Recognition and Treatment of Acute Cyanide Poisoning

CYANIDE SUPPLEMENT

Recognition and Treatment of Acute Cyanide Poisoning Author: Stephen W. Borron, MD, MS, San Antonio, Tex

Stephen W. Borron, Clinical Professor of Surgery, Division of Emergency Medicine, University of Texas Health Science Center, San Antonio, Tex. For correspondence, write: Stephen W. Borron, MD, MS, FACEP, FACMT, Division of Emergency Medicine (Surgery), MSC 7736, 7703 Floyd Curl Drive, San Antonio, TX 78229; E-mail: borron@ uthscsa.edu. J Emerg Nurs 2006;32:S12-8. 0099-1767/$32.00 Copyright n 2006 by the Emergency Nurses Association. doi: 10.1016/j.jen.2006.05.011

S12

A

recent publication describes the case of a teenager who arrived at a community emergency room in a hemodynamically unstable, apneic, and unresponsive state and later died in a pediatric intensive care unit.1 The cause of death, confirmed by laboratory results available 2 days after the onset of symptoms, was cyanide poisoning. The 17-year-old male was previously healthy, was not taking medications, and had no history of drug abuse. Toxicity was manifested suddenly and dramatically by seizures and loss of consciousness while the boy was visiting at a classmate’s house. Supportive care was initiated in the emergency room beginning shortly after the onset of toxicity and continued in the intensive care unit; however, the patient did not receive antidotal therapy until cyanide poisoning was presumptively diagnosed approximately 4 hours after symptom onset—far too late, the authors later concluded, to be effective, particularly given the amount of cyanide to which the patient was exposed.1 This case illustrates many of the challenges in the recognition and treatment of acute cyanide poisoning. Because cyanide poisoning can rapidly culminate in incapacitation and death, prompt recognition of cyanide toxicity and early initiation of treatment are necessary for saving lives and reducing morbidity.2-4 However, the nonspecific nature of the signs and symptoms of cyanide poisoning and the inability of most hospital laboratories to rapidly confirm the presence of cyanide make diagnosis difficult. These challenges notwithstanding, acute cyanide poisoning can be successfully treated. As part of the first line of care for the critically ill patient in the prehospital and hospital settings, the emergency nurse can play an integral role in the recognition and treatment of acute cyanide poisoning. This article discusses the recognition and treatment of acute

JOURNAL OF EMERGENCY NURSING

32:4S

August 2006

CYANIDE SUPPLEMENT/Borron

cyanide poisoning with emphasis on information that prepares the emergency nurse to respond to a cyanide emergency. Causes of Acute Cyanide Poisoning

A detailed discussion of the potential causes of acute cyanide poisoning—inhalation of fire smoke, accidental ingestion, occupational exposure, industrial incidents, homicide or suicide attempts, terrorism, and ingestion of cyanogenic substances—is presented by Schnepp elsewhere in this supplement.5 In western countries, the most common cause of cyanide poisoning is inhalation of smoke from structural fires. As hydrogen cyanide is produced during combustion of carbon- and nitrogen-based materials, it is generated in nearly every fire.6 Modern structural fires, in particular, can produce high concentrations of hydrogen cyanide because of the abundance of substrates such as plastics and other polymers, synthetic fibers, wool, and silk. In keeping with the pervasiveness of cyanide in modern fires, cyanide is found, often at toxic-to-lethal concentrations, in the blood of most fire victims in which its presence is assessed.7 Toxicologic evidence suggests that cyanide is at least as important as carbon monoxide as cause of smoke-inhalation morbidity and mortality in many fires.6-9 Besides fire smoke, other causes of cyanide poisoning include occupational and industrial incidents and use in suicide, murder, and terrorism. The 17-year-old described above was poisoned by intentional adulteration of a beverage with 1.5 g potassium cyanide.1 Recognition of Acute Cyanide Poisoning

Clinical manifestations and laboratory findings in acute cyanide poisoning reflect hypoxia caused by cyanide’s deactivation of cellular oxygen-utilization mechanisms.10 Cyanide inhibits the activity of mitochondrial cytochrome oxidase, an enzyme necessary for the normal use of oxygen in cellular metabolism, and thereby prevents cells from extracting and using oxygen from arterial blood. CLINICAL MANIFESTATIONS

