Sodium Thiosulfate or Hydroxocobalamin for the Empiric Treatment of Cyanide Poisoning?
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TOXICOLOGY/REVIEW ARTICLE
Sodium Thiosulfate or Hydroxocobalamin for the Empiric
Treatment of Cyanide Poisoning?
Alan H. Hall, MD From the Toxicology Consulting and Medical Translating Services, Inc., Elk Mountain, WY (Hall);
Richard Dart, MD, PhD the Rocky Mountain Poison and Drug Center, Denver Health, Denver, CO (Dart, Bogdan); and the
Departments of Preventive Medicine and Biometrics (Hall), Surgery [Emergency Medicine] (Dart),
Gregory Bogdan, PhD
and Pharmaceutical Sciences (Bogdan), the University of Colorado Health Sciences Center,
Denver, CO.
Cyanide poisoning must be seriously considered in victims of smoke inhalation from enclosed space
fires; it is also a credible terrorism threat agent. The treatment of cyanide poisoning is empiric
because laboratory confirmation can take hours or days. Empiric treatment requires a safe and
effective antidote that can be rapidly administered by either out-of-hospital or emergency department
personnel. Among several cyanide antidotes available, sodium thiosulfate and hydroxocobalamin have
been proposed for use in these circumstances. The evidence available to assess either sodium
thiosulfate or hydroxocobalamin is incomplete. According to recent safety and efficacy studies in
animals and human safety and uncontrolled efficacy studies, hydroxocobalamin seems to be an
appropriate antidote for empiric treatment of smoke inhalation and other suspected cyanide poisoning
victims in the out-of-hospital setting. Sodium thiosulfate can also be administered in the out-of-hospital
setting. The efficacy of sodium thiosulfate is based on individual case studies, and there are
contradictory conclusions about efficacy in animal models. The onset of antidotal action of sodium
thiosulfate may be too slow for it to be the only cyanide antidote for emergency use.
Hydroxocobalamin is being developed for potential introduction in the United States and may represent
a new option for emergency personnel in cases of suspected or confirmed cyanide poisoning in the
out-of-hospital setting. [Ann Emerg Med. 2007;49:806-813.]
0196-0644/$-see front matter
Copyright © 2007 by the American College of Emergency Physicians.
doi:10.1016/j.annemergmed.2006.09.021
SEE EDITORIAL, P. 814. and causes central nervous system and cardiovascular dysfunction
because of cellular hypoxia, primarily by binding to and
inactivating the enzyme cytochrome oxidase (cytochrome a3).5,9
INTRODUCTION
Cyanide poisoning requires immediate and aggressive
Cyanide has been used as an agent for suicide, homicide,
treatment. The emergency diagnosis is usually difficult because
chemical warfare, and genocide and can contribute to death of
victims of smoke inhalation in enclosed space fires.1-4 In the there are no pathognomonic symptoms or signs,10 and
United States, smoke inhalation causes as many as 10,000 laboratory confirmation of cyanide poisoning takes hours to
fatalities each year.5 Of US annual burn fatalities, 60% to 80% days to obtain. A confirmed diagnosis of cyanide poisoning is
are likely due to smoke inhalation.6 Fire smoke contains a not possible in out-of-hospital emergency situations. Therefore,
complex mixture of gases that contribute to smoke inhalation- the decision to administer specific cyanide antidotes must be
associated death, including hydrogen cyanide that is released made on clinical characteristics. These can include hypotension,
from natural and synthetic materials on combustion.1,4 Cyanide altered mental status, elevated plasma lactate concentrations
and cyanogenic compounds are also potential weapons of (ⱖ10 mmol/L), and relatively normal oxygen saturation. In
terrorism.7,8 Because cyanide can be released from both smoke inhalation victims, the presence of soot in the mouth and
synthetic and natural materials, terrorist acts with explosives or nose, with concurrent altered mental status and hypotension,
incendiaries, resulting in enclosed space fires, could result in suggests the possibility of cyanide poisoning.5
poisoning, even if cyanide or cyanogenic compounds are not used. Because of diagnostic uncertainty, a cyanide antidote may be
Cyanide reacts with high affinity with metals such as ferric administered to patients who may not be poisoned. A favorable
iron (Fe3⫹) and cobalt and binds to numerous critical enzyme risk:benefit ratio is thus highly desirable.11-15 There are 4
