Overveiw..

2000 Plant species contain cyanogenic

glycosides therefore have potential to produce
HCN toxicity.
Cyanide toxicity Cyanide toxicity (also known
as prussic (also known as prussic acid
poisoning)
 OVERVIEW
Cyanide is a potentially lethal toxic agent that can
be found in liquid and gaseous form.
First discovered in 1786 by Scheele, who extracted
it from the dye Prussian blue – and promptly died
from exposure to the vapours.
Average lethal dose of prussic acid (hydrogen
cyanide, HCN) taken by mouth between 60 and 90
mg (adult)
This corresponds to about 1 teaspoonful of a 2%
solution of hydrocyanic acid and to about 200 mg of
potassium cyanide
 Physical and Chemical Properties..
• HCN and CO – “The Toxic Twins”
• 24 times more toxic than Carbon Monoxide
• Magnifies the toxicity of HCN when combined with CO (“Toxic
Twins”)
• Hydrogen cyanide (AC) is a pale blue or colorless liquid below 78° F
and a colorless gas at higher temperatures. It has a bitter almond
odor and is highly volatile and flammable at room temperature.
• Sodium cyanide and potassium cyanide are white powders which
may have a bitter almond-like odor. In the presence of moisture,
either can form hydrogen cyanide.
• Cyanogen compounds can generate cyanides. Cyanogen chloride
(CK) is a colorless liquefied gas that is heavier than air and has a
pungent, highly irritating odor. It is soluble in water and organic
solvents.
Physical and Chemical Properties..
• In liquid form, hydrogen cyanide (HCN) is also
known as "prussic acid."
• Pure hydrogen cyanide is a gas usually made by
mixing an acid with cyanide salts.
• It is more commonly found in the form of sodium,
potassium, or calcium salts, which are crystalline
materials.
• Industrial cyanide can take the form of large
nuggets called "cyanide eggs."
• Color: Sodium and potassium salts of HCN are
white.
 Cyanide:
• Cyanide contains a carbon atom connected to a
nitrogen atom, hence the chemical formula CN.
• Cyanides can be manufactured but they also occur in
nature.
• In the natural environment, cyanide containing
chemicals are produced by a wide range of organisms
and plants as part of their normal metabolism. Bacteria
and fungi are known producers of cyanide.
• A few species of centipedes, millipedes, insects,
beetles, mothsand butterflies secrete cyanide for
defensive purposes in repelling predators such as toads
and birds.
 What is hydrogen cyanide?
• At room temperature, hydrogen cyanide is a
volatile, colorless -to-blue liquid (also called
hydrocyanicacid). It rapidly becomes a gas that
can produce death in minutes if breathed.
Hydrogen cyanide is used in making fibers,
plastics, dyes, pesticides, and other chemicals,
and as a fumigant to kill rats. It is also used in
electroplating metals and in developing
photographic film
 What is Cyanide Poisoning?
• A condition that results from exposure to cyanide.
• Fatal dose:
For humans can be as low as 1.5 mg/kg body weight.
LETHAL DOSES
60- 90 mg Hydrogen Cyanide (HCN)
200 mg Potassium Cyanide (KCN)
• Half life:
10–30 minutes
• Thiocyanate has a long half life of >24hrs, and is
typically eliminated through the kidneys.
 SOURCES
Include:
1. Smoke inhalation (fires burning plastics, wools, silk and other natural and
synthetic polymers)
2. Cyanogenic glycosides such as amygdalin (e.g. almonds, apricot kernels and
other Prunus species such as peach, apple, cherry and plum)
3. Sodium nitroprusside
4. Industrial exposure (e.g. cyanide salts used in metal extraction and refining,
electroplating, photography and fumigation)
5. acetonitrile (industrial solvent used as cosmetic remover and in
laboratories)
6. Chemical warfare and acts of terrorism (e.g. deliberate contamination of
medications and food)
7. Poison for feral animal control (e.g. rodenticide)
8. Alternative medicines (e.g. derived from apricot kernels)
9. Fumigant in airplanes, buildings, ships
Carbon Dioxide
 Mechanism of toxicity
• Cyanide ions bind to the iron atom of the enzyme
cytochrome c oxidase (also known as aa3) in the fourth
complex in the mitochondrial membrane in the
mitochondria of cells. This deactivates the enzyme, and
the final transport of electrons from cytochrome c
oxidase to oxygen cannot be completed. As a result,
the electron transport chain is disrupted, meaning that
the cell can no longer aerobically produce ATP for
energy.
(Inhibits cellular respiration Cytochrome a-a3
Tissues cannot utilize oxygen,“Arterialization of venous
blood”)
 Mechanism of toxicity
• Tissues that mainly depend on aerobic
respiration, such as the central nervous system
and the heart, are particularly affected.
• binds to sulfhydryl groups and sulphur , disrupts
sulfhydryl or sulphur-containing enzymes.
• Stimulates biogenic amine release causing
pulmonary and coronary vasoconstriction, which
results in pulmonary edema and heart failure.
• 3. Stimulates neurotransmitter release, such as N-
methyl-D-aspartate (NMDA), causing
neurotoxicity and seizures.
 TOXICODYNAMICS
• primary mechanism of cyanide excretion is formation
of thiocyanate within the liver.
• catalyzes the conversion of cyanide to thiocyanate, and
thiocyanate is then excreted via the kidneys
• Endogenous thiosulfate catalyzed by Rhodanese and
Thiocyanate forms.
• Cyanide is quickly metabolized to 2-amino-2-thiazoline-
4-carboxylic acid and thiocyanate with a half life of 10–
30 minutes as a detoxifying mechanism.
• Within a few hours of single ingestion, no cyanide can
be detected, since all of it is metabolized unless death
occurs first.
 Cyanide precursors
Cyanide precursors
• Acetonitrile is slowly metabolised by the liver and
may lead to cyanide toxicity over 24 hours.
• Amygdalin is hydrolysed by two enzymes
(amygdalin hydrolase and prunasin hydrolase)
most effectively in crushed, moistened kernels,
resulting in the formation of HCN and glucose.
• Sodium nitroprusside, metabolised to cyanide
and may accumulate with prolonged high dose
infusions.
 TOXICOKINETICS
• Absorption
Cyanide is rapidly absorbed and taken up into cells. Liquid forms of cyanide can be absorbed through the skin.