Development of toxicity is generally rapid, at a rate dependent on the form of cyanide and the amount and route of exposure.11 Exposure to large doses, particularly by inhalation or ingestion, can produce marked symptoms nearly immediately and can result in death in minutes. Less rapid progression of symptoms with survival times of several

August 2006

32:4S

hours has also been reported, particularly in cases of exposure by ingestion.12 The variability in absorption and onset of toxicity can be explained by the presence or absence of food in the stomach, the solubility of the cyanide salt involved, and other factors. In the case of ingestion of nitriles, which release cyanide when they are metabolized, onset of toxicity may be delayed for hours. These observations illustrate the existence of a window of time, albeit narrow, for effective intervention.

In western countries, the most common cause of cyanide poisoning is inhalation of smoke from structural fires. The clinical presentation in acute cyanide poisoning can change quickly.13 Health care providers typically first encounter patients after severe toxicity has developed. Severe or advanced poisoning is manifested by hypotension, seizures, coma, respiratory depression, cardiovascular collapse, and cardiorespiratory arrest (Table 1).2-4,13,14 In a series of 101 patients treated by the Paris Fire Brigade for smoke inhalation-associated cyanide poisoning from 1995 to 2003, 37.6% were found in cardiac arrest, and 45.5% were neurologically impaired.15 Respiratory depression is generally not accompanied by cyanosis because of increased venous oxygen saturation.10,11 Often very transitory, early signs and symptoms include hypertension with ref lex bradycardia; neurologic symptoms such as faintness, confusion, headache, and anxiety; and tachypnea and dyspnea.2-4,10,11,13,14 As these signs and symptoms illustrate, the heart and the brain are especially vulnerable to cyanide poisoning because of their high requirements for oxygen. Other findings that can, but do not always, occur in cyanide poisoning include bright-red retinal veins because of elevated venous oxygen concentration; and a bitteralmond odor of victims’ breath or gastric contents.11 As the gene necessary for detecting the bitter-almond odor is absent in approximately half of the population, absence of the bitter-almond odor does not necessarily ref lect the absence of cyanide toxicity. The almond odor may be masked by the odor of smoke in the case of smoke inhalation. LABORATORY FINDINGS

Hallmark laboratory findings in acute cyanide poisoning are metabolic acidosis with markedly elevated plasma

JOURNAL OF EMERGENCY NURSING

S13

CYANIDE SUPPLEMENT/Borron

TABLE 1

Clinical manifestations and laboratory abnormalities in acute cyanide poisoning2-4,13,14 Clinical manifestations

Early manifestations

. . . . . . . . . . .

Later manifestations

. . . . . . . .

Faintness Flushing Anxiety Excitement Drowsiness Vertigo Headache Dyspnea Perspiration Tachypnea Tachycardia Altered consciousness Tremulousness Seizure Respiratory depression Noncardiogenic pulmonary edema Respiratory arrest Cardiac arrhythmia Cardiovascular collapse

Laboratory abnormalities

Elevated plasma lactate

High venous oxygen concentration

Possibly indicative of cyanide poisoning: z8 mmol/L in pure cyanide poisoning, N10 mmol/L in smoke inhalation Possibly indicative of cyanide poisoning: arteriovenous oxygen saturation difference b10 mm Hg

lactate and excessive venous oxygenation (Table 1).2,10,16 Elevations in plasma lactate are caused by the shift of cyanide-poisoned cells from aerobic metabolism to anaerobic metabolism, which generates lactate as a toxic byproduct. Plasma lactate concentration normally ranges from 0.5 to 2.2 mmol/L. A concentration z8 mmol/L suggests the possibility of cyanide poisoning.2,10,16 However, elevated plasma lactate is not specific to cyanide poisoning and therefore does not definitively signify cyanide toxicity. For example, plasma lactate concentration is also elevated in cardiac arrest of any cause and in carbon monoxide

S14

poisoning,10 which, like cyanide poisoning, is common in smoke-inhalation victims. The elevation of lactate observed in pure carbon monoxide poisoning17 is generally less than that in cyanide poisoning such that markedly elevated plasma lactate in the setting of smoke inhalation is more suggestive of cyanide.

