Elsevier

Clinical Biochemistry

Volume 73, November 2019, Pages 115-117
Clinical Biochemistry

Short Communication
An investigation of enzymatic creatinine interference in a patient receiving dopamine and dobutamine

https://doi.org/10.1016/j.clinbiochem.2019.08.001Get rights and content

Highlights

  • Dopamine or dobutamine specimen contamination may produce interference with enzymatic creatinine measurement procedures.

  • Peripherally inserted central catheter specimen line draws are not recommended during a dopamine and dobutamine infusion.

  • A siphoning mechanism potentially contaminates specimens during simultaneous collection while the infusion pump running.

Abstract

Background

A laboratory investigation was initiated after a renal failure patient had a 2.18 mg/dL decrease in serum creatinine, which was not explained through medical intervention. The investigation revealed specimens providing questionably low results had been collected from a peripherally inserted central catheter (PICC) line.

Methods

Patient specimens and serum pools were analyzed by the Siemens Vista enzymatic creatinine measurement procedure. A simulation of the patient's infusion protocol examined potential PICC line carryover and specimen collection technique.

Results

A simultaneously collected specimen set, arterial line and PICC line, yielded a difference of 1.86 mg/dL. Infusion and collection simulation studies suggested the most likely scenario was the infusion pump was not shut off while the specimen collection occurred and contaminated the specimen.

Conclusion

Providers should be aware of erroneously low creatinine results when administering catecholamine drugs and collecting specimens through the same catheter. The mechanism of specimen contamination is consistent with a siphoning effect from one lumen to the other during collection with the infusion pumps still running.

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

References (21)

  • J.A. Weber et al.

    Interferences in current methods for measurements of creatinine

    Clin. Chem.

    (1991)
  • A.K. Petrides et al.

    Fluctuating creatinine in the cardiac unit

    Clin. Chim. Acta

    (2015)
  • J.H. Nichols et al.

    Evaluation of the IRMA TRUpoint and i-STAT creatinine assays

    Clin. Chim. Acta

    (2007)
  • National Kidney Foundation

    K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification

    Am. J. Kidney Dis.

    (2002)
  • L.D. Bowers et al.

    Kinetic serum creatinine assays. II. A critical evaluation and review

    Clin. Chem.

    (1980)
  • K. Spencer

    Analytical reviews in clinical biochemistry: the estimation of creatinine

    Ann. Clin. Biochem.

    (1986)
  • H. Crocker et al.

    Evaluation of an enzymatic method for determining creatinine in plasma

    J. Clin. Pathol.

    (1988)
  • C.M. Cobbaert et al.

    Prime time for enzymatic creatinine methods in pediatrics

    Clin. Chem.

    (2009)
  • T.M. Daly et al.

    "Bouncing" creatinine levels

    N. Engl. J. Med.

    (1996)
  • K.T. Koprowicz et al.

    Influence of dopamine on peroxidase-based assays

    Clin. Chem.

    (1996)
There are more references available in the full text version of this article.

Cited by (5)

  • Performance evaluation of all analytes on the epoc® Blood Analysis System for use in hospital surgical and intensive care units

    2020, Practical Laboratory Medicine
    Citation 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.

1

Current address: Hennepin Healthcare Clinical Laboratory, Minneapolis, MN, United States

View full text