Rapid absorption
1. Respiratory tract
2. Mucous membranes

Slow absorption
1. Skin
2. GI tract

Metabolism
Cyanide is metabolised via the liver enzyme rhodanese (named before international enzyme nomenclature was
standardised, hence -ese not -ase!).
Rhodanese catalyses the reaction of CN + thiosulfate to form thiocyanate and sulphite.
Thiocyanate is non-toxic (unless it accumulates with high levels) and is excreted in the urine.
• Elimination
The elimination half-life of cyanide is 2-3 hours
• DISTRIBUTION:
Cyanide distributes rapidly and uniformly throughout the
body following absorption. HCN enters the systemic
circulation when inhaled or dermally absorbed.
For example, cyanide was found in the lung, heart, blood,
kidneys, and brain of humans who died following cyanide
inhalation.
Immediately following oral cyanide exposure, the
stomach contents appear to contain the highest
concentration of cyanide.Other tissues containing cyanide
included the liver, brain, spleen, blood, kidneys, and lungs
 CLINICAL FEATURES

• Acute inhalation or ingestion

Rapid loss of consciousness and seizures with inhalation
Onset of symptoms over ~30 minutes with ingestion (depending on
the dose)
• Milder exposures result in non-specific features including:
Nausea, vomiting, headache, dyspnoea, increased respiratory rate,
hypertension, tachycardia, altered level of consciousness and seizures
• Severe exposures:
Progressive features will result from end-organ damage secondary to
anaerobic respiration and histotoxic hypoxia,hypotension, bradycardia,
reduced GCS and respiratory depression, cardiovascular
collapse,hyperlactaemia may appear ‘pink’ due to high SvO2 following
oxygen administration.
 Signs and symptoms
• Acute exposure
If cyanide is inhaled,it can cause a coma with
seizures, apnea, and cardiac arrest, with death
following in a matter of seconds.
At lower doses, loss of consciousness may be
preceded by general weakness, giddiness,
headaches, vertigo, confusion, and perceived
difficulty in breathing.
A cherry red skin color that changes to dark may be
present as the result of increased venous
hemoglobin oxygen saturation.
 Signs and symptoms
• Chronic exposure
Exposure to lower levels of cyanide over a long
period (e.g., after use of improperly processed
cassava roots as a primary food source in tropical
Africa) results in increased blood cyanide levels,
which can result in weakness and a variety of
symptoms, including permanent paralysis, nervous
lesions,hypothyroidism and miscarriages.
Other effects include mild liver and kidney damage.
 Signs and symptoms
Mild Toxicity
• Nausea
• Dizziness
• Drowsiness
Moderate Toxicity
• Loss of consciousness for a short period
• Convulsion
• Vomiting
• Cyanosis
Severe Toxicity
• Deep coma
• Dilated non-reactive pupils
• Deteriorating cardio-respiratory function
 Clinical Effects of Cyanide
CNS
• Headache
• Dizziness
• Seizures
• Coma

Cardiovascular
• Hypertension, bradycardia
• Hypotension, later in course
• Cardiovascular collapse
 Clinical Effects of Cyanide
Pulmonary
• Dyspnea
• Tachypnea
• Pulmonary edema
• Apnea

Gastrointestinal
• Nausea, vomiting
• Caustic effects
 Detection.
• Old methods of detection involve colorimetric assays such as the
Prussian Blue test, the pyridine-barbiturate assay, also known as the
"Conway diffusion method"and the taurine fluorescence-HPLC but
like all colorimetric assays these can be prone to false positives.
• Lipid peroxidation, an artifact of heart attack produces dialdehydes
that cross-react with the pyridine-barbiturate assay.
• Meanwhile, the taurine-fluorescence-HPLC assay used for cyanide
detection is identical to the assay used to detect glutathione in
spinal fluid.
• Recently, cyanide and thiocyanate assays have been run with mass
spectrometry (LC/MS/MS), which are considered specific tests.
• Since cyanide has such a short half-life, the main metabolite,
thiocyanate is typically measured to determine exposure.
 INVESTIGATIONS
Electrolytes
-Elevated anion gap (lactic acidosis)
ABG
-Metabolic acidosis (lactic acidosis)
Normal PO2
SaO2-Normal

