Cellular Toxic Agents
Hydrogen cyanide is one of several agents known formally as blood
agents, although the term is a misnomer because the agent acts at the
mitochondrial level in the cell.[68]
Hydrogen cyanide
is a highly volatile liquid used widely in industry and therefore potentially available
to terrorists. It has been used since World War I as a chemical warfare agent.
Its very short persistence means that decontamination is usually not required after
release. It is not absorbed by the activated charcoal of level C respirators (see
"Anesthesiologists in the Management of Casualties from Chemical and Biological Warfare
Agents") but is removed by impregnating the charcoal with silver salts, with which
hydrogen cyanide reacts. Hydrogen cyanide in high concentrations is rapidly fatal.
The LCt50
has been estimated at 200 mg/m3
for 10 minutes.
Hydrogen cyanide acts by binding to the iron atom in cytochrome oxidase enzymes,
inhibiting the catalytic function that allows oxygen to act as an electron receptor
and produce ATP. This means that hypoxia occurs at the tissue level, which cannot
theoretically be reversed by restoring oxygenation of the blood by resuscitation
measures. Hydrogen cyanide is unique as a chemical warfare agent in this respect.
Signs and Symptoms
The first sign of exposure in humans is hyperventilation, which
has the effect of increasing the absorbed dose. This is followed by dizziness, rapid
loss of consciousness, and convulsions, which are followed by respiratory arrest.
At levels that are not fatal, patients report a smell of almonds and a feeling of
apprehension. There is a metallic taste in the mouth, and victims may have dyspnea.
Because of the rapid action of hydrogen cyanide, patients suffering from acute intoxication
are unlikely to be encountered in hospital. Antidote therapy plays a key role and,
if successful, is curative. Long-term management of the consequences of hydrogen
cyanide poisoning is unlikely, although survivors of near-fatal doses can suffer
long-term effects such as intellectual deterioration, mental confusion, and parkinsonism.
Treatment
In the body, hydrogen cyanide is broken down by rhodanase, which
detoxifies cyanide to thiocyanate.[69]
[70]
This process can be accelerated by provision of sodium thiosulfate, which provides
a store of sulfane sulfur for the enzyme.[71]
The
usual dose of sodium thiosulfate is 50 mL of a 25% solution (pediatric dose is 1.65
mL/kg of a 50% solution). It is usually administered in conjunction with sodium
nitrite (300 mg given intravenously over 10 minutes; pediatric dose is 0.15 to 0.33
mL/kg of a 3% solution), which causes the formation of methemoglobin. This acts
as a scavenger for hydrogen cyanide and reduces its plasma levels. Sympathomimetic
support may be required for hypotension produced by sodium nitrite. Hydrogen cyanide
also reacts with heavy metals, and this is the basis of the use of dicobalt edetate
and hydroxycobalamin as cobalt providers for this reaction. Cobalt ions themselves
are toxic, but the toxicity can be countered by giving glucose, which is part of
standard therapy. Dicobalt edetate is thought to be more effective in the binding
of cyanide ions than methemoglobin despite its secondary effects of hypertension
and nausea. It has long been believed that oxygen therapy and ventilation have no
role in the treatment of cyanide intoxication because the blood is fully oxygenated
in this condition. However, this view has been challenged because some studies have
shown that oxygen enhances the antidotal effects of the classic cyanide antidotes.
[72]
Table
64-10
details antidote treatment approaches.
 |
