We conducted a multicentre retrospective study to evaluate the clinical characteristics and outcomes in mechanically ventilated patients according to gender and age. The main finding of this study was that gender- and age-related differences in clinical outcomes among mechanically ventilated patients exist. More importantly, we found that the male gender was independently associated with hospital mortality in the overall study population as well as among patients 65 years or older but not among patients less than 65 years old.
As reported in other studies (2, 3, 7–11), we found that men account for more than half of patients (63.2%) receiving mechanical ventilation in the ICU. These findings are even more surprising when we consider the gender distribution of the Chinese urban adult population. For example, in 2010, women accounted for nearly 50% of the Chinese urban adult population, and this proportion increased with age (14). It is not clear why the proportion of women receiving mechanical ventilation in the ICU is generally lower than that of men, but this may be due to differences in treatment preferences or gender bias. Women were less likely than men to be admitted to an ICU and to receive care and life-supporting treatments such as mechanical ventilation, despite the fact that the severity of illness was similar in men and women or even higher in women (3, 15–18). This difference in care may stem from less aggressive treatment preferences by women (or their surrogates) (16, 19, 20). Men preferred life-sustaining treatments more than women overall, for specific treatments, and in response to specific health scenarios. Furthermore, Sagy et al (21) reported that having the female gender of both the physician and the patient was associated with a decreased ICU admission rate of critically ill patients. Their findings indicated the existence of possible gender bias where having the female gender of the patient and the treating physician diminish the likelihood of restricted health resource use.
In this study we found that the overall hospital mortality rate for men was greater than the overall hospital mortality rate for women (35.4% vs 28.7%, respectively; p = 0.042), despite similar age, the severity of illness, type of admitting ICU, and the number of comorbidities between both genders. When we analysed the overall study population according to age (< or ≥ 65 years) and gender, in the younger age group, despite the fact that the duration of MV, ICU LOS and hospital LOS were significantly longer for men than for women, we found that the ICU and hospital mortality rates were slightly higher for women than for men (20.0% vs.17.8% in the ICU and 20.8% vs.19.2% in the hospital, respectively), although these differences were not statistically significant. However, in the group of those 65 years or older who had similarities in age, severity of illness, type of admitting ICU, and the number of comorbidities, we found statistically significant differences in ICU and hospital mortality rates according to gender (p ≤ 0.011). The ICU and hospital mortality rates were significant higher for men than for women. In addition, using multiple logistic regression analysis, we found that gender had no effect of among the younger age group. However, among the older age group, after adjusting for all other factors, we found that the male gender was independently associated with hospital mortality (p = 0.002). Therefore, the results of this study demonstrated that there were gender- and age-related differences in clinical outcomes among mechanically ventilated ICU patients. We believe that there may be an interaction between age and gender, and that this interaction usually intensifies with age. The association of old age and male gender may be strongly related to mortality in mechanically ventilated ICU patients.
Although previous studies have explored the effects of gender on the outcomes of mechanically ventilated ICU patients, the findings across these studies are often inconsistent (7, 10, 12). Our results are also inconsistent with or even contrary to these previous studies. Possible reasons for this inconsistency is that two of the three studies did not further explore the effect of the interaction between age and gender on the outcome of mechanically ventilated patients, the mean age of patients included in the three studies was significantly different, and all patients studied were less than 65 years old. Age has been shown to be independently associated with mortality in mechanically ventilated ICU patients, and this correlation increases with age (5, 7, 12). Our study also supports this finding. Moreover, Fowler et al (3) found that sex- and age-related differences exist among ICU admissions, receipt of specific life-supporting interventions, and in short- and long-term outcomes. Mahmood et al (17) also found that there was a statistically significant interaction between gender and age among critically ill patients. Women less than 50 years of age had a lower ICU mortality rate compared to men, while women 50 years of age or older did not have a significant difference when compared to men. Therefore, when evaluating the effect of gender on the outcome of mechanically ventilated patients, we should not ignore the age-related effect. Another possible reason for this inconsistency may be due to referral bias or differences in the composition of ICU admission diagnoses. In previous studies, mechanically ventilated patients were either all medical patients (10), mainly medical patients (7), or half medical and half surgical patients (12). In this study, among the younger age group, more than half of the mechanically ventilated patients came from the surgical ward, while in the older age group, this proportion decreased significantly. Compared with women, men were more frequently admitted to the ICU from both the medical ward and surgical ward, although the difference was not significant. In the study by Reinikainen et al., male gender was found to be independently associated with increased hospital mortality among postoperative patients and among patients aged 75 years or older but not among medical patients (22). Women had a higher mortality compared to men after coronary artery bypass graft surgery and lower mortality with COPD exacerbation. There was no difference in mortality in acute coronary syndrome, sepsis, or trauma among the critically ill patients (17).
Our findings confirmed that there were gender- and age- related differences in mortality among mechanically ventilated ICU patients, but the reasons for these differences are poorly understood. When investigating the outcome of critically ill patients, in addition to considering age, hormonal status is also an important factor. In numerous clinical and experimental studies, sex hormones have been shown to affect gender-specific immune responses and organ functions after shock, trauma, and sepsis. Specifically, studies indicate that female hormones are protective in both immune responses and organ functions, whereas male sex hormones are deleterious (23–26). In fact, the inflammatory response to infection seems exacerbated in males, as compared with females (27). The available information indicates that sex hormones play a key role in regulating immune response and organ function. In addition, there were gender differences in neuroendocrine and endothelial responses in critically ill patients, possibly mediated or regulated by sex hormones (26). Thus, differences in the hormonal status of critically ill patients may partly explain the gender-related differences in the rate of disease progression and response to treatment in ICU patients. In our study, we found that the duration of MV, ICU LOS and hospital LOS were significantly longer for men than for women both in the overall study population and in different age subgroups. These results imply that women may be more capable of recovering from critical illness or surgery than men. However, despite sex hormones playing a very important role, it is not enough to comprehensively account for the gender differences in the clinical outcomes of critically ill patients.
In an international multicentre prospective study, Esteban et al (7) used multivariate analysis to show that the main conditions independently associated with increased mortality in mechanically ventilated ICU patients included not only the factors present at the start of MV (such as age, prior functional status, etc.), but also factors related to patient management (such as having a plateau pressure > 35 cmH2O, tracheostomy, etc.) and factors that developed during MV (such as barotrauma, organ failures, etc.). Similarly, in our study we found that in the overall study population, the type of admitting ICU, APACHE II score, hospital LOS, presence of complications of MV, and withholding or withdrawing of life-sustaining treatments were also independently associated with hospital mortality. However, our study showed that differences in baseline characteristics and management of MV in male and female patients did not seem to be significant, so these factors did not seem to explain the differences in mortality between males and females.
To the best of our knowledge, this is the first multicentre retrospective study in China providing data that indicate gender- and age-related differences in clinical outcomes among mechanically ventilated ICU patients. However, we also are aware of several limitations of our study. First, this study is a retrospective study, and the data were obtained between 2012–2013, which may impose temporal limitations on the applicability of this data set. Second, the 14 ICUs included in our study population are all in Beijing, and these ICUs may not be representative of a random sample of Chinese ICUs. Thus, our research results may not be applicable to other regions or countries. Third, our study did not include other important variables, including nutritional status, degree of organ dysfunction, and other invasive procedures, which may also account for gender differences in outcomes. The effect of gender on the outcomes of critically ill patients is complex, and the underlying mechanisms remain unclear. Therefore, it is necessary to conduct more prospective studies, specifically designed to address gender differences and their underlying mechanisms; hormonal status should also be examined.