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0.2.1 SUMMARY OF EXPOSURE
A) SOURCES: Genera that contain cyanogenic compounds
include: Eriobotrya (toxic part: pit kernel), Hydrangea
(toxic part: flower bud), Malus (toxic part: seeds),
Prunus (toxic part: pit kernel) and Sambucus (toxic
part: whole plant in particular the root; the fruit is
harmless with cooking). Common cyanogenic plant species
include: bitter almond, apricot, peach, apple, black or
wild cherry, choke berry, elderberry, hydrangea, jetbead
or jetberry bush, and Puerto Rican lima bean. The
cyanide content of cyanogenic plant species may vary
significantly.
B) PHARMACOLOGY: Rapid cellular energy fails because
cyanide can inhibit the final step of the mitochondrial
electron transport chain. Cyanogenic compounds must be
metabolized to release cyanide.
C) TOXICOLOGY: Amygdalin is the cyanogenic diglucoside
D-mandelonitrile- beta-D-gentiobioside and is not toxic
until it is metabolized by the enzyme emulsin which is
present in the seeds of these plants. Inadvertent
ingestion of whole seeds or pits is unlikely to result
in acute cyanide toxicity. Toxicity occurs after
enzymatic hydrolysis in the GI tract. Onset of symptoms
is often delayed up to 2 hours or more after ingesting
masticated pits that contain amygdalin. The most common
plants to produce human cyanide toxicity in the US are
the seeds of the Rosacea family, including apricots
(Prunus armeniaca) bitter almond (Prunus amygdalus),
peach (Prunus persica), pear (Pyrus communis), apple
(Malus sylvestris) and plum (Prunus domestica).
D) EPIDEMIOLOGY: Acute cyanide ingestion due to inadvertent
ingestion of these plants is very rare. Acute cyanide
toxicity occasionally results from ingestion of
significant amounts of masticated pits of fruits and
chronic consumption of "nontraditional" preparation of
cyanogenic plants which may result in spastic paresis
and tropical ataxic neuropathy. Most cases are due to
use of these plants as food in less developed countries.
E) WITH POISONING/EXPOSURE
1) MILD TO MODERATE TOXICITY: Signs and symptoms
association with ingestion of significant amount of
masticated pits containing amygdalin include dyspnea,
cyanosis, weakness, and lightheadedness.
2) SEVERE TOXICITY: Coma, seizures, stupor, dysrhythmias,
cardiovascular collapse, and metabolic acidosis.
3) CHRONIC TOXICITY: Chronic consumption of cyanogenic
glycoside containing plants as a food staple may result
in chronic polyneuropathies which includes spastic
paresis and tropical ataxic neuropathy. Spastic paresis
is characterized by bilateral and symmetrical
involvement of the pyramidal tracts affecting the lower
extremities resulting in spastic gait, paraplegia,
extensor plantar responses, spastic bladder,
constipation and impotence, with visual involvement
rarely reported. Chronic poisoning should be considered
when nonspecific or neurologic symptomatology is
associated with a large or chronic ingestion of
cyanogenic plants.
0.2.3 VITAL SIGNS
A) WITH POISONING/EXPOSURE
1) TACHYPNEA - Initial tachypnea is replaced by
respiratory depression and cyanosis in severe
poisonings.
2) KUSSMAUL'S RESPIRATION - Rapid deep respirations may be
evidence of acidosis.
3) RESPIRATORY ARREST may occur initially or be delayed.
4) HYPOTHERMIA - A 41-year-old woman presented with mild
hypothermia (rectal temperature 33.6 C) after ingesting
30 apricot kernels.
5) HYPOTENSION and shock may be present.
0.2.5 CARDIOVASCULAR
A) Initial hypertension followed by hypotension and
cardiovascular collapse may occur.
0.2.6 RESPIRATORY
A) Initial tachypnea and dyspnea followed by depressed,
labored respirations may occur which may progress to
respiratory arrest. Kussmaul's respiration may be
evident.
0.2.7 NEUROLOGIC
A) Headaches, dizziness, lightheadedness, disorientation,
irritability, unresponsiveness, lethargy, stupor,
weakness, paralysis, areflexia, syncope coma, and
seizures may follow gastrointestinal symptoms.
B) Chronic consumption of plants containing high
concentrations of cyanogenic glycosides has been
associated with polyneuropathy which include optic
atrophy, nerve deafness, spastic paraparesis, ataxia,
clonus and peripheral neuropathy.
0.2.8 GASTROINTESTINAL
A) Nausea, vomiting, diarrhea, and epigastric pain may be
the first symptoms. Pancreatitis and endemic goiter have
been reported in patients from cassava-consuming areas.
0.2.11 ACID-BASE
A) Metabolic acidosis and lactic acidosis may be present.
