MEMC V:

Cyanide Toxicity from Common

Housefires

Joseph Rella, MD
Assistant Professor, Emergency
Medicine
New Jersey Medical School
2009

Chemistry of CN

Various salts

Various routes of access

pKa ~ 9.2
Na-, K-, CaOften a massive poisoning
Ingestion, inhalation, transdermal

Cellular inhibition

CN readily complexes with metals

Cytochrome oxidase complex (4) (myoglobin, nitrate
reductase)

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Oxidative Phosphorylation

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pH and

Intermembrane
space

4 H+

4 H+

2 H+
cyto C

I
e-

eII

eIII

eIV

O2 + 2 H+

H2O

Succinate

NADH
NAD + H+

Fumarate

ADP + Pi

ATP synthase

ATP

Matrix

H+

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pH and

Intermembrane
space

cyto C

I
e-

NADH
+
Pyruvate

eII

CN

III

O2 + 2 H+

Succinate

ADP + Pi

ATP synthase

Lactate

Matrix (pyruvate dehydrogenase and Krebs cycle stop as well!)

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H+

Inhibitors of the System

Electron transport inhibitors

Uncouplers

CN (azide, CO) binds to Cu ligands in complex IV

Some dissipate

Energy transfer inhibitors

Inhibitory uncouplers

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Physical effects of CN

A potent neurotoxin

White matter is the more sensitive tissue

Histotoxic anoxia
Sudden loss of electrical activity in brain

Inhibits glutamate decarboxylase!

Severe metabolic acidosis

Clinical effects:

Headache, agitation, confusion, dyspnea,

seizures, cardiovascular collapse - arrest
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Clinical symptoms among 36 cyanide

intoxications
Symptom

% of total

Asymptomatic

22

Cardiovascular collapse

10

28

Coma

13

36

17

18

50

Post-anoxic coma and

death

14

Psychomotor retardation

17

Respiratory arrest

22

Convulsions
Metabolic acidosis

Boron SW, Baud FJ. Acute cyanide poisoning: clinical spectrum, diagnosis, and treatment. Arh hig rada toksikol 1996;47:307

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Sources of CN
Industrial/laboratory reagents

Plastics, electroplating, mining, photography,

precious metal reclamation
Fumigants

And

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Combustion!

Silk, wool, nylon, polyurethane, melamine, polyacetonitrile,

polyamide plastics
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The Part CN Plays in Housefires

Product of combustion
Acts as a knockdown agent

Decreases patients ability to evacuate

Now more vulnerable to flame, CO, smoke,

etc.

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Supporting Data of the Risk

Symington I
Clark CJ
Birky MM
Silverman SH
Baud FJ
Jones J
Kulig K
Chaturvedi AK
Shusterman D
Ferrari L
Alarie Y
Yeoh M
Borron SW

Lancet 1978
Lancet 1981
Bull NY Acad Med 1981
J Trauma 1988
NEJM 1991
Am J Emerg Med 1987
NEJM 1991
J Appl Toxicol 1995
J Toxicol Clin Toxicol 1996
Forensic Sci Int 2001
Crit Rev Toxicol 2002
J Toxicol Clin Toxicol 2004
NEJM 2004

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The Controversy: How good are the

data?

Varied exposures
Complicated sampling, storage, analysis
Animal models of smoke inhalation
Years of relying on CO and MetHb
measurements

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Evaluation of Potentially Exposed

Patients

Clinically: comatose patients are easy to identify

Be suspicious of awake, confused/agitated patients

BP < 100mmHg without trauma

Emergency laboratory testing:

Save blood in a heparinized tube at 4C for later an alysis

Elevated lactate is the best we have for now
Baud FJ, et al. Crit Care Med 2002;30:2044

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Antidotal Therapies

Taylor kit

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Taylor Kit

Amyl nitrite / Sodium nitrite

Cyanomethemoglobin outcompetes CN for Cyto aa3 to

restore function

MetHb lags toxicity resolution

Works despite methylene blue
Possibly due to vasodilation, NO
Some side effects

Sodium thiosulfate

Sulfur supplier for sulfurtransferase transformation and

detoxification
Very safe to give
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Hydroxycobalamin

Actively complexes cyanide

Directly detoxifies

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Hydroxycobalamine

OxyHb

Nitrites

CN
CN
(Fe) Cyto aa3
CN
CN

MetHb

S2O32-

Rhodanese

SCN- + SO32-

Cyanomethemoglobin
Cyanocobalamine

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Summary

CN is a potent, rapid acting toxin

CN is commonly found in victims of
housefires
Be suspicious that seemingly mildly ill
persons may be toxic
Save blood, get lactate
Taylor or Hydroxycobalamine
Good supportive care
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