Table Of Content

CYANIDE The deadly terror weapon that every EMS provider must know about by Robert A. De Lorenzo, MD, FACEP You’re dispatched to a hotel downtown that’s hosting a high-school prom in one of its ballrooms. On arrival, you observe well-dressed attendees doubled over near the curb vomiting and gasping for air. As you exit your unit, you see bodies littering the steps leading to the hotel’s interior. Something is very wrong. You call for assistance and reposition your unit one block from the scene. As you relocate, panicked bystanders scream at you for leaving. This scene, unlike anything you’ve ever witnessed, is your foray into the deadly world of cyanide terrorism. Cyanide, a deadly poison found throughout industry and manufacturing sectors, looms as a potential terrorist threat. As little as 7 grams of the compound can prove lethal to one individual if ingested. (To put it in perspective, a nickel weighs about 5 grams.) Cyanide concentrations as low as 2.5 parts per million (ppm) can be rapidly fatal. (Inhaled carbon monoxide requires a concentration of 500 ppm or greater to achieve similar lethality.) Each year, thousands of tons of cyanide are manufactured and shipped throughout the world. Manufactured cyanide is a byproduct of plastic combustion, making it an important toxin to be aware of in smoke inhalation cases. The natural compound also can be found in small quantities in the pits of cherries, peaches and apricots. Several countries manufacture cyanide as a potential chemical warfare agent. Because it is easy to make, buy or steal, cyanide poses a significant terrorist threat of mass destruction. Self-styled, budget-conscious terrorist splinter groups that lack large bankrolls or sophisticated weaponry seem particularly interested in cyanide Jems Magazine -- Online Content http://www.jems.com/jems/f0110a.html (1 of 9) [5/16/2002 9:49:36 PM] SITE INDEX capabilities. The combination of the widespread legal use of cyanide in manufacturing in combination with the terrorist appeal makes it imperative that EMS providers be familiar with the recognition and treatment of cyanide casualties. This article reviews the history, potential threat, clinical recognition and management of patients exposed to cyanide. We also discuss self-protection and decontamination principles. History In World War I the French used some 4,000 tons of cyanide as chemical weapons (although to little military effect). Before and during World War II, Japan allegedly used cyanide against China. And the United States kept a stockpile of cyanide munitions during that period as well. In the 1980s, Iraq reportedly used cyanide against the Kurds. Several chemical-weapons-use bans treaties have been signed this century. The latest one, signed in 1997 by most nations of the world, banned stockpiling, manufacturing and using all chemical weapons—including cyanide.(1) From a military standpoint, such treaties offer some degree of assurance that chemical weapons will not be used on future battlefields. Unfortunately, as the risk of military use of chemical agents declines, the risk of terrorist attacks rises. Example: In 1995, a terrorist group manufactured and used the nerve agent sarin on a Tokyo subway, injuring more than 4,500 people and killing 12. Sarin is technically more difficult to make and handle than cyanide. This leads some experts to believe that we can expect terrorist attack using cyanide in the future. Properties of cyanide In its simplest form, cyanide is a compound containing carbon and nitrogen. You’ll see this depicted in chemical shorthand as -CN. Normally, the carbon-nitrogen anion (a negatively charged ion) bonds to a cation (a positively charged ion), such as hydrogen, sodium or potassium: HCN NaCN KCN In some cases cyanide forms part of a larger organic compound, which is liberated by an enzymatic breakdown in the body. These compounds are sometimes referred to as cyanogens. For purposes of likely terrorist threats, hydrogen cyanide and cyanogen chloride are the prototypical agents of interest. Physical properties of cyanide are depicted in Table 1. Jems Magazine -- Online Content http://www.jems.com/jems/f0110a.html (2 of 9) [5/16/2002 9:49:36 PM] Table 1: Physical Properties of Cyanide Compounds Agent Vapor density (air=1.0) Freezing point ¾C Boiling point ¾C Volatility at 25¾C Hydrogen cyanide (AC) 0.99 -13.3 25.7 1,080,000 Cyanogen chloride (CK) 2.1 -6.9 12.8 2,600,000 As chemical warfare agents go, cyanide is fairly volatile. It has a propensity to evaporate to the vapor phase. It’s usually stored as a liquid, but presents a vapor hazard when deployed as a rapidly evaporating aerosol. Thus, highly lethal concentrations can develop rapidly from aerosolized cyanide liquid, but these vapors also have a tendency to disperse rapidly. Closed spaces (rooms, auditoriums, malls) delay the dispersal of cyanide for up to several hours, but open spaces allow