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The 2 antidotes for acute cyanide poisoning in the United States must be administered by intravenous injection. In the out-of-hospital setting, intravenous injection is not practical, particularly for mass casualties, and intramuscular injection would be preferred. The purpose of this study is to determine whether sodium nitrite and sodium thiosulfate are effective cyanide antidotes when administered by intramuscular injection.We used a randomized, nonblinded, parallel-group study design in 3 mammalian models: cyanide gas inhalation in mice, with treatment postexposure; intravenous sodium cyanide infusion in rabbits, with severe hypotension as the trigger for treatment; and intravenous potassium cyanide infusion in pigs, with apnea as the trigger for treatment. The drugs were administered by intramuscular injection, and all 3 models were lethal in the absence of therapy.We found that sodium nitrite and sodium thiosulfate individually rescued 100% of the mice, and that the combination of the 2 drugs rescued 73% of the rabbits and 80% of the pigs. In all 3 species, survival in treated animals was significantly better than in control animals (log rank test, P.05). In the pigs, the drugs attenuated an increase in the plasma lactate concentration within 5 minutes postantidote injection (difference: plasma lactate, saline solution-treated versus nitrite- or thiosulfate-treated 1.76 [95% confidence interval 1.25 to 2.27]).We conclude that sodium nitrite and sodium thiosulfate administered by intramuscular injection are effective against severe cyanide poisoning in 3 clinically relevant animal models of out-of-hospital emergency care.

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.

Smoke inhalation is an important cause of fire-related morbidity and mortality, accounting for several thousand deaths annually in the United States. 1 Like carbon monoxide, hydrogen cyanide is a gaseous combustion product found in individuals with closed-space smoke exposure, and empiric treatment of smoke inhalation victims with a cyanide antidote has been recommended by some authors. 2-4 Until recently, the only approved antidote in the United States was the multicomponent cyanide antidote package (Akorn Inc, Taylor Pharmaceuticals, Decatur, IL); Cyanokit® (manufactured for EMD Pharmaceuticals Inc by Merck Sante s.a.s. in Semoy, France, packaged by Dey L.P., Napa, CA) consisting of amyl nitrite, sodium nitrite, and sodium thiosulfate. Unfortunately, nitrites can cause hypotension and excessive methemoglobinemia, precluding their use for smoke inhalation, and sodium thiosulfate may act too slowly to benefit. Outside the United States, an alternative antidote h long been available in the form of hydroxocobalamin. Cumulative data from animal models of cyanide poisoning suggest it has an efficacy comparable to the cyanide antidote package; however, like the cyanide antidote package, human efficacy data are limited to anecdotal reports, case series, and uncontrolled studies. Since hydroxocobalamin is associated with neither methemoglobinemia nor hypotension, clinicians in some countries consider it safe for empiric administration to smoke inhalation victims. 3,4

Study objective Management of chemical weapon casualties includes the timely administration of antidotes without contamination of rescuers. Personal protective equipment makes intravenous access difficult but does not prevent intraosseous drug administration. We therefore measured the systemic bioavailability of antidotes for organophosphorus nerve agent and cyanide poisoning when administered by the intraosseous, intravenous, and intramuscular routes in a small study of Gottingen minipigs. Methods Animals were randomly allocated to sequentially receive atropine (0.12 mg/kg by rapid injection), pralidoxime (25 mg/kg by injection during 2 minutes), and hydroxocobalamin (75 mg/kg during 10 minutes) by the intravenous or intraosseous route, or atropine and pralidoxime by the intramuscular route. Plasma concentrations were measured for 6 hours to characterize the antidote concentration-time profiles for each route. Results Maximum plasma concentrations of atropine and pralidoxime occurred within 2 minutes when administered by the intraosseous route compared with 8 minutes by the intramuscular route. Maximum plasma hydroxocobalamin concentration occurred at the end of the infusion when administered by the intraosseous route. The mean area under the concentration-time curve by the intraosseous route was similar to the intravenous route for all 3 drugs and similar to the intramuscular route for atropine and pralidoxime. Conclusion This study showed rapid and substantial antidote bioavailability after intraosseous administration that appeared similar to that of the intravenous route. The intraosseous route of antidote administration should be considered when intravenous access is difficult.

