Measurement of Serum Ketones At Least 2 hrs After Ingestion (in Absence of Alcohol Dehydrogenase Inhibitors, Ethanol or Fomepizole): low serum ketone concentration excludes a significant isopropanol ingestion
Physiology
Types of Serum Ketones
Acetoacetate (Acetoacetic Acid)
Acetoacetate is the Only One of the Three Which is a True Ketoacid
Acetone (see Acetone): formed by the decarboxylation of acetoacetate
Acetone is a True Ketone, Not an Acid
β-Hydroxybutyrate (see Serum β-Hydroxybutyrate): hydroxyacid formed by the reduction of acetoacetate
Ratio of β-hydroxybutyrate/Acetoacetate May Increase as High as 10:1 in DKA
Ratio of β-hydroxybutyrate/Acetoacetate Also Increases When Lactic Acidosis Coexists with Ketoacidosis
Technique
Nitroprusside Reaction
Principle of Nitroprusside Reaction: nitro-Russian reaction detects acetoacetate (and to a much lesser degree, acetone)
Positive Assay Exhibits a Purple Color Change
Specimen
Urine
Acetest (Using Nitroprusside Tablets)
Ketostix (Using Nitroprusside Reagent Sticks)
Serum
Testing Errors
False-Positive Nitroprusside Test
Drugs with Sulfhydryl Groups Which React with Nitroprusside
Captopril
Mesna
Penicillamine
False-Negative Nitroprusside Test
Although Not Technically a “False-Negative” Nitroprusside Test, the Presence of Relatively Larger Amounts of β-Hydroxybutyrate than Acetoacetate in Diseases Such as Diabetic Ketoacidosis (As Noted Above) Results in a Clinical Scenario Where the Patient Has Significant Ketonemia, But May Have a Negative Serum Nitroprusside Test: in these cases, β-Hydroxybutyrate assay will demonstrate the predominant serum ketone present (see Serum β-Hydroxybutyrate)
For This Reason, Serum Ketone Testing by the Nitroprusside Reaction Has Been Largely Replaced by β-Hydroxybutyrate Testing (Even Though β-Hydroxybutyrate Cannot Be Quantitated at Levels >6 mEq/L)
Additionally, β-Hydroxybutyrate Levels Can Be Useful to Follow Response to Therapy