Thiene, C. Basso, Anabolic androgenic steroids abuse and

cardiac death in athletes: Morphological and toxicological findings in four fatal cases, For. Sci. Int. (2012) 217:13–18

� 4 previously healthy athletes ⇒ 3 bodybuilders & 1 cyclist

� Anabolic Androgenic Steroids users

Stanozolol (hair): 5.0 pg/ng

Toxicological investigations in a wide range of biological matrices

Chronic consumption of AAS in SDS

National Institute for Alcohol Abuse and Alcoholism

(NIAAA)

�Men

� ≥ 40 - 60 grams of pure alcohol per day over several months

� Women� ≥ 30 - 45 grams of pure alcohol per day over several months

WHO (World Health Organization)

� Heavy drinking > 60 grams of alcohol per day

�Alcohol abuse ⇒ Social and Economic problems to the

Society

�Adverse effects on Human Health due to:

� Recent Consumption: overdose & intoxication ⇒

violence, accidents …… Sudden Death

� Chronic consumption: chronic diseases ⇒ cirrhosis,

cardiovascular diseases, infections, mental

disorders……. Sudden Death

� Ethyl alcohol

� Ethanol metabolites � Fatty acid ethyl esters (FAEE)

� Ethyl-glucuronide (EtG)

� Cocaethylene

� Follow-up products of

acetaldehyde � Acetaldehyde-modified

proteins

� Salsolinol

Recent Cons. Blood

Chronic Cons. Hair

� Enzymes � GGT

� ASAT and ALAT

� HEX

� ALDH

� Alcohol related metabolic

changes � CDT

� Phosphatidylethanol

� 5-Hydroxytryptophol

� Dolichol

� Ketone bodies

� Macrocytosis (MCV)

� Light to moderate alcohol consumption:� Not associated with higher risk of SCD

� May provide benefits in prevention SCD

Chiuve S., Rimm E., Mukamal K., Rexrode K., Stampfer M., Manson J., Albert C, Light to Moderate Alcohol Consumption and

Risk of Sudden Cardiac Death in Women, Heart Rhythm. (2010) 7(10): 1374–1380

Heavy drinking is associated with an increased risk of

sudden death.

Wannamethee G., Shaper A.G., Alcohol and sudden cardiac death, Br. Heart J. (1992) 68:443-448

� 7735 men 40-59 years of age

� Study performed over eight years in 24 towns in England

� Alcohol intake classification: none, occasional, light,

moderate and heavy

But …………

0

20

40

60

80

100

120

<30 30-40 40-50 50-60 60-70 70-80 80-90

� Period studied January 1, 2017 – December 31, 2017.

� Total number of cases ⇒ 4773

EtOH Positives

Natural Diseases

Post-mortem cases

Total number4773

3645

1906

271

� Men ⇒ 229 (84.5%)

� Women ⇒ 42 (15.5%)

Distribution by AgeNº cases

Age (Years)

Population Study

Recent Consumption

� 57 years old man. Collapsed when

getting off the car.

� Family report:� Relatives MI death

� In a party before death

Toxicology

� Ethanol …………………..

� Drugs of abuse………......

� Medical drugs……………

3.19 g/L

Negativo

Negativo

� 74 years old man. Collapsed while

speaking wiht some friends

� Autopsy report:� Intense pulmonary edema

� Left ventricular hypertrophy

� Aortic and coronary atheromatosis

Toxicology

� Ethanol …………………..

� Drugs of abuse ………...

� Medical drugs ………….

3.02 g/L

Negativo

Negativo

44 years old male. Medical history: hepatitis, alcoholism and drug

consumption (some years before). High alcohol consumption the week before

death and very exited de day he passed away.

Autopsy:� Liver failure,

� pulmonary congestion and oedema,

� esophageal varices,

� gastrointestinal bleeding

�Toxicological analysis ⇒ blood, urine and hair.

Blood

0.12 g/L

Trazes

N.D.

Urine

N.A.

0.12 mg/L

0.03 mg/L

Ethanol

Codeine

Morphine

Pelo (7 cm.)

N.D.

N.D.

N.D.

N.D.

N.D.