0.2.14 DERMATOLOGIC
A) WITH POISONING/EXPOSURE
1) Face petechiae has been reported following Cycas seed
poisoning.
0.2.20 REPRODUCTIVE
A) The use of cassava or Laetrile(R) in animal studies
produced limb defects, open eye defects, microcephaly,
fetal growth retardation in fetuses. Sodium thiosulfate
administration protected the fetus from teratogenic
effects. |
0.4.2 ORAL/PARENTERAL EXPOSURE
A) MANAGEMENT OF MILD TO MODERATE TOXICITY
1) In symptomatic patients, advance life support including
the use of a cyanide antidote should be initiated as
gastrointestinal decontamination is being prepared.
Supplemental oxygen should be administered immediately
with continuous monitoring of vital signs. Establish IV
access immediately. An antidote kit should available at
the bedside. Worsening or severe acidosis, hypotension,
seizures, dysrhythmias and coma indicate a more severe
poisoning.
B) MANAGEMENT OF SEVERE TOXICITY
1) Elevated lactate, increased anion gap metabolic
acidosis, and an elevated venous oxygen saturation all
suggest a significant cyanide exposure. Manage airway
early. Patients who are comatose or severely ill due to
suspected cyanide toxicity should be administered a
cyanide antidote kit. In addition, standard ACLS or
PALS therapy should be provided to manage symptoms.
Administer sodium bicarbonate for severe acidemia.
C) DECONTAMINATION
1) PREHOSPITAL: Prehospital activated charcoal can be
considered for large ingestions in which there will be
a delay in definitive healthcare; however, a poison
center should initially be consulted. Avoid inducing
vomiting.
2) HOSPITAL: Activated charcoal binds poorly to cyanide
salts; however, the lethal dose is so small that the
use of activated charcoal should be considered in a
symptomatic patient. Symptoms are often delayed up to 2
hours or more after ingestion of the masticated pits
containing amygdalin.
D) AIRWAY MANAGEMENT
1) Patients who are comatose or with altered mental status
need early endotracheal intubation and mechanical
ventilation.
E) CYANIDE ANTIDOTE
1) A cyanide antidote, either hydroxocobalamin OR the
sodium nitrite/sodium thiosulfate kit, should be
administered to symptomatic patients (metabolic
acidosis, depressed mental status, hypotension,
dysrhythmias, seizures).
2) HYDROXOCOBALAMIN
a) ADULT: Administer 5 g IV over 15 minutes. A second
dose may be given (infused over 15 to 120 minutes) in
patients with severe toxicity. PEDIATRIC: A dose of 70
mg/kg has been used. Hydroxocobalamin forms
cyanocobalamin which is a nontoxic, water soluble
metabolite that is eliminated in the urine. It is
generally safer and easier to use than other antidotes
(i.e., cyanide antidote (sodium nitrite and sodium
thiosulfate). Sodium thiosulfate may also be
administered with hydroxocobalamin, but it is not part
of the kit. ADVERSE EFFECTS: Flushing is common.
Hydroxocobalamin is bright red and causes
discoloration of the skin, urine, and serum. It can
also interfere with many colorimetric based tests.
3) CYANIDE ANTIDOTE KIT
a) An alternative, a sodium nitrite/sodium thiosulfate
kit, is administered as follows: SODIUM NITRITE:
ADULT: Administer 300 mg (10 mL of 3% solution) IV at
a rate of 2.5 to 5 mL/min; PEDIATRIC (with normal
hemoglobin concentration): 0.2 mL/kg of a 3% solution
(6 mg/kg) IV at a rate of 2.5 to 5 mL/min, not to
exceed 10 mL (300 mg). The dose may be lowered if the
patient is severely anemic, but administration should
not be delayed for laboratory results. Nitrites may
also cause vasodilatory effects which may contribute
to hypotension. A second dose, one-half of the first
dose, may be administered 30 minutes later if there is
inadequate clinical response. Use with caution if
carbon monoxide poisoning is also suspected. SODIUM
THIOSULFATE: Follow sodium nitrite with IV sodium
thiosulfate. ADULT: Administer 50 mL (12.5 g) of a 25%
solution IV; PEDIATRIC: 1 mL/kg of a 25% solution (250
mg/kg), not to exceed 50 mL (12.5 g) total dose. A
second dose, one-half of the first dose, may be
administered if signs of cyanide toxicity reappear.
This agent enhances conversion of cyanide to
thiocyanate which is eliminated in the urine. Patients
with renal failure may need dialysis to eliminate
thiocyanate. ALTERNATE ANTIDOTES: Kelocyanor(R)
(dicobalt-EDTA) and 4-DMAP (4-dimethylaminophenol) are
among the cyanide antidotes in clinical use outside
the US.
