What's New in Critical Illness and Injury Science? Evidence and limitations for using S100β to diagnose and risk stratify critically ill patients with delirium

Delirium is a transient fluctuating global disorder of cognition associated with increased morbidity and mortality and has a prevalence of up to 80% among intensive care unit (ICU) patients.[1–3] ICU delirium may be a predictor of increased complications, prolonged ICU and non-ICU hospital length of stay (LOS), increased hospital costs, long-term disability, long-term cognitive impairment, decreased odds of discharge home, and increased hospital mortality.[1] Moreover, ICU delirium has been associated with the development of incident neuropsychiatric disorders, including depression, anxiety, trauma, stress-related disorders, and neurocognitive disorders.[4] However, clinical management has been limited by the lack of an effective, reliable, and readily available biomarker to aid in the diagnosis, severity, and prognosis, and to aid clinical management. S100b protein is a calcium-binding protein that is mainly found in astrocytes and oligodendrocytes of the central nervous system and Schwann cells of the peripheral nervous system.[5] As such, S100β has been investigated as a biomarker for injury to the blood–brain barrier and/or astrocyte injury and has been reported to correlate with the degree of blood–brain barrier destruction and the severity and scope of brain injury.[5–7] Previously, S100β has been correlated with the development of delirium and cognitive changes after surgery in patients who are not critically ill.[6,8–11] Similarly, others have reported that delirium and neurologic outcomes may correlate with S100β in critically ill patients.[6,7,12–14] However, there are significant limitations and gaps in the available literature. The current studies display a predominance of male subjects (up to 65%), advanced age, and low levels of racial diversity among the study groups.[6,7,12–17] All current studies among critically ill populations have all been performed in China (n = 3),[5,12,13] the United States (n = 2),[6,7] Belgium (n = 2),[14,15] the Netherlands (n = 1),[17] or Brazil (n = 1).[16] Furthermore, limitations in study design limit the generalizability of the reported findings, including small sample sizes, differences in the study group populations (trauma vs. medical), differences in illness severity as evidenced by wide ranges on validated illness severity indices, and an absence of randomized studies (e.g. only observational and case–control studies).[5–7,12–17] In addition, the comparability of the preillness baseline health of the study populations across studies is unclear as only the US studies have reported a validated index for this (e.g. the Charlson Comorbidity Index).[5–7,12–17] Among the ICU populations, S100β levels have been reported to positively correlate with ICU LOS and readmission (trauma populations),[5,13] and adverse outcomes (mixed medical/surgical, trauma populations).[13,14] In addition, S100B was negatively correlated with global cognition up to 12 months after hospital discharge in a mixed medical/surgical ICU population; however, no difference in executive function was observed.[6] Despite these findings, the data for delirium have been mixed. Among mixed medical and surgical populations, S100β has been variably reported to correlate (positive vs. none) with delirium incidence (n = 134),[7,14] delirium duration,[7] and mortality.[5,16] Of note, each of these studies either excluded or did not report on pregnant patients. In the current issue of the International Journal of Critical Illness and Injury Science, Shyam et al. addressed important knowledge gaps by assessing a younger, female, South Asian obstetric population.[18] Shyam et al. performed a nested case–control study (n = 112) of S100β levels in critically ill obstetric patients in India. In this study, a positive correlation was noted between S100β and delirium levels.[18] Despite promising results, further prospective study in larger and more diverse (ethnically and clinically) populations is needed to establish discriminatory thresholds and the clinical utility of S100β for the diagnosis and prognosis or to guide clinical management in critically ill patients with delirium. Research quality and ethics statement This report was exempt from the requirement of approval by the Institutional Review Board/Ethics Committee. The authors followed applicable EQUATOR Network (http://www.equator- network.org/) guidelines; however, no specific guideline is available for editorials.