Introduction:
Sepsis is characterized by inappropriate host immune-inflammatory response. Plasma ceruloplasmin (Cp) is known to increase as part of the acute phase response. Mice lacking Cp gene are more likely than normal mice to die from sepsis.
Hypothesis:
We hypothesize that increased gene expression of Cp is protective and could be correlated with an improved survival outcome.
Methods:
Study Design: Prospective cohort. Settings: Adult patients with septic shock in medical and surgical ICUs. Sample: 118 patients were enrolled between January 2008 and March 2010 within 24-48 h of diagnosis. Exposure measure: Cp gene expression. Cp was measured in PBMC by RT-PCR. Outcome measures: 60 day mortality. Statistics: To assess the prospective association of Cp levels with mortality, we used Cox proportional hazard models. With 60 day mortality as the outcome and hospital days as the time metric, crude models for the outcome and log2 transformed Cp gene expressions were run. Statistical analyses were adjusted as follows: 1) crude model; 2)model adjusted for age, gender, race, body mass index (BMI), and baseline APACHE (Acute Physiology and Chronic Health Evaluation) II score. Hazard ratios are presented.
Results:
At 60 days 67/118 (56.8%) patients were alive and 51/118 (43.2%) patients were dead. The hazard ratio for doubling the Cp gene expression was significant in the crude model (HR = 1.27; C.l. 1.10, 1.46): for each doubling in Cp gene expression there is a 27% increased instant threat of dying; adjusted for age, gender, race, and body mass index (BMI): HR = 1.25; C.I. 1.09,1.45). Once adjusted for severity of illness (Apache 2 score) the effect was still statistically significant: HR = 1.17; C.I. 1.01, 1.35. Ventilator days and days of vasopressor support were not statistically different between Cp mRNA levels.
Conclusions:
Higher Cp mRNA expression at enrolhnent is associated with higher 60 day mortality based on the crude hazard ratio for Cp gene expression level and adjusted for age, gender, race, and BMl. Since this effect is still present once adjusted for severity of illness, we postulate that Cp gene expression level is an independent predictor of mortality. Therefore, we have to reject our hypothesis.
