Printer Friendly

Response to Cembrowski et al. regarding "Could Susceptibility to Low Hematocrit Interference Have Compromised the Results of the NICE-SUGAR Trial?".

To the Editor:

Cembrowski et al. (1) hypothesize that the hematocrit effect (i.e., the tendency of many blood glucose meter systems toward a positive bias at low hematocrits) in the SureStep[R]Flexx[R] meter (LifeScan) may have caused false hyperglycemia, which, when treated with insulin, may have led to some of the hypoglycemic events observed in the NICE-SUGAR (Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation) study.

We believe that the authors' data do not support this assertion.

First, the authors do not present any SureStep[R]Flexx[R] data related to hypoglycemic events, the hematocrit, or NICE-SUGAR. Therefore, there is no evidence that SureStep[R]Flexx[R] was associated with hypoglycemia during the NICE-SUGAR study.

Second, they show in their Fig. 1 that most of the data fell within the expected limits of [+ or -] 20% accuracy. Indeed, the mean bias of the 3 test strip lots in question, compared with the Radiometer 800 blood gas analyzer, was 13.6%. The mean relative bias for these 3 test strip lots at lower glucose values was 0.83 mmol/L, vs the expected limits of [+ or -] 1.1 mmol/L ([+ or -] 20 mg/ dL). The authors do not state which, if any, of these data points were associated with the NICESUGAR study. Furthermore, the actual "trueness" of either glucose method is not known because laboratory glucose reference values are not provided.

Third, SureStep[R]Flexx[R] data points were included only when the sample was collected within 15 min of the blood gas analyzer sample. If the reason for this additional testing was a factor known to cause inaccuracy (e.g., operator error, hematocrit outside the labeled interval, shock, and so forth), then a difference between the 2 methods might be expected.

Finally, the authors concede that the NICE-SUGAR protocol contained many factors that might explain the increased prevalence of hypoglycemic events in the intensively treated group. The authors did not investigate these other factors, however, but instead chose to focus on the relative performance of2 glucose methods.

In summary, the authors allege that a positive bias in SureStep[R]Flexx[R] measurement at low hematocrit values contributed to hypoglycemic episodes in the NICE-SUGAR study, but they do not present supportive evidence. A more cogent argument would have included details of hypoglycemic events along with the actual bias associated with the glucose-measuring device and the patient's hematocrit. Because these data are not presented, the premise that a hematocrit effect, or device performance, caused hypoglycemic events in the NICE-SUGAR study is unfounded.

Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.

Authors' Disclosures of Potential Conflicts of Interest: Upon manuscript submission, all authors completed the Disclosures of Potential Conflict of Interest form. Potential conflicts of interest:

Employment or Leadership: J.J. Mahoney, LifeScan, Inc.; P. Maguire, LifeScan, Inc.; J.M. Ellison, LifeScan, Inc.; A.T. Cariski, LifeScan, Inc.

Consultant or Advisory Role: None declared.

Stock Ownership: J.J. Mahoney, Johnson & Johnson; P. Maguire, Johnson & Johnson; J.M. Ellison, Johnson & Johnson; A.T. Cariski, Johnson & Johnson.

Honoraria: None declared.

Research Funding: None declared.

Expert Testimony: None declared.

Role of Sponsor: The funding organization played a direct role in the preparation and final approval of the manuscript.

Reference

(1.) Cembrowski GS, Tran DV, Slater-MacLean L, Chin D, Noel Gibney RT, Jacka M. Could susceptibility to low hematocrit interference have compromised the results of the NICE-SUGAR trial? Clin Chem 2010;56:1193-5.

John J. Mahoney

Patricia Maguire

John M. Ellison *

Alan T. Cariski

LifeScan, Inc.

Milpitas, CA

* Address correspondence to this author at:

LifeScan, Inc.