rapid dispersal (as short as a few minutes). Warm temperatures, too, increase vaporization and dispersal. Toxicology Cyanide is a toxin that directly poisons the cellular respiratory mechanism, leading to cellular hypoxia and death. Cyanide acts quickly: Serious symptoms begin 30 to 45 seconds after an exposure. Cyanide can enter the body through the respiratory tract, gastrointestinal tract or the skin. By far, the respiratory tract is the most efficient port of entry, and cyanide vapor represents the greatest threat to victims and rescuers alike. The relative toxicities of cyanide are shown in Table 2. LD50 refers to the dose that is consistently fatal to 50% of victims, and LCt50 refers to the product of concentration and time (duration) of vapor exposure consistently fatal to 50% of victims. Jems Magazine -- Online Content http://www.jems.com/jems/f0110a.html (3 of 9) [5/16/2002 9:49:36 PM] Table 2: Toxicity Profile of Cyanide Agent Skin exposure Oral exposure Respiratory exposure Hydrogen cyanide (AC) LD50, mg/kg 100 LD50, mg/kg 100 LCt50, mg.min/m3 2500–5000 Cyanogen chloride (CK) NA NA 11,000 LD50 is the dose that is lethal to 50% of exposed individuals. LCt50 is the product of concentration and exposure time that is lethal to 50% of exposed individuals Once cyanide enters the body, it is rapidly distributed by the blood (hence the misnomer “blood agent,” which incorrectly assigns cyanide’s site of action as the blood) and reaches the body’s cells. The heart and brain are the organs most sensitive to cyanide, thanks to the high metabolic requirements of their tissues.(2) Inside the cell, cyanide bonds to and deactivates the critical enzyme cytochrome a3. Cytochrome a3 is involved in the utilization of oxygen, and virtually all cells depend on it. Because cyanide so effectively inhibits cellular respiration, the cell immediately begins to starve for oxygen and die. No amount of supplemental oxygen can overcome this deficit in affected cells. (However, supplemental oxygen is still important to maximize oxygen delivery to as yet unaffected cells.)(2) Thus cyanide causes profound cellular hypoxia despite adequate blood oxygen saturation. Cellular and organ death ensue within minutes unless immediate intervention occurs. Cyanide also shows an interesting bi-modal outcome following exposure. High concentrations usually result in death while low exposures often lead to eventual recovery—even without medical care. This “all-or-nothing” phenomenon has important implications for triage and treatment, as we discuss later. However, a subset of exposed victims will benefit from out-of-hospital intervention. Signs & symptoms Within 15 seconds after inhaling a high concentration of cyanide, the victim experiences hyperpnea or rapid respirations. Unconsciousness and seizures occur 15 to 30 seconds later, and respirations cease two to three minutes later. Death occurs approximately six to eight minutes following exposure. This rapid onset characterizes inhalation of a high concentration. Victims of Jems Magazine -- Online Content http://www.jems.com/jems/f0110a.html (4 of 9) [5/16/2002 9:49:36 PM] high cyanide concentrations literally “die in place.” Ingestion or skin exposure or low inhaled concentrations progress similarly but at a much slower rate. This provides a good opportunity for intervention.(2) In lower exposure cases, the general symptoms of hypoxia dominate: anxiety, apprehension headache, weakness, nausea and vomiting. With prolonged exposure, this may progress to unconsciousness, seizures, apnea and death. Physical findings of mild-to-moderate cyanide exposure also reflect hypoxia, dyspnea and respiratory distress. Vital signs reflect tachycardia and tachypnea. The cherry red color classically ascribed to cyanide poisoning is unreliable as a symptom and often not present. Similarly, the bitter almond odor supposedly detectable on the breath of cyanide victims is unreliable because 50% of the population can’t smell this odor. Serious cyanide exposures present with unconsciousness and seizures, and severe respiratory distress or apnea likely will be present. Management Victims of high cyanide concentrations will likely die before help reaches them. Lower concentrations of vapor or oral and skin exposures, however, provide an opportunity for effective out-of-hospital intervention. If involved in a cyanide incident, you will most likely be called on to focus your prehospital management efforts on these patients. Medical care for cyanide poisoning victims consists of a two-pronged attack: airway and breathing control and antidote therapy. Airway/breathing support maximize oxygen delivery to unaffected cells, while antidotes counteract cyanide’s lethal effects. Both are important, and neither is likely to be successful if used alone.