Severe or advanced cyanide poisoning is manifested by hypotension, seizures, coma, respiratory depression, cardiovascular collapse, and cardiorespiratory arrest. Based on the observation of a direct relationship between plasma lactate concentration and clinical indices of cyanide toxicity, plasma lactate concentration has been suggested as a marker of severity of cyanide toxicity both immediately after poisoning and during recovery.9,16 Plasma lactate may be inf luenced by factors other than cyanide toxicity in the critically ill patient.11 Plasma lactate concentration can be affected by seizures, apnea, cardiovascular failure, and endogenous or administered catecholamines.10 In one study, for example, the specificity of a plasma lactate concentration for a toxic blood cyanide concentration (z1.0 mg/L) was affected by whether or not catecholamines (e.g., epinephrine, norepinephrine, dobutamine, dopamine) had been given.16 Specificity was 85% in patients who had not been treated with catecholamines compared with 70% in the overall sample, which included both patients who had received catecholamines and patients who had not.

Hallmark laboratory findings in acute cyanide poisoning are metabolic acidosis with markedly elevated plasma lactate and excessive venous oxygenation. Excessive venous oxygenation, the second main laboratory finding in acute cyanide poisoning, is ref lected in a low (b10 mm Hg) arteriovenous oxygen saturation difference (Sa02-Sv02) on arterial and venous blood gas analysis.1 Excessive venous oxygenation is attributed to the inability of cells to extract and use oxygen from arterial blood.

JOURNAL OF EMERGENCY NURSING

32:4S

August 2006

CYANIDE SUPPLEMENT/Borron

Blood cyanide concentrations currently have only a confirmatory role in the initial management of acute cyanide poisoning because the results of standard assays are generally not available within the time required to initiate intervention.2 Although blood cyanide concentrations are not practical in initial management, they are used to confirm toxicity. Cyanide should be measured in whole blood because red blood cells concentrate cyanide more than other constituents of blood do.11 The usefulness of blood cyanide concentrations depends on early sampling and careful storage and analysis because of the rapid metabolism of cyanide, its instability in blood samples, and the vulnerability of cyanide assays to multiple sources of interference.11,18 For cyanide in whole blood, the toxicity threshold for cyanide alone ranges from 0.5 to 1.0 mg/L, and the lethal threshold ranges from 2.5 to 3.0 mg/L.2,7,9,10 DIAGNOSIS OF ACUTE CYANIDE POISONING

Given the absence of a point-of-care blood cyanide test that can rapidly confirm poisoning, acute cyanide poisoning is presumptively diagnosed based on index of suspicion and clinical presentation.11 Rapid loss of consciousness or development of coma and cardiovascular instability in the presence of elevated (N8 mmol/L) plasma lactate suggest the possibility of acute cyanide poisoning.2,10,16 Contextual clues to cyanide poisoning can provide pivotal diagnostic information when considered in conjunction with the clinical presentation.18 Information useful for assessing the possibility of cyanide poisoning includes the patient’s occupation, the patient’s mental status before poisoning, and the location and circumstances of the poisoning. Occupations with potential exposure to cyanide include laboratory scientists and technicians, metal workers and miners, aircraft workers, firefighters, exterminators, and fumigators. Exposure to fire smoke, in particular, increases the clinical suspicion of cyanide poisoning. Acute cyanide poisoning should be suspected in anyone who inhales smoke in a closed-space fire, particularly in the presence of soot in the mouth, altered mental status, and hypotension.2,6,19 Smoke-inhalation victims are likely to suffer concurrent cyanide and carbon monoxide poisoning.7 Although contextual clues such as exposure to fire smoke can be critical in diagnosing acute cyanide poisoning, the apparent absence of such clues does not exclude a

August 2006

32:4S

diagnosis. The relative ease of obtaining cyanide can facilitate concealment of contextual clues in cases of intentional poisonings such as suicide, murder, and terrorism. In recent poisonings, such as the March 5, 2006, suicide of a Minnesota State University student,20 individuals otherwise unlikely to be in a position to procure cyanide ordered it over the Internet. In the case of the 17-year-old described above,1 contextual clues available at the time of poisoning did not lead to suspicion of cyanide toxicity. The previously healthy victim with no history of depression was visiting a classmate’s house when he complained of feeling unwell and lost consciousness. Only after the window of opportunity for effective intervention had passed did investigators learn that the patient was poisoned by intentional adulteration of a beverage with potassium cyanide that the perpetrator had purchased via the Internet.

