Short CommunicationAn investigation of enzymatic creatinine interference in a patient receiving dopamine and dobutamine
Introduction
Serum creatinine is a biomarker for estimating glomerular filtration rate (eGFR) in patients [1]. Serum creatinine results are input into estimating equations and provide clinicians with an assessment of renal function. Two laboratory creatinine measurement procedures are the Jaffe and the enzymatic reagent systems. The Jaffe reagents utilize picric acid to produce a colorimetric response and enzymatic reagents employ enzymes throughout the reaction. The Jaffe reaction's non-specificity is well documented [[2], [3], [4], [5]]. Given these analytical specificity issues, laboratories are moving to enzymatic creatinine measurement procedures, which are viewed as more creatinine specific.
Reports of enzymatic creatinine reagents providing falsely low results when patients are receiving dopamine and or dobutamine have been published [[6], [7], [8], [9], [10], [11], [12]]. Karon et al. proposed two separate chemical mechanisms for this interference, both producing negative interference [9]. One was dopamine in the presence of peroxide reacts with assay reagents to produce a chromophore with a smaller absorptivity and falsely lowers signal. The other is in the presence of peroxidase, dobutamine reacts with and depletes peroxide to levels inhibiting chromophore generation.
This study was pursued after an inpatient with renal failure had a 2.18 mg/dL decrease in serum creatinine with no medical intervention. The initial result was 4.25 mg/dL and 6 h later was 2.07 mg/dL. All creatinine measurements were obtained using the Siemens Dimension® Vista 1500 employing enzymatic creatininase reagents. Repeat specimen analysis on the laboratory's 2nd Vista instrument provided the same result. Further investigation revealed the specimens providing questionable results were collected from a peripherally inserted central catheter (PICC) line. During the third PICC line collection, a simultaneous arterial line specimen collection was analyzed by the Vista and provided values consistent with previous.
Specimen collection protocol, drug carryover studies and in vitro drug delivery simulations using the patient's same PICC line model and infusion rate were investigated.
Section snippets
Chemicals and reagents
Creatinine results were acquired on the Siemens Dimension® Vista 1500 (Siemens Healthcare Diagnostics Inc. Tarrytown, NY USA) and Abbott i-STAT® (Abbott Point of Care Inc. Princeton, NJ USA) systems and testing was performed per manufacturer's instructions.
Infusion simulation studies
A 60 cm 4 French Dual-Lumen Polyurethane Catheter reorder number 3264155 (Bard Access Systems, Inc., Salt Lake City, Utah USA) PICC line was used. Dopamine HCL 400 mg/250 mL (Baxter Deerfield, Illinois, USA) and Dobutamine 500 mg/250 mL
Results
The patient's creatinine results are plotted in Fig. 1 for both platforms. The i-STAT results were acquired 24–48 h after the initial Vista analysis.
Dopamine and dobutamine interference was examined in spiking experiments and details are given in the supplemental section.
The in vitro infusion simulation results are given in Table 1. Control specimens prior to infusions verified the transit through the catheter's lumen did not impact the creatinine results. The “waste” and “draw” specimens were
Discussion
The patient's creatinine results suggest low Vista results occur from PICC line collections. When examined by the i-STAT, no decrease was observed, rather an increasing creatinine trend was seen fitting the clinical situation. Paired arterial line (4.7 mg/dL) and PICC line (2.9 mg/dL) draws at 17.2 h showed a 1.8 mg/dL difference suggesting an analytical interference with the specimens collected from the PICC line. Upon medical record examination, the patient was receiving a dopamine and
Conclusions
We conclude the potential mechanism for dopamine and dobutamine specimen contamination arises from specimen collection while the infusion pump is running, likely by a siphoning mechanism at the PICC line end. This fits nursing staff accounts and the context for dopamine infusions should not be abruptly stopped. Line contamination by carryover for either drug was not observed to suppress creatinine results. This information should be shared with phlebotomy and nursing staff, as collection during
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2020, Practical Laboratory MedicineCitation Excerpt :However, other than the association with a diagnosis of renal dysfunction, the Straseski et al. report does not show any contribution of an interfering substance or differences in the whole-blood matrix for the discrepant patients. Different interferences can potentially affect Jaffe creatinine assays, such as bilirubin, glucose, or protein, or enzymatic assays, such as dopamine, although the susceptibility and extent of interference can vary depending on the assay configuration [25–29]. However, none of the samples included in our study showed any lipemia or hemolysis when running the creatinine assay on either the Architect c8000 or Cobas c702 instruments.
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