Keir, G

Petzold, A

Sharpe, LT

English

UCL Discovery

n engl j med 351;16 www.nejm.org october 14, 2004correspondence1695betic wounds. Although some data support the useof hyperbaric oxygen in patients with ischemic footulcers that are not amenable to either bypass surgeryor angioplasty, there is a lack of evidence to supportits use in the management of neuropathic nonis-chemic foot ulcers, the topic of this article. The factthat the Center for Medicare and Medicaid Services,as well as other insurance carriers, recognizes theuse of hyperbaric oxygen as an approved reim-bursable treatment for problematic diabetic footwounds cannot be regarded as confirmation of ef-ficacy. At present, the role of hyperbaric oxygen inthe management of purely neuropathic foot ulcer-ation remains unsubstantiated.Andrew J.M. Boulton, M.D.University of ManchesterManchester M13 9WL, United Kingdomaboulton@med.miami.eduRobert S. Kirsner, M.D.University of MiamiMiami, FL 33101Loretta Vileikyte, M.D.University of ManchesterManchester M13 9WL, United Kingdom1. Boulton AJM, Malik RA, Arezzo JC, Sosenko JM. Diabetic so-matic neuropathies. Diabetes Care 2004;27:1458-86.2. The Diabetes Control and Complications Trial Research Group.The effect of intensive diabetes therapy on the development and pro-gression of neuropathy. Ann Intern Med 1995;122:561-8.Spectrophotometry for Xanthochromiato the editor: Xanthochromia, or a yellow appear-ance of the cerebrospinal fluid, is often used to con-firm suspected subarachnoid hemorrhage.1,2 It isassociated with the presence of bilirubin, a bloodproduct that arises only in vivo by the enzymatictransformation of hemoglobin. However, visual as-sessment of the cerebrospinal fluid for xanthochro-mia is highly subjective and unreliable, especially incases in which other blood products, such as oxy-hemoglobin, are present.1,2 The differential diag-nosis may be further complicated by a high proteinlevel and a high cell count, as in meningitis and ne-crosis, or by the presence of other pigments (namely,carotenoids). To distinguish pigments in the cere-brospinal fluid, such as bilirubin, that are clinicallyimportant for diagnosing subarachnoid hemor-rhage and other types of intracerebral bleeding fromthose that are not important, objective spectropho-tometry, rather than visual assessment, is recom-mended. Because bilirubin has a characteristic sig-nature — absorbance in the blue range (450 to 460nm) — it can be readily identified by spectropho-tometry. Moreover, by standard colorimetric proce-dures, which have been established by the Com-mission Internationale de l’Eclairage (CIE, or theInternational Commission on Illumination), theReddish (79%)Greenish yellow(7%) Yellow(14%)y Chromaticity Coordinate0.600.650.550.500.400.350.300.450.30 0.35 0.40 0.45 0.50 0.55 0.60 0.65 0.70 0.75 0.80x Chromaticity Coordinate0.70550560570575580590600610620D65Figure 1. Chromaticity Diagram.A section of the Commission Internationale de l’Eclair-age (CIE) 1931 chromaticity diagram is shown, with the x–y chromaticity coordinates of 72 samples of cerebro-spinal fluid containing bilirubin (yellow dots) with re-spect to CIE illuminant D65 (white cross). For reference, the x–y chromaticity coordinates and the wavelengths of the spectral colors from 550 nm (corresponding to greenish yellow) to 620 nm (corresponding to red) are indicated. The region corresponding to pure yellow, which ranges between 575 and 580 nm (as noted by Petzold and Sharpe4), is shown in gray. The pie chart in-dicates the proportions of samples visually identified as greenish, yellow (xanthochromic), and reddish by trained clinical observers. The full chromaticity diagram is shown in the lower left-hand corner.The New England Journal of Medicine Downloaded from nejm.org at UNIVERSITY COLLEGE LONDON on September 11, 2012. For personal use only. No other uses without permission.  Copyright © 2004 Massachusetts Medical Society. All rights reserved. correspondence1696 n engl j med 351;16 www.nejm.org october 14, 2004spectrophotometric trace can be converted to itschromaticity coordinates.3 These procedures allowthe trace to be plotted in a geometric diagram (theCIE 1931 chromaticity diagram for the 2-degreefield of view) and allow its dominant wavelength(corresponding to hue) to be defined with respect toaverage daylight conditions (CIE standard illumi-nant D65) (Fig. 1).Spectrophotometric analysis of 632 samples ofcerebrospinal fluid, obtained at the National Hospi-tal for Neurology and Neurosurgery in London be-tween January 1996 and April 2004, indicated that72 contained bilirubin. Of these, only 15 (21 per-cent) contained bilirubin alone and appeared pureyellow (14 percent) or greenish yellow (7 percent)(Fig. 1). A significantly