Spectrophotometry, not visual inspection for the detection of xanthochromia in suspected subarachnoid haemorrhage: A debate

The measurement of bilirubin in the cerebral spinal fluid (CSF) for the diagnostic work-up of suspected subarachnoid haemorrhage (SAH) is informed by basic science. Following a spontaneous SAH, red blood cells (RBCs) are lysed in the CSF. Free haemoglobin is converted to oxyhaemoglobin, which is then metabolised by macrophages to bilirubin. The former reaction occurs in vitro and in vivo. The latter reaction occurs only in vivo, with bilirubin appearing some 6 to 12 h post-haemorrhage. The presence of bilirubin resulting in yellow discolouration of the CSF is the contemporary definition for xanthochromia. The finding of xanthochromia implies a SAH, a condition that is infrequent but has catastrophic morbidity and mortality if missed. A cerebral angiogram in search of a treatable aneurysmal cause is indicated on finding xanthochromia or more specifically on detecting bilirubin in the CSF. Spectrophotometry is a technique for measuring bilirubin in the CSF. The usual laboratory analytical techniques cannot be used because bilirubin appears in too low a concentration. A spectrophotometer measures the light absorption of a material, thus quantifying its presence, analogous to the clinically ubiquitous pulse oximeter. Spectrophotometry is able to detect low concentrations of bilirubin in the CSF. Moreover, it can distinguish between bilirubin and oxyhaemoglobin. It is an objective test that is sensitive for SAH. Visual inspection is a subjective test that is insensitive for xanthochromia. Unlike spectrophotometry, visual inspection is incapable of detecting low concentrations of bilirubin and differentiating between bilirubin and oxyhaemoglobin. Moreover, its intraobserver and interobserver agreement is poor. In sufficient concentrations, oxyhaemoglobin appears orangered whereas bilirubin is yellow. When present, both contribute to the discolouration of the CSF. Visual inspection cannot reliably detect and distinguish between the two. The distinction between oxyhaemoglobin and bilirubin is central to the analysis and interpretation of the CSF. Oxyhaemoglobin appears in both a traumatic lumbar puncture (LP) and following a SAH. A traumatic LP confounds the interpretation of the CSF findings. The incidence of a traumatic LP is around 20% when arbitrarily defined as the presence of greater than 400 × 10 RBCs per litre of CSF. In conventional teaching, a decreasing RBC count from the first to third or fourth collection tube is indicative of a traumatic LP, whereas a steady RBC count is said to be diagnostic of a SAH. However, a falling RBC count cannot reliably be equated to trauma unless it falls close to zero, because a traumatic LP can occur in the presence of a SAH. Bilirubin will only appear following a SAH. Following centrifuge after a traumatic LP, the CSF might look discoloured because of the presence of oxyhaemoglobin and not bilirubin. The presence of bilirubin is the key finding in SAH. CSF bilirubin spectrophotometry is supported by National Guidelines in the UK. Proposed in 2003 and revised in 2008, the United Kingdom National External Quality Assurance Service (UKNEQAS) guidelines set out procedures for specimen requirements, transport, handling, analysis and interpretation. The guidelines also articulate the requirements for clinical governance and participation in an appropriate external quality assurance scheme. There is no equivalent framework for visual inspection. In Australia, CSF bilirubin spectrophotometry is available, although there is variability in its perceived need. In Queensland, spectrophotometry is provided by Pathology Queensland, which services public hospitals in the state. A spectrophotometer is a piece of desktop printer-sized equipment sitting on the Correspondence: Associate Professor Kevin H Chu, Department of Emergency Medicine, Royal Brisbane and Women’s Hospital, Butterfield Street, Herston, QLD 4029, Australia. Email: k.chu@uq.edu. au