systems in the body. Cyanide inhibits oxidative phosphorylation antidotes used in various countries for treatment of cyanide
806 Annals of Emergency Medicine Volume , . : June Hall et al Empiric Treatments for Cyanide Poisoning
poisoning: the Cyanide Antidote Kit (amyl nitrite, sodium EFFICACY OF HYDROXOCOBALAMIN
nitrite, and sodium thiosulfate), hydroxocobalamin (Cyanokit), The effectiveness of hydroxocobalamin as a cyanide antidote
dicobalt– ethylenediamine tetraacetic acid (EDTA) was first demonstrated in 1952.26 The mechanism of action is
(Kelocyanor), and 4-dimethylaminophenol (DMAP). direct binding to cyanide to form nontoxic cyanocobalamin
Unfortunately, dicobalt-EDTA, DMAP, and the sodium nitrite (vitamin B12) that is excreted in the urine.11 In an in vitro study
component of the cyanide antidote kit have serious adverse using human fibroblasts incubated in a cyanide solution,
effects (including hypotension and the formation of addition of hydroxocobalamin resulted in a 75% decrease in
methemoglobin that can exacerbate carbon monoxide–induced intracellular cyanide concentrations and formation of
hypoxemia) that make them less desirable for empiric use, intracellular cyanocobalamin, indicating that hydroxocobalamin
especially outside a health care facility.12 Only 2 cyanide penetrates cells and can act intracellularly.27
antidotes, hydroxocobalamin and a component of the Cyanide
Antidote kit, sodium thiosulfate, have been proposed for
Animal Studies
empiric therapy in cyanide poisoning (P. Edelman, written
Hydroxocobalamin crosses the blood-brain barrier and enters
communication, 2003).16
the cerebrospinal fluid in experimental animals.28 It has been
Sodium thiosulfate has been proposed for use alone in
tested as a cyanide antidote in animal models using mice,21,26
victims of chemical terrorism by the US Department of Health
rabbits,29,30 guinea pigs,31,32 dogs,33-38 and baboons.39 The
and Human Services (P. Edelman, written communication,
majority of these studies demonstrated antidotal efficacy of
2003). However, this idea has been challenged because of its
hydroxocobalamin even if administered after cyanide. No
slow onset of action.17 Lang first demonstrated the antidotal
animal study compared hydroxocobalamin and sodium
efficacy of sodium thiosulfate for cyanide poisoning in 1885,
thiosulfate by using the same experimental protocol.
and before 1929, sodium thiosulfate was the only known
The efficacy of hydroxocobalamin was compared to saline
specific cyanide antidote.18 There is little recent information
solution vehicle for the treatment of dogs administered
available about the efficacy of sodium thiosulfate for treatment
potassium cyanide (0.4 mg/kg per minute, intravenously).36 In
of cyanide poisoning.19
vehicle-treated animals, the overall mortality rate was 82% (14/
Hydroxocobalamin (vitamin B12a), the natural form of
17), and death occurred within 4 hours to 4 days. In contrast,
vitamin B12, is a hemelike molecule with a complexed cobalt
79% (15/19) and 100% (18/18) of animals treated with
(Co) atom.20 It is used for cyanide poisoning and smoke
hydroxocobalamin 75 mg/kg or 150 mg/kg, respectively,
inhalation in France,21 where it is administered by the out-of-
survived through 14 days after poisoning, with no neurologic or
hospital system and has been in clinical use for more than
other sequelae and no significant effects on clinical chemistry or
30 years. Hydroxocobalamin is also used in other countries,
hematology tests. Administration of hydroxocobalamin was
including Sweden, Denmark, Spain, Japan, and Hong
associated with beneficial increases in blood pressure beginning
Kong.17, 22-25
1 to 3 minutes after initiation of infusion. The
The purpose of this analysis is to evaluate and review the
hydroxocobalamin doses used were designed to mimic
literature on hydroxocobalamin and sodium thiosulfate
recommended doses (5 to 10 g) administered to humans.36
monotherapy so that emergency personnel and clinical
toxicologists are better able to develop practice for the empiric
treatment of cyanide poisoning. Human Studies, Case Series, and Reports
In humans, the published efficacy data for hydroxocobalamin
EVALUATION OF MEDICAL LITERATURE consist of 1 prospective and 1 retrospective study in victims of
A review of published and recently presented studies on smoke inhalation,40,41 as well as case reports and case series.
