Biomedical Engineering Reference
In-Depth Information
in a two-step process. First, a methemoglobin-
forming agent such as amyl (inhalant use) or
sodium nitrite (for IV use) is administered. The
ferric ion Fe
3
+
in methemoglobin has a higher
affinity for cyanide than cytochrome a
3
. The equi-
librium of this reaction causes dissociation of
bound cyanide from cytochrome a3 and frees
the enzyme to produce ATP. The orthostatic
hypotension produced by nitrite administration is
not usually a concern in a severely intoxicated
and prostrate cyanide casualty, but overproduction
of methemoglobin may compromise oxygen-
carrying capacity. Thus, nitrite therapy is rela-
tively contraindicated in smoke-inhalation victims.
The initial adult dose, equivalent to one of the
two sodium nitrite vials in the standard Pasadena
(formerly Lilly) Cyanide Antidote Kit (Table 6.9).
In an average adult one vial will attain a circu-
lating methemoglobin level of about 20%, is 10ml.
Pediatric dosing is dependent on body weight
(Table 6.9).
The second step is provision of a sulfur donor,
typically sodium thiosulfate, which is utilized as a
substrate by the liver enzyme rhodanase for conver-
sion of cyanide to thiocyanate. Sodium thiosul-
fate itself is efficacious, relatively benign, and also
synergistic with oxygen administration and thus
may be used without nitrites in situations such
as smoke inhalation with high carboxyhemoglobin
levels. The initial adult dose, equivalent to one
of the two large bottles in the Pasadena Kit, is
50ml (Table 6.9). The initial thiosulfate dose for
pediatric patients is 1.65ml/kg of the standard 25%
solution, IV (Table 6.9). Second treatments with
each of the two antidotes may be given at up to
half the original dose if needed [15,16].
It is important to realize that, although
the_combination of sodium nitrite and sodium
thiosulfate may save victims exposed to 10-20
lethal doses of cyanide and are effective even
after breathing has stopped, many patients will
recover even without specific antidotal treatment if
vigorous general supportive care is administered.
Lack of availability of antidotes is therefore not
a reason to consider even apneic cyanide casual-
ties expectant. It is also important to realize that
administration of antidotes, if administered to fast
or in extremely large doses, are also associated
with morbidity and even mortality.
Several alternative therapies and experimental
antidotes are used in other countries. Germany uses
dimethylaminophenol (DMAP), a rapid methe-
moglobin former developed for intramuscular (IM)
use. However, muscle necrosis at the site of injec-
tion occurs, and only the IV route of administration
is recommended [17].
Certain cobalt compounds directly combine with
cyanide to reduce its toxicity. Because cobalt
compounds do not depend upon the formation
of methemoglobin, they may exert their anti-
dotal activity more quickly than do methemoglobin
formers. Great Britain and France use cobalt
edetate (Kelocyanor), but clear superiority to the
methemoglobin formers has not been demon-
strated, and cobalt toxicity is occasionally seen,
particularly if the patient has only a mild exposure.
The other cobalt compound sometimes used in
France is hydroxycobalamin (vitamin B
12a
), which
complexes with cyanide on a molar basis forming
cyanocobalamine. Clinical trials of this compound
are underway in the U.S. [18].
Table 6.9
Cyanide therapy
Drug
Dosing recommendation
Oxygen
100% for all victims
Sodium nitrate
(methemoglobin
former)
Adult—300mg IV over 5-10
minutes
Pediatric—0.33ml/kg IV of a 10%
solution
6.4 Vesicants
Vesicant (blister) agents, specifically sulfur
mustard (H, HD), have been major military threat
agents since their introduction in World War I.
They constitute both a vapor and a liquid threat to
all exposed skin and mucous membranes. The vesi-
cant agents include sulfur mustard (HD), nitrogen
Sodium thiosulfate
(thiocyanate
former)
Adult—12.5 grams IV (25%
solution) over 10 minutes
Pediatric—1.65ml/kg IV of a 25%
solution
Both antidotes may be repeated at half the initial dose if signs/symptoms
recur.
