University of Groningen
Studies on delirium and associated cognitive and functional decline in older surgical patients
Beishuizen, Sara
DOI:
10.33612/diss.135861414
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Publication date: 2020
Link to publication in University of Groningen/UMCG research database
Citation for published version (APA):
Beishuizen, S. (2020). Studies on delirium and associated cognitive and functional decline in older surgical patients: The time is now to improve perioperative care and outcomes. University of Groningen.
https://doi.org/10.33612/diss.135861414
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Chapter 2
Timing is critical in determining the association between
delirium and S100 calcium-binding protein B
Sara J. Beishuizen
Rikie M. Scholtens
Annelies E. Vellekoop
Bart C. Vrouenraets
Dunja Westhoff
Diederik van de Beek
Sophia E. de Rooij
Barbara C. van Munster
Delirium and S100B: timing is critical To the Editor: The pathophysiology of delirium is poorly understood, but the higher incidence of
dementia after delirium has led to the hypothesis that some delirious patients might suffer from irreversible brain damage. The S100 calcium-binding protein B (S100B) is a possible marker of this brain damage.1 S100B is expressed by astrocytes and, to a lesser extent, by extraneuronal
tissues. At nanomolar concentrations, S100B exerts trophic effects on neuronal tissue, at micromolar concentrations, its effects are merely toxic.2 Previous research has shown that S100B
serum levels are elevated after trauma or surgery, during inflammation and in patients with Alzheimer’s disease.1,2
Elevated S100B levels have been found in serum of delirious patients in different settings.3-7 A
disadvantage of measuring S100B levels in serum is that they do not necessarily reflect brain damage, as extraneuronal sources can also contribute to elevated S100B levels.8 Studying
cerebrospinal fluid (CSF) levels of S100B can bypass this problem. Higher CSF levels of S100B were found in eight hip fracture patients who were delirious at the time of CSF sampling compared to 38 patients who were not (yet) delirious.9
We studied CSF S100B levels of delirious patients and non-delirious patients. We hypothesized that delirious patients would have higher levels of S100B compared to non-delirious patients.
Sixty-six patients, aged 65-97 years, who were acutely admitted for surgical treatment of hip fracture in a teaching hospital in Amsterdam, were included. Demographic data and medical history were recorded. The Informant Questionnaire on Cognitive Decline Short Form (IQCODE-sf) was completed by their caregiver. Cognitive impairment was defined as a IQCODE-score of 3.4 or higher or documented dementia diagnosis. We assessed the presence of delirium in nursing and medical records, using the criteria of the Diagnostic and Statistical
Manual of Mental Disorders, IV edition (DMS-IV-R). CSF samples were collected
preoperatively during cannulation for spinal anesthesia, before administration of anesthetics. Samples were centrifuged and stored at -80°C until required. S100B concentration was measured with an enzyme-linked immunosorbent assay (ELISA) against human S100B (Millipore, Darmstadt, Germany). The lowest detection limit of this assay is 2.7 pg/mL, levels below this limit were set at half this value. Difference in S100B levels between groups was assessed with Mann-Whitney U test. The hospital’s medical ethical committee approved the study.
Fifteen patients developed delirium during hospitalization, two of whom were already delirious prior to surgery. There was no difference in baseline characteristics between delirious and non-delirious patients. Mean age of non-delirious patients was 86.1 years (standard deviation (SD) 8.4), and 82.9 years (SD 8.0) of non-delirious patients (P=0.18). Four delirious patients had preexistent cognitive impairment (26.7%) compared to 11 non-delirious patients (21.6%,
P=0.68).
Pre-operative S100B levels did not differ between delirious and non-delirious patients (median: 1053pg/mL, Inter Quartile Range (IQR): 601-1178 versus median: 862 pg/mL, IQR: 701-1156,
P=0.76). The two patients with pre-operative delirium had S100B levels of 1052pg/mL and
2258pg/mL. Both are above the median levels of patients with postoperative or no delirium (median: 848 pg/mL, IQR: 595-1177 and median 862 pg/mL, IQR: 701-1156) (figure 1).
The present study in 66 elderly hip fracture patients showed no difference in pre-operative CSF S100B levels between patients with and without delirium after hip fracture. The higher S100B levels that were found in two patients with delirium at the time of CSF sampling suggests that timing is important in determining the association between delirium and S100B levels. This is in accordance with research of Munster and Hall, who found that S100B was most markedly elevated if measured during a delirious episode compared to before or after delirium.4,9
Delirium and S100B: timing is critical
Only two studies have previously investigated an association between CSF S100B levels and delirium. The elevated CSF S100B levels in delirious patients found by Hall must be interpreted with caution because of the small sample size.9 Caplan and colleagues found no difference in
CSF S100B levels between 20 patients with long-lasting delirium and 20 patients with probable Alzheimer’s disease (AD).10 Due to lack of a comparison group without both delirium and AD,
interpretation of these data remains difficult.
There is a clear demand for more research on the association between delirium and S100B to establish its role as an end-stage disease marker in delirium. A high priority topic is the release pattern of S100B in CSF during delirium and the interaction with inflammatory markers. Additionally, more knowledge on the relationship between S100B levels during delirium and long-term cognitive and functional outcomes is of interest, as this might shed light on the assumed relationship between delirium and subsequent cognitive and functional decline.
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