Acute cyanide poisoning is presumptively diagnosed based on index of suspicion and clinical presentation. Rapid loss of consciousness or development of coma and cardiovascular instability in the presence of elevated ( N8 mmol/L) plasma lactate suggest the possibility of acute cyanide poisoning. The challenges in recognizing acute cyanide poisoning could be heightened in multiple-victim events such as industrial accidents and terrorist attacks. A diagnosis could be missed if the nonspecific early symptoms of toxicity such as dizziness, weakness, diaphoresis, and hyperpnea are misconstrued as anxiety or mass hysteria, which are observed commonly in multiple-victim incidents.11 Conversely, manifestations of anxiety or panic could be misinterpreted as signs and symptoms of cyanide exposure.13 Symptoms of respiratory distress and other nonspecific findings in a possible mass-exposure incident should educe a search for other physical signs, such as mydriasis, altered mental status, or hemodynamic instability to increase confidence in the diagnosis. Point-of-care measurement of lactate might also help in eliminating panic as the etiology

JOURNAL OF EMERGENCY NURSING

S15

CYANIDE SUPPLEMENT/Borron

TABLE 2

Management of acute cyanide poisoning2,14 Measure

Termination of exposure

Supportive care

Antidotal treatment

Action

For inhalation exposure, removal of victim from site of exposure, using appropriate personal protective equipment . For exposure by ingestion, gastric lavage and activated charcoal unless contraindicated . For dermal exposure, decontamination of skin with soap and water Basic Life Support . 100% oxygen . Cardiopulmonary support or resuscitation Advanced Life Support . Sodium bicarbonate for metabolic acidosis . Anticonvulsants for seizures . Epinephrine for cardiovascular collapse . Cyanide Antidote Kit (amyl nitrite + sodium nitrite + thiosulfate) (not generally recommended in smoke-inhalation victims) . Hydroxocobalamin (proposed antidote in the United States; can be used regardless of suspected cyanide source, including fire smoke) .

although this diagnostic tool is unlikely to be available at the incident scene. Treatment of Acute Cyanide Poisoning

Acute cyanide poisoning is treated by terminating exposure and administering supportive care and antidotal therapy (Table 2).2,14 These aspects of care are discussed further in this supplement in Koschel’s article, Management of the Cyanide-Poisoned Patient. 21

reactivate mitochondrial enzymes inhibited by cyanide, and activate oxidative systems other than mitochondrial cytochrome oxidase.10,11 Administration of 100% oxygen is essential to effective treatment of concurrent carbon monoxide exposure. Advanced life support for acute cyanide poisoning includes endotracheal intubation for comatose patients, epinephrine infusion for cardiovascular collapse, sodium bicarbonate for metabolic acidosis and anticonvulsants for seizures.10 ANTIDOTAL THERAPY

DECONTAMINATION

Termination of cyanide exposure can entail removal of the patient from the contaminated environment in the case of inhalation exposure, removal of contaminated clothing and rinsing of the skin in the case of dermal exposure, and gastric lavage and administration of activated charcoal in the case of ingestion unless contraindicated.22 SUPPORTIVE CARE

Initial supportive care involves the basic life support airway, breathing, and circulation (ABC) triad.2,11 Administration of 100% oxygen is viewed as an important component of supportive care despite the fact that cyanide poisoning involves deficient oxygen utilization rather than deficient oxygen availability.11 It is hypothesized that increased oxygen delivery could increase respiratory excretion of cyanide,

