EM Toxicology 6: Cyanide

Question 1

Cyanide in history

Answer 1

• used by Nazi Germany in the gas chambers during the Holocaust

-World Trace Center bombing in 1993

Question 2

pathophy of cyanide poisoning

Answer 2

binding with very high affinity to the ferric ion cytochroma a3 portion of CYTOCHROME OXIDASE withtin the mitochondria, resulting in an abrupt cessation of electron transport and oxidative phosphorylation, thus INHIBITING AEROBIC METABOLISM

THUS, following an acute exposure, organs and tissues with high O2 consumption are the first and most severely affected

Question 3

cyanide in food

Answer 3

Cassave, a tropical root, contains the cyanogenic glycosides linamarin and lotaustralin that liberate cyanide when metabolized in the body

Chronic exposure to dietary cyanisde is linked to tropical ataxic neuropathy

Question 4

the primary mechanism for detoxification of cyanide is

Answer 4

its metabolism in the liver by RHODANESE to THIOCYANATE, a nontoxic compound that’s renally excreted.

Toxicity occurse when this mechanism is rapidly overwhelmed

Question 5

other sources of cyanide

Answer 5

Burning of wool, nylon, silk, acrylic

fabricatoin of plastics, mining, photography

bamboo shoots, seeds from cherries, peaches

illicit phencylidine manufacturing
cigarette smoke
vehicle exhaust

Question 6

symptoms of cyanide poisoning

Answer 6

restlessness
anxiety
palpitation
dyspnea headache

dyspnea
LOC
seizures
cardiac dysrhythmias

Coma
cardiovascular collapse
detah

Question 7

median lethal dose of hydrogen cyanide for humans

Answer 7

200 parts per milion for a 30-min exposure

600-700 parts per million for a 5-min exposure

Question 8

other clinical features of cynaide poisoning

Answer 8

typical for serious poison:
altered consciouness, hyperventilating, hypotensive, BRADYCARDIC

smell of BITTER ALMONDS and a CHERRY-RED SKIN COLOR (from inc’d venous hgb O2 saturation) - altho unreliable

SEVERE UNEXPLAINED METABOLIC ACIDOSIS is a consistent clinical features ⭐️

Question 9

slow release of cyanide happens from spontaneou degradation of this compound

Answer 9

sodium nitroprusside
spontaneous degradation is increased by exposure to sunlight

Question 10

Main management of cyanide toxicity

Answer 10

1 - 100% oxygen
2 - crystaloid +/- vasopressors

3 - Hydroxocobalamin
-cobalt component binds cyanide, removing it from cytochrome oxidase and forming cyanocobalamin, which is exreted via the kidneys
-5 g IV for 15 mins, 2nd dose of 5g IV may be repeated for a total of 10 g

Cyanide antidote kit
-production of methemoglobin (by nitrites) makes this 2nd line if exposure involves fire smoke or any other potential source of concomitant carbon monoxide poisoning

Question 11

anticipated laboratory findings in cyanide poisoning

Answer 11

HAGMA
Lactate >90mg/dL (>10 mmol/L)
-correlates with toxic cyanide level

normal SpO2
-hgb rtains normal O2-carrying capacity

whole blood cyanide level
Toxic >0.5 mcg/mL
(>12 mmol/L)
Fatal >2.5 mcg/mL
(>60 mmol/L)
note: plasma cyanide levels are roughly 1/10 of the whole blood cyanide levels

Question 12

management of cyanide poisoning (summary)

Answer 12

1 - 100% O2
2 - crystalloids and vasopressors
3 - +/- sodium bicarbonate
4 - antidote:
hydroxocobalamin
or
cyanide antidote kit
-amyl nitrite inhaler
-sodium nititrite 3% solution
-sodium thiosulfate 25% solution

Question 13

indication for hydroxocobalamin

Answer 13

exposure to smoke and/or fire
GCS <10 with signs of end-organ damage (i.e., cardiac arrest, seizures, respiratory distress)
carboxyhemoglobin level >10%
lactate >8 mmol/L

Question 14

remarks on hydroxocobalamin

Answer 14

vitamin B12a
-a metalloprotein with a cobalt center that binds cyanide, removing it from cytochrom oxidase and forming CYANOCOBALAMIN, which is then eliminated via the kidneys

dose:
5 g IV over 15 mins
2nd dose of 5 g IV may be repeated once (total of 10g)

children:
70 mg/kg (max of 5g) IV over 15 mins

Question 15

hydroxocobalamin side effects

Answer 15

transient hypertension
reddish discoloration of skin and mucous membranes
rare anaphylactic reactions

Question 16

content of cyanide antidote kit

Answer 16

ampules of amyl nitrite for inhalation

10-mL vials of 3% sodium nitrite (300 mg)

50-mL vials of 25% sodium thiosulfate (12.5g)

Question 17

remarks on cyanide antidote kit

Answer 17

1 - NITRITES
-forms methemoglobin, which binds cyanide more avidly than the ferric iron of cytochrome oxidase, thus removing cyanide from the cytochrome

amyl nitrite is NOT needed when sodium nitrite can be given IV

2 - SODIUM THIOSULFATE
-given AFTER the administration of sodium nitrite
-enhances the activity of the enz rhodanese, which catalyzes the transfer of sulfate from sodium thiosulfate to cyanide to form thiocyanate —> kidneys

Question 18

adverse effects of nitrite therapy

Answer 18

HYPOTENSION
however, hypotension is NOT a contraindication to nitrate therapy in SEVERE cyanide poisoning

excessive methemoglobinemia
-> further decrease oxygen delivery with concomitant carbon monoxide poisoning

Question 19

remarks on sodium thiosulfate

Answer 19

has very limited toxicity in comparison with nitrites and should be used as a sole therapy for victims of cyanide poisoning from inhalation injury if there’s a concern for concomitant carbon monoxide exposure IF hydroxocobalamin is UNAVAILABLE

considered first line in early pregnancy