(3) Once you determine that the scene is safe and establish a patient’s responsiveness, open their airway manually. If breathing is inadequate, perform positive pressure ventilation using a bag-valve mask. Mouth-to-mouth or mouth-to-mask ventilation is contraindicated due to the small risk of off-gassing cyanide from the victim’s expired breath. Oral or nasal airways may help maintain an open airway. However, definitive airway control is best accomplished through orotracheal intubation. All cyanide-exposure victims should receive high-flow oxygen. If breathing is adequate, use a non-rebreather mask. If inadequate, provide high-flow oxygen using a concentrator attached to the bag-valve mask. Jems Magazine -- Online Content http://www.jems.com/jems/f0110a.html (5 of 9) [5/16/2002 9:49:36 PM] Once you ensure the patient’s airway and breathing, move rapidly to antidotal therapy. The current antidote for cyanide is the two-stage administration of a nitrite and a thiosulfate.(3) Nitrite causes the iron in hemoglobin (Hgb) to convert to the trivalent (Fe 3+) form called methemoglobin (Met-Hgb). Hgb + nitrite >> Met-Hgb Methemoglobin has a high affinity for cyanide and can actually draw the poison off the cytochrome a3 and out of the cells. Met-Hgb + cyanide >> CN-Met-Hgb The cyanide-methemoglobin complex is still toxic (but less so than cyanide bound to cytochrome a3) and must be detoxified by thiosulfate. CN-Met-Hgb + thiosulfate >> thiocyanate + Met-Hgb The relatively nontoxic thiocyanate formed is then excreted by the kidneys. Methemoglobin gradually returns to normal hemoglobin through natural processes. Two nitrites are available for clinical use: amyl nitrite and sodium nitrite. Amyl nitrite is available in ampules for inhalation. An ampule is crushed, and the patient inhales the vapors. Place the ampule in the non-rebreather or bag-valve mask oxygen reservoir/concentrator. Avoid dropping the ampule in the patient’s mouth and causing airway obstruction. The advantage of amyl nitrite is that therapy can begin immediately—even before IV access is established. If an IV is available, administer sodium nitrite as a 300 mg slow IV push.(4) (The pediatric dose is six to 10 mg/kg up to 300 mg.) It is not necessary to use inhaled amyl nitrite if an IV has been established and sodium nitrite can be quickly administered. Immediately following sodium nitrite administration, inject sodium thiosulfate 12.5 gm slow IV push. (The most common dosage for pediatric poisonings is 250-400 mg/kg. Because the drug is available as a 25% concentration, this works out to approximately 1-1.65 mL/kg) Use 5 ml of sodium thiosulfate for each ml of sodium nitrite. Do not use sodium thiosulfate unless a nitrite has already been administered to the patient, because it does not work by itself. Don’t expect rapid or dramatic improvement from antidotal therapy. Instead, expect to see gradual improvement over minutes to hours. Continue supportive care including high-flow oxygen, adequate ventilation and warming the patient. Jems Magazine -- Online Content http://www.jems.com/jems/f0110a.html (6 of 9) [5/16/2002 9:49:36 PM] Nitrite therapy has risks. Vasodilation and hypotension are common and should be anticipated. Treat severe hypotension (systolic BP<80 in an adult) with IV normal saline boluses. Life-threatening methemoglobinemia (a clinical condition in which more than 1% of hemoglobin in blood has been oxidized to the ferric form) is also possible. Methemoglobin, an inefficient oxygen-carrying molecule, can cause severe hypoxia. Thiosulfate has relatively few side effects when compared to nitrites. Amyl nitrite ampules, sodium nitrite (10 ml) and sodium thiosulfate (50 ml) are available in the Pasadena cyanide antidote kit (formerly the Lilly Kit), which can be ordered through any pharmaceutical distributor. Amyl nitrite has abuse potential because it can be inhaled to cause euphoria and must be properly secured. A safer alternative to conventional antidotes may be on the horizon: hydroxocobalamin. Related to vitamin B12, hydroxocobalamin is free of most serious side effects. It is available in Europe and may be approved in the United States within a few years. Triage The most challenging decision in suspected cyanide poisoning remains whether to initiate antidotal therapy. Because current antidotes pose some risk to the patient, consider the decision carefully. Unfortunately, there is often little immediate and solid evidence of a cyanide attack.(5) Helpful clues include information from attack warnings, multiple casualties succumbing in rapid succession and compatible signs and symptoms. Triage decision-making in mass casualty incidents takes advantage of the all-or-nothing phenomenon of cyanide poisoning.