S16

Several cyanide antidotes are available in one or more countries around the world, but the Cyanide Antidote Kit (CAK) is the only one currently available in the United States.23 The CAK is composed of amyl nitrite, sodium nitrite, and sodium thiosulfate. Amyl nitrite, available as perles, is given by inhalation, sometimes via a mechanical ventilation device to initiate methemoglobin formation before intravenous administration of sodium nitrite and sodium thiosulfate. The nitrites reduce blood cyanide concentrations by forming methemoglobin, to which cyanide binds with higher affinity than it binds cytochrome oxidase.10 Binding of cyanide to methemoglobin liberates cytochrome oxidase, which is necessary for aerobic cellular respiration. Another mechanism of action of nitrite therapy is generation of nitric oxide, which is also involved in cellular respiration.24 Sodium

JOURNAL OF EMERGENCY NURSING

32:4S

August 2006

CYANIDE SUPPLEMENT/Borron

thiosulfate enhances transformation of cyanide to less toxic thiocyanates, which are renally excreted.10 The potential for toxicity caused by the CAK is significant. At antidotal doses, sodium nitrite can cause profound vasodilation associated with syncope, hypotension, tachycardia, dizziness, and nausea and vomiting.25 Nitriteinduced methemoglobinemia, one therapeutic mechanism of amyl nitrite and sodium nitrite, reduces the ability of blood to transport oxygen to the cells.26,27 Nitrite-induced methemoglobinemia may be particularly dangerous for smoke-inhalation victims, who likely also have carboxyhemoglobinemia secondary to concomitant carbon monoxide poisoning.27-29 Like methemoglobinemia, carboxyhemoglobinemia reduces the ability of blood to transport oxygen to the cells. Nitrite-induced methemoglobinemia superimposed on carboxyhemoglobinemia from carbon monoxide exposure could lead to potentially fatal reduction in the oxygen-carrying capacity of the blood. Because of the potential for dangerous disruption of oxygen transport to the cells, the CAK is generally considered unsuitable for prehospital use in victims of smoke inhalation, the most common cause of cyanide poisoning.3,6,18 The Clinical Dilemma: to Treat or Not to Treat in the Context of an Uncertain Diagnosis

Successful treatment of acute cyanide poisoning is greatly enhanced by antidotal treatment. Supportive care alone impacts signs and symptoms but does not affect the body’s cyanide burden or the time course of cyanide in the body.10 In cases of suspected cyanide poisoning, the need for rapid administration of an antidote in the context of an uncertain diagnosis creates a predicament for the clinician deciding whether or not to administer the CAK. Use of the CAK entails the risk of causing harm to nonpoisoned patients if the presumptive diagnosis is incorrect. However, the consequences of failure to use the CAK because of an uncertain diagnosis include death if cyanide toxicity is present. In an attempt to improve the risk:benefit ratio in the antidotal treatment of cyanide poisoning, the vitamin B12 precursor hydroxocobalamin has been proposed for introduction in the United States. Hydroxocobalamin detoxifies cyanide by binding it to form vitamin B12, which is excreted in urine.10 First licensed as an antidote in France in 1996, hydroxocobalamin has been used safely

August 2006

32:4S

and effectively in both prehospital and hospital settings to treat acute cyanide poisoning associated with smoke inhalation, industrial exposure to cyanide gas, and ingestion of cyanide salts.12,15,30,31 Hydroxocobalamin has a favorable tolerability pro12,15,30,31 file. It does not impair blood oxygenation and seems to generally improve hemodynamic stability victims of cyanide poisoning. The most common side effects are caused by the red color of the compound: hydroxocobalamin is associated with transient pink discoloration of the urine and mucous membranes and may interfere with some colorimetric laboratory tests.12,15,30-33 These effects have limited clinical impact and typically resolve within a few days of administration of hydroxocobalamin. Transient elevations in blood pressure rarely requiring treatment may also occur after treatment with hydroxocobalamin.34 Hydroxocobalamin, like all medications, has been associated with occasional allergic reactions, primarily with long-term, lowdose use for applications other than cyanide poisoning.35,36 The apparently low risk of introducing significant harm with hydroxocobalamin could allow for more confident empiric treatment of acute cyanide poisoning than is currently possible in the United States and could enhance the feasibility of early prehospital treatment of suspected cyanide poisoning from all causes including smoke inhalation. Conclusions

