It is absolutely necessary for a medicolegal system to have access to a
well-equipped, adequately staffed toxicology laboratory. Without this, rulings
as to cause and manner of death may be erroneous.
All physicians and toxicologists have had cases where an individual was
found to have a fatal level of drug in the blood but was functioning with this
level; the drug had nothing to do with the death. This is seen typically in
drug abusers who acquire a tolerance to drug levels that would kill an ordinary
person, but are normal functioning levels to them. This same situation is seen
by clinical physicians — the patient admitted to the emergency room conscious
and coherent, with drug levels that would be associated with unconsciousness or
death in most individuals. In all
autopsy cases, at a minimum, blood, urine, bile, and vitreous should be
collected if available.
All specimens should be collected with a clean needle and a new syringe. The specimens of blood, urine, bile, and vitreous should be placed in glass
containers, not plastic, because these fluids can leach out plastic polymers
from the wall of a plastic container. If the blood is subsequently analyzed by
gas chromatography, the polymers will give peaks that could mask certain
compounds and interfere with analysis. In some cases, substances such as
volatiles can be lost, due to absorption by the plastic.
• Collect the blood from the femoral vessels. If this is not possible,
the other sites for collection, in descending order of preference, are:
• The subclavian vessels
• The root of the aorta
• The pulmonary artery
• The superior vena cava
• The heart
• Collect a minimum of 50 mL of blood.
• 20 ml in a 20-mL red-top glass test tube
• 20 ml in two 10 mL gray-top glass test tubes (preservative potassium oxalate
and sodium fluoride)
• 10 ml in a purple top glass test tube (preservative EDTA) for DNA analysis
• Collect all the vitreous
• Collect 20 ml of urine
• Collect up to 20 ml of bile
Label the specimens with name of deceased; case number; date of examination;
name of the pathologist and, in the case of the blood, the source of the blood,
e.g., the femorals. If the blood is to be analyzed for volatiles, some should
be kept in a test tube with a Teflon-lined screw top rather than a rubber
stopper through which volatile compounds can diffuse. The practice of opening
the pericardial sac, positioning a tube or jar under the heart, then cutting
the heart and letting blood drain into the receptacle should be condemned,
because it is very easy to contaminate the contents of the jar with pericardial
fluid and other material that might be present in the chest cavities. This may
dilute the blood (with resultant fallacious low levels) or, if there has been
diffusion of a drug from the stomach into pericardial or chest fluid, may
actually contaminate it with the drug such that inaccurately high levels are
detected in the “heart blood.”
The best examples are the tricyclic antidepressants. In cases involving
these drugs, quantitation of the liver has been suggested as being superior to
blood levels in determining whether one is dealing with an acute overdose or
levels caused by chronic medication. Pounder et al., however, have called this
into question by demonstrating postmortem diffusion of drugs from the stomach
into the liver, principally the left lobe. Diffusion of alcohol into the
cardiac chambers, the superior vena cava and the aorta is more controversial. The
general feeling is that, while this can occur, it is uncommon. Diffusion
appears to be associated with very high concentrations of alcohol in the
stomach; failure to refrigerate the body for more that 24 hours, and an
increasing time from death to collection of the blood.
In individuals who have died after several hours or days of
hospitalization, one would expect that any drugs in the blood at the time of
admission would be metabolized. This is usually, but not always, the case. In
these instances, not only should blood be obtained at autopsy, but the hospital
in which the individual was a patient should be contacted to see if any blood obtained
at or shortly after hospitalization is still in existence. This should then be
obtained for toxicologic analysis. In trauma cases, blood is usually drawn
immediately on admission to the emergency room and sent to the blood bank for
typing and cross-match; it should then be retained in the blood bank for at
least 2 weeks. Unless there has been unusually prolonged survival, the drug
that causes death will be present in the blood. Even with prolonged survival,
the drug can usually be detected in the vitreous, bile, or urine. Blood is
collected from either the femoral or subclavian vessels. Blood should never be collected by way of a blind stab
through the anterior chest wall into the heart. This is to preclude inadvertent contamination of the
blood with fluid contents from the esophagus, pericardial sac, stomach or
pleural cavity. Toxicologic analysis should be oriented to analysis of blood. With
rare exception, virtually all drugs and their major metabolites can now be
detected in blood in any modern toxicology lab. [1]Heroin
is an exception. But even in this case one can usually prove conclusively that
it was taken. Thus, heroin (di-acetylmorphine) is almost immediately
metabolized to mono-acetylmorphine and then to morphine in the blood after
injection. The detection of morphine in the blood was assumed to indicate that
the individual died of an overdose of heroin. In some deaths in an emergency
room, it was contended that the individual was inadvertently given morphine,
thus causing death, i.e., the deceased was not a drug addict.