hydroxocobalamin and sodium thiosulfate was performed in Preclinical studies in heavily smoking human volunteers showed
several languages (English, French, Spanish, Danish, Swedish, clearing of the small amounts of cyanide (⬍2 mol/L)
German, and Japanese; professional translations were obtained) detectable in the blood of heavy smokers.42
and with electronic and hardcopy literature searches from the A prospective open-label noncomparative trial in victims of
1930s to the present. Searches were conducted at the National enclosed space fire-smoke inhalation (defined as extrication
Library of Medicine, Bethesda, MD, with MEDLINE, from an enclosed space fire scene; soot in the nose, mouth, or
TOXLINE, and other reference resources. Search terms throat; and some degree of neurologic impairment) was
included “hydroxocobalamin,” “sodium thiosulfate,” “cyanide performed in Paris from 1989 to 1994.40 Results have been
poisoning,” “cyanide antidotes,” “toxic terrorism,” and “smoke published in abstract form. Of 69 patients, 37 were comatose
inhalation.” The extensive collection of relevant books and and 14 were initially in cardiopulmonary arrest (apneic and
articles of one of the authors (A.H.H.) was also reviewed. More pulseless). In addition to standard resuscitation measures,
than 250 references were reviewed, as well as Google searches hydroxocobalamin was administered in the out-of-hospital
for recent media reports of cyanide poisoning, toxic terrorism, and setting (5 to 15 g intravenously). The survival rate was 72%
smoke inhalation incidents. References involving chronic cyanide (50/69). There were no neuropsychiatric sequelae in the
dietary exposure from cyanogenic plants were not reviewed. majority (41/50) of the survivors (82%). The main causes of
Volume , . : June Annals of Emergency Medicine 807Empiric Treatments for Cyanide Poisoning Hall et al
death were infectious complications (unrelated to cyanide the medication itself. The discoloration clears during several
poisoning) and decerebration. days in poisoned patients administered an antidotal dose14 and
Fortin et al41 retrospectively reported effects of appears to be harmless. In burn patients, discoloration of the
hydroxocobalamin in 101 smoke inhalation victims. Among 72 skin and exudates can complicate the subsequent evaluation of
patients for whom survival status was known, survival rate was lesion depth if this is not done before hydroxocobalamin
41.7% after administration of hydroxocobalamin. Of the 38 administration.56
patients found in cardiac arrest, 21 had a return of spontaneous In the serum, the peak light absorption of hydroxocobalamin
circulation during out-of-hospital care. Twelve patients were at 325, 364, 525, and 564.5 nm can interfere with colorimetric
initially hemodynamically unstable (systolic blood pressure 0 blood chemistry analyses for liver enzymes, bilirubin, creatinine,
to ⱕ90 mm Hg), and 9 recovered systolic blood pressure creatine kinase, phosphorus, glucose, magnesium, and iron,
approximately 30 minutes after the start of hydroxocobalamin which are autoanalyzer-dependent. Either falsely high or low
infusion. Those with significant neurologic impairment had results may be obtained, but none appear to be of major clinical
little improvement after hydroxocobalamin administration, as significance.57-60
assessed by Glasgow Coma Scale scores. After chronic administration, rare cases of anaphylaxis,
Survival of severe acute cyanide poisoning from sources anaphylactoid reactions (including bronchospasm and
other than smoke inhalation after administration of oropharyngeal angioedema), pruritus, or urticaria have been
hydroxocobalamin alone has been documented.43-46 In a case reported in patients receiving low-dose hydroxocobalamin (1 to
series, 9 adult patients were poisoned by ingestion of cyanide 10 mg intramuscularly per month) for vitamin B12 deficiency or
salts (n⫽7), ingestion of acetonitrile (n⫽1), and exposure to other indications.61-67 One case of transient facial acne49 and 1
cyanogen bromide gas (n⫽1).43 All received hydroxocobalamin case of urticaria and Quinke’s edema50 have been reported in
(average dose 8.1 g). Five of the 9 patients were comatose, patients receiving antidotal doses. Both patients were
and 6 had a systolic blood pressure less than 90 mm Hg. administered an older formulation of 4 g of lyophilized
Administration of hydroxocobalamin was associated with hydroxocobalamin dissolved in 10% sodium thiosulfate solution
improved blood pressure in patients presenting with stabilized with sodium sulfite, and dicobalt-EDTA was also
hypotensive shock. Six patients survived, and 3 patients who
administered. The current hydroxocobalamin formulation
were in cardiac arrest ultimately died. All 3 patients who died
available in France contains lyophilized hydroxocobalamin
were admitted several hours after the onset of the poisoning,
alone.
