Female Sex is an Independent Risk Factor for Mortality Following Post-Burn Sepsis

Authors:
Diana Julia Tedesco, Maria Fernanda Hutter, Fadi Khalaf, Marc Jeschke

Body of Abstract:
Background: Sepsis is the leading cause of morbidity and mortality among burn patients, affecting approximately 1 in 5 adults. Previous research has shown that adult female burn patients face an increased risk of mortality after injury compared to their male counterparts. However, the underlying reasons for this disparity remain unclear. It is uncertain whether the increased mortality in females is due to differences in sepsis risk, distinct physiological responses to sepsis, or variations in the timing of sepsis onset. Thus, in this study, we aim to clarify whether sex-based differences in post-burn mortality emerge primarily after sepsis develops, rather than through differential incidence of sepsis.

Methods: We conducted a cohort study at two provincial burn centres between 2006 and 2025. Patients ≥18 years with acute burn injuries covering ≥5% of total body surface area were included and stratified based on biological sex recorded on admission and sepsis diagnosis using the Sepsis-3 and ABA guidelines. Multivariable logistic regression was used to evaluate (1) the association between sex and mortality, (2) the association between sex and sepsis incidence, and (3) sex differences in 30-day mortality among patients with sepsis, adjusting for age, burn size, inhalation injury, and sepsis onset timing.

Results: A total of 1483 burn patients were included, including 223 males diagnosed with sepsis, 844 male controls, 82 females diagnosed with sepsis, and 334 female controls. At admission, female patients were older (median (IQR) 48 (36-62) vs. 46 (22-59) years, p=0.020), had similar burn size (median (IQR) 11 (7-19) vs 12 (8-21) %, p=0.068), and similar incidence of inhalation injury (26% vs 20%, p=0.462) compared to all male patients. Overall 30-day mortality was higher in females than males (8% vs 4%, p=0.002), an association that persisted after adjustment (adjusted OR 2.20, 95% CI 1.29–3.74). Sepsis incidence (20% vs 21%, p=0.668) and the timing of sepsis onset (median (IQR) 9.5 (5-15) vs 10 (6-15) days post-injury, p=0.503) did not differ between sexes. However, among sepsis patients, females had higher 30-day mortality compared to males (20% vs 10%, p=0.031) and female sex remained independently associated with mortality after adjustment for age, burn size, inhalation injury, and sepsis onset (adjusted OR 2.97, 95% CI 1.27–6.95).

Conclusion: Female burn patients experienced higher mortality overall, and this disparity became more pronounced following sepsis. These differences were not attributable to differential sepsis incidence or timing, suggesting sex-specific biological responses to infection rather than differential exposure risk.