Uninterpretable cerebrospinal fluid absorbance scans caused by antibiotic therapy

Author(s):  
Jan Miller

Background The revised national guidelines for analysis of cerebrospinal fluid for bilirubin in suspected subarachnoid haemorrhage (UK) provide an objective means of assessing cerebrospinal fluid samples to determine the risk of subarachnoid haemorrhage. The guidelines are intended for general use, but samples rendered uninterpretable due to the presence of the antibiotic doxycycline have been described. Here, further cases of antibiotic-based interference, and their implications, are presented. Methods An archival search of cerebrospinal fluid spectra performed at Hallands County Hospital Halmstad was performed for the years 2011 and 2016–2019 in an attempt to locate instances of interference. Each case of suspected interference was further investigated with in vitro reproduction experiments as a means of confirmation and assessment of potential clinical impact. Results A total of 10 cases of cerebrospinal fluid curve interference were discovered: six due to doxycycline, three due to metronidazole and one due to tetracycline. Interference caused by the tetracycline class was revealed through in vitro experimentation to cause an apparent decrease in the sample’s net bilirubin absorbance; the presence of xanthochromia on visual inspection was, however, conserved. Conclusions The problem of cerebrospinal fluid absorbance curve interference might be more common than previously suspected. Due to the potential net bilirubin absorbance-lowering effect of tetracyclines, the author recommends visual examination of cerebrospinal fluid samples in every case.

Author(s):  
Jan Miller

Background The revised national guidelines for analysis of cerebrospinal fluid for bilirubin in suspected subarachnoid haemorrhage (UK) provide an objective means of assessing cerebrospinal fluid (CSF) samples to determine risk of subarachnoid haemorrhage (SAH). The guidelines are intended for general use, but samples rendered uninterpretable due to the presence of the antibiotic doxycycline have been described. Here, further cases of antibiotic- based interference, and their implications, are presented. Methods An archival search of CSF spectra performed at Hallands County Hospital Halmstad was performed for the years 2011 and 2016- 2019 in an attempt to locate instances of interference. Each case of suspected interference was further investigated with in vitro reproduction experiments as a means of confirmation and assessment of potential clinical impact. Results A total of 10 cases of CSF curve interference were discovered: 6 due to doxycycline, 3 due to metronidazole and 1 due to tetracycline. Interference due to the tetracycline class was revealed through in vitro experimentation to cause an apparent decrease in the sample’s net bilirubin absorbance(NBA); the presence of xanthochromia on visual inspection was, however, conserved. Conclusions The problem of CSF absorbance curve interference might be more common than previously suspected. Due to the potential NBA- lowering effect of tetracyclines, the author recommends visual examination of CSF samples in every case.


Author(s):  

It is crucially important to detect subarachnoid haemorrhage (SAH) in all patients in whom it has occurred in order to select patients for angiography and preventative surgery. A computed tomography (CT) scan is positive in up to 98% of patients with SAH presenting within 12h but is positive in only 50% of patients presenting within 1 week. Cerebrospinal fluid (CSF) bilirubin spectrophotometry can be used to determine the need for angiography in those few CT-negative patients in whom clinical suspicion of a SAH remains high; it may remain positive for up to 2 weeks after the event. The lumbar puncture (LP) should only be performed >12h after the onset of presenting symptoms. Whenever possible, collect four sequential CSF specimens. Always ensure that the last CSF sample taken is sent for bilirubin analysis. Protect the CSF from light and avoid vacuum tube transport systems if possible. Always use spectrophotometry in preference to visual inspection. All CSF specimens are precious and should be analysed no matter how they were transported, where necessary with appropriate notice of the caveats regarding oxyhaemoglobin. Centrifuge the specimen at >2000 rpm for 5 min as soon as possible after receipt in the laboratory and in any case within 1 h of collection. Store the supernatant at 4°C in the dark until analysis. An increase in CSF bilirubin is the key finding which supports the occurrence of SAH, but it is not specific for this. In most positive cases bilirubin will occur with oxyhaemoglobin. Oxyhaemoglobin occurring on its own is difficult to interpret and may be increased as a result of in vitro haemolysis of red cells introduced into the CSF during lumbar puncture. This process is exacerbated by vacuum tube transport systems. Results should be interpreted in the light of other investigations (e.g. if scan shows bilirubin then measure serum bilirubin and CSF oxyhaemoglobin and protein) and other confounding variables such as the time elapsed from presentation to LP.


Author(s):  
Jan Miller

The revised national guidelines for the analysis of cerebrospinal fluid for bilirubin in suspected subarachnoid haemorrhage (UK) provide a framework for the analysis of cerebrospinal fluid samples for the purpose of investigation of subarachnoid haemorrhage. In principle, as long as samples are collected and analysed according to the guidelines, any absorbance scan thus obtained ought to be amenable to interpretation. The case presented involves a cerebrospinal fluid sample with an absorbance scan which could not be interpreted with the guidelines. An archive search for similar cases suggested interference from doxycycline therapy as the cause. Doxycycline was confirmed to be the cause through experimental in vitro reproduction of the interference. Difficulties arising from this interference are discussed. It is hoped that a future version of the guidelines may mention, and propose a means of dealing with, the issue of doxycycline interference.


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