The Annals as a disseminator of guidelines and promoter of best practice

From time-to-time, the Annals has published ^1,2 or, critically appraised ^{3 –5} national guidelines. Where guidelines involve clinical biochemistry then their publication in the Annals enables them to be disseminated to relevant professionals in laboratories, not just in the UK, but also internationally. Such dissemination helps increase the uptake of any guideline and, hopefully, speeds up consequent improvements in practice. I will illustrate this point by considering the national guidelines for analysis of cerebrospinal fluid (CSF) for bilirubin in suspected subarachnoid haemorrhage (SAH). ⁶ These guidelines first appeared in 2003 and were the culmination of much ‘behind the scenes’ work of many with an interest in this field.

Until these guidelines were published, the analysis of CSF for bilirubin in relation to the investigation of SAH left much to be desired. The most important use of the test was/is to exclude SAH in patients who are negative for blood following computerised tomography (CT) scanning and thus to avoid subsequent cerebral angiography. In present times, due to pressure on acute beds, the test has developed greater importance in identifying these patients as they are unlikely to have suffered SAH and can therefore be safely discharged from acute locations. Much reliance has therefore been placed on this test by clinical staff.

Historically, there has been much debate as to which is the best way of looking for bilirubin in CSF. Prior to the publication of the guidelines, the majority of laboratories used visual inspection of CSF, performed in microbiology laboratories as part of standard cellular and microbiological analysis. Visual evidence of a straw coloured fluid (hence xanthochromia) was used as evidence of altered blood in the CSF and publications at the time described findings based on visual examination, ⁷ even though these may have not been well controlled. Such investigations, however, have one major flaw; namely they are subject to differences in human interpretation.

In a desire to remove subjectivity from the investigation, in 1989, workers in the Netherlands recommended xanthochromia be ‘investigated by spectrophotometry’. ⁸ This publication in turn led to an editorial appearing the same year in the Lancet. ⁹ Although some laboratories took up the mantle of spectrophotometry following this editorial, much uncertainty remained as to the role of spectrophotometry and result interpretation. In response to this uncertainty, one of the first papers that appeared in the Annals in this area was published. ¹⁰ It consisted of a Personal View, prepared under the auspices of the former Analytical Investigations Standing Committee of the Scientific Committee of the Association for Clinical Biochemistry. I believe this publication helped to kick-start the work that has appeared over the last 15 years, much of it in the Annals, that has turned this field from an art, to a more evidence-based science.

Both the Dutch paper ⁸ and the Lancet editorial, ⁹ advocated the investigation of xanthochromia by spectrophotometry. Xanthochromia was defined as, ‘an absorbance, at 415 nm, of greater than 0.023 AU and/or a peak in the absorbance curve in the 450–460 nm region’. In their Personal View, Beetham et al. ¹⁰ found this definition of xanthochromia ‘unclear and ambiguous.’ One aspect of their critique was that an increase in the concentration of CSF protein will result in an absorbance at 415 nm of more than 0.023 AU. Another was that the definition of xanthochromia had been interpreted by many investigators, for example the 1995 study of van der Wee et al., ¹¹ to be either a peak of oxyhaemoglobin (>0.023 AU), or a peak in oxyhaemoglobin and a peak at 450 nm due to bilirubin or a peak at 450 nm of bilirubin only. The main issue in the Personal View with this definition was that it allowed for oxyhaemoglobin alone to support the diagnosis of SAH, when in practice oxyhaemoglobin may have been generated either in vivo or in vitro by a traumatic tap.

An ad hoc Advisory Group was subsequently established under the auspices of the United Kingdom National External Quality Assessment Scheme (UKNEQAS) for Immunology and Immunochemistry. This group first met in June 2000 and in 2004 evolved to a formal Specialist Advisory Group (SAG) to UKNEQAS for CSF Proteins and Biochemistry. Included in the remit of the ad hoc Advisory Group, and latterly the SAG, was the dissemination of best practice in the investigation of CSF. This included the production of national guidelines that, where possible, would be evidence based and remove any of the ambiguity alluded to above in either what to measure or how to interpret results. Their preparation included comprehensive literature searches, review of existing guidelines and various audits, and a review of outcomes following a retrospective review of 740 spectrophotometric scans collected from four UKNEQAS participating laboratories. ⁶ They included sample requirements, transport and handling, analysis, reporting and interpretation and aimed to be as up to date as possible with included material. For example, whilst in preparation, it became apparent that transport of CSF to the laboratory by pneumatic tube was not recommended as evidence was provided that increased haemolysis of bloodstained CSF may occur. ¹² Following various consultations and dissemination of the guidelines to various professional groups and bodies, the first edition of them was published in the Annals in November 2003. ⁶

Following publication of these guidelines, follow-up publications began to appear concerning audit of their performance in everyday practice. ^{13 –16} One of these audits, a national audit of CSF testing ¹⁴ had been initiated by the SAG itself. On the basis of the findings of this audit, and correspondence from UKNEQAS scheme participants, in 2005, a review of the guidelines was undertaken. After extensive consultation, the amended guidelines were published in the Annals in May 2008, ¹⁷ together with an editorial indicating the reasons for the amendments. ¹⁸ Since their publication, an audit of 93 spectrophotometric scans concluded that the revised guidelines offered greater clarity in reporting without adversely affecting patient outcome. ¹⁹ In 2011, a further Personal View appeared in the Annals in relation to the UKNEQAS for CSF haem pigments. ²⁰ Among the outcomes of audit described in that article were (a) the number of participant numbers in the UKNEQAS above had risen from 63 to 150; (b) the percentage of scheme participants using visual inspection, ‘a poor practice indicator’ fell from 27% to less than 1%; and (c) more than 93% of participants were able to interpret analytical results linked to straightforward clinical scenarios. It is reasonable to conclude that these positive findings can be attributed to a direct effect of the guidelines and their incorporation into routine practice.

In conclusion, the Annals has published various guidelines over the years and in doing so has helped to disseminate knowledge and encourage best practice. The guidelines referred to in this article are but one example. However, the Annals also serves another important function, which I hope is also apparent after reading this Observation from the Archives; namely the informing of guidelines, since much of the evidence cited in the guidelines above was published in the Annals itself.

Declaration of conflicting interests

PRW was a member of the ad hoc Advisory Group and SAG and contributed to the development of the 2003 Guidelines. He left the SAG prior to development of revised guidelines that were published in 2008.

Funding

Not applicable.

Ethical approval

Not applicable.

Guarantor

PRW.

Contributorship

PRW is the sole author.