1000 Gibraltar Dr.

Mailstop 3D

Milpitas, CA 95035

Fax 408-942-5600

E-mail jellison@its.jnj.com

Previously published online at DOI: 10.1373/clinchem.2010.150995

In Reply

We published our findings to alert the diabetes-research community that multiple lots of SureStep[R]Flexx[R] strips (LifeScan/ Johnson & Johnson) demonstrated increased glucose sensitivity in anemic patients in the intensive care unit. Given that these nonoptimally performing strip lots were used during the NICE-SUGAR (Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation) trial, their use may have compromised the study's primary conclusion, that intensive insulin therapy was harmful to intensive care unit patients. We did not hypothesize but merely quoted the 2010 study of Pidcoke et al., which demonstrated that treating artifactual hyperglycemia can produce iatrogenic hypoglycemia (1). In their prospective observational study, the authors compared the hypoglycemia rates in a burn intensive care unit before and after they corrected artifactually increased SureStep[R]Flexx[R] glucose measurements with a calculation that incorporated the hematocrit and the original whole-blood glucose measurement. During the 4 months of providing lowered but corrected glucose measurements, the authors achieved a 78% decrease in the prevalence of hypoglycemia in critically ill anemic patients treated with insulin and tight glucose control (P < 0.001)! As for the LifeScan argument about trueness, we deemed that arterial blood gas glucose measurements were truth; Pidcoke et al. used plasma glucose measurements produced by a highly accurate central laboratory analyzer. Finally, the allowable error limits for in-hospital testing of whole-blood glucose will be tightening. It is almost fallacious to invoke the [+ or -]20% limits; these limits were devised for patient self-monitoring, not for intensive insulin treatment. At the recent US Food and Drug Administration meeting in Gaithersburg, one of us suggested narrowing these 95% limits for in-hospital whole-blood glucose testing to [+ or -] 12.5% (2).

Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.

Authors' Disclosures of Potential Conflicts of Interest: Upon manuscript submission, all authors completed the Disclosures of Potential Conflict of Interest form. Potential conflicts of interest:

Employment or Leadership: None declared.

Consultant or Advisory Role: None declared.

Stock Ownership: G.S. Cembrowski, Johnson & Johnson (immediate family member).

Honoraria: G.S. Cembrowski, Radiometer. Research Funding: None declared.

Expert Testimony: None declared.

Role of Sponsor: The funding organizations played no role in the design of study, choice of enrolled patients, review and interpretation of data, or preparation or approval of manuscript.

References

(1.) Pidcoke HF, Wade CE, Mann EA, Salinas J, Cohee BM, Holcomb JB, Wolf SE. Anemia causes hypoglycemia in intensive care unit patients due to error in single-channel glucometers: methods of reducing patient risk. Crit Care Med 2010;38: 471-6.

(2.) Cembrowski GS. Comments at FDA public meeting: clinical accuracy requirements for point of care blood glucose meters. March 17, 2010. p 56. http://www.fda.gov/downloads/MedicalDevices/ NewsEvents/WorkshopsConferences/UCM208601. pdf (Accessed July 2010).

George S. Cembrowski *

Dave Tran

Linda Slater-MacLean

Wu Dat Chin

Noel Gibney

Michael J. Jacka

University of Alberta Hospital Edmonton, Alberta, Canada

* Address correspondence to this author at: University of Alberta Hospital Site Lab Med/Rm 4B1.24, WCM Center 8440 112th St.

Edmonton, Alberta, T6G 2B7 Canada

Fax 780-407-8599

E-mail cembr001@cha.ab.ca

Previously published online at DOI: 10.1373/clinchem.2010.152041
COPYRIGHT 2010 American Association for Clinical Chemistry, Inc.
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2010 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Title Annotation:Letters to the Editor
Author:Mahoney, John J.; Maguire, Patricia; Ellison, John M.; Cariski, Alan T.
Publication:Clinical Chemistry
Article Type:Letter to the editor
Date:Oct 1, 2010
Words:1234
Previous Article:Mass spectrometry-based protein biomarker discovery: solving the remaining challenges to reach the promise of clinical benefit.
Next Article:An unlikely pregnancy.

Terms of use | Privacy policy | Copyright © 2022 Farlex, Inc. | Feedback | For webmasters |