Cyanide Toxicity & Hydroxocobalamin

Cyanide ($CN^-$) is a rapidly lethal cellular poison that diffuses instantly across cell membranes and binds with high affinity to the trivalent ferric ($Fe^{3+}$) iron atom of cytochrome c oxidase (complex IV) within mitochondria. This immediately blocks the terminal step of the electron transport chain, arresting oxidative phosphorylation. Cells can no longer utilize oxygen to generate ATP, forcing an immediate, desperate shift to anaerobic glycolysis. Lactic acid is produced in massive quantities, generating profound high anion gap metabolic acidosis (HAGMA) within minutes.

Because tissues cannot extract oxygen from circulating capillaries, venous blood returning to the heart remains fully oxygenated. This produces arterialization of central venous blood (bright red retinal veins on fundoscopy, high central venous oxygen saturation [$ScvO_2 > 90\%$], and a narrowed arterial-venous oxygen gradient).

In residential and industrial structure fires, combustion of synthetic polymers, plastics, polyurethanes, wool, and silk releases large quantities of hydrogen cyanide gas ($HCN$). In acute smoke inhalation, laboratory cyanide assays take days to return; bedside decisions must be made empirically. A plasma lactate concentration $\ge 8$ to $10\text{ mmol/L}$ in a smoke inhalation victim with altered mental status or hemodynamic instability has a $> 90\%$ sensitivity for toxic blood cyanide levels ($> 40\text{ mcmol/L}$ or $> 1.0\text{ mg/L}$) and mandates immediate empiric antidote administration.