S100B measurement could reduce CT scan use by a quarter in low-risk head injuries

14th November 2022

S100B measurement in head injured patients rules out serious intracranial pathology avoiding the need for a CT scan in a quarter of cases

Assessment of S100B levels in low-risk head injury patients seen in an emergency department is a potential diagnostic marker to rule-out serious intracranial pathology that reduces the need for a CT-head scan in more than a quarter of cases according to a study by New Zealand researchers.

In a 2016 study it was estimated that globally, there were 27·08 million new cases of traumatic brain injury (TBI) caused primarily by falls and road injuries. Moreover, assessing patients with a head injury in an emergency department (ED) takes time with and has been estimated at 6.6 hours with the time related to head CT responsible for about half of the total length of stay.

Despite increased availability of CT scans and its potential value as a diagnostic tool, over 90% of head CT scans in those referred from ED to exclude a significant intracranial injury have been found to be normal prompting the search for alternative assessment tools. One potential biomarker protein is S100B, which has been described as a useful neuro-biochemical marker of brain damage such as in circulatory arrest, stroke and traumatic brain injury.

However, a recent systematic review concluded that the diagnostic accuracy of single biomarkers as a rule out for significant intracranial injury seen on CT head scans in ED patients with TBI is low. Nevertheless, the authors of the review added that S100B is the only single biomarker with a validated clinical platform making it the biomarker of choice.  Despite this, there is little evidence on the diagnostic performance of S100B, particularly in low-risk head injury patients, where it is likely to be of greatest value in reducing the need for a CT-head scan.

In the present study, the New Zealand team examined the diagnostic value of the biomarker for excluding significant intracranial pathology in patients who presented at an ED within 6 and 24 hours of their head injury. Included patients were those able to give consent and without signs of post-traumatic amnesia and blood samples were taken to measure S100B levels.

All patients were assessed and sent for a CT-head scan when deemed clinically appropriate and categorised as CT-positive (i.e., needing a scan) or CT-negative. The primary outcome was the diagnostic accuracy of S100B within 6 hours after a head injury.

S100B diagnostic value in low-risk head injury

A total of 265 patients of whom, 133 with a median age of 69.5 years (35.8% female) presented within 6 hours of their head injury were included in the study.

Among those presenting within 6 hours, the median S100B level in those who were CT-positive was 0.36 and compared to 0.15 in the CT-negative group (p < 0.01). The sensitivity of S100B in the 6-hour group was 93.8% and the specificity of 30.8%.

The authors calculated that using a clinically validated cut-off threshold for S100B of 0.1 μg/mL, if patients with levels below this threshold did not have a CT-head scan, the use of scans would be reduced by 27.1%. Similarly, for those attending within 24 hours of their head injury and using the same threshold, would lead to a 37.4% reduction in CT scans. In fact, the authors also determined that the risk of missing a significant injury with this approach would result in missing only 0.75% of significant injuries within 6 hours or 2.3% within 24 hours.

They concluded measurement of S100B performed well as a diagnostic aid to exclude significant intracranial injury in low-risk patients with a head injury.

Citation
Rogan A et al. Diagnostic performance of S100B as a rule-out test for intracranial pathology in head-injured patients presenting to the emergency department who meet NICE Head Injury Guideline criteria for CT-head scan Emerg Med 2022

Clopidogrel monotherapy and the risk of brain bleed after head injury

17th October 2022

Whether clopidogrel monotherapy increased the risk of an intracranial bleed after a head injury was the subject of a recent meta-analysis

Clopidogrel monotherapy could increase the risk of a traumatic intracranial haemorrhage (tICH) but the risk is currently unclear. Nevertheless, previous data among trauma patients prescribed anticoagulants such as warfarin or aspirin and who sustain an intracranial injury, suggest a four-to-fivefold higher risk of death compared to those not prescribed anticoagulants. Additionally, a 2005 retrospective analysis of 90 patients older than 50 years of age, found that the use of aspirin, clopidogrel, or a combination, significantly increased the risk of mortality when head injury involves intracranial haemorrhage. Despite these findings, a study examining direct acting oral anticoagulants, found that the risk of adverse outcome following mild head injury appeared to be low.

For the present study, UK researchers set out to explore whether there was a higher risk of an intracranial bleed as determined from a CT scan, within 24 hours of presentation for a head injury, among patients prescribed clopidogrel monotherapy prior to their injury. The researchers undertook a meta-analysis and searched for studies in which there was a non-antithrombotic control group compared to those only prescribed clopidogrel. The primary outcome was set as a traumatic intracranial haemorrhage within 24 hours of presentation after a head injury. The secondary outcomes were the need for neurosurgical intervention and mortality up to 28 days later.

Clopidogrel mono-therapy and intracranial bleeds

After the literature search, a total of 7 studies with 21,898 participants were included in the final analysis. All of the studies contained a representative cohort of patients with a head injury and included those who had sustained a fall from standing and road traffic accidents although none were specifically designed to compare the rates of tICH.

The pooled odds ratio (OR) for the risk of an tICH for clopidogrel monotherapy compared to no anticoagulant treatment was 0.97 (95% CI 0.54 – 1.75). However, the I² was 75% thus indicating a high level of heterogeneity.

Only two studies provided data on neurosurgical interventions which was non-significant (OR = 0.92, 95% CI 0.61 – 1.37, p = 0.67) though only one study provided usable data on in-hospital mortality and therefore this outcome was not reported.

The authors concluded that their meta-analysis did not provide statistically significant evidence to suggest that clopidogrel monotherapy patients were at an increased risk of tICH following a head injury compared to those not prescribed antithrombotic agents.

Citation
Moffatt S et al. Does pre-injury clopidogrel use increase the risk of intracranial haemorrhage post head injury in adult patients? A systematic review and meta-analysis Emerg Med J 2022