Mono-acetylmorphine can often be detected in the vitreous after it has
disappeared from the blood. In cases of head trauma, where there is a subdural
collection of blood and the individual survives a number of days, subdural
blood can be analyzed for alcohol. The results will be a crude approximation of
the alcohol level of the deceased at the time the head trauma was incurred.
Most drugs are excreted in the urine. Analysis of urine for drugs is
easy because there is no protein binding to hinder extraction and many drugs
are concentrated in the urine. It should be realized, however, that the level
of a drug in the urine is usually of no significance in the interpretation of
the cause of death. It is the level in the blood that determines whether an
individual lives or dies. An example would be the case of an individual who
died of hypoxic encephalopathy believed caused by a heroin overdose. In such a
case, an analysis for morphine in the bile is conducted to see if an opiate had
been used in the past several days. Liver and kidney are rarely used nowadays
because there is no direct correlation between levels in these organs and blood
levels. Hair and fingernails can be retained for analysis if one suspects
arsenic poisoning. The muscle, especially that of the thigh, is often well
preserved, in spite of advanced decomposition. In one case involving cocaine,
even after embalming and disinterment of the body months after burial, cocaine
and two of its metabolites, in lethal levels, were identified and quantitated
in the muscle. Levels of drugs in the muscle more accurately reflect blood
levels than the liver or kidney. Analysis of insects, e.g., maggots, feeding on
a severely decomposed body have demonstrated the presence of drugs such as
barbiturates, benzodiazepines, opiates and cocaine.
Analysis of biological tissues for toxicological purposes involves three
fundamental steps applicable to any specimen:
1.
Separation of the drug from the biological tissue
2.
Purification of the drug
3. Analytical detection and quantitation
Separation of a drug from the biological specimen, e.g., blood, is
usually accomplished using a solvent. Purification is carried out by additional
extraction procedures using alkaline and acid solutions. Analysis is then conducted
by gas chromatography (GC), gas chromatography-mass spectrometry (GC-MS), high
performance liquid chromatography, immunoassay or UV spectrophotometry. It must
be realized that, except for GC-MS, none of the methods is totally specific.
One of the more recently developed tools of the forensic toxicologist is
the immunoassays. There are four types:
- radioimmunoassay,
- enzyme
immunoassay,
- fluorescent
immunoassay and
- kinetic interaction of microparticles.
The major advantage to these systems is that large numbers of tests can
be performed in a small amount of time using an extremely small volume of specimen,
with semi-automated and automated systems to speed the rate of analysis. While
radio-immuoassays can be used on blood, the other types of immunoassay should
be confined to analysis of urine. There are two disadvantages to immunoassay
techniques. First, the analysis is usually very narrow in scope; i.e., one
analyzes for either a specific drug or a specific family of drugs, rather than
for the several hundred drugs that can be analyzed for in one test with a GC or
GC-MS. In addition, this method of analysis is not absolutely specific,
although, with some of the newer kits, the specificity is extremely good. A
positive test result must be confirmed by another analytical method, usually
GC-MS. In a high-volume forensic lab, immunoassay methods can be used to screen
for opiates, cocaine, amphetamines and methamphetamines, barbiturates, and
cannabinoids in the urine. Negative results indicate that the compounds are not
present; positive results indicate that the compound may be present. Generally,
toxicological screens can be divided into four general groups. First is the
screen for lower alcohols. This involves analysis by gas chromatography. and
will identify acetone, isopropyl alcohol, n-propyl alcohol, ethyl alcohol, and
methyl alcohol. Blood for this test should be collected in a tube containing sodium
fluoride and potassium oxalate to prevent postmortem alcohol formation or loss.
