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

Cyanide PoisoningToxicityAlthough generally considered to be very toxicsubstances when compared with other lethal chemicalwarfare agents, cyanides are among the least toxic.The LCt 50for HCN is generally stated to be 2,500 to5,000 mg•min/m 3 ; for cyanogen chloride, about 11,000mg•min/m 3 . (Comparable values for the nerve agentsare 10–200 mg•min/m 3 ; for sulfur mustard, 1,500mg•min/m 3 ; and for phosgene, 3,000 mg•min/m 3 .) 65The estimated intravenous dose of HCN for humansthat is lethal to 50% of the exposed population (LD 50)is approximately 1.0 mg/kg, and the estimated LD 50for liquid on the skin is about 100 mg/kg.DETECTION OF CYANIDE AND CYANIDE METABOLITESThe determination of cyanide, or its metabolitesthiocyanate and ATCA, in biological fluids is oftenneeded for forensics, clinical, research, or veterinarypurposes. Although the detection of cyanide andcyanide compounds in other matrices is important toindustrial, environmental, and research applications,it is not discussed in this chapter. This chapter willbriefly discuss the available techniques and identifyproblems in cyanide analysis. Analytical methods fordirect determination of cyanide and cyanide metabolitesin biological samples have been reviewed. 15,54,66,67Methods of analysis include spectrochemical absorptionor luminescence methods, 21,35,68–104 electrochemicalmethods, 68–76 capillary electrophoresis, 77,78 and gas 105–126or liquid chromatography techniques 127–149 coupledto a variety of detection techniques. The number ofliterature references (more than 200) that examinethe detection of cyanide and cyanide metabolites inbiological fluids can add to the difficulty in choosinga method. In addition, the numerous uncertainties anddiscrepancies in the literature have made comparisonand selection of a method complicated for the novice.Obviously the first decision will be whether to choosecyanide, one of its metabolites, or both as the substanceor substances to look for. Factors that influence thischoice are cellular absorption and detoxification kinetics,sampling and analysis time, sample storage timeand conditions, sample matrix, interferences, detectionlimits, available equipment and expertise, and budgetallowances.The analytical determination of cyanide and/or cyanidemetabolites before antidotal treatment providesa more accurate assessment of the severity of poisoningand insight into antidote dose levels (especiallybecause high doses of antidotes can also be toxic). 19,79,80However, no available method is simple, accurate, andfast enough to justify waiting for test results beforeantidotal treatment is administered (ie, cyanide can killfaster than the analysis can be performed). Measurementof cyanide and its metabolites may have diagnosticor therapeutic value when sublethal; minimallyor moderately symptomatic exposure is part of thedifferential diagnosis. In addition, biological samplesshould be assessed for confirmation or refutation of aputative diagnosis of cyanide intoxication.Blood has been the biological sample of choicewhen determining cyanide concentrations. However,cyanide is rapidly removed from blood by detoxificationprocesses, binding to proteins and enzymes thatcontain metal centers or heme moieties, or sequesteringin other favorable cellular entities. 21,40,67,81–92 Cyanidecharacteristics 93,94 suggest that a biological sampleshould be collected quickly, and analysis should beperformed as soon as possible. If analysis of cyanidecannot be performed quickly, then the sampling andstorage of biological samples for later testing shouldconsider the following:• Cyanide resides mainly in erythrocytesrather than plasma. Cyanide in blood primarilyresides in erythrocytes (red bloodcells) 40,82,89–92,95 by binding to methemoglobin,forming cyanomethemoglobin, but may alsobe present in plasma, especially if cyanideconcentrations exceed erythrocyte concentrations.40,82,89 Test results are improved by workingwith whole blood that is not coagulated.Heparinized vials should be used in the collectionof the blood sample for determinationof cyanide concentration. Containers thatcontain anticoagulants such as heparin andethylenediaminetetraacetate (EDTA) helpprevent clotting and also ensure efficientharvesting of plasma after the blood has beencentrifuged. Lundquist et al demonstratedthat the cyanide binding capacity of erythrocytesdue to methemoglobin increased from89,000 nM to 517,000 nM upon addition ofsodium nitrite. 82• Cyanide may evaporate because of HCNvolatility at the physiological pH, and cyanidenucleophilic action should be reduced.The next considerations should be reducingthe evaporation and loss of cyanide frombiological samples and preventing nucleophilicreactions. Using tightly sealed vials,377