Sex differences in advance directives and their clinical translation among critically ill adults: results from the ADVISE study.

Background: Advance directives (ADs) are legally binding documents outlining individual preferences for medical care in the event of incapacitation. Evidence regarding their significance and implementation in critical care is scarce. Thus, this retrospective cohort study assesses sex differences in ADs' frequency, content, clinical translation, and associated outcomes in critically ill adults. The study was performed in two interdisciplinary tertiary Swiss intensive care units (ICUs). It included patients with ADs treated in the ICUs for > 48 h. The primary endpoint was the frequency of ADs. Secondary endpoints included the content of ADs, sex differences in baseline and treatment characteristics, the clinical implementation of ADs, and in-hospital outcomes.

Results: 5242 patients were treated for > 48 h in the ICUs, of which 313 (6.0%) had ADs (124 females [6.8% of 1813 females] and 189 males [5.5% of 3429 males], p = 0.054). No sex-related differences were observed regarding baseline characteristics except that females with ADs were more frequently single, divorced, or widowed (57% vs. 37%, p = 0.001), more frequently had acute stroke as main diagnosis (13% vs. 3%, p = 0.001), and more often refused cardiopulmonary resuscitation (CPR) (42% vs. 25%, p = 0.002) than males with ADs. In multivariable analyses, female sex was associated with refusing CPR independent of relationship status. Compared to males, females' ADs were more frequently violated (24% vs. 10%, p < 0.001), primarily by receiving unwanted treatments (24% vs. 8%, p < 0.001) and/or undesired ICU admission (10.5% vs 2.1%, p = 0.002). Despite these differences, treatment adaptations during intensive care, in-hospital outcomes, and discharge destinations did not differ between sexes.

Conclusions: This study revealed sex disparities in the content and translation of ADs between females and males admitted to ICUs. Females' ADs were more frequently violated, indicating a potential sex bias in the interpretation and translation of ADs in critical care. Clinicians must remain vigilant against violations of ADs and strive to deliver equitable care. Further prospective research is needed to investigate the causes of disparities in ICU end-of-life decision-making, integrating both qualitative and quantitative measures, to ensure equal treatment for all patients, regardless of sex or gender.