Pseudohyperchloremia and Negative Anion Gap - Think Salicylate!

Area of Science:

• Clinical Chemistry
• Toxicology
• Medical Diagnostics

Background:

• Pseudohyperchloremia, characterized by a low or negative anion gap, was historically linked to bromide poisoning.
• With the removal of bromide from medications, bromism has become rare.
• The advent of chloride ion selective sensing electrodes (Cl-ISEs) has introduced a new cause: salicylate poisoning.

Purpose of the Study:

• To investigate and quantify the pseudohyperchloremia artifact caused by salicylate poisoning using Cl-ISEs.
• To compare Cl-ISE measurements with a standard chloridometer in the presence of salicylate toxicity.

Main Methods:

• Chloride concentrations were measured in five patients with salicylate poisoning using Cl-ISEs from various manufacturers and of different ages.
• Results were compared against measurements obtained via chloridometry (coulometric titration), a method unaffected by salicylate.

Main Results:

• Different Cl-ISEs exhibited varying degrees of artifactual chloride elevation.
• The same Cl-ISE showed increased pseudohyperchloremia with electrode aging (repeated use).
• High salicylate levels can lead to significant pseudohyperchloremia and a falsely low or negative anion gap.

Conclusions:

• Salicylate interferes with Cl-ISE measurements of blood chloride concentration.
• The severity of pseudohyperchloremia depends on salicylate level, Cl-ISE type, and electrode age.
• Salicylate poisoning is now a common cause of pseudohyperchloremia, masking typical anion gap metabolic acidosis; physicians should suspect salicylate toxicity in cases of unexplained hyperchloremia with a narrow anion gap.