when neurologic impairment seemed irreversible.
In normal human volunteers administered 5 g of
Espinoza et al47 reported 8 pediatric patients (aged 8 to 11
hydroxocobalamin intravenously during 20 minutes, mild,
years) with acute cyanide poisoning from ingestion of
transient, self-limited hypertension (mean increase of 13.6%
improperly prepared bitter cassava (Manihot esculenta) in
systolic and 25.9% diastolic blood pressures) accompanied by
Venezuela. These children presented to the hospital with
reflex bradycardia (mean decrease of 16.3% in pulse rate) was
vomiting, excessive weakness, respiratory failure, bradycardia,
noted.42 There were no changes on ECG and no clinically
hypotension, and cardiovascular collapse. Because of limited
significant abnormalities of CBC counts, liver and kidney
drug supply, only the 4 most acutely ill children were treated
with sodium nitrite; the remaining 4 children were each treated function test results, serum electrolyte levels, prothrombin and
with 500 mg of hydroxocobalamin. Both groups of children partial thromboplastin times, or blood glucose levels. All
improved within a few minutes, remained asymptomatic subjects remained asymptomatic and all findings returned to
thereafter, and were discharged the following day, with normal baseline without treatment.
neurologic assessment results. A randomized, double-blind, placebo-controlled, ascending
Hydroxocobalamin became available in France on an dose study was conducted to evaluate the safety of
investigational use basis in about 1970 as the Anphar-Rolland hydroxocobalamin in healthy volunteers.68 One hundred
trousse anticyanure containing 4 g of lyophilized thirty-six volunteers were randomized to receive either
hydroxocobalamin to be reconstituted in 8 g of 10% sodium hydroxocobalamin (2.5 g, 5 g, 7.5 g, 10 g) or placebo by
thiosulfate solution stabilized with sodium sulfite. Between intravenous infusion during 7.5 to 30 minutes. The most
1970 and 1984, 10 patients with acute cyanide poisoning common hydroxocobalamin-related effects were chromaturia
treated with the trousse anticyanure were reported, as well as 1 and reddening of the skin. Other common adverse events were
patient treated with 200 mg of intravenous hydroxocobalamin pustular or papular rash, headache, erythema at the injection
without sodium thiosulfate.48-55 In only 2 cases was the site, decrease in lymphocyte percentage, and chest pressure.
hydroxocobalamin/sodium thiosulfate antidote combination Hydroxocobalamin was associated with a modest increase in
the only cyanide antidote administered.52,54 blood pressure that was self-limiting. The clinical relevance of
the increase in blood pressure in this and other studies is unclear
SAFETY OF HYDROXOCOBALAMIN but may be desirable in cyanide poisoning because it avoids the
In humans, a transient reddish-brown discoloration of the hypotension associated with nitrite-containing cyanide
skin, mucous membranes, and urine occurs from the color of antidotes.12 Two allergic reactions occurred within minutes of
808 Annals of Emergency Medicine Volume , . : June Hall et al Empiric Treatments for Cyanide Poisoning
initiation of infusion in volunteers assigned to receive the 5-g thiosulfate, which was practically nontoxic in normal animals,
and 10-g doses, respectively, and were successfully managed caused shock and decreased the time to cardiac arrest and death
with dexamethasone, dimethindene maleate, or both. This when subsequently administered to the poisoned animals. These
finding is similar to isolated reports of allergic reactions to effects were also noted when sodium thiosulfate was mixed with
hydroxocobalamin during chronic intramuscular administration sodium nitrite and administered. The effects were exacerbated
for vitamin B12 deficiency.61-64 More severe manifestations, when the sodium thiosulfate dose was increased. The best
including wheezing, hypotension, or stridor, did not occur. results were obtained when sodium nitrite was administered
No cases of allergic reactions have been reported after first, followed by sodium thiosulfate. Hug72 concluded that
administration to 170 acutely poisoned patients.40,41 sodium thiosulfate “. . . requires a certain latent period to
Breton et al69 reported 2 children who experienced smoke exert its antidotal action . . . it has a preventive [eg, must be
inhalation and presented comatose, covered in soot, but without administered prophylactically before the cyanide] but not a
burns. Both patients received hydroxocobalamin in the out-of- curative [eg, efficacious after poisoning symptoms develop]
hospital setting. The 11-month-old child was cyanotic but not effect on cyanide poisoning.”
