Serum bilirubin levels on ICU admission are associated with ARDS development and mortality in sepsis.
BACKGROUND
Hyperbilirubinaemia is a common complication of sepsis. Elevated bilirubin may induce inflammation and apoptosis. It was hypothesised that increased serum bilirubin on Intensive Care Unit (ICU) admission contributes to sepsis-related acute respiratory distress syndrome (ARDS).


METHODS
Serum bilirubin on ICU admission was measured in 1006 patients with sepsis. Serial serum bilirubin was analysed prospectively in patients with sepsis who had ARDS for a period of 28 days. The effects of clinical factors and variants of the UGT1A1 gene on serum bilirubin levels were determined. Outcomes were ARDS risk and mortality.


RESULTS
During 60-day follow-up, 326 patients with sepsis developed ARDS, of whom 144 died from ARDS. The hyperbilirubinaemia (>or=2.0 mg/dl) rate in patients with ARDS (22.4%) was higher than in those without ARDS (14.1%, p = 0.002). For each 1.0 mg/dl increase in admission bilirubin, ARDS risk and 28- and 60-day ARDS mortalities were increased by 7% (OR = 1.07; p = 0.003), 20% (OR = 1.20; p = 0.002) and 18% (OR = 1.18; p = 0.004), respectively. Compared with subjects with bilirubin levels <2.0 mg/dl, patients with hyperbilirubinaemia had higher risks of ARDS (OR = 2.12; p = 0.0007) and 28-day (OR = 2.24; p = 0.020) and 60-day ARDS mortalities (OR = 2.09; p = 0.020). In sepsis-related ARDS, serial bilirubin levels in non-survivors were consistently higher than in survivors (p<0.0001). Clinical variables explained 29.5% of the interindividual variation in bilirubin levels, whereas genetic variants of UGT1A1 contributed 7.5%.


CONCLUSIONS
In sepsis, a higher serum bilirubin level on ICU admission is associated with subsequent ARDS development and mortality.
Zhai
R
R
Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA.
Sheu
C C
CC
Su
L
L
Gong
M N
MN
Tejera
P
P
Chen
F
F
Wang
Z
Z
Convery
M P
MP
Thompson
B T
BT
Christiani
D C
DC
D001663:Bilirubin / Q000097:blood* / Q000235:genetics; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D004812:Epidemiologic Methods; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics; D006801:Humans; D006932:Hyperbilirubinemia / Q000235:genetics / Q000378:metabolism*; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D010343:Patient Admission; D012128:Respiratory Distress Syndrome / Q000097:blood* / Q000209:etiology / Q000401:mortality; D018805:Sepsis / Q000097:blood* / Q000150:complications / Q000401:mortality; D000099148:UGT1A1 Enzyme
D001663:Bilirubin; D015415:Biomarkers; D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme