Sepsis in the Critically Ill-Does Gender Matter?

Critical Care Medicine www.ccmjournal. org 1957 enrolled 1,533 (938 males, 595 females) patients with 1,815 admissions (1,108 males, 707 females) with probable or definite sepsis, with an ICU length of stay (LOS) of over 24 hours, via an “opt-out” study inclusion method. Of note, the patients were mostly older adults, with a female mean age of 59.4 ± 16.2 years and male mean age of 60.8 ± 14.2 years. Nearly 88% of admissions were white. The admissions were largely medical (~73%), with respiratory infection followed by abdominal infection as the most common causes of sepsis in both genders. With regards to lesser frequency etiologies, more females had urinary tract infections; more males had mediastinal infections. Overall comorbidity scores were comparable (Charlson Comorbidity Index [CCI] of 4), the severity of comorbidities varied with a (CCI) interquartile range of 2–6. Illness severity on ICU admission, other than a slightly higher Acute Physiology and Chronic Health Evaluation IV score in females, was comparable between genders. With regards to outcomes, ICU LOS, frequency of acute kidney injury, acute respiratory distress syndrome, and myocardial infarction were comparable. Notably, there were no differences in mortality at multiple time frames, for example, approximately 30% in-hospital mortality for both genders, the 1-year study conclusion, and 45.5% male versus 43.4% female mortality at the 1 year study conclusion, p value equals to 0.36. Further, there was no difference in 90-day mortality in the 239 patients with age less than 45 years. To examine the host response, plasma levels of 19 key protein-based biomarkers (coagulation mediators and markers, cytokines, vascular endothelial cell adhesion molecules, among others) were determined in 1,205 critically ill sepsis admissions (729 men and 476 women) (9). Coagulation variables were not different between genders (D-dimer, prothrombin time, partial thromboplastin time, protein C, and antithrombin). However, women had significantly higher C-reactive protein levels. Systemic tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-13, and interferon (IFN)-γ were not detectable in most patients and when detected, their levels were not different between genders. The reason for nondetection of some of these cytokines is not clear—perhaps because of severity of illness, timeframe of sample collection, threshold for cytokine detection, others? Indeed, some of these cytokines were thought to be so important in sepsis that multiple trials were A genomic storm in critically injured humans. J Exp Med 2011; 208:2581–2590 10. Terpstra ML, Aman J, van Nieuw Amerongen GP, et al: Plasma biomarkers for acute respiratory distress syndrome: A systematic review and meta-analysis. Crit Care Med 2014; 42:691–700 11. Janz DR, Ware LB: Plasma biomarkers in acute respiratory distress syndrome: A work in progress. Crit Care Med 2014; 42:755–756 12. Shankar-Hari M, McAuley DF: Divide and conquer: Identifying acute respiratory distress syndrome subphenotypes. Thorax 2017 Jul 17. [Epub ahead of print] 13. Ferguson JJ, Califf RM, Antman EM, et al; SYNERGY Trial Investigators: Enoxaparin vs unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes managed with an intended early invasive strategy: Primary results of the SYNERGY randomized trial. JAMA 2004; 292:45–54 14. Piaggio G, Elbourne DR, Pocock SJ, et al; CONSORT Group: Reporting of noninferiority and equivalence randomized trials: Extension of the CONSORT 2010 statement. JAMA 2012; 308:2594–2604 15. Fremont RD, Koyama T, Calfee CS, et al: Acute lung injury in patients with traumatic injuries: Utility of a panel of biomarkers for diagnosis and pathogenesis. J Trauma 2010; 68:1121–1127