The second screen is the acidic and neutral screen. This is performed on urine
by immunoassay. It detects primarily barbiturates, salicylates, ethclorvynol, and
carbarnates. Confirmation and quantitation is usually by GC-MS. The third
screen is the basic screen. It detects tranquilizers, synthetic narcotics,
local anesthetics, antihistamines, antidepressants, alkaloids, and other agents
extractable from alkaline aqueous solution. Hundreds of drugs and metabolites
can be detected by this procedure, depending on how it is structured. The
equipment necessary for these screens is either a GC or GCMS. General screening
can be done with a GC, with confirmation and quantitation by GC-MS. The fourth
screen is the narcotics screen. It can be readily accomplished nowadays with
immunoassay on urine. This test screens for the opiates, cocaine, and
methadone. A positive test by the immunoassay requires positive identification
and quantitation by a GC-MS on blood. Drugs not detected in the aforementioned
screen include some whose blood therapeutic or abuse levels are extremely low. These
can be picked up by GC-MS. Examples are phencyclidine, fentanyl derivatives,
etc. If these drugs are suspected or common in one’s population, an immunoassay
screen can be performed on urine. Cyanide can be analyzed for by using a
specific ion electrode or other chemical techniques. Alkaloid poisons, such as
strychnine and nicotine, are detected in the basic screen.
In all homicides, accidents, and suicides, the authors recommend the lower
alcohol screen; the acidic and neutral screen; and the basic screen. In
stranger-to-stranger homicides and those in which the use of narcotics is
suspected, the narcotic screen is also recommended. In natural deaths, the
authors recommend the alcohol, the acidic and neutral screen, and the basic
screen. Deaths caused by ingestion, injection, snorting, or inhalation of drugs
fall into four categories by manner: homicide, suicide, accident, and undetermined.
The last category is used when a decision as to manner of death cannot be made.
For the most part, the accidental category is made up of deaths caused by drug
abuse. In the nineteenth century, the “three curses of mankind” were said to be
alcohol, morphine, and cocaine.
After alcohol and marijuana, the most commonly abused drugs are probably
heroin and cocaine. There are numerous other drugs of abuse: the synthetic
narcotics, phencyclidine, amphetamine and methamphetamine, propoxyphene,
inhalants, and so on.
Any drink containing from 0.5 to 95% alcohol is considered an alcoholic beverage.
The term “proof” is used to describe the strength of an alcoholic beverage.
Proof is defined as twice the percentage of the alcohol content of the drink.
Thus, an 80-proof beverage is 40% alcohol. The alcohol content of beer ranges
between 3.2 and 4%, table wines 7.1 to 14%, whiskey 40–75%, vodka 40–50%, gin
40–85%, and rum 40–95%. Alcohol is rapidly absorbed from all the mucosal
surfaces of the gastrointestinal tract. In fasting individuals, 20–25% of a
dose of alcohol is absorbed from the stomach and 75–80% from the small
intestine. Food delays the absorption of alcohol. Following ingestion of
alcohol on an empty stomach, peak blood alcohol concentration occurs within one
half to 2 h (average 0.75–1.35 h), whereas with food in the stomach, peak
levels are reached within 1–6 h (average 1.06–2.12 h). Alcohol is soluble in
water, it is present in the body tissue in direct relation to the amount of
water content of the tissue or fluid. Specimens with high water content, such
as blood or vitreous, will have high concentrations of alcohol compared with
tissues such as the liver or brain. Forensic pathologists tend to deal in whole
blood when performing alcohol determinations, while clinicians often use serum
or plasma. The plasma or serum to whole blood alcohol concentration ratio
averages 1.18 (a range of 1.10 to 1.35). It is often not realized that there
may be a significant difference in the alcohol concentration of arterial blood
and venous blood in the absorptive phase, with arterial blood up to 40% higher
in alcohol concentration than venous blood. The next-best tissue to analylze
for alcohol is muscle. We prefer muscle from the thigh since it is isolated
from other organs, unlike psoas muscle, it appears to be fairly resistant to
decomposition.Immediately on entering the body, alcohol begins to undergo metabolism.
