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

Cyanide PoisoningDose (mg/kg)16.014.012.010.08.06.04.02.00.0BSA 6 mL/m 2BSA 7 mL/m 2BSA 8 mL/m 24 mg/kg6.7 mg/kg10 mg/kg00.5 11.5 22.5 3 4 5 6 7 8 9 101112131415Age in YearsFig. 11-5. Body surface area versus weight dosing. This figuredescribes the relative dose in mg/kg when charted againstmedian weight and height for age. These data illustratewhy the authors propose that dosing children with sodiumnitrite at greater than the package insert recommended 6.6mg/kg is excessive and potentially harmful. Curves weredrawn after converting to dose per body surface area using50th percentile for weights and length/stature, based on theCenters for Disease Control and Prevention 2001 weightfor-agepercentiles, ages birth to 36 months and ages 2 to 20years. For conversion purposes, 4 mg/kg is equivalent to0.13 mL/kg of 3% solution, 6.6 mg/kg is 0.2 mg/kg of 3%solution, and 10 mg/kg is 0.33 mL/kg of 3% sodium nitritesolution. Body surface area calculated using the DuBois andDuBois formula.BSA: body surface areaChart: Courtesy of MAJ Thomas B Talbot, US Army MedicalResearch Institute of Chemical Defense, Aberdeen ProvingGround, Md.The awareness that carbon monoxide has thedominant effect on time of survival, but that bothcarbon monoxide and HCN, when present, appearto synergistically affect hypoxic fatality, guides somegeneral recommendations. Oxygen, general supportivemeasures, and burn and trauma management aregenerally indicated, with high benefit-to-risk ratios.Analysis for carboxyhemoglobin, lactic acidosis, oxygenation,and HCN levels should be accomplished atthe earliest opportunity. HCN-specific treatment maybe a reasonable option for severely affected smokeinhalation victims who have been properly stabilizedotherwise. Thiosulfate is reasonable, effective, andsafe, and appropriate for mass casualty situations. Itdoes not diminish oxygen carrying capacity and iswidely available; however, it does require a parenteralline be established. Hydroxocobalamin is alsoreasonable, effective, and safe. It is typically used withthiosulfate, and it does not diminish oxygen carryingcapacity. It does require a parenteral line. Amyl nitriteis reasonable and effective; it does not require parenteralaccess and can be given to persons on supportedventilation. It does reduce oxygen carrying capacitymodestly. Because treatment requires close monitoringfor hypotension, amyl nitrite is not the first choice ina mass casualty situation. Similarly, sodium nitrite iseffective and likely reasonably safe if a high level ofoversight is available. 190 The other antidotes describedin this chapter have demonstrated general effectivenessagainst cyanide poisoning but not necessarilyagainst fire exposures. They also require parenterallines and substantially more monitoring because oftheir side effect profiles.In summary, clinical management of cyanide intoxications,regardless of the victim’s age or sourceof intoxication, is based on early recognition, aggressivegeneral support measures, and early antidotalenhancement for severely ill persons otherwise atrisk for hypoxic injury. In the absence of history ofcyanide exposure, clinicians have to proceed withouta confirmed diagnosis, maintaining high levels ofawareness for adverse effects of therapy and changesin clinical course. Successful acute intervention mustbe followed with sustained care directed at underlyingcauses of intoxication and detection of delayedsequelae.CYANIDE-CAUSED CARDIAC TOXICITYHistopathologic ChangesCyanide is deposited heterogeneously in cardiactissue, with the ventricles heavily affected. The resultinghistological changes include cell swellingand hemorrhaging. 193 Cell swelling activates chloridemembrane currents, as part of the ionic derangement,changing the homeostasis of the tissue. Substratechanges include formation of lactic acid and secretionof catecholamines.One of the first manifestations of the changed electrophysiologyis bradycardia, which may soon changeto torsade de pointes and possibly culminate in ventricularfibrillation (Figure 11-6). Katzman and Penneyand Wexler et al provide additional details. 194,195On the cellular level, changes in the ion concentrationsbecome important, especially calcium overloadof the cell and increase in the extracellular potassiumconcentration, [K + ] o. The cell’s energy homeostasis 196is profoundly disturbed, and several compensatorymembrane currents are activated and others diminished.Three of the most important ones are the ATP-391