Intraobserver and Interobserver Agreement in
Visual Inspection for Xanthochromia: Implications
for Subarachnoid Hemorrhage Diagnosis,
Computed Tomography Validation Studies, and
the Walton Rule
BACKGROUND: Visual inspection for xanthochromia is used to diagnose subarachnoid
hemorrhage (SAH), to validate computed tomography subarachnoid hemorrhage diagnosis
and was used to determine the Walton rule. No study has assessed the reliability of xan-
thochromia.
OBJECTIVE: To determine intraobserver and interobserver xanthochromia agreement.
METHODS: Mock cerebrospinal fluid samples contained increasing concentrations of
human oxyhemoglobin, bilirubin, and albumin. Non-color-blind observers randomly
assessed samples against a white background twice under significantly differing illu-
mination. Specimens were recorded as red, orange, yellow, or clear.
RESULTS: Results were obtained for 26 observers (11 male, 15 female observers). We
found that 19.2% of samples were misclassified: red, 11.7%; orange, 28.5%; yellow, 29.6%;
and clear, 22.1% (x
2
= 213.2; P , .001). Of the yellow misclassifications, 88% were mis-
classified as clear. Female observers correctly classified samples significantly more fre-
quently than male observers (P = .03). Intraobserver agreement differed significantly from
expected for both male (x
2
= 105.6; P , .001) and female (x
2
= 99.9; P , .001) observers
regardless of illumination. Interobserver agreement was poor regardless of sex (x
2
for male
observers = 176.96, P , .001; x
2
for female observers = 182.69, P , .001) or illumination (x
2
for bright = 125.64, P , .001; x
2
for dark = 148.48, P , .001). Overall, there was 75%
agreement in 46% of the tests and 90% agreement in only 36% of the tests.
CONCLUSION: This simple laboratory study would be expected to maximize agreement
relative to clinical practice. Although non-color-blind female observers significantly out-
performed non-color-blind male observers, both intraobserver agreement and interob-
server agreement for xanthochromia were prohibitively poor regardless of sex or
illumination. Yellow was most frequently misclassified, 88% as clear (ie, true positives
were commuted to false negatives). Xanthochromia is therefore highly unreliable for
subarachnoid hemorrhage diagnosis and computed tomography validation. The Walton
rule requires urgent clinical revalidation.
KEY WORDS: Observer agreement, Xanthochromia
Neurosurgery 74:395–400, 2014 DOI: 10.1227/NEU.0000000000000291 www.neurosurgery-online.com
X
anthochromia is the yellow hue present in
the cerebrospinal fluid (CSF) supernatant
of a patient with a recent subarachnoid
hemorrhage (SAH) after centrifugation. Visual
inspection for xanthochromia, the result of in vivo
bilirubin formation from catabolized extruded
oxyhemoglobin, has represented a diagnostic cri-
terion for SAH since Froin’s discovery in 1903.
1
No study, however, has validated the absolute
reliability of xanthochromia, whether intraob-
server (observer consistency within the same
sample) or interobserver (perceptual consistency
across observers).
Laurence A.G. Marshman, MD,
FRCSN*
Ryan Duell, MBBS*
Donna Rudd, BSc‡
Ross Johnston, BSc (Hons)§
Cassandra Faris, MBBS*
*Department of Neurosurgery, Institute of
Surgery, The Townsville Hospital, Queens-
land, Australia; Departments of ‡Physiology
and, §Marine and Tropical Biology, James
Cook University, Queensland, Australia
Correspondence:
Laurence A.G. Marshman, MD, FRCSN,
Department of Neurosurgery,
Institute of Surgery,
IMB 20, PO Box 670,
The Townsville Hospital,
Douglas, Townsville 4810,
Queensland, Australia.
E-mail: l.a.g.marshman@btinternet.com
Received, December 12, 2012.
Accepted, December 29, 2013.
Published Online, January 19, 2014.
Copyright © 2014 by the
Congress of Neurological Surgeons.
Abbreviation: SAH, subarachnoid hemorrhage
RESEARCH—LABORATORY
TOPIC RESEARCH—LABORATORY
NEUROSURGERY VOLUME 74 | NUMBER 4 | APRIL 2014 | 395
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