(1) Pulseless or apneic casualties have little chance of survival and should be classified as expectant (lowest priority). Casualties who are ambulatory require little treatment beyond bringing them to fresh air. Consequently, they may be categorized as minimal (low priority). Consider casualties with moderate symptoms as delayed (intermediate priority). A casualty who is acutely affected but still breathing and who has a pulse would likely benefit from antidotal therapy and should be considered immediate (highest priority). Such casualties include those suffering seizures and severe respiratory distress. Decon & personal protection All victims of cyanide attack require decontamination. Fortunately, cyanide is relatively volatile and evaporates quickly, making decontamination relatively easy.(5) All standard hazmat procedures Jems Magazine -- Online Content http://www.jems.com/jems/f0110a.html (7 of 9) [5/16/2002 9:49:36 PM] for patient decontamination apply to cyanide. No discussion of cyanide or any other hazardous material is complete without mentioning personal protective equipment (PPE). The usual hazmat principles of PPE apply equally well to cyanide. In fact, because cyanide and related compounds are a common industrial and fire-ground toxin, all rescue personnel should already be familiar with PPE for cyanide exposure. All people entering an area that has potentially been contaminated by cyanide need full protection against contact and inhalation, ideally a level A or B positive-pressure, self-contained breathing apparatus and full-body ensemble.(6) However, even a level C ensemble specially designed to work in a cyanide-contaminated area can be effective. The military uses such a system, which consists of a charcoal-impregnated body suit, butyl rubber gloves, vinyl boots and a well-fitted mask and hood. No matter what equipment is chosen, prehospital providers must be thoroughly familiarized with its use. Frequent drills are a critical component of preparation against a cyanide attack. Make sure decon personnel are all properly dressed and protected before starting the decon process. Once the patient has arrived at the decontamination station, remove all their clothing carefully and systematically to avoid the spread of contamination. If the victim is wearing a protective mask, remove it last and only in a safe atmosphere (cold zone). Copious water and mild detergent are effective dilute decontaminants. The biggest drawback to this method is the large volume of water needed and the necessity of containing and disposing of the waste water. The military standard method consists of using a hypochlorite solution. A 5% (straight household bleach) solution is used on equipment (except masks), while a dilute 0.5% solution is used on the patient’s skin and protective mask. Because you won’t always know what type of chemical warfare agent is involved, use hypochlorite because it can neutralize virtually all chemical and biological agents. For optimal effectiveness, use hypochlorite in contact with the suspected chemical agent for at least 10 to 15 minutes. Because chlorine evaporates rapidly, mix fresh hypochlorite solution each time it is used for decontamination. Never decontaminate eyes with hypochlorite solution. Instead, use normal saline, Ringer’s lactate or plain water. Conclusion Cyanide represents a deadly terrorist threat. Its ease of manufacture, plus the widespread availability in industry make it Jems Magazine -- Online Content http://www.jems.com/jems/f0110a.html (8 of 9) [5/16/2002 9:49:36 PM] an attractive terrorist weapon. By understanding the mechanism of toxicity, symptoms and treatment of cyanide exposure, prehospital providers can mitigate the threat. Prehospital care is focused on airway and breathing control and early use of antidotes. Of course PPE and decontamination are important elements in the overall response to a cyanide incident. Robert A. De Lorenzo, MD, FACEP, a major in the U.S. Army, is a national expert on tactical and operational EMS. He has authored numerous EMS and emergency medicine articles and two books: Tactical Emergency Care and Emergency Care: Weapons of Mass Destruction. Disclaimer: The opinions or assertions contained herein are solely those of the author and do not necessarily reflect the official views of the Army Medical Department or the Department of Defense. References 1. Medical Management of Chemical Casualties, second edition: Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Md., 1995. 2. Zajtchuk R, Bellamy RF: Medical Aspects of Chemical and Biological Warfare. Department of the Army, Office of the Surgeon General, Washington, D.C., 1997. 3. Field Manual 8-285, Treatment of Chemical Agent Casualties and Conventional Military Chemical Casualties. Department of the Army, Washington, D.C., 1995. 4. Field Manual 8-9, NATO Handbook on Medical Aspects of NBC Defensive Operations, Department of the Army, Washington, D.C., 1996. 5. Field Manual 3-5, NBC Decontamination. Department of the Army, Washington, D.C., 1993. 6. Borak J, Callan M, Abbott W: Hazardous Materials Exposure. Brady, Englewood Cliffs, N.J., 1991. top Jems Magazine -- Online Content http://www.jems.com/jems/f0110a.html (9 of 9) [5/16/2002 9:49:36 PM]