acidotic. The 4 1/2-year-old child was not cyanotic and had In a sodium cyanide continuous infusion dog model, sodium
an initial pH of 7.21; however, the arterial blood gas values thiosulfate was not effective if administered any later in the
suggested a respiratory rather than a lactic acidosis. Neither had poisoning than the beginning of the phase of primary apnea.73
plasma lactate concentrations suggestive of a significant cyanide Sodium nitrite with sodium thiosulfate, hydroxocobalamin with
poisoning component to their smoke inhalation (plasma lactate sodium thiosulfate, 4-DMAP, and dicobalt-EDTA were all
concentrations ⬍10.0 mmol/L). Both children developed effective at later phases of the poisoning.73
chronic respiratory sequelae. Although neither child appeared In a recent study, rats were administered potassium cyanide
to have significant cyanide poisoning, out-of-hospital intraperitoneally, followed 6 to 16 minutes later (when
administration of the recommended hydroxocobalamin dose blood cyanide concentrations were expected to peak) by
was not associated with any adverse effects. intraperitoneal sodium thiosulfate or normal saline solution at
225 mg/kg.74 In the sodium thiosulfate–treated animals, there
were significantly lower arterial blood cyanide concentrations,
EFFICACY OF SODIUM THIOSULFATE
arterial and venous lactate concentrations, and venous PO2s,
Sodium thiosulfate removes cyanide from the blood through
indicating curative efficacy for improving these cyanide toxicity
the action of the enzyme rhodanese.10 Sodium thiosulfate has
markers.74 The authors observed that caution should be used in
limited distribution into the brain, an organ highly susceptible
extrapolating these results to humans.74 The intraperitoneal
to the effects of cyanide-induced histotoxic anoxia, and has
route is an unlikely route of cyanide exposure and would not be
limited penetration into the mitochondria, where the
used for sodium thiosulfate administration in humans. The dose
endogenous cyanide-detoxifying enzyme rhodanese is located.18
used was somewhat higher than that recommended in humans
No clinical trials of sodium thiosulfate are available, and efficacy
(approximately 179 mg/kg), and survival or death was not an
has been extrapolated from case studies and series of acute
endpoint.
cyanide poisoning.
Human Studies, Case Series, and Case Reports
Animal Studies No clinical trials in humans that assess the efficacy of sodium
Most experimental animal studies have compared sodium thiosulfate alone were found. Case reports have associated
thiosulfate alone to its combination with other antidotes, most sodium thiosulfate with survival. Chin and Calderon75
often sodium nitrite or hydroxocobalamin. In dog studies with described a 19-year-old woman who drank an unknown
a continuous infusion of hydrocyanic acid at 0.1 mg/kg per substance containing a “high concentration” of cyanide. Coma,
minute, Hug and Marenzi70 reported that both methylene blue hypotension, and dilated pupils were noted. Initial arterial
and sodium nitrite were clearly more efficacious than sodium blood gases showed a severe acidosis, with a pH of 7.01, and the
thiosulfate alone. plasma lactate level was 10.0 mmol/L. Initial treatment with
Kinetic studies have shown that administration of sodium 12.5 g of sodium thiosulfate intravenously was followed by
thiosulfate accelerates by more than 3 times the conversion of improvement of the pH to 7.17. The patient survived with
cyanide to much less toxic thiocyanate by the endogenous sodium nitrite and further sodium thiosulfate plus supportive
rhodanese enzyme.71 However, sodium thiosulfate has generally measures, but sequelae of short-term memory difficulties and
been thought to have only a preventive action and not a curative bradykinesia developed.