F) METHEMOGLOBINEMIA
1) Blood methemoglobin levels should be monitored for 30
to 60 minutes following the infusion of sodium nitrite
to prevent severe toxicity. Treat with methylene blue
if patient is symptomatic (usually at methemoglobin
concentrations greater than 20% to 30% or at lower
concentrations in patients with anemia, underlying
pulmonary or cardiovascular disease). METHYLENE BLUE:
INITIAL DOSE/ADULT OR CHILD: 1 mg/kg IV over 5 to 30
minutes; a repeat dose of up to 1 mg/kg may be given 1
hour after the first dose if methemoglobin levels
remain greater than 30% or if signs and symptoms
persist. NOTE: Methylene blue is available as follows:
50 mg/10 mL (5 mg/mL or 0.5% solution) single-dose
ampules and 10 mg/1 mL (1% solution) vials. Additional
doses may sometimes be required. Improvement is usually
noted shortly after administration if diagnosis is
correct. Consider other diagnoses or treatment options
if no improvement has been observed after several
doses. If intravenous access cannot be established,
methylene blue may also be given by intraosseous
infusion. Methylene blue should not be given by
subcutaneous or intrathecal injection. NEONATES: DOSE:
0.3 to 1 mg/kg.
G) ENHANCED ELIMINATION
1) Antidotes increase elimination, however, the role of
hemodialysis is uncertain.
H) PATIENT DISPOSITION
1) HOME CRITERIA: Home management is not indicated in
patients with acute cyanide toxicity following exposure
to a cyanogenic glycoside. Toxicity can vary widely
depending on the plant and stage of development.
Asymptomatic children with exploratory or "taste"
ingestions of cyanogenic plants can generally be
managed at home with telephone follow up.
2) OBSERVATION CRITERIA: Symptomatic patients should be
referred to a healthcare facility. If laboratory
evaluations are normal and the patient remains
asymptomatic for at least 8 hours, they may be
discharged from the hospital with appropriate follow-up
instructions.
3) ADMISSION CRITERIA: Any patient with symptomatic
poisoning should be admitted to an intensive care unit.
4) CONSULT CRITERIA: Consult a poison center or medical
toxicologist for assistance in managing symptomatic
patients.
I) PITFALLS
1) Treatment should not be delayed for laboratory results
if a cyanide exposure is strongly suspected.
J) PHARMACOKINETICS
1) Cyanogenic glycosides release hydrogen cyanide after
complete hydrolysis. Amygdalin is a cyanogenic
diglucoside D-mandelonitrile-beta-D- gentiobioside,
which is not toxic until it is metabolized by the
enzyme emulsin which is present in the seeds of the
plants. The presence of amygdalin in the seed kernels
of a plant is usually not considered dangerous.
However, the crushed (masticated) moistened seed
release emulsin, an enzyme that catalyzes the
hydrolysis of amygdalin to glucose, benzaldehyde, and
cyanide.
K) TOXICOKINETICS
1) Toxicity is highly variable and dependent on multiple
factors including the amount of glycosides present in a
plant, which can vary with species, the stage of plant
development and plant part. Cassava species (including
linamarin and Prunus species) contain amygdalin which
are of most concern to humans. Cyanogenic glycosides
need to be hydrolyzed in the gastrointestinal tract
before the release of cyanide; therefore, the onset of
symptoms are often delayed up to 2 hours after
ingestion of masticated pits containing amygdalin.
Chronic consumption of cyanogenic glycoside containing
plants as food staple may result in chronic
polyneuropathies which includes spastic paresis and
tropical ataxic neuropathy.
L) DIFFERENTIAL DIAGNOSIS
1) Ingestion of plants that may produce similar symptoms.
Other agents that may produce metabolic acidosis. |
A) Inadvertent ingestion of whole seeds or pits is unlikely
to result in acute cyanide toxicity.
B) TOXICITY: For 100 grams of moistened seed; the peach pit
contains approximately 88 mg of hydrocyanic acid,
cultivated apricot pit 8.9 mg, wild apricot pit 217 mg.
The ingestion of 500 mg of amygdalin may release as much
as 30 mg of cyanide. The amount of hydrogen cyanide (HCN)
potentially released from bitter almond seeds, apricot
seeds, peach seeds, and apple seeds are 0.9 to 4.9 mg
HCN/g, 0.1 to 4.1 mg HCN/g, 0.4 to 2.6 mg HCN/g, and 0.6
mg HCN/g, respectively. CYANIDE: Lethal dose has been
estimated to be 50 to 300 mg for an adult, depending on
the specific agent, but not well defined. The fatal dose
of cyanide salts is estimated at 200 to 300 mg for an
adult, and 50 to 100 mg of hydrocyanic acid. |