0.73 ng/mg

Opiates

Cocainics

Cannabis

Methadone

Amphetamines

EtG

ToxicologyBlood y Urine ⇒ Codeine

consumption …..some time before

death

Hair ⇒ Chronic excessive alcohol

consumption 7 months (at least)

Chronic Consumption

� Cocaine is the drug of abuse most frequently consumed after

cannabis

� Chronic consumption ⇒ Cardiac and cerebrovascular

abnormalities

�Risk of cardiac arrhythmia and sudden death

69

44

32 30

14

0

10

20

30

40

50

60

70

80

DOA Suicide DUI Nat.

Disease

Others

Year 2017 ⇒ 188 Cases cocaine consumption

�January 1, 2017 – December 31, 2017.

4773

188

30

Total Number of cases received at the lab

Cases with cocaine consumption

Cocaine in natural diseases

Population Study

J. L. Pilgrim, N. Woodford, O. H. Drummer, Cocaine in sudden and unexpected death: A review of 49 post-mortem

cases, For. Sci. Int. 227 (2013) 52–59

� Study performed in Australia from January 2000 – December 2011.

� 49 cases cocaine consumption ⇒ 5 natural deaths

� All of them males from 26 to 70 year old.

2477

1114

668

21

� Prospective study November 2003 – June 2006.

� Study performed in Sevilla ⇒ South West Spain

� 2477 autopsies performed at the Institute of

Legal Medicine in Sevilla.

J. Lucena, M. Blanco, C. Jurado, A. Rico, M. Salguero, R. Vazquez, G. Thiene, C. Basso., Cocaine-related sudden death: a prospective investigation in south-west Spain, European Hearth Journal (2011)

Autopsies

Natural DeathsSudden Deaths

Cocainepositives

� 3.14% (21/668) Sudden Deaths ⇒

Cocaine related.

� All of them men

Cocaine findings� COC + EtOH⇒ 76.2%

� Only one case with lethal blood conc. ⇒

2.23 mg/L

Blood

Urine

35 year old man ⇒ Cardiorrespiratory arrest in a night club. Exitus during transport

to hospital

Autopsy findings

� Pulmonary oedema

� Brain Congestion and edema

� Hypertrophy L.V. wall.

Toxicological Analysis ⇒ Blood & Urine

Cocaine

0.68

6.19

BE

3.34

24.84

Blood

Urine

EME

+

++

Lidocaine

0.63

+

Sildenafyl

N.D.

+

EtOH

Trazas

N.D.

Concentrations mg/L

ToxicologyConsumption:

� Cocaine

� Sildenafyl

Lidocaine ⇒ Intensive Therapy

Recent Consumption

Cocaine

N.D.

N.D.

BE

N.D.

N.D.

Blood

Urine

Toxicological analysis ⇒ Negative in

blood and urine

30 year old man, who was found death in his bed. No previous medical history.

Friends suspected cocaine consumption.

Blood, Urine and Hair for toxicological analysis

0

20

40

60

Co

nc.

(n

g/

mg)

cm from the root

Cocaine

BE2 4 6

Chronic Consumption

R. Gow, D. Pereg, G. Koren, M.J. Rieder, S. Van Uum, Elevated hair cortisol levels in patients with acute myocardial infarction, Can. J.

Clin. Pharmacol. 16 (2) (2009) E301.

� Cortisol or Hydrocortisone ⇒ Stress hormone

� Chronic physical or emotional stress ⇒ Accelerate myocardial infarction (MI)

A. 45 patients with MI during previous

48 hours.

B. 45 control patients hospitalized for

other indications.

Analysis of 3 cm proximal segment

�Cortisol ↑↑↑ en hair of patients with MI

versus control patients

�High Cortisol concentrations during 3

months before MI.

�Cortisol in hair ⇒ Chronic Stress Marker

230,6

419,5

0100200300400500600700800900

1000

Control Pat. MI Pat.

� Toxicological analysis in all the cases related to

sudden cardiac death ⇒ Recommended

� Toxicological investigations in several biological

matrices ⇒ demonstrate type, magnitude and time of

exposure:

� First in urine and blood ⇒ Recent consumption

� Hair analysis ⇒When negative results in

biological fluids

� Other determinations to prevent Sudden Deaths ⇒

Also Recommended

carmen.jurado@justicia.es

¡Thank you!