Validation of S100B Use in Managing Mild Head Injury
Validation of S100B Use in Managing Mild Head Injury
The first report concerning serum S100B as a possible biomarker in MHI was published in 1995. Since then, numerous reports and a meta-analysis, documenting the potential of S100B to safely reduce CT scans following MHI, have increased the evidence for clinical use. However, actual clinical validation has never been reported despite the biomarker being used clinically in several European countries. In 2007, S100B was introduced as a clinical tool in the management of MHI in our hospital, in an attempt to reduce CT scans after these injuries. This study shows that this implementation has been successful and that S100B, using a cut-off of less than 0.10 μg/L for normal values and a time window of 3 hours from injury, shows similar predictive values to the derivation studies.
Low compliance to guidelines is a common problem. 32% of patients with normal S100B levels were over-triaged with CT, admission or both. None of these had any intracranial complications. It is natural to expect caution when using new routines, especially concerning an injury where biomarkers have never been used before. Also, physicians must always be free to exert clinical judgement since management guidelines are merely an aid in the clinical process. Some patients cannot be sent home from the ED irrespective of S100B and/or CT findings (for example; elderly patients without support in their home environment, serious intoxication and patients with other injuries).
Our adapted guidelines are based upon the evidence-based SNC management guidelines from the year 2000. Since this publication, considerable new evidence has emerged in this field, including validated guidelines based upon patient history and clinical examination. The impact of including S100B in other guidelines is unknown. However, the SNC guidelines have proved accurate in comparison studies so the implementation of S100B into these is justifiable. Despite this, the examination of S100B within other guidelines is naturally warranted.
Owing to the predictive properties of S100B, the biomarker is best adapted into an intermediate risk group of patients, such as in this study. The prevalence of traumatic intracranial injury in this group was 4.7%, similar to other cohorts. These patients would normally receive a CT recommendation according to the SNC guidelines, which is justifiable considering the prevalence level. However, interpreting S100B levels in minimal head injury would lead to substantial over-triage (false positives) and using levels in more severe head injuries could lead to under-triage and may risk missing important complications (false negatives).
This study has several limitations. Firstly, one may argue that our method of determining the outcome measure, significant intracranial complications, may miss patients that may in fact have CT abnormalities. However, if these exist, these abnormalities would not have resulted in any change in management and/or outcome for these patients. The organisation of the state-owned Swedish health care system, with personal identification numbers connected with all medical journals, allows us to accurately identify new neuroimaging, neurosurgery and/or death in all patients who were not followed up with the questionnaire and therefore identifies any cases of important intracranial injury. This also allows us to minimise recall bias arising from the questionnaire. Secondly, none of our patients needed neurosurgery. If this was the endpoint, one could suggest that all our patients could have been discharged without S100B or CT. This management, however, would not be accepted in Sweden and the results must be considered in relation to the existing guidelines, which recommend CT in all these patients, similar to guidelines in other countries. Thirdly, the timing of S100B sampling after injury may be of importance. We used a time window of 3 hours based upon the evidence at this time and worries concerning the short half-life of S100B in blood. Recently, a large prospective study has utilised a time window of 6 hours with maintained predictive ability of S100B. It seems reasonable that a time window of 6 hours may be more applicable to this population and should be considered in future studies and/or clinical practice. Finally, deviation from the guidelines was seen. Although this was allowed in the study protocol, reasons for the deviation were not explored in depth and would have been an interesting point to examine. Future studies should include a comparison of clinical rules with unstructured physician assessment, in order to fully explore this aspect, including reasons for deviation from a guideline.
Discussion
The first report concerning serum S100B as a possible biomarker in MHI was published in 1995. Since then, numerous reports and a meta-analysis, documenting the potential of S100B to safely reduce CT scans following MHI, have increased the evidence for clinical use. However, actual clinical validation has never been reported despite the biomarker being used clinically in several European countries. In 2007, S100B was introduced as a clinical tool in the management of MHI in our hospital, in an attempt to reduce CT scans after these injuries. This study shows that this implementation has been successful and that S100B, using a cut-off of less than 0.10 μg/L for normal values and a time window of 3 hours from injury, shows similar predictive values to the derivation studies.
Low compliance to guidelines is a common problem. 32% of patients with normal S100B levels were over-triaged with CT, admission or both. None of these had any intracranial complications. It is natural to expect caution when using new routines, especially concerning an injury where biomarkers have never been used before. Also, physicians must always be free to exert clinical judgement since management guidelines are merely an aid in the clinical process. Some patients cannot be sent home from the ED irrespective of S100B and/or CT findings (for example; elderly patients without support in their home environment, serious intoxication and patients with other injuries).
Our adapted guidelines are based upon the evidence-based SNC management guidelines from the year 2000. Since this publication, considerable new evidence has emerged in this field, including validated guidelines based upon patient history and clinical examination. The impact of including S100B in other guidelines is unknown. However, the SNC guidelines have proved accurate in comparison studies so the implementation of S100B into these is justifiable. Despite this, the examination of S100B within other guidelines is naturally warranted.
Owing to the predictive properties of S100B, the biomarker is best adapted into an intermediate risk group of patients, such as in this study. The prevalence of traumatic intracranial injury in this group was 4.7%, similar to other cohorts. These patients would normally receive a CT recommendation according to the SNC guidelines, which is justifiable considering the prevalence level. However, interpreting S100B levels in minimal head injury would lead to substantial over-triage (false positives) and using levels in more severe head injuries could lead to under-triage and may risk missing important complications (false negatives).
This study has several limitations. Firstly, one may argue that our method of determining the outcome measure, significant intracranial complications, may miss patients that may in fact have CT abnormalities. However, if these exist, these abnormalities would not have resulted in any change in management and/or outcome for these patients. The organisation of the state-owned Swedish health care system, with personal identification numbers connected with all medical journals, allows us to accurately identify new neuroimaging, neurosurgery and/or death in all patients who were not followed up with the questionnaire and therefore identifies any cases of important intracranial injury. This also allows us to minimise recall bias arising from the questionnaire. Secondly, none of our patients needed neurosurgery. If this was the endpoint, one could suggest that all our patients could have been discharged without S100B or CT. This management, however, would not be accepted in Sweden and the results must be considered in relation to the existing guidelines, which recommend CT in all these patients, similar to guidelines in other countries. Thirdly, the timing of S100B sampling after injury may be of importance. We used a time window of 3 hours based upon the evidence at this time and worries concerning the short half-life of S100B in blood. Recently, a large prospective study has utilised a time window of 6 hours with maintained predictive ability of S100B. It seems reasonable that a time window of 6 hours may be more applicable to this population and should be considered in future studies and/or clinical practice. Finally, deviation from the guidelines was seen. Although this was allowed in the study protocol, reasons for the deviation were not explored in depth and would have been an interesting point to examine. Future studies should include a comparison of clinical rules with unstructured physician assessment, in order to fully explore this aspect, including reasons for deviation from a guideline.
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