SEX DIFFERENCES IN SEPSIS-RELATED ACUTE RESPIRATORY DISTRESS SYNDROME AND OTHER SHORT-TERM OUTCOMES AMONG CRITICALLY ILL PATIENTS WITH SEPSIS: A RETROSPECTIVE STUDY IN CHINA

Abstract

Background: The evidence of sex disparity in acute respiratory distress syndrome (ARDS) is scarce and varies widely. Objective: This observational, retrospective study aimed to determine the effect of sex on the sepsis-related ARDS and other short outcomes in critically ill patients with sepsis. Methods: A total of 2,111 adult patients with sepsis who were admitted to three central intensive care units (ICUs) of Wuhan Tongji Hospital between 2012 and 2022 were included in our analysis. Sex was considered as an exposure factor, with sepsis-related ARDS as the primary outcome, and in-hospital mortality, invasive mechanical ventilation support, septic shock, and other complications as secondary outcomes. Results: Among the 2,111 enrolled patients, 1,287 were males (61%) and 824 were females (39%). The incidence of sepsis-related ARDS was higher in males compared to females ( P = 0.001), as well as in-hospital mortality ( P = 0.009). Multivariate logistic analysis demonstrated that male sex remained independently associated with an increased risk of sepsis-related ARDS (adjusted odds ratio [aOR] = 1. 493 [1.034-2.156], P = 0.032). Propensity score matching analysis also indicated that males had 58% higher odds of developing sepsis-related ARDS (aOR = 1.584 [1.022-2.456], P = 0.040). Regarding secondary outcomes, male sex was identified as a risk factor for in-hospital mortality (aOR = 1.536 [1.087-2.169], P = 0.015) and invasive mechanical ventilation support (aOR = 1.313 [1.029-1.674], P = 0.028) in the fully adjusted model. Sensitivity analysis that included postmenopausal females and age-matched male counterparts showed that male sex still remained to be a risk factor of developing sepsis-related ARDS (aOR = 1.968 [1.241-3.120], P = 0.004). Conclusions: Male sex was identified as an independent risk factor for sepsis-related ARDS and in-hospital mortality among critically ill patients with sepsis. Given the retrospective design of this study, the relationship between sex and sepsis-related ARDS requires further validation through large-scale randomized controlled trials in the future.

Keywords: Sex difference; critical care; male; mortality; sepsis-related acute respiratory distress syndrome.

Fig. 1

Study flow diagram.

Fig. 2

Risk factors for sepsis-related ARDS. Logistic regression analysis with sepsis-related ARDS as the dependent variable in patients with sepsis. Multivariate: LR χ2 = 92.25, P = 0.0000; Hosmer Lemeshow χ2 = 4.88, P = 0.7704. ALB, albumin; BUN, blood urea nitrogen; CCI, Charlson Comorbidity Index; CKD, chronic kidney disease; CI, confidence interval; COPD, chronic obstructive pulmonary disease; CRE, creatinine; DD, D-dimer; DBP, diastolic blood pressure; G+, gram-positive (bacteria); G−, gram-negative (bacteria); HGB, hemoglobin; hsCRP, high-sensitivity C-reactive protein; LAC, lactate; OR, odds ratio; RR, respiratory rate; SBP, systolic blood pressure; SOFA, Sequential Organ Failure Assessment; WBC, white blood cell.

Fig. 3

Sex and secondary outcomes (female as ref.). Model 1 was the crude model without adjusting any underlying confounders. Model 2, we adjusted for age, smoker, drinker, blood type, marital status, insurance. Model 3, we further adjusted for vital signs, initial SOFA score, CCI, comorbidities (hypertension, diabetes mellitus, coronary artery disease, chronic obstructive pulmonary disease, chronic kidney disease, and chronic liver disease, tumor), source of infection (pulmonary, abdominal, bloodstream, urinary, skin and soft tissue, central nervous system), and type of microorganism cultured (G+, G−, fungi). Model 4, we incorporated further adjustments for laboratory indicators (WBC, HGB, BUN, CR, DD, hsCRP, ALB, LAC). CI, confidence interval; MV, mechanical ventilation; OR, odds ratio.