COHb (suspect coexistent carbon monoxide poisoning if

smoke inhalation)
• Cyanide is concentrated 10 fold by RBCs, therefore whole
blood levels give the best information on the potential for a
toxic level.
 INVESTIGATIONS
• Cyanide levels
• Not rapid enough for clinical utility
• Serum cyanide level
Toxic = >0.5mg/L
Fatal = >3.0 mg/L
• Erythrocyte cyanide level
Normal = <1.9 uM/L (50ug/L)
Fatal = > 40 uM/L (1mg/L)
 INVESTIGATIONS
• Serum lactate – elevated
ECG
• Sinus bradycardia
• Sinus tachycardia
Blood levels of cyanide can be measured but take time.
1. Levels of 0.5–1 mg/L are mild.
2. Level of 1–2 mg/L are moderate.
3. Level of 2–3 mg/L are severe.
4. Level greater than 3 mg/L generally result in death.
Toxic Levels:
Blood Urine
12.4 mg/L 0.1 mg/L
 MANAGEMENT
• If the patient is unconscious:
Commence forced artificial ventilation with 100%
oxygen using a mask and bag with a “non-return”
valve (to prevent inspiration of inhaled gases)
Amyl nitrite may be administered via the ambu bag
0.2 - 0.4 mL for adults and 0.1 mL for children
• NOTE:
Amyl nitrite forms a flammable mixture when
combined with oxygen. It must therefore not be
used in situations where it may be ignited.
 MANAGEMENT
1. Removal from the source
2. Personal protection
3. Cyanide is a potential danger to healthcare workers through the dermal
route and through inhalation
4. Patient vomitus can liberate hydrogen cyanide gas
5. Avoid mouth-to-mouth/nose ventilation
6. Resuscitation
7. Attend to ABCs and administer high flow oxygen
8. provide haemodynamic support
9. inotropes/ vasopressors
10. consider extracorporeal support
11. Give antidote if suspected toxicity
ohydroxocobalamin then sodium thiosulfate is generally preferred if available.
 MANAGEMENT
12. Supportive care and monitoring.
13. Seek and treat underlying causes and complications.
14. Decontamination.
15. Remove any contaminated clothing and bag these.
16. Wash contaminated skin with soap and water.
17. Avoid activated charcoal unless intubated.
18. Enhance elimination.
19. Antidotes.
20. Disposition.
21. Asymptomatic patients with normal blood gases can be discharged
at 6 hours.
22. Critically ill patients will require ICU admission.
23. Consult a clinical toxicologist early.
 ANTIDOTES
“Hydroxocobalamin” is an antidote that seems to have many of the
characteristics of the ideal cyanide antidote: ( rapid onset of action,
neutralizes cyanide without interfering with cellular oxygen use, tolerability
and safety profiles conducive to prehospital use, safe for use with smoke-
inhalation victims, not harmful when administered to non-poisoned patients,
easy to administer.)
• The main cyanide antidotes that may be given are:
Cobalt-containing cyanide binders.
Dicobalt edetate and hydroxocobalamin (the latter forms cyanocobalamine).
Sulfur donors.
(such as sodium thiosulfate, which acts as a sulfur donor to the endogenous
rhodanese enzyme that detoxifies cyanide by converting it to thiocyanate.)
Methemoglobin generators
Oxidants such as amyl nitrite (inhaled), sodium nitrite (IV) and dimethyl
aminophenol (IV/IM) convert hemoglobin (Fe2+) to methemoglobin (Fe3+)
which binds cyanide forming cyanhemoglobin.
 ANTIDOTES
• Dicobalt edetate:
Dicobalt edetate is administered 300 mg IV (7.5
mg/kg in children) over 1 minute followed by 50 mL
of 50% glucose.
This is repeated up to 3 times if an immediate
clinical response is not seen.
This cobalt salt is toxic — it causes seizures, chest
pain and dyspnoea, head and neck swelling,
hypotension, urticaria and vomiting.
Due to this toxicity it should only be given if severe
cyanide poisoning is strongly suspected.
 ANTIDOTES
• Hydroxocobalamin and thiosulfate:
If available, hydroxocobalamin together with thiosulfate
(but do not mix them in the same infusion as they will
form a complex!) may be a better option as they are
much less toxic than dicobalt edetate.
Administer 5g hydroxocobalamin diluted in 200 mL of 5%
dextrose IV over 30 minutes (binds 100mg cyanide — use
a larger inital dose if necessary)
Then administer 12.5g sodium thiosulfate (50 mL of 25%
solution) IV over 10 minutes.
Repeat both doses if there is no improvement within 15
minutes.
 ANTIDOTES
• Adverse effects of these agents are:
Hydroxocobalamin — occasional hypertension,
bradycardia or tachycardia (not requiring
treatment),orange-red skin and body fluid
discolouration.(benign, lasts up to 48 hours)
Sodium thiosulfate — nausea and vomiting with rapid
injection; minor nonspecific effects such as hypotension,
headache, abdominal pain and confusion.
Methemoglobin generators
Effectively contra-indicated in the setting of smoke