It is metabolized to acetaldehyde, acetaldehyde to acetic acid, and acetic acid
to carbon dioxide and water. The vast majority of the metabolism (95%) occurs
in the liver. Blood alcohol in males is metabolized at an average rate of 15
mg/dL per hour (a range of 11–22 mg), and in females at 18 mg/ dL per hour (a
range of 11–22 mg). Alcohol, being a drug, has measurable effect on many of the
physiological activities of the body. Alcohol impairs visual acuity, adaption
to both light and darkness, discrimination of colors, persistence or speed of
response to visual stimulation, focusing… . Most deaths caused by acute alcohol
intoxication occur with blood alcohol levels of 400 mg% or greater. Inexperienced
drinkers are more susceptible than chronic alcoholics. Chronic alcoholics have
been apprehended operating motor vehicles with blood alcohols of 450–500 mg%
and have actually survived alcohol levels as high as 600–700 mg%.
Some of Intoxicating substances:
Methanol is oxidized by the liver to formaldehyde, which in turn is
oxidized to formic acid. Formic acid is six times more toxic than methanol. Symptoms
of acute
methanol poisoning are weakness, nausea, vomiting, headache, epigastric pain,
dyspnea, and cyanosis. Inebriation is not a prominent symptom. The symptoms may
occur within half an hour after ingestion or may not appear for 24 h. If a
fatal amount of methyl alcohol has been ingested, the aforementioned symptoms
will be followed by stupor, coma, convulsions, hypothermia, and death. Death is
nearly always preceded by blindness. If the individual does survive, he may be
permanently blind, due apparently to a specific toxicity for the retinal cells.
Death in methyl alcohol poisoning is caused by the acidosis from production of
organic acids and the CNS depressant action of the alcohol.
Isopropanol is available to the public as rubbing alcohol in a 70% aqueous
solution. It has twice the CNS depressant potential of ethanol. Unlike methanol, it is not in itself toxic. It is
metabolized in the liver to acetone. A lethal dose of isopropanol is estimated
at 250 mL for an adult. It should be noted that the appearance of small amounts
of isopropanol in the blood is not necessarily indicative of ingestion of this
alcohol. In diabetics with ketoacidosis, and in cases of starvation with high
levels of acetone, acetone may be converted to isopropyl alcohol.
Ethylene glycol is the principal component of most automotive antifreeze
solutions. In humans, it is metabolized to a number of compounds, the most important
of which is oxalic acid. Ethylene glycol itself is not toxic; it is the
metabolites (principally oxalic acid) that are. Minimum lethal dose is
estimated at 100 mL for an adult, though individuals have survived
significantly higher amounts. The clinical manifestations of acute ethylene
glycol intoxication can be divided into neurological, cardiorespiratory, and
renal. Neurological symptoms usually develop within a half hour to 12h after
ingestion. The individual develops nausea,
vomiting, convulsions, and coma.
Heroin was introduced to medicine and the public in the early part of
the 20th century as a replacement for morphine and codeine. In all cases,
individuals who die of an overdose of heroin are either under the influence of
alcohol or intoxicated at the time of death. More recently, we have seen a
number of deaths caused by “speedballs,” a combination of heroin and cocaine. At
autopsy of an individual who has died of an overdose of heroin, the lungs are
heavy and show congestion, though the classic pulmonary edema mentioned in some
of the older textbooks is not always present. Microscopic examination of the
lungs commonly reveals foreign-body granulomas with talc crystals and cotton
fibers. The cotton originates from the “strainer.” The talc probably has been
used as a cutting agent. There is usually enlargement of the periportal lymph
nodes. Microscopic examination of the liver will reveal a chronic triaditis
with a mononuclear cell infiltrate.
Fentanyl is 50–100 times more potent than morphine. It is the preferred
drug of abuse of anesthesiologists. It is available both in hospitals and
clandestinely. It can be taken intravenously, orally, smoked, snorted or by way
of skin patches, with the intravenous route the most common. Therapeutic levels
are in the low ng/mL levels (1–3 ng/mL). Fatalities are seen at levels begining
at 3 ng/mL.
