Prevalence and detection of citrate contamination in clinical laboratory

To study the prevalence of trisodium citrate (Na₃Citrate) contamination in hypernatraemic serum samples by direct measurement of citrate and to evaluate the performance of indirect markers for identification of Na₃Citrate contamination.

Serum citrate was measured in all hypernatraemic serum samples (sodium ≥148 mmol/L) over a three-month period. The performance of serum chloride, sodium-chloride gap, indirect ion selective electrode (ISE)-direct ISE sodium disparity and osmolar gap in identification of Na₃Citrate contaminated samples was assessed against the 'gold-standard' direct citrate measurement.

In total, 27 Na₃Citrate contaminated samples were identified based on serum citrate concentration ≥1.5 mmol/L. The prevalence of citrate contamination was 3.1 % of hypernatraemic samples (n=875) and 0.017 % of all samples received for urea and electrolyte analysis (n=153,404). Most contaminated samples were from patients receiving haemodialysis (59.3 %), and the rest from inpatients. Cut-offs to give 100 % sensitivity were chloride ≤105 nmol/L (specificity 93.4 %), sodium-chloride gap ≥47 mmol/L (specificity 95.3 %), indirect ISE-direct ISE sodium disparity ≥3 mmol/L (specificity 81.9 %), and osmolar gap ≥39 mOsm/kg (specificity 2.8 %).

Trisodium citrate contamination is uncommon. Most contaminated samples were from patients receiving haemodialysis, likely because of contamination with citrate catheter locking solution. Screening with serum chloride or sodium-chloride gap can confidently exclude Na₃Citrate contamination in over 90 % of hypernatraemic samples, and in nearly all samples with sodium ≥155 mmol/L if metabolic alkalosis has been excluded. In the remaining samples, Na₃Citrate contamination can only be definitively confirmed or excluded by measurement of serum citrate. We propose algorithms to identify spurious hypernatraemia.