Utility and effectiveness of the Scandinavian guidelines to exclude computerized tomography scanning in mild traumatic brain injury - a prospective cohort study

The effects of the introduction of S100B in a clinical setting does – in addition to the test’s properties – depend on the compliance to these new guidelines. The 63.0% compliance to the guidelines found in this study is somewhat better than the 51% compliance to the first guidelines published by SNC in 2000 found in a previous study from a different Norwegian university hospital [14]. This study was followed by an education program that instructed the doctors about these guidelines which was found to increase the compliance to 63% [15]. The ability to make decisions according to the guidelines are better in this study conducted at AHUS than reported in the first study, and equally as good as the results after the education program in the second study.

Reasons for deviating from a guideline could be based on lack of knowledge about the guidelines, but also based on clinical judgment and experience. Guidelines are just guidelines, they are not strict rules of management, and the clinical judgment can therefore overrule them [12]. However, when looking at the details for cases where the guidelines were not followed (Table 1) it is clear that the vast majority of the decisions to deviate from the guidelines were within the groups where a CT scan was either “evidently” indicated or “most likely not” indicated where a “just in case” S100B-sample was performed. The most evident were the 75 S100B samples from the patients where a head CT was directly indicated and 65 of these patients (86.7%) went on to have a head CT irrespective of the S100B result. Another possible reason for overtriaging was that the patients with MTHI were considered to be in the second highest urgency level on triage, and the S100B test was ordered by default by the nurses when the patient was entering the ED to save time. This overuse of the S100B tests have little effect on the clinical value of the test but are more interesting from a financial point of view. Simultaneously the number of clinically undertriaged patients who theoretically could have an undetected intracranial injury (6.6%, Table 1) is comparable to the numbers reported for the previous guidelines, where undertriaging was observed in 7% of the cases [15].

Effective patient turnover is always in focus in a busy emergency department and such diagnostic impatience might trigger doctors to try to make shortcuts with regard to the guidelines. This was most likely the case for many of the patients in this study where a direct CT examination was indicated, but a S100B sample was ordered as well while they were waiting for an CT examination. On the other hand, since the patient’s stay at the hospital could be extended 2 h because of the S100B test, there are also several cases where a CT examination is carried out even though the patient is only indicated for the S100B test. Thus, it is evident that there is both clinical and administrative overruling of the guidelines in addition to the non-compliance due to lack of knowledge.

The two previously mentioned studies by Heskestad et al. [14, 15] indicated that deviations from the guidelines were mostly overtriaging with an excessive use of CT examinations and unnecessary hospital admissions. This is also the case in the study conducted at AHUS, but the 18.9% overtriage found in this study is lower than the results obtained in Heskestad’s study from 2012 where this was the case for 30% of the patients [15].

The over- and undertriaging seem to occur in random and no relation is identified to other factors such as certain clinicians, age of the patient, mechanism of injury, comorbidities, certain time of the day or day of the week.

In the updated guidelines it is estimated that the S100B test could replace the CT examination in approximately 30% of the patients based on several studies that have shown a negative predictive value of 97–100% and specificity above 30% with a cutoff value at 0.10 μg/L [9, 11, 13, 16, 17]. Although we were able to reproduce the same ratio of negative samples as previously described in the literature [13], the negative S100B result was ignored for almost 50% of the cases. And if looking at the spectrum of the MTHI patients admitted to AHUS in the study period that would potentially require a head CT, S100B sampling changed the pathway for only 8.2% cases compared to the old guidelines published in 2000 [4]. Optimal compliance to the guidelines would double the percentage, but still for our MTHI group, S100B sampling would only be indicated in one in three patients and then useful for only one in three of those. As a result, doctors might find the guideline less useful and this could also be an explanation for the low adherence to the guidelines and the blood sample result.

However, S100B has better sensitivity, negative predictive value and specificity than D-dimer, which is widely used in ruling out thromboembolism [9]. A negative S100B test makes it safe to send the patient home when a clinical evaluation cannot rule out brain injury and the patients are spared for a significant amount of radiation when a CT scan is avoided. This is particularly important for the younger age groups. One of the more frequent indications for direct CT within guidelines are ages ≥65 and anticoagulants and consequently there is a potentially larger percentage of the young MTHI patients that are within the group where S100B is indicated.