Cocaine can be sniffed, shot intravenously, or smoked as “crack.” While
originally said to be nonaddictive (just like heroin), it is now realized that
it is a very potent addictive compound, especially the crack (free base) form. When
smoked as crack, it is immediately absorbed by the lungs and reaches the brain
within seconds. It takes slightly longer for its action to affect the brain
when injected intravenously. Cocaine is a relatively short-acting drug such
that to maintain a high, one has to take it every 15 min to an hour. Since it
is a potent vasoconstrictor, snorting the drug can occasionally cause
ulceration and perforation of the nasal septum with long-term use. Cocaine has
also been linked to myocardial infarctions, cerebral hemorrhages and dissecting
aortic aneurysms. Cocaine-related deaths are generally not dose related. Cocaine is
rapidly hydrolyzed to benzoylecgonine and other derivatives by blood
cholinesterases. Continued breakdown of cocaine will continue in the test tube
unless it is inhibited by the addition of fluoride. After being taken, cocaine
appears almost immediately in the urine. Habitual, prolonged, heavy use of
cocaine can make an individual aggressive, violent, and paranoid. Such
individuals may become extremely violent and assaultive.
Methamphetamine is also a cardiovascular stimulant. It blocks re-uptake
of norepinephrine and causes an increase in catecholamine release. The euphoric
effect is similar to cocaine but may last as long as ten times that of cocaine.
Methamphetamine is metabolized to amphetamine, its major active metabolite.
Amphetamine itself is rarely encountered. In overdoses, methamphetamine causes
restlessness, confusion, hallucinations, coma, convulsions, and cardiac
arrhythmias. With chronic abuse, just like cocaine, it can produce a chemical
paranoid psychosis.
Acknowledgements:
The Police Department;
https://www.politie.nl/mijnbuurt/politiebureaus/05/burgwallen.html and a Chief Inspector – Mr. Erik
Akerboom
©
Bibliography:
- Criminal Investigations – Crime Scene Investigation.2000
- Forensic Science.2006
- Techniques of Crime Scene Investigation.2012
- Forensics Pathology.2001
- Pathology.2005
- Forensic DNA Technology (Lewis Publishers,New York, 1991).
- The Examination and Typing of Bloodstains in the Crime
Laboratory (U.S. Department of Justice, Washington, D.C., 1971).
- „A Short History of the Polymerase Chain Reaction". PCR Protocols. Methods in
Molecular Biology.
- Molecular Cloning: A Laboratory Manual (3rd ed.).
- "Antibodies as Thermolabile Switches: High Temperature
Triggering for the Polymerase Chain Reaction". Bio/Technology.1994
- Forensic Science Handbook, vol. III (Regents/Prentice
Hall, Englewood Cliffs, NJ, 1993).
- "Thermostable DNA Polymerases for a Wide Spectrum of
Applications: Comparison of a Robust Hybrid TopoTaq to other
enzymes". In Kieleczawa J. DNA
Sequencing II: Optimizing Preparation and Cleanup. Jones and Bartlett.
2006
- Nielsen B, et al., Acute and adaptive
responses in humans to exercise in a
warm, humid environment, Eur J Physiol 1997
- Molnar GW, Survival of hypothermia by men
immersed in the ocean. JAMA 1946
- Simpson K, Exposure to cold-starvation and
neglect, in Simpson K (Ed): Modem Trends in Forensic
Medicine. St Louis, MO, Mosby Co, 1953.
- Fitzgerald FT, Hypoglycemia and accidental
hypothermia in an alcoholic population.