action (eg, it has to be administered before the onset of cyanide Perrson19 described 5 cases of cyanide poisoning, 4 treated
poisoning symptoms and signs to be efficacious). In studies of with sodium thiosulfate alone and 1 treated initially with
rabbits administered potassium cyanide by gastric instillation, sodium thiosulfate followed by dicobalt-EDTA. For some of
Hug and Marenzi70 found that 7 of 10 animals died despite these patients, blood cyanide concentrations were reported.
administration of 1 g of sodium thiosulfate intravenously after Potentially toxic concentrations of cyanide are 1 mg/L
cyanide administration. They also noted that sodium (39 mol/L), and potentially lethal concentrations are
Volume , . : June Annals of Emergency Medicine 809Empiric Treatments for Cyanide Poisoning Hall et al
approximately 2.7 mg/L (100 mol/L), as reported in forensic decreased alkali reserve (7.2 mmol/L) in both children. Both
medicine.44 recovered with supportive care and intravenous infusion of
Twin brothers aged 2 1/2 years were found unconscious 50 mL of 25% sodium thiosulfate and made full recoveries.
during an enclosed space fire. Both were severely acidotic on One of 7 patients exposed to hydrogen cyanide by inhalation
presentation. Carbon monoxide concentrations were not in a chemical trading company office, a 19-year-old woman was
significantly elevated. Treatment with oxygen, hyperbaric discovered unconscious and hypotensive (blood pressure 77/65
oxygen, and approximately 400 mg/kg of sodium thiosulfate mm Hg), with severe metabolic acidosis.78 The patient received
was followed by recovery without sequelae. Blood cyanide amyl nitrite, and sodium thiosulfate 12.5 g was administered
concentrations were 1.15 mg/L and 1.1 mg/L.19 intravenously. The patient had repeated seizures, requiring
A 28-year-old man ingested an unknown amount of a anticonvulsant therapy. She was extubated 15 hours after
cyanide solution. On presentation, he was talkative, anxious, admission. At 1-year follow-up, complaints of mild impairment
and hyperventilating. Sodium thiosulfate, 15 g, was of recent memory and concentration ability were confirmed by
administered by slow intravenous infusion. This patient never neuropsychological testing.
lost consciousness but became calm and mentally clear, and the A 23-year-old German man attempted suicide by ingesting
mild acidosis resolved. The blood cyanide concentration was 1,500 mg of potassium cyanide.20 Six hours after hospital
9.9 mg/L.19 This cyanide concentration is inconsistent with the admission, his blood cyanide level was 6 mg/L. Supportive
clinical presentation and course. treatments, administration of supplemental oxygen, correction
A 32-year-old man was deeply comatose and slightly cyanotic of metabolic acidosis, and administration of 1 g of sodium
after ingesting an unknown amount of a potassium cyanide thiosulfate per hour for 24 hours were associated with survival.
solution. There was improvement 30 minutes after
administration of oxygen and 8 g of sodium thiosulfate.
SAFETY OF SODIUM THIOSULFATE
Dicobalt-EDTA was then administered, resulting in return of Dogs administered sodium thiosulfate at 3,000 mg/kg
intravenously developed metabolic acidosis, hypoxemia,
normal consciousness. The blood cyanide concentration was
hypernatremia, ECG abnormalities, and changes in blood
3.7 mg/L.19
pressure.19 Dogs and rabbits administered sodium thiosulfate
A 54-year-old man was comatose and in respiratory arrest
at 500 to 4,000 mg/kg intravenously developed hypotension.31
after ingesting 3 g of potassium cyanide. Metabolic acidosis was
For comparison, the recommended adult dose of sodium
present (pH 7.31). An initial dose of 12 g of sodium thiosulfate
thiosulfate from the Cyanide Antidote kit is 12.5 g, or about
was administered, followed by an additional 3-g dose.
179 mg/kg for a 70-kg person.
