Association of Serum Bilirubin with the Severity and Outcomes of Intracerebral Hemorrhages

Abstract

Intracerebral hemorrhage (ICH) is the second most common subtype of stroke, and it is often associated with a high mortality rate and significant morbidity among survivors. Recent studies have shown that bilirubin, a product of heme metabolism, can exhibit cytoprotective, antioxidant and, anti-inflammatory properties. However, little is known about the role of bilirubin in combating several pathophysiological pathways caused by intracerebral bleeding in patients with ICH. In this study, data were collected retrospectively on 276 patients with ICH who were admitted to a university hospital between 5 January 2014 and 31 December 2017. We assessed the relationship between levels of total, direct, and indirect serum bilirubin and assessments of initial stroke severity and clinical outcomes by using Spearman's rank correlation and Kruskal-Wallis H tests. A secondary examination of the carrier protein albumin was also undertaken. Our study found that higher levels of direct bilirubin were correlated with worse admission Glasgow Coma Scales (GCS) (r_s = -0.17, p = 0.011), worse admission ICH Scores (r_s = 0.19, p = 0.008), and worse discharge modified Rankin Scales (mRS) (r_s = 0.15, p = 0.045). Direct bilirubin was still significantly correlated with discharge mRS after adjusting for temperature at admission (r_s = 0.16, p = 0.047), oxygen saturation at admission (r_s = 0.15, p = 0.048), white blood cell count (r_s = 0.18, p = 0.023), or Troponin T (r_s = 0.25, p = 0.001) using partial Spearman's correlation. No statistical significance was found between levels of total or indirect bilirubin and assessments of stroke severity and outcomes. In contrast, higher levels of albumin were correlated with better admission GCS (r_s = 0.13, p = 0.027), discharge GCS (r_s = 0.15, p = 0.013), and discharge mRS (r_s = -0.16, p = 0.023). We found that levels of total bilirubin, direct bilirubin, and albumin were all significantly related to discharge outcomes classified by discharge destinations (p = 0.036, p = 0.014, p = 0.016, respectively; Kruskal-Wallis H tests). In conclusion, higher direct bilirubin levels were associated with greater stroke severity at presentation and worse outcomes at discharge among patients with ICH. Higher levels of albumin were associated with lower stroke severity and better clinical outcomes. Future prospective studies on the free bioactive bilirubin are needed to better understand the intricate relationships between bilirubin and ICH.

Keywords: albumin; free bilirubin; hemoglobin; intracranial bleeding; stroke.

Figure 1

Boxplots of total bilirubin levels observed in “Death” (n = 61), “Negative” (n = 136), and “Positive” (n = 80) discharge outcome groups (p = 0.036). Mean values are represented as white diamonds; outliers are represented as white circles.

Figure 2

Boxplots of albumin levels observed in “Death” (n = 61), “Negative” (n = 136), and “Positive” (n = 80) discharge outcome groups (p = 0.016). Mean values are represented as white diamonds; outliers are represented as white circles.