West J Med 1980
- Stoner HB et al., Metabolic aspects of
hypothermia in the elderly. Clin Sci 1980
- MacGregor DC et al., The effects of
ether, ethanol, propanol and butanol on tolerance to deep hypothermia. Dis Chest 1966
- Cooper KE, Hunter AR, and Keatinge WR,
Accidental hypothermia. Int Anesthesia Clin 1964
- Keatinge WR. The effects of subcutaneous
fat and of previous exposure to cold
on the body temperature, peripheral blood flow and metabolic rate of men in cold water. J Physiol 1960
- Sloan REG and Keatinge WR, Cooling rates of
young people swimming in cold
water. J Appl Physiol 1973
- Keatinge WR, Role of cold and immersion
accidents. In Adam JM (Ed) Hypothermia – Ashore and
Afloat. 1981, Chapter 4,
- Keatinge WR and Evans M, The respiratory
and cardiovascular responses to immersion
in cold and warm water. QJ Exp Physiol 1961
- Keatinge WR and Nadel JA, Immediate
respiratory response to sudden cooling of the skin. J Appl Physiol 1965
- Golden
- Burton AC and Bazett HC, Study of average
temperature of tissue, of exchange
of heat and vasomotor responses in man by means of bath
coloremeter. Am J Physiol 1936
- Adam JM, Cold Weather: Its characteristics,
dangers and assessment, In Adam JM
(Ed). Hypothermia – Ashore and Afloat,
- Modell JH and
Davis JH, Electrolyte changes in human drowning victims. Anesthesiology 1969
- Bolte RG, et
al., The use of extracorporeal rewarming in a child submerged for 66
minutes. JAMA 1988
- Ornato JP,
The resuscitation of near-drowning victims. JAMA 1986
- Reh H, On the
early postmortem course of “washerwoman’s skin at the fingertips.” Z Rechtsmed 1984;
- Gonzales TA,
Vance M, Helpern M, Legal Medicine and Toxicology. New York,
Appleton-Century Co, 1937.
- Peabody AJ,
Diatoms and drowning – A review, Med Sci Law 1980
- Foged N,
Diatoms and drowning — Once more.Forens Sci Int 1983
- "Microscale chaotic advection enables robust convective DNA
replication.". Analytical
Chemistry. 2013
- Sourcebook in Forensic Serology, Immunology, and Biochemistry (U.S.
Department of Justice, National Institute of Justice, Washington,
D.C.,1983).
- C. A. Villee et al., Biology (Saunders College Publishing,
Philadelphia, 2nd ed.,1989).
- Molecular Biology of the Gene (Benjamin/Cummings
Publishing Company, Menlo Park, CA, 4th ed., 1987).
- Molecular Evolutionary Genetics (Plenum Press, New York,1985).
- Human Physiology. An Integrate. 2016
- Dumas JL and Walker N, Bilateral scapular
fractures secondary to electrical
shock. Arch. Orthopaed & Trauma
Surg, 1992; 111(5)
- Stueland DT, et al., Bilateral humeral
fractures from electrically induced
muscular spasm. J. of Emerg. Med. 1989
- Shaheen MA and Sabet NA, Bilateral
simultaneous fracture of the femoral
neck following electrical shock. Injury. 1984
- Rajam KH, et al., Fracture of vertebral
bodies caused by accidental electric
shock. J. Indian Med Assoc. 1976
- Wright RK, Broisz HG, and Shuman M, The
investigation of electrical injuries
and deaths. Presented at the meeting of the
- Wetli CV, Keraunopathology: An analysis of 45 fatalities, Am J Forens Med Path 1996
[1] Heroin, also known as diamorphine among other names, is an opioid most commonly used as
a recreational drug for its euphoric effects. Medically
it is used in several countries to relieve pain or in opioid replacement therapy.
Heroin is typically injected, usually into a vein; however, it can also be
smoked, snorted or inhaled. Onset of
effects is usually rapid and lasts for a few hours.
Molecular weight: 369.4 g/mol
Diamorphine (diacetylmorphine; CAS-561-27-3) is
produced by the acetylation of crude morphine. The systematic name (IUPAC) is
(5α,6α)-7,8-didehydro-4,5-epoxy-17-methylmorphinan-3,6-diol
acetate. Although five pairs of enantiomers are theoretically possible in
morphine, only one occurs naturally (5R, 6S, 9R, 13S,
14R).
Common side effects include respiratory
depression (decreased breathing), dry mouth, euphoria, and addiction. Other side effects can include abscesses, infected
heart valves, blood borne infections, constipation, and pneumonia. After a history of long-term use, withdrawal
symptoms can begin within hours of last use. When
given by injection into a vein, heroin has two to three times the effect as a
similar dose of morphine. It typically comes as a white or brown powder.
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