Pathophysiology of Septicemia in Adult Burn Patients

Author(s):
Mile Stanojcic; Sarah Rehou; Abdikarim Abdullahi; Marc Jeschke

Background:

Burns are a common form of trauma that account for over 300,000 deaths each year worldwide. Survival rates have improved over the past decades due to improvements in nutritional and fluid support, burn wound care, and infection control practices. However, mortality remains unacceptably high. The primary cause of death has changed over the last decades from anoxic causes to now predominantly infections and sepsis. Despite the importance of infections and sepsis, the diagnosis and prediction remain a major challenge.

Hypothesis:

The aim of this study was undertaken to examine the pathophysiology or immune-metabolic trajectories of adult burn patients to delineate indicators of aberrant responses.

Methods:

Adult burn patients admitted to our burn centre between 2011 and 2017 were included in the study and further stratified based on clinical outcomes (sepsis, mortality, etc.). White adipose tissue from the site of injury was collected from the time of OR and blood was routinely withdrawn during the course of hospital stay. Gene and protein expression was conducted for various markers (NLRP3 inflammasome, ER stress, mitochondrial function, hypermetabolism) using RT-PCR and western blotting. Systemic biomarkers in plasma were analyzed at multiple time points post injury using the multiplex system to characterize chemokine and inflammatory cytokine expression.

Results:

Here we show that white adipose tissue of adult septic burn patients had increased expression of NLRP3 inflammasome components, ER stress and mitochondrial dysfunction. Interestingly, acute phase mediators of inflammation (NLRP3, IL-1β) persisted well beyond two weeks after injury. Systemically, sepsis burn patients had increased inflammation, chemokines, metabolic mediators than non-septics and trajectories supported a non-parabolic decline over time. Decreased systemic free fatty acids were present acutely after injury in septics where as hypermetabolsim was significantly increased, relative to non-sepsis burn patients. Lastly, when comparing only sepsis adults, non-survivors displayed hyper-responsiveness beginning at 11-20 days post injury that was not present in survivors.

Conclusions:

Our findings indicate that adult burn patients with sepsis display unique immune and metabolic trajectories. Furthermore, it sheds light on new insights and considerations when managing burn patients to delineate early indicators of sepsis.