Medical Aspects of Chemical Warfare (2008) - The Black Vault

Medical Diagnosticsurine samples. The blood assay for both bound and freeCVAA will potentially provide a longer opportunityfor retrospective confirmation of exposure (based onone animal study), but also indicates a substantialdecrease (90%) in concentration levels observed overa 10-day period.CYANIDEBackgroundCyanide is an important industrial chemical that hasmany uses. It is produced in large quantities across theworld and people are exposed to cyanide in a varietyof ways. Many plants, including cassava roots, limabeans, and bamboo shoots, contain small amountsof cyanogenic glycosides. 131–133 Polymers that containcarbon and nitrogen release cyanide when burned.For example, large amounts of cyanide can be releasedduring house and forest fires and from tobacco smoke(100–1600 parts per million [ppm]). 131 Some drugs alsocontain cyanide or have active ingredients that areconverted to cyanide in the body, including sodiumnitroprusside, which is given for the critical care ofhypertension. 131 Synonyms for hydrogen cyanide(HCN) include prussic acid, formic anamminide, andfromonitrile. Deaths due to cyanide intoxication areusually due to the inhalation of HCN or the ingestionof cyanide salts. The signs of cyanide poisoning includeheadache, nausea, vomiting, tachypnoea, dyspnoea to131, 134–137convulsion, unconsciousness, and death.Cyanide in the Human BodyCyanide, the CN- ion, exists as HCN in the body atphysiological pH. The mechanism of cyanide toxicityis believed to be the inactivation of iron III (ferric)enzymes in the body. The inhibition of cytochromeoxidase, which disrupts mitochondrial oxidativephosphorylation, is thought to be the most importantmechanism for cyanide toxicity. 131, 138–141 Cyanide alsobinds to the hemoglobin in erythrocytes. 142 The bindingof cyanide to iron III enzymes and proteins isreversible. 140,141At low concentrations, 93% to 99% of total cyanideis bound to methemaglobin (metHb) in the erythocytes.131 The metHb is the deoxygenated iron III formof hemoglobin. Cyanide has a very high affinity tometHb and a low affinity to the oxygenated form ofhemoglobin. Usually less than 1% of the total hemoglobinis in the metHb form, so at increased concentrationsof cyanide in the blood, a larger amount isfound in the serum. In tissue, cyanide binds to theheme group in mitochondrial cytochrome oxidaseand inhibits electron transport. 140,141 All tissues are affectedby this enzymatic inhibition, but especially thosethat require high amounts of oxygen and adenosine5’-triphosphate. Other proteins and enzymes are alsoaffected by cyanide, such as superoxide dismutase andxanthine oxidase, and may also contribute to cyanide’stoxic effects. 131Cyanide’s metabolism in the body is very rapid andcan occur at 0.017 mg/min/kg. 131 The most commonform of metabolism is the conversion to thiocyanate(SCN - ), which is then excreted via the kidneys. 143,144 Themitochondrial enzyme rhodanese (thiosulfate sulfurtransferase) is thought to be the main catalyst for theformation of SCN - , but β-mercaptopyruvate-cyanidetransferase can transform cyanide to SCN - through adifferent route. 141,145 The conversion to SCN - is thoughtto be limited by the amount of thiosulfate. Cysteine,cystine, GSH, and β-mercaptopyruvic acid can also besulfur sources. 131, 141,145 The reaction with cystine is alsoan important pathway leading to 15% of the total cyanidedose excreted in the urine as 2-iminothiozoline-4-carboxylic acid. 144 Other elimination pathways are theexhalation of HCN and oxidation to cyanate and reactionswith vitamin B 12to form cyanocobalamin. 146Analytical MethodsSeveral matrices have been used to assess cyanideexposure. Whole blood is the most common, but measurementshave been made in serum, plasma, saliva,tissues, gastric aspirate, and urine.Whole BloodWhole blood has been the matrix of choice, thus far,to determine cyanide exposure in humans. However,there are problems associated with cyanide and SCN -measurements in blood. Sample collection, storage,and preparation are very important. Different levelsof cyanide have been found in samples collected fromdifferent vessels (venous, arterial, and ventricular).Different whole blood samples can contain differentamounts of metHb, which has a high affinity to cyanide.Also, free HCN may be more important becauseit is the form that reacts with cytochrome oxidase andcauses the most significant adverse health effects. 131Storage of the whole blood is also critical but not wellunderstood. Some studies have shown an increase incyanide of up to 40% upon storage of whole blood for1 week and a 14% increase after 1 day at 4°C, whileothers have shown a decrease of 20% to 30% within 1731