Role of Toxicology in SCD. C. Jurado
Transcript of Role of Toxicology in SCD. C. Jurado
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 ⇒
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