A 41-year-old woman ingested apricot kernels purchased at a health food store and became weak and dyspneic within 20 minutes. The patient was comatose and hypothermic on presentation but responded promptly to antidotal therapy for cyanide poisoning. She was later treated with a continuous thiosulfate infusion for persistent metabolic acidosis. This is the first reported case of cyanide toxicity from apricot kernel ingestion in the United States since 1979.

Study objective To assess outcomes in patients treated with hydroxocobalamin at the fire scene or in the ICU for suspected smoke inhalation-associated cyanide poisoning. Methods Adult smoke inhalation victims with suspected cyanide poisoning as determined by soot in the face, mouth, or nose or expectorations and neurologic impairment received an intravenous infusion of hydroxocobalamin 5 g (maximum 15 g) at the fire scene or in the ICU in this observational case series conducted from 1987 to 1994. Blood cyanide specimens were collected before administration of hydroxocobalamin. The threshold for cyanide toxicity was predefined as greater than or equal to 39 μmol/L. Results The sample included 69 patients (mean age 49.6 years; 33 men), of whom 39 were comatose. Out-of-hospital deaths were excluded. Fifty of the 69 patients (72%) admitted to the ICU survived after administration of hydroxocobalamin. In the group in which cyanide poisoning was confirmed a posteriori (n=42), 67% (28/42) survived after administration of hydroxocobalamin. The most common adverse events were chromaturia (n=6), pink or red skin discoloration (n=4), hypertension (n=3), erythema (n=2), and increased blood pressure (n=2). No serious adverse events were attributed to hydroxocobalamin. Laboratory tests revealed transient alterations in renal and hepatic function consistent with the critical condition of the patients and mild anemia consistent with progressive hemodilution. Conclusion Empiric administration of hydroxocobalamin was associated with survival among 67% of patients confirmed a posteriori to have had cyanide poisoning. Hydroxocobalamin was well tolerated irrespective of the presence of cyanide poisoning. Hydroxocobalamin appears to be safe for the out-of-hospital treatment of presumptive cyanide poisoning from smoke inhalation.

Study objective Concentrated aqueous solutions of hydroxocobalamin (OHCob) are administered intravenously for cyanide poisoning victims, many of whom also have concurrent smoke inhalation. Because of its intense light absorbance in visible wavelengths (absorption peak at 532 nm), we investigate potential interference effects of OHCob on total hemoglobin concentration (tHb), carboxyhemoglobin (COHb), methemoglobin (MetHb), and oxyhemoglobin (Hb-O 2 ) cooximetry measurement values in blood. Methods In vivo cooximetry measurements were conducted with 3 specific pathogen-free white New Zealand rabbits (3.80±0.21 kg) during the intravenous infusion of OHCob (625 mg during a 100-minute period). Resultant changes in tHb, Hb-O 2 , COHb, and MetHb values were measured and correlated with respect to estimated in vivo OHCob concentrations. In vitro measurements were conducted with rabbit blood to confirm in vivo measurements. Results The introduction of OHCob clearly interfered with the cooximetry measurements of each of the hemoglobin component fractions in whole blood and resulted in altered measurement values from the baseline values. The presence of OHCob in blood interferes with cooximetry measurements of COHb, MetHb, and Hb-O 2 . The increase in measured COHb fraction with increasing concentrations of OHCob was most notable. Conclusion The presence of OHCob in blood interferes with cooximetry measurements of COHb, MetHb, and Hb-O 2 . These effects need to be considered during OHCob treatment of cyanide poisoning, particularly in smoke inhalation victims with potential for concurrent carbon monoxide exposure, because it may lead to potentially erroneous reported COHb levels.

