450,948 patients admitted to either the ICU (n = 77,803, 17.3%) or general ward (n = 373,145, 82.7%) with the diagnoses of pulmonary embolism (n = 24,077, 5.3%), heart failure (89,326, 19.8%), rhythm disturbance (n = 72,975, 16.2%), acute coronary syndrome including cardiac arrest patients (n = 183,762, 40.8%), and stroke (n = 80,808, 17.9%) between 01/2012 and 12/2016 were included in our analysis (Table 1). Women were less often admitted to the ICU, independent of diagnoses (pulmonary embolism 10.6 vs. 12.3%, heart failure 10.0 vs. 14.5%, rhythm disturbance 11.2 vs. 13.0%, acute coronary syndrome including cardiac arrest 21.7 vs. 22.3%, stroke 16.5 vs. 19.3%, Table 1), independent of age category (Supplementary Table S1). Conversely, more women than men were admitted to the general wards (pulmonary embolism 89.4 vs. 87.7%, heart failure 90.0 vs. 85.5%, rhythm disturbance 88.8 vs. 87.0%, acute coronary syndrome 78.3 vs. 77.7%, stroke 83.5 vs. 80.7%, Table 1). Men who were transferred from another hospital were more often admitted to the ICU than women (13.5 vs. 16.1% in men, p < 0.001, Table 1), while direct ICU admissions were more frequent in women (74.6 vs. 74.0% in men, p < 0.001, Table 1).
Age at admission
In ICU patients, median age was higher in women as compared to men (75 [interquartile range [IQR] 64;82] years in women vs. 68 [IQR 58;77] years in men, p < 0.001) Accordingly, overall peak ages at admission (ICUs and general wards) were significantly higher in women as compared to men, independent of diagnosis (Fig. 1, Supplementary Table S2).
In ICU patients, median SAPS II was higher in women as compared to men [29 (IQR 23;40) in women and 27 (IQR 20;38) in men, p < 0.001]. Accordingly, multivariate linear regression models showed higher estimates for SAPS II in women admitted to the ICUs as compared to men [8.47 (6.71–10.23) in women and 4.06 (2.74–5.39) in men, ratio women:men 4.40 (2.20–6.61), p < 0.001]. When stratified by age, younger women < 45 years had consistently higher baseline estimates for SAPS II as compared to men; while, an opposite trend was observed at the age > 65 years (Supplementary Fig. S1). Hence, sex differences in median SAPS II were most pronounced in younger individuals, with younger women presenting with higher SAPS II than younger men (Supplementary Fig. S1). When stratified by diagnoses, baseline estimates of SAPS II were significantly higher in women across all diagnoses (Supplementary Table S3).
Probability of ICU admission (primary outcome)
Overall, women had a lower likelihood to be admitted to the ICU than men [odds ratio (OR) 0.78 (0.76–0.79), Table 2]. Multivariate Bayesian regression analysis adjusted for admission diagnosis, age categories (< 45 years, > 65 years) and proximity to peak age revealed that the odds for ICU admission were significantly lower in women as compared to men for heart failure [women 0.17 (0.16–0.18); men 0.24 (0.23–0.25); women:men OR 0.73 (0.69–0.77)] and stroke [women 0.29 (0.28–0.31); men 0.32 (0.31–0.33); women:men OR 0.92 (0.87–0.98), Table 2]. In contrast, women presenting with an acute coronary syndrome including cardiac arrest had a higher probability than men to be admitted to the ICU [women odds 0.40 (0.39–0.42); men odds 0.37 (0.36–0.39); women:men OR 1.08 (1.03–1.14), Table 2]. When the overall study population was stratified by age categories, women < 45 years of age showed a trend towards a lower admission probability as compared to men (Fig. 2), yet the odds ratio women:men did not reach significance in the adjusted Bayesian model [admission probabilities women:men < 45 years OR 1.03 (0.94–1.13), Table 2]. Women > 65 years had a lower probability to be admitted to the ICU than men [women:men OR 0.94 (0.89–0.99), Fig. 2 and Table 2].
Secondary outcome measures
No significant sex differences were observed for NEMS in the overall population (Table 1) and in age-stratified subgroups (Supplementary Table S1). When individual components of the NEMS were analyzed, men had higher rates of mechanical ventilation (23.40 vs. 22.51% in women, p = 0.005, Table 1), while women more often received non-invasive respiratory support (73.50 vs. 71.74% in men, p < 0.001, Table 1). Men had a greater use of vasoactive substances (12.68 vs. 11.77% in women, p < 0.001 for multiple vasoactives, Table 1) and a higher rate of renal replacement therapy (RRT, 2.68 vs. 2.02%, p < 0.001, Table 1). When stratified by age, women < 45 years had higher rates of mechanical ventilation (25.25 vs. 21.02% in men, p = 0.004), received more often multiple vasoactives (14.71 vs. 11.41% in men, p = 0.004) and RRT (4.25 vs. 2.47% in men, p = 0.003) than men (Supplementary Table S1). An opposite trend was observed in women > 65 years with regard to these treatments (p < 0.001, Supplementary Table S1).
Amongst patients with an acute coronary syndrome, 21,845 patients underwent percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). Significantly more men than women underwent PCI (53.97 vs. 43.73%, p < 0.001, Table 1) or CABG (2.07 vs. 3.04%, p < 0.001, Table 1). This was also true when the study sample was stratified by age categories, with gender differences being most pronounced in the younger age group < 45 years (PCI: 13.56 vs. 33.38% in men, p < 0.001, Supplementary Table 1).
Frequentist statistics revealed that ICU mortality was 6.7% in women and 6.1% in men (p < 0.001, Table 1). Women < 45 years and women aged 45–65 years died more often during ICU stay than men in the same age category (< 45 years: 7.03 vs. 5.30%, p = 0.039 and 45–65 years: 6.23 vs. 4.04%, p < 0.001, Supplementary Table S1). In contrast, in individuals > 65 years, ICU mortality was lower in women as compared to men in the same age category (6.86 vs. 7.35%; p = 0.039). Binomial logistic regression of the probability of all-cause death during ICU stay using unscaled covariates (diagnoses, age < 45 years, age > 65 years, SAPS II, NEMS /LOS) showed a significantly higher mortality in women with an acute coronary syndrome [OR 1.479 (1.21–1.81), p < 0.001, Fig. 3, Supplementary Table S4] or pulmonary embolism [OR 1.793 (1.11–2.90), p < 0.05, Fig. 3, Supplementary Table S4], as compared to men, while mortality for heart failure, rhythm disturbance, and stroke did not differ significantly between sexes (Fig. 3, Supplementary Table S4). In both sexes, a higher SAPS II was associated with a higher ICU mortality [women 1.096 (1.09–1.10), p < 0.001 and men 1.088 (1.085–1.090), p < 0.001, Fig. 3, Supplementary Table S4], but the association between increased SAPS II and the risk of death was significantly stronger in women as compared to men [OR 1.008 (1.004–1.012), p < 0.001, Fig. 3, Supplementary Table S4].