What explains the development of lactic acidosis in cyanide (cyanide) poisoning, characterized by metabolic acidosis with low pH, low bicarbonate levels, and elevated lactate levels?

From the Guidelines

Cyanide poisoning causes lactic acidosis by inhibiting cytochrome c oxidase in the mitochondrial electron transport chain, which blocks cellular respiration, as noted in the most recent guidelines 1. This inhibition prevents cells from using oxygen for aerobic metabolism, forcing them to switch to anaerobic metabolism even when oxygen is present in the blood. The key points to consider are:

• Anaerobic metabolism produces lactic acid as a byproduct, leading to elevated lactate levels.
• The accumulation of lactic acid in the bloodstream causes metabolic acidosis, characterized by low pH and low bicarbonate levels as the body attempts to buffer the excess acid.
• This explains the classic triad of laboratory findings in cyanide poisoning: low pH, low bicarbonate, and elevated lactate, which is a sensitive and specific finding 1. Some important considerations for treatment include:
• Hydroxocobalamin (Cyanokit) 5g IV is a recommended antidote, which works by binding cyanide, allowing restoration of aerobic metabolism and resolution of lactic acidosis.
• Sodium thiosulfate 12.5g IV combined with sodium nitrite 300mg IV is an alternative treatment, which provides alternative binding sites for cyanide, also allowing restoration of aerobic metabolism and resolution of lactic acidosis, as supported by previous guidelines 1. It is essential to prioritize the most recent and highest quality study, which in this case is 1, to ensure the best possible outcome in terms of morbidity, mortality, and quality of life.

From the FDA Drug Label

Plasma Lactate Concentration ≥ 8 mmol/L Also indicative of cyanide poisoning is a plasma lactate concentration greater than or equal to 10 mmol/L (a value higher than that typically listed in the table of signs and symptoms of isolated cyanide poisoning because carbon monoxide associated with smoke inhalation also contributes to lactic acidemia)

Lactic Acidosis in Cyanide Poisoning: Lactic acidosis in cyanide poisoning is likely due to the inhibition of cellular respiration, leading to a shift from aerobic to anaerobic metabolism and the subsequent production of lactate.

• Key Factors:
  • Inhibition of cellular respiration
  • Shift to anaerobic metabolism
  • Production of lactate This results in elevated lactate levels, which can be used as an indicator of cyanide poisoning, particularly in smoke inhalation victims where carbon monoxide exposure may also contribute to lactic acidemia 2, 3.

From the Research

Lactic Acidosis in Cyanide Poisoning

• Lactic acidosis is a hallmark of cyanide poisoning, characterized by elevated lactate levels and metabolic acidosis 4, 5, 6, 7, 8
• The mechanism of lactic acidosis in cyanide poisoning is related to the inhibition of cellular respiration, leading to a shift from aerobic to anaerobic metabolism and the production of lactate 4, 5
• Studies have shown that plasma lactate concentrations > 10 mmol/L in fire victims without severe burns and > 8 mmol/L in pure cyanide poisoned patients are sensitive and specific indicators of cyanide intoxication 4

Treatment of Lactic Acidosis in Cyanide Poisoning

• Treatment of lactic acidosis in cyanide poisoning involves the administration of antidotes such as hydroxocobalamin, sodium thiosulfate, and sodium nitrite 4, 5, 7, 8
• Hydroxocobalamin is an effective first-line antidote that can be used in combination with sodium thiosulfate to potentiate its effects 8
• Sodium thiosulfate can help to correct the metabolic acidosis and remove the cyanide ion from the body 5, 7, 8
• Hemodialysis can also be used to remove the cyanide ion and correct the metabolic acidosis 5

Clinical Presentation and Outcome

• Patients with cyanide poisoning may present with severe metabolic acidosis, elevated lactate levels, and hemodynamic instability 6, 7, 8
• Prompt recognition and treatment of cyanide poisoning can lead to improved outcomes and reduced morbidity and mortality 4, 6, 7, 8
• Combination therapy with hydroxocobalamin and sodium thiosulfate may have a positive effect on survival and reduce the risk of long-term neurological and visual sequelae 8