Background
Cyanide has historically been an uncommon warfare agent; however, its lethality and availability worldwide make it a realistic and potential agent of terrorism. Cyanide was found in the Tokyo subway after the Sarin attacks3,4 and reported to have possibly been a contaminant in the explosives of the World Trade Center bombing in 1993.5,6 Cyanide is most likely to be employed in the volatile, water soluble, and liquid forms of hydrogen cyanide (AC) and cyanogen chloride (CK). The reactive salt forms of cyanide (potassium, sodium, and calcium cyanide) are also used in industry and produce hydrogen cyanide (HCN) gas when mixed with an acid. Cyanide is highly volatile and readily transforms from liquid to the potent gas form (HCN). HCN is released by pyrolysis of synthetic polymers such as burning plastics and may be released in structural fires. Because it is lighter than air, it disperses quickly in open spaces. Cyanogen chloride, however, is heavier than air and thus is a more persistent agent.
Signs and symptoms
Cyanide can cause symptoms within seconds to minutes of inhalational exposure. While it is classified as a blood agent, the early symptoms are cardiotoxicity and central nervous system (CNS) effects. The initial symptoms can be non-specific and transient. Dizziness, headache, weakness, diaphoresis, and dyspnea are all possible and leave a broad differential diagnosis. The well-described odor of bitter almonds is not a reliable sign as many cannot detect the odor. The hallmark clinical presentation that leads to diagnosis is tissue hypoxia without cyanosis (pulse oximetry may be normal) with the finding of metabolic acidosis. Without rapid treatment, the patient is likely to rapidly progress to coma, hemodynamic compromise, arrhythmias, seizures, secondary cardiac arrest, and eventually death.
Decontamination
Victims exposed to cyanide should be rapidly removed from the location of exposure while ensuring that the rescuer is protected. For gas exposure, evacuating from the location and then removing all clothing addresses the majority of decontamination. Further decontamination with irrigation solutions can be done, but treatment with antidote is the first priority and should not be delayed.
Diagnostics
Prompt diagnosis to facilitate treatment is essential. However, in a tactical environment, the availability of diagnostic adjuncts is limited. Cyanide levels are not rapidly available and not useful in the acute phase of care. The clinical picture coupled with arterial blood gas demonstrating metabolic acidosis and very high lactate levels should alert the clinician to possible cyanide exposure.7 This can be an extremely challenging diagnosis in the setting of trauma with massive hemorrhage and hypovolemic shock. Thus a high index of suspicion and awareness of intelligence indicating risk of exposure are key to early diagnosis. Drawing an arterial and venous blood gas at the same time and comparing the oxygen content can be helpful. “Arterialization of venous blood” (similar color/PaO2 of samples) can help round out the clinical picture. From a practical standpoint, it is unlikely that the provider will have diagnostic support in the hot or warm zone, so the decision to treat will be entirely clinical. Fortunately, with the availability of hydroxocobalamin (discussed in detail below), the side effects of empiric administration of the antidote are minimized when compared to the previously used cyanide antidote kit.
Treatment
The mainstay of treatment is antidote therapy with hydroxocobalamin. Attention to supportive care is a critical part of the resuscitation. Airway management, intravenous access, and cardiac monitoring can support a cyanide-poisoned patient. Supplemental oxygen is beneficial and may enhance antidote efficacy and promote cyanide respiratory excretion along with other metabolic processes. Historically, cyanide was treated with the cyanide antidote kit consisting of amyl nitrite, sodium nitrite, and sodium thiosulfate. The nitrites induce methemoglobinemia, as a side effect which may be detrimental in a patient with concomitant trauma. The preferred antidote is now hydroxocobalamin (Cyanokit ®). However, if hydroxocobalamin is not available, the cyanide antidote kit can be used. An inhaled ampule of amyl nitrite can be a temporizing measure until IV/IO access is established.
Hydroxocobalamin (vitamin B12a) acts as a chelating agent and binds with cyanide to form cyanocobalamin (vitamin B12). The dose of hydroxocobalamin for cyanide toxicity is much higher than the dose used for other therapeutic indications, therefore the commercially prepared hydroxocobalamin is needed to get the optimal dose without volume overload: 5gm IV (70mg/kg in pediatric patients) over 15 minutes. The dose can be repeated for severe toxicity or inadequate response to the initial dose. It is as effective as epinephrine in the setting of cardiac arrest from cyanide. It may cause a red discoloration of the skin and urine that persists for several weeks. Other side effects are mild. The decision to administer hydroxocobalamin within the hot or warm zone has to be weighed against the tactical risk of stopping to gain IV or IO access and establishing the infusion.
Other treatment regimens as well as prophylactic measures have been explored in the literature and are summarized in the table below.