Spontaneous respiration resumed 30 minutes later, and he was
In normal volunteers administered 4 g of hydroxocobalamin
alert at 6 hours after admission. There were no sequelae. The
plus 12.5 g of sodium thiosulfate intravenously, nausea,
blood cyanide concentration was 0.26 mg/L.19
retching, vomiting, and injection site pain, irritation, and a
Of 4 previously published cases reviewed by Perrson,19 burning sensation were observed.42,79 When sodium thiosulfate
3 involved cyanide toxicity from infusion of sodium was removed from the study protocol, these effects were no
nitroprusside, which improved after administration of sodium longer observed, suggesting that they were due to sodium
thiosulfate. The fourth was a 30-year-old man who ingested an thiosulfate. In another normal volunteer study of sodium
unknown amount of a cyanide-containing insecticide and was thiosulfate infusion alone, nausea and vomiting were also
found comatose, apneic, and cyanotic 30 minutes later. observed.80
Supportive measures and administration of sodium thiosulfate
(dose not specified) was followed by return of consciousness, CONCLUSION
although persistent neurologic symptoms developed. The treatment of suspected cyanide poisoning presents a
A 31-year-old male Japanese patient was found in bed dilemma for first-response emergency personnel. It is important
comatose and having seizures after ingesting potassium to initiate treatment as soon as possible, but some available
cyanide.76 The patient had severe metabolic acidosis, an antidotes have undesirable safety profiles and cannot be
elevated central venous PO2, and normal oxygen saturation level, administered empirically in an out-of-hospital setting.
consistent with cyanide poisoning. Three pearls of amyl nitrite The evidence available to assess the 2 cyanide antidotes that
were administered, followed by 10 g sodium thiosulfate. The can be used empirically, sodium thiosulfate or
patient recovered during the following 30 minutes. Cyanide hydroxocobalamin, is incomplete. Some practitioners in the
concentration in stored plasma was found to be approximately United States have used sodium thiosulfate, but there are no
1.2 mg/L when measured 6 months later.76 clinical trials to assess efficacy. In France and other countries,
Two Malaysian children developed acute cassava poisoning hydroxocobalamin is used for empiric treatment, and there are
after eating “tapioca” cake (M utilissima).77 Both had vomiting, retrospective and prospective clinical studies. Because of ethical
drowsiness, and weakness. The 2 1/2-year-old boy also had considerations, prospective, controlled clinical trial efficacy data
reactive mydriasis, and the 1 1/2-year-old girl had dyspnea in humans are not available for either agent, and there are no
and cyanosis. Potential metabolic acidosis was reflected as a animal or human comparative studies.
810 Annals of Emergency Medicine Volume , . : June Hall et al Empiric Treatments for Cyanide Poisoning
Based on recent safety and efficacy studies in animals, safety 4. Stefanidou M, Athanaselis S. Toxicological aspects of fire. Vet
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KZEPharmAssociates, LLC, Chapel Hill, NC, for assistance with 641.
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Supervising editor: Donald M. Yealy, MD 18. Baskin SI, Horowitz AM, Nealley EW. The antidotal action of
sodium nitrite and sodium thiosulfate against cyanide poisoning.
Funding and support: Dr. Hall’s work on this article was J Clin Pharmacol. 1992;32:368-375.
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Request for Abstracts for ACEP’s Research Forum (non-moderated)
Researchers have a unique opportunity to showcase emergency medicine research published or presented in other
specialties’ journals or meetings in the past year.
ACEP’s Research Forum is providing emergency medicine researchers with another opportunity this year to present
scientific emergency medicine research at the 2007 conference, which will be held October 8-9 in conjunction with
Scientific Assembly in Seattle, WA.
Abstracts from emergency physicians who have presented or published in non-emergency medicine specialty meetings or
journals within the past 12 months will be considered. Case reports or subject reviews are not considered original
research. These abstracts will be accepted on a space available basis as non-moderated posters. If accepted the
presenter is obligated to be available to discuss their poster(s) with Research Forum attendees.
This is an excellent venue to showcase outstanding emergency medicine research from competing meetings or journals.
Please submit your research absract(s) to the academic affairs department by September 7, 2007 at
academicaffairs@acep.org, or by fax at 972-580-2816. For questions, please call 800-798-1822, ext. 3291.
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