In this current study, over 40% of the patients were within the group where a head CT was directly indicated. This is about twice as many as reported in a previous study assessing the potential impact of the new SNC guidelines [13], and this shift towards the left of the guidelines will significantly lower clinical contribution of S100B sampling. The main reason for being classified in the “direct CT” groups in our study was age ≥ 65 and anti-platelet medication and our population was on average almost 10 years older than the population studied retrospectively by Undén et al. [13]. AHUS is located in close proximity to Oslo University Hospital, which is responsible for the management of the most severe traumas. The population attending the ED of AHUS is therefore dominated by minimal and mild injuries, intoxicated patients and elderly with moderate injuries. The patients being older in average could explain both the higher percentage of patients in the “direct CT” group and the higher prevalence of positive CT scans. One might argue that the guidelines therefore should only be applied for the population between 18 and 65 years only, but a recent study did find a reasonable specificity of 18.7% in patients aged 65 or older which supports the rationale for keeping the 65+ included in the guidelines [18].

Still the clinical usefulness of S100B is likely to be higher for the younger age groups. Applying the guidelines for MTHI patients under the age of 18 is therefore tempting, but due to large variation in the normal values for S100B in the younger age group, this is still not recommended by the SNC group [19].

As shown in a recent study, the clinicians should keep in mind that the S100B levels might be affected by the patient’s ethnicity, with especially African Americans showing significant deviations in S100B levels compared to Caucasians [20]. As the population of this study and the patient population of AHUS consist of 99% Caucasians, we do not think that this will significantly influence our results.

As previously mentioned, the clinical usefulness of S100B also depends on the time it takes from the clinical evaluation to the presence of a test result, which in the case of a positive S100B test will be the same as a delay in having an indicated CT examination. A near 2-h delay, as was the case in this study, for diagnosis and management of a traumatic brain haemorrhage may in some cases have severe or even fatal consequences. However, no such incidents were found in this study nor other previous studies examining the use of S100B as a marker for brain injury [9, 11, 17]. Further on, it is recommended that the patients are observed while waiting for the S100B results, and deterioration in GCS at this time will indicate an acute CT examination.

Nevertheless, when the S100B-test is used, there will be a near 2-h delay before the results are ready, and if the test is positive and a CT examination has to be supplemented, approximately three and a half hours would have been spent from the time the S100B-test was requisitioned until the CT examination can be analysed. This could affect the willingness to comply with the guidelines and has the potential to create insecurity both for the patient and the healthcare workers involved.

The main reason to introduce these guidelines was to reduce the number of unnecessary CT scans, and thereby reduce the costs and the radiation exposure to the patients. The estimated number of CTs that will lead to the development of a cancer vary depending on the specific type of CT examination, patient’s age and sex. A recent study estimated that 1 in 8.100 women who undergo a head CT will develop cancer from that CT, while the number was 1 in 11.080 men. For 20-year olds the risks were approximately doubled, and for 60-year olds, the risk was approximately 50% lower [21]. Avoiding up to 20% of the CT scans with optimal compliance might therefore make a substantial change for the MTHI patients.

As to the costs of a CT scanning, they will include the using of the machine itself and the wages of the staff who perform the scans and analyse the pictures. The costs do also vary between countries and are therefore hard to estimate. A study from the United States showed average price for upper-tier academic hospitals $1390.12 ± $686.13 [22], which means that AHUS, with a prize of about 14 USD per S100B analysis, throughout a year will save a six figure number in US dollars with the introduction of these guidelines.

In conclusion the clinical usefulness of the new guidelines and S100B in particular, depends on both the characteristics of the patient population and the compliance with the guidelines. Further efforts need to focus on increasing the adherence to a negative test result and avoid the “just in case” blood samples or CT scans. The responsibility must be put on the doctors who refer the patients to CT and we believe that education, information and experience with both the guidelines and the S100B test in particular, would increase the compliance within this group and consequently increase the clinical value of updated Scandinavian guidelines for initial management of minimal, mild and moderate head injuries.

The main limitation in this study is that the compliance of the guidelines was assessed more or less during the introduction period of these guidelines. This was partly tactical believing that a study itself will increase the focus on the new guidelines and facilitate the introduction. Secondly, in the study period a study form was included for each MTHI patient containing information of the new guidelines with check boxes to fill in, which to some degree dictated the pathway in the guidelines. It is also likely that there will be some overuse of S100B in the introduction period just to “get familiar” with the test which might be reduced and stabilized by time. The long-term compliance in an “unsupervised” setting is therefore unknown. Uncertainty of the time of injury could represent a source of error in the interpretation of the S100B, but the information is considered reliable as a big majority of the patients attend the ER directly from the site of trauma, many of them by ambulance, and because of the short distances in the catchment area.