Study hypothesis: Concentrated aqueous solutions of hydroxocobalamin (OHCob) are given intravenously for the treatment of cyanide poisoning. Because OHCob solutions are intensely red and have peak light absorptions at 352 nm and 525 nm, we investigated whether the presence of OHCob in serum would interfere with various automated, colorimetric chemistry measurements. Design: Selected serum chemistry colorimetric measurements were compared in seven patients, using their own serum as control, with serum containing OHCob at the following concentrations: 100 mg/L, 500 mg/L, and 1,000 mg/L. These concentrations are in the range achieved with therapeutic doses of OHCob when given for cyanide poisoning. Measurements and main results: Statistically significant alterations in serum values for aspartate aminotransferase, total bilirubin, creatinine, magnesium, and iron were seen in the presence of OHCob. Conclusion: The presence of OHCob in serum interferes with several chemistry methodologies, and such interference should be anticipated when this antidote is used. [Curry SC, Connor DA, Raschke RA: Effect of the cyanide antidote hydroxocobalamin on commonly ordered serum chemistry studies. Ann Emerg Med July 1994;24:65-67.]

Study objectives: To determine if toxic concentrations of cyanide in blood result in a difference between calculated and measured percent hemoglobin oxygen saturation (percent saturation gap). Design: An in vitro laboratory study. Setting: Hospital laboratory. Type of participants: Arterial blood from five stable patients residing in a tertiary hospital ICU. Venous blood samples obtained from five healthy volunteers. Interventions: Two-mL aliquots from each blood sample were placed into four test tubes and mixed with phosphate buffer. Cyanide was added to three of the tubes so that the four tubes contained 0, 6, 12, and 25 mg/L cyanide. Measurements and main results: The percent saturation gap was calculated by subtracting the percent oxyhemoglobin measured on an oximeter from the percent saturation calculated by a blood gas analyzer. Using two-tailed, paired t tests, we could not demonstrate a difference in mean percent saturation gaps between arterial samples or venous samples with and without cyanide. All blood samples had a normal percent saturation gap ( P > .99 by Fisher's exact test). We had greater than a 95% chance of demonstrating a difference in mean percent saturation gaps of only 0.46% in arterial blood and of 3.3% in venous blood if such a difference existed. Conclusions: Our results, as well as a review of the literature, indicate that there are no data supporting the suggestion that a percent saturation gap should imply the diagnosis of poisoning by inorganic cyanide.

A 29-year-old man was found unresponsive a few minutes after self-injecting undetermined amounts of potassium cyanide and sodium arsenite intravenously in a suicide attempt. Treatment with the Lilly Cyanide Antidote kit rapidly resolved the initial coma, despite a whole blood cyanide level of 4.4 micrograms/mL. A 12-hour urine arsenic collection begun on admission showed 10,065 micrograms arsenic/12 hr. The patient received intramuscular BAL initially, which was followed by two ten-day courses of oral D-penicillamine. Complications included upper gastrointestinal tract bleeding requiring transfusion, transient elevations of liver function tests, self-limited complaints of decreased vision with conjunctival hyperemia and photophobia, and an abscess at the injection site. Although specific antidote therapy completely resolved the cyanide toxicity, early and prolonged arsenic chelation did not prevent a mild sensory peripheral neuropathy from developing with onset about 17 days after self-injection.

A case of cyanide poisoning from laetrile ingestion is presented as an illustration of the recognition and treatment of cyanide intoxication. The pharmacology of laetrile, of cyanide, and of antidotes to cyanide intoxication are discussed as they relate to the acute management and successful treatment of this patient after this highly lethal ingestion.

Cyanide poisoning causes a high incidence of severe symptomatology and fatality. There are numerous sources of potential cyanide exposure. Without the history of cyanide exposure, diagnosis is often difficult. Treatment with supportive measures and available specific and efficacious antidotes frequently allows survival. The toxicology of cyanide, including sources, clinical features, diagnosis, and treatment, is reviewed.

We report two cases of cyanide poisoning from accidental ingestion of an imported metal cleaning solution used by some Southeast Asians for shining coins. Both patients received specific therapy and recovered completely after a dramatic sequence of sudden collapse and severe cardiovascular compromise.

Sublingual nitroglycerin 0.8 mg every five minutes for a total of 4.8 mg was administered to 11 healthy volunteers. One volunteer had to withdraw due to a hypotensive bradycardic reaction after 2.4 mg. In the remaining subjects, methemoglobinemia over the next hour never significantly increased from baseline levels, reaching a peak of only 0.71%. We conclude that commonly used doses of sublingual nitroglycerin do not induce significant methemoglobinemia and that nitroglycerin would not be useful in the treatment of cyanide poisoning.