higher number, 57 (79 per-cent; chi-square=49.0, P<0.001), contained oxy-hemoglobin as well as bilirubin. Their appear-ance ranged from red and reddish pink to orange.These findings reveal that about 80 percent of ce-rebrospinal fluid samples containing substantialamounts of bilirubin are not typically perceived asxanthochromic (i.e., yellow). Equally important, thepresence of bilirubin cannot reliably be ruled out inthe case of cerebrospinal fluid samples that are vis-ibly red.In the United Kingdom, the rate of visual assess-ment of the cerebrospinal fluid fell from 24 percentto 6 percent, whereas the use of spectrophotometryrose from 76 percent to 94 percent, after the intro-duction of new guidelines for the detection of cere-brospinal fluid pigments. This shift has reduced theestimated error rate from 40 percent to 9 percent.5Clearly, xanthochromia on the basis of mere visualassessment is an ambiguous concept clinically,physiologically, and biochemically. Two recent sur-veys, however, have shown that visual assessmentof cerebrospinal fluid samples for xanthochromiais still the most common method used in the UnitedStates.2,6 We believe that this practice should imme-diately be reevaluated.Axel Petzold, M.D., Ph.D.National Hospital for Neurology and NeurosurgeryLondon WC1N 3BG, United Kingdoma.petzold@ion.ucl.ac.ukGeoffrey Keir, Ph.D.Institute of NeurologyLondon WC1N 3BG, United KingdomLindsay T. Sharpe, Ph.D.Institute of OphthalmologyLondon EC1V 9EL, United Kingdom1. UK National External Quality Assessment Scheme for Immuno-histochemistry Working Group. National guidelines for analysis ofcerebrospinal fluid for bilirubin in suspected subarachnoid haem-orrhage. Ann Clin Biochem 2003;40:481-8.2. Edlow JA, Bruner KS, Horowitz GL. Xanthochromia. ArchPathol Lab Med 2002;126:413-5.3. Wyszecki G, Stiles WS. Color science: concepts and methods,quantitative data and formulae. 2nd ed. New York: John Wiley, 1982.4. Petzold A, Sharpe LT. Hue memory and discrimination in youngchildren. Vision Res 1998;38:3759-72.5. Patel D, White P, Egner W, Beetham R. National guidelines foranalysis of CSF bilirubin and their impact. In: Proceedings of the As-sociation of Clinical Biochemists National Meeting, Birmingham,England, May 18–20, 2004. abstract.6. Judge B. Laboratory analysis of xanthochromia in patients withsuspected subarachnoidal hemorrhage: a national survey. In: Pro-ceedings of the American College of Emergency Physicians Scientif-ic Assembly, Philadelphia, October 23–25, 2000. abstract.Correspondence Copyright © 2004 Massachusetts Medical Society.instructions for letters to the editorLetters to the Editor are considered for publication, subject to editing and abridgment, provided they do not contain material that has been submitted or published elsewhere. Please note the following: •Letters in reference to a Journal article must not exceed 175 words (excluding references), must be received within three weeks after publication of the article, and must be submitted over the Internet at http://authors.nejm.org. Letters not related to a Journal article must not exceed 400 words and may be submitted over the Internet or sent, typewritten and triple-spaced, by mail. •A letter can have no more than five references and one figure or table. •A letter can be signed by no more than three authors. •Financial associations or other possible conflicts of interest must be disclosed. (Such disclosures will be published with the letters. For authors of Journal articles who are responding to letters, this information appears in the original articles.) •Include your full mailing address, telephone number, fax number, and e-mail address with your letter.  Our address:  Letters to the Editor  • New England Journal of Medicine • 10 Shattuck St. • Boston, MA  02115Our Web address: http://authors.nejm.orgOur fax numbers:  617-739-9864 and 617-734-4457We cannot acknowledge receipt of your letter, but we will notify you when we have made a decision about publication. Letters that do not adhere to these instructions will not be considered. Rejected letters and figures will not be returned. We are unable to provide prepublication proofs. Submission of a letter constitutes permission for the Massachusetts Medical Society, its licensees, and its assignees to use it in the Journal’s various print and electronic publications and in collections, revisions, and any other form or medium.The New England Journal of Medicine Downloaded from nejm.org at UNIVERSITY COLLEGE LONDON on September 11, 2012. For personal use only. No other uses without permission.  Copyright © 2004 Massachusetts Medical Society. All rights reserved. 

Spectrophotometry for xanthochromia

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