Acute cyanide poisoning constitutes a formidable clinical challenge. The need for early intervention and the lack of a point-of-care test for confirming cyanide toxicity necessitate administration of antidotal therapy based on a presumptive diagnosis. Rapid presumptive diagnosis is difficult because of the relatively nonspecific nature of signs and symptoms. The differential diagnosis is broad. Cyanide poisoning should be considered in any individual with rapid loss of consciousness or development of coma and cardiovascular instability in the presence of elevated (N8 mmol/L) plasma lactate—especially in the presence of a recent history consistent with possible exposure. Altered mental status or hemodynamic instability after exposure to smoke in a structural fire, suggests the probability of cyanide poisoning. When cyanide poisoning is strongly suspected, rapid administration of an antidote is required.

JOURNAL OF EMERGENCY NURSING

S17

CYANIDE SUPPLEMENT/Borron

The decision to administer an antidote for presumptive cyanide poisoning involves consideration of the risk of antidote-induced toxicity as well as the risk of withholding treatment if cyanide poisoning is present. The introduction of hydroxocobalamin may help to improve the risk:benefit ratio in the antidotal treatment of cyanide poisoning in the United States. Acknowledgment The author acknowledges the assistance of Jane Saiers, PhD, in writing this manuscript. Dr. Saiers’ and the author’s work on this manuscript was funded by EMD Pharmaceuticals.

REFERENCES 1. Peddy SB, Rigby MR, Shaffner DH. Acute cyanide poisoning. Pediatr Crit Care Med 2006;7:79-82. 2. Dart RC, Bogdan GM. Acute cyanide poisoning: causes, consequences, recognition and management. Frontline First Responder 2004;2:19-22. 3. Gracia R, Shepherd G. Cyanide poisoning and its treatment. Pharmacotherapy 2004;24:1358-65. 4. Morocco AP. Cyanides. Crit Care Clin 2005;21:691-705. 5. Schnepp JR. Sources of human exposure to cyanide. J Emerg Med 2006;32(suppl):S3-7. 6. Walsh DW, Eckstein M. Hydrogen cyanide in fire smoke: an under appreciated threat. Emerg Med Serv 2004;33:160-3. 7. Alarie Y. Toxicity of fire smoke. Crit Rev Toxicol 2002;32:259-89. 8. Augustine JJ. Smoke and fire: recognizing cyanide as a toxic agent. fireEMS 2005;May:18-23. 9. Baud F, Barriot P, Toffis V, et al. Elevated blood cyanide concentrations in victims of smoke inhalation. N Engl J Med 1991; 325:1761-6. 10. Megarbane B, Delahaye A, Goldgran-Toledano D, Baud FJ. Antidotal treatment of cyanide poisoning. J Chin Med Assoc 2003;66:193-203. 11. Gracia R. Cyanide. In: Keyes DC, editor. Medical response to terrorism: preparedness and clinical practice Philadelphia: Lippincott Williams & Wilkins; 2005. p. 26Q37. 12. Borron S, Me´garbane B, Baud FJ. Hydroxocobalamin is an effective antidote in severe acute cyanide poisoning in man. Abstract. Int J Toxicol 2004;23:399-400. 13. Baskin SI, Rockwood GA. Neurotoxicological and behavioral effects of cyanide and its potential therapies. Mil Psychol 2002; 14:159-77. 14. Baskin SI, Brewer TG. Cyanide poisoning. Textbook of military medicine: medical aspects of chemical and biological warfare. Chapter 10. The Virtual Naval Hospital. Available from URL: www.vnh.org/MedAspChemBioWar/chapters/chapter_10.hrm. Accessed February 22, 2004. 15. Fortin JL, Ruttiman M, Domanski L, Kowalski JJ. Hydroxocobalamin: treatment for smoke inhalation-associated cyanide poisoning. Meeting the needs of fire victims. JEMS 2004;29(suppl): 18-21. 16. Baud FJ, Borron SW, Megarbane B, Trout H, Lapostolle F, Vicaut E, et al. Value of lactic acidosis in the assessment of the severity of acute cyanide poisoning. Crit Care Med 2002;30:2044-50.

