Evaluation of Potential Lactate/Lactate Dehydrogenase Interference with an Enzymatic Alcohol Analysis

Abstract

The Connecticut Department of Public Safety laboratory recently addressed a legal challenge to a hospital alcohol dehydrogenase (ADH)-based serum ethanol determination based on the suggestion of interference by lactate dehydrogenase (LDH)-catalyzed oxidation of lactate. Both ADH- and LDH-oxidations require NAD(+) (present in excess in the assay). NADH produced by LDH-catalyzed lactate oxidation in the assay is interpreted as derived from ethanol. Hepatic trauma was suggested as the basis for elevated levels of lactate and LDH. Clinical laboratory results were evaluated, specifically serum hepatic enzymes, ions, and anion gap. Aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) were 229 and 144 U/L, respectively (approximately 8x and 4x reference range midpoint values). Na(+), K(+), Cl(-), and CO(2) levels were 143, 3.0, 112, and 20 meq/L, respectively, yielding an anion gap of 8 meq/L (ref. range 8-15). Serum lactate contributes to "unmeasured anions"; hence, the anion gap was inconsistent with a significant lactate elevation. Based on the slight elevation of ASAT and ALAT, LDH levels were estimated to be elevated to no more than 10-fold. Calculation of the amount of LDH and ADH present in the ethanol assay suggest an ADH/LDH ratio of 200:1. Hence, contribution by lactate oxidation to the serum ethanol concentration in this case would have been negligible.

Monitoring a ‘metabolic shift’ after surgical resection of oral squamous cell carcinomas by serum lactate dehydrogenase

“…Currently, little is known about other predisposal factors influencing LDH and LDH isoenzyme expression, like wound healing processes , cytokines , tobacco , or alcohol abuse . More than 80% of the OSCCs are associated with the two main exogenous carcinogenic factors, alcohol, and tobacco abuse .…”

“…Therefore, the pre-and postoperative levels of LDH and its isoenzymes could be of potential interest to predict response to radiation or chemotherapy (e.g., therapeutic resistance) (10,28,36). Currently, little is known about other predisposal factors influencing LDH and LDH isoenzyme expression, like wound healing processes (40), cytokines (41), tobacco (42), or alcohol abuse (32). More than 80% of the OSCCs are associated with the two main exogenous carcinogenic factors, alcohol, and tobacco abuse (43).…”

“…History and laboratory parameters of patients with cancer gave no indication for heart disease (LDH‐1, creatine kinase, CK, and glutamic‐oxaloacetic transaminase, GOT values), muscle (CK value), lung (LDH‐3 value), kidney (creatinine value), or hepatic dysfunction (GOT, gamma‐glutamyl transferase, GGT values). Patients with hepatic trauma, for example acute alcoholism/alcohol abuse (<14 days) leading potentially to increase of LDH values accompanied with elevation of GOT/glutamic pyruvic transaminase (GPT), and/or GGT values were excluded from the study. In our patient cohort, only one case showed slightly increased GOT value, and in further one case, isolated GGT value was slightly increased before surgery.…”

Case of acute hepatic injury and elevated ethanol levels in a non-alcoholic adult

“…Gas chromatography/mass spectrometry (GC/MS) is the gold standard and is used in forensic laboratories to measure whole blood ethanol levels. Meanwhile, enzymatic ethanol assay to measure ethanol concentration in the serum or plasma is often used in hospital laboratories 1 2. However, elevated lactate and lactate dehydrogenase can theoretically cause false positive results of enzymatic ethanol assay and has been proven in post-mortem cases 3…”

Comparative analysis of hospital and forensic laboratory ethanol concentrations: A 15 month investigation of antemortem specimens

“…4 Unfortunately, some small molecules oxidized by their respective enzymes can also produce NADH, therefore possibly increasing the perceived concentration of ethanol. 5,6 Calibration differences between methods may also play a role in the variability of quantitation between different methods. This study compared the ethanol quantitation values of 39 ethanol positive cases, where samples in the same collection set were analyzed first at the hospital of origin and then again at the San Diego County Medical Examiner's Office (SDCMEO).…”