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Heparin interferes with tobramycin serum concentration determinations by Emit
Abstract:
Enzyme multiplied immunoassay (Emit) commonly is used to determine aminoglycoside concentrations. Its accuracy generally is comparable to that of radioimmunoassay (RIA). Poor reproducibility and questionable quantitation by the Emit assay have been reported when heparinized, severely lipemic, or icteric samples have been used. However, the significance of these interferences is documented poorly. We observed a ESRD patient in whom the underestimation by Emit of the tobramycin concentration in a plasma sample (heparin concentration of 41 U/ml) could have resulted in excessive drug administration and potential toxicity. Tobramycin therapy was initiated with a loading dose of 1.6 mg/kg and three tobramycin concentrations were obtained (2, 12, and 36 hours post-infusion) to define the patient's pharmacokinetic parameters. The first and third samples were collected in serum specimen tubes while the second sample was collected in a plasma tube. The tobramycin concentration in the plasma sample measured by Emit was 82 percent lower than the RIA value. Analyses of other samples by both procedures revealed no clinically significant differences. This case demonstrates that the presence of heparin may interfere with the Emit tobramycin assay in the clinical setting. The degree of reduction in tobramycin concentrations may be dramatic and potentially can alter a patients apparent tobramycin dosing requirements. Further investigation is warranted.
Insights
Enzyme multiplied immunoassay (Emit) may underestimate tobramycin levels in patients receiving heparin. This interference can lead to inaccurate drug dosing and potential toxicity, highlighting the need for careful sample selection.
Area of Science:
- Clinical Chemistry
- Pharmacokinetics
- Analytical Toxicology
Background:
- Enzyme multiplied immunoassay (Emit) is a common method for determining aminoglycoside concentrations, often comparable to radioimmunoassay (RIA).
- Previous reports suggest potential issues with Emit assay reproducibility and quantitation in specific sample types, including heparinized specimens.
- The clinical significance of these interferences, particularly with heparin, remains poorly documented.
Observation:
- A case involving an end-stage renal disease (ESRD) patient highlighted a significant underestimation of tobramycin concentration using Emit.
- The patient's plasma sample, collected in a heparinized tube (41 U/ml), showed an 82% lower tobramycin level compared to RIA.
- This discrepancy occurred despite other samples showing no clinically significant differences between Emit and RIA.
Findings:
- Heparin interference in the Emit tobramycin assay can lead to dramatic reductions in measured drug concentrations.
- The observed underestimation in a heparinized sample could have led to excessive tobramycin administration and potential toxicity.
- This case demonstrates a critical limitation of the Emit assay in clinical settings with heparinized samples.
Implications:
- Clinicians must be aware of potential heparin interference with Emit tobramycin assays.
- Careful consideration of sample collection tubes is crucial to ensure accurate tobramycin quantitation.
- Further research is warranted to fully understand and mitigate heparin's impact on Emit assays for aminoglycosides.