inhalation and possible carbon monoxide poisoning as
they are likely to aggravate tissue hypoxia.
 ANTIDOTES
• Consider just giving sodium thiosulfate together
with oxygen and meticulous supportive care in
doubtful cases of mild-to-moderate severity
cyanide toxicity – onset of action may be too slow
if used alone for severe cyanide toxicity.
• As cyanide is generally rapidly lethal, paramedics
should be trained in the pre-hospital
administration of cyanide antidotes in regions or
situations where poisoning can be anticipated.
aNtidotes should be stored in high areas (e.g. at
relevant industrial sites)
 Cyanide Antidote Kit
Contents
Amyl nitrite 0.3 ml x 12
Inhaled while IV access established
Not necessary if immediate IV access
Can be given in pre-hospital setting
Sodium nitrite 300mg/10cc x 2
Sodium thiosulfate 12.5g/50cc x2
syringes, needles, tourniquet, stomach tube,
instructions
 ANTIDOTES
Cyanide ion binding
 What is methemoglobinemia?
• Oxidation of iron within heme from Fe2+ to Fe
3+.
• Methemoglobinemia is due to an imbalance
of MHb production and MHb reduction.
 History
• Burnings
On December 5, 2009, a fire in the night club Lame
Horse (Khromaya Loshad) in the Russian city of
Perm took the lives of 156 people.
111 people died on the spot and 45 later in
hospitals. One of the main causes of death was
poisoning from cyanide and other toxic gases
released by the burning of plastic and polystyrene
foam used in the construction of club interiors.
 History
• On January 27, 2013, a fire at the Kiss
nightclub in the city of Santa Maria, in the
south of Brazil, caused the poisoning of
hundreds of young people by cyanide released
by the combustion of soundproofing foam
made with polyurethane. By March 2013, 241
fatalities were confirmed.
 History
• Hydrogen cyanide in the form of Zyklon B was used in
German extermination camps during World War II, and
especially from March 1942 onwards, when it was first
used experimentally to murder Russian prisoners of
war at Auschwitz.
• Hydrogen cyanide gas has also been used for judicial
execution in some states of the United States, where
cyanide was generated by reaction between potassium
cyanide (or sodium cyanide[38][39]) dropped into a
compartment containing sulfuric acid, directly below
the chair in the gas chamber.
 History
• War
Cyanide was stockpiled in chemical weapons
arsenals in both the Soviet Union and the United
States in the 1950s and 1960s.
Suicide
Cyanide salts are sometimes used as fast-acting
suicide devices. Cyanide reacts at a higher level
with high stomach acidity.
 History
• In the 1943 Operation Gunnerside to destroy the
Vemork Heavy Water Plant in World War II (an attempt
to stop or slow German atomic bomb progress), the
commandos were given cyanide tablets (cyanide
enclosed in rubber) kept in the mouth and were
instructed to bite into them in case of German capture.
• Members of the Sri Lankan LTTE (Liberation Tigers of
Tamil Eelam, whose insurgency lasted from 1983 to
2009), used to wear cyanide vials around their necks
with the intention of committing suicide if captured by
the government forces.
 History
• Mining and industrial
In 2000, a spill at Baia Mare, Romania resulted in
the worst environmental disaster in Europe since
Chernobyl.
In 2000, Allen Elias,CEO of Evergreen Resources was
convicted of knowing endangerment for his role in
the cyanide poisoning of employee Scott
Dominguez.
This was one of the first successful criminal
prosecutions of a corporate executive by the
Environmental Protection Agency.
 Cyanide pollution
1997 - 4,513,410 cyanide released by top 100
polluters in USA
Bhopal, 1984
worst industrial poisoning in history
25,000 kg methyl isocyanate and combustion
products released into atmosphere
1,800 - 5,000 deaths
200,000 injuries
 Cyanide pollution
Man carries his wife past the Union Carbide factory in Bhopal,
India. Fumes from the factory killed her the previous day
 Cyanide pollution

Skulls from victims of the Union Carbide disaster in

the Hamidia Hospital in Bhopal, India.
 Cyanide and terrorism
• 1984 - 7 Chicago area residents killed after
ingesting cyanide-laced Tylenol
• Cyanide gas precursors (cyanide salt + acid)
found in Tokyo subway bathrooms following
sarin gas attacks
• Cyanide believed to be involved in World
Trade Center bombing (incinerated in attack)
• I SELECTED CYANIDE HOMICIDE CASES
Theodosius Boughton (1781) Dr. Collidge
(1847) Mrs. MacFarland (1911) Twigg/Elosser
(1911) Jessie Costello (1933) Ronald O'Bryan
(1974) People's Temple/Rev. Jim Jones (1978)
Tylenol tampering (Chicago) (1982) Donald
Harvey (1987) Stella Nickel (1988)