S18

17. Benaissa ML, Megarbane B, Borron SW, Baud FJ. Is elevated plasma lactate a useful marker in the evaluation of pure carbon monoxide poisoning? Intensive Care Med 2003;29:1372-5. 18. Agency for Toxic Substances and Disease Registry. US Department of Health and Human Services, Public Health Service. Cyanide toxicity. Am Fam Physician 1993;48:107-14. 19. Koschel MJ. Where thereTs smoke, there may be cyanide. Am J Nurs 2002;102:39-42. 20. Anonymous. Mankato studentTs death ruled suicide. CBS Broadcasting Inc., WCCO.com News. March 15, 2006. 21. Koschel MJ. Management of the cyanide-poisoned patient. J Emerg Med 2006;32(suppl):S19-26. 22. American Academy of Clinical Toxicology, European Association of Poisons Centres and Clinical Toxicologists. Position statements: single-dose activated charcoal. Available from URL: http://www.clintox.org/Pos_Statements/Charcoal.html. Accessed April 2, 2006. 23. Sauer SW, Keim ME. Hydroxocobalamin: improved public health readiness for cyanide disasters. Ann Emerg Med 2001;37: 635-41. 24. Pearce LL, Bominaar EL, Hill BC, Peterson J. Reversal of cyanide inhibition of cytochrome c oxidase by the auxiliary substrate nitric oxide: an endogenous antidote to cyanide poisoning? J Biol Chem 2003;278:52139-45. 25. Baskin SI, Horowitz AM, Nealley EW. The antidotal action of sodium nitrite and sodium thiosulfate against cyanide poisoning. J Clin Pharmacol 1992;32:368-75. 26. Wananukul W, Kaojarern S. Acute cyanide poisoning: a case report with toxicokinetic study. J Med Assoc Thai 1992;75:304-9. 27. Hall AH, Kulig KW, Rumack BH. Suspected cyanide poisoning in smoke inhalation: complications of sodium nitrite therapy. J Toxicol Clin Exp 1989;9:3-9. 28. Jones J, McMullen MJ, Dougherty J. Toxic smoke inhalation: cyanide poisoning in fire victims. Am J Emerg Med 1987;5:317-21. 29. Becker CE. The role of cyanide in fires. Vet Hum Toxicol 1985; 27:487-90. 30. Borron SW, Barriot P, Imbert M. Hydroxocobalamin for empiric treatment of smoke inhalation-associated cyanide poisoning: results of a prospective study in the prehospital setting. Abstract. Ann Emerg Med 2005;46:S77. 31. Fortin JL, Waroux S, Ruttimann M, Astaud C, Kowalski JJ. Hydroxocobalamin for poisoning caused by ingestion of potassium cyanide: a case study. Abstract. Clin Toxicol 2005;43:731. 32. Curry SC, Connor DA, Raschke RA. Effect of the cyanide antidote hydroxocobalamin on commonly ordered serum chemistry studies. Ann Emerg Med 1994;24:65-7. 33. Gourlain H, Caliez C, Laforge M, Buneaux F, Levillain P. Study of the mechanisms involved in hydroxocobalamin interference with determination of some biochemical parameters. Ann Biol Clin 1994;52:121-4. 34. Forsyth JC, Mueller PD, Becker CE, Osterloh J, Benowitz NL, Rumack BH, et al. Hydroxocobalamin as a cyanide antidote: safety, efficacy and pharmacokinetics in heavily smoking normal volunteers. J Toxicol Clin Toxicol 1993;31:277-94. 35. Heyworth-Smith D, Hogan PG. Allergy to hydroxocobalamin, with tolerance of cyanocobalamin. Med J Aust 2002;177:162-3. 36. Branco-Ferreira M, Clode MH, Pereira-Barbosa MA, PalmaCarlos AG. Anaphylactic reaction to hydroxocobalamin. Allergy 1997;52:118-9.

JOURNAL OF EMERGENCY NURSING

32:4S

August 2006